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Tic disorders proliferate in bipolar patients with OCD
Bipolar disorder patients with comorbid obsessive-compulsive disorder were significantly more likely to suffer from tic disorders, as well as hoarding, excoriation, and body dysmorphic disorder, than were those without comorbid OCD, data from 70 patients suggest.
Between 10% and 20% of patients with bipolar disorder (BD) also meet criteria for obsessive-compulsive disorder (OCD), and these patients are more likely to experience treatment resistance and poor prognosis than are BD patients without OCD. In addition, preliminary indications suggest a specific association between OCD and bipolar depression (BP-D) in particular, wrote Leonid Braverman, MD, of Ma’ale HaCarmel Mental Health Center, Tirat Carmel, Israel, and colleagues.
In addition, “there is compelling evidence indicating that OCD-spectrum and tic disorders share with OCD clinical characteristics, familial inheritance, neurobiological underpinnings and some aspects of pharmacotherapy,” and investigations into the clinical characteristics of OCD spectrum behaviors in BP-D patients with and without OCD are ongoing, they said.
In a study published in the Journal of Obsessive-Compulsive and Related Disorders (2021 Mar 21. doi: 10.1016/j.jocrd.2021.100643), the researchers reviewed data from 87 adults who met the DSM-5 criteria for BP-D. Of these, 27 also met criteria for OCD, 17 for subthreshold OCD, and 43 had neither OCD nor subthreshold OCD. The researchers compared the 27 OCD patients and the 43 non-OCD patients; the OCD patients had significantly higher rates overall of body dysmorphic disorder, hoarding disorder, excoriation disorder, and tic disorder, compared with non-OCD patients (P range from < .05-0.01 for all). No differences between the groups appeared for trichotillomania.
Also, the researchers found significant between-group differences in the number of patients with at least one OCD spectrum disorder and tic disorders (13 of 19 patients in the OCD group vs. 3 of 37 patients in the non-OCD group) and in the co-occurrence of two OCD-spectrum and tic disorders (3 of 19 patients in the OCD group vs. 1 patient in the non-OCD group).
The most common comorbid psychiatric disorders in both groups were substance use and combined anxiety disorders, followed by eating disorders, but no between-group differences were found in the frequencies of any of these conditions.
“From the clinical perspective, in BP-D patients,” the researchers noted.
The study findings were limited by several factors, including the small sample size, cross-sectional design, and exclusion of subsyndromic disorders, the researchers noted. However, the results support findings from previous studies, and the study emphasizes the clinical complexity and poor prognosis for these patients. Therefore, additional research is needed in patients with BP-D verse the manic/hypomanic phases of bipolar illness to determine similar patterns, they said. Medication trials are needed to address functional impairments in these patients, given the differences in treatment of BDD, hoarding, excoriation, and tic disorders, compared with “pure” OCD, they concluded.
The study received no outside funding. The researchers reported no financial conflicts.
Bipolar disorder patients with comorbid obsessive-compulsive disorder were significantly more likely to suffer from tic disorders, as well as hoarding, excoriation, and body dysmorphic disorder, than were those without comorbid OCD, data from 70 patients suggest.
Between 10% and 20% of patients with bipolar disorder (BD) also meet criteria for obsessive-compulsive disorder (OCD), and these patients are more likely to experience treatment resistance and poor prognosis than are BD patients without OCD. In addition, preliminary indications suggest a specific association between OCD and bipolar depression (BP-D) in particular, wrote Leonid Braverman, MD, of Ma’ale HaCarmel Mental Health Center, Tirat Carmel, Israel, and colleagues.
In addition, “there is compelling evidence indicating that OCD-spectrum and tic disorders share with OCD clinical characteristics, familial inheritance, neurobiological underpinnings and some aspects of pharmacotherapy,” and investigations into the clinical characteristics of OCD spectrum behaviors in BP-D patients with and without OCD are ongoing, they said.
In a study published in the Journal of Obsessive-Compulsive and Related Disorders (2021 Mar 21. doi: 10.1016/j.jocrd.2021.100643), the researchers reviewed data from 87 adults who met the DSM-5 criteria for BP-D. Of these, 27 also met criteria for OCD, 17 for subthreshold OCD, and 43 had neither OCD nor subthreshold OCD. The researchers compared the 27 OCD patients and the 43 non-OCD patients; the OCD patients had significantly higher rates overall of body dysmorphic disorder, hoarding disorder, excoriation disorder, and tic disorder, compared with non-OCD patients (P range from < .05-0.01 for all). No differences between the groups appeared for trichotillomania.
Also, the researchers found significant between-group differences in the number of patients with at least one OCD spectrum disorder and tic disorders (13 of 19 patients in the OCD group vs. 3 of 37 patients in the non-OCD group) and in the co-occurrence of two OCD-spectrum and tic disorders (3 of 19 patients in the OCD group vs. 1 patient in the non-OCD group).
The most common comorbid psychiatric disorders in both groups were substance use and combined anxiety disorders, followed by eating disorders, but no between-group differences were found in the frequencies of any of these conditions.
“From the clinical perspective, in BP-D patients,” the researchers noted.
The study findings were limited by several factors, including the small sample size, cross-sectional design, and exclusion of subsyndromic disorders, the researchers noted. However, the results support findings from previous studies, and the study emphasizes the clinical complexity and poor prognosis for these patients. Therefore, additional research is needed in patients with BP-D verse the manic/hypomanic phases of bipolar illness to determine similar patterns, they said. Medication trials are needed to address functional impairments in these patients, given the differences in treatment of BDD, hoarding, excoriation, and tic disorders, compared with “pure” OCD, they concluded.
The study received no outside funding. The researchers reported no financial conflicts.
Bipolar disorder patients with comorbid obsessive-compulsive disorder were significantly more likely to suffer from tic disorders, as well as hoarding, excoriation, and body dysmorphic disorder, than were those without comorbid OCD, data from 70 patients suggest.
Between 10% and 20% of patients with bipolar disorder (BD) also meet criteria for obsessive-compulsive disorder (OCD), and these patients are more likely to experience treatment resistance and poor prognosis than are BD patients without OCD. In addition, preliminary indications suggest a specific association between OCD and bipolar depression (BP-D) in particular, wrote Leonid Braverman, MD, of Ma’ale HaCarmel Mental Health Center, Tirat Carmel, Israel, and colleagues.
In addition, “there is compelling evidence indicating that OCD-spectrum and tic disorders share with OCD clinical characteristics, familial inheritance, neurobiological underpinnings and some aspects of pharmacotherapy,” and investigations into the clinical characteristics of OCD spectrum behaviors in BP-D patients with and without OCD are ongoing, they said.
In a study published in the Journal of Obsessive-Compulsive and Related Disorders (2021 Mar 21. doi: 10.1016/j.jocrd.2021.100643), the researchers reviewed data from 87 adults who met the DSM-5 criteria for BP-D. Of these, 27 also met criteria for OCD, 17 for subthreshold OCD, and 43 had neither OCD nor subthreshold OCD. The researchers compared the 27 OCD patients and the 43 non-OCD patients; the OCD patients had significantly higher rates overall of body dysmorphic disorder, hoarding disorder, excoriation disorder, and tic disorder, compared with non-OCD patients (P range from < .05-0.01 for all). No differences between the groups appeared for trichotillomania.
Also, the researchers found significant between-group differences in the number of patients with at least one OCD spectrum disorder and tic disorders (13 of 19 patients in the OCD group vs. 3 of 37 patients in the non-OCD group) and in the co-occurrence of two OCD-spectrum and tic disorders (3 of 19 patients in the OCD group vs. 1 patient in the non-OCD group).
The most common comorbid psychiatric disorders in both groups were substance use and combined anxiety disorders, followed by eating disorders, but no between-group differences were found in the frequencies of any of these conditions.
“From the clinical perspective, in BP-D patients,” the researchers noted.
The study findings were limited by several factors, including the small sample size, cross-sectional design, and exclusion of subsyndromic disorders, the researchers noted. However, the results support findings from previous studies, and the study emphasizes the clinical complexity and poor prognosis for these patients. Therefore, additional research is needed in patients with BP-D verse the manic/hypomanic phases of bipolar illness to determine similar patterns, they said. Medication trials are needed to address functional impairments in these patients, given the differences in treatment of BDD, hoarding, excoriation, and tic disorders, compared with “pure” OCD, they concluded.
The study received no outside funding. The researchers reported no financial conflicts.
FROM THE JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS
Helping psychiatric patients heal holistically
When I was asked to write a regular “Holistic Mental Health” column, I decided to write about the Herculean forces that must come together to create a holistic psychiatrist – someone who specializes in helping patients off their medications rather than on.
My journey began when I told a training psychiatrist that I wanted to stop being a psychiatrist. It was a year after my daughter was born, and I had started my third year of adult psychiatry residency at the University of Maryland in Baltimore. I was stressed and exhausted from working on inpatient psychiatric wards for 2 years, countless unpleasant nights on call, and additional sleepless nights caring for an infant.
I told the training psychiatrist that life wasn’t worth living. Was I suicidal, he asked? I laughed bitterly: “All the time!” Once he heard the S-word, he wanted me to take an antidepressant. I finally gave in and began taking Zoloft 25 mg every morning. Within a week, my angst disappeared; but 5 years, another child, and a fellowship later, I was still taking Zoloft. Why? Without much thought, I stopped it. A month later, I found myself brooding on the sofa, numb with depression, and feeling astonishingly suicidal. This “depression” led me to restart my Zoloft. In a week, my mood normalized. I did this on and off for about a year until a light bulb went off: This can’t be depression. It’s withdrawal. I’ve become dependent on Zoloft! Once I realized this, I began taking some St. John’s wort, an herbal alternative that was supposed to help with depression. I used cheaper brands and discovered that brands do matter, because the cheaper ones didn’t work. Through my haphazard exploration of natural alternatives, I came off Zoloft completely. During this time, I developed greater empathy for my patients, openness to natural alternatives, appreciation for supplement quality, and learned about psychotropic withdrawal. Most importantly, I came to understand a patient’s need to be free.
Five years later, in 2002, I had a thriving, but conventional, private practice. Instead of being content, however, I once again wanted to quit psychiatry. Medicating patients felt unrewarding, but I didn’t have another approach. Simultaneously, my practice was filling up with chronically ill, heavily medicated, bipolar patients. Their intense suffering combined with my discontent with psychiatry made me desperate for something better. In this ripe setting, the mother of a patient with bipolar disorder casually mentioned a supplement called EMPower by Truehope that lessened bipolar symptoms. Though my withdrawal from Zoloft allowed me to be more open to holistic approaches, I waited 3 months before calling. I used the supplement for the first time to help a heavily medicated bipolar patient in her 30’s, whose Depakote side effects caused her to wear a diaper, lack any emotions, and suffer severe tremors. Once I made this decision to walk down this new path, I never went back. With guidance from the company, I used this supplement to help many patients lower their medications. At the time, I wondered whether EMPower would be the solution for all my patients. The simplicity and ease of one supplement approach for all mental illnesses appealed to my laziness, so I continued down the holistic path.
Hundreds of supplements, glandulars, essential oils, and homeopathic remedies later, I learned that every patient requires their own unique approach. A year into using the supplement, I discovered that, if patients took too much of it, their old symptoms would reappear. Eventually, I moved out of my comfort zone and tried other supplements. Subsequently, the universe orchestrated two people to tell me about the miraculous outcomes from “thought-field therapy,” an energy-medicine technique. I began exploring “energy medicine” through the support and instruction of a holistic psychotherapist, Mark Bottinick, LCSW-C. Soon, I was connecting the dots between emotional freedom technique and immediate positive changes. Energy medicine allowed me to heal problems without using a pill! I felt as if I had arrived at Solla Sollew by the banks of the Beautiful River Wah-Hoo.
As I discovered and attended conferences in holistic medicine, I got certified in integrative medicine and became a Reiki master. Even as a novice in holistic medicine, I began to experience patients crying with joy, rather than sadness. One psychotic patient got better on some supplements and got a new job in just 2 weeks.
On Feb. 17, 2021, I launched a podcast called “The Holistic Psychiatrist,” with interviews of patients, conversations with practitioners, and insights from me. Of the initial interviews, two of the three patients had bipolar disorder, and were able to safely and successfully withdraw from many medications. They are no longer patients and are free to move on with their lives. A patient who smoothly and successfully lowered six psychiatric medications will be sharing her wisdom and healing journey soon. A naturopathic doctor will also be sharing his insights and successes. He once was a suicidal high school student failing his classes, depressed and anxious, and dependent on marijuana. His recovery occurred more than a decade ago in my holistic practice.
These patients are living proof that holistic approaches can be very powerful and effective. They demonstrate that chronicity may reflect inadequate treatment and not a definition of disease. Over the course of this Holistic Mental Health column, I want to share many incredible healing journeys and insights on holistic psychiatry. I hope that you will be open to this new paradigm and begin your own holistic journey.
Dr. Lee is a psychiatrist with a solo private practice in Lehi, Utah. She integrates functional/orthomolecular medicine and mind/body/energy medicine in her work with patients. Contact her at holisticpsychiatrist.com. She has no conflicts of interest.
When I was asked to write a regular “Holistic Mental Health” column, I decided to write about the Herculean forces that must come together to create a holistic psychiatrist – someone who specializes in helping patients off their medications rather than on.
My journey began when I told a training psychiatrist that I wanted to stop being a psychiatrist. It was a year after my daughter was born, and I had started my third year of adult psychiatry residency at the University of Maryland in Baltimore. I was stressed and exhausted from working on inpatient psychiatric wards for 2 years, countless unpleasant nights on call, and additional sleepless nights caring for an infant.
I told the training psychiatrist that life wasn’t worth living. Was I suicidal, he asked? I laughed bitterly: “All the time!” Once he heard the S-word, he wanted me to take an antidepressant. I finally gave in and began taking Zoloft 25 mg every morning. Within a week, my angst disappeared; but 5 years, another child, and a fellowship later, I was still taking Zoloft. Why? Without much thought, I stopped it. A month later, I found myself brooding on the sofa, numb with depression, and feeling astonishingly suicidal. This “depression” led me to restart my Zoloft. In a week, my mood normalized. I did this on and off for about a year until a light bulb went off: This can’t be depression. It’s withdrawal. I’ve become dependent on Zoloft! Once I realized this, I began taking some St. John’s wort, an herbal alternative that was supposed to help with depression. I used cheaper brands and discovered that brands do matter, because the cheaper ones didn’t work. Through my haphazard exploration of natural alternatives, I came off Zoloft completely. During this time, I developed greater empathy for my patients, openness to natural alternatives, appreciation for supplement quality, and learned about psychotropic withdrawal. Most importantly, I came to understand a patient’s need to be free.
Five years later, in 2002, I had a thriving, but conventional, private practice. Instead of being content, however, I once again wanted to quit psychiatry. Medicating patients felt unrewarding, but I didn’t have another approach. Simultaneously, my practice was filling up with chronically ill, heavily medicated, bipolar patients. Their intense suffering combined with my discontent with psychiatry made me desperate for something better. In this ripe setting, the mother of a patient with bipolar disorder casually mentioned a supplement called EMPower by Truehope that lessened bipolar symptoms. Though my withdrawal from Zoloft allowed me to be more open to holistic approaches, I waited 3 months before calling. I used the supplement for the first time to help a heavily medicated bipolar patient in her 30’s, whose Depakote side effects caused her to wear a diaper, lack any emotions, and suffer severe tremors. Once I made this decision to walk down this new path, I never went back. With guidance from the company, I used this supplement to help many patients lower their medications. At the time, I wondered whether EMPower would be the solution for all my patients. The simplicity and ease of one supplement approach for all mental illnesses appealed to my laziness, so I continued down the holistic path.
Hundreds of supplements, glandulars, essential oils, and homeopathic remedies later, I learned that every patient requires their own unique approach. A year into using the supplement, I discovered that, if patients took too much of it, their old symptoms would reappear. Eventually, I moved out of my comfort zone and tried other supplements. Subsequently, the universe orchestrated two people to tell me about the miraculous outcomes from “thought-field therapy,” an energy-medicine technique. I began exploring “energy medicine” through the support and instruction of a holistic psychotherapist, Mark Bottinick, LCSW-C. Soon, I was connecting the dots between emotional freedom technique and immediate positive changes. Energy medicine allowed me to heal problems without using a pill! I felt as if I had arrived at Solla Sollew by the banks of the Beautiful River Wah-Hoo.
As I discovered and attended conferences in holistic medicine, I got certified in integrative medicine and became a Reiki master. Even as a novice in holistic medicine, I began to experience patients crying with joy, rather than sadness. One psychotic patient got better on some supplements and got a new job in just 2 weeks.
On Feb. 17, 2021, I launched a podcast called “The Holistic Psychiatrist,” with interviews of patients, conversations with practitioners, and insights from me. Of the initial interviews, two of the three patients had bipolar disorder, and were able to safely and successfully withdraw from many medications. They are no longer patients and are free to move on with their lives. A patient who smoothly and successfully lowered six psychiatric medications will be sharing her wisdom and healing journey soon. A naturopathic doctor will also be sharing his insights and successes. He once was a suicidal high school student failing his classes, depressed and anxious, and dependent on marijuana. His recovery occurred more than a decade ago in my holistic practice.
These patients are living proof that holistic approaches can be very powerful and effective. They demonstrate that chronicity may reflect inadequate treatment and not a definition of disease. Over the course of this Holistic Mental Health column, I want to share many incredible healing journeys and insights on holistic psychiatry. I hope that you will be open to this new paradigm and begin your own holistic journey.
Dr. Lee is a psychiatrist with a solo private practice in Lehi, Utah. She integrates functional/orthomolecular medicine and mind/body/energy medicine in her work with patients. Contact her at holisticpsychiatrist.com. She has no conflicts of interest.
When I was asked to write a regular “Holistic Mental Health” column, I decided to write about the Herculean forces that must come together to create a holistic psychiatrist – someone who specializes in helping patients off their medications rather than on.
My journey began when I told a training psychiatrist that I wanted to stop being a psychiatrist. It was a year after my daughter was born, and I had started my third year of adult psychiatry residency at the University of Maryland in Baltimore. I was stressed and exhausted from working on inpatient psychiatric wards for 2 years, countless unpleasant nights on call, and additional sleepless nights caring for an infant.
I told the training psychiatrist that life wasn’t worth living. Was I suicidal, he asked? I laughed bitterly: “All the time!” Once he heard the S-word, he wanted me to take an antidepressant. I finally gave in and began taking Zoloft 25 mg every morning. Within a week, my angst disappeared; but 5 years, another child, and a fellowship later, I was still taking Zoloft. Why? Without much thought, I stopped it. A month later, I found myself brooding on the sofa, numb with depression, and feeling astonishingly suicidal. This “depression” led me to restart my Zoloft. In a week, my mood normalized. I did this on and off for about a year until a light bulb went off: This can’t be depression. It’s withdrawal. I’ve become dependent on Zoloft! Once I realized this, I began taking some St. John’s wort, an herbal alternative that was supposed to help with depression. I used cheaper brands and discovered that brands do matter, because the cheaper ones didn’t work. Through my haphazard exploration of natural alternatives, I came off Zoloft completely. During this time, I developed greater empathy for my patients, openness to natural alternatives, appreciation for supplement quality, and learned about psychotropic withdrawal. Most importantly, I came to understand a patient’s need to be free.
Five years later, in 2002, I had a thriving, but conventional, private practice. Instead of being content, however, I once again wanted to quit psychiatry. Medicating patients felt unrewarding, but I didn’t have another approach. Simultaneously, my practice was filling up with chronically ill, heavily medicated, bipolar patients. Their intense suffering combined with my discontent with psychiatry made me desperate for something better. In this ripe setting, the mother of a patient with bipolar disorder casually mentioned a supplement called EMPower by Truehope that lessened bipolar symptoms. Though my withdrawal from Zoloft allowed me to be more open to holistic approaches, I waited 3 months before calling. I used the supplement for the first time to help a heavily medicated bipolar patient in her 30’s, whose Depakote side effects caused her to wear a diaper, lack any emotions, and suffer severe tremors. Once I made this decision to walk down this new path, I never went back. With guidance from the company, I used this supplement to help many patients lower their medications. At the time, I wondered whether EMPower would be the solution for all my patients. The simplicity and ease of one supplement approach for all mental illnesses appealed to my laziness, so I continued down the holistic path.
Hundreds of supplements, glandulars, essential oils, and homeopathic remedies later, I learned that every patient requires their own unique approach. A year into using the supplement, I discovered that, if patients took too much of it, their old symptoms would reappear. Eventually, I moved out of my comfort zone and tried other supplements. Subsequently, the universe orchestrated two people to tell me about the miraculous outcomes from “thought-field therapy,” an energy-medicine technique. I began exploring “energy medicine” through the support and instruction of a holistic psychotherapist, Mark Bottinick, LCSW-C. Soon, I was connecting the dots between emotional freedom technique and immediate positive changes. Energy medicine allowed me to heal problems without using a pill! I felt as if I had arrived at Solla Sollew by the banks of the Beautiful River Wah-Hoo.
As I discovered and attended conferences in holistic medicine, I got certified in integrative medicine and became a Reiki master. Even as a novice in holistic medicine, I began to experience patients crying with joy, rather than sadness. One psychotic patient got better on some supplements and got a new job in just 2 weeks.
On Feb. 17, 2021, I launched a podcast called “The Holistic Psychiatrist,” with interviews of patients, conversations with practitioners, and insights from me. Of the initial interviews, two of the three patients had bipolar disorder, and were able to safely and successfully withdraw from many medications. They are no longer patients and are free to move on with their lives. A patient who smoothly and successfully lowered six psychiatric medications will be sharing her wisdom and healing journey soon. A naturopathic doctor will also be sharing his insights and successes. He once was a suicidal high school student failing his classes, depressed and anxious, and dependent on marijuana. His recovery occurred more than a decade ago in my holistic practice.
These patients are living proof that holistic approaches can be very powerful and effective. They demonstrate that chronicity may reflect inadequate treatment and not a definition of disease. Over the course of this Holistic Mental Health column, I want to share many incredible healing journeys and insights on holistic psychiatry. I hope that you will be open to this new paradigm and begin your own holistic journey.
Dr. Lee is a psychiatrist with a solo private practice in Lehi, Utah. She integrates functional/orthomolecular medicine and mind/body/energy medicine in her work with patients. Contact her at holisticpsychiatrist.com. She has no conflicts of interest.
Contradictions abound in ‘The End of Mental Illness’
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Antidepressants, TMS, and the risk of affective switch in bipolar depression
Because treatment resistance is a pervasive problem in bipolar depression, the use of neuromodulation treatments such as transcranial magnetic stimulation (TMS) is increasing for patients with this disorder.1-7 Patients with bipolar disorder tend to spend the majority of the time with depressive symptoms, which underscores the importance of providing effective treatment for bipolar depression, especially given the chronicity of this disease.2,3,5 Only a few medications are FDA-approved for treating bipolar depression (Table).
In this article, we describe the case of a patient with treatment-resistant bipolar depression undergoing adjunctive TMS treatment who experienced an affective switch from depression to mania. We also discuss evidence regarding the likelihood of treatment-emergent mania for antidepressants vs TMS in bipolar depression.
CASE
Ms. W, a 60-year-old White female with a history of bipolar I disorder and attention-deficit/hyperactivity disorder (ADHD), presented for TMS evaluation during a depressive episode. Throughout her life, she had experienced numerous manic episodes, but as she got older she noted an increasing frequency of depressive episodes. Over the course of her illness, she had completed adequate trials at therapeutic doses of many medications, including second-generation antipsychotics (SGAs) (aripiprazole, lurasidone, olanzapine, quetiapine), mood stabilizers (lamotrigine, lithium), and antidepressants (bupropion, venlafaxine, fluoxetine, mirtazapine, trazodone). A course of electroconvulsive therapy was not effective. Ms. W had a long-standing diagnosis of ADHD and had been treated with stimulants for >10 years, although it was unclear whether formal neuropsychological testing had been conducted to confirm this diagnosis. She had >10 suicide attempts and multiple psychiatric hospitalizations.
At her initial evaluation for TMS, Ms. W said she had depressive symptoms predominating for the past 2 years, including low mood, hopelessness, poor sleep, poor appetite, anhedonia, and suicidal ideation without a plan. At the time, she was taking clonazepam, 0.5 mg twice a day; lurasidone, 40 mg/d at bedtime; fluoxetine, 60 mg/d; trazodone, 50 mg/d at bedtime; and methylphenidate, 40 mg/d, and was participating in psychotherapy consistently.
After Ms. W and her clinicians discussed alternatives, risks, benefits, and adverse effects, she consented to adjunctive TMS treatment and provided written informed consent. The treatment plan was outlined as 6 weeks of daily TMS therapy (NeuroStar; Neuronetics, Malvern, PA), 1 treatment per day, 5 days a week. Her clinical status was assessed weekly using the Quick Inventory of Depressive Symptomatology (QIDS) for depression, Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety, and Young Mania Rating Scale (YMRS) for mania. The Figure shows the trends in Ms. W’s QIDS, GAD-7, and YMRS scores over the course of TMS treatment.
Prior to initiating TMS, her baseline scores were QIDS: 25, GAD-7: 9, and YMRS: 7, indicating very severe depression, mild anxiety, and the absence of mania. Ms. W’s psychotropic regimen remained unchanged throughout the course of her TMS treatment. After her motor threshold was determined, her TMS treatment began at 80% of motor threshold and was titrated up to 95% at the first treatment. By the second treatment, it was titrated up to 110%. By the third treatment, it was titrated up to 120% of motor threshold, which is the percentage used for the remaining treatments.
Initially, Ms. W reported some improvement in her depression, but this improvement was short-lived, and she continued to have elevated QIDS scores throughout treatment. By treatment #21, her QIDS and GAD-7 scores remained elevated, and her YMRS score had increased to 12. Due to this increase in YMRS score, the YMRS was repeated on the next 2 treatment days (#22 and #23), and her score was 6 on both days. When Ms. W presented for treatment #25, she was disorganized, irritable, and endorsed racing thoughts and decreased sleep. She was involuntarily hospitalized for mania, and TMS was discontinued. Unfortunately, she did not complete any clinical scales on that day. Upon admission to the hospital, Ms. W reported that at approximately the time of treatment #21, she had a fluctuation in her mood that consisted of increased goal-directed activity, decreased need for sleep, racing thoughts, and increased frivolous spending. She was treated with lithium, 300 mg twice a day. Lurasidone was increased to 80 mg/d at bedtime, and she continued clonazepam, trazodone, and methylphenidate at the previous doses. Over 14 days, Ms. W’s mania gradually resolved, and she was discharged home.
Continue to: Mixed evidence on the risk of switching
Mixed evidence on the risk of switching
Currently, several TMS devices are FDA-cleared for treating unipolar major depressive disorder, obsessive-compulsive disorder, and certain types of migraine. In March 2020, the FDA granted Breakthrough Device Designation for one TMS device, the NeuroStar Advanced Therapy System, for the treatment of bipolar depression.8 This designation created an expedited pathway for prioritized FDA review of the NeuroStar Advanced Therapy clinical trial program.
Few published clinical studies have evaluated using TMS to treat patients with bipolar depression.9-15 As with any antidepressant treatment for bipolar depression, there is a risk of affective switch from depression to mania when using TMS. Most of the literature available regarding the treatment of bipolar depression focuses on the risk of antidepressant medications to induce an affective switch. This risk depends on the class of the antidepressant,16 and there is a paucity of studies examining the risk of switch with TMS.
Interpretation of available literature is limited due to inconsistencies in the definition of an affective switch, the variable length of treatment with antidepressants, the use of concurrent medications such as mood stabilizers, and confounders such as the natural course of switching in bipolar disorder.17 Overall, the evidence for treatment-emergent mania related to antidepressant use is mixed, and the reported rate of treatment-emergent mania varies. In a systematic review and meta-analysis of >20 randomized controlled trials that included 1,316 patients with bipolar disorder who received antidepressants, Fornaro et al18 found that the incidence of treatment-emergent mania was 11.8%. It is generally recommended that if antidepressants are used to treat patients with bipolar disorder, they should be given with a traditional mood stabilizer to prevent affective switches, although whether mood stabilizers can prevent such switches is unproven.19
In a literature review by Xia et al,20 the affective switch rate in patients with bipolar depression who were treated with TMS was 3.1%, which was not statistically different from the affective switch rate with sham treatment.However, most of the patients included in this analysis were receiving other medications concurrently, and the length of treatment was 2 weeks, which is shorter than the average length of TMS treatment in clinical practice. In a recent literature review by Rachid,21 TMS was found to possibly induce manic episodes when used as monotherapy or in combination with antidepressants in patients with bipolar depression. To reduce the risk of treatment-emergent mania, current recommendations advise the use of a mood stabilizer for a minimum of 2 weeks before initiating TMS.1
In our case, Ms. W was receiving antidepressants (fluoxetine and trazodone), lurasidone (an SGA that is FDA-approved for bipolar depression), and methylphenidate before starting TMS treatment. Fluoxetine, trazodone, and methylphenidate may possibly contribute to an increased risk of an affective switch.1,22 Further studies are needed to clarify whether mood stabilizers or SGAs can prevent the development of mania in patients with bipolar depression who undergo TMS treatment.20
Continue to: Because bipolar depression poses...
Because bipolar depression poses a major clinical challenge,23,24 it is imperative to consider alternate treatments. When evaluating alternative treatment strategies, one may consider TMS in conjunction with a traditional mood stabilizer because this regimen may have a lower risk of treatment-emergent mania compared with antidepressants.1,25
Acknowledgment
The authors thank Dr. Sy Saeed for his expertise and guidance on this article.
Bottom Line
For patients with bipolar depression, treatment with transcranial magnetic stimulation in conjunction with a mood stabilizer may have lower rates of treatment-emergent mania than treatment with antidepressants.
Related Resources
- Transcranial magnetic stimulation: clinical applications for psychiatric practice. Bermudes RA, Lanocha K, Janicak PG, eds. American Psychiatric Association Publishing; 2017.
- Gold AK, Ornelas AC, Cirillo P, et al. Clinical applications of transcranial magnetic stimulation in bipolar disorder. Brain Behav. 2019;9(10):e01419. doi: 10.1002/brb3.1419
Drug Brand Names
Aripiprazole • Abilify
Bupropion • Wellbutrin
Cariprazine • Vraylar
Clonazepam • Klonopin
Fluoxetine • Prozac
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Methylphenidate • Ritalin, Concerta
Mirtazapine • Remeron
Olanzapine • Zyprexa
Olanzapine-fluoxetine • Symbyax
Quetiapine • Seroquel
Trazodone • Desyrel
Venlafaxine • Effexor
1. Aaronson ST, Croarkin PE. Transcranial magnetic stimulation for the treatment of other mood disorders. In: Bermudes RA, Lanocha K, Janicak PG, eds. Transcranial magnetic stimulation: clinical applications for psychiatric practice. American Psychiatric Association Publishing; 2017:127-156.
2. Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672-1682.
3. Gitlin M. Treatment-resistant bipolar disorder. Molecular Psychiatry. 2006;11(3):227-240.
4. Harrison PJ, Geddes JR, Tunbridge EM. The emerging neurobiology of bipolar disorder. Trends Neurosci. 2018;41(1):18-30.
5. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry. 2011;68(3):241-251.
6. Myczkowski ML, Fernandes A, Moreno M, et al. Cognitive outcomes of TMS treatment in bipolar depression: safety data from a randomized controlled trial. J Affect Disord. 2018;235: 20-26.
7. Tavares DF, Myczkowski ML, Alberto RL, et al. Treatment of bipolar depression with deep TMS: results from a double-blind, randomized, parallel group, sham-controlled clinical trial. Neuropsychopharmacology. 2017;42(13):2593-2601.
8. Neuronetics. FDA grants NeuroStar® Advanced Therapy System Breakthrough Device Designation to treat bipolar depression. Accessed February 2, 2021. https://www.globenewswire.com/news-release/2020/03/06/1996447/0/en/FDA-Grants-NeuroStar-Advanced-Therapy-System-Breakthrough-Device-Designation-to-Treat-Bipolar-Depression.html
9. Cohen RB, Brunoni AR, Boggio PS, et al. Clinical predictors associated with duration of repetitive transcranial magnetic stimulation treatment for remission in bipolar depression: a naturalistic study. J Nerv Ment Dis. 2010;198(9):679-681.
10. Connolly KR, Helmer A, Cristancho MA, et al. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry. 2012;73(4):e567-e573.
11. Dell’osso B, D’Urso N, Castellano F, et al. Long-term efficacy after acute augmentative repetitive transcranial magnetic stimulation in bipolar depression: a 1-year follow-up study. J ECT. 2011;27(2):141-144.
12. Dell’Osso B, Mundo E, D’Urso N, et al. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord. 2009;11(1):76-81.
13. Harel EV, Zangen A, Roth Y, et al. H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World J Biol Psychiatry. 2011;12(2):119-126.
14. Nahas Z, Kozel FA, Li X, et al. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord. 2003;5(1):40-47.
15. Tamas RL, Menkes D, El-Mallakh RS. Stimulating research: a prospective, randomized, double-blind, sham-controlled study of slow transcranial magnetic stimulation in depressed bipolar patients. J Neuropsychiatry Clin Neurosci. 2007;19(2):198-199.
16. Tundo A, Cavalieri P, Navari S, et al. Treating bipolar depression - antidepressants and alternatives: a critical review of the literature. Acta Neuropsychiatrica. 2011:23(3):94-105.
17. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):1537-1547.
18. Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant‐emergent mania in bipolar depression: a systematic review and meta‐analysis. Bipolar Disord. 2018;20(3):195-227.
19. Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170(11):1249-1262.
20. Xia G, Gajwani P, Muzina DJ, et al. Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2008;11(1):119-130.
21. Rachid F. Repetitive transcranial magnetic stimulation and treatment-emergent mania and hypomania: a review of the literature. J Psychiatr Pract. 2017;23(2):150-159.
22. Victorin A, Rydén E, Thase M, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry. 2017;174(4):341-348.
23. Hidalgo-Mazzei D, Berk M, Cipriani A, et al. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition. Br J Psychiatry. 2019;214(1):27-35.
24. Baldessarini RJ, Vázquez GH, Tondo L. Bipolar depression: a major unsolved challenge. Int J Bipolar Disord. 2020;8(1):1.
25. Phillips AL, Burr RL, Dunner DL. Repetitive transcranial magnetic stimulation in the treatment of bipolar depression: Experience from a clinical setting. J Psychiatr Pract. 2020;26(1):37-45.
Because treatment resistance is a pervasive problem in bipolar depression, the use of neuromodulation treatments such as transcranial magnetic stimulation (TMS) is increasing for patients with this disorder.1-7 Patients with bipolar disorder tend to spend the majority of the time with depressive symptoms, which underscores the importance of providing effective treatment for bipolar depression, especially given the chronicity of this disease.2,3,5 Only a few medications are FDA-approved for treating bipolar depression (Table).
In this article, we describe the case of a patient with treatment-resistant bipolar depression undergoing adjunctive TMS treatment who experienced an affective switch from depression to mania. We also discuss evidence regarding the likelihood of treatment-emergent mania for antidepressants vs TMS in bipolar depression.
CASE
Ms. W, a 60-year-old White female with a history of bipolar I disorder and attention-deficit/hyperactivity disorder (ADHD), presented for TMS evaluation during a depressive episode. Throughout her life, she had experienced numerous manic episodes, but as she got older she noted an increasing frequency of depressive episodes. Over the course of her illness, she had completed adequate trials at therapeutic doses of many medications, including second-generation antipsychotics (SGAs) (aripiprazole, lurasidone, olanzapine, quetiapine), mood stabilizers (lamotrigine, lithium), and antidepressants (bupropion, venlafaxine, fluoxetine, mirtazapine, trazodone). A course of electroconvulsive therapy was not effective. Ms. W had a long-standing diagnosis of ADHD and had been treated with stimulants for >10 years, although it was unclear whether formal neuropsychological testing had been conducted to confirm this diagnosis. She had >10 suicide attempts and multiple psychiatric hospitalizations.
At her initial evaluation for TMS, Ms. W said she had depressive symptoms predominating for the past 2 years, including low mood, hopelessness, poor sleep, poor appetite, anhedonia, and suicidal ideation without a plan. At the time, she was taking clonazepam, 0.5 mg twice a day; lurasidone, 40 mg/d at bedtime; fluoxetine, 60 mg/d; trazodone, 50 mg/d at bedtime; and methylphenidate, 40 mg/d, and was participating in psychotherapy consistently.
After Ms. W and her clinicians discussed alternatives, risks, benefits, and adverse effects, she consented to adjunctive TMS treatment and provided written informed consent. The treatment plan was outlined as 6 weeks of daily TMS therapy (NeuroStar; Neuronetics, Malvern, PA), 1 treatment per day, 5 days a week. Her clinical status was assessed weekly using the Quick Inventory of Depressive Symptomatology (QIDS) for depression, Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety, and Young Mania Rating Scale (YMRS) for mania. The Figure shows the trends in Ms. W’s QIDS, GAD-7, and YMRS scores over the course of TMS treatment.
Prior to initiating TMS, her baseline scores were QIDS: 25, GAD-7: 9, and YMRS: 7, indicating very severe depression, mild anxiety, and the absence of mania. Ms. W’s psychotropic regimen remained unchanged throughout the course of her TMS treatment. After her motor threshold was determined, her TMS treatment began at 80% of motor threshold and was titrated up to 95% at the first treatment. By the second treatment, it was titrated up to 110%. By the third treatment, it was titrated up to 120% of motor threshold, which is the percentage used for the remaining treatments.
Initially, Ms. W reported some improvement in her depression, but this improvement was short-lived, and she continued to have elevated QIDS scores throughout treatment. By treatment #21, her QIDS and GAD-7 scores remained elevated, and her YMRS score had increased to 12. Due to this increase in YMRS score, the YMRS was repeated on the next 2 treatment days (#22 and #23), and her score was 6 on both days. When Ms. W presented for treatment #25, she was disorganized, irritable, and endorsed racing thoughts and decreased sleep. She was involuntarily hospitalized for mania, and TMS was discontinued. Unfortunately, she did not complete any clinical scales on that day. Upon admission to the hospital, Ms. W reported that at approximately the time of treatment #21, she had a fluctuation in her mood that consisted of increased goal-directed activity, decreased need for sleep, racing thoughts, and increased frivolous spending. She was treated with lithium, 300 mg twice a day. Lurasidone was increased to 80 mg/d at bedtime, and she continued clonazepam, trazodone, and methylphenidate at the previous doses. Over 14 days, Ms. W’s mania gradually resolved, and she was discharged home.
Continue to: Mixed evidence on the risk of switching
Mixed evidence on the risk of switching
Currently, several TMS devices are FDA-cleared for treating unipolar major depressive disorder, obsessive-compulsive disorder, and certain types of migraine. In March 2020, the FDA granted Breakthrough Device Designation for one TMS device, the NeuroStar Advanced Therapy System, for the treatment of bipolar depression.8 This designation created an expedited pathway for prioritized FDA review of the NeuroStar Advanced Therapy clinical trial program.
Few published clinical studies have evaluated using TMS to treat patients with bipolar depression.9-15 As with any antidepressant treatment for bipolar depression, there is a risk of affective switch from depression to mania when using TMS. Most of the literature available regarding the treatment of bipolar depression focuses on the risk of antidepressant medications to induce an affective switch. This risk depends on the class of the antidepressant,16 and there is a paucity of studies examining the risk of switch with TMS.
Interpretation of available literature is limited due to inconsistencies in the definition of an affective switch, the variable length of treatment with antidepressants, the use of concurrent medications such as mood stabilizers, and confounders such as the natural course of switching in bipolar disorder.17 Overall, the evidence for treatment-emergent mania related to antidepressant use is mixed, and the reported rate of treatment-emergent mania varies. In a systematic review and meta-analysis of >20 randomized controlled trials that included 1,316 patients with bipolar disorder who received antidepressants, Fornaro et al18 found that the incidence of treatment-emergent mania was 11.8%. It is generally recommended that if antidepressants are used to treat patients with bipolar disorder, they should be given with a traditional mood stabilizer to prevent affective switches, although whether mood stabilizers can prevent such switches is unproven.19
In a literature review by Xia et al,20 the affective switch rate in patients with bipolar depression who were treated with TMS was 3.1%, which was not statistically different from the affective switch rate with sham treatment.However, most of the patients included in this analysis were receiving other medications concurrently, and the length of treatment was 2 weeks, which is shorter than the average length of TMS treatment in clinical practice. In a recent literature review by Rachid,21 TMS was found to possibly induce manic episodes when used as monotherapy or in combination with antidepressants in patients with bipolar depression. To reduce the risk of treatment-emergent mania, current recommendations advise the use of a mood stabilizer for a minimum of 2 weeks before initiating TMS.1
In our case, Ms. W was receiving antidepressants (fluoxetine and trazodone), lurasidone (an SGA that is FDA-approved for bipolar depression), and methylphenidate before starting TMS treatment. Fluoxetine, trazodone, and methylphenidate may possibly contribute to an increased risk of an affective switch.1,22 Further studies are needed to clarify whether mood stabilizers or SGAs can prevent the development of mania in patients with bipolar depression who undergo TMS treatment.20
Continue to: Because bipolar depression poses...
Because bipolar depression poses a major clinical challenge,23,24 it is imperative to consider alternate treatments. When evaluating alternative treatment strategies, one may consider TMS in conjunction with a traditional mood stabilizer because this regimen may have a lower risk of treatment-emergent mania compared with antidepressants.1,25
Acknowledgment
The authors thank Dr. Sy Saeed for his expertise and guidance on this article.
Bottom Line
For patients with bipolar depression, treatment with transcranial magnetic stimulation in conjunction with a mood stabilizer may have lower rates of treatment-emergent mania than treatment with antidepressants.
Related Resources
- Transcranial magnetic stimulation: clinical applications for psychiatric practice. Bermudes RA, Lanocha K, Janicak PG, eds. American Psychiatric Association Publishing; 2017.
- Gold AK, Ornelas AC, Cirillo P, et al. Clinical applications of transcranial magnetic stimulation in bipolar disorder. Brain Behav. 2019;9(10):e01419. doi: 10.1002/brb3.1419
Drug Brand Names
Aripiprazole • Abilify
Bupropion • Wellbutrin
Cariprazine • Vraylar
Clonazepam • Klonopin
Fluoxetine • Prozac
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Methylphenidate • Ritalin, Concerta
Mirtazapine • Remeron
Olanzapine • Zyprexa
Olanzapine-fluoxetine • Symbyax
Quetiapine • Seroquel
Trazodone • Desyrel
Venlafaxine • Effexor
Because treatment resistance is a pervasive problem in bipolar depression, the use of neuromodulation treatments such as transcranial magnetic stimulation (TMS) is increasing for patients with this disorder.1-7 Patients with bipolar disorder tend to spend the majority of the time with depressive symptoms, which underscores the importance of providing effective treatment for bipolar depression, especially given the chronicity of this disease.2,3,5 Only a few medications are FDA-approved for treating bipolar depression (Table).
In this article, we describe the case of a patient with treatment-resistant bipolar depression undergoing adjunctive TMS treatment who experienced an affective switch from depression to mania. We also discuss evidence regarding the likelihood of treatment-emergent mania for antidepressants vs TMS in bipolar depression.
CASE
Ms. W, a 60-year-old White female with a history of bipolar I disorder and attention-deficit/hyperactivity disorder (ADHD), presented for TMS evaluation during a depressive episode. Throughout her life, she had experienced numerous manic episodes, but as she got older she noted an increasing frequency of depressive episodes. Over the course of her illness, she had completed adequate trials at therapeutic doses of many medications, including second-generation antipsychotics (SGAs) (aripiprazole, lurasidone, olanzapine, quetiapine), mood stabilizers (lamotrigine, lithium), and antidepressants (bupropion, venlafaxine, fluoxetine, mirtazapine, trazodone). A course of electroconvulsive therapy was not effective. Ms. W had a long-standing diagnosis of ADHD and had been treated with stimulants for >10 years, although it was unclear whether formal neuropsychological testing had been conducted to confirm this diagnosis. She had >10 suicide attempts and multiple psychiatric hospitalizations.
At her initial evaluation for TMS, Ms. W said she had depressive symptoms predominating for the past 2 years, including low mood, hopelessness, poor sleep, poor appetite, anhedonia, and suicidal ideation without a plan. At the time, she was taking clonazepam, 0.5 mg twice a day; lurasidone, 40 mg/d at bedtime; fluoxetine, 60 mg/d; trazodone, 50 mg/d at bedtime; and methylphenidate, 40 mg/d, and was participating in psychotherapy consistently.
After Ms. W and her clinicians discussed alternatives, risks, benefits, and adverse effects, she consented to adjunctive TMS treatment and provided written informed consent. The treatment plan was outlined as 6 weeks of daily TMS therapy (NeuroStar; Neuronetics, Malvern, PA), 1 treatment per day, 5 days a week. Her clinical status was assessed weekly using the Quick Inventory of Depressive Symptomatology (QIDS) for depression, Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety, and Young Mania Rating Scale (YMRS) for mania. The Figure shows the trends in Ms. W’s QIDS, GAD-7, and YMRS scores over the course of TMS treatment.
Prior to initiating TMS, her baseline scores were QIDS: 25, GAD-7: 9, and YMRS: 7, indicating very severe depression, mild anxiety, and the absence of mania. Ms. W’s psychotropic regimen remained unchanged throughout the course of her TMS treatment. After her motor threshold was determined, her TMS treatment began at 80% of motor threshold and was titrated up to 95% at the first treatment. By the second treatment, it was titrated up to 110%. By the third treatment, it was titrated up to 120% of motor threshold, which is the percentage used for the remaining treatments.
Initially, Ms. W reported some improvement in her depression, but this improvement was short-lived, and she continued to have elevated QIDS scores throughout treatment. By treatment #21, her QIDS and GAD-7 scores remained elevated, and her YMRS score had increased to 12. Due to this increase in YMRS score, the YMRS was repeated on the next 2 treatment days (#22 and #23), and her score was 6 on both days. When Ms. W presented for treatment #25, she was disorganized, irritable, and endorsed racing thoughts and decreased sleep. She was involuntarily hospitalized for mania, and TMS was discontinued. Unfortunately, she did not complete any clinical scales on that day. Upon admission to the hospital, Ms. W reported that at approximately the time of treatment #21, she had a fluctuation in her mood that consisted of increased goal-directed activity, decreased need for sleep, racing thoughts, and increased frivolous spending. She was treated with lithium, 300 mg twice a day. Lurasidone was increased to 80 mg/d at bedtime, and she continued clonazepam, trazodone, and methylphenidate at the previous doses. Over 14 days, Ms. W’s mania gradually resolved, and she was discharged home.
Continue to: Mixed evidence on the risk of switching
Mixed evidence on the risk of switching
Currently, several TMS devices are FDA-cleared for treating unipolar major depressive disorder, obsessive-compulsive disorder, and certain types of migraine. In March 2020, the FDA granted Breakthrough Device Designation for one TMS device, the NeuroStar Advanced Therapy System, for the treatment of bipolar depression.8 This designation created an expedited pathway for prioritized FDA review of the NeuroStar Advanced Therapy clinical trial program.
Few published clinical studies have evaluated using TMS to treat patients with bipolar depression.9-15 As with any antidepressant treatment for bipolar depression, there is a risk of affective switch from depression to mania when using TMS. Most of the literature available regarding the treatment of bipolar depression focuses on the risk of antidepressant medications to induce an affective switch. This risk depends on the class of the antidepressant,16 and there is a paucity of studies examining the risk of switch with TMS.
Interpretation of available literature is limited due to inconsistencies in the definition of an affective switch, the variable length of treatment with antidepressants, the use of concurrent medications such as mood stabilizers, and confounders such as the natural course of switching in bipolar disorder.17 Overall, the evidence for treatment-emergent mania related to antidepressant use is mixed, and the reported rate of treatment-emergent mania varies. In a systematic review and meta-analysis of >20 randomized controlled trials that included 1,316 patients with bipolar disorder who received antidepressants, Fornaro et al18 found that the incidence of treatment-emergent mania was 11.8%. It is generally recommended that if antidepressants are used to treat patients with bipolar disorder, they should be given with a traditional mood stabilizer to prevent affective switches, although whether mood stabilizers can prevent such switches is unproven.19
In a literature review by Xia et al,20 the affective switch rate in patients with bipolar depression who were treated with TMS was 3.1%, which was not statistically different from the affective switch rate with sham treatment.However, most of the patients included in this analysis were receiving other medications concurrently, and the length of treatment was 2 weeks, which is shorter than the average length of TMS treatment in clinical practice. In a recent literature review by Rachid,21 TMS was found to possibly induce manic episodes when used as monotherapy or in combination with antidepressants in patients with bipolar depression. To reduce the risk of treatment-emergent mania, current recommendations advise the use of a mood stabilizer for a minimum of 2 weeks before initiating TMS.1
In our case, Ms. W was receiving antidepressants (fluoxetine and trazodone), lurasidone (an SGA that is FDA-approved for bipolar depression), and methylphenidate before starting TMS treatment. Fluoxetine, trazodone, and methylphenidate may possibly contribute to an increased risk of an affective switch.1,22 Further studies are needed to clarify whether mood stabilizers or SGAs can prevent the development of mania in patients with bipolar depression who undergo TMS treatment.20
Continue to: Because bipolar depression poses...
Because bipolar depression poses a major clinical challenge,23,24 it is imperative to consider alternate treatments. When evaluating alternative treatment strategies, one may consider TMS in conjunction with a traditional mood stabilizer because this regimen may have a lower risk of treatment-emergent mania compared with antidepressants.1,25
Acknowledgment
The authors thank Dr. Sy Saeed for his expertise and guidance on this article.
Bottom Line
For patients with bipolar depression, treatment with transcranial magnetic stimulation in conjunction with a mood stabilizer may have lower rates of treatment-emergent mania than treatment with antidepressants.
Related Resources
- Transcranial magnetic stimulation: clinical applications for psychiatric practice. Bermudes RA, Lanocha K, Janicak PG, eds. American Psychiatric Association Publishing; 2017.
- Gold AK, Ornelas AC, Cirillo P, et al. Clinical applications of transcranial magnetic stimulation in bipolar disorder. Brain Behav. 2019;9(10):e01419. doi: 10.1002/brb3.1419
Drug Brand Names
Aripiprazole • Abilify
Bupropion • Wellbutrin
Cariprazine • Vraylar
Clonazepam • Klonopin
Fluoxetine • Prozac
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Methylphenidate • Ritalin, Concerta
Mirtazapine • Remeron
Olanzapine • Zyprexa
Olanzapine-fluoxetine • Symbyax
Quetiapine • Seroquel
Trazodone • Desyrel
Venlafaxine • Effexor
1. Aaronson ST, Croarkin PE. Transcranial magnetic stimulation for the treatment of other mood disorders. In: Bermudes RA, Lanocha K, Janicak PG, eds. Transcranial magnetic stimulation: clinical applications for psychiatric practice. American Psychiatric Association Publishing; 2017:127-156.
2. Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672-1682.
3. Gitlin M. Treatment-resistant bipolar disorder. Molecular Psychiatry. 2006;11(3):227-240.
4. Harrison PJ, Geddes JR, Tunbridge EM. The emerging neurobiology of bipolar disorder. Trends Neurosci. 2018;41(1):18-30.
5. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry. 2011;68(3):241-251.
6. Myczkowski ML, Fernandes A, Moreno M, et al. Cognitive outcomes of TMS treatment in bipolar depression: safety data from a randomized controlled trial. J Affect Disord. 2018;235: 20-26.
7. Tavares DF, Myczkowski ML, Alberto RL, et al. Treatment of bipolar depression with deep TMS: results from a double-blind, randomized, parallel group, sham-controlled clinical trial. Neuropsychopharmacology. 2017;42(13):2593-2601.
8. Neuronetics. FDA grants NeuroStar® Advanced Therapy System Breakthrough Device Designation to treat bipolar depression. Accessed February 2, 2021. https://www.globenewswire.com/news-release/2020/03/06/1996447/0/en/FDA-Grants-NeuroStar-Advanced-Therapy-System-Breakthrough-Device-Designation-to-Treat-Bipolar-Depression.html
9. Cohen RB, Brunoni AR, Boggio PS, et al. Clinical predictors associated with duration of repetitive transcranial magnetic stimulation treatment for remission in bipolar depression: a naturalistic study. J Nerv Ment Dis. 2010;198(9):679-681.
10. Connolly KR, Helmer A, Cristancho MA, et al. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry. 2012;73(4):e567-e573.
11. Dell’osso B, D’Urso N, Castellano F, et al. Long-term efficacy after acute augmentative repetitive transcranial magnetic stimulation in bipolar depression: a 1-year follow-up study. J ECT. 2011;27(2):141-144.
12. Dell’Osso B, Mundo E, D’Urso N, et al. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord. 2009;11(1):76-81.
13. Harel EV, Zangen A, Roth Y, et al. H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World J Biol Psychiatry. 2011;12(2):119-126.
14. Nahas Z, Kozel FA, Li X, et al. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord. 2003;5(1):40-47.
15. Tamas RL, Menkes D, El-Mallakh RS. Stimulating research: a prospective, randomized, double-blind, sham-controlled study of slow transcranial magnetic stimulation in depressed bipolar patients. J Neuropsychiatry Clin Neurosci. 2007;19(2):198-199.
16. Tundo A, Cavalieri P, Navari S, et al. Treating bipolar depression - antidepressants and alternatives: a critical review of the literature. Acta Neuropsychiatrica. 2011:23(3):94-105.
17. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):1537-1547.
18. Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant‐emergent mania in bipolar depression: a systematic review and meta‐analysis. Bipolar Disord. 2018;20(3):195-227.
19. Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170(11):1249-1262.
20. Xia G, Gajwani P, Muzina DJ, et al. Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2008;11(1):119-130.
21. Rachid F. Repetitive transcranial magnetic stimulation and treatment-emergent mania and hypomania: a review of the literature. J Psychiatr Pract. 2017;23(2):150-159.
22. Victorin A, Rydén E, Thase M, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry. 2017;174(4):341-348.
23. Hidalgo-Mazzei D, Berk M, Cipriani A, et al. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition. Br J Psychiatry. 2019;214(1):27-35.
24. Baldessarini RJ, Vázquez GH, Tondo L. Bipolar depression: a major unsolved challenge. Int J Bipolar Disord. 2020;8(1):1.
25. Phillips AL, Burr RL, Dunner DL. Repetitive transcranial magnetic stimulation in the treatment of bipolar depression: Experience from a clinical setting. J Psychiatr Pract. 2020;26(1):37-45.
1. Aaronson ST, Croarkin PE. Transcranial magnetic stimulation for the treatment of other mood disorders. In: Bermudes RA, Lanocha K, Janicak PG, eds. Transcranial magnetic stimulation: clinical applications for psychiatric practice. American Psychiatric Association Publishing; 2017:127-156.
2. Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672-1682.
3. Gitlin M. Treatment-resistant bipolar disorder. Molecular Psychiatry. 2006;11(3):227-240.
4. Harrison PJ, Geddes JR, Tunbridge EM. The emerging neurobiology of bipolar disorder. Trends Neurosci. 2018;41(1):18-30.
5. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry. 2011;68(3):241-251.
6. Myczkowski ML, Fernandes A, Moreno M, et al. Cognitive outcomes of TMS treatment in bipolar depression: safety data from a randomized controlled trial. J Affect Disord. 2018;235: 20-26.
7. Tavares DF, Myczkowski ML, Alberto RL, et al. Treatment of bipolar depression with deep TMS: results from a double-blind, randomized, parallel group, sham-controlled clinical trial. Neuropsychopharmacology. 2017;42(13):2593-2601.
8. Neuronetics. FDA grants NeuroStar® Advanced Therapy System Breakthrough Device Designation to treat bipolar depression. Accessed February 2, 2021. https://www.globenewswire.com/news-release/2020/03/06/1996447/0/en/FDA-Grants-NeuroStar-Advanced-Therapy-System-Breakthrough-Device-Designation-to-Treat-Bipolar-Depression.html
9. Cohen RB, Brunoni AR, Boggio PS, et al. Clinical predictors associated with duration of repetitive transcranial magnetic stimulation treatment for remission in bipolar depression: a naturalistic study. J Nerv Ment Dis. 2010;198(9):679-681.
10. Connolly KR, Helmer A, Cristancho MA, et al. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry. 2012;73(4):e567-e573.
11. Dell’osso B, D’Urso N, Castellano F, et al. Long-term efficacy after acute augmentative repetitive transcranial magnetic stimulation in bipolar depression: a 1-year follow-up study. J ECT. 2011;27(2):141-144.
12. Dell’Osso B, Mundo E, D’Urso N, et al. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord. 2009;11(1):76-81.
13. Harel EV, Zangen A, Roth Y, et al. H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World J Biol Psychiatry. 2011;12(2):119-126.
14. Nahas Z, Kozel FA, Li X, et al. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord. 2003;5(1):40-47.
15. Tamas RL, Menkes D, El-Mallakh RS. Stimulating research: a prospective, randomized, double-blind, sham-controlled study of slow transcranial magnetic stimulation in depressed bipolar patients. J Neuropsychiatry Clin Neurosci. 2007;19(2):198-199.
16. Tundo A, Cavalieri P, Navari S, et al. Treating bipolar depression - antidepressants and alternatives: a critical review of the literature. Acta Neuropsychiatrica. 2011:23(3):94-105.
17. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):1537-1547.
18. Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant‐emergent mania in bipolar depression: a systematic review and meta‐analysis. Bipolar Disord. 2018;20(3):195-227.
19. Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170(11):1249-1262.
20. Xia G, Gajwani P, Muzina DJ, et al. Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2008;11(1):119-130.
21. Rachid F. Repetitive transcranial magnetic stimulation and treatment-emergent mania and hypomania: a review of the literature. J Psychiatr Pract. 2017;23(2):150-159.
22. Victorin A, Rydén E, Thase M, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry. 2017;174(4):341-348.
23. Hidalgo-Mazzei D, Berk M, Cipriani A, et al. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition. Br J Psychiatry. 2019;214(1):27-35.
24. Baldessarini RJ, Vázquez GH, Tondo L. Bipolar depression: a major unsolved challenge. Int J Bipolar Disord. 2020;8(1):1.
25. Phillips AL, Burr RL, Dunner DL. Repetitive transcranial magnetic stimulation in the treatment of bipolar depression: Experience from a clinical setting. J Psychiatr Pract. 2020;26(1):37-45.
Steroid-induced psychiatric symptoms: What you need to know
Ms. N, age 30, presents to the emergency department for altered mental status, insomnia, and behavioral changes, which she has experienced for 1 week. On evaluation, she grabs a clinician’s hand and details her business ideas and life story with no prompting. Ms. N’s mental status examination is significant for hyperverbal speech with increased rate and volume; tangential thought process; and bright, expanded affect.
One week earlier, Ms. N was hospitalized for sudden-onset chest pain, weakness, and dizziness. She received 45 minutes of cardiopulmonary resuscitation prior to presentation and was found to have a ST-segment elevation myocardial infarction that required emergent left anterior descending coronary artery and right coronary artery percutaneous coronary intervention to place drug-eluting stents. Her recovery was complicated by acute cardiogenic shock, pulmonary edema, and hypoxic respiratory failure. Subsequently, she was intubated, admitted to the ICU, and received high-dose corticosteroids, including IV methylprednisolone, 40 mg every 12 hours, which was tapered prior to discharge. Her husband reports that since Ms. N came home, she has been more talkative and irritable, ruminating about past events, unable to sleep (<1 hour/night), and crying frequently. She has also been endorsing visual and auditory hallucinations, with increased praying and listening to religious music.
The frequent clinical use of steroids necessitates an understanding of these medications’ various adverse effects. The manifestations of steroid-induced psychiatric symptoms are broad and can involve affective, behavioral, and cognitive domains. While the current mechanism is unknown, this phenomenon may be related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity, as well as effects on brain regions such as the hippocampus and amygdala. The best interventions for steroid-induced psychiatric symptoms are awareness and early diagnosis. There are no FDA-approved treatments for steroid-induced psychiatric symptoms; initial measures should include tapering or discontinuing corticosteroids.
In this article, we review the literature on the incidence, characteristics, differential diagnoses, proposed mechanism, risk factors, and proposed treatments of steroid-induced psychiatric symptoms.
A wide range of presentations
Steroid use has increased over the past 2 decades, with 10% of medical and surgical inpatients and 1% to 3% of the general population taking long-term glucocorticoids.1 Even with topical application, steroid therapy is often systemically absorbed, and thus may lead to steroid-induced psychiatric symptoms. The incidence of steroid-induced psychiatric symptoms is difficult to assess because there can be a wide range of reactions that are dose- and time-related. Three reviews of a total of 122 cases reports found that an estimated 5% of patients treated with steroids experience severe psychiatric reactions.1-3
Steroid-induced psychopathology can include mood, behavioral, and/or cognitive impairments. Mania/hypomania is the most common overall psychiatric symptom; the most common mood manifestations are anxiety and depression.4,5 Other possible steroid-induced symptoms include psychosis, dementia, panic disorder, delirium, suicidal thinking and behavior, aggressive behavior, insomnia, agitation, depersonalization, and euphoria.5 The most common cognitive impairment is verbal or declarative memory deficit; others include distractibility and deficits in attention and psychomotor speed.5 These psychiatric symptoms can have a rapid onset, possibly within hours of starting steroids.1 However, studies have reported a median time to onset of 11.5 days; 39% of cases had onset during the first week and 62% within 2 weeks.3,6 After reducing or stopping the steroid, it may take days to weeks before symptoms start to subside.2
What to consider in the differential Dx
Psychiatric symptoms that are induced by steroids can mimic metabolic, neurologic, or toxic disorders. Other factors to consider include drug withdrawal/intoxication, infections, and paraneoplastic syndromes.4,5 Although there is no reported correlation between the location of neurologic lesions and the development of specific psychiatric symptoms, manic symptoms appear most commonly with lesions in the right frontal lobe. 4 Other factors to note include the presence of new-onset psychiatric illnesses such as bipolar, mood, or thought disorders,4 as well as psychosocial stressors that might be contributing to the patient’s presentation.5
Continue to: Proposed mechanisms
Proposed mechanisms
Although the exact mechanism by which steroids induce psychiatric symptoms is unknown, several mechanisms have been proposed. One hypothesis is that steroid-induced psychopathology is related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity.4,5,7 This may explain why many patients with major depressive disorder have elevated cortisol production and/or lack of suppression of cortisol secretion during a dexamethasone stimulation test, and why approximately one-half of patients with Cushing’s disease experience depressive symptoms.8 This is also likely why antipsychotics, which typically reduce cortisol, are efficacious treatments for some steroid-induced psychiatric symptoms.9
Cognitive impairments from steroid use may be related to these agents’ effects on certain brain regions. One such area is the hippocampus, an important mediator in the creation and maintenance of episodic and declarative memories.5,8,9 Acute glucocorticoid use is associated with decreased activity in the left hippocampus, reduced hippocampal glucose metabolism, and reduced cerebral blood flow in the posterior medial temporal lobe.10 Long-term glucocorticoid exposure is associated with smaller hippocampal volume and lower levels of temporal lobe N-acetylaspartate, a marker of neuronal viability.10 Because working memory depends on the prefrontal cortex and declarative memory relies on the hippocampus, deficits in these functions can be attributed to the effect of prolonged glucocorticoid exposure on glucocorticoid or mineralocorticoid receptors in the hippocampus, reduction of hippocampal volume, or elevated glutamate accumulation in that area.11 In addition, high cortisol levels inhibit brain-derived neurotrophic factor, which plays a crucial role in maintaining neural architecture in key brain regions such as the hippocampus and prefrontal cortex.11 There is also a correlation between the duration of prednisone treatment and atrophy of the right amygdala, which is an important regulator of mood and anxiety.11 Both the hippocampus and amygdala have dense collections of glucocorticoid receptors. This may explain why patients who receive high-dose corticosteroids can have reversible atrophy in the hypothalamus and amygdala, leading to deficits in emotional learning and the stress response.
Factors that increase risk
Several factors can increase the risk of steroid-induced psychopathology. The most significant is the dose; higher doses are more likely to produce psychiatric symptoms.1,5 Concurrent use of drugs that increase circulating levels of corticosteroids, such as inhibitors of the cytochrome P450 (CYP) enzyme (eg, clarithromycin), also increases the likelihood of developing psychiatric symptoms.1,5 Risk is also increased in patients with liver or renal dysfunction.1 Cerebral spinal fluid/serum albumin ratio, a marker of blood-brain barrier damage, and low serum complement levels were also reported to be independent risk factors,12 with the thought that increased permeability of the blood-brain barrier may allow hydrophobic steroid molecules to more easily penetrate the CNS, leading to increased neuropsychiatric effects. Hypoalbuminemia is another reported risk factor, perhaps because lower levels of serum albumin are related to higher levels of free and active glucocorticoids, which are normally inactive when bound to albumin.13 There also appears to be an increased prevalence of steroid-induced psychopathology in women, perhaps due to greater propensity in women to seek medical care or a higher prevalence of women with medical disorders that are treated with steroids.5 A previous history of psychiatric disorders may not increase risk.5
Several methods for reducing risk have been proposed, including using a divided-dosing regimens that may lower peak steroid plasma concentrations.13,14 However, the best prevention of steroid-induced psychiatric symptoms are awareness, early diagnosis, and intervention. Studies have suggested that N-methyl-
Treatment options
There are no FDA-approved medications for managing steroid-induced psychiatric symptoms.1,16 Treatment is based on evidence from case reports and a few small case series (Table2-5,17,18).
Continue to: When possible, initial treatment...
When possible, initial treatment should include discontinuing or tapering corticosteroids to <40 mg/d of prednisone-equivalent.1,4,10,18 Most studies have reported rapid reversal of deficits in declarative memory and of hippocampal volume loss once corticosteroids were tapered and discontinued.1,18 One study reported that >90% of patients recovered within 6 weeks, with patients with delirium recovering more quickly (mean: 5.4 days) than those with depression, mania, or psychosis (mean: 19.3 days).3 Another found that the vast majority (92%) of patients treated only with a steroid taper achieved clinical recovery, and 84% recovered with administration of antipsychotics without a steroid taper.3 In this study, all patients who received electroconvulsive therapy (ECT) recovered, as did those who received a steroid taper plus lithium or antipsychotics. Steroid tapering regimens are especially important for patients who have received long-term glucocorticoid treatment. Patients need to be closely monitored for signs of new or increased depression, delirium, or confusion during the taper. If these symptoms occur, the patient should be checked for adrenocortical insufficiency, which can be resolved by re-administering or increasing the dosage of the glucocorticoid.10
Mania. The treatment of mania/hypomania includes mood stabilizers (valproate, lithium, lamotrigine) and antipsychotics (quetiapine, olanzapine, haloperidol).2,4,5,10,14,18 Valproate has been reported to be an effective prophylactic of corticosteroid-induced mania,2 perhaps because it dampens neuronal hyperexcitability by attenuating NMDA receptors, blocking voltage-dependent sodium channels, and inhibiting the synthesis of cortical GABAergic steroids. Starting valproate while continuing corticosteroids (if necessary) may help lessen mania.2 Benzodiazepines also may be useful on a short-term basis.
Depression. Steroid-induced depression may be treated with sertraline or other first-line antidepressants.5,14 Consider ECT for patients with severe depression. Support for the use of antipsychotic medications stems from studies that reported steroids’ role in disrupting dopamine and 5HT2 activity. Lithium also has been used successfully to manage and prevent glucocorticoid-associated affective disorder.10,18 It can be used alone or in combination with selective serotonin reuptake inhibitors to alleviate depressive symptoms.10 Tricyclic antidepressants are generally avoided because their anticholinergic effects can exacerbate or worsen delirium.18 In general, ECT is an effective treatment for persistent and/or unresponsive steroid-induced depression,2,10 but may be difficult to use in patients with serious medical illnesses.
Agitation. Medications that have been proposed for treating steroid-induced agitation include benzodiazepines, haloperidol, and second-generation antipsychotics.5,17
Other considerations. Clinicians, patients, and families should discuss in detail the risks of steroid-induced psychiatric symptoms so an early diagnosis and appropriate intervention can be implemented. Before starting steroids, it is important to review the patient’s current medication list to ensure that steroid treatment is indicated, and to check for potential drug–drug interactions. In addition, the medical condition that is being treated with steroids also needs to be carefully reviewed, because certain illnesses are associated with the development of psychiatric symptoms. 5,10
Continue to: Young children...
Young children (age <6) and older adults appear to be at greater risk for cognitive and memory disturbances from steroid use.10 In addition, patients have individual levels of susceptibility to steroid-induced psychiatric symptoms that can vary over time. The risk for adverse effects may be elevated based on response to previous courses of glucocorticoid treatment.10 While gender, age, dosage, and duration of treatment influence risk, it is not possible to predict which patients will experience psychiatric effects during a given course of glucocorticoid therapy. Therefore, all patients should be considered to have the potential of developing such effects, and should be monitored during glucocorticoid treatment and withdrawal.
Goals for future research
To help reduce the severity of and cost associated with steroid-induced psychiatric symptoms,5,14 future studies should focus on controlled trials of preventative strategies. In particular, recent advances in genetic mapping may help identify involvement of certain genes or polymorphisms.5 Because current guidelines for the prevention and treatment of steroid-induced psychiatric symptoms are not evidence-based, controlled clinical trials are needed to elucidate the optimal management of such symptoms. There is much interplay between many of the proposed mechanisms of steroid-induced psychiatric symptoms, and future studies can help uncover a deeper understanding of the intricacies of this phenomenon.
CASE CONTINUED
Mrs. N is admitted for altered mental status. Medical workup includes MRI of the brain, MRI of the neck, cardiac echocardiogram, and EEG. There is no evidence of acute structural pathology. She is started on olanzapine, 10 mg/d at bedtime for manic and psychotic symptoms, and is discharged after 5 days. After 1 month, the outpatient psychiatrist gradually decreases and discontinues olanzapine as Mrs. N steadily returns to baseline. One year after discharge, Mrs. N continues to report resolution of her manic and psychotic symptoms.
Bottom Line
Steroids can induce a wide range of psychiatric symptoms, including mania/ hypomania, anxiety, and depression. Initial treatment typically includes tapering or discontinuing the steroid when possible. Other proposed treatments include certain antipsychotics, antidepressants, and other psychotropics, but the supporting evidence is largely anecdotal or based on case studies. Additional research is needed to elucidate the mechanism and treatment recommendations.
Related Resources
- Janes M, Kuster S, Goldson TM, et al. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615.
- Mayo Clinic. Prednisone and other corticosteroids. https://www.mayoclinic.org/steroids/art-20045692
Drug Brand Names
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Methylprednisolone injection • Solu-Medrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Phenytoin • Dilantin
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Valproate • Depakote
1. Dubovsky AN, Arvikar S, Stern TA, et al. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103-115.
2. Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581.
3. Lewis DA, Smith RE. Steroid‐induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5(4):319-332.
4. Warren KN, Katakam J, Espiridion ED. Acute-onset mania in a patient with non-small cell lung cancer. Cureus. 2019;11(8):e5436.
5. Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549-560.
6. Ling MH, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen. Psychiatry. 1981;38(4):471-477.
7. Ularntinon S, Tzuang D, Dahl G, et al. Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone. Pediatrics. 2010;125(5):e1241-e1245.
8. Pokladinkova J, Meyboom RH, Vlcek J, et al. Intranasally administered corticosteroids and neuropsychiatric disturbances: a review of the international pharmacovigilance programme of the World Health Organization. Ann Allergy Asthma Immunol. 2008;101(1):67-73.
9. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study. Biol Psychiatry. 2013;74(6):410-417.
10. Wolkowitz OM, Reus UI. Treatment of depression with antiglucocorticoid drugs. Psychosom Med. 1999;61(5):698-711.
11. Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014;171(10):1045-1051.
12. Appenzeller S, Cendes F, Costallat LT. Acute psychosis in systemic lupus erythematosus. Rheumatol Int. 2008;28(3):237-243.
13. Glynne-Jones R, Vernon CC, Bell G. Is steroid psychosis preventable by divided doses? Lancet. 1986;2(8520):1404.
14. Ismail MF, Lavelle C, Cassidy EM. Steroid-induced mental disorders in cancer patients: a systematic review. Future Oncol. 2017;13(29):2719-2731.
15. Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69(1):89-98.
16. Brown BS, Stuard G, Liggin JDM, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biol Psychiatry. 2005;57(5):543-548.
17. Desai S, Khanani S, Shad MU, et al. Attenutation of amygdala atrophy with lamotrigine in patients receiving corticosteroid therapy. J Clin Psychopharmacol. 2009;29(3):284-287.
18. Gable M, Depry D. Sustained corticosteroid-induced mania and psychosis despite cessation: a case study and brief literature review. Int J Psychiatry Med. 2015;50(4):398-404.
Ms. N, age 30, presents to the emergency department for altered mental status, insomnia, and behavioral changes, which she has experienced for 1 week. On evaluation, she grabs a clinician’s hand and details her business ideas and life story with no prompting. Ms. N’s mental status examination is significant for hyperverbal speech with increased rate and volume; tangential thought process; and bright, expanded affect.
One week earlier, Ms. N was hospitalized for sudden-onset chest pain, weakness, and dizziness. She received 45 minutes of cardiopulmonary resuscitation prior to presentation and was found to have a ST-segment elevation myocardial infarction that required emergent left anterior descending coronary artery and right coronary artery percutaneous coronary intervention to place drug-eluting stents. Her recovery was complicated by acute cardiogenic shock, pulmonary edema, and hypoxic respiratory failure. Subsequently, she was intubated, admitted to the ICU, and received high-dose corticosteroids, including IV methylprednisolone, 40 mg every 12 hours, which was tapered prior to discharge. Her husband reports that since Ms. N came home, she has been more talkative and irritable, ruminating about past events, unable to sleep (<1 hour/night), and crying frequently. She has also been endorsing visual and auditory hallucinations, with increased praying and listening to religious music.
The frequent clinical use of steroids necessitates an understanding of these medications’ various adverse effects. The manifestations of steroid-induced psychiatric symptoms are broad and can involve affective, behavioral, and cognitive domains. While the current mechanism is unknown, this phenomenon may be related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity, as well as effects on brain regions such as the hippocampus and amygdala. The best interventions for steroid-induced psychiatric symptoms are awareness and early diagnosis. There are no FDA-approved treatments for steroid-induced psychiatric symptoms; initial measures should include tapering or discontinuing corticosteroids.
In this article, we review the literature on the incidence, characteristics, differential diagnoses, proposed mechanism, risk factors, and proposed treatments of steroid-induced psychiatric symptoms.
A wide range of presentations
Steroid use has increased over the past 2 decades, with 10% of medical and surgical inpatients and 1% to 3% of the general population taking long-term glucocorticoids.1 Even with topical application, steroid therapy is often systemically absorbed, and thus may lead to steroid-induced psychiatric symptoms. The incidence of steroid-induced psychiatric symptoms is difficult to assess because there can be a wide range of reactions that are dose- and time-related. Three reviews of a total of 122 cases reports found that an estimated 5% of patients treated with steroids experience severe psychiatric reactions.1-3
Steroid-induced psychopathology can include mood, behavioral, and/or cognitive impairments. Mania/hypomania is the most common overall psychiatric symptom; the most common mood manifestations are anxiety and depression.4,5 Other possible steroid-induced symptoms include psychosis, dementia, panic disorder, delirium, suicidal thinking and behavior, aggressive behavior, insomnia, agitation, depersonalization, and euphoria.5 The most common cognitive impairment is verbal or declarative memory deficit; others include distractibility and deficits in attention and psychomotor speed.5 These psychiatric symptoms can have a rapid onset, possibly within hours of starting steroids.1 However, studies have reported a median time to onset of 11.5 days; 39% of cases had onset during the first week and 62% within 2 weeks.3,6 After reducing or stopping the steroid, it may take days to weeks before symptoms start to subside.2
What to consider in the differential Dx
Psychiatric symptoms that are induced by steroids can mimic metabolic, neurologic, or toxic disorders. Other factors to consider include drug withdrawal/intoxication, infections, and paraneoplastic syndromes.4,5 Although there is no reported correlation between the location of neurologic lesions and the development of specific psychiatric symptoms, manic symptoms appear most commonly with lesions in the right frontal lobe. 4 Other factors to note include the presence of new-onset psychiatric illnesses such as bipolar, mood, or thought disorders,4 as well as psychosocial stressors that might be contributing to the patient’s presentation.5
Continue to: Proposed mechanisms
Proposed mechanisms
Although the exact mechanism by which steroids induce psychiatric symptoms is unknown, several mechanisms have been proposed. One hypothesis is that steroid-induced psychopathology is related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity.4,5,7 This may explain why many patients with major depressive disorder have elevated cortisol production and/or lack of suppression of cortisol secretion during a dexamethasone stimulation test, and why approximately one-half of patients with Cushing’s disease experience depressive symptoms.8 This is also likely why antipsychotics, which typically reduce cortisol, are efficacious treatments for some steroid-induced psychiatric symptoms.9
Cognitive impairments from steroid use may be related to these agents’ effects on certain brain regions. One such area is the hippocampus, an important mediator in the creation and maintenance of episodic and declarative memories.5,8,9 Acute glucocorticoid use is associated with decreased activity in the left hippocampus, reduced hippocampal glucose metabolism, and reduced cerebral blood flow in the posterior medial temporal lobe.10 Long-term glucocorticoid exposure is associated with smaller hippocampal volume and lower levels of temporal lobe N-acetylaspartate, a marker of neuronal viability.10 Because working memory depends on the prefrontal cortex and declarative memory relies on the hippocampus, deficits in these functions can be attributed to the effect of prolonged glucocorticoid exposure on glucocorticoid or mineralocorticoid receptors in the hippocampus, reduction of hippocampal volume, or elevated glutamate accumulation in that area.11 In addition, high cortisol levels inhibit brain-derived neurotrophic factor, which plays a crucial role in maintaining neural architecture in key brain regions such as the hippocampus and prefrontal cortex.11 There is also a correlation between the duration of prednisone treatment and atrophy of the right amygdala, which is an important regulator of mood and anxiety.11 Both the hippocampus and amygdala have dense collections of glucocorticoid receptors. This may explain why patients who receive high-dose corticosteroids can have reversible atrophy in the hypothalamus and amygdala, leading to deficits in emotional learning and the stress response.
Factors that increase risk
Several factors can increase the risk of steroid-induced psychopathology. The most significant is the dose; higher doses are more likely to produce psychiatric symptoms.1,5 Concurrent use of drugs that increase circulating levels of corticosteroids, such as inhibitors of the cytochrome P450 (CYP) enzyme (eg, clarithromycin), also increases the likelihood of developing psychiatric symptoms.1,5 Risk is also increased in patients with liver or renal dysfunction.1 Cerebral spinal fluid/serum albumin ratio, a marker of blood-brain barrier damage, and low serum complement levels were also reported to be independent risk factors,12 with the thought that increased permeability of the blood-brain barrier may allow hydrophobic steroid molecules to more easily penetrate the CNS, leading to increased neuropsychiatric effects. Hypoalbuminemia is another reported risk factor, perhaps because lower levels of serum albumin are related to higher levels of free and active glucocorticoids, which are normally inactive when bound to albumin.13 There also appears to be an increased prevalence of steroid-induced psychopathology in women, perhaps due to greater propensity in women to seek medical care or a higher prevalence of women with medical disorders that are treated with steroids.5 A previous history of psychiatric disorders may not increase risk.5
Several methods for reducing risk have been proposed, including using a divided-dosing regimens that may lower peak steroid plasma concentrations.13,14 However, the best prevention of steroid-induced psychiatric symptoms are awareness, early diagnosis, and intervention. Studies have suggested that N-methyl-
Treatment options
There are no FDA-approved medications for managing steroid-induced psychiatric symptoms.1,16 Treatment is based on evidence from case reports and a few small case series (Table2-5,17,18).
Continue to: When possible, initial treatment...
When possible, initial treatment should include discontinuing or tapering corticosteroids to <40 mg/d of prednisone-equivalent.1,4,10,18 Most studies have reported rapid reversal of deficits in declarative memory and of hippocampal volume loss once corticosteroids were tapered and discontinued.1,18 One study reported that >90% of patients recovered within 6 weeks, with patients with delirium recovering more quickly (mean: 5.4 days) than those with depression, mania, or psychosis (mean: 19.3 days).3 Another found that the vast majority (92%) of patients treated only with a steroid taper achieved clinical recovery, and 84% recovered with administration of antipsychotics without a steroid taper.3 In this study, all patients who received electroconvulsive therapy (ECT) recovered, as did those who received a steroid taper plus lithium or antipsychotics. Steroid tapering regimens are especially important for patients who have received long-term glucocorticoid treatment. Patients need to be closely monitored for signs of new or increased depression, delirium, or confusion during the taper. If these symptoms occur, the patient should be checked for adrenocortical insufficiency, which can be resolved by re-administering or increasing the dosage of the glucocorticoid.10
Mania. The treatment of mania/hypomania includes mood stabilizers (valproate, lithium, lamotrigine) and antipsychotics (quetiapine, olanzapine, haloperidol).2,4,5,10,14,18 Valproate has been reported to be an effective prophylactic of corticosteroid-induced mania,2 perhaps because it dampens neuronal hyperexcitability by attenuating NMDA receptors, blocking voltage-dependent sodium channels, and inhibiting the synthesis of cortical GABAergic steroids. Starting valproate while continuing corticosteroids (if necessary) may help lessen mania.2 Benzodiazepines also may be useful on a short-term basis.
Depression. Steroid-induced depression may be treated with sertraline or other first-line antidepressants.5,14 Consider ECT for patients with severe depression. Support for the use of antipsychotic medications stems from studies that reported steroids’ role in disrupting dopamine and 5HT2 activity. Lithium also has been used successfully to manage and prevent glucocorticoid-associated affective disorder.10,18 It can be used alone or in combination with selective serotonin reuptake inhibitors to alleviate depressive symptoms.10 Tricyclic antidepressants are generally avoided because their anticholinergic effects can exacerbate or worsen delirium.18 In general, ECT is an effective treatment for persistent and/or unresponsive steroid-induced depression,2,10 but may be difficult to use in patients with serious medical illnesses.
Agitation. Medications that have been proposed for treating steroid-induced agitation include benzodiazepines, haloperidol, and second-generation antipsychotics.5,17
Other considerations. Clinicians, patients, and families should discuss in detail the risks of steroid-induced psychiatric symptoms so an early diagnosis and appropriate intervention can be implemented. Before starting steroids, it is important to review the patient’s current medication list to ensure that steroid treatment is indicated, and to check for potential drug–drug interactions. In addition, the medical condition that is being treated with steroids also needs to be carefully reviewed, because certain illnesses are associated with the development of psychiatric symptoms. 5,10
Continue to: Young children...
Young children (age <6) and older adults appear to be at greater risk for cognitive and memory disturbances from steroid use.10 In addition, patients have individual levels of susceptibility to steroid-induced psychiatric symptoms that can vary over time. The risk for adverse effects may be elevated based on response to previous courses of glucocorticoid treatment.10 While gender, age, dosage, and duration of treatment influence risk, it is not possible to predict which patients will experience psychiatric effects during a given course of glucocorticoid therapy. Therefore, all patients should be considered to have the potential of developing such effects, and should be monitored during glucocorticoid treatment and withdrawal.
Goals for future research
To help reduce the severity of and cost associated with steroid-induced psychiatric symptoms,5,14 future studies should focus on controlled trials of preventative strategies. In particular, recent advances in genetic mapping may help identify involvement of certain genes or polymorphisms.5 Because current guidelines for the prevention and treatment of steroid-induced psychiatric symptoms are not evidence-based, controlled clinical trials are needed to elucidate the optimal management of such symptoms. There is much interplay between many of the proposed mechanisms of steroid-induced psychiatric symptoms, and future studies can help uncover a deeper understanding of the intricacies of this phenomenon.
CASE CONTINUED
Mrs. N is admitted for altered mental status. Medical workup includes MRI of the brain, MRI of the neck, cardiac echocardiogram, and EEG. There is no evidence of acute structural pathology. She is started on olanzapine, 10 mg/d at bedtime for manic and psychotic symptoms, and is discharged after 5 days. After 1 month, the outpatient psychiatrist gradually decreases and discontinues olanzapine as Mrs. N steadily returns to baseline. One year after discharge, Mrs. N continues to report resolution of her manic and psychotic symptoms.
Bottom Line
Steroids can induce a wide range of psychiatric symptoms, including mania/ hypomania, anxiety, and depression. Initial treatment typically includes tapering or discontinuing the steroid when possible. Other proposed treatments include certain antipsychotics, antidepressants, and other psychotropics, but the supporting evidence is largely anecdotal or based on case studies. Additional research is needed to elucidate the mechanism and treatment recommendations.
Related Resources
- Janes M, Kuster S, Goldson TM, et al. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615.
- Mayo Clinic. Prednisone and other corticosteroids. https://www.mayoclinic.org/steroids/art-20045692
Drug Brand Names
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Methylprednisolone injection • Solu-Medrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Phenytoin • Dilantin
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Valproate • Depakote
Ms. N, age 30, presents to the emergency department for altered mental status, insomnia, and behavioral changes, which she has experienced for 1 week. On evaluation, she grabs a clinician’s hand and details her business ideas and life story with no prompting. Ms. N’s mental status examination is significant for hyperverbal speech with increased rate and volume; tangential thought process; and bright, expanded affect.
One week earlier, Ms. N was hospitalized for sudden-onset chest pain, weakness, and dizziness. She received 45 minutes of cardiopulmonary resuscitation prior to presentation and was found to have a ST-segment elevation myocardial infarction that required emergent left anterior descending coronary artery and right coronary artery percutaneous coronary intervention to place drug-eluting stents. Her recovery was complicated by acute cardiogenic shock, pulmonary edema, and hypoxic respiratory failure. Subsequently, she was intubated, admitted to the ICU, and received high-dose corticosteroids, including IV methylprednisolone, 40 mg every 12 hours, which was tapered prior to discharge. Her husband reports that since Ms. N came home, she has been more talkative and irritable, ruminating about past events, unable to sleep (<1 hour/night), and crying frequently. She has also been endorsing visual and auditory hallucinations, with increased praying and listening to religious music.
The frequent clinical use of steroids necessitates an understanding of these medications’ various adverse effects. The manifestations of steroid-induced psychiatric symptoms are broad and can involve affective, behavioral, and cognitive domains. While the current mechanism is unknown, this phenomenon may be related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity, as well as effects on brain regions such as the hippocampus and amygdala. The best interventions for steroid-induced psychiatric symptoms are awareness and early diagnosis. There are no FDA-approved treatments for steroid-induced psychiatric symptoms; initial measures should include tapering or discontinuing corticosteroids.
In this article, we review the literature on the incidence, characteristics, differential diagnoses, proposed mechanism, risk factors, and proposed treatments of steroid-induced psychiatric symptoms.
A wide range of presentations
Steroid use has increased over the past 2 decades, with 10% of medical and surgical inpatients and 1% to 3% of the general population taking long-term glucocorticoids.1 Even with topical application, steroid therapy is often systemically absorbed, and thus may lead to steroid-induced psychiatric symptoms. The incidence of steroid-induced psychiatric symptoms is difficult to assess because there can be a wide range of reactions that are dose- and time-related. Three reviews of a total of 122 cases reports found that an estimated 5% of patients treated with steroids experience severe psychiatric reactions.1-3
Steroid-induced psychopathology can include mood, behavioral, and/or cognitive impairments. Mania/hypomania is the most common overall psychiatric symptom; the most common mood manifestations are anxiety and depression.4,5 Other possible steroid-induced symptoms include psychosis, dementia, panic disorder, delirium, suicidal thinking and behavior, aggressive behavior, insomnia, agitation, depersonalization, and euphoria.5 The most common cognitive impairment is verbal or declarative memory deficit; others include distractibility and deficits in attention and psychomotor speed.5 These psychiatric symptoms can have a rapid onset, possibly within hours of starting steroids.1 However, studies have reported a median time to onset of 11.5 days; 39% of cases had onset during the first week and 62% within 2 weeks.3,6 After reducing or stopping the steroid, it may take days to weeks before symptoms start to subside.2
What to consider in the differential Dx
Psychiatric symptoms that are induced by steroids can mimic metabolic, neurologic, or toxic disorders. Other factors to consider include drug withdrawal/intoxication, infections, and paraneoplastic syndromes.4,5 Although there is no reported correlation between the location of neurologic lesions and the development of specific psychiatric symptoms, manic symptoms appear most commonly with lesions in the right frontal lobe. 4 Other factors to note include the presence of new-onset psychiatric illnesses such as bipolar, mood, or thought disorders,4 as well as psychosocial stressors that might be contributing to the patient’s presentation.5
Continue to: Proposed mechanisms
Proposed mechanisms
Although the exact mechanism by which steroids induce psychiatric symptoms is unknown, several mechanisms have been proposed. One hypothesis is that steroid-induced psychopathology is related to decreased levels of corticotropin, norepinephrine, and beta-endorphin immunoreactivity.4,5,7 This may explain why many patients with major depressive disorder have elevated cortisol production and/or lack of suppression of cortisol secretion during a dexamethasone stimulation test, and why approximately one-half of patients with Cushing’s disease experience depressive symptoms.8 This is also likely why antipsychotics, which typically reduce cortisol, are efficacious treatments for some steroid-induced psychiatric symptoms.9
Cognitive impairments from steroid use may be related to these agents’ effects on certain brain regions. One such area is the hippocampus, an important mediator in the creation and maintenance of episodic and declarative memories.5,8,9 Acute glucocorticoid use is associated with decreased activity in the left hippocampus, reduced hippocampal glucose metabolism, and reduced cerebral blood flow in the posterior medial temporal lobe.10 Long-term glucocorticoid exposure is associated with smaller hippocampal volume and lower levels of temporal lobe N-acetylaspartate, a marker of neuronal viability.10 Because working memory depends on the prefrontal cortex and declarative memory relies on the hippocampus, deficits in these functions can be attributed to the effect of prolonged glucocorticoid exposure on glucocorticoid or mineralocorticoid receptors in the hippocampus, reduction of hippocampal volume, or elevated glutamate accumulation in that area.11 In addition, high cortisol levels inhibit brain-derived neurotrophic factor, which plays a crucial role in maintaining neural architecture in key brain regions such as the hippocampus and prefrontal cortex.11 There is also a correlation between the duration of prednisone treatment and atrophy of the right amygdala, which is an important regulator of mood and anxiety.11 Both the hippocampus and amygdala have dense collections of glucocorticoid receptors. This may explain why patients who receive high-dose corticosteroids can have reversible atrophy in the hypothalamus and amygdala, leading to deficits in emotional learning and the stress response.
Factors that increase risk
Several factors can increase the risk of steroid-induced psychopathology. The most significant is the dose; higher doses are more likely to produce psychiatric symptoms.1,5 Concurrent use of drugs that increase circulating levels of corticosteroids, such as inhibitors of the cytochrome P450 (CYP) enzyme (eg, clarithromycin), also increases the likelihood of developing psychiatric symptoms.1,5 Risk is also increased in patients with liver or renal dysfunction.1 Cerebral spinal fluid/serum albumin ratio, a marker of blood-brain barrier damage, and low serum complement levels were also reported to be independent risk factors,12 with the thought that increased permeability of the blood-brain barrier may allow hydrophobic steroid molecules to more easily penetrate the CNS, leading to increased neuropsychiatric effects. Hypoalbuminemia is another reported risk factor, perhaps because lower levels of serum albumin are related to higher levels of free and active glucocorticoids, which are normally inactive when bound to albumin.13 There also appears to be an increased prevalence of steroid-induced psychopathology in women, perhaps due to greater propensity in women to seek medical care or a higher prevalence of women with medical disorders that are treated with steroids.5 A previous history of psychiatric disorders may not increase risk.5
Several methods for reducing risk have been proposed, including using a divided-dosing regimens that may lower peak steroid plasma concentrations.13,14 However, the best prevention of steroid-induced psychiatric symptoms are awareness, early diagnosis, and intervention. Studies have suggested that N-methyl-
Treatment options
There are no FDA-approved medications for managing steroid-induced psychiatric symptoms.1,16 Treatment is based on evidence from case reports and a few small case series (Table2-5,17,18).
Continue to: When possible, initial treatment...
When possible, initial treatment should include discontinuing or tapering corticosteroids to <40 mg/d of prednisone-equivalent.1,4,10,18 Most studies have reported rapid reversal of deficits in declarative memory and of hippocampal volume loss once corticosteroids were tapered and discontinued.1,18 One study reported that >90% of patients recovered within 6 weeks, with patients with delirium recovering more quickly (mean: 5.4 days) than those with depression, mania, or psychosis (mean: 19.3 days).3 Another found that the vast majority (92%) of patients treated only with a steroid taper achieved clinical recovery, and 84% recovered with administration of antipsychotics without a steroid taper.3 In this study, all patients who received electroconvulsive therapy (ECT) recovered, as did those who received a steroid taper plus lithium or antipsychotics. Steroid tapering regimens are especially important for patients who have received long-term glucocorticoid treatment. Patients need to be closely monitored for signs of new or increased depression, delirium, or confusion during the taper. If these symptoms occur, the patient should be checked for adrenocortical insufficiency, which can be resolved by re-administering or increasing the dosage of the glucocorticoid.10
Mania. The treatment of mania/hypomania includes mood stabilizers (valproate, lithium, lamotrigine) and antipsychotics (quetiapine, olanzapine, haloperidol).2,4,5,10,14,18 Valproate has been reported to be an effective prophylactic of corticosteroid-induced mania,2 perhaps because it dampens neuronal hyperexcitability by attenuating NMDA receptors, blocking voltage-dependent sodium channels, and inhibiting the synthesis of cortical GABAergic steroids. Starting valproate while continuing corticosteroids (if necessary) may help lessen mania.2 Benzodiazepines also may be useful on a short-term basis.
Depression. Steroid-induced depression may be treated with sertraline or other first-line antidepressants.5,14 Consider ECT for patients with severe depression. Support for the use of antipsychotic medications stems from studies that reported steroids’ role in disrupting dopamine and 5HT2 activity. Lithium also has been used successfully to manage and prevent glucocorticoid-associated affective disorder.10,18 It can be used alone or in combination with selective serotonin reuptake inhibitors to alleviate depressive symptoms.10 Tricyclic antidepressants are generally avoided because their anticholinergic effects can exacerbate or worsen delirium.18 In general, ECT is an effective treatment for persistent and/or unresponsive steroid-induced depression,2,10 but may be difficult to use in patients with serious medical illnesses.
Agitation. Medications that have been proposed for treating steroid-induced agitation include benzodiazepines, haloperidol, and second-generation antipsychotics.5,17
Other considerations. Clinicians, patients, and families should discuss in detail the risks of steroid-induced psychiatric symptoms so an early diagnosis and appropriate intervention can be implemented. Before starting steroids, it is important to review the patient’s current medication list to ensure that steroid treatment is indicated, and to check for potential drug–drug interactions. In addition, the medical condition that is being treated with steroids also needs to be carefully reviewed, because certain illnesses are associated with the development of psychiatric symptoms. 5,10
Continue to: Young children...
Young children (age <6) and older adults appear to be at greater risk for cognitive and memory disturbances from steroid use.10 In addition, patients have individual levels of susceptibility to steroid-induced psychiatric symptoms that can vary over time. The risk for adverse effects may be elevated based on response to previous courses of glucocorticoid treatment.10 While gender, age, dosage, and duration of treatment influence risk, it is not possible to predict which patients will experience psychiatric effects during a given course of glucocorticoid therapy. Therefore, all patients should be considered to have the potential of developing such effects, and should be monitored during glucocorticoid treatment and withdrawal.
Goals for future research
To help reduce the severity of and cost associated with steroid-induced psychiatric symptoms,5,14 future studies should focus on controlled trials of preventative strategies. In particular, recent advances in genetic mapping may help identify involvement of certain genes or polymorphisms.5 Because current guidelines for the prevention and treatment of steroid-induced psychiatric symptoms are not evidence-based, controlled clinical trials are needed to elucidate the optimal management of such symptoms. There is much interplay between many of the proposed mechanisms of steroid-induced psychiatric symptoms, and future studies can help uncover a deeper understanding of the intricacies of this phenomenon.
CASE CONTINUED
Mrs. N is admitted for altered mental status. Medical workup includes MRI of the brain, MRI of the neck, cardiac echocardiogram, and EEG. There is no evidence of acute structural pathology. She is started on olanzapine, 10 mg/d at bedtime for manic and psychotic symptoms, and is discharged after 5 days. After 1 month, the outpatient psychiatrist gradually decreases and discontinues olanzapine as Mrs. N steadily returns to baseline. One year after discharge, Mrs. N continues to report resolution of her manic and psychotic symptoms.
Bottom Line
Steroids can induce a wide range of psychiatric symptoms, including mania/ hypomania, anxiety, and depression. Initial treatment typically includes tapering or discontinuing the steroid when possible. Other proposed treatments include certain antipsychotics, antidepressants, and other psychotropics, but the supporting evidence is largely anecdotal or based on case studies. Additional research is needed to elucidate the mechanism and treatment recommendations.
Related Resources
- Janes M, Kuster S, Goldson TM, et al. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615.
- Mayo Clinic. Prednisone and other corticosteroids. https://www.mayoclinic.org/steroids/art-20045692
Drug Brand Names
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Methylprednisolone injection • Solu-Medrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Phenytoin • Dilantin
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Valproate • Depakote
1. Dubovsky AN, Arvikar S, Stern TA, et al. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103-115.
2. Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581.
3. Lewis DA, Smith RE. Steroid‐induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5(4):319-332.
4. Warren KN, Katakam J, Espiridion ED. Acute-onset mania in a patient with non-small cell lung cancer. Cureus. 2019;11(8):e5436.
5. Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549-560.
6. Ling MH, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen. Psychiatry. 1981;38(4):471-477.
7. Ularntinon S, Tzuang D, Dahl G, et al. Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone. Pediatrics. 2010;125(5):e1241-e1245.
8. Pokladinkova J, Meyboom RH, Vlcek J, et al. Intranasally administered corticosteroids and neuropsychiatric disturbances: a review of the international pharmacovigilance programme of the World Health Organization. Ann Allergy Asthma Immunol. 2008;101(1):67-73.
9. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study. Biol Psychiatry. 2013;74(6):410-417.
10. Wolkowitz OM, Reus UI. Treatment of depression with antiglucocorticoid drugs. Psychosom Med. 1999;61(5):698-711.
11. Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014;171(10):1045-1051.
12. Appenzeller S, Cendes F, Costallat LT. Acute psychosis in systemic lupus erythematosus. Rheumatol Int. 2008;28(3):237-243.
13. Glynne-Jones R, Vernon CC, Bell G. Is steroid psychosis preventable by divided doses? Lancet. 1986;2(8520):1404.
14. Ismail MF, Lavelle C, Cassidy EM. Steroid-induced mental disorders in cancer patients: a systematic review. Future Oncol. 2017;13(29):2719-2731.
15. Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69(1):89-98.
16. Brown BS, Stuard G, Liggin JDM, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biol Psychiatry. 2005;57(5):543-548.
17. Desai S, Khanani S, Shad MU, et al. Attenutation of amygdala atrophy with lamotrigine in patients receiving corticosteroid therapy. J Clin Psychopharmacol. 2009;29(3):284-287.
18. Gable M, Depry D. Sustained corticosteroid-induced mania and psychosis despite cessation: a case study and brief literature review. Int J Psychiatry Med. 2015;50(4):398-404.
1. Dubovsky AN, Arvikar S, Stern TA, et al. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103-115.
2. Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581.
3. Lewis DA, Smith RE. Steroid‐induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5(4):319-332.
4. Warren KN, Katakam J, Espiridion ED. Acute-onset mania in a patient with non-small cell lung cancer. Cureus. 2019;11(8):e5436.
5. Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549-560.
6. Ling MH, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen. Psychiatry. 1981;38(4):471-477.
7. Ularntinon S, Tzuang D, Dahl G, et al. Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone. Pediatrics. 2010;125(5):e1241-e1245.
8. Pokladinkova J, Meyboom RH, Vlcek J, et al. Intranasally administered corticosteroids and neuropsychiatric disturbances: a review of the international pharmacovigilance programme of the World Health Organization. Ann Allergy Asthma Immunol. 2008;101(1):67-73.
9. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study. Biol Psychiatry. 2013;74(6):410-417.
10. Wolkowitz OM, Reus UI. Treatment of depression with antiglucocorticoid drugs. Psychosom Med. 1999;61(5):698-711.
11. Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014;171(10):1045-1051.
12. Appenzeller S, Cendes F, Costallat LT. Acute psychosis in systemic lupus erythematosus. Rheumatol Int. 2008;28(3):237-243.
13. Glynne-Jones R, Vernon CC, Bell G. Is steroid psychosis preventable by divided doses? Lancet. 1986;2(8520):1404.
14. Ismail MF, Lavelle C, Cassidy EM. Steroid-induced mental disorders in cancer patients: a systematic review. Future Oncol. 2017;13(29):2719-2731.
15. Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69(1):89-98.
16. Brown BS, Stuard G, Liggin JDM, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biol Psychiatry. 2005;57(5):543-548.
17. Desai S, Khanani S, Shad MU, et al. Attenutation of amygdala atrophy with lamotrigine in patients receiving corticosteroid therapy. J Clin Psychopharmacol. 2009;29(3):284-287.
18. Gable M, Depry D. Sustained corticosteroid-induced mania and psychosis despite cessation: a case study and brief literature review. Int J Psychiatry Med. 2015;50(4):398-404.
Reproductive safety of treatments for women with bipolar disorder
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Blood pressure meds tied to increased schizophrenia risk
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Inflammatory immune findings likely in acute schizophrenia, MDD, bipolar
Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.
“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”
The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”
A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.
Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.
The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”
Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.
According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.
“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”
“We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”
He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”
Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.
Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.
“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”
The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”
A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.
Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.
The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”
Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.
According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.
“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”
“We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”
He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”
Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.
Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.
“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”
The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”
A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.
Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.
The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”
Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.
According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.
“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”
“We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”
He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”
Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.
FROM NPA 2021
Cannabis tied to self-harm, death in youth with mood disorders
Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.
Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.
“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.
“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.
The study was published online Jan. 19, 2021, in JAMA Pediatrics.
Little research in youth
“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.
Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.
“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.
The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).
Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.
Researchers included demographic, clinical, and treatment factors as covariates.
Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).
One -tenth of the cohort (10.3%) were diagnosed with CUD.
CUD treatment referrals
“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.
Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.
Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.
She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
Open dialogue
In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.
However, “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”
Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”
In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”
Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”
He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”
The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth.
A version of this article first appeared on Medscape.com.
Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.
Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.
“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.
“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.
The study was published online Jan. 19, 2021, in JAMA Pediatrics.
Little research in youth
“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.
Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.
“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.
The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).
Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.
Researchers included demographic, clinical, and treatment factors as covariates.
Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).
One -tenth of the cohort (10.3%) were diagnosed with CUD.
CUD treatment referrals
“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.
Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.
Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.
She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
Open dialogue
In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.
However, “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”
Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”
In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”
Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”
He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”
The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth.
A version of this article first appeared on Medscape.com.
Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.
Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.
“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.
“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.
The study was published online Jan. 19, 2021, in JAMA Pediatrics.
Little research in youth
“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.
Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.
“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.
The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).
Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.
Researchers included demographic, clinical, and treatment factors as covariates.
Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).
One -tenth of the cohort (10.3%) were diagnosed with CUD.
CUD treatment referrals
“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.
Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.
Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.
She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
Open dialogue
In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.
However, “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”
Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”
In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”
Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”
He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”
The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth.
A version of this article first appeared on Medscape.com.
Give women's mental health a seat at the health care table
Why it’s time for women’s mental health to be recognized as the subspecialty it already is
It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.
All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.
By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.1 It is time for that to change.
Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.
What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.2 We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.
with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.
Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.3 The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.
Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.4 It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.5 Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.6
Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.
It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.7 Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.
A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.
The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.
Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.
References
1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.
2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.
3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.
4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.
5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.
6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.
7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.
Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.
Why it’s time for women’s mental health to be recognized as the subspecialty it already is
Why it’s time for women’s mental health to be recognized as the subspecialty it already is
It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.
All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.
By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.1 It is time for that to change.
Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.
What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.2 We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.
with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.
Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.3 The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.
Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.4 It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.5 Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.6
Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.
It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.7 Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.
A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.
The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.
Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.
References
1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.
2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.
3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.
4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.
5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.
6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.
7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.
Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.
It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.
All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.
By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.1 It is time for that to change.
Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.
What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.2 We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.
with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.
Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.3 The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.
Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.4 It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.5 Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.6
Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.
It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.7 Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.
A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.
The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.
Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.
References
1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.
2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.
3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.
4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.
5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.
6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.
7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.
Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.