Current Psychiatry

Mrs. D is a 28-year-old married woman who became depressed after her first pregnancy. The depression was treated successfully with paroxetine, 20 mg/d. Before beginning treatment, she reported low mood, spent most of the day in bed, was unable to care for herself, and confessed to thoughts of harming her child.

Mrs. D presents to your clinic asking whether she should continue her selective serotonin reuptake inhibitor (SSRI) because she and her husband are thinking about having a second child. Recently, she tells you, she saw a news article suggesting that anti­depressants show little benefit, and she is concerned that her baby might have a heart defect if she continues paroxetine.

Mrs. D wants to discontinue her medication, but her husband thought she should discuss doing so with you first. During this visit she takes a pregnancy test, which is positive. She wants to know what to do.

Evidence of risks and benefits

Clinicians should be aware of possible adverse effects of SSRI use and untreated depression (Table).^2-10 The available data precludes definitive associations between untreated depression and poor outcomes (Box). Studies of SSRI use during pregnancy have shown conflicting results for all potential outcomes. Absolute risk, with the exception of neonatal adaptation syndrome, is estimated to be small. Neonatal adaptation syndrome—which is characterized by jitteriness, poor muscle tone, weak cries, respiratory distress, hypoglycemia, low Apgar scores, and seizures—occurs in 15% to 30% of infants born to mothers taking SSRIs, but it is transient and resolves during the first weeks of life.

Treatment recommendations

Given the conflicting nature of the evidence, treatment plans should be individualized, weighing the risks and benefits of treatment and the patient’s beliefs and psychiatric history. Consider severity of symptoms and history, including effective therapy and history of relapse. For women with mild or moderate depression, cognitive-behavioral therapy might be an appropriate first-line therapy. However, non-pharmacotherapeutic interventions might not relieve severe depression or be available to all women. When discontinuing an SSRI before pregnancy, counsel the patient to not discontinue the medication abruptly and provide an appropriate taper schedule. See Related Resources for detailed recommendations from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.

Reviewing the SSRI literature regarding pregnancy

Sertraline, paroxetine, citalopram, and fluoxetine are the most studied SSRIs during pregnancy; little information is available on escitalopram and fluvoxamine.¹¹ Prescribing preference generally is given to the medications with the most evidence; paroxetine may be an exception. In 2005, the FDA requested a change in paroxetine’s pregnancy category from C to D, indicating that adequate studies demonstrated a risk of congenital cardiac malformations.¹¹ Additional studies have been conducted, and the teratogenicity of paroxetine is debatable. A recent review reports 8 studies that suggest a malformation risk, compared with 15 studies that show no risk.¹²

The American Academy of Pediatrics considers SSRIs to be compatible with breast-feeding.¹³ The best-studied drugs include sertraline and paroxetine. Fluoxetine should be avoided when possible because a long elimination half-life can cause the drug to accumulate in the newborn, increasing the risk of irritability, hypertonia, sedation, and poor suckle.⁷

There is no best SSRI for all pregnant women. Risks and benefits, including previous treatment success and failure, should be taken into account before starting or switching therapy. Whenever possible, consider monotherapy to avoid compounding the risk of harm.

Related Resources

• Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31:403-413.
• MGH Center for Women’s Mental Health. www.womensmentalhealth.org.

Drug Brand Names

Citalopram • Celexa      Escitalopram • Lexapro      Fluoxetine • Prozac

Fluvoxamine • Luvox     Paroxetine • Paxil             Sertraline • Zoloft

Disclosures
Dr. Leino reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Ellingrod receives grant support from the National Institute of Mental Health.

Mrs. D is a 28-year-old married woman who became depressed after her first pregnancy. The depression was treated successfully with paroxetine, 20 mg/d. Before beginning treatment, she reported low mood, spent most of the day in bed, was unable to care for herself, and confessed to thoughts of harming her child.

Mrs. D presents to your clinic asking whether she should continue her selective serotonin reuptake inhibitor (SSRI) because she and her husband are thinking about having a second child. Recently, she tells you, she saw a news article suggesting that anti­depressants show little benefit, and she is concerned that her baby might have a heart defect if she continues paroxetine.

Mrs. D wants to discontinue her medication, but her husband thought she should discuss doing so with you first. During this visit she takes a pregnancy test, which is positive. She wants to know what to do.

Evidence of risks and benefits

Clinicians should be aware of possible adverse effects of SSRI use and untreated depression (Table).^2-10 The available data precludes definitive associations between untreated depression and poor outcomes (Box). Studies of SSRI use during pregnancy have shown conflicting results for all potential outcomes. Absolute risk, with the exception of neonatal adaptation syndrome, is estimated to be small. Neonatal adaptation syndrome—which is characterized by jitteriness, poor muscle tone, weak cries, respiratory distress, hypoglycemia, low Apgar scores, and seizures—occurs in 15% to 30% of infants born to mothers taking SSRIs, but it is transient and resolves during the first weeks of life.

Treatment recommendations

Given the conflicting nature of the evidence, treatment plans should be individualized, weighing the risks and benefits of treatment and the patient’s beliefs and psychiatric history. Consider severity of symptoms and history, including effective therapy and history of relapse. For women with mild or moderate depression, cognitive-behavioral therapy might be an appropriate first-line therapy. However, non-pharmacotherapeutic interventions might not relieve severe depression or be available to all women. When discontinuing an SSRI before pregnancy, counsel the patient to not discontinue the medication abruptly and provide an appropriate taper schedule. See Related Resources for detailed recommendations from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.

Reviewing the SSRI literature regarding pregnancy

Sertraline, paroxetine, citalopram, and fluoxetine are the most studied SSRIs during pregnancy; little information is available on escitalopram and fluvoxamine.¹¹ Prescribing preference generally is given to the medications with the most evidence; paroxetine may be an exception. In 2005, the FDA requested a change in paroxetine’s pregnancy category from C to D, indicating that adequate studies demonstrated a risk of congenital cardiac malformations.¹¹ Additional studies have been conducted, and the teratogenicity of paroxetine is debatable. A recent review reports 8 studies that suggest a malformation risk, compared with 15 studies that show no risk.¹²

The American Academy of Pediatrics considers SSRIs to be compatible with breast-feeding.¹³ The best-studied drugs include sertraline and paroxetine. Fluoxetine should be avoided when possible because a long elimination half-life can cause the drug to accumulate in the newborn, increasing the risk of irritability, hypertonia, sedation, and poor suckle.⁷

There is no best SSRI for all pregnant women. Risks and benefits, including previous treatment success and failure, should be taken into account before starting or switching therapy. Whenever possible, consider monotherapy to avoid compounding the risk of harm.

Related Resources

• Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31:403-413.
• MGH Center for Women’s Mental Health. www.womensmentalhealth.org.

Drug Brand Names

Citalopram • Celexa      Escitalopram • Lexapro      Fluoxetine • Prozac

Fluvoxamine • Luvox     Paroxetine • Paxil             Sertraline • Zoloft

Disclosures
Dr. Leino reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Ellingrod receives grant support from the National Institute of Mental Health.

Mrs. D is a 28-year-old married woman who became depressed after her first pregnancy. The depression was treated successfully with paroxetine, 20 mg/d. Before beginning treatment, she reported low mood, spent most of the day in bed, was unable to care for herself, and confessed to thoughts of harming her child.

Mrs. D presents to your clinic asking whether she should continue her selective serotonin reuptake inhibitor (SSRI) because she and her husband are thinking about having a second child. Recently, she tells you, she saw a news article suggesting that anti­depressants show little benefit, and she is concerned that her baby might have a heart defect if she continues paroxetine.

Mrs. D wants to discontinue her medication, but her husband thought she should discuss doing so with you first. During this visit she takes a pregnancy test, which is positive. She wants to know what to do.

Evidence of risks and benefits

Clinicians should be aware of possible adverse effects of SSRI use and untreated depression (Table).^2-10 The available data precludes definitive associations between untreated depression and poor outcomes (Box). Studies of SSRI use during pregnancy have shown conflicting results for all potential outcomes. Absolute risk, with the exception of neonatal adaptation syndrome, is estimated to be small. Neonatal adaptation syndrome—which is characterized by jitteriness, poor muscle tone, weak cries, respiratory distress, hypoglycemia, low Apgar scores, and seizures—occurs in 15% to 30% of infants born to mothers taking SSRIs, but it is transient and resolves during the first weeks of life.

Treatment recommendations

Given the conflicting nature of the evidence, treatment plans should be individualized, weighing the risks and benefits of treatment and the patient’s beliefs and psychiatric history. Consider severity of symptoms and history, including effective therapy and history of relapse. For women with mild or moderate depression, cognitive-behavioral therapy might be an appropriate first-line therapy. However, non-pharmacotherapeutic interventions might not relieve severe depression or be available to all women. When discontinuing an SSRI before pregnancy, counsel the patient to not discontinue the medication abruptly and provide an appropriate taper schedule. See Related Resources for detailed recommendations from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.

Reviewing the SSRI literature regarding pregnancy

Sertraline, paroxetine, citalopram, and fluoxetine are the most studied SSRIs during pregnancy; little information is available on escitalopram and fluvoxamine.¹¹ Prescribing preference generally is given to the medications with the most evidence; paroxetine may be an exception. In 2005, the FDA requested a change in paroxetine’s pregnancy category from C to D, indicating that adequate studies demonstrated a risk of congenital cardiac malformations.¹¹ Additional studies have been conducted, and the teratogenicity of paroxetine is debatable. A recent review reports 8 studies that suggest a malformation risk, compared with 15 studies that show no risk.¹²

The American Academy of Pediatrics considers SSRIs to be compatible with breast-feeding.¹³ The best-studied drugs include sertraline and paroxetine. Fluoxetine should be avoided when possible because a long elimination half-life can cause the drug to accumulate in the newborn, increasing the risk of irritability, hypertonia, sedation, and poor suckle.⁷

There is no best SSRI for all pregnant women. Risks and benefits, including previous treatment success and failure, should be taken into account before starting or switching therapy. Whenever possible, consider monotherapy to avoid compounding the risk of harm.

Related Resources

• Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31:403-413.
• MGH Center for Women’s Mental Health. www.womensmentalhealth.org.

Drug Brand Names

Citalopram • Celexa      Escitalopram • Lexapro      Fluoxetine • Prozac

Fluvoxamine • Luvox     Paroxetine • Paxil             Sertraline • Zoloft

Disclosures
Dr. Leino reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Ellingrod receives grant support from the National Institute of Mental Health.

Psychiatrists often are required to obtain basic sexual information as part of a thorough clinical assessment.¹ Although a detailed sexual health assessment comprises multiple elaborate domains,² it’s important that mental health professionals remember a set of topics and related questions (Table) that can help investigate, diagnose, and treat sexual dysfunction, and contribute to a biopsychosocial formulation of your patient’s sexuality. The BIOTEACHERS mnemonic can remind you what to ask when taking a patient’s sexual history; it is not intended to be an alternative to a comprehensive sexual health evaluation.

Each letter stands for a component of the sexual assessment. The grouped letters of the acronym break down into different relevant areas that aid in remembering each category.

BIO

Background of the problem or the patient’s biophysical state

Identity

Orientation

BIO gathers basic medical information, then creates an opportunity to understand the patient’s gender identity. This step allows for nonjudgmental discussions about the patient’s sexual orientation.

TEACH

Thoughts of a sexual nature

Erotic desire or sexual interest

Arousal

Climax during sex

How often

TEACH incorporates a common chronology of sexual response and activity, starting with sexual thoughts, feelings of erotic desire, development of sexual arousal, ability and quality of a patient’s orgasm, as well as frequency of sexual activity.

ERS

Education

Repertoire or relationship dynamics

Self-stimulation

ERS comprises somewhat more complicated subjects: education (questions about a person’s sexual awareness and communication style); formal sexual knowledge; and health practices. These areas of questioning also normalize discussion of the patient’s sexual repertoire (what activities he [she] does and avoids), reviews qualities of the sexual relationship, and broaches the issue of self-stimulation.

Remember: All discussions of sexuality should be appropriate to the clinical context and considerate of the deeply personal nature of the information.

Disclosure

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors thank Sallie Foley, LMSW, Daniela Wittmann, LMSW, and the University of Michigan Sexual Health Certificate program for their assistance.

Psychiatrists often are required to obtain basic sexual information as part of a thorough clinical assessment.¹ Although a detailed sexual health assessment comprises multiple elaborate domains,² it’s important that mental health professionals remember a set of topics and related questions (Table) that can help investigate, diagnose, and treat sexual dysfunction, and contribute to a biopsychosocial formulation of your patient’s sexuality. The BIOTEACHERS mnemonic can remind you what to ask when taking a patient’s sexual history; it is not intended to be an alternative to a comprehensive sexual health evaluation.

Each letter stands for a component of the sexual assessment. The grouped letters of the acronym break down into different relevant areas that aid in remembering each category.

BIO

Background of the problem or the patient’s biophysical state

Identity

Orientation

BIO gathers basic medical information, then creates an opportunity to understand the patient’s gender identity. This step allows for nonjudgmental discussions about the patient’s sexual orientation.

TEACH

Thoughts of a sexual nature

Erotic desire or sexual interest

Arousal

Climax during sex

How often

TEACH incorporates a common chronology of sexual response and activity, starting with sexual thoughts, feelings of erotic desire, development of sexual arousal, ability and quality of a patient’s orgasm, as well as frequency of sexual activity.

ERS

Education

Repertoire or relationship dynamics

Self-stimulation

ERS comprises somewhat more complicated subjects: education (questions about a person’s sexual awareness and communication style); formal sexual knowledge; and health practices. These areas of questioning also normalize discussion of the patient’s sexual repertoire (what activities he [she] does and avoids), reviews qualities of the sexual relationship, and broaches the issue of self-stimulation.

Remember: All discussions of sexuality should be appropriate to the clinical context and considerate of the deeply personal nature of the information.

Disclosure

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors thank Sallie Foley, LMSW, Daniela Wittmann, LMSW, and the University of Michigan Sexual Health Certificate program for their assistance.

Psychiatrists often are required to obtain basic sexual information as part of a thorough clinical assessment.¹ Although a detailed sexual health assessment comprises multiple elaborate domains,² it’s important that mental health professionals remember a set of topics and related questions (Table) that can help investigate, diagnose, and treat sexual dysfunction, and contribute to a biopsychosocial formulation of your patient’s sexuality. The BIOTEACHERS mnemonic can remind you what to ask when taking a patient’s sexual history; it is not intended to be an alternative to a comprehensive sexual health evaluation.

Each letter stands for a component of the sexual assessment. The grouped letters of the acronym break down into different relevant areas that aid in remembering each category.

BIO

Background of the problem or the patient’s biophysical state

Identity

Orientation

BIO gathers basic medical information, then creates an opportunity to understand the patient’s gender identity. This step allows for nonjudgmental discussions about the patient’s sexual orientation.

TEACH

Thoughts of a sexual nature

Erotic desire or sexual interest

Arousal

Climax during sex

How often

TEACH incorporates a common chronology of sexual response and activity, starting with sexual thoughts, feelings of erotic desire, development of sexual arousal, ability and quality of a patient’s orgasm, as well as frequency of sexual activity.

ERS

Education

Repertoire or relationship dynamics

Self-stimulation

ERS comprises somewhat more complicated subjects: education (questions about a person’s sexual awareness and communication style); formal sexual knowledge; and health practices. These areas of questioning also normalize discussion of the patient’s sexual repertoire (what activities he [she] does and avoids), reviews qualities of the sexual relationship, and broaches the issue of self-stimulation.

Remember: All discussions of sexuality should be appropriate to the clinical context and considerate of the deeply personal nature of the information.

Disclosure

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors thank Sallie Foley, LMSW, Daniela Wittmann, LMSW, and the University of Michigan Sexual Health Certificate program for their assistance.

With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.

The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.

The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.

Ignorance has many faces

The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.

Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!¹ Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”

I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.

A ‘colossal body of scientific evidence’ informs psychiatry

There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.

There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.

The hazard of obsolete knowledge

Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.

With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.

The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.

The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.

Ignorance has many faces

The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.

Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!¹ Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”

I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.

A ‘colossal body of scientific evidence’ informs psychiatry

There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.

There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.

The hazard of obsolete knowledge

Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.

With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.

The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.

The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.

Ignorance has many faces

The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.

Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!¹ Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”

I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.

A ‘colossal body of scientific evidence’ informs psychiatry

There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.

There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.

The hazard of obsolete knowledge

Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.

I found “Chronic non-cancer pain and substance use disorders: Challenges and strategies.” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO) interesting. However, as an author of one of the references cited, I feel I should speak up when there is a factual error. The authors cite our Moore et al 2009¹ study as finding that “the SOAPP-R is 90% sensitive in detecting CNCP/SUD.”

First, what was identified was those patients misusing opioid medications in some way that might or might not represent a substance use disorder. Second, the sensitivity was 73%, not 90%. Most important, the instrument to which the authors are referring is the SOAPP, not the SOAPP-R. Our later studies have shown that the SOAPP-R has much less sensitivity than the SOAPP and, therefore, the two tools are not comparable.

Ted W. Jones, PhD

Psychologist

Behavioral Medicine Institute, P.C.

Pain Consultants of East Tennessee

Knoxville, Tennessee

Reference

1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

I found “Chronic non-cancer pain and substance use disorders: Challenges and strategies.” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO) interesting. However, as an author of one of the references cited, I feel I should speak up when there is a factual error. The authors cite our Moore et al 2009¹ study as finding that “the SOAPP-R is 90% sensitive in detecting CNCP/SUD.”

First, what was identified was those patients misusing opioid medications in some way that might or might not represent a substance use disorder. Second, the sensitivity was 73%, not 90%. Most important, the instrument to which the authors are referring is the SOAPP, not the SOAPP-R. Our later studies have shown that the SOAPP-R has much less sensitivity than the SOAPP and, therefore, the two tools are not comparable.

Ted W. Jones, PhD

Psychologist

Behavioral Medicine Institute, P.C.

Pain Consultants of East Tennessee

Knoxville, Tennessee

Reference

1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

I found “Chronic non-cancer pain and substance use disorders: Challenges and strategies.” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO) interesting. However, as an author of one of the references cited, I feel I should speak up when there is a factual error. The authors cite our Moore et al 2009¹ study as finding that “the SOAPP-R is 90% sensitive in detecting CNCP/SUD.”

First, what was identified was those patients misusing opioid medications in some way that might or might not represent a substance use disorder. Second, the sensitivity was 73%, not 90%. Most important, the instrument to which the authors are referring is the SOAPP, not the SOAPP-R. Our later studies have shown that the SOAPP-R has much less sensitivity than the SOAPP and, therefore, the two tools are not comparable.

Ted W. Jones, PhD

Psychologist

Behavioral Medicine Institute, P.C.

Pain Consultants of East Tennessee

Knoxville, Tennessee

Reference

1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

‘Farewell’ to haloperidol?

In response to “Haloperidol clearly is neurotoxic. Should it be banned?” (Current Psychiatry, From the Editor, July 2013, p. 7-8; http://bit.ly/1eMegnr), let me clarify several issues before a consensus is established on whether to discontinue the use of haloperidol.

Remember that­ since the first use of haloperidol—one of the butyrophenones—more than a half a century ago, practitioners and researchers were aware of its neurotoxicity. Nevertheless, butyrophenones are unique chemicals capable of controlling psychotic symptoms and severe brain dysfunctions, such as extrapyramidal reactions, neuroleptic malignant syndrome, akathisia, tardive dyskinesia, and galactorrhea, among others. Dr. Paul Janssen—founder of the laboratory that first released haloperidol—made a fortune that subsequently prevented him from being awarded the Nobel Prize in Physiology or Medicine.¹

A product that was the cornerstone of psychiatric treatment for half a century deserves a better farewell than the one Dr. Nasrallah is offering. Atypical antipsychotics present a number of drawbacks and have dangerous toxicity levels that still need study. I am concerned about metabolic syndrome (diabetes mellitus, hypercholesterolemia, gynecomastia, severe obesity, etc.), which may cost even more to treat than the cost of psychiatric care. In addition to the burden of their high and often unreasonable cost, quetiapine, olanzapine, clozapine, aripiprazole, risperidone, and other atypical antipsychotics have clinical limitations that often restrict their use.

If psychiatry needs a good, immediate fix, it would be in the development and approval of new chemicals that are both better tolerated than the butyrophenones and more affordable than atypical antipsychotics.²

Enrique S. Garza-Trevino, MD

Medical Director

San Antonio Mood Disorders Clinic

San Antonio, Texas

References

1. Healy D. The psychopharmacologist II: interviews by David Healy. Philadelphia, PA: Lippincott-Raven Publishers; 1998.

2. Garza-Trevino ES, Hollister LE, Overall JE. Combination of intramuscular hypnotics and neuroleptics for control of psychotic agitated patients. Am J Psychiatry. 1989;146:1598-1602.

Superior efficacy of atypical antipsychotics

Regarding Dr. Nasrallah’s editorial (July 2013) on the research delineating some of the neurotoxic aspects of first-generation antipsychotics, including haloperidol, he seems to shoot clinical psychiatry in the foot when he describes second-generation agents as having been “much safer for the brain than their older-generation counterparts (although they are not more efficacious).” This closing assertion is not followed by a reference. Indeed, one would anticipate that the newer agents would display greater efficacy given the neurotropic properties of the atypicals described by Dr. Nasrallah in his previous editorial, "Beyond dopamine: The 'other' effects of antipsychotics" (Current Psychiatry, June 2013, p. 8-9; http://bit.ly/1aA7MZw).

The only real study attempting to clarify this issue has been the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study; patients in that study were chronic and refractory to any intervention. In my practice, I have seen clear and compelling evidence supporting the superiority of atypical antipsychotics—as well as chronicity with multiple relapses and rehospitalizations.

More research into this matter is necessary. In the meantime, we need to be mindful of assertions that might be premature and damaging.   

Robert Barris, MD

Nassau University Medical Center

East Meadow, New York

Dr. Nasrallah responds

I appreciate the comments of Drs. Garza-Trevino and Barris in response to my editorial. Here is my reply to the points they addressed:

The efficacy and neurotoxicity of haloperidol are independent mechanisms. Blocking dopamine receptors controls psychotic symptoms, but neurotoxicity involves triggering apoptosis, increasing free radicals, binding to sigma receptors, increasing intracellular calcium, decreasing neurotropic factors, increasing P53, T-box, Jun kinase, etc. Neurotoxicity is separate from extrapyramidal side effects. Similarly, the neuroprotective effects of atypical antipsychotics, such as enhancement, neuroplasticity, increasing neurogenesis, and growth factors, are separate from their antipsychotic efficacy.

Only some of the CATIE study patients who responded to clozapine in phase II after not responding to any of the antipsychotics in phase I were refractory.

The assertion about the neurotoxicity of haloperidol is based on 28 published studies in neuroscience journals (which are rarely accessed or read by clinicians). Thus, the terms “premature and damaging” do not apply. I served as a messenger summarizing all these destructive properties of haloperidol¹ and I certainly was prepared to parry and deflect some arrows.

Meta-analysis of the efficacy of first- and second-generation antipsychotics
(SGAs) showed that most SGAs are similar to first-generation antipsychotics (FGAs).² What the SGAs do that gives the appearance of additional efficacy is avoid
the secondary negative and cognitive deficits associated with extrapyramidal side effects, which are much lower with SGAs.

The treatment of primary negative symptoms and cognitive impairment of schizophrenia remains a huge, unmet need—but there is some emerging data on glutamate modulation as a path to improving negative symptoms.

Finally, just as the FGAs vary in their extrapyramidal side effect profile, so do SGAs in their metabolic adverse effects. There are several SGAs that are metabolically benign, and there are also some FGAs that can cause serious weight gain and hyperglycemia.

Henry A. Nasrallah, MD

Editor-In-Chief

References

1. Nasrallah HA, Rush S. First generation antipsychotics are neurotoxic and impair neuroplasticity via multiple mechanisms. Biol Psychiatry. 2013;73:61S.

2. Davis JM, Chen N, Glick ID. A meta-analysis of second-generation antipsychotics. Arch Gen Psychiatry. 2003;60:553-564.

‘Farewell’ to haloperidol?

In response to “Haloperidol clearly is neurotoxic. Should it be banned?” (Current Psychiatry, From the Editor, July 2013, p. 7-8; http://bit.ly/1eMegnr), let me clarify several issues before a consensus is established on whether to discontinue the use of haloperidol.

Remember that­ since the first use of haloperidol—one of the butyrophenones—more than a half a century ago, practitioners and researchers were aware of its neurotoxicity. Nevertheless, butyrophenones are unique chemicals capable of controlling psychotic symptoms and severe brain dysfunctions, such as extrapyramidal reactions, neuroleptic malignant syndrome, akathisia, tardive dyskinesia, and galactorrhea, among others. Dr. Paul Janssen—founder of the laboratory that first released haloperidol—made a fortune that subsequently prevented him from being awarded the Nobel Prize in Physiology or Medicine.¹

A product that was the cornerstone of psychiatric treatment for half a century deserves a better farewell than the one Dr. Nasrallah is offering. Atypical antipsychotics present a number of drawbacks and have dangerous toxicity levels that still need study. I am concerned about metabolic syndrome (diabetes mellitus, hypercholesterolemia, gynecomastia, severe obesity, etc.), which may cost even more to treat than the cost of psychiatric care. In addition to the burden of their high and often unreasonable cost, quetiapine, olanzapine, clozapine, aripiprazole, risperidone, and other atypical antipsychotics have clinical limitations that often restrict their use.

If psychiatry needs a good, immediate fix, it would be in the development and approval of new chemicals that are both better tolerated than the butyrophenones and more affordable than atypical antipsychotics.²

Enrique S. Garza-Trevino, MD

Medical Director

San Antonio Mood Disorders Clinic

San Antonio, Texas

References

1. Healy D. The psychopharmacologist II: interviews by David Healy. Philadelphia, PA: Lippincott-Raven Publishers; 1998.

2. Garza-Trevino ES, Hollister LE, Overall JE. Combination of intramuscular hypnotics and neuroleptics for control of psychotic agitated patients. Am J Psychiatry. 1989;146:1598-1602.

Superior efficacy of atypical antipsychotics

Regarding Dr. Nasrallah’s editorial (July 2013) on the research delineating some of the neurotoxic aspects of first-generation antipsychotics, including haloperidol, he seems to shoot clinical psychiatry in the foot when he describes second-generation agents as having been “much safer for the brain than their older-generation counterparts (although they are not more efficacious).” This closing assertion is not followed by a reference. Indeed, one would anticipate that the newer agents would display greater efficacy given the neurotropic properties of the atypicals described by Dr. Nasrallah in his previous editorial, "Beyond dopamine: The 'other' effects of antipsychotics" (Current Psychiatry, June 2013, p. 8-9; http://bit.ly/1aA7MZw).

The only real study attempting to clarify this issue has been the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study; patients in that study were chronic and refractory to any intervention. In my practice, I have seen clear and compelling evidence supporting the superiority of atypical antipsychotics—as well as chronicity with multiple relapses and rehospitalizations.

More research into this matter is necessary. In the meantime, we need to be mindful of assertions that might be premature and damaging.   

Robert Barris, MD

Nassau University Medical Center

East Meadow, New York

Dr. Nasrallah responds

I appreciate the comments of Drs. Garza-Trevino and Barris in response to my editorial. Here is my reply to the points they addressed:

The efficacy and neurotoxicity of haloperidol are independent mechanisms. Blocking dopamine receptors controls psychotic symptoms, but neurotoxicity involves triggering apoptosis, increasing free radicals, binding to sigma receptors, increasing intracellular calcium, decreasing neurotropic factors, increasing P53, T-box, Jun kinase, etc. Neurotoxicity is separate from extrapyramidal side effects. Similarly, the neuroprotective effects of atypical antipsychotics, such as enhancement, neuroplasticity, increasing neurogenesis, and growth factors, are separate from their antipsychotic efficacy.

Only some of the CATIE study patients who responded to clozapine in phase II after not responding to any of the antipsychotics in phase I were refractory.

The assertion about the neurotoxicity of haloperidol is based on 28 published studies in neuroscience journals (which are rarely accessed or read by clinicians). Thus, the terms “premature and damaging” do not apply. I served as a messenger summarizing all these destructive properties of haloperidol¹ and I certainly was prepared to parry and deflect some arrows.

Meta-analysis of the efficacy of first- and second-generation antipsychotics
(SGAs) showed that most SGAs are similar to first-generation antipsychotics (FGAs).² What the SGAs do that gives the appearance of additional efficacy is avoid
the secondary negative and cognitive deficits associated with extrapyramidal side effects, which are much lower with SGAs.

The treatment of primary negative symptoms and cognitive impairment of schizophrenia remains a huge, unmet need—but there is some emerging data on glutamate modulation as a path to improving negative symptoms.

Finally, just as the FGAs vary in their extrapyramidal side effect profile, so do SGAs in their metabolic adverse effects. There are several SGAs that are metabolically benign, and there are also some FGAs that can cause serious weight gain and hyperglycemia.

Henry A. Nasrallah, MD

Editor-In-Chief

References

1. Nasrallah HA, Rush S. First generation antipsychotics are neurotoxic and impair neuroplasticity via multiple mechanisms. Biol Psychiatry. 2013;73:61S.

2. Davis JM, Chen N, Glick ID. A meta-analysis of second-generation antipsychotics. Arch Gen Psychiatry. 2003;60:553-564.

‘Farewell’ to haloperidol?

In response to “Haloperidol clearly is neurotoxic. Should it be banned?” (Current Psychiatry, From the Editor, July 2013, p. 7-8; http://bit.ly/1eMegnr), let me clarify several issues before a consensus is established on whether to discontinue the use of haloperidol.

Remember that­ since the first use of haloperidol—one of the butyrophenones—more than a half a century ago, practitioners and researchers were aware of its neurotoxicity. Nevertheless, butyrophenones are unique chemicals capable of controlling psychotic symptoms and severe brain dysfunctions, such as extrapyramidal reactions, neuroleptic malignant syndrome, akathisia, tardive dyskinesia, and galactorrhea, among others. Dr. Paul Janssen—founder of the laboratory that first released haloperidol—made a fortune that subsequently prevented him from being awarded the Nobel Prize in Physiology or Medicine.¹

A product that was the cornerstone of psychiatric treatment for half a century deserves a better farewell than the one Dr. Nasrallah is offering. Atypical antipsychotics present a number of drawbacks and have dangerous toxicity levels that still need study. I am concerned about metabolic syndrome (diabetes mellitus, hypercholesterolemia, gynecomastia, severe obesity, etc.), which may cost even more to treat than the cost of psychiatric care. In addition to the burden of their high and often unreasonable cost, quetiapine, olanzapine, clozapine, aripiprazole, risperidone, and other atypical antipsychotics have clinical limitations that often restrict their use.

If psychiatry needs a good, immediate fix, it would be in the development and approval of new chemicals that are both better tolerated than the butyrophenones and more affordable than atypical antipsychotics.²

Enrique S. Garza-Trevino, MD

Medical Director

San Antonio Mood Disorders Clinic

San Antonio, Texas

References

1. Healy D. The psychopharmacologist II: interviews by David Healy. Philadelphia, PA: Lippincott-Raven Publishers; 1998.

2. Garza-Trevino ES, Hollister LE, Overall JE. Combination of intramuscular hypnotics and neuroleptics for control of psychotic agitated patients. Am J Psychiatry. 1989;146:1598-1602.

Superior efficacy of atypical antipsychotics

Regarding Dr. Nasrallah’s editorial (July 2013) on the research delineating some of the neurotoxic aspects of first-generation antipsychotics, including haloperidol, he seems to shoot clinical psychiatry in the foot when he describes second-generation agents as having been “much safer for the brain than their older-generation counterparts (although they are not more efficacious).” This closing assertion is not followed by a reference. Indeed, one would anticipate that the newer agents would display greater efficacy given the neurotropic properties of the atypicals described by Dr. Nasrallah in his previous editorial, "Beyond dopamine: The 'other' effects of antipsychotics" (Current Psychiatry, June 2013, p. 8-9; http://bit.ly/1aA7MZw).

The only real study attempting to clarify this issue has been the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study; patients in that study were chronic and refractory to any intervention. In my practice, I have seen clear and compelling evidence supporting the superiority of atypical antipsychotics—as well as chronicity with multiple relapses and rehospitalizations.

More research into this matter is necessary. In the meantime, we need to be mindful of assertions that might be premature and damaging.   

Robert Barris, MD

Nassau University Medical Center

East Meadow, New York

Dr. Nasrallah responds

I appreciate the comments of Drs. Garza-Trevino and Barris in response to my editorial. Here is my reply to the points they addressed:

The efficacy and neurotoxicity of haloperidol are independent mechanisms. Blocking dopamine receptors controls psychotic symptoms, but neurotoxicity involves triggering apoptosis, increasing free radicals, binding to sigma receptors, increasing intracellular calcium, decreasing neurotropic factors, increasing P53, T-box, Jun kinase, etc. Neurotoxicity is separate from extrapyramidal side effects. Similarly, the neuroprotective effects of atypical antipsychotics, such as enhancement, neuroplasticity, increasing neurogenesis, and growth factors, are separate from their antipsychotic efficacy.

Only some of the CATIE study patients who responded to clozapine in phase II after not responding to any of the antipsychotics in phase I were refractory.

The assertion about the neurotoxicity of haloperidol is based on 28 published studies in neuroscience journals (which are rarely accessed or read by clinicians). Thus, the terms “premature and damaging” do not apply. I served as a messenger summarizing all these destructive properties of haloperidol¹ and I certainly was prepared to parry and deflect some arrows.

Meta-analysis of the efficacy of first- and second-generation antipsychotics
(SGAs) showed that most SGAs are similar to first-generation antipsychotics (FGAs).² What the SGAs do that gives the appearance of additional efficacy is avoid
the secondary negative and cognitive deficits associated with extrapyramidal side effects, which are much lower with SGAs.

The treatment of primary negative symptoms and cognitive impairment of schizophrenia remains a huge, unmet need—but there is some emerging data on glutamate modulation as a path to improving negative symptoms.

Finally, just as the FGAs vary in their extrapyramidal side effect profile, so do SGAs in their metabolic adverse effects. There are several SGAs that are metabolically benign, and there are also some FGAs that can cause serious weight gain and hyperglycemia.

Henry A. Nasrallah, MD

Editor-In-Chief

References

1. Nasrallah HA, Rush S. First generation antipsychotics are neurotoxic and impair neuroplasticity via multiple mechanisms. Biol Psychiatry. 2013;73:61S.

2. Davis JM, Chen N, Glick ID. A meta-analysis of second-generation antipsychotics. Arch Gen Psychiatry. 2003;60:553-564.

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.

In private practice, government, and (especially) academically affiliated settings, chart notations that are neither erroneous nor accurate but just imprecise are seen regularly. Academic supervisors may overlook these ambiguous notations by medical students and residents because of their regularity; others may be actively taught by supervisors who use ambiguous notations themselves.

In my experience, the most frequently seen imprecisions are in diagnoses of personality disorders: for example, the terms “clusters” and “deferred,” and the symptomatic overlap between antisocial personality disorder (APD) and substance abuse. Least helpful are qualifying phrases added to substance abuse diagnoses, along with an abundance of abbreviations. The latter occurs despite efforts by the U.S. Department of Veteran Affairs and other agencies to standardize acceptable lists of abbreviations. Many imprecisions could qualify for highlighting; here are 5 of the most unhelpful:

Clusters. Personality disorders are grouped into 3 “clusters,” according to similar characteristics (eg, Cluster A includes paranoid, schizoid, and schizotypal personality disorders and focuses on patients’ oddities and eccentricities). The need for identifying “clusters” could be debated, but a “cluster” is not a diagnosis. A psychiatric evaluation that notes “Cluster B traits” in lieu of a specific personality disorder is not informative, especially to a nonpsychiatric clinician. Which Cluster B traits apply? Is the patient unstable? Self-absorbed? Needy? Dramatic? Criminal? Assaultive?

In complicated or ambiguous cases, the diagnosis of a personality disorder not otherwise specified is appropriate, indicating that traits need to be clarified.

Deferred. This notation frequently is seen under axis II, and often is carried through the medical record for months or years. Psychiatrists are reluctant to diagnose a personality disorder because of the pejorative nature a diagnosis conveys. Nevertheless, by the second or third visit—after 2 or 3 hours of interview contact—it should be evident whether a personality disorder exists. If none does, “no diagnosis” should be documented. This notation can be adjusted if such evidence comes to light.

APD (or APD traits). This diagnosis often is made mistakenly when the root problem is in fact a substance abuse disorder. A multi-decade study of alcoholism and antisocial personality attributes in university students illustrated this phenomenon.¹

To be a successful substance abuser—that is, to satisfy the overwhelming urge to drink or use drugs—it’s essential to lie, cheat, and steal. Substance abusers might become belligerent when intoxicated. They might be arrested in bar fights, drive while intoxicated, and buy illegal substances. The result is incarceration, a common consequence of substance abuse and of APD. The latter diagnosis should be made only if the patient has exhibited a pattern of criminal behavior—often starting in adolescence—irrespective of substance abuse, such as breaking and entering, robbery, or assault with a deadly weapon.

Substance abusers often feel guilt and self-loathing for their “weakness,” and cannot gain control over their addiction; the APD patient, on the other hand, feels entitled to plunder and often justifies his (her) actions by attributing fault to the victim.

Keep in mind that many APD patients also are substance abusers; both diagnoses should be listed in the chart when that is the determination. Recognize that substance abuse and APD are distinct entities that should not be confused by the common denominator of having spent time in jail.

Early, late, full remission. These qualifiers often are appended to substance abuse disorders, but they do not convey useful information. How early is “early”? How late is “late”? Perhaps the most misleading term is “full” or “partial” remission,
because there is no clear definition of either.

If one is referring to length of time sober or a reduction in volume consumed, noting the date of the last use is more helpful—eg, “alcohol abuse in remission since summer of 2012.” If “partial” remission means the patient has reduced his intake, then that is not remission. The reduction can be specified—eg, “alcohol abuse, reduced to 1 or 2 beers per weekend.”

Abbreviations. Psychiatric evaluations should contain only standard, well-known medical shorthand (such as MSE for mental status exam). The military may be the biggest offender, devising acronyms and abbreviations for everything.

Two examples of abbreviations that I see in military psychiatric progress notes are AEB (“as evidenced by”) and LLGD (“linear, logical, and goal-directed”). Psychiatrists have a leg up on deciphering abbreviations in psychiatric notes; other providers might be compelled to resort to consultation. That wastes more time than typing out the words and results in frustration and lost productivity.

In private practice, government, and (especially) academically affiliated settings, chart notations that are neither erroneous nor accurate but just imprecise are seen regularly. Academic supervisors may overlook these ambiguous notations by medical students and residents because of their regularity; others may be actively taught by supervisors who use ambiguous notations themselves.

In my experience, the most frequently seen imprecisions are in diagnoses of personality disorders: for example, the terms “clusters” and “deferred,” and the symptomatic overlap between antisocial personality disorder (APD) and substance abuse. Least helpful are qualifying phrases added to substance abuse diagnoses, along with an abundance of abbreviations. The latter occurs despite efforts by the U.S. Department of Veteran Affairs and other agencies to standardize acceptable lists of abbreviations. Many imprecisions could qualify for highlighting; here are 5 of the most unhelpful:

Clusters. Personality disorders are grouped into 3 “clusters,” according to similar characteristics (eg, Cluster A includes paranoid, schizoid, and schizotypal personality disorders and focuses on patients’ oddities and eccentricities). The need for identifying “clusters” could be debated, but a “cluster” is not a diagnosis. A psychiatric evaluation that notes “Cluster B traits” in lieu of a specific personality disorder is not informative, especially to a nonpsychiatric clinician. Which Cluster B traits apply? Is the patient unstable? Self-absorbed? Needy? Dramatic? Criminal? Assaultive?

In complicated or ambiguous cases, the diagnosis of a personality disorder not otherwise specified is appropriate, indicating that traits need to be clarified.

Deferred. This notation frequently is seen under axis II, and often is carried through the medical record for months or years. Psychiatrists are reluctant to diagnose a personality disorder because of the pejorative nature a diagnosis conveys. Nevertheless, by the second or third visit—after 2 or 3 hours of interview contact—it should be evident whether a personality disorder exists. If none does, “no diagnosis” should be documented. This notation can be adjusted if such evidence comes to light.

APD (or APD traits). This diagnosis often is made mistakenly when the root problem is in fact a substance abuse disorder. A multi-decade study of alcoholism and antisocial personality attributes in university students illustrated this phenomenon.¹

To be a successful substance abuser—that is, to satisfy the overwhelming urge to drink or use drugs—it’s essential to lie, cheat, and steal. Substance abusers might become belligerent when intoxicated. They might be arrested in bar fights, drive while intoxicated, and buy illegal substances. The result is incarceration, a common consequence of substance abuse and of APD. The latter diagnosis should be made only if the patient has exhibited a pattern of criminal behavior—often starting in adolescence—irrespective of substance abuse, such as breaking and entering, robbery, or assault with a deadly weapon.

Substance abusers often feel guilt and self-loathing for their “weakness,” and cannot gain control over their addiction; the APD patient, on the other hand, feels entitled to plunder and often justifies his (her) actions by attributing fault to the victim.

Keep in mind that many APD patients also are substance abusers; both diagnoses should be listed in the chart when that is the determination. Recognize that substance abuse and APD are distinct entities that should not be confused by the common denominator of having spent time in jail.

Early, late, full remission. These qualifiers often are appended to substance abuse disorders, but they do not convey useful information. How early is “early”? How late is “late”? Perhaps the most misleading term is “full” or “partial” remission,
because there is no clear definition of either.

If one is referring to length of time sober or a reduction in volume consumed, noting the date of the last use is more helpful—eg, “alcohol abuse in remission since summer of 2012.” If “partial” remission means the patient has reduced his intake, then that is not remission. The reduction can be specified—eg, “alcohol abuse, reduced to 1 or 2 beers per weekend.”

Abbreviations. Psychiatric evaluations should contain only standard, well-known medical shorthand (such as MSE for mental status exam). The military may be the biggest offender, devising acronyms and abbreviations for everything.

Two examples of abbreviations that I see in military psychiatric progress notes are AEB (“as evidenced by”) and LLGD (“linear, logical, and goal-directed”). Psychiatrists have a leg up on deciphering abbreviations in psychiatric notes; other providers might be compelled to resort to consultation. That wastes more time than typing out the words and results in frustration and lost productivity.

In private practice, government, and (especially) academically affiliated settings, chart notations that are neither erroneous nor accurate but just imprecise are seen regularly. Academic supervisors may overlook these ambiguous notations by medical students and residents because of their regularity; others may be actively taught by supervisors who use ambiguous notations themselves.

In my experience, the most frequently seen imprecisions are in diagnoses of personality disorders: for example, the terms “clusters” and “deferred,” and the symptomatic overlap between antisocial personality disorder (APD) and substance abuse. Least helpful are qualifying phrases added to substance abuse diagnoses, along with an abundance of abbreviations. The latter occurs despite efforts by the U.S. Department of Veteran Affairs and other agencies to standardize acceptable lists of abbreviations. Many imprecisions could qualify for highlighting; here are 5 of the most unhelpful:

Clusters. Personality disorders are grouped into 3 “clusters,” according to similar characteristics (eg, Cluster A includes paranoid, schizoid, and schizotypal personality disorders and focuses on patients’ oddities and eccentricities). The need for identifying “clusters” could be debated, but a “cluster” is not a diagnosis. A psychiatric evaluation that notes “Cluster B traits” in lieu of a specific personality disorder is not informative, especially to a nonpsychiatric clinician. Which Cluster B traits apply? Is the patient unstable? Self-absorbed? Needy? Dramatic? Criminal? Assaultive?

In complicated or ambiguous cases, the diagnosis of a personality disorder not otherwise specified is appropriate, indicating that traits need to be clarified.

Deferred. This notation frequently is seen under axis II, and often is carried through the medical record for months or years. Psychiatrists are reluctant to diagnose a personality disorder because of the pejorative nature a diagnosis conveys. Nevertheless, by the second or third visit—after 2 or 3 hours of interview contact—it should be evident whether a personality disorder exists. If none does, “no diagnosis” should be documented. This notation can be adjusted if such evidence comes to light.

APD (or APD traits). This diagnosis often is made mistakenly when the root problem is in fact a substance abuse disorder. A multi-decade study of alcoholism and antisocial personality attributes in university students illustrated this phenomenon.¹

To be a successful substance abuser—that is, to satisfy the overwhelming urge to drink or use drugs—it’s essential to lie, cheat, and steal. Substance abusers might become belligerent when intoxicated. They might be arrested in bar fights, drive while intoxicated, and buy illegal substances. The result is incarceration, a common consequence of substance abuse and of APD. The latter diagnosis should be made only if the patient has exhibited a pattern of criminal behavior—often starting in adolescence—irrespective of substance abuse, such as breaking and entering, robbery, or assault with a deadly weapon.

Substance abusers often feel guilt and self-loathing for their “weakness,” and cannot gain control over their addiction; the APD patient, on the other hand, feels entitled to plunder and often justifies his (her) actions by attributing fault to the victim.

Keep in mind that many APD patients also are substance abusers; both diagnoses should be listed in the chart when that is the determination. Recognize that substance abuse and APD are distinct entities that should not be confused by the common denominator of having spent time in jail.

Early, late, full remission. These qualifiers often are appended to substance abuse disorders, but they do not convey useful information. How early is “early”? How late is “late”? Perhaps the most misleading term is “full” or “partial” remission,
because there is no clear definition of either.

If one is referring to length of time sober or a reduction in volume consumed, noting the date of the last use is more helpful—eg, “alcohol abuse in remission since summer of 2012.” If “partial” remission means the patient has reduced his intake, then that is not remission. The reduction can be specified—eg, “alcohol abuse, reduced to 1 or 2 beers per weekend.”

Abbreviations. Psychiatric evaluations should contain only standard, well-known medical shorthand (such as MSE for mental status exam). The military may be the biggest offender, devising acronyms and abbreviations for everything.

Two examples of abbreviations that I see in military psychiatric progress notes are AEB (“as evidenced by”) and LLGD (“linear, logical, and goal-directed”). Psychiatrists have a leg up on deciphering abbreviations in psychiatric notes; other providers might be compelled to resort to consultation. That wastes more time than typing out the words and results in frustration and lost productivity.