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Antidepressants: Is less more?
When it comes to antidepressant prescribing, less may be more, new research suggests.
A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.
“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.
He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.
“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.
However, at least one expert urged caution in interpreting the review’s findings.
“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.
The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
Personal experience
Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.
Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”
The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”
Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.
“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.
Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”
“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).
“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.
The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.
“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.
Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
Relapse or withdrawal?
The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”
“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”
He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.
“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.
“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.
He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
Helpful in the short term
Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”
The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.
Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.
Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.
“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.
Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
Lack of balance
Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.
However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.
“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.
The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.
Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.
“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.
Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When it comes to antidepressant prescribing, less may be more, new research suggests.
A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.
“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.
He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.
“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.
However, at least one expert urged caution in interpreting the review’s findings.
“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.
The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
Personal experience
Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.
Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”
The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”
Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.
“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.
Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”
“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).
“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.
The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.
“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.
Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
Relapse or withdrawal?
The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”
“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”
He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.
“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.
“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.
He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
Helpful in the short term
Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”
The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.
Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.
Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.
“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.
Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
Lack of balance
Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.
However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.
“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.
The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.
Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.
“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.
Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When it comes to antidepressant prescribing, less may be more, new research suggests.
A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.
“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.
He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.
“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.
However, at least one expert urged caution in interpreting the review’s findings.
“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.
The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
Personal experience
Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.
Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”
The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”
Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.
“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.
Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”
“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).
“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.
The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.
“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.
Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
Relapse or withdrawal?
The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”
“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”
He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.
“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.
“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.
He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
Helpful in the short term
Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”
The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.
Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.
Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.
“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.
Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
Lack of balance
Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.
However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.
“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.
The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.
Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.
“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.
Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE DRUG AND THERAPEUTICS BULLETIN
Virtual reality making progress as depression treatment
Virtual reality (VR) has been taking positive steps in a variety of treatment areas for some time. Now a Japanese company is asking the question: Can people with depression benefit from watching VR scenarios in which actors portray characters coping with the condition?
That’s the assertion of the Tokyo-based company Jolly Good, a VR start-up that introduced the U.S. version of its VRDTx program at the annual meeting of the Consumer Electronics Show.
“Using this as an adjunct for psychotherapy to help someone see an example of someone who’s struggling with depression can be a helpful tool,” said Katharine Larsson, PhD, RN, clinical director of Boston Behavioral Medicine in Brookline. Larsson and her BBM colleague, Amaro J. Laria, PhD, are helping Jolly Good to adapt the program for use in the United States.
VRDTx uses techniques from cognitive-behavioral therapy (CBT). Donning goggles, viewers watch people acting out situations common to depression.
One technique frequently used in CBT is to make a detailed plan, Dr. Laria said. For example, VRDTx users might watch a character with depression struggling to get out of bed but resolving to get up for at least 10 minutes one day, to go for a walk the next day, etc. “The virtual reality allows you to watch a person actually going through the process of applying the intervention,” he said.
In this way, the program could work like hypnotherapy or imaginal therapy where patients picture themselves in a situation that might trigger their depression and then picture themselves coping with that situation.
Dr. Larsson advised using the program primarily as a sort of homework. “ she said. “Using it to substitute or replace the time with a therapist, I don’t think it could begin to have any kind of real efficacy.”
Deploying virtual reality to treat mood disorders is not new, said Preethi Premkumar, PhD, a senior lecturer in psychology at London South Bank University, who has no relationship to Jolly Good.
Dr. Premkumar is first author of a study of a VR program used to treat people who have anxiety about speaking in public. The program depicts the user speaking before an audience and allows the user to vary the number of people in the audience and the audience’s reactions. The users gave it high marks, Dr. Premkumar said. “They felt that it encouraged them to take on public speaking more in reality.”
VR could work in a similar way for depressed people because they tend to catastrophize about specific situations. “Virtual reality can recreate those scenes and then make people confront it without overexposing them,” Dr. Premkumar said.
One recent review article found several studies on VR as a treatment for anxiety. While only a handful focused on depression, they had mostly favorable results.
Jolly Good sponsored one such study, presented Sept. 17, 2021, at the European Association for Behavioural and Cognitive Therapies. “Results indicate improvement in the scores of the targeted patients with depression,” according to an abstract the company published online. “Use of VR caused no adverse events, demonstrating that VR can be used safely in the CBT for of depression.” The company did not respond to a request for more details.
After viewing scenarios created for Japanese patients, Dr. Larsson and Dr. Laria offered Jolly Good several tips about making the transition to the United States. The actors should be more emotionally expressive. They should portray a more diverse cast of characters, including some female bosses. And not all scenes should be set in the workplace.
“In the U.S., at least in our experience, a lot of what depressed patients talk about is just their personal lives, their intimate relationship with a significant other, family relations, friends,” Dr. Laria said. “We gave them a whole list of topics that we felt would be more relevant for a U.S. audience.”
Dr. Larsson and Dr. Laria are consultants to Jolly Good. Dr. Premkumar reported no relevant financial interests.
A version of this article first appeared on Medscape.com.
Virtual reality (VR) has been taking positive steps in a variety of treatment areas for some time. Now a Japanese company is asking the question: Can people with depression benefit from watching VR scenarios in which actors portray characters coping with the condition?
That’s the assertion of the Tokyo-based company Jolly Good, a VR start-up that introduced the U.S. version of its VRDTx program at the annual meeting of the Consumer Electronics Show.
“Using this as an adjunct for psychotherapy to help someone see an example of someone who’s struggling with depression can be a helpful tool,” said Katharine Larsson, PhD, RN, clinical director of Boston Behavioral Medicine in Brookline. Larsson and her BBM colleague, Amaro J. Laria, PhD, are helping Jolly Good to adapt the program for use in the United States.
VRDTx uses techniques from cognitive-behavioral therapy (CBT). Donning goggles, viewers watch people acting out situations common to depression.
One technique frequently used in CBT is to make a detailed plan, Dr. Laria said. For example, VRDTx users might watch a character with depression struggling to get out of bed but resolving to get up for at least 10 minutes one day, to go for a walk the next day, etc. “The virtual reality allows you to watch a person actually going through the process of applying the intervention,” he said.
In this way, the program could work like hypnotherapy or imaginal therapy where patients picture themselves in a situation that might trigger their depression and then picture themselves coping with that situation.
Dr. Larsson advised using the program primarily as a sort of homework. “ she said. “Using it to substitute or replace the time with a therapist, I don’t think it could begin to have any kind of real efficacy.”
Deploying virtual reality to treat mood disorders is not new, said Preethi Premkumar, PhD, a senior lecturer in psychology at London South Bank University, who has no relationship to Jolly Good.
Dr. Premkumar is first author of a study of a VR program used to treat people who have anxiety about speaking in public. The program depicts the user speaking before an audience and allows the user to vary the number of people in the audience and the audience’s reactions. The users gave it high marks, Dr. Premkumar said. “They felt that it encouraged them to take on public speaking more in reality.”
VR could work in a similar way for depressed people because they tend to catastrophize about specific situations. “Virtual reality can recreate those scenes and then make people confront it without overexposing them,” Dr. Premkumar said.
One recent review article found several studies on VR as a treatment for anxiety. While only a handful focused on depression, they had mostly favorable results.
Jolly Good sponsored one such study, presented Sept. 17, 2021, at the European Association for Behavioural and Cognitive Therapies. “Results indicate improvement in the scores of the targeted patients with depression,” according to an abstract the company published online. “Use of VR caused no adverse events, demonstrating that VR can be used safely in the CBT for of depression.” The company did not respond to a request for more details.
After viewing scenarios created for Japanese patients, Dr. Larsson and Dr. Laria offered Jolly Good several tips about making the transition to the United States. The actors should be more emotionally expressive. They should portray a more diverse cast of characters, including some female bosses. And not all scenes should be set in the workplace.
“In the U.S., at least in our experience, a lot of what depressed patients talk about is just their personal lives, their intimate relationship with a significant other, family relations, friends,” Dr. Laria said. “We gave them a whole list of topics that we felt would be more relevant for a U.S. audience.”
Dr. Larsson and Dr. Laria are consultants to Jolly Good. Dr. Premkumar reported no relevant financial interests.
A version of this article first appeared on Medscape.com.
Virtual reality (VR) has been taking positive steps in a variety of treatment areas for some time. Now a Japanese company is asking the question: Can people with depression benefit from watching VR scenarios in which actors portray characters coping with the condition?
That’s the assertion of the Tokyo-based company Jolly Good, a VR start-up that introduced the U.S. version of its VRDTx program at the annual meeting of the Consumer Electronics Show.
“Using this as an adjunct for psychotherapy to help someone see an example of someone who’s struggling with depression can be a helpful tool,” said Katharine Larsson, PhD, RN, clinical director of Boston Behavioral Medicine in Brookline. Larsson and her BBM colleague, Amaro J. Laria, PhD, are helping Jolly Good to adapt the program for use in the United States.
VRDTx uses techniques from cognitive-behavioral therapy (CBT). Donning goggles, viewers watch people acting out situations common to depression.
One technique frequently used in CBT is to make a detailed plan, Dr. Laria said. For example, VRDTx users might watch a character with depression struggling to get out of bed but resolving to get up for at least 10 minutes one day, to go for a walk the next day, etc. “The virtual reality allows you to watch a person actually going through the process of applying the intervention,” he said.
In this way, the program could work like hypnotherapy or imaginal therapy where patients picture themselves in a situation that might trigger their depression and then picture themselves coping with that situation.
Dr. Larsson advised using the program primarily as a sort of homework. “ she said. “Using it to substitute or replace the time with a therapist, I don’t think it could begin to have any kind of real efficacy.”
Deploying virtual reality to treat mood disorders is not new, said Preethi Premkumar, PhD, a senior lecturer in psychology at London South Bank University, who has no relationship to Jolly Good.
Dr. Premkumar is first author of a study of a VR program used to treat people who have anxiety about speaking in public. The program depicts the user speaking before an audience and allows the user to vary the number of people in the audience and the audience’s reactions. The users gave it high marks, Dr. Premkumar said. “They felt that it encouraged them to take on public speaking more in reality.”
VR could work in a similar way for depressed people because they tend to catastrophize about specific situations. “Virtual reality can recreate those scenes and then make people confront it without overexposing them,” Dr. Premkumar said.
One recent review article found several studies on VR as a treatment for anxiety. While only a handful focused on depression, they had mostly favorable results.
Jolly Good sponsored one such study, presented Sept. 17, 2021, at the European Association for Behavioural and Cognitive Therapies. “Results indicate improvement in the scores of the targeted patients with depression,” according to an abstract the company published online. “Use of VR caused no adverse events, demonstrating that VR can be used safely in the CBT for of depression.” The company did not respond to a request for more details.
After viewing scenarios created for Japanese patients, Dr. Larsson and Dr. Laria offered Jolly Good several tips about making the transition to the United States. The actors should be more emotionally expressive. They should portray a more diverse cast of characters, including some female bosses. And not all scenes should be set in the workplace.
“In the U.S., at least in our experience, a lot of what depressed patients talk about is just their personal lives, their intimate relationship with a significant other, family relations, friends,” Dr. Laria said. “We gave them a whole list of topics that we felt would be more relevant for a U.S. audience.”
Dr. Larsson and Dr. Laria are consultants to Jolly Good. Dr. Premkumar reported no relevant financial interests.
A version of this article first appeared on Medscape.com.
Despite the stigma, ECT remains a gold standard
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
Effective alternatives to psychotherapy for borderline personality disorder
Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.
Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.
The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.
“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.
The findings were published online in JAMA Psychiatry.
Extreme sensitivity
Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.
The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.
Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.
Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.
The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.
A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.
In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.
For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.
‘High satisfaction’
Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.
The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.
The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.
All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.
For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.
“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”
‘Turns things upside down’
That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.
he added.
They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.
When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.
On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.
The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
Unique contribution
Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.
“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.
Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.
There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.
“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.
Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”
He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.
The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.
Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.
The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.
“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.
The findings were published online in JAMA Psychiatry.
Extreme sensitivity
Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.
The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.
Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.
Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.
The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.
A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.
In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.
For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.
‘High satisfaction’
Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.
The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.
The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.
All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.
For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.
“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”
‘Turns things upside down’
That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.
he added.
They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.
When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.
On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.
The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
Unique contribution
Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.
“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.
Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.
There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.
“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.
Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”
He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.
The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.
Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.
The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.
“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.
The findings were published online in JAMA Psychiatry.
Extreme sensitivity
Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.
The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.
Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.
Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.
The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.
A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.
In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.
For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.
‘High satisfaction’
Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.
The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.
The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.
All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.
For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.
“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”
‘Turns things upside down’
That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.
he added.
They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.
When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.
On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.
The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
Unique contribution
Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.
“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.
Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.
There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.
“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.
Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”
He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.
The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Novel antidepressant shows promise as add-on therapy
as add-on therapy
Adjunctive treatment with the novel oral medication REL-1017 (esmethadone) is effective in adults with major depressive disorder (MDD) who have failed other antidepressants, new research suggests.
REL-1017, from Relmada Therapeutics, is a novel N-methyl-D-aspartate receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission.
Results from a phase 2a study showed rapid “therapeutic efficacy,” with a statistical difference by day 4, and the improvement was “robust,” with an effect size of 0.7 to 1. The positive outcome was also sustained for at least 1 week after treatment discontinuation, coinvestigator Paolo L. Manfredi, MD, chief scientific officer, Relmada Therapeutics, noted.
“Considering that the available traditional antidepressants have an average effect size around 0.3, this novel, potential rapid-acting antidepressant … holds great promise for millions of patients suffering from depression,” Dr. Manfredi told this news organization.
These results were obtained with a “very-well-tolerated once-daily oral NMDAR antagonist, without the dissociative effects seen with ketamine,” he added.
The findings were published online in the American Journal of Psychiatry.
‘Clear need’ for better therapies
It is estimated that more than half of patients with MDD fail to respond adequately following their first standard antidepressant treatment. In addition, responses are often delayed by 4-8 weeks after starting an antidepressant.
Therefore, there is a “clear need” to develop drugs for MDD that act quickly and with improved efficacy, the investigators note.
The phase 2a study of REL-1017 enrolled 62 adult patients (45% women) aged 18-65 years with moderate to severe MDD and no significant psychiatric comorbidity. All had failed to benefit from one to three standard antidepressant treatments in their current major depressive episode.
The researchers evaluated two doses of REL-1017 (25 mg and 50 mg once daily) vs. placebo given as adjunctive treatment. The assigned treatment lasted 7 days.
The primary study objectives were safety and tolerability. Results showed no serious adverse events (AEs), and no patients experienced treatment-emergent AEs that led to the stopping of treatment.
In addition, patients receiving the active drug experienced mild or moderate transient AEs comparable to placebo, with no opioid, dissociative, or psychotomimetic symptoms, or withdrawal effects when treatment ended.
The most common AEs reported were headache, constipation, nausea, and sleepiness.
Significant efficacy
The primary efficacy endpoint was the Montgomery–Åsberg Depression Scale (MADRS) score.
MADRS scores showed improvement on day 4 of treatment in both REL-1017 groups, and the improvement continued through day 7 (last dose) and day 14 (7 days after the last dose), with P ≤ .0308 and effect sizes ranging from 0.7 to 1.0.
Mean change from baseline in MADRS scores showed more improvement at the end of the dosing period for both dosing groups (–16.8 with 25 mg and –16.6 with 50 mg) vs. –8.8 with placebo.
Results of the other efficacy endpoints of Symptoms of Depression Questionnaire (SDQ) score and Clinical Global Impressions severity scale (CGI-S) and improvement scale (CGI-I) scores were similar to that of the MADRS.
Remission rates (defined as a MADRS score ≤10) on day 14, the last day of efficacy assessment, were 5% with placebo vs. 31% (P = .035) with REL-1017 25 mg and 39% (P = .01) with REL-1017 50 mg.
The number needed to treat to achieve remission on day 14 was four with the 25-mg dose and three with the 50-mg dose.
Phase 3 trials to confirm the efficacy and safety of REL-1017 are in progress, with topline results expected later this year, the investigators report.
The study was funded by Relmada Therapeutics. Dr. Manfredi has received personal fees from and/or held stock ownership in Relmada. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
Adjunctive treatment with the novel oral medication REL-1017 (esmethadone) is effective in adults with major depressive disorder (MDD) who have failed other antidepressants, new research suggests.
REL-1017, from Relmada Therapeutics, is a novel N-methyl-D-aspartate receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission.
Results from a phase 2a study showed rapid “therapeutic efficacy,” with a statistical difference by day 4, and the improvement was “robust,” with an effect size of 0.7 to 1. The positive outcome was also sustained for at least 1 week after treatment discontinuation, coinvestigator Paolo L. Manfredi, MD, chief scientific officer, Relmada Therapeutics, noted.
“Considering that the available traditional antidepressants have an average effect size around 0.3, this novel, potential rapid-acting antidepressant … holds great promise for millions of patients suffering from depression,” Dr. Manfredi told this news organization.
These results were obtained with a “very-well-tolerated once-daily oral NMDAR antagonist, without the dissociative effects seen with ketamine,” he added.
The findings were published online in the American Journal of Psychiatry.
‘Clear need’ for better therapies
It is estimated that more than half of patients with MDD fail to respond adequately following their first standard antidepressant treatment. In addition, responses are often delayed by 4-8 weeks after starting an antidepressant.
Therefore, there is a “clear need” to develop drugs for MDD that act quickly and with improved efficacy, the investigators note.
The phase 2a study of REL-1017 enrolled 62 adult patients (45% women) aged 18-65 years with moderate to severe MDD and no significant psychiatric comorbidity. All had failed to benefit from one to three standard antidepressant treatments in their current major depressive episode.
The researchers evaluated two doses of REL-1017 (25 mg and 50 mg once daily) vs. placebo given as adjunctive treatment. The assigned treatment lasted 7 days.
The primary study objectives were safety and tolerability. Results showed no serious adverse events (AEs), and no patients experienced treatment-emergent AEs that led to the stopping of treatment.
In addition, patients receiving the active drug experienced mild or moderate transient AEs comparable to placebo, with no opioid, dissociative, or psychotomimetic symptoms, or withdrawal effects when treatment ended.
The most common AEs reported were headache, constipation, nausea, and sleepiness.
Significant efficacy
The primary efficacy endpoint was the Montgomery–Åsberg Depression Scale (MADRS) score.
MADRS scores showed improvement on day 4 of treatment in both REL-1017 groups, and the improvement continued through day 7 (last dose) and day 14 (7 days after the last dose), with P ≤ .0308 and effect sizes ranging from 0.7 to 1.0.
Mean change from baseline in MADRS scores showed more improvement at the end of the dosing period for both dosing groups (–16.8 with 25 mg and –16.6 with 50 mg) vs. –8.8 with placebo.
Results of the other efficacy endpoints of Symptoms of Depression Questionnaire (SDQ) score and Clinical Global Impressions severity scale (CGI-S) and improvement scale (CGI-I) scores were similar to that of the MADRS.
Remission rates (defined as a MADRS score ≤10) on day 14, the last day of efficacy assessment, were 5% with placebo vs. 31% (P = .035) with REL-1017 25 mg and 39% (P = .01) with REL-1017 50 mg.
The number needed to treat to achieve remission on day 14 was four with the 25-mg dose and three with the 50-mg dose.
Phase 3 trials to confirm the efficacy and safety of REL-1017 are in progress, with topline results expected later this year, the investigators report.
The study was funded by Relmada Therapeutics. Dr. Manfredi has received personal fees from and/or held stock ownership in Relmada. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
Adjunctive treatment with the novel oral medication REL-1017 (esmethadone) is effective in adults with major depressive disorder (MDD) who have failed other antidepressants, new research suggests.
REL-1017, from Relmada Therapeutics, is a novel N-methyl-D-aspartate receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission.
Results from a phase 2a study showed rapid “therapeutic efficacy,” with a statistical difference by day 4, and the improvement was “robust,” with an effect size of 0.7 to 1. The positive outcome was also sustained for at least 1 week after treatment discontinuation, coinvestigator Paolo L. Manfredi, MD, chief scientific officer, Relmada Therapeutics, noted.
“Considering that the available traditional antidepressants have an average effect size around 0.3, this novel, potential rapid-acting antidepressant … holds great promise for millions of patients suffering from depression,” Dr. Manfredi told this news organization.
These results were obtained with a “very-well-tolerated once-daily oral NMDAR antagonist, without the dissociative effects seen with ketamine,” he added.
The findings were published online in the American Journal of Psychiatry.
‘Clear need’ for better therapies
It is estimated that more than half of patients with MDD fail to respond adequately following their first standard antidepressant treatment. In addition, responses are often delayed by 4-8 weeks after starting an antidepressant.
Therefore, there is a “clear need” to develop drugs for MDD that act quickly and with improved efficacy, the investigators note.
The phase 2a study of REL-1017 enrolled 62 adult patients (45% women) aged 18-65 years with moderate to severe MDD and no significant psychiatric comorbidity. All had failed to benefit from one to three standard antidepressant treatments in their current major depressive episode.
The researchers evaluated two doses of REL-1017 (25 mg and 50 mg once daily) vs. placebo given as adjunctive treatment. The assigned treatment lasted 7 days.
The primary study objectives were safety and tolerability. Results showed no serious adverse events (AEs), and no patients experienced treatment-emergent AEs that led to the stopping of treatment.
In addition, patients receiving the active drug experienced mild or moderate transient AEs comparable to placebo, with no opioid, dissociative, or psychotomimetic symptoms, or withdrawal effects when treatment ended.
The most common AEs reported were headache, constipation, nausea, and sleepiness.
Significant efficacy
The primary efficacy endpoint was the Montgomery–Åsberg Depression Scale (MADRS) score.
MADRS scores showed improvement on day 4 of treatment in both REL-1017 groups, and the improvement continued through day 7 (last dose) and day 14 (7 days after the last dose), with P ≤ .0308 and effect sizes ranging from 0.7 to 1.0.
Mean change from baseline in MADRS scores showed more improvement at the end of the dosing period for both dosing groups (–16.8 with 25 mg and –16.6 with 50 mg) vs. –8.8 with placebo.
Results of the other efficacy endpoints of Symptoms of Depression Questionnaire (SDQ) score and Clinical Global Impressions severity scale (CGI-S) and improvement scale (CGI-I) scores were similar to that of the MADRS.
Remission rates (defined as a MADRS score ≤10) on day 14, the last day of efficacy assessment, were 5% with placebo vs. 31% (P = .035) with REL-1017 25 mg and 39% (P = .01) with REL-1017 50 mg.
The number needed to treat to achieve remission on day 14 was four with the 25-mg dose and three with the 50-mg dose.
Phase 3 trials to confirm the efficacy and safety of REL-1017 are in progress, with topline results expected later this year, the investigators report.
The study was funded by Relmada Therapeutics. Dr. Manfredi has received personal fees from and/or held stock ownership in Relmada. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
as add-on therapy
as add-on therapy
Psychiatry and semantics
I am a psychiatrist, which means I am a mental health professional, which means I work with people with mental illness. Sometimes people with mental health conditions who suffer from mental illness need to take a day off work – also called a mental health day – because they are too symptomatic to work, and sometimes people who don’t have a mental illness need to take a day off work, also called a mental health day, because they are feeling stressed.
Sometimes professional athletes don’t do things they agreed to do in their contracts because they realize that doing these things is very upsetting and will be detrimental to their mental health, or maybe they have a mental illness and doing these things will worsen their mental health condition, which is, in fact, a mental illness. Other times people with mental health conditions need to have pets travel with them because this mitigates the symptoms of their mental illness or perhaps it’s just good for their mental health. And finally, some people suffer from mental illnesses, or sometimes from learning problems, which are severe enough that a person with these conditions has a disability and needs special accommodations to function optimally in educational or occupational settings, or needs public financial support because their difficulties disable them to the point that they can’t work at all.
Is your head spinning yet? who we serve, and differentiating the fact that what someone with a psychiatric disorder needs to do to function or to alleviate emotional suffering may be entirely different from the things that everyone needs to do, regardless of whether they have a psychiatric disorder, to feel their emotional best.
The National Alliance on Mental Illness tells us that one in five Americans are suffering from a mental illness, while the Epidemiologic Catchment Area Program revealed that half of people will meet criteria for a mental illness at some point in their lives. We hear about “the mentally ill” constantly in the news – often in relation to mass shooters or homelessness – yet even psychiatrists might be pressed to define who exactly the “mentally ill” are. And how many of us could not somehow, at some time, find ourselves in 1 of the 157 disorders that DSM-5 lists – down from 365 disorders in the DSM-IV-TR?
Differentiating mental health from mental illness is just the beginning of our semantic confusion. As psychiatrists we treat major depression, and yet the illness “depression,” a syndromic constellation of symptoms, includes the key symptom of sadness. People often say they are “depressed” when they mean they are sad or demoralized, and yet, if their sadness persists in the absence of other symptoms, they may well want, or feel they “should” have medications, even in the absence of a disorder. And maybe those medications help them feel better, so that the presence or absence of a verified illness doesn’t really matter. But if the medications cause adverse reactions, then psychiatry might have done a better job by that person’s sadness. Melancholia, or perhaps any designation than “depression,” with its multiple meanings, might better serve our patients and our profession. This is only one example, as the number of people who tell me they have obsessive-compulsive disorder – or more often announce, “I’m OCD!” because they are well organized in a productive way is remarkable. And while I have treated only a few people who meet the criteria for narcissistic personality disorder, from general conversation it would seem that they are at every dinner table and by every water cooler.
Does it matter? A diagnostic lexicon can be so helpful when it guides treatment, provides a heterogeneous group of patients for research studies, and allows for an understanding of the etiology, course, and prognosis of a given condition. When someone is so depressed that they can’t get out of bed, or is so disorganized that they can’t perform their job and might cause a disturbance in their workplace, it is good to instruct them to take time off work and send them back well with a doctor’s note. But this is different from the person who doesn’t want to face a difficult situation, who simply doesn’t like their job or their boss, or who wants their pet declared an emotional support animal to avoid the fee the airlines charge to bring an animal on board if one does not have a psychiatric diagnosis. Sometimes these lines are blurry – if someone does not want to do something because it makes them anxious, does it matter how deep the pit in their stomach is, or if they are having full-blown panic attacks? When do we agree that their distress is reason to allow them to avoid responsibilities without repercussions versus a violation of their obligations and an infringement on others?
Diagnoses offer solace to some patients: There is a name for their suffering, available treatment, and often others with the same condition to look to for guidance and community. For others, a psychiatric diagnosis is a source of shame, a label they see as damaging to their character and sometimes to their careers – including in medicine – where we have been particularly unsympathetic to those who announce a psychiatric history.
In some cultures, the label itself decreases someone’s attractiveness as a potential marriage partner. We would all like to see the stigma of mental illness vanish, but we have a long way to go.
Psychiatric diagnoses move over time and with our politics and culture. This is good; we don’t hold on to what we learn to be untrue. But they may well add to issues of inequity. Those who can afford to pay for expensive educational assessments can request educational accommodations, including untimed standardized tests. This advantage may not be available to those without the resources to pay for these evaluations, and one might wonder why all comers can’t take untimed tests so as not to favor the privileged. Psychiatry has long been accused of diagnosing people of color with poor prognosis illnesses and women with conditions that imply emotional weakness.
While our diagnoses have clinical utility, it is unfortunate that they have come to be about reimbursement. A diagnosis needs to be assigned for insurers to pay for care, and so we create diagnostic categories to allow for treatment. Is this reasonable? Do we need to say that someone who is suffering after the death of a loved one has a mental illness in order to allow them to seek relief from their suffering? It leads us to believe that all suffering is about pathology, that we should expect pain-free emotional lives. Perhaps we need a diagnostic category of psychic pain, not otherwise specified, to allow for treatment for those who simply ache.
Mental illness is about interventions to alleviate the suffering of those with disorders. Mental health is about interventions that may benefit everyone, whether they suffer from a mental illness or not. Sleep, nutrition, exercise, sunlight, nature, entertainment and escape, yoga, meditation, vacations in beautiful places with loving people – these are things that potentially help us all whether we do or do not have an illness. With so much confusion about what it is we do, and about who “should” get help, who can get help, who might want help, and where they should go to seek help, perhaps it would be better if our lingo were more precise.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). The has a private practice and is assistant professor of psychiatry ad behavioral sciences at Johns Hopkins University, both in Baltimore. She has no disclosures.
I am a psychiatrist, which means I am a mental health professional, which means I work with people with mental illness. Sometimes people with mental health conditions who suffer from mental illness need to take a day off work – also called a mental health day – because they are too symptomatic to work, and sometimes people who don’t have a mental illness need to take a day off work, also called a mental health day, because they are feeling stressed.
Sometimes professional athletes don’t do things they agreed to do in their contracts because they realize that doing these things is very upsetting and will be detrimental to their mental health, or maybe they have a mental illness and doing these things will worsen their mental health condition, which is, in fact, a mental illness. Other times people with mental health conditions need to have pets travel with them because this mitigates the symptoms of their mental illness or perhaps it’s just good for their mental health. And finally, some people suffer from mental illnesses, or sometimes from learning problems, which are severe enough that a person with these conditions has a disability and needs special accommodations to function optimally in educational or occupational settings, or needs public financial support because their difficulties disable them to the point that they can’t work at all.
Is your head spinning yet? who we serve, and differentiating the fact that what someone with a psychiatric disorder needs to do to function or to alleviate emotional suffering may be entirely different from the things that everyone needs to do, regardless of whether they have a psychiatric disorder, to feel their emotional best.
The National Alliance on Mental Illness tells us that one in five Americans are suffering from a mental illness, while the Epidemiologic Catchment Area Program revealed that half of people will meet criteria for a mental illness at some point in their lives. We hear about “the mentally ill” constantly in the news – often in relation to mass shooters or homelessness – yet even psychiatrists might be pressed to define who exactly the “mentally ill” are. And how many of us could not somehow, at some time, find ourselves in 1 of the 157 disorders that DSM-5 lists – down from 365 disorders in the DSM-IV-TR?
Differentiating mental health from mental illness is just the beginning of our semantic confusion. As psychiatrists we treat major depression, and yet the illness “depression,” a syndromic constellation of symptoms, includes the key symptom of sadness. People often say they are “depressed” when they mean they are sad or demoralized, and yet, if their sadness persists in the absence of other symptoms, they may well want, or feel they “should” have medications, even in the absence of a disorder. And maybe those medications help them feel better, so that the presence or absence of a verified illness doesn’t really matter. But if the medications cause adverse reactions, then psychiatry might have done a better job by that person’s sadness. Melancholia, or perhaps any designation than “depression,” with its multiple meanings, might better serve our patients and our profession. This is only one example, as the number of people who tell me they have obsessive-compulsive disorder – or more often announce, “I’m OCD!” because they are well organized in a productive way is remarkable. And while I have treated only a few people who meet the criteria for narcissistic personality disorder, from general conversation it would seem that they are at every dinner table and by every water cooler.
Does it matter? A diagnostic lexicon can be so helpful when it guides treatment, provides a heterogeneous group of patients for research studies, and allows for an understanding of the etiology, course, and prognosis of a given condition. When someone is so depressed that they can’t get out of bed, or is so disorganized that they can’t perform their job and might cause a disturbance in their workplace, it is good to instruct them to take time off work and send them back well with a doctor’s note. But this is different from the person who doesn’t want to face a difficult situation, who simply doesn’t like their job or their boss, or who wants their pet declared an emotional support animal to avoid the fee the airlines charge to bring an animal on board if one does not have a psychiatric diagnosis. Sometimes these lines are blurry – if someone does not want to do something because it makes them anxious, does it matter how deep the pit in their stomach is, or if they are having full-blown panic attacks? When do we agree that their distress is reason to allow them to avoid responsibilities without repercussions versus a violation of their obligations and an infringement on others?
Diagnoses offer solace to some patients: There is a name for their suffering, available treatment, and often others with the same condition to look to for guidance and community. For others, a psychiatric diagnosis is a source of shame, a label they see as damaging to their character and sometimes to their careers – including in medicine – where we have been particularly unsympathetic to those who announce a psychiatric history.
In some cultures, the label itself decreases someone’s attractiveness as a potential marriage partner. We would all like to see the stigma of mental illness vanish, but we have a long way to go.
Psychiatric diagnoses move over time and with our politics and culture. This is good; we don’t hold on to what we learn to be untrue. But they may well add to issues of inequity. Those who can afford to pay for expensive educational assessments can request educational accommodations, including untimed standardized tests. This advantage may not be available to those without the resources to pay for these evaluations, and one might wonder why all comers can’t take untimed tests so as not to favor the privileged. Psychiatry has long been accused of diagnosing people of color with poor prognosis illnesses and women with conditions that imply emotional weakness.
While our diagnoses have clinical utility, it is unfortunate that they have come to be about reimbursement. A diagnosis needs to be assigned for insurers to pay for care, and so we create diagnostic categories to allow for treatment. Is this reasonable? Do we need to say that someone who is suffering after the death of a loved one has a mental illness in order to allow them to seek relief from their suffering? It leads us to believe that all suffering is about pathology, that we should expect pain-free emotional lives. Perhaps we need a diagnostic category of psychic pain, not otherwise specified, to allow for treatment for those who simply ache.
Mental illness is about interventions to alleviate the suffering of those with disorders. Mental health is about interventions that may benefit everyone, whether they suffer from a mental illness or not. Sleep, nutrition, exercise, sunlight, nature, entertainment and escape, yoga, meditation, vacations in beautiful places with loving people – these are things that potentially help us all whether we do or do not have an illness. With so much confusion about what it is we do, and about who “should” get help, who can get help, who might want help, and where they should go to seek help, perhaps it would be better if our lingo were more precise.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). The has a private practice and is assistant professor of psychiatry ad behavioral sciences at Johns Hopkins University, both in Baltimore. She has no disclosures.
I am a psychiatrist, which means I am a mental health professional, which means I work with people with mental illness. Sometimes people with mental health conditions who suffer from mental illness need to take a day off work – also called a mental health day – because they are too symptomatic to work, and sometimes people who don’t have a mental illness need to take a day off work, also called a mental health day, because they are feeling stressed.
Sometimes professional athletes don’t do things they agreed to do in their contracts because they realize that doing these things is very upsetting and will be detrimental to their mental health, or maybe they have a mental illness and doing these things will worsen their mental health condition, which is, in fact, a mental illness. Other times people with mental health conditions need to have pets travel with them because this mitigates the symptoms of their mental illness or perhaps it’s just good for their mental health. And finally, some people suffer from mental illnesses, or sometimes from learning problems, which are severe enough that a person with these conditions has a disability and needs special accommodations to function optimally in educational or occupational settings, or needs public financial support because their difficulties disable them to the point that they can’t work at all.
Is your head spinning yet? who we serve, and differentiating the fact that what someone with a psychiatric disorder needs to do to function or to alleviate emotional suffering may be entirely different from the things that everyone needs to do, regardless of whether they have a psychiatric disorder, to feel their emotional best.
The National Alliance on Mental Illness tells us that one in five Americans are suffering from a mental illness, while the Epidemiologic Catchment Area Program revealed that half of people will meet criteria for a mental illness at some point in their lives. We hear about “the mentally ill” constantly in the news – often in relation to mass shooters or homelessness – yet even psychiatrists might be pressed to define who exactly the “mentally ill” are. And how many of us could not somehow, at some time, find ourselves in 1 of the 157 disorders that DSM-5 lists – down from 365 disorders in the DSM-IV-TR?
Differentiating mental health from mental illness is just the beginning of our semantic confusion. As psychiatrists we treat major depression, and yet the illness “depression,” a syndromic constellation of symptoms, includes the key symptom of sadness. People often say they are “depressed” when they mean they are sad or demoralized, and yet, if their sadness persists in the absence of other symptoms, they may well want, or feel they “should” have medications, even in the absence of a disorder. And maybe those medications help them feel better, so that the presence or absence of a verified illness doesn’t really matter. But if the medications cause adverse reactions, then psychiatry might have done a better job by that person’s sadness. Melancholia, or perhaps any designation than “depression,” with its multiple meanings, might better serve our patients and our profession. This is only one example, as the number of people who tell me they have obsessive-compulsive disorder – or more often announce, “I’m OCD!” because they are well organized in a productive way is remarkable. And while I have treated only a few people who meet the criteria for narcissistic personality disorder, from general conversation it would seem that they are at every dinner table and by every water cooler.
Does it matter? A diagnostic lexicon can be so helpful when it guides treatment, provides a heterogeneous group of patients for research studies, and allows for an understanding of the etiology, course, and prognosis of a given condition. When someone is so depressed that they can’t get out of bed, or is so disorganized that they can’t perform their job and might cause a disturbance in their workplace, it is good to instruct them to take time off work and send them back well with a doctor’s note. But this is different from the person who doesn’t want to face a difficult situation, who simply doesn’t like their job or their boss, or who wants their pet declared an emotional support animal to avoid the fee the airlines charge to bring an animal on board if one does not have a psychiatric diagnosis. Sometimes these lines are blurry – if someone does not want to do something because it makes them anxious, does it matter how deep the pit in their stomach is, or if they are having full-blown panic attacks? When do we agree that their distress is reason to allow them to avoid responsibilities without repercussions versus a violation of their obligations and an infringement on others?
Diagnoses offer solace to some patients: There is a name for their suffering, available treatment, and often others with the same condition to look to for guidance and community. For others, a psychiatric diagnosis is a source of shame, a label they see as damaging to their character and sometimes to their careers – including in medicine – where we have been particularly unsympathetic to those who announce a psychiatric history.
In some cultures, the label itself decreases someone’s attractiveness as a potential marriage partner. We would all like to see the stigma of mental illness vanish, but we have a long way to go.
Psychiatric diagnoses move over time and with our politics and culture. This is good; we don’t hold on to what we learn to be untrue. But they may well add to issues of inequity. Those who can afford to pay for expensive educational assessments can request educational accommodations, including untimed standardized tests. This advantage may not be available to those without the resources to pay for these evaluations, and one might wonder why all comers can’t take untimed tests so as not to favor the privileged. Psychiatry has long been accused of diagnosing people of color with poor prognosis illnesses and women with conditions that imply emotional weakness.
While our diagnoses have clinical utility, it is unfortunate that they have come to be about reimbursement. A diagnosis needs to be assigned for insurers to pay for care, and so we create diagnostic categories to allow for treatment. Is this reasonable? Do we need to say that someone who is suffering after the death of a loved one has a mental illness in order to allow them to seek relief from their suffering? It leads us to believe that all suffering is about pathology, that we should expect pain-free emotional lives. Perhaps we need a diagnostic category of psychic pain, not otherwise specified, to allow for treatment for those who simply ache.
Mental illness is about interventions to alleviate the suffering of those with disorders. Mental health is about interventions that may benefit everyone, whether they suffer from a mental illness or not. Sleep, nutrition, exercise, sunlight, nature, entertainment and escape, yoga, meditation, vacations in beautiful places with loving people – these are things that potentially help us all whether we do or do not have an illness. With so much confusion about what it is we do, and about who “should” get help, who can get help, who might want help, and where they should go to seek help, perhaps it would be better if our lingo were more precise.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). The has a private practice and is assistant professor of psychiatry ad behavioral sciences at Johns Hopkins University, both in Baltimore. She has no disclosures.
New data support a causal role for depression in Alzheimer’s
Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.
As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.
“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.
The findings were published online Dec. 16, 2021, in Biological Psychiatry.
Postmortem data
The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.
They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.
The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.
They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.
The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.
After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.
suggesting the two conditions have a shared genetic basis.
The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.
After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
One-way relationship
The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.
“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.
In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.
“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.
It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.
These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.
The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”
However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.
For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
Need for further research
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.
“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.
While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.
However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.
A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.
Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.
The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.
“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.
Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.
As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.
“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.
The findings were published online Dec. 16, 2021, in Biological Psychiatry.
Postmortem data
The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.
They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.
The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.
They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.
The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.
After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.
suggesting the two conditions have a shared genetic basis.
The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.
After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
One-way relationship
The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.
“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.
In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.
“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.
It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.
These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.
The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”
However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.
For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
Need for further research
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.
“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.
While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.
However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.
A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.
Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.
The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.
“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.
Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.
As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.
“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.
The findings were published online Dec. 16, 2021, in Biological Psychiatry.
Postmortem data
The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.
They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.
The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.
They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.
The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.
After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.
suggesting the two conditions have a shared genetic basis.
The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.
After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
One-way relationship
The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.
“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.
In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.
“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.
It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.
These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.
The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”
However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.
For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
Need for further research
Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.
“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.
While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.
However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.
A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.
Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.
The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.
“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.
Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BIOLOGICAL PSYCHIATRY
Opioid agonist therapy guards against self-harm, suicide
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Confusing messages on COVID taking a psychological toll
The Centers for Disease Control and Prevention’s decision to shorten the length of isolation time for asymptomatic Americans with COVID-19, regardless of their vaccination status, to 5 days from 10 days is confusing. I hope the agency reconsiders this decision.
After all, one of the CDC’s key messages during this pandemic has been that even people with asymptomatic COVID who have been vaccinated and boosted can transmit the disease. So it seems to me that the Dec. 27, 2021, recommendation about shortening the isolation time for COVID-19–positive people, like the agency’s earlier guidance encouraging people who are vaccinated to stop wearing masks while in indoor settings, runs contrary to good public health principles.
As an expert in human behavior, I am worried about the impact of these confusing messages on the psyche of people in general, as well as on our patients.
Mental health impact
Soon after the United States went on lockdown in March 2020, I wrote about the likelihood of a pandemic of PTSD, anxiety, and depression that would occur in the wake of rising COVID-19 rates. Well, it happened.
Many people have felt a sense of existential despair, depression, and anxiety. As we head into year No. 3 of disruption of our daily lives – and face the loss of more than 825,000 Americans to COVID – we continue to navigate this uncertainty. And now we must deal with Omicron, a variant that is so highly transmissible that it is apparently able to, in some cases, evade two-dose regimens of mRNA vaccines, boosters, and immunity from past infections, according to a report from Imperial College London. Yet, we are being told by some that Omicron might be less severe, compared with other variants. I worry that this assessment is misleading. In that same report, the Imperial College said it “found no evidence” that Omicron is less virulent than Delta, based on the risk of hospitalization and symptom status.
Meanwhile, animal studies suggest that the Omicron variant might lead to less lung damage than previous variants. A preprint article that is being considered for publication by a Nature Portfolio journal suggests that hamsters and mice infected with the Omicron variant do not have as much lung damage as those infected with other variants. More data need to come in for us to get a true understanding of Omicron’s virulence and transmissibility. We should keep an eye on Israel, which is launching a clinical trial of a second booster, or fourth mRNA shot.
As clinicians, we should give our patients and other people with whom we come in contact a sense of hope. In addition to urging people to get boosters, let’s tell them to err on the side of safety when it comes to this pandemic. That means encouraging them to remain isolated for longer than 5 days – until they test negative for COVID. It also means encouraging patients to wear high-quality face masks while inside public spaces – even in the absence of mandates. I have found it heartbreaking to watch televised broadcasts of sporting events held at some stadiums across the country where masks are not being worn. This absence of face coverings is counterintuitive at a time when some Broadway shows are closing. Even the great Radio City Rockettes shut down their holiday shows early in December 2021 because of COVID.
And, as I’ve argued before, we must not give up on unvaccinated people. I have had success in changing the minds of a few patients and some acquaintances with gentle, respectful prodding and vaccine education.
I would also like to see public health principles implemented in our schools and colleges. To protect the health of our children and young adults, we must continue to be nimble – which means school districts should implement layered prevention strategies, as the CDC recommends. This includes not only encouraging eligible staff members and students to get vaccinated, but requiring face masks inside school facilities, maintaining a physical distance of at least 3 feet, “screening testing, ventilation, handwashing, and staying home when sick.”
Furthermore, in deciding whether schools should remain open or be closed after positive COVID cases are discovered, officials should look at the vaccine demographics of that particular school. For example, if 15% of students are vaccinated in one school and 70% are vaccinated in another, the judgment would be different. Of course, it’s clearly best for schools to remain open, but perhaps closing them temporarily – perhaps for a week or 10 days – should be on the table if infection rates reach a certain level.
Now that we know more and have the benefit of getting more than 200 million Americans fully vaccinated, we can be far more selective about closings and openings. An important part of our strategy must be to communicate honestly with the public about which measures are best for safety. As a key tenet of cognitive-behavioral therapy tells us, “all-or-nothing” thinking is not productive. That should also be the case with our approach to managing COVID-19.
We don’t know the future of the pandemic. Yes, it will end, and possibly COVID will become endemic – like the flu. However, in the meantime, in addition to promoting vaccinations and boosters, we must rigorously encourage our patients to follow public health standards of masking, social distancing, and closing down businesses – and schools – temporarily.
This pandemic has taken a horrendous mental health toll on all of us – especially our patients and frontline health care workers. I’ve spoken with numerous people who were anxious, depressed, and showed signs of PTSD in early 2020; after they got vaccinated, COVID spread diminished, and as public health protocols began to lift, so did their spirits. Clearly for some, the benefit of psychiatric/psychological care centering on the pandemic has proven invaluable. In some ways, the pandemic has brought to the surface the importance of mental health care and removed some of the stigma from mental illness. And that’s a good thing.
Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
The Centers for Disease Control and Prevention’s decision to shorten the length of isolation time for asymptomatic Americans with COVID-19, regardless of their vaccination status, to 5 days from 10 days is confusing. I hope the agency reconsiders this decision.
After all, one of the CDC’s key messages during this pandemic has been that even people with asymptomatic COVID who have been vaccinated and boosted can transmit the disease. So it seems to me that the Dec. 27, 2021, recommendation about shortening the isolation time for COVID-19–positive people, like the agency’s earlier guidance encouraging people who are vaccinated to stop wearing masks while in indoor settings, runs contrary to good public health principles.
As an expert in human behavior, I am worried about the impact of these confusing messages on the psyche of people in general, as well as on our patients.
Mental health impact
Soon after the United States went on lockdown in March 2020, I wrote about the likelihood of a pandemic of PTSD, anxiety, and depression that would occur in the wake of rising COVID-19 rates. Well, it happened.
Many people have felt a sense of existential despair, depression, and anxiety. As we head into year No. 3 of disruption of our daily lives – and face the loss of more than 825,000 Americans to COVID – we continue to navigate this uncertainty. And now we must deal with Omicron, a variant that is so highly transmissible that it is apparently able to, in some cases, evade two-dose regimens of mRNA vaccines, boosters, and immunity from past infections, according to a report from Imperial College London. Yet, we are being told by some that Omicron might be less severe, compared with other variants. I worry that this assessment is misleading. In that same report, the Imperial College said it “found no evidence” that Omicron is less virulent than Delta, based on the risk of hospitalization and symptom status.
Meanwhile, animal studies suggest that the Omicron variant might lead to less lung damage than previous variants. A preprint article that is being considered for publication by a Nature Portfolio journal suggests that hamsters and mice infected with the Omicron variant do not have as much lung damage as those infected with other variants. More data need to come in for us to get a true understanding of Omicron’s virulence and transmissibility. We should keep an eye on Israel, which is launching a clinical trial of a second booster, or fourth mRNA shot.
As clinicians, we should give our patients and other people with whom we come in contact a sense of hope. In addition to urging people to get boosters, let’s tell them to err on the side of safety when it comes to this pandemic. That means encouraging them to remain isolated for longer than 5 days – until they test negative for COVID. It also means encouraging patients to wear high-quality face masks while inside public spaces – even in the absence of mandates. I have found it heartbreaking to watch televised broadcasts of sporting events held at some stadiums across the country where masks are not being worn. This absence of face coverings is counterintuitive at a time when some Broadway shows are closing. Even the great Radio City Rockettes shut down their holiday shows early in December 2021 because of COVID.
And, as I’ve argued before, we must not give up on unvaccinated people. I have had success in changing the minds of a few patients and some acquaintances with gentle, respectful prodding and vaccine education.
I would also like to see public health principles implemented in our schools and colleges. To protect the health of our children and young adults, we must continue to be nimble – which means school districts should implement layered prevention strategies, as the CDC recommends. This includes not only encouraging eligible staff members and students to get vaccinated, but requiring face masks inside school facilities, maintaining a physical distance of at least 3 feet, “screening testing, ventilation, handwashing, and staying home when sick.”
Furthermore, in deciding whether schools should remain open or be closed after positive COVID cases are discovered, officials should look at the vaccine demographics of that particular school. For example, if 15% of students are vaccinated in one school and 70% are vaccinated in another, the judgment would be different. Of course, it’s clearly best for schools to remain open, but perhaps closing them temporarily – perhaps for a week or 10 days – should be on the table if infection rates reach a certain level.
Now that we know more and have the benefit of getting more than 200 million Americans fully vaccinated, we can be far more selective about closings and openings. An important part of our strategy must be to communicate honestly with the public about which measures are best for safety. As a key tenet of cognitive-behavioral therapy tells us, “all-or-nothing” thinking is not productive. That should also be the case with our approach to managing COVID-19.
We don’t know the future of the pandemic. Yes, it will end, and possibly COVID will become endemic – like the flu. However, in the meantime, in addition to promoting vaccinations and boosters, we must rigorously encourage our patients to follow public health standards of masking, social distancing, and closing down businesses – and schools – temporarily.
This pandemic has taken a horrendous mental health toll on all of us – especially our patients and frontline health care workers. I’ve spoken with numerous people who were anxious, depressed, and showed signs of PTSD in early 2020; after they got vaccinated, COVID spread diminished, and as public health protocols began to lift, so did their spirits. Clearly for some, the benefit of psychiatric/psychological care centering on the pandemic has proven invaluable. In some ways, the pandemic has brought to the surface the importance of mental health care and removed some of the stigma from mental illness. And that’s a good thing.
Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
The Centers for Disease Control and Prevention’s decision to shorten the length of isolation time for asymptomatic Americans with COVID-19, regardless of their vaccination status, to 5 days from 10 days is confusing. I hope the agency reconsiders this decision.
After all, one of the CDC’s key messages during this pandemic has been that even people with asymptomatic COVID who have been vaccinated and boosted can transmit the disease. So it seems to me that the Dec. 27, 2021, recommendation about shortening the isolation time for COVID-19–positive people, like the agency’s earlier guidance encouraging people who are vaccinated to stop wearing masks while in indoor settings, runs contrary to good public health principles.
As an expert in human behavior, I am worried about the impact of these confusing messages on the psyche of people in general, as well as on our patients.
Mental health impact
Soon after the United States went on lockdown in March 2020, I wrote about the likelihood of a pandemic of PTSD, anxiety, and depression that would occur in the wake of rising COVID-19 rates. Well, it happened.
Many people have felt a sense of existential despair, depression, and anxiety. As we head into year No. 3 of disruption of our daily lives – and face the loss of more than 825,000 Americans to COVID – we continue to navigate this uncertainty. And now we must deal with Omicron, a variant that is so highly transmissible that it is apparently able to, in some cases, evade two-dose regimens of mRNA vaccines, boosters, and immunity from past infections, according to a report from Imperial College London. Yet, we are being told by some that Omicron might be less severe, compared with other variants. I worry that this assessment is misleading. In that same report, the Imperial College said it “found no evidence” that Omicron is less virulent than Delta, based on the risk of hospitalization and symptom status.
Meanwhile, animal studies suggest that the Omicron variant might lead to less lung damage than previous variants. A preprint article that is being considered for publication by a Nature Portfolio journal suggests that hamsters and mice infected with the Omicron variant do not have as much lung damage as those infected with other variants. More data need to come in for us to get a true understanding of Omicron’s virulence and transmissibility. We should keep an eye on Israel, which is launching a clinical trial of a second booster, or fourth mRNA shot.
As clinicians, we should give our patients and other people with whom we come in contact a sense of hope. In addition to urging people to get boosters, let’s tell them to err on the side of safety when it comes to this pandemic. That means encouraging them to remain isolated for longer than 5 days – until they test negative for COVID. It also means encouraging patients to wear high-quality face masks while inside public spaces – even in the absence of mandates. I have found it heartbreaking to watch televised broadcasts of sporting events held at some stadiums across the country where masks are not being worn. This absence of face coverings is counterintuitive at a time when some Broadway shows are closing. Even the great Radio City Rockettes shut down their holiday shows early in December 2021 because of COVID.
And, as I’ve argued before, we must not give up on unvaccinated people. I have had success in changing the minds of a few patients and some acquaintances with gentle, respectful prodding and vaccine education.
I would also like to see public health principles implemented in our schools and colleges. To protect the health of our children and young adults, we must continue to be nimble – which means school districts should implement layered prevention strategies, as the CDC recommends. This includes not only encouraging eligible staff members and students to get vaccinated, but requiring face masks inside school facilities, maintaining a physical distance of at least 3 feet, “screening testing, ventilation, handwashing, and staying home when sick.”
Furthermore, in deciding whether schools should remain open or be closed after positive COVID cases are discovered, officials should look at the vaccine demographics of that particular school. For example, if 15% of students are vaccinated in one school and 70% are vaccinated in another, the judgment would be different. Of course, it’s clearly best for schools to remain open, but perhaps closing them temporarily – perhaps for a week or 10 days – should be on the table if infection rates reach a certain level.
Now that we know more and have the benefit of getting more than 200 million Americans fully vaccinated, we can be far more selective about closings and openings. An important part of our strategy must be to communicate honestly with the public about which measures are best for safety. As a key tenet of cognitive-behavioral therapy tells us, “all-or-nothing” thinking is not productive. That should also be the case with our approach to managing COVID-19.
We don’t know the future of the pandemic. Yes, it will end, and possibly COVID will become endemic – like the flu. However, in the meantime, in addition to promoting vaccinations and boosters, we must rigorously encourage our patients to follow public health standards of masking, social distancing, and closing down businesses – and schools – temporarily.
This pandemic has taken a horrendous mental health toll on all of us – especially our patients and frontline health care workers. I’ve spoken with numerous people who were anxious, depressed, and showed signs of PTSD in early 2020; after they got vaccinated, COVID spread diminished, and as public health protocols began to lift, so did their spirits. Clearly for some, the benefit of psychiatric/psychological care centering on the pandemic has proven invaluable. In some ways, the pandemic has brought to the surface the importance of mental health care and removed some of the stigma from mental illness. And that’s a good thing.
Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
Fish oil: ‘No net benefit’ for depression prevention?
Fish oil supplementation does not help prevent depression or boost mood, new research suggests.
The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.
“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.
The findings were published online Dec. 21 in JAMA.
Assessing general population risk
For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.
“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.
The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.
Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.
“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
No significant benefit
Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.
The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).
There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).
“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.
“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.
“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.
Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
Cautionary notes
Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.
First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.
He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.
Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”
VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.
A version of this article first appeared on Medscape.com.
Fish oil supplementation does not help prevent depression or boost mood, new research suggests.
The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.
“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.
The findings were published online Dec. 21 in JAMA.
Assessing general population risk
For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.
“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.
The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.
Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.
“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
No significant benefit
Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.
The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).
There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).
“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.
“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.
“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.
Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
Cautionary notes
Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.
First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.
He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.
Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”
VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.
A version of this article first appeared on Medscape.com.
Fish oil supplementation does not help prevent depression or boost mood, new research suggests.
The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.
“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.
The findings were published online Dec. 21 in JAMA.
Assessing general population risk
For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.
“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.
The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.
Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.
“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
No significant benefit
Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.
The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).
There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).
“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.
“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.
“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.
Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
Cautionary notes
Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.
First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.
He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.
Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”
VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.
A version of this article first appeared on Medscape.com.