Mental Health

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

Early education is right up there with motherhood and apple pie as unarguable positive concepts. How could exposing young children to a school-like atmosphere not be a benefit, particularly in communities dominated by socioeconomic challenges? While there are some questions about the value of playing Mozart to infants, early education in the traditional sense continues to be viewed as a key strategy for providing young children a preschool foundation on which a successful academic career can be built. Several oft-cited randomized controlled trials have fueled both private and public interest and funding.

However, a recent commentary published in Science suggests that all programs are “not unequivocally positive and much more research is needed.” “Worrisome results in Tennessee,” “Success in Boston,” and “Largely null results for Headstart” are just a few of the article’s section titles and convey a sense of the inconsistency the investigators found as they reviewed early education systems around the country.

Wilkoff_William_G_2_web.jpg

While there may be some politicians who may attempt to use the results of this investigation as a reason to cancel public funding of underperforming early education programs, the authors avoid this baby-and-the-bathwater conclusion. Instead, they urge more rigorous research “to understand how effective programs can be designed and implemented.”

The kind of re-thinking and brainstorming these investigators suggest takes time. While we’re waiting for this process to gain traction, this might be a good time to consider some of the benefits of early education that we don’t usually consider when our focus is on academic metrics.

A recent paper in Children’s Health Care by investigators at the Boston University Medical Center and School of Medicine considered the diet of children attending preschool. Looking at the dietary records of more than 300 children attending 30 childcare centers, the researchers found that the children’s diets before arrival at daycare was less healthy than while they were in daycare. “The hour after pickup appeared to be the least healthful” of any of the time periods surveyed. Of course, we will all conjure up images of what this chaotic post-daycare pickup may look like and cut the harried parents and grandparents some slack when it comes to nutritional choices. However, the bottom line is that for the group of children surveyed being in preschool or daycare protected them from a less healthy diet they were being provided outside of school hours.

Our recent experience with pandemic-related school closures provides more evidence that being in school was superior to any remote experience academically. School-age children and adolescents gained weight when school closures were the norm. Play patterns for children shifted from outdoor play to indoor play — often dominated by more sedentary video games. Both fatal and non-fatal gun-related injuries surged during the pandemic and, by far, the majority of these occur in the home and not at school.

Stepping back to look at this broader picture that includes diet, physical activity, and safety — not to mention the benefits of socialization — leads one to arrive at the unfortunate conclusion that for many children in this country, being at home is considerably less healthy than being in school. Of course there will be those who point to the belief that schools are petri dishes putting children at greater risk for respiratory infections. On the other hand, we must accept that schools haven’t proved to be a major factor in the spread of COVID that many had feared.

The authors of the study in Science are certainly correct in recommending a more thorough investigation into the academic benefits of preschool education. However, we must keep in mind that preschool offers an environment that can be a positive influence on young children.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Early education is right up there with motherhood and apple pie as unarguable positive concepts. How could exposing young children to a school-like atmosphere not be a benefit, particularly in communities dominated by socioeconomic challenges? While there are some questions about the value of playing Mozart to infants, early education in the traditional sense continues to be viewed as a key strategy for providing young children a preschool foundation on which a successful academic career can be built. Several oft-cited randomized controlled trials have fueled both private and public interest and funding.

However, a recent commentary published in Science suggests that all programs are “not unequivocally positive and much more research is needed.” “Worrisome results in Tennessee,” “Success in Boston,” and “Largely null results for Headstart” are just a few of the article’s section titles and convey a sense of the inconsistency the investigators found as they reviewed early education systems around the country.

Wilkoff_William_G_2_web.jpg

While there may be some politicians who may attempt to use the results of this investigation as a reason to cancel public funding of underperforming early education programs, the authors avoid this baby-and-the-bathwater conclusion. Instead, they urge more rigorous research “to understand how effective programs can be designed and implemented.”

The kind of re-thinking and brainstorming these investigators suggest takes time. While we’re waiting for this process to gain traction, this might be a good time to consider some of the benefits of early education that we don’t usually consider when our focus is on academic metrics.

A recent paper in Children’s Health Care by investigators at the Boston University Medical Center and School of Medicine considered the diet of children attending preschool. Looking at the dietary records of more than 300 children attending 30 childcare centers, the researchers found that the children’s diets before arrival at daycare was less healthy than while they were in daycare. “The hour after pickup appeared to be the least healthful” of any of the time periods surveyed. Of course, we will all conjure up images of what this chaotic post-daycare pickup may look like and cut the harried parents and grandparents some slack when it comes to nutritional choices. However, the bottom line is that for the group of children surveyed being in preschool or daycare protected them from a less healthy diet they were being provided outside of school hours.

Our recent experience with pandemic-related school closures provides more evidence that being in school was superior to any remote experience academically. School-age children and adolescents gained weight when school closures were the norm. Play patterns for children shifted from outdoor play to indoor play — often dominated by more sedentary video games. Both fatal and non-fatal gun-related injuries surged during the pandemic and, by far, the majority of these occur in the home and not at school.

Stepping back to look at this broader picture that includes diet, physical activity, and safety — not to mention the benefits of socialization — leads one to arrive at the unfortunate conclusion that for many children in this country, being at home is considerably less healthy than being in school. Of course there will be those who point to the belief that schools are petri dishes putting children at greater risk for respiratory infections. On the other hand, we must accept that schools haven’t proved to be a major factor in the spread of COVID that many had feared.

The authors of the study in Science are certainly correct in recommending a more thorough investigation into the academic benefits of preschool education. However, we must keep in mind that preschool offers an environment that can be a positive influence on young children.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Early education is right up there with motherhood and apple pie as unarguable positive concepts. How could exposing young children to a school-like atmosphere not be a benefit, particularly in communities dominated by socioeconomic challenges? While there are some questions about the value of playing Mozart to infants, early education in the traditional sense continues to be viewed as a key strategy for providing young children a preschool foundation on which a successful academic career can be built. Several oft-cited randomized controlled trials have fueled both private and public interest and funding.

However, a recent commentary published in Science suggests that all programs are “not unequivocally positive and much more research is needed.” “Worrisome results in Tennessee,” “Success in Boston,” and “Largely null results for Headstart” are just a few of the article’s section titles and convey a sense of the inconsistency the investigators found as they reviewed early education systems around the country.

Wilkoff_William_G_2_web.jpg

While there may be some politicians who may attempt to use the results of this investigation as a reason to cancel public funding of underperforming early education programs, the authors avoid this baby-and-the-bathwater conclusion. Instead, they urge more rigorous research “to understand how effective programs can be designed and implemented.”

The kind of re-thinking and brainstorming these investigators suggest takes time. While we’re waiting for this process to gain traction, this might be a good time to consider some of the benefits of early education that we don’t usually consider when our focus is on academic metrics.

A recent paper in Children’s Health Care by investigators at the Boston University Medical Center and School of Medicine considered the diet of children attending preschool. Looking at the dietary records of more than 300 children attending 30 childcare centers, the researchers found that the children’s diets before arrival at daycare was less healthy than while they were in daycare. “The hour after pickup appeared to be the least healthful” of any of the time periods surveyed. Of course, we will all conjure up images of what this chaotic post-daycare pickup may look like and cut the harried parents and grandparents some slack when it comes to nutritional choices. However, the bottom line is that for the group of children surveyed being in preschool or daycare protected them from a less healthy diet they were being provided outside of school hours.

Our recent experience with pandemic-related school closures provides more evidence that being in school was superior to any remote experience academically. School-age children and adolescents gained weight when school closures were the norm. Play patterns for children shifted from outdoor play to indoor play — often dominated by more sedentary video games. Both fatal and non-fatal gun-related injuries surged during the pandemic and, by far, the majority of these occur in the home and not at school.

Stepping back to look at this broader picture that includes diet, physical activity, and safety — not to mention the benefits of socialization — leads one to arrive at the unfortunate conclusion that for many children in this country, being at home is considerably less healthy than being in school. Of course there will be those who point to the belief that schools are petri dishes putting children at greater risk for respiratory infections. On the other hand, we must accept that schools haven’t proved to be a major factor in the spread of COVID that many had feared.

The authors of the study in Science are certainly correct in recommending a more thorough investigation into the academic benefits of preschool education. However, we must keep in mind that preschool offers an environment that can be a positive influence on young children.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.