Zuranolone: FAQs for clinicians and patients

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Mon, 10/16/2023 - 23:35

The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill
Dr. Julia Riddle

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABAA receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABAA receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill
Dr. Elizabeth Richardson

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill
Dr. Margo Nathan

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill
Dr. David Rubinow

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

 

 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Dr. Samantha Meltzer-Brody

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

 

 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

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The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill
Dr. Julia Riddle

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABAA receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABAA receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill
Dr. Elizabeth Richardson

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill
Dr. Margo Nathan

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill
Dr. David Rubinow

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

 

 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Dr. Samantha Meltzer-Brody

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

 

 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill
Dr. Julia Riddle

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABAA receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABAA receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill
Dr. Elizabeth Richardson

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill
Dr. Margo Nathan

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill
Dr. David Rubinow

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

 

 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Dr. Samantha Meltzer-Brody

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

 

 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

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BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

 

 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

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BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

 

 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

 

 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

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ADHD rates holding steady in U.S. children

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Changed
Wed, 10/11/2023 - 12:05

 

TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

  • Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
  • The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
  • Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

  • A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
  • The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
  • There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
  • The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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

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TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

  • Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
  • The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
  • Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

  • A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
  • The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
  • There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
  • The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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

 

TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

  • Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
  • The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
  • Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

  • A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
  • The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
  • There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
  • The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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

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Burnout in medical profession higher among women, younger clinicians

Article Type
Changed
Tue, 10/10/2023 - 16:39

The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

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The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

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History of depression, stress tied to Alzheimer’s, MCI risk

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Changed
Mon, 10/09/2023 - 13:36

 

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

  • Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
  • Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

  • SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
  • Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
  • Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
  • Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

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TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

  • Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
  • Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

  • SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
  • Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
  • Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
  • Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

 

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

  • Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
  • Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

  • SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
  • Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
  • Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
  • Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

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Depression tied to higher all-cause and cardiovascular mortality

Article Type
Changed
Wed, 10/11/2023 - 09:42

In a large prospective study, a graded higher risk of all-cause mortality and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) emerged in adults with moderate to severe depressive symptoms, compared with those with no such symptoms.

Participants with mild depressive symptoms had a 35%-49% higher risk of all-cause and CVD mortality, respectively, while for those with moderate to severe depressive symptoms, the risk of all-cause, CVD, and IHD mortality was 62%, 79%, and 121% higher, respectively.

Dr. Zefeng Zhang, CDC
Dr. Zefeng Zhang

“This information highlights the importance for clinicians to identify patients with depressive symptoms and help them engage in treatment,” lead author Zefeng Zhang, MD, PhD, of the division for heart disease and stroke prevention at the U.S. Centers for Disease Control and Prevention, Atlanta, said in an interview.

The study appears in JAMA Network Open.

A nonclassic risk factor for CVD death

This graded positive association between depressive symptoms and CVD death was observed in data from the National Health and Nutrition Examination Survey 2005-2018, which were linked with the National Death Index through 2019 for adults aged 20 and older. Data analysis occurred from March 1 to May 26, 2023. According to the authors, their analyses extend findings from previous research by assessing these associations in a large, diverse, and nationally representative sample. Using more nuanced CVD-related causes of death, depressive symptoms emerged as a nontraditional risk factor for CVD mortality.

The study

In a total cohort of 23,694, about half male, mean overall age 44.7 years, prevalences of mild and moderate to severe depression were 14.9% and 7.2%, respectively, with depressive symptoms assessed by the nine-item Patient Health Questionnaire asking about symptoms over the past 2 weeks.

Adults with depression had significantly lower CV health scores in six of the American Heart Association Life’s Essential 8 metrics for heart health. For all-cause mortality, hazard ratios were 1.35 (95% confidence interval, 1.07-1.72) for mild depressive symptoms vs. none and 1.62 (95% CI, 1.24-2.12) for moderate to severe depressive symptoms vs. none.

The corresponding hazard ratios were 1.49 (95% CI, 1.11-2.0) and 1.79 (95% CI,1.22-2.62) for CVD mortality and 0.96 (95% CI, 0.58-1.60) and 2.21 (95% CI, 1.24-3.91) for IHD death, with associations largely consistent across subgroups.

At the highest severity of depressive symptoms (almost daily for past 2 weeks), feeling tired or having little energy, poor appetite or overeating, and having little interest in doing things were significantly associated with all-cause and CVD mortality after adjusting for potential confounders.

Approximately 11%-16% of the positive associations could be explained by lifestyle factors such as excess alcohol consumption, overeating, and inactivity as per the AHA’s Life’s Essential 8 metrics.

“Taken together with the body of literature on associations between depression and CVD mortality, these findings can support public health efforts to develop a comprehensive, nationwide strategy to improve well-being, including both mental and cardiovascular health,” Dr. Zhang and associates wrote.

This research was funded by the U.S. Centers for Disease Control and Prevention. The authors had no conflicts of interest to disclose.

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In a large prospective study, a graded higher risk of all-cause mortality and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) emerged in adults with moderate to severe depressive symptoms, compared with those with no such symptoms.

Participants with mild depressive symptoms had a 35%-49% higher risk of all-cause and CVD mortality, respectively, while for those with moderate to severe depressive symptoms, the risk of all-cause, CVD, and IHD mortality was 62%, 79%, and 121% higher, respectively.

Dr. Zefeng Zhang, CDC
Dr. Zefeng Zhang

“This information highlights the importance for clinicians to identify patients with depressive symptoms and help them engage in treatment,” lead author Zefeng Zhang, MD, PhD, of the division for heart disease and stroke prevention at the U.S. Centers for Disease Control and Prevention, Atlanta, said in an interview.

The study appears in JAMA Network Open.

A nonclassic risk factor for CVD death

This graded positive association between depressive symptoms and CVD death was observed in data from the National Health and Nutrition Examination Survey 2005-2018, which were linked with the National Death Index through 2019 for adults aged 20 and older. Data analysis occurred from March 1 to May 26, 2023. According to the authors, their analyses extend findings from previous research by assessing these associations in a large, diverse, and nationally representative sample. Using more nuanced CVD-related causes of death, depressive symptoms emerged as a nontraditional risk factor for CVD mortality.

The study

In a total cohort of 23,694, about half male, mean overall age 44.7 years, prevalences of mild and moderate to severe depression were 14.9% and 7.2%, respectively, with depressive symptoms assessed by the nine-item Patient Health Questionnaire asking about symptoms over the past 2 weeks.

Adults with depression had significantly lower CV health scores in six of the American Heart Association Life’s Essential 8 metrics for heart health. For all-cause mortality, hazard ratios were 1.35 (95% confidence interval, 1.07-1.72) for mild depressive symptoms vs. none and 1.62 (95% CI, 1.24-2.12) for moderate to severe depressive symptoms vs. none.

The corresponding hazard ratios were 1.49 (95% CI, 1.11-2.0) and 1.79 (95% CI,1.22-2.62) for CVD mortality and 0.96 (95% CI, 0.58-1.60) and 2.21 (95% CI, 1.24-3.91) for IHD death, with associations largely consistent across subgroups.

At the highest severity of depressive symptoms (almost daily for past 2 weeks), feeling tired or having little energy, poor appetite or overeating, and having little interest in doing things were significantly associated with all-cause and CVD mortality after adjusting for potential confounders.

Approximately 11%-16% of the positive associations could be explained by lifestyle factors such as excess alcohol consumption, overeating, and inactivity as per the AHA’s Life’s Essential 8 metrics.

“Taken together with the body of literature on associations between depression and CVD mortality, these findings can support public health efforts to develop a comprehensive, nationwide strategy to improve well-being, including both mental and cardiovascular health,” Dr. Zhang and associates wrote.

This research was funded by the U.S. Centers for Disease Control and Prevention. The authors had no conflicts of interest to disclose.

In a large prospective study, a graded higher risk of all-cause mortality and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) emerged in adults with moderate to severe depressive symptoms, compared with those with no such symptoms.

Participants with mild depressive symptoms had a 35%-49% higher risk of all-cause and CVD mortality, respectively, while for those with moderate to severe depressive symptoms, the risk of all-cause, CVD, and IHD mortality was 62%, 79%, and 121% higher, respectively.

Dr. Zefeng Zhang, CDC
Dr. Zefeng Zhang

“This information highlights the importance for clinicians to identify patients with depressive symptoms and help them engage in treatment,” lead author Zefeng Zhang, MD, PhD, of the division for heart disease and stroke prevention at the U.S. Centers for Disease Control and Prevention, Atlanta, said in an interview.

The study appears in JAMA Network Open.

A nonclassic risk factor for CVD death

This graded positive association between depressive symptoms and CVD death was observed in data from the National Health and Nutrition Examination Survey 2005-2018, which were linked with the National Death Index through 2019 for adults aged 20 and older. Data analysis occurred from March 1 to May 26, 2023. According to the authors, their analyses extend findings from previous research by assessing these associations in a large, diverse, and nationally representative sample. Using more nuanced CVD-related causes of death, depressive symptoms emerged as a nontraditional risk factor for CVD mortality.

The study

In a total cohort of 23,694, about half male, mean overall age 44.7 years, prevalences of mild and moderate to severe depression were 14.9% and 7.2%, respectively, with depressive symptoms assessed by the nine-item Patient Health Questionnaire asking about symptoms over the past 2 weeks.

Adults with depression had significantly lower CV health scores in six of the American Heart Association Life’s Essential 8 metrics for heart health. For all-cause mortality, hazard ratios were 1.35 (95% confidence interval, 1.07-1.72) for mild depressive symptoms vs. none and 1.62 (95% CI, 1.24-2.12) for moderate to severe depressive symptoms vs. none.

The corresponding hazard ratios were 1.49 (95% CI, 1.11-2.0) and 1.79 (95% CI,1.22-2.62) for CVD mortality and 0.96 (95% CI, 0.58-1.60) and 2.21 (95% CI, 1.24-3.91) for IHD death, with associations largely consistent across subgroups.

At the highest severity of depressive symptoms (almost daily for past 2 weeks), feeling tired or having little energy, poor appetite or overeating, and having little interest in doing things were significantly associated with all-cause and CVD mortality after adjusting for potential confounders.

Approximately 11%-16% of the positive associations could be explained by lifestyle factors such as excess alcohol consumption, overeating, and inactivity as per the AHA’s Life’s Essential 8 metrics.

“Taken together with the body of literature on associations between depression and CVD mortality, these findings can support public health efforts to develop a comprehensive, nationwide strategy to improve well-being, including both mental and cardiovascular health,” Dr. Zhang and associates wrote.

This research was funded by the U.S. Centers for Disease Control and Prevention. The authors had no conflicts of interest to disclose.

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Irritable temperament predicts bipolar disorder risk

Article Type
Changed
Mon, 10/09/2023 - 09:05

Evaluation of temperament in mental health outpatients showed a significant association between the irritable temperament type and a diagnosis of bipolar I and bipolar II disorders, based on data from more than 1,700 individuals.

When German psychiatrist Emil Kraepelin (1856-1926) studied emotions in patients with affective disorders, he identified four temperaments: the depressive (DT), the hyperthymic (HT), the irritable (IT), and the cyclothymic (CT). Subsequent researchers later identified an anxious temperament (AT).

“The notion that temperaments can be useful in predicting bipolar disorders sparked a plethora of research,” wrote Elie G. Karam, MD, of Saint George Hospital, Beirut, and colleagues. In particular, the cyclothymic (CT) and irritable (IT) temperament types have been targeted in studies of patients with bipolar disorders, but previous studies of temperament and bipolar have been limited by methodological issues, they said.

In a study published in European Psychiatry, the researchers reviewed data from 1,723 consecutive adult outpatients who presented to a university-based mental health clinic with various symptoms between January 2014 and September 2019.

Patients were assessed using the Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A), then were diagnosed by psychiatrists using DSM-5 criteria. Patients with any bipolar types as defined by the DSM-5 underwent simple and multiple binary logistic regression analyses. The analysis included continuous scores and categorical normalized z-scores.

A total of 369 patients had confirmed DSM-5 diagnosis of bipolar disorder (52 with type I, 176 with type II, 102 with other specified bipolar and related disorder, and 39 with substance- or medication-induced bipolar disorder. The mean age of the participants was 38 years, and 54% were female.

In a bivariate analysis, all continuous temperament scores were significant predictors of bipolar disorder; all except AT remained significant in multivariate analysis. Increasing scores of IT, CT, and HT were associated with bipolar disorder, but increasing scores of DT were reflective of lower chance of bipolar disorder, the researchers noted.

In multivariate analysis of categorical normalized z-scores, IT and CT were significant predictors of bipolar disorder. At the highest point, CT was the stronger predictor, compared with IT (odds ratio, 3.84 vs. 2.55); having a higher DT score significantly reduced the odds of bipolar disorder (OR, 0.50).

However, “after adjusting for the presence of all temperaments as well as age and gender, only IT remained a significant predictor of patients with bipolar I disorder with adjusted OR of 1.19,” the researchers wrote.

“Correlations among temperaments were solid whether looking at patients with bipolarity or not, further emphasizing the necessity of controlling for them,” the researchers wrote in their discussion.

The findings were limited by several factors including the lack of structured interviews, the use of an outpatient-only sample, and the small number of bipolar I patients, the researchers noted.

However, the result suggest that IT can serve as a predictor of bipolar I and bipolar II disorders they said. Given the underdiagnosis of bipolar disorder in many studies, the incorporation of temperaments into the assessment of patients and research participants alike is likely to help us detect the presence of bipolarity more readily and quite importantly help us in our quest to understand their genesis,” they concluded.

The study was supported in part by anonymous private unrestricted donations to IDRAAC, Lebanon, and by Eli Lilly. The researchers had no financial conflicts to disclose.

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Evaluation of temperament in mental health outpatients showed a significant association between the irritable temperament type and a diagnosis of bipolar I and bipolar II disorders, based on data from more than 1,700 individuals.

When German psychiatrist Emil Kraepelin (1856-1926) studied emotions in patients with affective disorders, he identified four temperaments: the depressive (DT), the hyperthymic (HT), the irritable (IT), and the cyclothymic (CT). Subsequent researchers later identified an anxious temperament (AT).

“The notion that temperaments can be useful in predicting bipolar disorders sparked a plethora of research,” wrote Elie G. Karam, MD, of Saint George Hospital, Beirut, and colleagues. In particular, the cyclothymic (CT) and irritable (IT) temperament types have been targeted in studies of patients with bipolar disorders, but previous studies of temperament and bipolar have been limited by methodological issues, they said.

In a study published in European Psychiatry, the researchers reviewed data from 1,723 consecutive adult outpatients who presented to a university-based mental health clinic with various symptoms between January 2014 and September 2019.

Patients were assessed using the Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A), then were diagnosed by psychiatrists using DSM-5 criteria. Patients with any bipolar types as defined by the DSM-5 underwent simple and multiple binary logistic regression analyses. The analysis included continuous scores and categorical normalized z-scores.

A total of 369 patients had confirmed DSM-5 diagnosis of bipolar disorder (52 with type I, 176 with type II, 102 with other specified bipolar and related disorder, and 39 with substance- or medication-induced bipolar disorder. The mean age of the participants was 38 years, and 54% were female.

In a bivariate analysis, all continuous temperament scores were significant predictors of bipolar disorder; all except AT remained significant in multivariate analysis. Increasing scores of IT, CT, and HT were associated with bipolar disorder, but increasing scores of DT were reflective of lower chance of bipolar disorder, the researchers noted.

In multivariate analysis of categorical normalized z-scores, IT and CT were significant predictors of bipolar disorder. At the highest point, CT was the stronger predictor, compared with IT (odds ratio, 3.84 vs. 2.55); having a higher DT score significantly reduced the odds of bipolar disorder (OR, 0.50).

However, “after adjusting for the presence of all temperaments as well as age and gender, only IT remained a significant predictor of patients with bipolar I disorder with adjusted OR of 1.19,” the researchers wrote.

“Correlations among temperaments were solid whether looking at patients with bipolarity or not, further emphasizing the necessity of controlling for them,” the researchers wrote in their discussion.

The findings were limited by several factors including the lack of structured interviews, the use of an outpatient-only sample, and the small number of bipolar I patients, the researchers noted.

However, the result suggest that IT can serve as a predictor of bipolar I and bipolar II disorders they said. Given the underdiagnosis of bipolar disorder in many studies, the incorporation of temperaments into the assessment of patients and research participants alike is likely to help us detect the presence of bipolarity more readily and quite importantly help us in our quest to understand their genesis,” they concluded.

The study was supported in part by anonymous private unrestricted donations to IDRAAC, Lebanon, and by Eli Lilly. The researchers had no financial conflicts to disclose.

Evaluation of temperament in mental health outpatients showed a significant association between the irritable temperament type and a diagnosis of bipolar I and bipolar II disorders, based on data from more than 1,700 individuals.

When German psychiatrist Emil Kraepelin (1856-1926) studied emotions in patients with affective disorders, he identified four temperaments: the depressive (DT), the hyperthymic (HT), the irritable (IT), and the cyclothymic (CT). Subsequent researchers later identified an anxious temperament (AT).

“The notion that temperaments can be useful in predicting bipolar disorders sparked a plethora of research,” wrote Elie G. Karam, MD, of Saint George Hospital, Beirut, and colleagues. In particular, the cyclothymic (CT) and irritable (IT) temperament types have been targeted in studies of patients with bipolar disorders, but previous studies of temperament and bipolar have been limited by methodological issues, they said.

In a study published in European Psychiatry, the researchers reviewed data from 1,723 consecutive adult outpatients who presented to a university-based mental health clinic with various symptoms between January 2014 and September 2019.

Patients were assessed using the Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A), then were diagnosed by psychiatrists using DSM-5 criteria. Patients with any bipolar types as defined by the DSM-5 underwent simple and multiple binary logistic regression analyses. The analysis included continuous scores and categorical normalized z-scores.

A total of 369 patients had confirmed DSM-5 diagnosis of bipolar disorder (52 with type I, 176 with type II, 102 with other specified bipolar and related disorder, and 39 with substance- or medication-induced bipolar disorder. The mean age of the participants was 38 years, and 54% were female.

In a bivariate analysis, all continuous temperament scores were significant predictors of bipolar disorder; all except AT remained significant in multivariate analysis. Increasing scores of IT, CT, and HT were associated with bipolar disorder, but increasing scores of DT were reflective of lower chance of bipolar disorder, the researchers noted.

In multivariate analysis of categorical normalized z-scores, IT and CT were significant predictors of bipolar disorder. At the highest point, CT was the stronger predictor, compared with IT (odds ratio, 3.84 vs. 2.55); having a higher DT score significantly reduced the odds of bipolar disorder (OR, 0.50).

However, “after adjusting for the presence of all temperaments as well as age and gender, only IT remained a significant predictor of patients with bipolar I disorder with adjusted OR of 1.19,” the researchers wrote.

“Correlations among temperaments were solid whether looking at patients with bipolarity or not, further emphasizing the necessity of controlling for them,” the researchers wrote in their discussion.

The findings were limited by several factors including the lack of structured interviews, the use of an outpatient-only sample, and the small number of bipolar I patients, the researchers noted.

However, the result suggest that IT can serve as a predictor of bipolar I and bipolar II disorders they said. Given the underdiagnosis of bipolar disorder in many studies, the incorporation of temperaments into the assessment of patients and research participants alike is likely to help us detect the presence of bipolarity more readily and quite importantly help us in our quest to understand their genesis,” they concluded.

The study was supported in part by anonymous private unrestricted donations to IDRAAC, Lebanon, and by Eli Lilly. The researchers had no financial conflicts to disclose.

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Substance-induced psychosis tied to schizophrenia risk

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Fri, 10/06/2023 - 16:31

 

TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

  • In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
  • Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
  • Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

  • There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
  • Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
  • Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
  • ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
  • Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

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TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

  • In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
  • Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
  • Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

  • There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
  • Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
  • Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
  • ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
  • Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

 

TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

  • In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
  • Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
  • Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

  • There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
  • Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
  • Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
  • ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
  • Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

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Adolescents’ acute care use for eating disorders has risen

Article Type
Changed
Fri, 10/06/2023 - 10:09

Emergency department visits and hospital admissions for eating disorders have increased significantly among adolescents during the COVID-19 pandemic, according to new research.

In a repeated cross-sectional study that examined population-based data from January 2017 through August 2022, ED visits increased by 121% above expected levels, and hospital admissions increased by 54% above expected among patients aged 10-17 years during the pandemic.

“We are hoping this study continues to heighten awareness of the importance of eating disorders, and also to bolster support for eating disorder programs so that we can adequately care for patients and address the increasing demand for treatment and services,” lead author Alene Toulany, MD, adolescent medicine specialist and researcher at the Hospital for Sick Children in Toronto, told this news organization.

The study was published in the Canadian Medical Association Journal.
 

‘A pressing concern’

The researchers used linked health administrative databases that included all patients in Ontario who were eligible for the Ontario Health Insurance Plan, which is publicly funded. They compared observed and expected rates of ED visits and hospitalizations for eating disorders between a prepandemic period (Jan. 1, 2017, to Feb. 29, 2020) and a pandemic period (Mar. 1, 2020, to Aug. 31, 2022). The researchers examined the following four age categories: adolescents (aged 10-17 years), young adults (aged 18-26 years), adults (aged 27-40 years), and older adults (aged 41-105 years).

Among adolescents, the observed rate of ED visits during the 30 pandemic months studied was 7.38 per 100,000 population, compared with 3.33 per 100,000 before the pandemic (incidence rate ratio [IRR], 2.21).

The rate of ED visits among young adults increased by 13% above the expected rate. It reached 2.79 per 100,000, compared with 2.46 per 100,000 in the prepandemic period (IRR, 1.13).

Among older adults, ED visits increased from 0.11 per 100,000 in the prepandemic period to 0.14 per 100,000 in the pandemic period (IRR, 1.15). The rate of ED visits among adults remained approximately the same.

The rate of hospital admissions among adolescents increased by 54% above the expected rate during the pandemic. The observed rate of hospital admissions before the pandemic was 5.74 per 100,000, vs. 8.82 per 100,000 during the pandemic (IRR, 1.54). Hospital admissions remained stable or decreased for the other age groups.

“Eating disorders have increased globally in children and adolescents during COVID,” said Dr. Toulany. “There are a number of risk factors contributing to this pandemic rise, including isolation, more time on social media, decreased access to care (as many in-person services were not available due to the pandemic), as well as fear of getting infected. All of these could contribute to an increased risk of developing an eating disorder or of making an existing one worse.”

Regardless of the cause, more investment in eating disorders research and eating disorder programs for adolescents and adults is needed, she said.

“The pandemic served as a catalyst, because it started to shed light on the prevalence of eating disorders, especially in young people. But it’s very important that we recognize that this has been a long-standing issue and a pressing concern that has been consistently overlooked and underfunded,” said Dr. Toulany.
 

 

 

Surging eating disorders

Commenting on the findings, Victor Fornari, MD, director of child and adolescent psychiatry at Zucker Hillside Hospital/Northwell Health in Glen Oaks, N.Y., said, “Our experience in the United States parallels what is described in this Canadian paper. This was a surge of eating disorders the likes of which I had not experienced in my career.” Dr. Fornari did not participate in the current study.

“I’ve been here for over 40 years, and the average number of our inpatients in our eating disorder program has been three to five and about a dozen patients in our day clinic at any one time. But in the spring of 2020, we surged to 20 inpatients and over 20 day patients,” Dr. Fornari said.

“We can speculate as to the reasons for this,” he continued. “Kids were isolated. School was closed. They spent more time on social media and the Internet. Their sports activities were curtailed. There was anxiety because the guidance that we were all offered to prevent contagion was increasing people’s anxiety about safety and danger. So, I think we saw dramatic rises in eating disorders in the same way we saw dramatic rises in anxiety and depression in adolescents, as well.”

Dr. Fornari cited social media as an important contributing factor to eating disorders, especially among vulnerable teenagers. “Many of these vulnerable kids are looking at pictures of people who are very thin and comparing themselves, feeling inadequate, feeling sad. Social media is one of the reasons why the rates of psychopathology amongst teens has skyrocketed in the last decade. The surgeon general recently said we should delay access to social media until age 16 because the younger kids are impressionable and vulnerable. I think there is wisdom there, but it is very hard to actually put into practice.”
 

Worsening mental health

“I thought this was very relevant research and an important contribution to our understanding of eating disorders during pandemic times,” said Simon Sherry, PhD, professor of psychology and neuroscience at Dalhousie University in Halifax, Nova Scotia. “It also dovetails with my own experience as a practitioner.” Dr. Sherry was not involved in the research.

The pandemic has been difficult for people with disordered eating for many reasons, Dr. Sherry said. “There was a massive disruption or ‘loss of normal’ around food. Restaurants closed, grocery shopping was disrupted, scarcity of food occurred, hoarding of food occurred. That meant that eating was difficult for all of us, but especially for individuals who were rigid and controlling around the consumption of food. In this COVID era, you would need flexibility and acceptance around eating, but if you had a narrow range of preferred foods and preferred shopping locations, no doubt the pandemic made this a lot worse.”

Certain forms of disordered eating would be much more likely during the pandemic, Dr. Sherry noted. “For example, binge eating is often triggered by psychological, social, and environmental events,” and those triggers were abundant at the beginning of the pandemic. Boredom, anxiety, depression, stress, loneliness, confinement, and isolation are among the triggers. “COVID-19-related stress was and is very fertile ground for the growth of emotional eating, binge eating, or turning to food to cope. Eating disorders tend to fester amid silence and isolation and inactivity, and that was very much our experience during the lockdown phase of the pandemic,” he said.

Dr. Sherry agrees with the need for more funding for eating disorders research. “We know in Canada that eating disorders are a very important and deadly issue that is chronically underfunded. We are not funding disordered eating in proportion to its prevalence or in proportion to the amount of harm and destruction it creates for individuals, their family members, and our society at large. The authors are absolutely correct to advocate for care in proportion to the prevalence and the damage associated with eating disorders,” he said.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health, the Ministry of Long-Term Care, and the Canadian Institutes of Health Research (CIHR). Dr. Toulany, Dr. Fornari, and Dr. Sherry reported no relevant financial relationships. One study author reported receiving personal fees from the BMJ Group’s Archives of Diseases in Childhood and grants from CIHR, the Ontario Ministry of Health, the Centre for Addiction and Mental Health, and the Hospital for Sick Children. A second author reported funding from CIHR.

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

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Emergency department visits and hospital admissions for eating disorders have increased significantly among adolescents during the COVID-19 pandemic, according to new research.

In a repeated cross-sectional study that examined population-based data from January 2017 through August 2022, ED visits increased by 121% above expected levels, and hospital admissions increased by 54% above expected among patients aged 10-17 years during the pandemic.

“We are hoping this study continues to heighten awareness of the importance of eating disorders, and also to bolster support for eating disorder programs so that we can adequately care for patients and address the increasing demand for treatment and services,” lead author Alene Toulany, MD, adolescent medicine specialist and researcher at the Hospital for Sick Children in Toronto, told this news organization.

The study was published in the Canadian Medical Association Journal.
 

‘A pressing concern’

The researchers used linked health administrative databases that included all patients in Ontario who were eligible for the Ontario Health Insurance Plan, which is publicly funded. They compared observed and expected rates of ED visits and hospitalizations for eating disorders between a prepandemic period (Jan. 1, 2017, to Feb. 29, 2020) and a pandemic period (Mar. 1, 2020, to Aug. 31, 2022). The researchers examined the following four age categories: adolescents (aged 10-17 years), young adults (aged 18-26 years), adults (aged 27-40 years), and older adults (aged 41-105 years).

Among adolescents, the observed rate of ED visits during the 30 pandemic months studied was 7.38 per 100,000 population, compared with 3.33 per 100,000 before the pandemic (incidence rate ratio [IRR], 2.21).

The rate of ED visits among young adults increased by 13% above the expected rate. It reached 2.79 per 100,000, compared with 2.46 per 100,000 in the prepandemic period (IRR, 1.13).

Among older adults, ED visits increased from 0.11 per 100,000 in the prepandemic period to 0.14 per 100,000 in the pandemic period (IRR, 1.15). The rate of ED visits among adults remained approximately the same.

The rate of hospital admissions among adolescents increased by 54% above the expected rate during the pandemic. The observed rate of hospital admissions before the pandemic was 5.74 per 100,000, vs. 8.82 per 100,000 during the pandemic (IRR, 1.54). Hospital admissions remained stable or decreased for the other age groups.

“Eating disorders have increased globally in children and adolescents during COVID,” said Dr. Toulany. “There are a number of risk factors contributing to this pandemic rise, including isolation, more time on social media, decreased access to care (as many in-person services were not available due to the pandemic), as well as fear of getting infected. All of these could contribute to an increased risk of developing an eating disorder or of making an existing one worse.”

Regardless of the cause, more investment in eating disorders research and eating disorder programs for adolescents and adults is needed, she said.

“The pandemic served as a catalyst, because it started to shed light on the prevalence of eating disorders, especially in young people. But it’s very important that we recognize that this has been a long-standing issue and a pressing concern that has been consistently overlooked and underfunded,” said Dr. Toulany.
 

 

 

Surging eating disorders

Commenting on the findings, Victor Fornari, MD, director of child and adolescent psychiatry at Zucker Hillside Hospital/Northwell Health in Glen Oaks, N.Y., said, “Our experience in the United States parallels what is described in this Canadian paper. This was a surge of eating disorders the likes of which I had not experienced in my career.” Dr. Fornari did not participate in the current study.

“I’ve been here for over 40 years, and the average number of our inpatients in our eating disorder program has been three to five and about a dozen patients in our day clinic at any one time. But in the spring of 2020, we surged to 20 inpatients and over 20 day patients,” Dr. Fornari said.

“We can speculate as to the reasons for this,” he continued. “Kids were isolated. School was closed. They spent more time on social media and the Internet. Their sports activities were curtailed. There was anxiety because the guidance that we were all offered to prevent contagion was increasing people’s anxiety about safety and danger. So, I think we saw dramatic rises in eating disorders in the same way we saw dramatic rises in anxiety and depression in adolescents, as well.”

Dr. Fornari cited social media as an important contributing factor to eating disorders, especially among vulnerable teenagers. “Many of these vulnerable kids are looking at pictures of people who are very thin and comparing themselves, feeling inadequate, feeling sad. Social media is one of the reasons why the rates of psychopathology amongst teens has skyrocketed in the last decade. The surgeon general recently said we should delay access to social media until age 16 because the younger kids are impressionable and vulnerable. I think there is wisdom there, but it is very hard to actually put into practice.”
 

Worsening mental health

“I thought this was very relevant research and an important contribution to our understanding of eating disorders during pandemic times,” said Simon Sherry, PhD, professor of psychology and neuroscience at Dalhousie University in Halifax, Nova Scotia. “It also dovetails with my own experience as a practitioner.” Dr. Sherry was not involved in the research.

The pandemic has been difficult for people with disordered eating for many reasons, Dr. Sherry said. “There was a massive disruption or ‘loss of normal’ around food. Restaurants closed, grocery shopping was disrupted, scarcity of food occurred, hoarding of food occurred. That meant that eating was difficult for all of us, but especially for individuals who were rigid and controlling around the consumption of food. In this COVID era, you would need flexibility and acceptance around eating, but if you had a narrow range of preferred foods and preferred shopping locations, no doubt the pandemic made this a lot worse.”

Certain forms of disordered eating would be much more likely during the pandemic, Dr. Sherry noted. “For example, binge eating is often triggered by psychological, social, and environmental events,” and those triggers were abundant at the beginning of the pandemic. Boredom, anxiety, depression, stress, loneliness, confinement, and isolation are among the triggers. “COVID-19-related stress was and is very fertile ground for the growth of emotional eating, binge eating, or turning to food to cope. Eating disorders tend to fester amid silence and isolation and inactivity, and that was very much our experience during the lockdown phase of the pandemic,” he said.

Dr. Sherry agrees with the need for more funding for eating disorders research. “We know in Canada that eating disorders are a very important and deadly issue that is chronically underfunded. We are not funding disordered eating in proportion to its prevalence or in proportion to the amount of harm and destruction it creates for individuals, their family members, and our society at large. The authors are absolutely correct to advocate for care in proportion to the prevalence and the damage associated with eating disorders,” he said.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health, the Ministry of Long-Term Care, and the Canadian Institutes of Health Research (CIHR). Dr. Toulany, Dr. Fornari, and Dr. Sherry reported no relevant financial relationships. One study author reported receiving personal fees from the BMJ Group’s Archives of Diseases in Childhood and grants from CIHR, the Ontario Ministry of Health, the Centre for Addiction and Mental Health, and the Hospital for Sick Children. A second author reported funding from CIHR.

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

Emergency department visits and hospital admissions for eating disorders have increased significantly among adolescents during the COVID-19 pandemic, according to new research.

In a repeated cross-sectional study that examined population-based data from January 2017 through August 2022, ED visits increased by 121% above expected levels, and hospital admissions increased by 54% above expected among patients aged 10-17 years during the pandemic.

“We are hoping this study continues to heighten awareness of the importance of eating disorders, and also to bolster support for eating disorder programs so that we can adequately care for patients and address the increasing demand for treatment and services,” lead author Alene Toulany, MD, adolescent medicine specialist and researcher at the Hospital for Sick Children in Toronto, told this news organization.

The study was published in the Canadian Medical Association Journal.
 

‘A pressing concern’

The researchers used linked health administrative databases that included all patients in Ontario who were eligible for the Ontario Health Insurance Plan, which is publicly funded. They compared observed and expected rates of ED visits and hospitalizations for eating disorders between a prepandemic period (Jan. 1, 2017, to Feb. 29, 2020) and a pandemic period (Mar. 1, 2020, to Aug. 31, 2022). The researchers examined the following four age categories: adolescents (aged 10-17 years), young adults (aged 18-26 years), adults (aged 27-40 years), and older adults (aged 41-105 years).

Among adolescents, the observed rate of ED visits during the 30 pandemic months studied was 7.38 per 100,000 population, compared with 3.33 per 100,000 before the pandemic (incidence rate ratio [IRR], 2.21).

The rate of ED visits among young adults increased by 13% above the expected rate. It reached 2.79 per 100,000, compared with 2.46 per 100,000 in the prepandemic period (IRR, 1.13).

Among older adults, ED visits increased from 0.11 per 100,000 in the prepandemic period to 0.14 per 100,000 in the pandemic period (IRR, 1.15). The rate of ED visits among adults remained approximately the same.

The rate of hospital admissions among adolescents increased by 54% above the expected rate during the pandemic. The observed rate of hospital admissions before the pandemic was 5.74 per 100,000, vs. 8.82 per 100,000 during the pandemic (IRR, 1.54). Hospital admissions remained stable or decreased for the other age groups.

“Eating disorders have increased globally in children and adolescents during COVID,” said Dr. Toulany. “There are a number of risk factors contributing to this pandemic rise, including isolation, more time on social media, decreased access to care (as many in-person services were not available due to the pandemic), as well as fear of getting infected. All of these could contribute to an increased risk of developing an eating disorder or of making an existing one worse.”

Regardless of the cause, more investment in eating disorders research and eating disorder programs for adolescents and adults is needed, she said.

“The pandemic served as a catalyst, because it started to shed light on the prevalence of eating disorders, especially in young people. But it’s very important that we recognize that this has been a long-standing issue and a pressing concern that has been consistently overlooked and underfunded,” said Dr. Toulany.
 

 

 

Surging eating disorders

Commenting on the findings, Victor Fornari, MD, director of child and adolescent psychiatry at Zucker Hillside Hospital/Northwell Health in Glen Oaks, N.Y., said, “Our experience in the United States parallels what is described in this Canadian paper. This was a surge of eating disorders the likes of which I had not experienced in my career.” Dr. Fornari did not participate in the current study.

“I’ve been here for over 40 years, and the average number of our inpatients in our eating disorder program has been three to five and about a dozen patients in our day clinic at any one time. But in the spring of 2020, we surged to 20 inpatients and over 20 day patients,” Dr. Fornari said.

“We can speculate as to the reasons for this,” he continued. “Kids were isolated. School was closed. They spent more time on social media and the Internet. Their sports activities were curtailed. There was anxiety because the guidance that we were all offered to prevent contagion was increasing people’s anxiety about safety and danger. So, I think we saw dramatic rises in eating disorders in the same way we saw dramatic rises in anxiety and depression in adolescents, as well.”

Dr. Fornari cited social media as an important contributing factor to eating disorders, especially among vulnerable teenagers. “Many of these vulnerable kids are looking at pictures of people who are very thin and comparing themselves, feeling inadequate, feeling sad. Social media is one of the reasons why the rates of psychopathology amongst teens has skyrocketed in the last decade. The surgeon general recently said we should delay access to social media until age 16 because the younger kids are impressionable and vulnerable. I think there is wisdom there, but it is very hard to actually put into practice.”
 

Worsening mental health

“I thought this was very relevant research and an important contribution to our understanding of eating disorders during pandemic times,” said Simon Sherry, PhD, professor of psychology and neuroscience at Dalhousie University in Halifax, Nova Scotia. “It also dovetails with my own experience as a practitioner.” Dr. Sherry was not involved in the research.

The pandemic has been difficult for people with disordered eating for many reasons, Dr. Sherry said. “There was a massive disruption or ‘loss of normal’ around food. Restaurants closed, grocery shopping was disrupted, scarcity of food occurred, hoarding of food occurred. That meant that eating was difficult for all of us, but especially for individuals who were rigid and controlling around the consumption of food. In this COVID era, you would need flexibility and acceptance around eating, but if you had a narrow range of preferred foods and preferred shopping locations, no doubt the pandemic made this a lot worse.”

Certain forms of disordered eating would be much more likely during the pandemic, Dr. Sherry noted. “For example, binge eating is often triggered by psychological, social, and environmental events,” and those triggers were abundant at the beginning of the pandemic. Boredom, anxiety, depression, stress, loneliness, confinement, and isolation are among the triggers. “COVID-19-related stress was and is very fertile ground for the growth of emotional eating, binge eating, or turning to food to cope. Eating disorders tend to fester amid silence and isolation and inactivity, and that was very much our experience during the lockdown phase of the pandemic,” he said.

Dr. Sherry agrees with the need for more funding for eating disorders research. “We know in Canada that eating disorders are a very important and deadly issue that is chronically underfunded. We are not funding disordered eating in proportion to its prevalence or in proportion to the amount of harm and destruction it creates for individuals, their family members, and our society at large. The authors are absolutely correct to advocate for care in proportion to the prevalence and the damage associated with eating disorders,” he said.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health, the Ministry of Long-Term Care, and the Canadian Institutes of Health Research (CIHR). Dr. Toulany, Dr. Fornari, and Dr. Sherry reported no relevant financial relationships. One study author reported receiving personal fees from the BMJ Group’s Archives of Diseases in Childhood and grants from CIHR, the Ontario Ministry of Health, the Centre for Addiction and Mental Health, and the Hospital for Sick Children. A second author reported funding from CIHR.

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

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New insight into genetic link between schizophrenia and CVD

Article Type
Changed
Thu, 10/05/2023 - 13:35

 

TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

  • Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
  • Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
  • They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

  • Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
  • A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
  • Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
  • The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
  • There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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

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TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

  • Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
  • Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
  • They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

  • Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
  • A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
  • Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
  • The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
  • There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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

 

TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

  • Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
  • Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
  • They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

  • Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
  • A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
  • Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
  • The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
  • There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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

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FROM THE AMERICAN JOURNAL OF PSYCHIATRY

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