Bipolar Disorder

Investigators might have detected brain circuitry dysfunction in euthymic bipolar II patients, according to an imaging study published online in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The team compared functional MRIs of 19 adult patients euthymic for at least 2 weeks with 18 adult controls with no personal or family history of mental illness. The subjects ranged in age from 21 to 45. Participants with bipolar disorder scored significantly lower on the Wechsler Test of Adult Reading, which suggested that they had lower IQs and socioeconomic status. None of the study participants with bipolar disorder reported ever experiencing a manic or mixed episode, or catatonic symptoms.

On the day of the scan, the subjects’ mood and psychomotor symptoms were assessed using the Youth Mania Rating Scale for hypomanic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, and the CORE for psychomotorsymptoms, reported Dr. William R. Marchand, a psychiatrist at the Veterans Affairs Medical Center in Salt Lake City, and his colleagues (Prog. Neuropsychopharmacol. Biol. Psychiatry. 2014 Jan. 16 [doi:10.1016/j.pnpbp.2014.01.004]).

"We found [statistically significant] increased functional connectivity among bipolar subjects compared to healthy controls in two [cortical midline structure] circuits," reported Dr. Marchand, who also is affiliated with the departments of psychiatry and psychology at the University of Utah. "One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus, and the right medial frontal gyrus and surrounding region."

Specifically, in the left medial superior frontal region, significantly increased connectivity was found (cluster size 628 voxels; P = .0008), compared with controls. In the dorsolateral region of the left superior frontal gyrus, in one cluster, the investigators also found significantly increased connectivity (cluster size 673 voxels; P = .0004) among the subjects with bipolar disorder, compared with controls.

The investigators said cortical midline structure (CMS) circuitry is thought to play a key role in the neurobiology of affective illness because the "medial cortex is involved in emotional regulation, self-referential thinking, the default mode network and may mediate the relationship between aberrant self-referential thinking and negative affect in mood disorders."

Previously, the investigators identified similar problems in depressed patients with bipolar disorder. That the problems persist even when patients are doing well indicates that the findings "may represent trait pathology." Among the implications, they said, is that "nonmedication approaches that impact medical cortical function, such as mindfulness-based interventions, may warrant evaluation as adjunctive treatments for relapse prevention."

One limitation of the study cited by the investigators is the relatively small sample size. They suggested that future studies focus on whether CMS circuits affect cognitive processes.

No financial disclosures were reported. The study was funded by the Department of Veterans Affairs.

[email protected]

Investigators might have detected brain circuitry dysfunction in euthymic bipolar II patients, according to an imaging study published online in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The team compared functional MRIs of 19 adult patients euthymic for at least 2 weeks with 18 adult controls with no personal or family history of mental illness. The subjects ranged in age from 21 to 45. Participants with bipolar disorder scored significantly lower on the Wechsler Test of Adult Reading, which suggested that they had lower IQs and socioeconomic status. None of the study participants with bipolar disorder reported ever experiencing a manic or mixed episode, or catatonic symptoms.

On the day of the scan, the subjects’ mood and psychomotor symptoms were assessed using the Youth Mania Rating Scale for hypomanic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, and the CORE for psychomotorsymptoms, reported Dr. William R. Marchand, a psychiatrist at the Veterans Affairs Medical Center in Salt Lake City, and his colleagues (Prog. Neuropsychopharmacol. Biol. Psychiatry. 2014 Jan. 16 [doi:10.1016/j.pnpbp.2014.01.004]).

"We found [statistically significant] increased functional connectivity among bipolar subjects compared to healthy controls in two [cortical midline structure] circuits," reported Dr. Marchand, who also is affiliated with the departments of psychiatry and psychology at the University of Utah. "One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus, and the right medial frontal gyrus and surrounding region."

Specifically, in the left medial superior frontal region, significantly increased connectivity was found (cluster size 628 voxels; P = .0008), compared with controls. In the dorsolateral region of the left superior frontal gyrus, in one cluster, the investigators also found significantly increased connectivity (cluster size 673 voxels; P = .0004) among the subjects with bipolar disorder, compared with controls.

The investigators said cortical midline structure (CMS) circuitry is thought to play a key role in the neurobiology of affective illness because the "medial cortex is involved in emotional regulation, self-referential thinking, the default mode network and may mediate the relationship between aberrant self-referential thinking and negative affect in mood disorders."

Previously, the investigators identified similar problems in depressed patients with bipolar disorder. That the problems persist even when patients are doing well indicates that the findings "may represent trait pathology." Among the implications, they said, is that "nonmedication approaches that impact medical cortical function, such as mindfulness-based interventions, may warrant evaluation as adjunctive treatments for relapse prevention."

One limitation of the study cited by the investigators is the relatively small sample size. They suggested that future studies focus on whether CMS circuits affect cognitive processes.

No financial disclosures were reported. The study was funded by the Department of Veterans Affairs.

[email protected]

Investigators might have detected brain circuitry dysfunction in euthymic bipolar II patients, according to an imaging study published online in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The team compared functional MRIs of 19 adult patients euthymic for at least 2 weeks with 18 adult controls with no personal or family history of mental illness. The subjects ranged in age from 21 to 45. Participants with bipolar disorder scored significantly lower on the Wechsler Test of Adult Reading, which suggested that they had lower IQs and socioeconomic status. None of the study participants with bipolar disorder reported ever experiencing a manic or mixed episode, or catatonic symptoms.

On the day of the scan, the subjects’ mood and psychomotor symptoms were assessed using the Youth Mania Rating Scale for hypomanic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, and the CORE for psychomotorsymptoms, reported Dr. William R. Marchand, a psychiatrist at the Veterans Affairs Medical Center in Salt Lake City, and his colleagues (Prog. Neuropsychopharmacol. Biol. Psychiatry. 2014 Jan. 16 [doi:10.1016/j.pnpbp.2014.01.004]).

"We found [statistically significant] increased functional connectivity among bipolar subjects compared to healthy controls in two [cortical midline structure] circuits," reported Dr. Marchand, who also is affiliated with the departments of psychiatry and psychology at the University of Utah. "One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus, and the right medial frontal gyrus and surrounding region."

Specifically, in the left medial superior frontal region, significantly increased connectivity was found (cluster size 628 voxels; P = .0008), compared with controls. In the dorsolateral region of the left superior frontal gyrus, in one cluster, the investigators also found significantly increased connectivity (cluster size 673 voxels; P = .0004) among the subjects with bipolar disorder, compared with controls.

The investigators said cortical midline structure (CMS) circuitry is thought to play a key role in the neurobiology of affective illness because the "medial cortex is involved in emotional regulation, self-referential thinking, the default mode network and may mediate the relationship between aberrant self-referential thinking and negative affect in mood disorders."

Previously, the investigators identified similar problems in depressed patients with bipolar disorder. That the problems persist even when patients are doing well indicates that the findings "may represent trait pathology." Among the implications, they said, is that "nonmedication approaches that impact medical cortical function, such as mindfulness-based interventions, may warrant evaluation as adjunctive treatments for relapse prevention."

One limitation of the study cited by the investigators is the relatively small sample size. They suggested that future studies focus on whether CMS circuits affect cognitive processes.

No financial disclosures were reported. The study was funded by the Department of Veterans Affairs.

[email protected]

Patients with serious mental illness who quit smoking with a standard 12-week course of varenicline and cognitive-behavioral therapy are three times more likely to maintain that abstinence if they take a maintenance dose of the drug than if they discontinue it, according to a report published online Jan. 7 in JAMA.

In what the researchers described as the first randomized controlled clinical trial of maintenance pharmacotherapy aimed at preventing smoking relapse in people with serious mental illness, the prevalence of smoking abstinence after 1 year was 60% (24 of 40 study participants) in patients assigned to maintenance varenicline, compared with 19% (9 of 47 participants) in those assigned to placebo.

"Such maintenance treatment may reduce the high prevalence of tobacco dependence and reduce the heavy burden of smoking-related morbidity and mortality in those with serious mental illness," said Dr. A. Eden Evins of Massachusetts General Hospital and Harvard Medical School, Boston, and her associates.

The open-label study, released in advance of the 50th anniversary of the Surgeon General’s Report on Smoking and Health, involved 203 adults with schizophrenia spectrum disorder (185 patients) or bipolar disorder (18 patients) who reported smoking 10 or more cigarettes per day and whose expired carbon monoxide levels were higher than 9 ppm at baseline. All were outpatients at 10 community health centers in Massachusetts, Michigan, New Hampshire, Indiana, Alabama, or Minnesota, and all were taking stable doses of antipsychotic or mood stabilizing medication.

A total of 87 of these participants successfully completed a 12-week smoking cessation program combining up to 1.0 mg of varenicline twice daily plus weekly 1-hour group cognitive-behavioral therapy (CBT) sessions. They were randomly assigned to continue for another 40 weeks with either CBT plus 1.0 mg of varenicline twice daily (40 patients) or CBT plus matching placebo (47 patients).

The CBT, which focused on relapse-prevention skills, was tapered from weekly to monthly sessions, for a total of 15 sessions during the 40 weeks.

At 52 weeks from baseline, smoking cessation treatment was stopped, and the 59 patients remaining in the study were followed through week 64 for biochemically verified smoking abstinence and safety outcomes.

At week 52, 24 of 40 participants taking maintenance varenicline (60%) were still abstaining from smoking, compared with only 9 of the 47 patients (19%) taking placebo, for an odds ratio of 6.2. At week 64, 18 participants (45%) in the varenicline group were still abstaining from smoking, compared with only 6 (13%) in the placebo group, for an odds ratio of 5.1, Dr. Evins and her associates reported (JAMA 2014 Jan. 7 [doi: 10.1001/jama.2013.285113]).

Patients in the varenicline group also had a longer interval until smoking relapse, with a median time of 358 days, compared with those in the placebo group (35 days).

During treatment and follow-up, the two study groups showed no differences in the severity of their psychiatric symptoms, nicotine withdrawal symptoms, or self-reported overall health. No serious adverse events were attributed to the study medication.

However, because of the small sample size and the high dropout rate of the study, "it is not possible to accurately estimate the risk of serious adverse effects or to make claims regarding safety," the investigators noted.

This study was funded by the National Institute on Drug Abuse and by Pfizer. Pfizer also supplied the study medication and provided other support. Dr. Evins reported ties to EnVivo Pharmaceuticals, GlaxoSmithKline, and Pfizer, and her associates reported ties to Publicis Healthcare Communications Group, Janssen, Otsuka, AssurEx, Eli Lilly, and Pfizer.

Patients with serious mental illness who quit smoking with a standard 12-week course of varenicline and cognitive-behavioral therapy are three times more likely to maintain that abstinence if they take a maintenance dose of the drug than if they discontinue it, according to a report published online Jan. 7 in JAMA.

In what the researchers described as the first randomized controlled clinical trial of maintenance pharmacotherapy aimed at preventing smoking relapse in people with serious mental illness, the prevalence of smoking abstinence after 1 year was 60% (24 of 40 study participants) in patients assigned to maintenance varenicline, compared with 19% (9 of 47 participants) in those assigned to placebo.

"Such maintenance treatment may reduce the high prevalence of tobacco dependence and reduce the heavy burden of smoking-related morbidity and mortality in those with serious mental illness," said Dr. A. Eden Evins of Massachusetts General Hospital and Harvard Medical School, Boston, and her associates.

The open-label study, released in advance of the 50th anniversary of the Surgeon General’s Report on Smoking and Health, involved 203 adults with schizophrenia spectrum disorder (185 patients) or bipolar disorder (18 patients) who reported smoking 10 or more cigarettes per day and whose expired carbon monoxide levels were higher than 9 ppm at baseline. All were outpatients at 10 community health centers in Massachusetts, Michigan, New Hampshire, Indiana, Alabama, or Minnesota, and all were taking stable doses of antipsychotic or mood stabilizing medication.

A total of 87 of these participants successfully completed a 12-week smoking cessation program combining up to 1.0 mg of varenicline twice daily plus weekly 1-hour group cognitive-behavioral therapy (CBT) sessions. They were randomly assigned to continue for another 40 weeks with either CBT plus 1.0 mg of varenicline twice daily (40 patients) or CBT plus matching placebo (47 patients).

The CBT, which focused on relapse-prevention skills, was tapered from weekly to monthly sessions, for a total of 15 sessions during the 40 weeks.

At 52 weeks from baseline, smoking cessation treatment was stopped, and the 59 patients remaining in the study were followed through week 64 for biochemically verified smoking abstinence and safety outcomes.

At week 52, 24 of 40 participants taking maintenance varenicline (60%) were still abstaining from smoking, compared with only 9 of the 47 patients (19%) taking placebo, for an odds ratio of 6.2. At week 64, 18 participants (45%) in the varenicline group were still abstaining from smoking, compared with only 6 (13%) in the placebo group, for an odds ratio of 5.1, Dr. Evins and her associates reported (JAMA 2014 Jan. 7 [doi: 10.1001/jama.2013.285113]).

Patients in the varenicline group also had a longer interval until smoking relapse, with a median time of 358 days, compared with those in the placebo group (35 days).

During treatment and follow-up, the two study groups showed no differences in the severity of their psychiatric symptoms, nicotine withdrawal symptoms, or self-reported overall health. No serious adverse events were attributed to the study medication.

However, because of the small sample size and the high dropout rate of the study, "it is not possible to accurately estimate the risk of serious adverse effects or to make claims regarding safety," the investigators noted.

This study was funded by the National Institute on Drug Abuse and by Pfizer. Pfizer also supplied the study medication and provided other support. Dr. Evins reported ties to EnVivo Pharmaceuticals, GlaxoSmithKline, and Pfizer, and her associates reported ties to Publicis Healthcare Communications Group, Janssen, Otsuka, AssurEx, Eli Lilly, and Pfizer.

Patients with serious mental illness who quit smoking with a standard 12-week course of varenicline and cognitive-behavioral therapy are three times more likely to maintain that abstinence if they take a maintenance dose of the drug than if they discontinue it, according to a report published online Jan. 7 in JAMA.

In what the researchers described as the first randomized controlled clinical trial of maintenance pharmacotherapy aimed at preventing smoking relapse in people with serious mental illness, the prevalence of smoking abstinence after 1 year was 60% (24 of 40 study participants) in patients assigned to maintenance varenicline, compared with 19% (9 of 47 participants) in those assigned to placebo.

"Such maintenance treatment may reduce the high prevalence of tobacco dependence and reduce the heavy burden of smoking-related morbidity and mortality in those with serious mental illness," said Dr. A. Eden Evins of Massachusetts General Hospital and Harvard Medical School, Boston, and her associates.

The open-label study, released in advance of the 50th anniversary of the Surgeon General’s Report on Smoking and Health, involved 203 adults with schizophrenia spectrum disorder (185 patients) or bipolar disorder (18 patients) who reported smoking 10 or more cigarettes per day and whose expired carbon monoxide levels were higher than 9 ppm at baseline. All were outpatients at 10 community health centers in Massachusetts, Michigan, New Hampshire, Indiana, Alabama, or Minnesota, and all were taking stable doses of antipsychotic or mood stabilizing medication.

A total of 87 of these participants successfully completed a 12-week smoking cessation program combining up to 1.0 mg of varenicline twice daily plus weekly 1-hour group cognitive-behavioral therapy (CBT) sessions. They were randomly assigned to continue for another 40 weeks with either CBT plus 1.0 mg of varenicline twice daily (40 patients) or CBT plus matching placebo (47 patients).

The CBT, which focused on relapse-prevention skills, was tapered from weekly to monthly sessions, for a total of 15 sessions during the 40 weeks.

At 52 weeks from baseline, smoking cessation treatment was stopped, and the 59 patients remaining in the study were followed through week 64 for biochemically verified smoking abstinence and safety outcomes.

At week 52, 24 of 40 participants taking maintenance varenicline (60%) were still abstaining from smoking, compared with only 9 of the 47 patients (19%) taking placebo, for an odds ratio of 6.2. At week 64, 18 participants (45%) in the varenicline group were still abstaining from smoking, compared with only 6 (13%) in the placebo group, for an odds ratio of 5.1, Dr. Evins and her associates reported (JAMA 2014 Jan. 7 [doi: 10.1001/jama.2013.285113]).

Patients in the varenicline group also had a longer interval until smoking relapse, with a median time of 358 days, compared with those in the placebo group (35 days).

During treatment and follow-up, the two study groups showed no differences in the severity of their psychiatric symptoms, nicotine withdrawal symptoms, or self-reported overall health. No serious adverse events were attributed to the study medication.

However, because of the small sample size and the high dropout rate of the study, "it is not possible to accurately estimate the risk of serious adverse effects or to make claims regarding safety," the investigators noted.

This study was funded by the National Institute on Drug Abuse and by Pfizer. Pfizer also supplied the study medication and provided other support. Dr. Evins reported ties to EnVivo Pharmaceuticals, GlaxoSmithKline, and Pfizer, and her associates reported ties to Publicis Healthcare Communications Group, Janssen, Otsuka, AssurEx, Eli Lilly, and Pfizer.

The recent nationwide decline in the rate of cigarette smoking in the general population of adults did not extend to those with mental illness, according to a report published online Jan. 7 in JAMA.

In a study of serial, nationally representative samples of noninstitutionalized American adults, the smoking rate significantly declined from 19.2% in 2004 to 16.5% in 2011 among adults without mental illness. But it declined only negligibly during that period among those with mental illness, from 25.3% to 24.9%, said Benjamin Lê Cook, Ph.D., of the department of psychiatry, Cambridge (Mass.) Health Alliance, and his associates.

"This suggests that tobacco control policies and cessation interventions targeting the general population have not worked as effectively for those with mental illness," they said.

Noting that until now "there have been no studies that examine smoking trends among persons with mental illness," Dr. Cookand his colleagues examined smoking rates over time using data from the Medical Expenditure Panel Survey. This survey assesses health care use in about 15,000 U.S. households each year, and it includes such data as smoking status and medical treatment.

For their study, Dr. Cook and his associates tracked smoking rates among 165,269 participants from 2004 through 2011. The overall smoking rate was higher among adults with mental illness (28.2%) than among those without mental illness (17.5%), which was expected, because many previous studies have noted an approximately twofold higher rate of smoking among people with mental illness.

In an initial, unadjusted analysis of the data, the smoking rate dropped from 19.5% to 15.6% in adults without mental illness, compared with a much smaller decline from 28.8% to 27.0% in those with mental illness. After the data were adjusted to account for numerous potentially confounding factors such as age, sex, race/ethnicity, marital status, income, and urban versus other areas of residence, those rates changed slightly, but the pattern persisted: Smoking rates were consistently higher and showed only a nominal decline among people with mental illness.

These findings remained robust in further analyses that varied the definition of mental illness to include milder neurotic, anxiety, and mood disorders, the researchers said (JAMA 2014 [doi:10.1001/jama.2013.284985]).

The investigators also performed a separate analysis of data regarding 14,057 adult smokers with mental illness who participated in the National Survey on Drug Use and Health in 2009-2011. They found that the rate of quitting smoking was significantly higher (37.2%) in those who received mental health treatment during that interval than among those who did not (33.1%).

In addition, receiving any mental health treatment significantly raised the likelihood of quitting smoking, even after the data were adjusted to account for substance use therapy, the severity of the mental illness, and other factors likely to affect smoking status.

"For many individuals receiving mental health treatment, interactions with mental health professionals are their only access to preventive health counseling," added Dr. Cook and his associates. "Effective tobacco treatments, interventions that integrate mental health and substance abuse treatment, and nicotine replacement therapies are now readily available and can dovetail easily with psychosocial treatments and prescription of psychotropic medications."

One barrier to these approaches is that some professionals in both primary care and behavioral health "continue to believe that smoking cessation can adversely affect psychiatric treatment." Even if they don’t believe that, smoking culture is normalized in many psychiatric treatment settings.

Some health professionals also consider individuals with mental illness to lack the willingness or ability to quit smoking, or think these individuals do not appreciate its adverse health effects. "Few mental health care professionals assess clients’ tobacco use, advise and assist them in quitting, or arrange follow-up, and most individuals with mental illness are not afforded the same cessation opportunities as the general population," Dr. Cook and his associates said.

Dr. Cook and his colleagues cited several limitations of the study. Among them is that the prevalence of smoking within the U.S. population might have been underestimated, because the survey excluded people with mental illness who were institutionalized.

Still, these results suggest that "smokers can quit and remain abstinent from cigarettes during mental health treatment and that this is a promising setting to promote smoking cessation," they wrote.

This work was supported by the National Institute of Mental Health and the William F. Milton Fund. No financial conflicts of interest were reported.

The recent nationwide decline in the rate of cigarette smoking in the general population of adults did not extend to those with mental illness, according to a report published online Jan. 7 in JAMA.

In a study of serial, nationally representative samples of noninstitutionalized American adults, the smoking rate significantly declined from 19.2% in 2004 to 16.5% in 2011 among adults without mental illness. But it declined only negligibly during that period among those with mental illness, from 25.3% to 24.9%, said Benjamin Lê Cook, Ph.D., of the department of psychiatry, Cambridge (Mass.) Health Alliance, and his associates.

"This suggests that tobacco control policies and cessation interventions targeting the general population have not worked as effectively for those with mental illness," they said.

Noting that until now "there have been no studies that examine smoking trends among persons with mental illness," Dr. Cookand his colleagues examined smoking rates over time using data from the Medical Expenditure Panel Survey. This survey assesses health care use in about 15,000 U.S. households each year, and it includes such data as smoking status and medical treatment.

For their study, Dr. Cook and his associates tracked smoking rates among 165,269 participants from 2004 through 2011. The overall smoking rate was higher among adults with mental illness (28.2%) than among those without mental illness (17.5%), which was expected, because many previous studies have noted an approximately twofold higher rate of smoking among people with mental illness.

In an initial, unadjusted analysis of the data, the smoking rate dropped from 19.5% to 15.6% in adults without mental illness, compared with a much smaller decline from 28.8% to 27.0% in those with mental illness. After the data were adjusted to account for numerous potentially confounding factors such as age, sex, race/ethnicity, marital status, income, and urban versus other areas of residence, those rates changed slightly, but the pattern persisted: Smoking rates were consistently higher and showed only a nominal decline among people with mental illness.

These findings remained robust in further analyses that varied the definition of mental illness to include milder neurotic, anxiety, and mood disorders, the researchers said (JAMA 2014 [doi:10.1001/jama.2013.284985]).

The investigators also performed a separate analysis of data regarding 14,057 adult smokers with mental illness who participated in the National Survey on Drug Use and Health in 2009-2011. They found that the rate of quitting smoking was significantly higher (37.2%) in those who received mental health treatment during that interval than among those who did not (33.1%).

In addition, receiving any mental health treatment significantly raised the likelihood of quitting smoking, even after the data were adjusted to account for substance use therapy, the severity of the mental illness, and other factors likely to affect smoking status.

"For many individuals receiving mental health treatment, interactions with mental health professionals are their only access to preventive health counseling," added Dr. Cook and his associates. "Effective tobacco treatments, interventions that integrate mental health and substance abuse treatment, and nicotine replacement therapies are now readily available and can dovetail easily with psychosocial treatments and prescription of psychotropic medications."

One barrier to these approaches is that some professionals in both primary care and behavioral health "continue to believe that smoking cessation can adversely affect psychiatric treatment." Even if they don’t believe that, smoking culture is normalized in many psychiatric treatment settings.

Some health professionals also consider individuals with mental illness to lack the willingness or ability to quit smoking, or think these individuals do not appreciate its adverse health effects. "Few mental health care professionals assess clients’ tobacco use, advise and assist them in quitting, or arrange follow-up, and most individuals with mental illness are not afforded the same cessation opportunities as the general population," Dr. Cook and his associates said.

Dr. Cook and his colleagues cited several limitations of the study. Among them is that the prevalence of smoking within the U.S. population might have been underestimated, because the survey excluded people with mental illness who were institutionalized.

Still, these results suggest that "smokers can quit and remain abstinent from cigarettes during mental health treatment and that this is a promising setting to promote smoking cessation," they wrote.

This work was supported by the National Institute of Mental Health and the William F. Milton Fund. No financial conflicts of interest were reported.

The recent nationwide decline in the rate of cigarette smoking in the general population of adults did not extend to those with mental illness, according to a report published online Jan. 7 in JAMA.

In a study of serial, nationally representative samples of noninstitutionalized American adults, the smoking rate significantly declined from 19.2% in 2004 to 16.5% in 2011 among adults without mental illness. But it declined only negligibly during that period among those with mental illness, from 25.3% to 24.9%, said Benjamin Lê Cook, Ph.D., of the department of psychiatry, Cambridge (Mass.) Health Alliance, and his associates.

"This suggests that tobacco control policies and cessation interventions targeting the general population have not worked as effectively for those with mental illness," they said.

Noting that until now "there have been no studies that examine smoking trends among persons with mental illness," Dr. Cookand his colleagues examined smoking rates over time using data from the Medical Expenditure Panel Survey. This survey assesses health care use in about 15,000 U.S. households each year, and it includes such data as smoking status and medical treatment.

For their study, Dr. Cook and his associates tracked smoking rates among 165,269 participants from 2004 through 2011. The overall smoking rate was higher among adults with mental illness (28.2%) than among those without mental illness (17.5%), which was expected, because many previous studies have noted an approximately twofold higher rate of smoking among people with mental illness.

In an initial, unadjusted analysis of the data, the smoking rate dropped from 19.5% to 15.6% in adults without mental illness, compared with a much smaller decline from 28.8% to 27.0% in those with mental illness. After the data were adjusted to account for numerous potentially confounding factors such as age, sex, race/ethnicity, marital status, income, and urban versus other areas of residence, those rates changed slightly, but the pattern persisted: Smoking rates were consistently higher and showed only a nominal decline among people with mental illness.

These findings remained robust in further analyses that varied the definition of mental illness to include milder neurotic, anxiety, and mood disorders, the researchers said (JAMA 2014 [doi:10.1001/jama.2013.284985]).

The investigators also performed a separate analysis of data regarding 14,057 adult smokers with mental illness who participated in the National Survey on Drug Use and Health in 2009-2011. They found that the rate of quitting smoking was significantly higher (37.2%) in those who received mental health treatment during that interval than among those who did not (33.1%).

In addition, receiving any mental health treatment significantly raised the likelihood of quitting smoking, even after the data were adjusted to account for substance use therapy, the severity of the mental illness, and other factors likely to affect smoking status.

"For many individuals receiving mental health treatment, interactions with mental health professionals are their only access to preventive health counseling," added Dr. Cook and his associates. "Effective tobacco treatments, interventions that integrate mental health and substance abuse treatment, and nicotine replacement therapies are now readily available and can dovetail easily with psychosocial treatments and prescription of psychotropic medications."

One barrier to these approaches is that some professionals in both primary care and behavioral health "continue to believe that smoking cessation can adversely affect psychiatric treatment." Even if they don’t believe that, smoking culture is normalized in many psychiatric treatment settings.

Some health professionals also consider individuals with mental illness to lack the willingness or ability to quit smoking, or think these individuals do not appreciate its adverse health effects. "Few mental health care professionals assess clients’ tobacco use, advise and assist them in quitting, or arrange follow-up, and most individuals with mental illness are not afforded the same cessation opportunities as the general population," Dr. Cook and his associates said.

Dr. Cook and his colleagues cited several limitations of the study. Among them is that the prevalence of smoking within the U.S. population might have been underestimated, because the survey excluded people with mental illness who were institutionalized.

Still, these results suggest that "smokers can quit and remain abstinent from cigarettes during mental health treatment and that this is a promising setting to promote smoking cessation," they wrote.

This work was supported by the National Institute of Mental Health and the William F. Milton Fund. No financial conflicts of interest were reported.

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

Variations in the GADL1 gene predicted the response to lithium maintenance therapy among patients of Han Chinese ethnicity who have bipolar I disorder, according to a report published online Dec. 25 in the New England Journal of Medicine.

In a genomewide association study that was confirmed in two replication samples, the presence of two single-nucleotide polymorphisms (rs17026688 and rs17026651) located in the introns of the GADL1 gene had a 93% sensitivity and 85% specificity for predicting a positive treatment response, and a novel variant (IVS8+48delG) located in intron 8 of the GADL1 gene also predicted treatment response among bipolar patients of Han descent, said Chien-Hsiun Chen, Ph.D., of the Institute of Biomedical Sciences, Academia Sinica, Taipei (Taiwan) and his associates.

"These alleles are rare in persons of European or African ancestry, but it is possible that other variants in GADL1 may influence the response to lithium therapy in these populations," the researchers noted.

They assessed 1,647 Han Chinese patients with bipolar disorder I who were treated at Academia Sinica, psychiatric departments of general hospitals, or psychiatric institutions across Taiwan. The investigators identified 294 patients who had received lithium therapy and had demonstrated good adherence for at least 2 years. They proceeded to perform a discovery genomewide association study.

The median age of these 294 patients was 49 years, and 49% were men. During periods in which these participants were not receiving lithium, they had a median of six bipolar episodes (range, 4-144) since disease onset, at a median frequency of 1 per year (range, 0.4-15 per year).

The two single-nucleotide polymorphisms (SNPs) on a single chromosome of the GADL1 gene were strongly associated with a positive response to lithium; no other chromosomal region showed a significant association. This gene encodes glutamate decarboxylase–like protein 1.

The investigators then performed a replication study in a sample of 100 different patients with bipolar I disorder who had been treated with lithium and had demonstrated good adherence for at least 10 years. Again, genotyping of rs17026688 and rs17026651, along with flanking SNPs in the GADL1 gene, showed that only the two target SNPs had a sensitivity of 93% for predicting lithium response and a specificity of 85%-86%.

A final replication study was performed in 24 randomly selected patients who were followed for at least 2 years. All 16 participants who carried the SNPs had a good response to lithium maintenance therapy, and all 8 noncarriers had a poor lithium response, the investigators reported (New Engl. J. Med. 2013 Dec. 25 [doi: 10.1056/NEJMoa1212444]).

Dr. Chen and his associates then looked for other local variants likely to affect the expression of GADL1. They found a one-base deletion in intron 8 (IVS8+48delG), genotyped it in samples from all patients in the discovery and replication cohorts, and found that it was in complete linkage disequilibrium with rs17026688.

Although the precise physiologic function of the GADL1 protein is not yet known, it may be similar to that of the related protein glutamate decarboxylase. The latter protein is abnormally expressed in the brains of patients with bipolar disorder. "Our results are consistent with those of the first genomewide association study of lithium treatment, which suggests the importance of the glutamate pathway in bipolar disorder and the mechanism by which lithium may affect glutamatergic neurotransmission," Dr. Chen and his associates said.

"Nearly half of the 1,761 patients with bipolar I disorder in this study (47.2%) carry the response allele T of rs17026688, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half of the patients with bipolar I disorder in Taiwan may benefit from lithium therapy," they noted.

Future research should assess whether these genetic variations can be used as biomarkers in affective disorders other than bipolar disorder, such as refractory major depressive disorder. Lithium often is used to augment the effects of antidepressants in MDD, the investigators added.

This study was funded by Academia Sinica and the National Science Council, Taiwan (National Center for Genomic Medicine, Translational Resource Center for Genomic Medicine, and National Research Program for Biopharmaceuticals).

Increased energy or motor activity is a more important symptom for diagnosing mania within bipolar disorder than are mood changes, a study of 117 hospitalized patients suggests.

Increased energy/activity has been proposed as a core symptom of manic episode in DSM-5. "The present results support the hypothesis that increased energy or activity ... represents the core feature of the manic syndrome," wrote Dr. Elie Cheniaux of the State University of Rio de Janeiro and his colleagues (J. Affect. Disord. 2014;152-4:256-61).

The investigators evaluated the symptoms of each patient hospitalized with an acute manic episode using several instruments. All of the patients took the Mini International Neuropsychiatric Interview, a tool that allows psychiatric diagnoses to be formulated based on DSM-IV and ICD-10 criteria. Those who met the DSM-IV criteria for a manic episode were administered the 37-item Schedule for Affective Disorders and Schizophrenia (SADS)–Change Version, a scale that evaluates the presence of manic, depressive, anxiety, and psychotic symptoms. Dr. Cheniaux and his colleagues performed a Confirmatory Factor Analysis to determine which items best fit the mania dimension. Additional tools such as an Item Response Theory (IRT) Analysis were used to determine the extent to which each symptom described different levels of severity.

Most of the patients (58.1%) were female, the average age was 42.4 years, and the average age at first crisis was 24.3 years. Mania proved to be more frequent than depression in the first crisis (P less than 0.001).

The IRT analysis assigned values to each symptom, and the highest values were assigned to "increased energy" (4.05), "elated mood" (2.54), "less need for sleep" (2.07), and "increased activity" (1.98). The item "anger" got the lowest value (1.02) and "differentiates patients with mania relatively little, with similar levels across severity levels," they wrote.

Dr. Cheniaux said in an interview that he had expected a higher factorial loading with anger. "It is possible that the angriest patients refused to participate in the study, so the symptom of anger could be underrepresented in our study," he said.

Ultimately, the investigators found that patients’ increased energy was the alteration that correlated "the most with the total severity of manic symptoms."

They cited several limitations of the study. For example, patients in the sample might not be representative of bipolar patients in the general population because they were evaluated while their manic symptoms were at their peak. In addition, the investigators suggested only six manic symptoms: increased activity, less need for sleep, increased energy, elated mood, increased self-esteem, and anger. Still, the results suggest that changes in the DSM-5 in the diagnostic criteria for a bipolar diagnosis could be more extensive, they wrote.

Dr. Cheniaux reported that he had no conflicts of interest.

[email protected]

Increased energy or motor activity is a more important symptom for diagnosing mania within bipolar disorder than are mood changes, a study of 117 hospitalized patients suggests.

Increased energy/activity has been proposed as a core symptom of manic episode in DSM-5. "The present results support the hypothesis that increased energy or activity ... represents the core feature of the manic syndrome," wrote Dr. Elie Cheniaux of the State University of Rio de Janeiro and his colleagues (J. Affect. Disord. 2014;152-4:256-61).

The investigators evaluated the symptoms of each patient hospitalized with an acute manic episode using several instruments. All of the patients took the Mini International Neuropsychiatric Interview, a tool that allows psychiatric diagnoses to be formulated based on DSM-IV and ICD-10 criteria. Those who met the DSM-IV criteria for a manic episode were administered the 37-item Schedule for Affective Disorders and Schizophrenia (SADS)–Change Version, a scale that evaluates the presence of manic, depressive, anxiety, and psychotic symptoms. Dr. Cheniaux and his colleagues performed a Confirmatory Factor Analysis to determine which items best fit the mania dimension. Additional tools such as an Item Response Theory (IRT) Analysis were used to determine the extent to which each symptom described different levels of severity.

Most of the patients (58.1%) were female, the average age was 42.4 years, and the average age at first crisis was 24.3 years. Mania proved to be more frequent than depression in the first crisis (P less than 0.001).

The IRT analysis assigned values to each symptom, and the highest values were assigned to "increased energy" (4.05), "elated mood" (2.54), "less need for sleep" (2.07), and "increased activity" (1.98). The item "anger" got the lowest value (1.02) and "differentiates patients with mania relatively little, with similar levels across severity levels," they wrote.

Dr. Cheniaux said in an interview that he had expected a higher factorial loading with anger. "It is possible that the angriest patients refused to participate in the study, so the symptom of anger could be underrepresented in our study," he said.

Ultimately, the investigators found that patients’ increased energy was the alteration that correlated "the most with the total severity of manic symptoms."

They cited several limitations of the study. For example, patients in the sample might not be representative of bipolar patients in the general population because they were evaluated while their manic symptoms were at their peak. In addition, the investigators suggested only six manic symptoms: increased activity, less need for sleep, increased energy, elated mood, increased self-esteem, and anger. Still, the results suggest that changes in the DSM-5 in the diagnostic criteria for a bipolar diagnosis could be more extensive, they wrote.

Dr. Cheniaux reported that he had no conflicts of interest.

[email protected]

Increased energy or motor activity is a more important symptom for diagnosing mania within bipolar disorder than are mood changes, a study of 117 hospitalized patients suggests.

Increased energy/activity has been proposed as a core symptom of manic episode in DSM-5. "The present results support the hypothesis that increased energy or activity ... represents the core feature of the manic syndrome," wrote Dr. Elie Cheniaux of the State University of Rio de Janeiro and his colleagues (J. Affect. Disord. 2014;152-4:256-61).

The investigators evaluated the symptoms of each patient hospitalized with an acute manic episode using several instruments. All of the patients took the Mini International Neuropsychiatric Interview, a tool that allows psychiatric diagnoses to be formulated based on DSM-IV and ICD-10 criteria. Those who met the DSM-IV criteria for a manic episode were administered the 37-item Schedule for Affective Disorders and Schizophrenia (SADS)–Change Version, a scale that evaluates the presence of manic, depressive, anxiety, and psychotic symptoms. Dr. Cheniaux and his colleagues performed a Confirmatory Factor Analysis to determine which items best fit the mania dimension. Additional tools such as an Item Response Theory (IRT) Analysis were used to determine the extent to which each symptom described different levels of severity.

Most of the patients (58.1%) were female, the average age was 42.4 years, and the average age at first crisis was 24.3 years. Mania proved to be more frequent than depression in the first crisis (P less than 0.001).

The IRT analysis assigned values to each symptom, and the highest values were assigned to "increased energy" (4.05), "elated mood" (2.54), "less need for sleep" (2.07), and "increased activity" (1.98). The item "anger" got the lowest value (1.02) and "differentiates patients with mania relatively little, with similar levels across severity levels," they wrote.

Dr. Cheniaux said in an interview that he had expected a higher factorial loading with anger. "It is possible that the angriest patients refused to participate in the study, so the symptom of anger could be underrepresented in our study," he said.

Ultimately, the investigators found that patients’ increased energy was the alteration that correlated "the most with the total severity of manic symptoms."

They cited several limitations of the study. For example, patients in the sample might not be representative of bipolar patients in the general population because they were evaluated while their manic symptoms were at their peak. In addition, the investigators suggested only six manic symptoms: increased activity, less need for sleep, increased energy, elated mood, increased self-esteem, and anger. Still, the results suggest that changes in the DSM-5 in the diagnostic criteria for a bipolar diagnosis could be more extensive, they wrote.

Dr. Cheniaux reported that he had no conflicts of interest.

[email protected]

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler