Bipolar Disorder

Borderline personality disorder and bipolar II disorder share some common features, but the illnesses can be distinguished by patients’ differences in emotion regulation strategies and perceptions of how their parents raised them, according to a report published online in the Journal of Affective Disorders.

Forty-eight psychiatric outpatients, half with borderline personality disorder and half with bipolar II, were recruited by Kathryn Fletcher of the University of New South Wales, Sydney, and the Black Dog Institute, Randwick, and her colleagues. The mean age of the outpatients was 33 years. Those with borderline reported a younger age of depression onset, and a higher proportion of patients in that group had more lifetime suicide and attempts at self-harm.

The participants completed the Cognitive Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, both 36-item tests aimed at assessing strategies to regulate emotion. They also completed the Measure of Parental Style, a test that seeks to assess perceived parent abuse, indifference, and overcontrol.

Overall, the investigators found that the outpatients with borderline personality disorder scored "significantly higher than those with [bipolar II] on a number of maladaptive emotion regulation strategies, including difficulty controlling impulsive behaviors, having limited access to emotion regulation strategies, and a tendency to self-blame, catastrophize, and blame others," Ms. Fletcher and her colleagues wrote (J. Affect. Disord. 2014;157:52-9).

They found that the outpatients with borderline personality disorder were "significantly less likely than those with [bipolar II] to use adaptive cognitive emotion regulation strategies, including planning, positive reappraisal, and putting things into perspective."

Those with borderline also scored significantly higher on most perceived parental style subscales, "indicating a maternal relationship characterized by indifference, abuse, and overcontrol and a paternal relationship characterized by abuse and overcontrol."

Identifying "maladaptive strategies to regulate emotion highlights specific targets for psychological intervention," the authors said. "However, given that those with [borderline personality disorder] and [bipolar II] displayed differing patterns of emotion dysregulation, there may be a need to tailor intervention strategies," such as positive reappraisal and promotion of acceptance in borderline.

Psychological therapies focusing on lessening the impact of "toxic childhood experiences" might help patients with both disorders, they said.

Ms. Fletcher and her colleagues cited several limitations. Among them were a relatively small sample size and the absence of statistical control for numerous sociodemographic and clinical characteristics that differed between the groups.

This study was supported by the National Health and Medical Research Council, Australia’s main funding body for medical research. The authors reported no relevant financial conflicts of interest.

Borderline personality disorder and bipolar II disorder share some common features, but the illnesses can be distinguished by patients’ differences in emotion regulation strategies and perceptions of how their parents raised them, according to a report published online in the Journal of Affective Disorders.

Forty-eight psychiatric outpatients, half with borderline personality disorder and half with bipolar II, were recruited by Kathryn Fletcher of the University of New South Wales, Sydney, and the Black Dog Institute, Randwick, and her colleagues. The mean age of the outpatients was 33 years. Those with borderline reported a younger age of depression onset, and a higher proportion of patients in that group had more lifetime suicide and attempts at self-harm.

The participants completed the Cognitive Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, both 36-item tests aimed at assessing strategies to regulate emotion. They also completed the Measure of Parental Style, a test that seeks to assess perceived parent abuse, indifference, and overcontrol.

Overall, the investigators found that the outpatients with borderline personality disorder scored "significantly higher than those with [bipolar II] on a number of maladaptive emotion regulation strategies, including difficulty controlling impulsive behaviors, having limited access to emotion regulation strategies, and a tendency to self-blame, catastrophize, and blame others," Ms. Fletcher and her colleagues wrote (J. Affect. Disord. 2014;157:52-9).

They found that the outpatients with borderline personality disorder were "significantly less likely than those with [bipolar II] to use adaptive cognitive emotion regulation strategies, including planning, positive reappraisal, and putting things into perspective."

Those with borderline also scored significantly higher on most perceived parental style subscales, "indicating a maternal relationship characterized by indifference, abuse, and overcontrol and a paternal relationship characterized by abuse and overcontrol."

Identifying "maladaptive strategies to regulate emotion highlights specific targets for psychological intervention," the authors said. "However, given that those with [borderline personality disorder] and [bipolar II] displayed differing patterns of emotion dysregulation, there may be a need to tailor intervention strategies," such as positive reappraisal and promotion of acceptance in borderline.

Psychological therapies focusing on lessening the impact of "toxic childhood experiences" might help patients with both disorders, they said.

Ms. Fletcher and her colleagues cited several limitations. Among them were a relatively small sample size and the absence of statistical control for numerous sociodemographic and clinical characteristics that differed between the groups.

This study was supported by the National Health and Medical Research Council, Australia’s main funding body for medical research. The authors reported no relevant financial conflicts of interest.

Borderline personality disorder and bipolar II disorder share some common features, but the illnesses can be distinguished by patients’ differences in emotion regulation strategies and perceptions of how their parents raised them, according to a report published online in the Journal of Affective Disorders.

Forty-eight psychiatric outpatients, half with borderline personality disorder and half with bipolar II, were recruited by Kathryn Fletcher of the University of New South Wales, Sydney, and the Black Dog Institute, Randwick, and her colleagues. The mean age of the outpatients was 33 years. Those with borderline reported a younger age of depression onset, and a higher proportion of patients in that group had more lifetime suicide and attempts at self-harm.

The participants completed the Cognitive Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, both 36-item tests aimed at assessing strategies to regulate emotion. They also completed the Measure of Parental Style, a test that seeks to assess perceived parent abuse, indifference, and overcontrol.

Overall, the investigators found that the outpatients with borderline personality disorder scored "significantly higher than those with [bipolar II] on a number of maladaptive emotion regulation strategies, including difficulty controlling impulsive behaviors, having limited access to emotion regulation strategies, and a tendency to self-blame, catastrophize, and blame others," Ms. Fletcher and her colleagues wrote (J. Affect. Disord. 2014;157:52-9).

They found that the outpatients with borderline personality disorder were "significantly less likely than those with [bipolar II] to use adaptive cognitive emotion regulation strategies, including planning, positive reappraisal, and putting things into perspective."

Those with borderline also scored significantly higher on most perceived parental style subscales, "indicating a maternal relationship characterized by indifference, abuse, and overcontrol and a paternal relationship characterized by abuse and overcontrol."

Identifying "maladaptive strategies to regulate emotion highlights specific targets for psychological intervention," the authors said. "However, given that those with [borderline personality disorder] and [bipolar II] displayed differing patterns of emotion dysregulation, there may be a need to tailor intervention strategies," such as positive reappraisal and promotion of acceptance in borderline.

Psychological therapies focusing on lessening the impact of "toxic childhood experiences" might help patients with both disorders, they said.

Ms. Fletcher and her colleagues cited several limitations. Among them were a relatively small sample size and the absence of statistical control for numerous sociodemographic and clinical characteristics that differed between the groups.

This study was supported by the National Health and Medical Research Council, Australia’s main funding body for medical research. The authors reported no relevant financial conflicts of interest.

Total sleep deprivation and light therapy relieve depression in bipolar patients but do not improve overall cognitive function, according to an Italian study published in the Journal of Affective Disorders.

In addition, bipolar patients "do not experience the well-known worsening of performance observed in healthy controls after sleep loss," said Sara Poletti, Ph.D., of the Scientific Institute and University Vita-Salute San Raffaele Turro, Milan, and her associates (J. Affect. Disord. 2014;156:144-9 [doi:10.1016/j.jad.2013.11.023]).

The investigators administered the Brief Assessment of Cognition in Schizophrenia (BACS) to 100 depressed bipolar I patients (DSM-IV) and 100 healthy controls, and then retested 42 subjects with bipolar disorder who underwent total sleep deprivation (TSD) and light therapy (LT), during which they were kept awake for three 36-hour periods over the course of a week, with bright lights shone on them for 30 minutes at 3 a.m. on TSD nights and in the morning after recovery sleep. The Hamilton Depression Rating Scale (HDRS) was administered to assess depression.

The mean age was 47 years in the bipolar group and 44 years in the control group. Both groups were made up of a majority of women. A quarter of the patients with bipolar disorder reported previous psychotic symptoms. Most of the TSD/LT patients were taking lithium, and some were taking other mood stabilizers, benzodiazepines, and antidepressants.

As expected from previous investigations, the 100 bipolar patients had significantly lower baseline cognitive function scores, showing impairment in verbal memory, working memory (digit sequencing), psychomotor coordination (token motor task), verbal fluency, selective attention (symbol coding), and executive function (Wisconsin Card Sorting Test).

Also in keeping with past studies, TSD/LT treatment caused an overall significant decrease in HDRS scores: 31 of the patients with bipolar (74%) achieved the strict remission criterion of HDRS score of less than 8 at day 7 and could be rated as full responders to treatment.

Regarding cognitive function, TSD and light therapy "showed a significant difference only for symbol coding (P less than 0.004). No significant differences were found for the remaining variables," Dr. Poletti and her associates said.

"Although most of the patients responded to TSD treatment reporting a clinical improvement of depressive symptomatology, cognitive deficits persisted in almost each function. The only improvement we observed was in symbol coding, confirming a positive effect of TSD on speed-of-information processing in bipolar patients," they wrote.

Also "in agreement with the literature, we found that as medication load decreases, cognitive performance improves. However, medication effects alone are not likely to fully account for the deficits described in these patients. We can hypothesize that TSD and LT act on cognitive functions through their effect on brain structures and neurotransmitter system[s]. Studies are needed to understand if remediation strategies such as those used for schizophrenia treatment could be introduced for bipolar patients," the investigators said.

Among the study limitations is that "the use and reporting of medications varied between patients, and it was very difficult to control for the potentially negative effect of medication on neurocognitive function, especially as the control group was not taking any medication," Dr. Poletti and her associates noted.

The study received no outside funding. The investigators said that they had no financial conflicts.

[email protected]

Total sleep deprivation and light therapy relieve depression in bipolar patients but do not improve overall cognitive function, according to an Italian study published in the Journal of Affective Disorders.

In addition, bipolar patients "do not experience the well-known worsening of performance observed in healthy controls after sleep loss," said Sara Poletti, Ph.D., of the Scientific Institute and University Vita-Salute San Raffaele Turro, Milan, and her associates (J. Affect. Disord. 2014;156:144-9 [doi:10.1016/j.jad.2013.11.023]).

The investigators administered the Brief Assessment of Cognition in Schizophrenia (BACS) to 100 depressed bipolar I patients (DSM-IV) and 100 healthy controls, and then retested 42 subjects with bipolar disorder who underwent total sleep deprivation (TSD) and light therapy (LT), during which they were kept awake for three 36-hour periods over the course of a week, with bright lights shone on them for 30 minutes at 3 a.m. on TSD nights and in the morning after recovery sleep. The Hamilton Depression Rating Scale (HDRS) was administered to assess depression.

The mean age was 47 years in the bipolar group and 44 years in the control group. Both groups were made up of a majority of women. A quarter of the patients with bipolar disorder reported previous psychotic symptoms. Most of the TSD/LT patients were taking lithium, and some were taking other mood stabilizers, benzodiazepines, and antidepressants.

As expected from previous investigations, the 100 bipolar patients had significantly lower baseline cognitive function scores, showing impairment in verbal memory, working memory (digit sequencing), psychomotor coordination (token motor task), verbal fluency, selective attention (symbol coding), and executive function (Wisconsin Card Sorting Test).

Also in keeping with past studies, TSD/LT treatment caused an overall significant decrease in HDRS scores: 31 of the patients with bipolar (74%) achieved the strict remission criterion of HDRS score of less than 8 at day 7 and could be rated as full responders to treatment.

Regarding cognitive function, TSD and light therapy "showed a significant difference only for symbol coding (P less than 0.004). No significant differences were found for the remaining variables," Dr. Poletti and her associates said.

"Although most of the patients responded to TSD treatment reporting a clinical improvement of depressive symptomatology, cognitive deficits persisted in almost each function. The only improvement we observed was in symbol coding, confirming a positive effect of TSD on speed-of-information processing in bipolar patients," they wrote.

Also "in agreement with the literature, we found that as medication load decreases, cognitive performance improves. However, medication effects alone are not likely to fully account for the deficits described in these patients. We can hypothesize that TSD and LT act on cognitive functions through their effect on brain structures and neurotransmitter system[s]. Studies are needed to understand if remediation strategies such as those used for schizophrenia treatment could be introduced for bipolar patients," the investigators said.

Among the study limitations is that "the use and reporting of medications varied between patients, and it was very difficult to control for the potentially negative effect of medication on neurocognitive function, especially as the control group was not taking any medication," Dr. Poletti and her associates noted.

The study received no outside funding. The investigators said that they had no financial conflicts.

[email protected]

Total sleep deprivation and light therapy relieve depression in bipolar patients but do not improve overall cognitive function, according to an Italian study published in the Journal of Affective Disorders.

In addition, bipolar patients "do not experience the well-known worsening of performance observed in healthy controls after sleep loss," said Sara Poletti, Ph.D., of the Scientific Institute and University Vita-Salute San Raffaele Turro, Milan, and her associates (J. Affect. Disord. 2014;156:144-9 [doi:10.1016/j.jad.2013.11.023]).

The investigators administered the Brief Assessment of Cognition in Schizophrenia (BACS) to 100 depressed bipolar I patients (DSM-IV) and 100 healthy controls, and then retested 42 subjects with bipolar disorder who underwent total sleep deprivation (TSD) and light therapy (LT), during which they were kept awake for three 36-hour periods over the course of a week, with bright lights shone on them for 30 minutes at 3 a.m. on TSD nights and in the morning after recovery sleep. The Hamilton Depression Rating Scale (HDRS) was administered to assess depression.

The mean age was 47 years in the bipolar group and 44 years in the control group. Both groups were made up of a majority of women. A quarter of the patients with bipolar disorder reported previous psychotic symptoms. Most of the TSD/LT patients were taking lithium, and some were taking other mood stabilizers, benzodiazepines, and antidepressants.

As expected from previous investigations, the 100 bipolar patients had significantly lower baseline cognitive function scores, showing impairment in verbal memory, working memory (digit sequencing), psychomotor coordination (token motor task), verbal fluency, selective attention (symbol coding), and executive function (Wisconsin Card Sorting Test).

Also in keeping with past studies, TSD/LT treatment caused an overall significant decrease in HDRS scores: 31 of the patients with bipolar (74%) achieved the strict remission criterion of HDRS score of less than 8 at day 7 and could be rated as full responders to treatment.

Regarding cognitive function, TSD and light therapy "showed a significant difference only for symbol coding (P less than 0.004). No significant differences were found for the remaining variables," Dr. Poletti and her associates said.

"Although most of the patients responded to TSD treatment reporting a clinical improvement of depressive symptomatology, cognitive deficits persisted in almost each function. The only improvement we observed was in symbol coding, confirming a positive effect of TSD on speed-of-information processing in bipolar patients," they wrote.

Also "in agreement with the literature, we found that as medication load decreases, cognitive performance improves. However, medication effects alone are not likely to fully account for the deficits described in these patients. We can hypothesize that TSD and LT act on cognitive functions through their effect on brain structures and neurotransmitter system[s]. Studies are needed to understand if remediation strategies such as those used for schizophrenia treatment could be introduced for bipolar patients," the investigators said.

Among the study limitations is that "the use and reporting of medications varied between patients, and it was very difficult to control for the potentially negative effect of medication on neurocognitive function, especially as the control group was not taking any medication," Dr. Poletti and her associates noted.

The study received no outside funding. The investigators said that they had no financial conflicts.

[email protected]

The DSM criteria requiring a duration of 4 or more days for the diagnosis of a hypomanic episode are unnecessary for the clinical definition of bipolar II disorder. These criteria probably also exclude patients who truly have the condition, according to an Australian study published in the Journal of Affective Disorders.

The investigators compared responses on the Mood Swings Questionnaire (MSQ) and the Mood Disorders Questionnaire (MDQ) from 315 adult patients diagnosed with bipolar II (BP II) disorder whose hypomanic episodes lasted less than 4 days, and 186 whose episodes met the DSM criteria of lasting 4 or more days. The mean age of both groups was about 35 years, and about 60% of each were women (J. Affect. Disord. 2014;156:87-91).

The mean total MSQ score was 49.6 in the brief-episode group and 57.0 in the standard-duration group, with the brief group also reporting slightly lower scores on most MSQ subscales. Results were similar on the MDQ among those who completed it, with the brief-duration group returning significantly lower scores on 6 of the 13 items, and a somewhat lower total score (9.5 vs. 10.3; P less than .05).

Overall, patients whose hypomania lasts less than 4 days scored 14% lower on the MSQ and 8% lower on the MDQ, "which, while formally significant, are relatively slight differences ... . A plausible explanation is that those with BP II disorder experiencing longer episodes tend to also have somewhat more severe hypomanic episodes," said Dr. Gordon Parker, of the University of New South Wales in Sydney, Australia, and his associates.

"Our study findings are strongly consistent with previous studies arguing that the clinical phenotype of BP II disorder ... is not dependent on a minimum duration of 4 days as imposed by DSM-IV and DSM-5, but further advanced by validation against a number of clinical correlates and not simply by examining phenomenological expression," Dr. Parker and his associates wrote.

"The current DSM-5 imposition therefore continues to risk those with a true bipolar disorder being excluded from receiving such a diagnosis. If our sample is indicative, the duration criterion may exclude the majority – in that 63% of our sample comprised the ‘brief’ group."

The two groups did not differ significantly in age of onset of depression and hypomania, age at formal diagnosis, and other key variables. Rates of bipolar disorder in first-degree relatives were comparable across the two groups, at a bit under 40% in each. "We interpret [that] finding ... as being a distinctive one, and supporting the validity of brief BP II states," the investigators said.

However, "the possibility of false positive BP II diagnoses, especially with brief hypomanic episodes, must be conceded while our examination of clinical symptoms was limited to two measures," they wrote, citing one of several limitations.

The authors said they had no relevant financial disclosures. The study was funded by the National Health and Medical Research Council of Australia and the New South Wales Department of Health.

[email protected]

The DSM criteria requiring a duration of 4 or more days for the diagnosis of a hypomanic episode are unnecessary for the clinical definition of bipolar II disorder. These criteria probably also exclude patients who truly have the condition, according to an Australian study published in the Journal of Affective Disorders.

The investigators compared responses on the Mood Swings Questionnaire (MSQ) and the Mood Disorders Questionnaire (MDQ) from 315 adult patients diagnosed with bipolar II (BP II) disorder whose hypomanic episodes lasted less than 4 days, and 186 whose episodes met the DSM criteria of lasting 4 or more days. The mean age of both groups was about 35 years, and about 60% of each were women (J. Affect. Disord. 2014;156:87-91).

The mean total MSQ score was 49.6 in the brief-episode group and 57.0 in the standard-duration group, with the brief group also reporting slightly lower scores on most MSQ subscales. Results were similar on the MDQ among those who completed it, with the brief-duration group returning significantly lower scores on 6 of the 13 items, and a somewhat lower total score (9.5 vs. 10.3; P less than .05).

Overall, patients whose hypomania lasts less than 4 days scored 14% lower on the MSQ and 8% lower on the MDQ, "which, while formally significant, are relatively slight differences ... . A plausible explanation is that those with BP II disorder experiencing longer episodes tend to also have somewhat more severe hypomanic episodes," said Dr. Gordon Parker, of the University of New South Wales in Sydney, Australia, and his associates.

"Our study findings are strongly consistent with previous studies arguing that the clinical phenotype of BP II disorder ... is not dependent on a minimum duration of 4 days as imposed by DSM-IV and DSM-5, but further advanced by validation against a number of clinical correlates and not simply by examining phenomenological expression," Dr. Parker and his associates wrote.

"The current DSM-5 imposition therefore continues to risk those with a true bipolar disorder being excluded from receiving such a diagnosis. If our sample is indicative, the duration criterion may exclude the majority – in that 63% of our sample comprised the ‘brief’ group."

The two groups did not differ significantly in age of onset of depression and hypomania, age at formal diagnosis, and other key variables. Rates of bipolar disorder in first-degree relatives were comparable across the two groups, at a bit under 40% in each. "We interpret [that] finding ... as being a distinctive one, and supporting the validity of brief BP II states," the investigators said.

However, "the possibility of false positive BP II diagnoses, especially with brief hypomanic episodes, must be conceded while our examination of clinical symptoms was limited to two measures," they wrote, citing one of several limitations.

The authors said they had no relevant financial disclosures. The study was funded by the National Health and Medical Research Council of Australia and the New South Wales Department of Health.

[email protected]

The DSM criteria requiring a duration of 4 or more days for the diagnosis of a hypomanic episode are unnecessary for the clinical definition of bipolar II disorder. These criteria probably also exclude patients who truly have the condition, according to an Australian study published in the Journal of Affective Disorders.

The investigators compared responses on the Mood Swings Questionnaire (MSQ) and the Mood Disorders Questionnaire (MDQ) from 315 adult patients diagnosed with bipolar II (BP II) disorder whose hypomanic episodes lasted less than 4 days, and 186 whose episodes met the DSM criteria of lasting 4 or more days. The mean age of both groups was about 35 years, and about 60% of each were women (J. Affect. Disord. 2014;156:87-91).

The mean total MSQ score was 49.6 in the brief-episode group and 57.0 in the standard-duration group, with the brief group also reporting slightly lower scores on most MSQ subscales. Results were similar on the MDQ among those who completed it, with the brief-duration group returning significantly lower scores on 6 of the 13 items, and a somewhat lower total score (9.5 vs. 10.3; P less than .05).

Overall, patients whose hypomania lasts less than 4 days scored 14% lower on the MSQ and 8% lower on the MDQ, "which, while formally significant, are relatively slight differences ... . A plausible explanation is that those with BP II disorder experiencing longer episodes tend to also have somewhat more severe hypomanic episodes," said Dr. Gordon Parker, of the University of New South Wales in Sydney, Australia, and his associates.

"Our study findings are strongly consistent with previous studies arguing that the clinical phenotype of BP II disorder ... is not dependent on a minimum duration of 4 days as imposed by DSM-IV and DSM-5, but further advanced by validation against a number of clinical correlates and not simply by examining phenomenological expression," Dr. Parker and his associates wrote.

"The current DSM-5 imposition therefore continues to risk those with a true bipolar disorder being excluded from receiving such a diagnosis. If our sample is indicative, the duration criterion may exclude the majority – in that 63% of our sample comprised the ‘brief’ group."

The two groups did not differ significantly in age of onset of depression and hypomania, age at formal diagnosis, and other key variables. Rates of bipolar disorder in first-degree relatives were comparable across the two groups, at a bit under 40% in each. "We interpret [that] finding ... as being a distinctive one, and supporting the validity of brief BP II states," the investigators said.

However, "the possibility of false positive BP II diagnoses, especially with brief hypomanic episodes, must be conceded while our examination of clinical symptoms was limited to two measures," they wrote, citing one of several limitations.

The authors said they had no relevant financial disclosures. The study was funded by the National Health and Medical Research Council of Australia and the New South Wales Department of Health.

[email protected]

NEW YORK – Treating children and teens with refractory bipolar disorder requires both persistence and faith, according to Dr. Gabrielle A. Carlson.

Although new data are trickling out, few of the medications available for treating both mania and depression have been extensively studied in children and teens, Dr. Carlson said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

"The first-generation antipsychotics have been grandfathered in with [Food and Drug Administration] approval. There are very little data for youngsters, and it’s unlikely that there ever will be, since they are generic now and no one will be spending the money" to further investigate them.

A few pediatric trials are in progress for some of the newer, second-generation antipsychotics, but most efficacy data are still from adult studies, said Dr. Carlson, professor of psychiatry and pediatrics at Stony Brook University, New York.

Michele G. Sullivan/Frontline Medical News

Most recently, paloperidone was found effective as an acute treatment for mania in children with bipolar disorder. But the open-label study was very small – just 15 patients – and was terminated early because of the slow enrollment. The study tested two doses (3 mg and 12 mg). There was a significant mean decline of almost 19 points on the Young Mania Rating Scale after 8 weeks of treatment. Children gained a mean of 4 pounds, however (Psychopharmacology [Berl.] 2013;227:449-58).

Sublingual treatment

Asenapine "is the new kid on the block," Dr. Carlson said. It was approved in 2009 for the acute treatment of schizophrenia and manic or mixed bipolar episodes in adults. It’s administered as a sublingual tablet that takes about 10 minutes to dissolve.

"This is good news if you’ve got a kid who has trouble swallowing pills. The bad news is that you have to hold it under your tongue for 10 minutes, and if you’ve got an aggressive, agitated kid – well, good luck with that. If he does it, though, you can get a good treatment response pretty quickly, because it has a peak concentration of 30-90 minutes and a half-life of about 24 hours."

The adult studies of asenapine showed a significant benefit in about 1 week, with many bipolar patients seeing a 50% reduction in symptoms. Two placebo-controlled trials in children are just wrapping up. The first, comprising 400 children, is complete, but no data have yet been published.

The second, a 50-week open-label study, is ongoing; about 300 children are enrolled.

In the adult studies of asenapine, the number needed to treat was about eight. "The NNT for many other drugs is four or five, so to me this looks like a contender, but not anything great. The sublingual route is the biggest benefit," although, Dr. Carlson cautioned, "it does make noncompliance a lot easier, just by swallowing it." The bioavailability when swallowed is only about 35%.

Asenapine is sedating, so it might be a good choice for as-needed treatment; the weight gain profile is similar to that of olanzapine. The twice-daily dosing is weight based, Dr. Carlson said. "Younger children are more sensitive to the initial dose, so they need a lower starting point and shorter up-titration, which isn’t necessary in the older kids."

For children with bipolar depression, there’s little evidence to support the use of quetiapine. There are no data in youngsters and few data to support its use in adults. A 2012 meta-analysis found that the drug is no better than placebo.

The combination of olanzapine and fluoxetine has been examined in children aged 10-17 years. The industry-sponsored placebo-controlled study treated 160 children for 8 weeks.

At the end of the study, remission rates were 59% in the active group and 43% in the placebo group – a significant difference. Children taking the combination gained significantly more weight than those taking placebo – an average of 4 vs. 0.5 kg. There were also significant increases in liver enzymes and prolactin in those taking the drugs, as well as a higher chance of prolonged QTc intervals.

Unpublished results of another study hint that lamotrigine also might be effective in children with bipolar depression, Dr. Carlson said.

The 8-week study looked at what happened to children aged 10-17 years who had lamotrigine withdrawn after they had responded to it. These patients were given the option of continuing the drug or switching to placebo.

"So far they have 250 enrolled," Dr. Carlson said. "Of these, 136 were willing to be randomized, meaning that at least 60% got better in the open-label phase."

There are no published pediatric data on lurasidone or ketamine, although both seem promising. Lurasidone has been approved for adults, and a study being done in youngsters is not specific for bipolar disorder. Children with schizophrenia, psychosis, autism disorders, Asperger’s syndrome, and refractory major depressive disorder also can enroll.

A recently published adult study, PREVAIL 2 (Program to Evaluate the Antidepressant Impact of Lurasidone), comprised 505 patients with bipolar I depression. They were randomized to once-daily, flexibly dosed lurasidone at either 20-60 mg/day or 80-120 mg/day, or to placebo.

After 6 weeks, depression scores fell in both the 20- to 60-mg/day group (–15.4; effect size = 0.51) and the 80- to 120-mg/day group (–15.4; effect size =0.51), compared with placebo (–10.7).

Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in Clinical Global Impressions-Bipolar Scale depression severity scores for both the 20- to 60-mg/day group (–1.8; effect size = 0.61) and the 80- to 120-mg/day group (–1.7; effect size = 0.50), compared with placebo (–1.1). Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms, and in patient-reported measures of quality of life and functional impairment. Response rates were 53% for the active group and 30% for the placebo group, with remission rates of 42% vs. 40%.

"The effect size was similar for the high and low doses, about 0.5, which is not terrible," Dr. Carlson said. "Discontinuation rates were fairly low, suggesting that it may be worth pursuing."

The main side effects were nausea, headache, akathisia, and somnolence, but very few changes were found in weight, lipids, or measures of glycemic control.

"Ketamine is something we’ve been hearing a lot about," Dr. Carlson said. "If we can come up with a way to give it that’s not intravenous and make it last for a while, it could be really valuable."

One study found that adults randomized to ketamine had significantly greater improvements in depression scores after 24 hours than did those who had midazolam.

The study comprised 73 patients. Response rates at 24 hours were 64% vs. 28% for placebo – with patients taking ketamine more than twice as likely to respond in the adjusted analysis.

The response was highest in the first 3 days after infusion; by day 7, it had dropped to about 45%. A review also highlighted ketamine's 'Achilles heel' – it just hasn’t got staying power. The paper looked at effect sizes in two depression studies and found that they peaked around 2 or 3 days after infusion. But 2 weeks later, the effect size was just about the same as with placebo.

"It’s a really interesting drug, and it does appear to hold some promise," Dr. Carlson said.

Dr. Carlson noted that she has received research funding from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co., Otsuka America Pharmaceutical, Pfizer, and Schering-Plough.

[email protected]

NEW YORK – Treating children and teens with refractory bipolar disorder requires both persistence and faith, according to Dr. Gabrielle A. Carlson.

Although new data are trickling out, few of the medications available for treating both mania and depression have been extensively studied in children and teens, Dr. Carlson said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

"The first-generation antipsychotics have been grandfathered in with [Food and Drug Administration] approval. There are very little data for youngsters, and it’s unlikely that there ever will be, since they are generic now and no one will be spending the money" to further investigate them.

A few pediatric trials are in progress for some of the newer, second-generation antipsychotics, but most efficacy data are still from adult studies, said Dr. Carlson, professor of psychiatry and pediatrics at Stony Brook University, New York.

Michele G. Sullivan/Frontline Medical News

Most recently, paloperidone was found effective as an acute treatment for mania in children with bipolar disorder. But the open-label study was very small – just 15 patients – and was terminated early because of the slow enrollment. The study tested two doses (3 mg and 12 mg). There was a significant mean decline of almost 19 points on the Young Mania Rating Scale after 8 weeks of treatment. Children gained a mean of 4 pounds, however (Psychopharmacology [Berl.] 2013;227:449-58).

Sublingual treatment

Asenapine "is the new kid on the block," Dr. Carlson said. It was approved in 2009 for the acute treatment of schizophrenia and manic or mixed bipolar episodes in adults. It’s administered as a sublingual tablet that takes about 10 minutes to dissolve.

"This is good news if you’ve got a kid who has trouble swallowing pills. The bad news is that you have to hold it under your tongue for 10 minutes, and if you’ve got an aggressive, agitated kid – well, good luck with that. If he does it, though, you can get a good treatment response pretty quickly, because it has a peak concentration of 30-90 minutes and a half-life of about 24 hours."

The adult studies of asenapine showed a significant benefit in about 1 week, with many bipolar patients seeing a 50% reduction in symptoms. Two placebo-controlled trials in children are just wrapping up. The first, comprising 400 children, is complete, but no data have yet been published.

The second, a 50-week open-label study, is ongoing; about 300 children are enrolled.

In the adult studies of asenapine, the number needed to treat was about eight. "The NNT for many other drugs is four or five, so to me this looks like a contender, but not anything great. The sublingual route is the biggest benefit," although, Dr. Carlson cautioned, "it does make noncompliance a lot easier, just by swallowing it." The bioavailability when swallowed is only about 35%.

Asenapine is sedating, so it might be a good choice for as-needed treatment; the weight gain profile is similar to that of olanzapine. The twice-daily dosing is weight based, Dr. Carlson said. "Younger children are more sensitive to the initial dose, so they need a lower starting point and shorter up-titration, which isn’t necessary in the older kids."

For children with bipolar depression, there’s little evidence to support the use of quetiapine. There are no data in youngsters and few data to support its use in adults. A 2012 meta-analysis found that the drug is no better than placebo.

The combination of olanzapine and fluoxetine has been examined in children aged 10-17 years. The industry-sponsored placebo-controlled study treated 160 children for 8 weeks.

At the end of the study, remission rates were 59% in the active group and 43% in the placebo group – a significant difference. Children taking the combination gained significantly more weight than those taking placebo – an average of 4 vs. 0.5 kg. There were also significant increases in liver enzymes and prolactin in those taking the drugs, as well as a higher chance of prolonged QTc intervals.

Unpublished results of another study hint that lamotrigine also might be effective in children with bipolar depression, Dr. Carlson said.

The 8-week study looked at what happened to children aged 10-17 years who had lamotrigine withdrawn after they had responded to it. These patients were given the option of continuing the drug or switching to placebo.

"So far they have 250 enrolled," Dr. Carlson said. "Of these, 136 were willing to be randomized, meaning that at least 60% got better in the open-label phase."

There are no published pediatric data on lurasidone or ketamine, although both seem promising. Lurasidone has been approved for adults, and a study being done in youngsters is not specific for bipolar disorder. Children with schizophrenia, psychosis, autism disorders, Asperger’s syndrome, and refractory major depressive disorder also can enroll.

A recently published adult study, PREVAIL 2 (Program to Evaluate the Antidepressant Impact of Lurasidone), comprised 505 patients with bipolar I depression. They were randomized to once-daily, flexibly dosed lurasidone at either 20-60 mg/day or 80-120 mg/day, or to placebo.

After 6 weeks, depression scores fell in both the 20- to 60-mg/day group (–15.4; effect size = 0.51) and the 80- to 120-mg/day group (–15.4; effect size =0.51), compared with placebo (–10.7).

Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in Clinical Global Impressions-Bipolar Scale depression severity scores for both the 20- to 60-mg/day group (–1.8; effect size = 0.61) and the 80- to 120-mg/day group (–1.7; effect size = 0.50), compared with placebo (–1.1). Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms, and in patient-reported measures of quality of life and functional impairment. Response rates were 53% for the active group and 30% for the placebo group, with remission rates of 42% vs. 40%.

"The effect size was similar for the high and low doses, about 0.5, which is not terrible," Dr. Carlson said. "Discontinuation rates were fairly low, suggesting that it may be worth pursuing."

The main side effects were nausea, headache, akathisia, and somnolence, but very few changes were found in weight, lipids, or measures of glycemic control.

"Ketamine is something we’ve been hearing a lot about," Dr. Carlson said. "If we can come up with a way to give it that’s not intravenous and make it last for a while, it could be really valuable."

One study found that adults randomized to ketamine had significantly greater improvements in depression scores after 24 hours than did those who had midazolam.

The study comprised 73 patients. Response rates at 24 hours were 64% vs. 28% for placebo – with patients taking ketamine more than twice as likely to respond in the adjusted analysis.

The response was highest in the first 3 days after infusion; by day 7, it had dropped to about 45%. A review also highlighted ketamine's 'Achilles heel' – it just hasn’t got staying power. The paper looked at effect sizes in two depression studies and found that they peaked around 2 or 3 days after infusion. But 2 weeks later, the effect size was just about the same as with placebo.

"It’s a really interesting drug, and it does appear to hold some promise," Dr. Carlson said.

Dr. Carlson noted that she has received research funding from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co., Otsuka America Pharmaceutical, Pfizer, and Schering-Plough.

[email protected]

NEW YORK – Treating children and teens with refractory bipolar disorder requires both persistence and faith, according to Dr. Gabrielle A. Carlson.

Although new data are trickling out, few of the medications available for treating both mania and depression have been extensively studied in children and teens, Dr. Carlson said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

"The first-generation antipsychotics have been grandfathered in with [Food and Drug Administration] approval. There are very little data for youngsters, and it’s unlikely that there ever will be, since they are generic now and no one will be spending the money" to further investigate them.

A few pediatric trials are in progress for some of the newer, second-generation antipsychotics, but most efficacy data are still from adult studies, said Dr. Carlson, professor of psychiatry and pediatrics at Stony Brook University, New York.

Michele G. Sullivan/Frontline Medical News

Most recently, paloperidone was found effective as an acute treatment for mania in children with bipolar disorder. But the open-label study was very small – just 15 patients – and was terminated early because of the slow enrollment. The study tested two doses (3 mg and 12 mg). There was a significant mean decline of almost 19 points on the Young Mania Rating Scale after 8 weeks of treatment. Children gained a mean of 4 pounds, however (Psychopharmacology [Berl.] 2013;227:449-58).

Sublingual treatment

Asenapine "is the new kid on the block," Dr. Carlson said. It was approved in 2009 for the acute treatment of schizophrenia and manic or mixed bipolar episodes in adults. It’s administered as a sublingual tablet that takes about 10 minutes to dissolve.

"This is good news if you’ve got a kid who has trouble swallowing pills. The bad news is that you have to hold it under your tongue for 10 minutes, and if you’ve got an aggressive, agitated kid – well, good luck with that. If he does it, though, you can get a good treatment response pretty quickly, because it has a peak concentration of 30-90 minutes and a half-life of about 24 hours."

The adult studies of asenapine showed a significant benefit in about 1 week, with many bipolar patients seeing a 50% reduction in symptoms. Two placebo-controlled trials in children are just wrapping up. The first, comprising 400 children, is complete, but no data have yet been published.

The second, a 50-week open-label study, is ongoing; about 300 children are enrolled.

In the adult studies of asenapine, the number needed to treat was about eight. "The NNT for many other drugs is four or five, so to me this looks like a contender, but not anything great. The sublingual route is the biggest benefit," although, Dr. Carlson cautioned, "it does make noncompliance a lot easier, just by swallowing it." The bioavailability when swallowed is only about 35%.

Asenapine is sedating, so it might be a good choice for as-needed treatment; the weight gain profile is similar to that of olanzapine. The twice-daily dosing is weight based, Dr. Carlson said. "Younger children are more sensitive to the initial dose, so they need a lower starting point and shorter up-titration, which isn’t necessary in the older kids."

For children with bipolar depression, there’s little evidence to support the use of quetiapine. There are no data in youngsters and few data to support its use in adults. A 2012 meta-analysis found that the drug is no better than placebo.

The combination of olanzapine and fluoxetine has been examined in children aged 10-17 years. The industry-sponsored placebo-controlled study treated 160 children for 8 weeks.

At the end of the study, remission rates were 59% in the active group and 43% in the placebo group – a significant difference. Children taking the combination gained significantly more weight than those taking placebo – an average of 4 vs. 0.5 kg. There were also significant increases in liver enzymes and prolactin in those taking the drugs, as well as a higher chance of prolonged QTc intervals.

Unpublished results of another study hint that lamotrigine also might be effective in children with bipolar depression, Dr. Carlson said.

The 8-week study looked at what happened to children aged 10-17 years who had lamotrigine withdrawn after they had responded to it. These patients were given the option of continuing the drug or switching to placebo.

"So far they have 250 enrolled," Dr. Carlson said. "Of these, 136 were willing to be randomized, meaning that at least 60% got better in the open-label phase."

There are no published pediatric data on lurasidone or ketamine, although both seem promising. Lurasidone has been approved for adults, and a study being done in youngsters is not specific for bipolar disorder. Children with schizophrenia, psychosis, autism disorders, Asperger’s syndrome, and refractory major depressive disorder also can enroll.

A recently published adult study, PREVAIL 2 (Program to Evaluate the Antidepressant Impact of Lurasidone), comprised 505 patients with bipolar I depression. They were randomized to once-daily, flexibly dosed lurasidone at either 20-60 mg/day or 80-120 mg/day, or to placebo.

After 6 weeks, depression scores fell in both the 20- to 60-mg/day group (–15.4; effect size = 0.51) and the 80- to 120-mg/day group (–15.4; effect size =0.51), compared with placebo (–10.7).

Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in Clinical Global Impressions-Bipolar Scale depression severity scores for both the 20- to 60-mg/day group (–1.8; effect size = 0.61) and the 80- to 120-mg/day group (–1.7; effect size = 0.50), compared with placebo (–1.1). Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms, and in patient-reported measures of quality of life and functional impairment. Response rates were 53% for the active group and 30% for the placebo group, with remission rates of 42% vs. 40%.

"The effect size was similar for the high and low doses, about 0.5, which is not terrible," Dr. Carlson said. "Discontinuation rates were fairly low, suggesting that it may be worth pursuing."

The main side effects were nausea, headache, akathisia, and somnolence, but very few changes were found in weight, lipids, or measures of glycemic control.

"Ketamine is something we’ve been hearing a lot about," Dr. Carlson said. "If we can come up with a way to give it that’s not intravenous and make it last for a while, it could be really valuable."

One study found that adults randomized to ketamine had significantly greater improvements in depression scores after 24 hours than did those who had midazolam.

The study comprised 73 patients. Response rates at 24 hours were 64% vs. 28% for placebo – with patients taking ketamine more than twice as likely to respond in the adjusted analysis.

The response was highest in the first 3 days after infusion; by day 7, it had dropped to about 45%. A review also highlighted ketamine's 'Achilles heel' – it just hasn’t got staying power. The paper looked at effect sizes in two depression studies and found that they peaked around 2 or 3 days after infusion. But 2 weeks later, the effect size was just about the same as with placebo.

"It’s a really interesting drug, and it does appear to hold some promise," Dr. Carlson said.

Dr. Carlson noted that she has received research funding from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co., Otsuka America Pharmaceutical, Pfizer, and Schering-Plough.

[email protected]

Parents with bipolar disorder generally know that their children have an increased risk for the condition, but whether they actively monitor their children for the disorder depends to some extent on how well they manage it themselves, according to a web survey of 266 parents.

Most of the survey respondents were white. Most were female (83.7%), and nearly two-thirds (63.7%) had more than one child. The median age range of the respondents was 41-45.

They rated themselves against statements signaling active monitoring for nascent bipolar disorder, such as "I watch my child’s moods," "I teach my child what to do if his/her moods become bad or unstable," and "I plan for what I would do if I notice symptoms in my child."

In addition, they responded to statements signaling what the researchers called "cognitive distancing" from the possibility that their children might develop bipolar disorder, including "my child’s personality makes him/her less likely to develop a mood disorder" and "the home environment my child has grown up in makes him/her less likely to develop a mood disorder." The parents answered questions about their own illness, as well (Soc. Sci. Med. 2014;104:194-200).

The degree to which parents with bipolar disorder paid attention to their children’s mood was associated with perceived control over the child’s well-being (P less than .005), coping with their own illness (P = .001), and a family history of bipolar disorder (P = .001), among other factors. Cognitive distancing was negatively associated with current mania (P = .007), perceiving bipolar disorder as genetic (P less than .001), and having more children (P = .004), perhaps because parents were more confident that they would spot a problem if they could compare one child to another. The findings were statistically significant.

The investigators said the main limitation of their study is that it used a sample with bipolar disorder that was self-reported. In addition, reports of relatives affected by bipolar were "unexpectedly high, indicating a biased study sample," an unclear survey question, and/or an overreporting of illness in relatives."

Still, the results mean that "health care providers need to move away from a model of parents with mental illness as vehicles of risk to offspring. They should capitalize on parents’ strengths, and help them identify and evaluate their coping strategies," said Holly Landrum Peay of the National Human Genome Research Institute in Bethesda, Md., and her associates.

The National Institutes of Health funded the study. The investigators reported that they have no financial conflicts.

[email protected]

Parents with bipolar disorder generally know that their children have an increased risk for the condition, but whether they actively monitor their children for the disorder depends to some extent on how well they manage it themselves, according to a web survey of 266 parents.

Most of the survey respondents were white. Most were female (83.7%), and nearly two-thirds (63.7%) had more than one child. The median age range of the respondents was 41-45.

They rated themselves against statements signaling active monitoring for nascent bipolar disorder, such as "I watch my child’s moods," "I teach my child what to do if his/her moods become bad or unstable," and "I plan for what I would do if I notice symptoms in my child."

In addition, they responded to statements signaling what the researchers called "cognitive distancing" from the possibility that their children might develop bipolar disorder, including "my child’s personality makes him/her less likely to develop a mood disorder" and "the home environment my child has grown up in makes him/her less likely to develop a mood disorder." The parents answered questions about their own illness, as well (Soc. Sci. Med. 2014;104:194-200).

The degree to which parents with bipolar disorder paid attention to their children’s mood was associated with perceived control over the child’s well-being (P less than .005), coping with their own illness (P = .001), and a family history of bipolar disorder (P = .001), among other factors. Cognitive distancing was negatively associated with current mania (P = .007), perceiving bipolar disorder as genetic (P less than .001), and having more children (P = .004), perhaps because parents were more confident that they would spot a problem if they could compare one child to another. The findings were statistically significant.

The investigators said the main limitation of their study is that it used a sample with bipolar disorder that was self-reported. In addition, reports of relatives affected by bipolar were "unexpectedly high, indicating a biased study sample," an unclear survey question, and/or an overreporting of illness in relatives."

Still, the results mean that "health care providers need to move away from a model of parents with mental illness as vehicles of risk to offspring. They should capitalize on parents’ strengths, and help them identify and evaluate their coping strategies," said Holly Landrum Peay of the National Human Genome Research Institute in Bethesda, Md., and her associates.

The National Institutes of Health funded the study. The investigators reported that they have no financial conflicts.

[email protected]

Parents with bipolar disorder generally know that their children have an increased risk for the condition, but whether they actively monitor their children for the disorder depends to some extent on how well they manage it themselves, according to a web survey of 266 parents.

Most of the survey respondents were white. Most were female (83.7%), and nearly two-thirds (63.7%) had more than one child. The median age range of the respondents was 41-45.

They rated themselves against statements signaling active monitoring for nascent bipolar disorder, such as "I watch my child’s moods," "I teach my child what to do if his/her moods become bad or unstable," and "I plan for what I would do if I notice symptoms in my child."

In addition, they responded to statements signaling what the researchers called "cognitive distancing" from the possibility that their children might develop bipolar disorder, including "my child’s personality makes him/her less likely to develop a mood disorder" and "the home environment my child has grown up in makes him/her less likely to develop a mood disorder." The parents answered questions about their own illness, as well (Soc. Sci. Med. 2014;104:194-200).

The degree to which parents with bipolar disorder paid attention to their children’s mood was associated with perceived control over the child’s well-being (P less than .005), coping with their own illness (P = .001), and a family history of bipolar disorder (P = .001), among other factors. Cognitive distancing was negatively associated with current mania (P = .007), perceiving bipolar disorder as genetic (P less than .001), and having more children (P = .004), perhaps because parents were more confident that they would spot a problem if they could compare one child to another. The findings were statistically significant.

The investigators said the main limitation of their study is that it used a sample with bipolar disorder that was self-reported. In addition, reports of relatives affected by bipolar were "unexpectedly high, indicating a biased study sample," an unclear survey question, and/or an overreporting of illness in relatives."

Still, the results mean that "health care providers need to move away from a model of parents with mental illness as vehicles of risk to offspring. They should capitalize on parents’ strengths, and help them identify and evaluate their coping strategies," said Holly Landrum Peay of the National Human Genome Research Institute in Bethesda, Md., and her associates.

The National Institutes of Health funded the study. The investigators reported that they have no financial conflicts.

[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]

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]