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Objective: The authors compared medication-induced mood switch risk (primary outcome), as well as treatment response and side effects (secondary outcomes) with three acute-phase treatments for bipolar II depression., Method: In a 16-week, double-blind, multisite comparison study, 142 participants with bipolar II depression were randomly assigned to receive lithium monotherapy (N=49), sertraline monotherapy (N=45), or combination treatment with lithium and sertraline (N=48). At each visit, mood was assessed using standardized rating scales. Rates of switch were compared, as were rates of treatment response and the presence and severity of treatment-emergent side effects., Results: Twenty participants (14%) experienced a switch during the study period (hypomania, N=17; severe hypomania, N=3). Switch rates did not differ among the three treatment groups, even after accounting for dropout. No patient had a manic switch or was hospitalized for a switch. Most switches occurred within the first 5 weeks of treatment. The treatment response rate for the overall sample was 62.7% (N=89), without significant differences between groups after accounting for dropout. The lithium/sertraline combination group had a significantly higher overall dropout rate than the monotherapy groups but did not have an accelerated time to response., Conclusions: Lithium monotherapy, sertraline monotherapy, and lithium/sertraline combination therapy were associated with similar switch and treatment response rates in participants with bipolar II depression. The dropout rate was higher in the lithium/sertraline combination treatment group, without any treatment acceleration advantage.

Objective: DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression., Method: In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology-Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit., Results: Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity., Conclusions: Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.

Objective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders., Method: An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder., Results: There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder., Conclusions: Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Objective: The authors assessed gender differences in the proportion of clinical visits spent depressed, manic, or euthymic in patients with bipolar disorder., Method: Data were analyzed from 711 patients with bipolar I or II disorder who were followed prospectively over 7 years (13,191 visits). The main outcome measures were the presence of symptoms of depression or of hypomania or mania, measured by the Inventory of Depressive Symptomatology and the Young Mania Rating Scale. Data were analyzed using three separate repeated-measures regressions with a logistic link function to model the probability that an individual was depressed, manic, or euthymic. The models controlled for bipolar I or bipolar II diagnosis, rapid cycling, age, time in the study, comorbid anxiety disorders, and comorbid substance use disorders., Results: In approximately half of visits, patients had depressive, manic, or hypomanic symptoms. The likelihood of having depressive symptoms was significantly greater for women than for men. This was accounted for by higher rates in women of rapid cycling and anxiety disorders, each of which was associated with increased rates of depression. All patient groups showed an increase in number of euthymic visits and a decrease in number of visits with depressive and manic symptoms with increased time in study., Conclusions: Bipolar patients spend a substantial proportion of their time ill. Significant gender differences exist, with women spending a greater proportion of their visits in the depressive pole. This finding appears to be related to the corresponding differences in rates of rapid cycling and anxiety disorders.

Objective: Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression., Method: A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania., Results: Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder., Conclusions: These data suggest that minimal manic symptoms at baseline coexisting with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression.

Objective: Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression, which is often characterized by excessive sleepiness and fatigue., Method: Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were randomly assigned to receive adjunctive modafinil (N=41) or placebo (N=44) for 6 weeks. The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms--Clinician Rated (IDS)., Results: The baseline-to-endpoint change in IDS score was significantly greater in the modafinil group (mean dose, 177 mg/day) compared with the placebo group. Improvement in depressive symptoms was significantly greater in the modafinil group by week 2, and this greater improvement was maintained at weeks 4, 5, and 6. Both the response and remission rates were significantly higher in the modafinil group (44% and 39%) compared with the placebo group (23% and 18%). During the 6-week study period, there was no difference between groups in treatment-emergent hypomania or mania (six patients in the modafinil group and five in the placebo group) or hospitalization for mania (one in each group)., Conclusions: These data suggest that adjunctive modafinil at doses of 100-200 mg a day may improve depressive symptoms in patients with bipolar disorder.

Objective: This study assessed the stability of binge eating disorder in a community sample., Method: The authors interviewed 888 first-degree relatives of 300 overweight or obese probands (150 with binge eating disorder and 150 with no lifetime eating disorder) who were recruited during a family study. They compared the total duration of illness among relatives with lifetime diagnoses of binge eating disorder (N=131), bulimia nervosa (N=17), and anorexia nervosa (N=18)., Results: The mean lifetime duration of binge eating disorder was 14.4 years (SD=13.9), significantly longer than for either bulimia nervosa (mean=5.8 years, SD=9.1) or anorexia nervosa (mean=5.9 years, SD=7.4). These differences changed little when analysis was restricted to female relatives or to relatives of the probands with no lifetime eating disorder., Conclusions: These findings suggest that binge eating disorder is at least as chronic as the well-validated disorders anorexia nervosa and bulimia nervosa and likely represents a stable syndrome.

Objective: The authors examined the comparative risks of switches in mood polarity into hypomania or mania during acute and continuation trials of adjunctive antidepressant treatment of bipolar depression., Method: One hundred fifty-nine patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation treatment for up to 1 year. Antidepressant response and the occurrence of subthreshold brief hypomania (emergence of brief hypomania [at least 1 but <7 days] or recurrent brief hypomania) and threshold switches (emergence of full-duration hypomania [> or =7 days] or mania) were blindly assessed by using clinician-rated daily reports of mood-associated dysfunction on the National Institute of Mental Health Life Chart Method., Results: Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch., Conclusions: Adjunctive treatment with antidepressants in bipolar depression was associated with substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment. Of the three antidepressants included in the study, venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest risk.

Objectives: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder., Method: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients' switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score >13 or a Clinical Global Impression (CGI) mania score > or =3 (mildly ill)., Results: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch., Conclusions: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer.

Objective: To detect risk factors for rapid cycling in bipolar disorder, the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective., Method: Outpatients with bipolar I disorder (N=419), bipolar II disorder (N=104), and bipolar disorder not otherwise specified (N=16) were prospectively evaluated with daily mood ratings for 1 year. Subjects were classified as having rapid cycling (defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year) or not having rapid cycling, and the two groups' demographic and retrospective and prospective illness characteristics were compared. Associated factors were also evaluated in relationship to episode frequency., Results: Patients with rapid cycling (N=206; 38.2%) significantly differed from those without rapid cycling (N=333) with respect to the following independent variables: history of childhood physical and/or sexual abuse, bipolar I disorder subtype, number of lifetime manic or depressive episodes, history of rapid cycling, and history of drug abuse. The prevalence of these characteristics increased progressively with episode frequency. The proportion of women was greater than the proportion of men only among patients with eight or more episodes per year. The average time spent manic/hypomanic increased as a function of episode frequency, but the average time spent depressed was comparable in patients with one episode and in those with more than one episode. Brief episodes were as frequent as full-duration DSM-IV-defined episodes., Conclusions: A number of heterogeneous risk factors were progressively associated with increasing episode frequency. Depression predominated in all bipolar disorder patients, but patients with rapid cycling were more likely to be characterized by manic features. The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency.

Objective: The purpose of the study was to examine potential correlates of outcome in patients treated for bipolar disorder., Method: During a 1-year period, 258 patients with DSM-IV bipolar disorder or schizoaffective disorder were rated with the prospective NIMH-Life Chart Method, which characterizes each day in terms of the severity of manic and depressive symptoms on the basis of patients' mood-related impairment in their usual educational, social, or occupational roles. Mean ratings for the severity of mania, depression, and overall bipolar illness and the number of manic, depressive, and overall illness episodes were calculated. Potential risk factors were assessed at the start of the study, and multivariate linear regression analysis was used to determine the correlates of the six 1-year outcome measures., Results: Three of the six outcome measures were largely independent of each other and were used in the analysis. The mean rating for severity of mania was associated with comorbid substance abuse, history of more than 10 prior manic episodes, and poor occupational functioning at study entry. The mean rating for severity of depression was associated with a history of more than 10 prior depressive episodes and poor occupational functioning at study entry. The total number of overall illness episodes was associated with a positive family history of drug abuse, a history of prior rapid cycling, and poor occupational functioning. In addition, the mean rating for severity of mania and the total number of overall illness episodes were both initially associated with a history of childhood abuse, but these relationships were lost with the addition of other illness variables to the analysis., Conclusions: Clinicians who treat patients with bipolar disorder should consider a family history of drug abuse, a history of childhood abuse, prior course of illness, comorbid substance abuse, and occupational functioning in determining prognosis and setting goals for further treatment.

Objective: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study., Method: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires., Results: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder., Conclusions: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study.

Objective: Binge eating disorder is associated with obesity. Topiramate is an antiepileptic agent associated with weight loss. The objective of this study was to evaluate topiramate in the treatment of binge eating disorder associated with obesity., Method: For this 14-week, double-blind, flexible-dose (25-600 mg/day) topiramate trial, 61 outpatients (53 women, eight men) with binge eating disorder who were obese (body mass index >/=30 kg/m(2)) were randomly assigned to receive topiramate (N=30) or placebo (N=31). The primary efficacy measure was binge frequency. The primary analysis of efficacy was a repeated-measures random regression with treatment-by-time as the effect measure., Results: Compared with placebo, topiramate was associated with a significantly greater rate of reduction in binge frequency, binge day frequency, body mass index, weight, and scores on the Clinical Global Impression severity scale and the Yale-Brown Obsessive Compulsive Scale (modified for binge eating). Topiramate was also associated with significantly greater reductions in binge frequency (topiramate: 94%, placebo: 46%) and binge day frequency (topiramate: 93%, placebo: 46%) and with a significantly higher level of response than placebo. The mean weight loss for topiramate-treated subjects who completed the study was 5.9 kg. Median topiramate dose was 212 mg/day (range=50-600). Nine patients (three receiving placebo, six given topiramate) discontinued because of adverse events. The most common reasons for discontinuing topiramate were headache (N=3) and paresthesias (N=2)., Conclusions: Topiramate was efficacious and relatively well tolerated in the short-term treatment of binge eating disorder associated with obesity.

Objective: Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables., Method: They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics., Results: One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time., Conclusions: Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.

Objective: Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire., Method: A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV., Results: A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90)., Conclusions: The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population.

Objective: The authors' goal was to assess the efficacy of sertraline in the treatment of binge eating disorder., Method: Thirty-four outpatients with DSM-IV binge eating disorder were randomly assigned to receive either sertraline (N=18) or placebo (N=16) in a 6-week, double-blind, flexible-dose (50-200 mg) study. Except for response level, outcome measures were analyzed by random regression methods, with treatment-by-time interaction as the effect measure., Results: Compared with placebo, sertraline was associated with a significantly greater rate of reduction in the frequency of binges, clinical global severity, and body mass index as well as a significantly greater rate of increase in clinical global improvement. Patients receiving sertraline who completed the study demonstrated a higher level of response, although the effect was not significant., Conclusions: In a 6-week trial, sertraline was effective and well tolerated in the treatment of binge eating disorder.

Objective: New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy., Method: A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states., Results: Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization., Conclusions: These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

Objective: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania., Method: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score., Results: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group., Conclusions: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Objective: The purpose of this study was to assess the efficacy of fluvoxamine in the treatment of binge-eating disorder. Binge-eating disorder is a newly described eating disorder characterized by recurrent episodes of binge eating but without purging behaviors. Uncontrolled reports have suggested that serotonin selective reuptake inhibitors (SSRIs) may be effective in treating this disorder., Method: Eighty-five outpatients with a DSM-IV diagnosis of binge-eating disorder were randomly assigned to receive either fluvoxamine (N=42) or placebo (N=43) in a 9-week, parallel-group, double-blind, flexible dose (50-300 mg) study at three centers. The primary outcome measures were frequency of binge eating, expressed as log ([binges/week]+1), and Clinical Global Impression (CGI) scale ratings. Secondary measures included the level of response (based on the percentage change in frequency of binges), body mass index, and Hamilton Rating Scale for Depression score. Except for the level of response, the outcome measures were analyzed by random regression methods; the treatment-by-time interaction was the measure of treatment effect., Results: Compared with placebo, fluvoxamine was associated with a significantly greater rate of reduction in the frequency of binges, rate of reduction in CGI severity scores, rate of increase in CGI improvement scores, level of response for patients who completed the 9-week study, and rate of reduction in body mass index. There was no significant difference between placebo and fluvoxamine groups in the rate of decrease in Hamilton depression scale scores. A significantly greater proportion of patients receiving fluvoxamine than those receiving placebo discontinued treatment because of an adverse medical event., Conclusions: In this placebo-controlled trial, fluvoxamine was found to be effective according to most outcome measures in the acute treatment of binge-eating disorder.

Objective: The authors studied the 12-month course of illness following hospitalization for a manic or mixed episode of bipolar disorder to identify potential outcome predictors., Method: They recruited 134 patients with DSM-III-R bipolar disorder who were consecutively admitted for the treatment of a manic or mixed episode. Diagnostic, symptomatic, and functional evaluations were obtained at the index hospitalization. Patients were reevaluated at 2, 6, and 12 months after discharge to assess syndromic, symptomatic, and functional outcome. Factors associated with outcome were identified by using multivariate analyses., Results: During the 12-month follow-up period, there were no significant differences in outcome between patients with manic compared with mixed bipolar disorder. Although syndromic recovery occurred in 48% of the overall group, symptomatic recovery occurred in only 26% and functional recovery in only 24%. Predictors of syndromic recovery included shorter duration of illness and full treatment compliance. Medication treatment compliance was inversely associated with the presence of comorbid substance use disorders. Symptomatic and functional recovery occurred more rapidly and in a greater percentage of patients from higher social classes., Conclusions: A minority of patients with bipolar disorder achieved a favorable outcome in the year following hospitalization for a manic or mixed episode. Shorter duration of illness, higher social class, and treatment compliance were associated with higher rates of recovery and more rapid recovery.

Objective: The authors compared the clinical characteristics and family history of patients with early-onset (before age 18), typical-onset (at 20-25 years), and late-onset (after age 35) affective psychosis at the time of first hospitalization., Method: Diagnostic, symptom, and family history information was obtained from 88 consecutively hospitalized patients., Results: Major depression was more common in the late-onset group, and a family history of affective and substance abuse disorders was more common among the early-onset patients. Affective symptoms differed significantly among groups; specifically, early-onset patients had more energy, minimal sleep disruption, and greater suicidality, while typical-onset patients had more severe abnormal thought content., Conclusions: Among patients with affective psychosis, there may be heterogeneity of symptoms and family history associated with age at first hospitalization.

Objective: Although available data suggest that bipolar disorder most commonly begins in adolescence, it has often been underrecognized and misdiagnosed in this age group. The authors hypothesized that this might in part be because adolescent mania is phenomenologically different from adult mania. To test this hypothesis, they compared a cohort of adolescents hospitalized for acute mania with a group of hospitalized acutely manic adults., Method: The authors compared symptomatic differences between 40 adolescent (ages 12-18 years) and 88 adult (ages 19-45 years) bipolar patients hospitalized for acute mania. They also compared the two groups with respect to demographic characteristics, psychiatric comorbidity, family history, and short-term outcome., Results: Compared with adults, adolescent patients displayed a significantly higher rate of mixed bipolar disorder and a significantly lower rate of psychotic features (by DSM-III-R criteria), as well as higher ratings for many depressive symptoms (including suicidality and depressed mood) and lower ratings for thought disorder and delusions. Adolescents also displayed a significantly lower rate of substance abuse and significantly higher rates of familial mood disorder and drug abuse or dependence., Conclusions: Significant differences were found in the phenomenology of adolescent and adult mania in this study. The reasons for these differences are not known. Possible explanations include artifact due to methodological limitations and differences between adolescents and adults in familial loading for mood or substance use disorders or in developmental or maturational stage.

Objective: Patients with mixed or manic bipolar disorder were studied to determine whether suicidality in mania is associated with increasing depression in general (i.e., a dimensional construct based on symptom severity) or with the presence of a mixed state per se (i.e., a categorical construct requiring the presence of a full depressive syndrome)., Method: Diagnostic (categorical) assessments of 91 consecutively hospitalized patients with DSM-III-R mixed or manic bipolar disorder were made by using the Structural Clinical Interview for DSM-III-R. Symptom (dimensional) assessments were made by using the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Scale of the Assessment of Positive Symptoms. Logistic regression models were employed to test the relative associations between suicidality and dimensional and categorical depression measures. Receiver operating characteristics analysis was performed to identify a potential threshold depression rating that predicted suicidality., Results: Suicidality was more common in mixed than manic bipolar disorder. However, when adjusted for total depression scores, this association with affective state did not persist, but the statistical model significantly improved. In the improved model, depressive symptom ratings were significantly associated with suicidality. Hamilton depression scale ratings greater than 18 identified over 90% of the patients with suicidality, although there was also a high rate of false positives (32%)., Conclusions: It is the severity of concurrent depressive symptoms in mania, rather than the presence of a depressive syndrome per se (i.e., mixed state), that is associated with suicidality in bipolar patients.

Objective: The purpose of this study was to examine the rate of attention deficit hyperactivity disorder in adolescents with bipolar disorder and to explore the potential effects of comorbid attention deficit hyperactivity disorder on the phenomenology of adolescent bipolar disorder., Method: The authors assessed the rate of attention deficit hyperactivity disorder for adolescents with bipolar disorder who were hospitalized for treatment of acute mania or hypomania., Results: Eight (57%) of 14 adolescent bipolar patients also met DSM-III-R criteria for attention deficit hyperactivity disorder. Patients with both disorders were more likely to be male and Caucasian and to have mixed rather than manic bipolar disorder. Patients with attention deficit hyperactivity disorder had a higher mean total score on the Young Mania Rating Scale than patients with bipolar disorder alone., Conclusions: Although preliminary, these findings may have important implications regarding the potential relationship between bipolar disorder and attention deficit hyperactivity disorder.

Objective: Body dysmorphic disorder, preoccupation with an imagined defect in appearance, is included in DSM-III-R but has received little empirical study. The authors investigated the demographics, phenomenology, course, associated psychopathology, family history, and response to treatment in a series of 30 patients with the disorder., Method: The patients (including 12 whose preoccupation was of probable delusional intensity) were assessed with a semistructured interview and the Structural Clinical Interview for DSM-III-R, and their family histories were obtained., Results: The 17 men and 13 women reported a lifetime average of four bodily preoccupations, most commonly "defects" of the hair, nose, and skin. The average age at onset of body dysmorphic disorder was 15 years, and the average duration was 18 years. Seventy-three percent of the patients reported associated ideas or delusions of reference; 73%, excessive mirror checking; and 63%, attempts to camouflage their "deformities." As a result of their symptoms, 97% avoided usual social and occupational activities, 30% had been housebound, and 17% had made suicide attempts. Ninety-three percent of the patients had an associated lifetime diagnosis of a major mood disorder; 33%, a psychotic disorder; and 73%, an anxiety disorder. The patients generally responded poorly to surgical, dermatologic, and dental treatments and to adequate trials of most psychotropic medications, with the exception of fluoxetine and clomipramine (to which more than half had a complete or partial response)., Conclusions: This often secret, chronic disorder can cause considerable distress and impairment, may be related to obsessive-compulsive disorder or mood disorder, and may respond to serotonin reuptake-blocking antidepressants.

Objective: The authors reviewed available evidence regarding the status of dysphoric or mixed mania as a distinct clinical state and formulated operational criteria for its diagnosis., Method: Studies of dysphoric mania or hypomania in patients with bipolar disorder were analyzed with regard to clinical characteristics, prevalence, demographic features, course of illness, outcome, family history, associated conditions, biological tests, and response to biological treatment., Results: Although some studies suggest that dysphoric and nondysphoric mania are similar conditions, others suggest that, compared with nondysphoric mania, dysphoric mania may be more severe; more likely to occur in women; more likely to be associated with suicidality, a younger age at onset, a longer duration of illness, higher rates of personal and familial depression, concomitant alcohol or sedative-hypnotic abuse, neuropsychiatric abnormalities, and poorer outcome; more frequently associated with cortisol nonsuppression; and less likely to respond adequately to lithium but perhaps more likely to respond to ECT or anticonvulsants., Conclusions: Substantial evidence suggests that dysphoric mania may be a distinct affective state. Contrary evidence, however, suggests that dysphoric mania may be a form of typical mania, a stage-related or severe form of mania, or a transitional state between mania and depression. Because the evidence may be inconsistent because of varying definitions of dysphoric mania among studies, the authors propose preliminary operational diagnostic criteria for the future study of dysphoric mania.

Objective: The authors reviewed available studies of DSM-III-R impulse control disorders not elsewhere classified in order to determine the relationship of these disorders to one another and to other psychiatric disorders., Method: The review focused on the demographic and clinical characteristics, phenomenology, family history, biology, and response to treatment of individuals with intermittent explosive disorder, kleptomania, pathological gambling, pyromania, and trichotillomania. Analysis was restricted to reports which either indicated use of operational diagnostic criteria or provided descriptions of the impulsive behavior detailed enough that patients could be judged as probably meeting the DSM-III-R criteria., Results: Although different impulse control disorders have different sex ratios, all have similar ages at onset and courses. Studies on phenomenology, family history, and response to treatment suggest that intermittent explosive disorder, kleptomania, pathological gambling, pyromania, and trichotillomania may be related to mood disorders, alcohol and psychoactive substance abuse, and anxiety disorders (especially obsessive-compulsive disorder). Biological studies indicate that intermittent explosive disorder and pyromania may share serotonergic abnormalities similar to those reported in mood disorders., Conclusions: The impulse control disorders not elsewhere classified appear to be related to one another and to mood, anxiety, and psychoactive substance use disorders. Thus, like major depression, obsessive-compulsive disorder, panic disorder, bulimia nervosa, and attention deficit hyperactivity disorder, they may represent forms of "affective spectrum disorder."

Objective: The authors investigated trends in the frequency of neuroleptic malignant syndrome at their center over a period of 8 years and assessed possible reasons for these trends., Method: They used previously defined operational criteria in conducting a prospective survey of cases of the syndrome among 2,695 neuroleptic-treated patients from Oct. 1, 1986, to Aug. 31, 1990. The frequency of neuroleptic malignant syndrome during this period was then compared with the frequency in a comparable period prior to October 1986. The investigators also assessed changes between the two periods in risk factors associated with the syndrome, including patients' mean age, sex ratio, diagnoses, and severity of illness; neuroleptic dosage, potency, and route of administration; concomitant use of lithium; and degree of agitation., Results: Four cases of neuroleptic malignant syndrome were diagnosed during the more recent 47-month survey period, yielding a frequency of 0.15% +/- 0.05%. This represents a significant decline in the frequency of the syndrome from the estimate of 1.10% +/- 0.40% for the earlier survey period. Significantly fewer patients in the recent period had received intramuscular doses of neuroleptics., Conclusions: The frequency of neuroleptic malignant syndrome has declined significantly at this center. The decline appears to be attributable to increasing clinical awareness of the features of the syndrome, allowing early intervention and treatment, and to a reduction in risk factors, such as use of intramuscular neuroleptics.

Objective: The authors' objective was to provide phenomenologic, family history, and treatment response data on a group of rigorously diagnosed patients with kleptomania., Method: Twenty consecutive inpatients and outpatients met DSM-III-R criteria for current kleptomania or a past history of kleptomania. These patients were given structured diagnostic interviews, and their family histories of psychiatric disorders were assessed blindly. The patients' responses to psychosocial and biological treatments were also assessed., Results: All of the kleptomanic patients had lifetime diagnoses of major mood disorders, 16 had lifetime diagnoses of anxiety disorders, and 12 had lifetime diagnoses of eating disorders. A high morbid risk of major mood disorders (0.31) was found in their first-degree relatives. Ten of 18 patients receiving thymoleptic medications reported reduction or remission of their stealing behavior., Conclusions: Kleptomania may be related to major mood disorder and perhaps may represent another form of "affective spectrum disorder."

Five depressed patients who had shown no improvement with trials of antidepressants from several chemical families, including fluoxetine, responded when lithium was given in conjunction with fluoxetine. Lithium augmentation of fluoxetine may represent a useful strategy in refractory depression.

Neuroleptic malignant syndrome, a dangerous but little-known complication of antipsychotic drugs, is often assumed to be rare. To assess the frequency of the syndrome in a large psychiatric hospital, the authors first reviewed the literature and developed operational diagnostic criteria. Using these criteria to survey nearly 500 neuroleptic-treated patients admitted during a 1-year period, they found that seven (1.4%) had experienced definite or probable neuroleptic malignant syndrome. In several cases, including one fatal case, the diagnosis of neuroleptic malignant syndrome was not immediately considered. The authors conclude that neuroleptic malignant syndrome may be more common than previously thought and may be underdiagnosed.

In an 18-month prospective assessment of 679 hospitalized, neuroleptic-treated patients, the authors, using previously defined operational criteria, diagnosed neuroleptic malignant syndrome in six cases (0.9%). This supports their earlier finding that the syndrome appeared in about 1% of neuroleptic-treated patients.

The authors reviewed relevant studies in an attempt to define the onset and time course of antipsychotic effects of neuroleptic drugs. After excluding open trials, studies of chronically psychotic patients, and studies not using a placebo or nonneuroleptic sedative as a control, they found only five reports suitable for analysis. Among these, the degree of patients' improvement during neuroleptic treatment was similar regardless of the duration of the study. Also, in studies comparing neuroleptics with sedatives, similar improvement was observed with both treatments. Although neuroleptic drugs have been used clinically for 35 years, the timing of their specific therapeutic effects remains unclear.