Course, outcomes, and psychosocial interventions for first-episode mania.

OBJECTIVES: The course of bipolar disorder tends to worsen over time, highlighting the importance of early intervention. Despite the recognized need for adjunctive psychosocial treatments in first-episode mania, very few studies have evaluated psychological interventions for this period of significant risk. In this empirical review, we evaluate existing research on first-episode bipolar disorder, compare this body of research to parallel studies of first-episode schizophrenia, and identify strategies for future research. METHODS: A comprehensive literature search of the MEDLINE and PsychINFO databases was conducted to identify studies of first-episode mania, as well as first-episode schizophrenia. Recovery and relapse rates were compared across studies. RESULTS: In contrast to a number of studies of first-episode schizophrenia, the authors identified only seven independent programs assessing first-episode mania. Findings from these studies suggest that, while pharmacological treatment helps patients achieve recovery from acute episodes, it fails to bring patients to sustained remission. Early psychosocial intervention may be imperative in reducing residual symptoms, preventing recurrence of mood episodes, and improving psychosocial functioning. However, very few studies of psychosocial interventions for first-episode mania have been systematically studied. CONCLUSIONS: Studies of first-episode mania indicate a gap between syndromal/symptomatic and functional recovery. Novel psychosocial interventions for first-episode mania may help bridge this gap, but require controlled study.

Risks for the transition from major depressive disorder to bipolar disorder in the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder. METHOD: We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions. Participants in this survey were interviewed twice over a period of 3 years, in 2000-2001 and in 2004-2005, and survey data were gathered using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. RESULTS: Approximately 1 in 25 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, black race/ethnicity, and less than high school education. Clinical characteristics of depression (eg, age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (odds ratio [OR] = 2.20; 95% confidence interval [CI], 1.47-3.30) and generalized anxiety disorder (OR = 1.58; 95% CI, 1.06-2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR = 1.26; 95% CI, 1.12-1.42) and past-year problems with one's social support group (OR = 1.79; 95% CI, 1.19-2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest. CONCLUSIONS: A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder.

Sleep disturbance in euthymic bipolar patients.

Sleep disturbance is a common feature during mood episodes in bipolar disorder. The aim of this study was to investigate the prevalence of such symptoms among euthymic bipolar patients, and their association with risk for mood episode recurrence. A cohort of bipolar I and II subjects participating in the Systematic Treatment Enhancement Program for Bipolar Disorder who were euthymic for at least 8 weeks were included in this analysis. Survival analysis was used to examine the association between sleep disturbance on the Montgomery-Asberg Depression Rating Scale (MADRS) and recurrence risk. A total of 73/483 bipolar I and II subjects reported at least mild sleep disturbance (MADRS sleep item ≥2) for the week prior to study entry. The presence of sleep problems was associated with a history of psychosis, number of previous suicide attempts, and anticonvulsant use. Sleep disturbance at study entry was significantly associated with risk for mood episode recurrence. Sleep disturbance is not uncommon between episodes for individuals with bipolar disorder and may be associated with a more severe course of illness. This suggests that sleep disturbance is an important prodromal symptom of bipolar disorder and should be considered a target for pharmacologic or psychosocial maintenance treatment.

The pharmacologic treatment of bipolar disorder.

Over the past half century, substantial clinical trial data have accumulated to guide clinical management of bipolar disorder, and 13 medications have gained US Food and Drug Administration approval for the treatment of mania or bipolar depression or the maintenance treatment of bipolar disorder. While the number of studies has grown and many controversies related to pharmacologic treatment of bipolar disorder are not yet resolved, the task of transforming the accumulated evidence into useful guidance for clinical practice becomes more manageable and less error prone by limiting consideration to the highest quality studies. Therefore, this article emphasizes points of relative clarity by highlighting findings supported by double-blind, placebo-controlled clinical trials with samples of at least 100 subjects. A MEDLINE search was conducted and augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings for randomized controlled trials published in English between 1950 and April 2010 with at least 100 subjects. Keywords used in the search included randomized controlled trial, mania, hypomania, depression, relapse prevention, placebo, antidepressant, switch, and maintenance treatment of bipolar disorder. A paradigm for implementing evidence-based treatment is offered along with consideration of patterns emerging across clinical trials.

A critical review of pharmacotherapy for major depressive disorder.

Newer generation antidepressant drugs, with improvements in safety and tolerability, have replaced tricyclic antidepressants as first-line treatment of depressive illness. However, no single antidepressant drug from any class has distinguished itself as the obvious first-line treatment of major depression. The choice of therapy is driven primarily by patient choice, with informed consent for the risks of adverse effects. Cost has become an additional factor in this decision as several of the newer antidepressant drugs are now available in generic form. Several augmentation and drug-switching strategies have demonstrated benefit in refractory illness. While no single strategy distinguished itself as superior to the others, some have been more rigorously tested. Ongoing efforts at improving effectiveness, time to response, and tolerability have led to novel drug therapies. Efforts at characterizing predictors of treatment outcomes now include pharmacogenetic studies.