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Objective: Bipolar disorder is a severe, chronic mental illness with a high incidence of medical and psychological comorbidities that make treatment and prevention of future episodes challenging. This study investigated the use of services among outpatients with bipolar disorder to further understanding of how to maximize and optimize personalization and accessibility of services for this difficult-to-treat population. Methods: The Lithium Treatment-Moderate Dose Use Study (LiTMUS) was a six-month multisite, comparative effectiveness trial that randomly assigned 283 individuals to receive lithium plus optimized care- defined as personalized, guideline-informed care-or optimized care without lithium. Relationships between treatment service utilization, captured by the Cornell Service Index, and demographic and illness characteristics were examined with generalized linear marginal models. Results: Analyses with complete data (week 12, N=246; week 24, N=236) showed that increased service utilization was related to more severe bipolar disorder symptoms, physical side effects, and psychiatric and general medical comorbidities. Middle-aged individuals and those living in die United States longer tended to use more services than younger individuals or recent immigrants, respectively. Conclusions: These data suggest that not all individuals with bipolar disorder seek treatment services at the same rate. Instead, specific clinical Or demographic features may affect the degree to which one seeks treatment, conveying clinical and public health implications and highlighting the need for specific approaches to correct such discrepancies. Future research is needed to elucidate potential moderators of service utilization in bipolar disorder to ensure that those most in need of additional services utilize them. [ABSTRACT FROM AUTHOR]

Objective: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT). Method: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone. The primary outcome measures were the Clinical Global Impression Scale for Bipolar Disorder-Severity (CGI-BP-S) and "necessary clinical adjustments" (medication adjustments per month). Secondary outcome measures included mood symptoms and functioning. The authors also assessed sustained remission (defined as a CGI-BP-S score 2 ≤ for 2 months) and treatment with second-generation antipsychotics. The authors hypothesized that lithium plus OPT would result in greater clinical improvement and fewer necessary clinical adjustments. Results: The authors observed no statistically significant advantage of lithium plus OPT on CGI-BP-S scores, necessary clinical adjustments, or proportion with sustained remission. Both groups had similar outcomes across secondary clinical and functional measures. Fewer patients in the lithium-plus-OPT group received secondgeneration antipsychotics compared with the OPT-only group (48.3% and 62.5%, respectively). Conclusions: In this pragmatic comparative effectiveness study, a moderate but tolerated dosage of lithium plus OPT conferred no symptomatic advantage when compared with OPT alone, but the lithium-plus-OPT group had less exposure to second-generation antipsychotics. Only about onequarter of patients in both groups achieved sustained remission of symptoms. These findings highlight the persistent and chronic nature of bipolar disorder as well as the magnitude of unmet needs in its treatment. [ABSTRACT FROM AUTHOR]

Objective: Clinicians have few evidence- based options for the management of treatment-resistant bipolar depression. This study represents the first randomized trial of competing options for treatment-resistant bipolar depression and assesses the effectiveness and safety of antidepressant augmentation with lamotrigine, inositol, and risperidone. Method: Participants (N=66) were patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant. Patients were randomly assigned to open-label adjunctive treatment with lamotrigine, inositol, or risperidone for up to 16 weeks. The primary outcome measure was the rate of recovery, defined as no more than two symptoms meeting DSM- IV threshold criteria for a mood episode and no significant symptoms present for 8 weeks. Results: No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure. However, the recovery rate with lamotrigine was 23.8%, whereas the recovery rates with inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone. Conclusions: No differences were found in primary pairwise comparison analyses of open-label augmentation with lamotrigine, inositol, or risperidone. Post hoc secondary analyses suggest that lamotrigine may be superior to inositol and risperidone in improving treatment-resistant bipolar depression. [ABSTRACT FROM AUTHOR]

Objective: There is a major unmet need for effective options in the treatment of bipolar depression. Method: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire. Results: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Åsberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (≥50% Montgomery-Åsberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of pa- tients meeting remission criteria (Montgomery-Åsberg Depression Rating Scale ≤12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Åsberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively). Conclusions: Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression. [ABSTRACT FROM AUTHOR]

Objective: This study compared demographic and phenomenological variables between bipolar patients with and without rapid cycling as a function of bipolar I versus bipolar II status. Method: The authors examined demographic, historical, and symptomatic features of patients with and without rapid cycling in a cross-sectional study of the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. Results: Rapid-cycling bipolar disorder occurred in 20% of the study group. Rapid cycling patients were more likely to be women, although the effect was somewhat more pronounced among bipolar I patients than bipolar II patients. In addition, rapid-cycling bipolar patients experienced onset of their illness at a younger age, were more often depressed at study entry, and had poorer global functioning in the year before study entry than nonrapid-cycling patients, Rapid-cycling patients also experienced a significantly greater number of depressive and hypomanic/manic episodes in the prior year. A lifetime history of psychosis did not distinguish between rapid and nonrapidcycling patients, although bipolar I patients were more likely to have experienced psychosis than bipolar II patients, Conclusions: Patients with rapid-cycling bipolar disorder demonstrate a greater severity of illness than nonrapid-cycling patients on a number of clinical measures. This study highlights the need to refine treatments for rapid cycling to reduce the overall morbidity and mortality of patients with this illness course modifier. [ABSTRACT FROM AUTHOR]

Objective: Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.Method: This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.Results: Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.Conclusions: In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ. [ABSTRACT FROM AUTHOR]

Investigates the relationships between peripheral thyroid hormone levels and cerebral blood flow (CBF) and cerebral glucose metabolism in mentally ill patients. Study on medication-free inpatients with major depression; Use of linear regression to correlate global CBF and cerebral glucose metabolism; Complex relationship of thyroid hormones and mood disorders.

Studies brain activity during transient sadness and happiness in healthy women. Association of positron emission tomography (PET) to changes in regional cerebral blood flow (rCBF) linked with transient sadness or happiness; Association of transient sadness and happiness to significant changes in regional brain activity in the limbic system.

The authors describe 10 patients who developed panic attacks only after substantial cocaine use. The timing of the onset of symptoms, i.e., after 1–6 years of cocaine use, and the fact that only one patient had a first-degree relative with panic disorder were more suggestive of acquired than primary panic disorder. The patients' atypical symptoms and responses to medications may be explained in terms of limbic-neuronal hyperexcitability induced by cocaine through a kindling mechanism. [ABSTRACT FROM AUTHOR]

Objective: This study assessed weight changes in a large cohort of patients with bipolar disorder who were treated with randomly assigned maintenance monotherapies. Method: A post hoc analysis was conducted to assess the effects of lamotrigine, lithium, and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind, placebo-controlled, 18-month studies. Results: Mean changes in weight among obese patients (N=155) at week 52 were -4.2, +6.1, and -0.6 kg with lamotrigine, lithium, and placebo, respectively (lamotrigine versus lithium and lithium versus placebo). Among nonobese patients (N= 399), mean changes in weight (kg) at week 52 were -0.5, +1.1, and +0.7 with lamotrigine, lithium, and placebo, respectively, with no significant differences among groups. Conclusions: Obese patients with bipolar 1 disorder lost weight while taking lamotrigine and gained weight while taking lithium. [ABSTRACT FROM AUTHOR]

Focuses on the symptomatology of mania, an altered mental state in the U.S. Association of facial emotion with mania behavior; Emergence of psychotic symptoms and grandiosity; Discussion on the clinical behaviors of patients with mania symptoms.