Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies.

This meta-analysis investigated the efficacy, safety, and tolerability of lamotrigine versus placebo in preventing relapse and recurrence of mood episodes in women of childbearing age with bipolar I disorder. Following up to 16 weeks' open-label lamotrigine treatment, responders were randomized to double-blind treatment, including lamotrigine 100-400 mg/day or placebo, in four trials of up to 76 weeks. Women aged 18-45 years who received ≥ 1 dose of study treatment and had ≥ 1 efficacy assessment in the double-blind phase were pooled for efficacy analysis. The primary outcome was median time to intervention for any mood episode (TIME). Of 717 eligible women in the open-label phase, 287 responded and were randomized to lamotrigine (n = 153) or placebo (n = 134). The randomized group had a mean (SD) of 2.0(2.02) manic and 2.5(2.02) depressive episodes in the 3 years before screening. Median TIME was 323 days with lamotrigine and 127 days with placebo (HR 0.69; 95% CI 0.49, 0.96; p = 0.030). Lamotrigine delayed time to intervention for any depressive episode (HR 0.59; 95% CI 0.39, 0.90; p = 0.014) with no treatment difference for manic episodes (HR 0.91; 95% CI 0.52, 1.58; p = 0.732). 2/717 (< 1%) participants experienced serious rash-related adverse events (AEs) during the open-label phase, and 52/717 (7%) had non-serious rash-related events leading to study withdrawal. Incidence of AEs and AEs leading to withdrawal were similar between lamotrigine and placebo groups. Lamotrigine delayed relapse and recurrence of mood episodes, largely by preventing depressive episodes, and was well tolerated in women of childbearing age.

Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder.

OBJECTIVE: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. METHOD: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. RESULTS: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. LIMITATIONS: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. CONCLUSION: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists' practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

Evaluation of antidepressant activity of ropinirole coadministered with fluoxetine in acute and chronic behavioral models of depression in rats.

BACKGROUND: Certain unknown aspects of ropinirole action, such as its antidepressant effect after chronic administration and on cotreatment with fluoxetine, remain to be evaluated, which formed the rationale for this study. METHODS: Wistar rats of either sex (weighing 150-200 g) were used. In the dose-finding study, oral dose of ropinirole (20 mg/kg) was selected. This was combined with two different doses of fluoxetine (10 and 20 mg/kg). Their antidepressant-like effects were compared in acute and chronic forced-swim test (FST). Acute FST was conducted in two sessions after administration of three doses within 24 h. Chronic FST was conducted over 14 days. Drugs were administered each day for 14 days. Effect on locomotor activity was tested in OFT. RESULTS: ANOVA with post hoc Tukey test was used. Dose-finding study of ropinirole showed that out of three doses, 20 mg/kg produced maximum reduction in immobility in acute FST (137±8 s). Coadministration of ropinirole with fluoxetine in acute FST further reduced immobility (107±8 s). This effect was more prominent in chronic forced-swim-stressed rats (74±2 s). Neither ropinirole nor its coadministration with fluoxetine increased locomotor activity in open-field test. CONCLUSIONS: The potential of ropinirole to act as an antidepressant agent is proven by the reduction in immobility time in FST. Further, there is an augmentation of the effect of fluoxetine by ropinirole, suggesting synergistic interaction of dopamine and serotonin pathway in brain.