The interpretation of results from earlier trials of carbamazepine were complicated by several methodological issues including crossover designs and evaluation of mixed cohorts containing unipolar and bipolar subjects.25-26 Initial interest in the use of divalproex

monotherapy for bipolar depression was provided by an open study that suggested benefit Inhibitors,research,lifescience,medical in medication-nai’ve subjects with BP-II/27 Subsequently, Sachs and colleagues conducted the first, multicenter trial comparing divalproex with placebo in 43 subjects with bipolar depression (types I, II, or not otherwise specified).28 In this 8-weck study, no significant, difference was observed between treatment arms in mean change from baseline on the HAM-D. Two smaller controlled trials in bipolar depression have been conducted that demonstrate superiority of monotherapy divalproex over placebo.29-30 In total, the controlled trial evidence evaluating divalproex in bipolar depression rests on the outcomes of 87 patients

spread across three separate trials. This Inhibitors,research,lifescience,medical limited population size beckons for larger studies to confirm or refute findings that suggest, divalproex may wield independent antidepressant efficacy in bipolar Inhibitors,research,lifescience,medical disorder. Olanzapine and the olanzapine-fluoxetine combination In 2003, an olanzapine-fluoxetine combination (OFC) was the first compound approved by the US FDA for the treatment, of bipolar depression. This decision directed attention to the atypical antipsychotic drugs as appealing considerations for treating Inhibitors,research,lifescience,medical both the manic and depressed phases of bipolar disorder. The evidence for QFC’s efficacy on categorical and continuous measures of depression was derived from two pooled, 8-week, placebo-controlled trials comparing olanzapine monotherapy and OFC against, placebo in BP-I depression.31 On the primary outcome measure of change from baseline to learn more endpoint Inhibitors,research,lifescience,medical severity in MADRS score, as well as key secondary

measures including rates of response and remission, olanzapine- and OFC-treatcd subjects achieved significantly greater improvement than placebo-treated subjects. An analysis of individual MADRS items showed OFC to improve sadness, reported sadness, lassitude, the inability to feel, and pessimistic thoughts; crotamiton whereas olanzapine monotherapy improved more vegetative symptoms of depression – reduced sleep, reduced appetite, and inner tension. Neither compound was found to reduce suicidal thinking. The clinical appeal of OFC is tempered by metabolic concerns of weight, gain and hyperglycemia that, are more highly associated with olanzapine than with other atypical antipsychotics.32 Quetiapine Quetiapine is the only monotherapeutic agent, approved by the US FDA for acute bipolar depression. Quetiapine’s approval for bipolar depression in 2006 was based on results of two identically-designed pivotal trials conducted in the US.