A systematic review of the evidence for the treatment of acute depression in bipolar I disorder

Abstract

In this article we examined evidence for the acute treatment of depression in bipolar I disorder, focusing on double-blind, placebo-controlled studies with a definite primary outcome measure and published in peer review journals. Quetiapine and olanzapine/fluoxetine are currently approved by the FDA for the treatment of bipolar depression and a number of additional agents (including other atypical antipsychotics, mood stabilizers, antidepressants, and novel compounds) have been studied with varying degrees of efficacy. The medication with the most evidence for efficacy in bipolar depression is quetiapine with five studies showing positive efficacy compared to placebo. In contrast five studies of lamotrigine were negative although meta-analyses of the pooled have found some treatment effects. Two studies of olanzapine and olanzapine/fluoxetine and three small studies of divalproex showed significant efficacy in treating bipolar depression. Two studies of aripiprazole found no differences compared to placebo. Early research on lithium in bipolar depression had significant methodological flaws and only one study of lithium met our primary search criteria. To better understand the role of anti-depressants we also examined studies of antidepressants as adjunctive treatment of bipolar depression in participants taking mood stabilizers or atypical antipsychotics. These studies reported mixed results for a variety of antidepressants but the majority found no differences compared to placebo. Other studies of adjunctive treatment were also discussed. There has been one positive adjunctive study each of lamotrigine, omega-3 fatty acids, modafinil, and Armodafinil while there was one negative trial each of omega-3 fatty acids, ziprasidone, and levetiracetam.

The development of lurasidone for bipolar depression

“…When the retrospective cohorts in the PREVAIL 3 and 1 studies were compared directly, the effect sizes were comparable (0.31 vs. 0.34), and both were lower than the effect size (0.51) observed in the monotherapy trial. This is consistent with previous studies that have shown that adjunctive trials in bipolar depression yield effect sizes that are smaller than those observed in monotherapy trials . Since lithium or valproate monotherapy has some antidepressant effects in its own right, adjunctive use of these agents may enhance placebo response and reduce effect size .…”

“…Antidepressants typically are coadministered with a mood stabilizer or an antipsychotic agent. Before the development of lurasidone, two atypical antipsychotic agents had been approved as monotherapies for acute bipolar depression in the United States—olanzapine–fluoxetine combination (OFC; 2003) and quetiapine (2006)—while two other agents (aripiprazole and ziprasidone) had failed to demonstrate efficacy . The results of one previous placebo‐controlled trial examining adjunctive therapy with ziprasidone were negative …”

The need for cost-effective choices to treat patients with bipolar 1 disorders including asenapine

“…Never-the-less, it is recognised by all healthcare professionals that the different AAPs have different mechanisms of action and different effectiveness and safety profiles in patients with major mental illness including BPD (1,(11)(12)(13)(14). Consequently, the choice of AAP prescribed should be tailored to the individual, especially as there are concerns with the effectiveness of some of the current AAPs for the management of depressive phases of bipolar disorders (10,13).…”

Efficacy of Lurasidone in Adults Aged 55 Years and Older With Bipolar Depression

“…16 Lower treatment effect sizes are notably more frequent in adjunctive therapy studies compared to monotherapy studies. 30 Lithium and valproate each has been shown to have antidepressant effects in some patients with bipolar depression, 31 and a systematic review 32 of older adults with refractory unipolar depression suggests that augmentation with lithium is associated with an increased antidepressant response. In the current older adult analyses, response rates in the placebo group were higher with adjunctive therapy compared to monotherapy (37.0% vs 14.8%), consistent with a contribution of adjunctive lithium and valproate to placebo group response.…”