Lurasidone in the Treatment of Bipolar Depression With Mixed (Subsyndromal Hypomanic) Features

Abstract

Objective: Mixed (subsyndromal hypomanic) features are prevalent in patients with bipolar depression and are associated with more severe and complex illness, including increased risk for suicide attempts, higher switch to mania during antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc analysis was to evaluate the efficacy and safety of lurasidone in the treatment of patients with bipolar depression presenting with mixed features.

Treatment of mixed features in bipolar disorder

“…Only 1 study was a primary RCT assessing treatment of depression with mixed features (using ziprasidone) a priori, while the remaining studies were post-hoc analyses assessing the efficacy of lurasidone, olanzapine, and the olanzapine-fluoxetine combination (OFC). [13][14][15][16][17] Three studies assessed the efficacy of treatment of manic/hypomanic episodes with mixed features with 2 post-hoc analyses assessing olanzapine and asenapine for mania with mixed features and 1 RCT assessing adjunctive quetiapine for hypomania with mixed features. [18][19][20] Treatment of mania with mixed features…”

“…20 For bipolar depression with mixed features, post-hoc analyses suggested antidepressant efficacy of olanzapine, OFC, and lurasidone compared to placebo. 13,16,17 One RCT showed antidepressant efficacy for ziprasidone in the acute treatment of a MDE with mixed features in subjects with BD-II or MDD, with a greater antidepressant effect in subjects with BD-II. 14 Taken together, SGAs show great promise for alleviating symptoms of both mania and depression in BD with mixed features.…”

“…14 Four post-hoc analyses were identified that re-analyzed RCT data through retrospectively identifying subjects that would have met criteria for bipolar depression with mixed features. 13,[15][16][17] All 5 studies assessed the efficacy of second-generation antipsychotics (SGAs), specifically ziprasidone, olanzapine, olanzapine-fluoxetine combination (OFC), and lurasidone. Of interest, 3 of the studies predated the publication of the DSM-5.…”

“…McIntyre et al 17 Post-hoc analysis of subjects with BD-I with MDE with mixed features in 6-week RCT of lurasidone (n = 186) versus placebo (n = 94) (The presence of mixed features was defined as YMRS score ≥ 4 at study baseline)…”

“…[9][10][11][12] Given the relative recency of this new nosological entity (May 2013), only a limited number of studies has directly examined the efficacy of treatments for mood states with DSM-5-defined mixed features. [13][14][15][16][17][18][19][20][21][22] Further, to date, only the Florida Medicaid Guidelines have specifically addressed the treatment of mixed features. 23 At the current time, inadequate evidence exists to adequately inform evidencebased treatment guidelines for mixed features in BD, as randomized controlled trials (RCTs) assessing the efficacy of various treatments specifically for BD mood episodes with mixed features have yet to be conducted.…”