Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

Abstract

Objective. The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.Methods. The data in this analysis were derived from a study of patients meeting the DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/day (n = 109) or placebo (n = 100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM-A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM-A ≤ 14) and moderate-to-severe anxiety (HAM-A ≥ 15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.Results. Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (-18.4 vs. -12.8, p < 0.01, effect size [ES] = 0.59) and moderate-to-severe anxiety (-22.0 vs. -13.0, p < 0.001, ES = 0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM-A total score for patients with both mild anxiety (-7.6 vs. -4.0, p < 0.01, ES = 0.62), and moderate-to-severe anxiety (-11.4 vs. -6.1, p < 0.0001, ES = 0.91).Conclusions. In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…A pooled analysis of two double‐blind RCTs demonstrated that quetiapine is more effective than placebo in relieving symptoms of anxiety co‐occurring alongside bipolar depression,313 and olanzapine‐fluoxetine combination has also been shown to be effective 314. In a post hoc analysis, lurasidone was effective in improving depressive as well as anxiety symptoms in patients with MDD who had mixed features and anxiety 315. The anxiolytic effects of divalproex, risperidone, and lamotrigine appear to be limited 199, 316…”

Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone

“…Low dosages, moreover, may have contributed to good tolerability: nausea and somnolence were the two most frequently reported adverse events (NNH of 8 for both). Post-hoc analyses showed that lurasidone is significantly useful in subgroups with mild and moderate-to-severe anxiety (Tsai et al, 2017), subjects with irritability (Swann et al, 2017) and post-menopausal women (Sramek et al, 2017).…”

Diagnosing and treating major depressive episodes that lie along the mood disorders spectrum: focus on depression with mixed features

“…43 Other common manic symptoms were irritability and distractibility. Post-hoc analyses of study data found that lurasidone also improved irritability 44 and anxiety symptoms 45 in this patient population without adversely affecting sexual function. 46 Additionally, lurasidone was associated with greater rates of response and remission 47 and was efficacious in post-menopausal women with major depressive disorder with mixed features.…”