Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis

Abstract

Objective. The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.Methods. The data in this analysis were derived from a study of patients meeting 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, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n = 109) or placebo (n = 100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.Results. Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, p < 0.0001, effect size [ES] = 1.4) and without (-19.9 vs. -13.8, p < 0.0001, ES = 0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (-1.4 vs. -0.3, p = 0.0012, ES = 1.0) and the YMRS disruptive-aggressive item (-1.0 vs. -0.3, p = 0.0002, ES = 1.2).Conclusions. In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review

“…Swann et al . 13) found that lurasidone significantly improved depressive symptoms in patients with and without irritability as measured by the irritability and disruptive aggression items on the YMRS. Moreover, compared with placebo, lurasidone significantly reduced irritability in those with MDE with mixed features with irritable features (irritability item: −1.4 vs. −0.3, respectively; p =0.0012, effect size=1.0; disruptive-aggressive item: −1.0 vs. −0.3, respectively; p =0.0002, effect size= 1.2).…”

“…Moreover, compared with placebo, lurasidone significantly reduced irritability in those with MDE with mixed features with irritable features (irritability item: −1.4 vs. −0.3, respectively; p =0.0012, effect size=1.0; disruptive-aggressive item: −1.0 vs. −0.3, respectively; p =0.0002, effect size= 1.2). 13) …”

Defining irritability as a diagnostic marker and a target for responsiveness

“…Fava, Ménard [3] showed reductions in scores of irritability and depressive symptoms when depressed patients were treated with adjunctive brexpiprazole, and a subsequent worsening of these symptoms upon its cessation. Swann, Fava [4] also demonstrated a reduction in irritability that corresponded with improvements in depressive symptoms when depressed patients with mixed features, were treated with lurasidone. And recently, Jha, Minhajuddin [5] showed that improvement in irritability scores within the first 4 weeks of treatment correlated with an increased likelihood of remission, regardless of baseline depression and irritability severity.…”

Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review

“…Lurasidone treatment was associated with significant improvement (vs. placebo) in patients with mild (−7.6 vs. −4.0, respectively; p＜0.01, effect size=0.62) and moderate-tosevere (−11.4 vs. −6.1, respectively; p＜ 0.0001, effect size=0.91) anxiety. Swann et al 13) found that lurasidone significantly improved depressive symptoms in patients with and without irritability as measured by the irritability and disruptive aggression items on the YMRS. Moreover, compared with placebo, lurasidone significantly reduced irritability in those with MDE with mixed features with irritable features (irritability item: −1.4 vs. −0.3, respectively; p=0.0012, effect size=1.0; disruptive-aggressive item: −1.0 vs. −0.3, respectively; p=0.0002, effect size= 1.2).…”

“…Moreover, compared with placebo, lurasidone significantly reduced irritability in those with MDE with mixed features with irritable features (irritability item: −1.4 vs. −0.3, respectively; p=0.0012, effect size=1.0; disruptive-aggressive item: −1.0 vs. −0.3, respectively; p=0.0002, effect size= 1.2). 13) Menopause is an important clinical variable of MDEs with mixed features. In a post-hoc study, Sramek et al 14) found that lurasidone was an effective treatment for patients with post-menopausal MDD with mixed features (p=0.0056, effect size=0.96).…”