In a study published in CNS Spectrums, lurasidone was linked with improvements in depression and anxiety in patients with major depressive disorder (MDD) with mixed features and co-occurring anxiety.1

Approximately one-quarter of patients with MDD have been shown to exhibit mixed features, and the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) includes a diagnostic specifier to indicate subthreshold hypomania in such patients.2 In addition, the lifetime prevalence of an anxiety disorder is more than 35% in patients with MDD, and this comorbidity is associated with increased illness severity and functional impairment.3-5

In patients with MDD with mixed features, initial evidence suggests that comorbid anxiety may be present in up to 65% of cases.6 While earlier findings demonstrated that co-occurring anxiety may decrease the likelihood that patients with MDD or bipolar depression will respond to antidepressant treatment, these effects have not previously been explored in patients with MDD with mixed features.7

In the current study, researchers from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and Sunovion Pharmaceuticals, the company that markets lurasidone in the United States, investigated the efficacy of the drug in treating patients with MDD with mixed features and either mild or moderate to severe anxiety. They conducted a post-hoc analysis of data from a 2016 randomized double-blind placebo-controlled trial that demonstrated the efficacy of the atypical antipsychotic lurasidone in the treatment of MDD with mixed features.8

In that trial, the treatment group (n=109) received 20 to 60 mg/day of lurasidone for 6 weeks; the placebo group included 100 patients. Participants had a score of ≥26 on the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, plus 2 or 3 specific manic symptoms on most days, such as racing thoughts and a reduced need for sleep.

In the present study, lurasidone was associated with a greater reduction vs placebo in MADRS scores in patients with mild anxiety (−18.4 vs −12.8, P <.01, effect size [ES] 0.59) as well as patients with moderate to severe anxiety (−22.0 vs −13.0, P <.001, ES .95). In addition, lurasidone was associated with a greater reduction vs placebo in Hamilton Anxiety Rating Scale (HAM-A) scores in both groups of patients (−7.6 vs −4.0, P <.01, ES .62, in patients with mild anxiety; −11.4 vs −6.1, P <.001, ES .91, in patients with moderate to severe anxiety).

Further analysis revealed that the improvement in depressive symptoms observed with lurasidone was partially mediated by the improvement in anxiety. “Given the high rates of anxiety reported in patients with a diagnosis of MDD with mixed features, the combined antidepressant and anxiolytic efficacy of lurasidone makes it a potentially useful treatment option in this common and difficult-to-treat clinical population,” the investigators concluded.

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  1. Tsai J, Thase MEMao YNg-Mak DPikalov ALoebel A. Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study. CNS Spectr. 2017; 22(2):236-245. doi:10.1017/S1092852917000074
  2. McIntyre RS, Soczynska JK, Cha DS, et al. The prevalence and illness characteristics of DSM–5-defined “mixed feature specifier” in adults with major depressive disorder and bipolar disorder: results from the International Mood Disorders Collaborative Project. J Affect Disord. 2015;172:259-264. doi:10.1016/j.jad.2014.09.026
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