A phase 2, randomized, double-blind, placebo-controlled ST of adjunctive pimavanserin in patients with major depressive disorder and an inadequate response to therapy (CLARITY)

Maurizio Fava, Bryan Dirks, Marlene P. Freeman, George I. Papakostas, Richard C. Shelton, Michael E. Thase, Madhukar H. Trivedi, Keith Liu, Srdjan Stankovic

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objective: Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD). Methods: This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score. Results: Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was −1.7 (0.85) (P=.039) and for the SDS score was −0.8 (0.29) (P=.004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (−4.0 [1.09], P=.0003) and SDS (−1.2 [0.40], P=.0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P<.05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache. Conclusions: Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience.

Original languageEnglish (US)
Article number19m12928
JournalJournal of Clinical Psychiatry
Volume80
Issue number6
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Psychiatry and Mental health

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