Effect of Adjunctive Pimavanserin on Sleep/Wakefulness in Patients With Major Depressive Disorder: Secondary Analysis From CLARITY.

Abstract

OBJECTIVE:

This was an analysis of the effect of pimavanserin, a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist, on dysregulated sleep in patients with major depressive disorder (MDD) by DSM-5 criteria and an inadequate antidepressant response.

METHODS:

For this analysis of CLARITY, a phase 2 study of adjunctive pimavanserin (N = 207) conducted between December 2016 and October 2018, sleep/wakefulness disturbances were measured with the 17-item Hamilton Depression Rating Scale (HDRS₁₇) insomnia items (sum of items 4, 5, and 6) and the Karolinska Sleepiness Scale (KSS). Outcomes included change from baseline in HDRS₁₇ insomnia factor score and KSS score, correlation between the HDRS₁₇ insomnia factor score and KSS score, and change from baseline in the Sheehan Disability Scale (SDS) total score and Unproductive Days subscore in patients with a baseline KSS score ≥ 6.

RESULTS:

At baseline, HDRS₁₇ insomnia factor score ≥ 3 occurred in 76% of patients receiving placebo and 85% of patients receiving pimavanserin. The overall least squares (LS) mean weighted difference (SE) was -0.5 (0.32) with a 95% CI of -1.2 to 0.1 (P = .088) at week 5. Improvement was observed with pimavanserin versus placebo at weeks 2, 3, and 4, with effect sizes (ESs) of 0.370 to 0.524 (P < .05). For KSS score, the LS mean difference (SE) at week 5 was -1.1 (0.30) (95% CI, -1.7 to -0.5; P = .0003; ES = 0.627) for pimavanserin versus placebo. Among those with a KSS score ≥ 6 at baseline (n = 120 placebo and n = 42 pimavanserin), the LS mean difference (SE) in the mean SDS score at week 5 was -1.1 (0.46) (95% CI, -2.0 to -0.2; P = .019; ES = 0.442) for pimavanserin versus placebo.

CONCLUSIONS:

Adjunctive pimavanserin significantly improved sleep/wakefulness disturbance during treatment of MDD, an improvement that was associated with greater improvement in function.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT03018340.

• Authors: Manish K Jha, Maurizio Fava, Marlene P Freeman, Michael E Thase, George I Papakostas, Richard C Shelton, Madhukar H Trivedi, Bryan Dirks, Keith Liu, Srdjan Stankovic
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 82 Issue 1 (12 01 2020) ISSN: 1555-2101 [Electronic] United States
• PMID: 33264819 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2020 Physicians Postgraduate Press, Inc.

Chemical References

• Antidepressive Agents
• Piperidines
• Serotonin 5-HT2 Receptor Antagonists
• Urea
• pimavanserin

Topics

• Adolescent
• Adult
• Aged
• Antidepressive Agents (therapeutic use)
• Depressive Disorder, Major (complications, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Linear Models
• Male
• Middle Aged
• Piperidines (therapeutic use)
• Serotonin 5-HT2 Receptor Antagonists (therapeutic use)
• Sleep Wake Disorders (diagnosis, drug therapy, etiology)
• Treatment Outcome
• Urea (analogs & derivatives, therapeutic use)
• Young Adult