Effect of Adjunctive Pimavanserin on Sleep/Wakefulness in Patients With Major Depressive Disorder

• DOI: 10.4088/jcp.20m13425
• Publication Date: 2020-12-01T18:13:06Z
• 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
• Keywords: Adult; Male; Sleep Wake Disorders; Depressive Disorder, Major; Adolescent; 610; Middle Aged; Antidepressive Agents; 3. Good health; Psychiatry and Mental health; Young Adult; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Double-Blind Method; Piperidines; Linear Models; Serotonin 5-HT2 Receptor Antagonists; Humans; Urea; Drug Therapy, Combination; Female; Aged

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.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.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.Adjunctive pimavanserin significantly improved sleep/wakefulness disturbance during treatment of MDD, an improvement that was associated with greater improvement in function.ClinicalTrials.gov identifier: NCT03018340.