Manish K Jha 1,2 , Maurizio Fava 3 , Marlene P Freeman 3 , Michael E Thase 4 , George I Papakostas 3 , Richard C Shelton 5 , Madhukar H Trivedi 6 , Bryan Dirks 7 , Keith Liu 7 , Srdjan Stankovic 7 Show Affiliations »
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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. © Copyright 2020 Physicians Postgraduate Press, Inc.
RCT Entities: Population
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Outcomes
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. © Copyright 2020 Physicians Postgraduate Press, Inc.
Entities: Chemical
Disease
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Year: 2020
PMID： 33264819 DOI： 10.4088/JCP.20m13425
Source DB: PubMed Journal: J Clin Psychiatry ISSN： 0160-6689 Impact factor: 4.384