TY - JOUR
T1 - Effect of Adjunctive Pimavanserin on Sleep/Wakefulness in Patients With Major Depressive Disorder
T2 - Secondary Analysis From CLARITY
AU - Jha, Manish K.
AU - Fava, Maurizio
AU - Freeman, Marlene P.
AU - Thase, Michael E.
AU - Papakostas, George I.
AU - Shelton, Richard C.
AU - Trivedi, Madhukar H.
AU - Dirks, Bryan
AU - Liu, Keith
AU - Stankovic, Srdjan
N1 - Publisher Copyright:
© Copyright 2020 Physicians Postgraduate Press, Inc.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.4088/JCP.20m13425
DO - 10.4088/JCP.20m13425
M3 - Article
C2 - 33264819
AN - SCOPUS:85097120535
VL - 82
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
SN - 0160-6689
IS - 1
ER -