Effect of Adjunctive Pimavanserin on Insomnia and Function in Patients With Major Depressive Disorder: Secondary Analysis From CLARITY

Up to 90% of patients with major depressive disorder (MDD) experience sleep disturbances. CLARITY was a phase 2 study of adjunctive pimavanserin, a 5-hydroxytryptamine2A antagonist/inverse agonist, in patients with MDD and inadequate antidepressant response. This exploratory analysis describes the effects of pimavanserin on insomnia. This was a double-blind, placebo-controlled study in patients with MDD and inadequate response to a selective serotonin reuptake inhibitor or serotonin/norepinephrine reuptake inhibitor. Using a 2-stage, sequential parallel-comparison design, 207 patients were initially randomized 3:1 to placebo or pimavanserin with ongoing SSRI/SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. At baseline, Hamilton Depression Rating Scale sleep disturbance score ≥3 occurred in 76% of placebo and 85% of pimavanserin patients. A significant (P < 0.05) improvement for pimavanserin versus placebo was observed for sleep disturbance scores at weeks 2, 3, and 4 in patients with a baseline score ≥3. On the Karolinska Sleepiness Scale (KSS), a significant (P≤0.05) reduction from baseline was observed with pimavanserin versus placebo from week 1 through 5. Among those with a baseline KSS ≥6 (n=120 placebo and n=42 pimavanserin), a significant (P < 0.05) improvement from baseline was observed from week 1 to 5 on the Sheehan Disability Scale overall score and Unproductive Days subscore. Concomitant sedative/hypnotic medications were taken by < 10% of patients during the study. Adjunctive pimavanserin significantly improved insomnia and sleepiness during MDD treatment. This exploratory analysis supports further study of pimavanserin for adjunctive treatment of MDD, especially in patients with insomnia.