Citation

Bugarski-Kirola D, Bitter I, Liu IY, Abbs B, Stankovic S. Schizophrenia Bulletin Open 2022; 3(1).

Copyright

(Copyright © 2022, Oxford University Press)

DOI

10.1093/schizbullopen/sgac006

PMID

unavailable

Abstract

Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, as adjunctive treatment in patients with inadequate response. This was a 6-week, randomized, double-blind, placebo-controlled, study conducted in North America and Europe. Adult outpatients with schizophrenia and inadequate response to current antipsychotic were enrolled. Inclusion criteria included Positive and Negative Syndrome Scale (PANSS) total score ≥65 and ≤110 and retrospective antipsychotic treatment stability of 8 weeks. Pimavanserin 20 mg/day or placebo added to ongoing antipsychotic was tested in a flexible-dose paradigm with dose adjustments allowed during the first 3 weeks. The primary efficacy endpoint, PANSS total score change from baseline to week 6, was not met, although improvement was greater with pimavanserin than placebo (LS mean difference: -2.1, [95% CI: -4.5, 0.4]; P =. 094). As a hierarchical testing procedure was used, additional efficacy analyses were exploratory. Clear separation from placebo was observed with pimavanserin at week 6 for the PANSS Negative Symptoms subscale (LS mean difference: -0.7, [95% CI: -1.5, 0.0]) and Marder Negative Symptom Factor score (-0.9, [-1.7, -0.1]). Analysis of European sites (81.5% of patients) revealed a difference for pimavanserin versus placebo on PANSS total score (LS mean difference: -3.1, [95% CI: -5.8, -0.4]) and Clinical Global Impressions-Severity score (-0.2, [-0.4, -0.0]). Treatment-emergent adverse events occurred in 39.9% with pimavanserin and 36.4% with placebo. Although statistical significance for the primary endpoint was not met, a trend toward improvement in negative symptoms was observed with pimavanserin, warranting further study. © 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.

Language: en

Keywords

adult; human; North America; female; male; incidence; Europe; insomnia; suicidal ideation; screening; schizophrenia; anxiety; randomized controlled trial; risk assessment; treatment outcome; outpatient; major clinical study; controlled study; questionnaire; priority journal; double blind procedure; hallucination; headache; phase 3 clinical trial; somnolence; physical examination; delusion; treatment withdrawal; drug safety; placebo; treatment refusal; follow up; drug efficacy; olanzapine; risperidone; drug tolerability; nausea; negative syndrome; drug withdrawal; multicenter study; akathisia; biperiden; side effect; parkinsonism; electrocardiogram; good clinical practice; heart palpitation; aripiprazole; benzatropine; Article; trihexyphenidyl; Clinical Global Impression scale; interrater reliability; Positive and Negative Syndrome Scale; Short Form 36; suspiciousness; telemedicine; asenapine; Abnormal Involuntary Movement Scale; DSM-5; benzatropine mesilate; lurasidone; Calgary Depression Scale; assessment of humans; Barnes Akathisia Scale; adverse event; Columbia suicide severity rating scale; pimavanserin; personal and social performance scale; cariprazine; brexpiprazole; drug attitude inventory; Clinical Global Impression-severity scale; antipsychotic agents; karolinska sleepiness scale; psychogenic visual disturbance; serotonin receptor 5-HT2A; Simpson-Angus Scale; treatment nonresponse