{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:11:05Z","timestamp":1782738665748,"version":"3.54.5"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pimavanserin, a selective 5-HT<jats:sub>2A<\/jats:sub> inverse agonist\/antagonist, is the only treatment approved by the US Food and Drug Administration for hallucinations and delusions associated with Parkinson's disease (PD) psychosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We aimed to evaluate motor- and cognition-related safety in pimavanserin-treated patients with PD psychosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This analysis included patients with PD psychosis treated with pimavanserin 34 mg from a pooled analysis of 3 randomized, double-blind, placebo-controlled, 6-week studies [NCT00477672 (study ACP-103-012), NCT00658567 (study ACP-103-014), and NCT01174004 (study ACP-103-020)] and a subgroup of patients with PD dementia with psychosis from HARMONY (NCT03325556), a randomized discontinuation study that included a 12-week open-label period followed by a randomized double-blind period of up to 26 weeks. Motor- and cognition-related safety were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The pooled analysis included 433 randomized patients (pimavanserin, 202; placebo, 231). Least squares mean (standard error [SE]) change from baseline to week 6 Unified Parkinson's Disease Rating Scale (UPDRS) II + III score was similar for pimavanserin [\u22122.4 (0.69)] and placebo [\u22122.3 (0.60)] (95% Confidence Interval [CI]:\u22121.9, 1.6). The change from baseline to week 6 for UPDRS II and UPDRS III scores was similar between groups. In the HARMONY open-label period, 49 patients with PD dementia with psychosis were treated with pimavanserin 34 mg, 36 of whom were randomized in the double-blind period (pimavanserin, 16; placebo, 20). In the open-label period, the mean (SE) change from baseline to week 12 (<jats:italic>n<\/jats:italic> = 39) Extra-Pyramidal Symptom Rating Scale (ESRS-A) score was \u22121.7 (0.74); in the double-blind period, the results were generally comparable between the pimavanserin and placebo arms. The change from baseline in Mini-Mental State Examination (MMSE) score was also comparable between pimavanserin- and placebo-treated patients in HARMONY [open-label (<jats:italic>n<\/jats:italic> = 37): mean (SE) change from baseline to week 12, 0.3 (0.66)]. Rates of motor- and cognition-related adverse events were similar between pimavanserin and placebo in both analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pimavanserin 34 mg was well tolerated and did not yield a negative impact on motor- or cognition-related function in patients with PD psychosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.919778","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T14:26:15Z","timestamp":1664979975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Motor- and cognition-related safety of pimavanserin in patients with Parkinson's disease 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