The antipsychotic effect of pimavanserin may be greater in patients with Parkinson disease (PD) psychosis who are cognitively impaired vs those who have no cognitive impairment, and the treatment may be more efficacious when combined with cognitive-enhancing medication, according to a study published in Movement Disorders.

Data from a 6-week randomized double-blind placebo-controlled phase 3 trial of pimavanserin conducted on 185 adults with PD psychosis were analyzed. Participants were stratified as cognitively impaired (n=50) vs cognitively unimpaired (n=135), and were further assessed based on concomitant cognitive-enhancing medication use (n=69) vs nonuse (n=116). Changes in scores on the Scale for Assessment of Positive Symptoms adapted for PD (SAPS-PD) were the study’s primary outcome.

The least squares mean change in SAPS-PD scores at day 43 were greater in study participants treated with pimavanserin vs placebo (cognitively-impaired patients: -6.62 vs -0.91, respectively; P =.002; cognitively unimpaired group: -5.50 vs -3.23, respectively; P =.046). The least squares mean change in SAPS-PD scores at day 43 from baseline was greater in patients taking concomitant cognitive-enhancing medication use vs no use (concomitant use: pimavanserin, -6.04; placebo, -2.18; P =.012; nonuse: pimavanserin, -5.66; placebo, -3.15; P =.041). Pimavanserin caused more adverse events compared with placebo in patients with cognitive impairment (9.4% vs 8.7%, respectively) and without cognitive impairment (9.9% vs 1.4%, respectively), but was similarly tolerated in both groups. Adverse event rates were comparable between concomitant cognitive-enhancing medications use vs nonuse; however, serious adverse events leading to discontinuation were significantly higher in patients taking cholinesterase inhibitors.

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Study limitations include the exclusion of patients with more significant cognitive impairment, assessment of cognitive impairment based on the Mini-Mental State Examination score, which is relatively insensitive for diagnosing mild impairment, and the short study period. “[W]e provide preliminary evidence that the effect of [pimavanserin] may be robust in cognitively impaired patients [with PD] and raise the possibility that concomitant use of cognitive-enhancing medication may provide additional antipsychotic benefit,” concluded the study authors.

Multiple authors declared affiliations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.


Espay AJ, Guskey MT, Norton JC, et al. Pimavanserin for Parkinson’s disease psychosis: effects stratified by baseline cognition and use of cognitive-enhancing medications [published online November 2, 2018]. Mov Disord. doi:10.1002/mds.27488