Pimavanserin is an oral serotonin 5HT2A inverse agonist and antagonist approved for the treatment of Parkinson’s disease psychosis. A phase 3, double-blind, randomized, placebo-controlled discontinuation trial examined efficacy of pimavanserin in patients with psychosis related to various dementia diagnoses: Alzheimer’s disease (66.3%), Parkinson’s disease dementia (15.1%), dementia with Lewy bodies (7.1%), frontotemporal dementia (1.8%), and vascular dementia (9.7%). The 12-week open-label phase of the study (n=351) identified patients who were responsive to pimavanserin (34 mg or 20 mg/day) based on Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions (SAPS–H+D) and Clinical Global Impression–Improvement scores (n=217). These patients were randomized 1:1 to pimavanserin or placebo in the double-blind phase of the study for up to 26 weeks. The primary endpoint was a relapse to psychosis. Among patients assessed at week 12 of the open-label phase, there was a 75.2% mean reduction from baseline in the SAPS–H+D score. The mean duration of exposure in the double-blind phase was 17.7 weeks with pimavanserin and 10.9 weeks with placebo. A pre-specified interim analysis stopped the trial due to efficacy. At that point, frequency of relapse was 13% in the pimavanserin group and 28% in the placebo group (hazard ratio [HR]: 0.35; 95% confidence interval [CI]: 0.17-0.73; p=0.005). The most common adverse events that occurred more frequently with pimavanserin than with placebo were headache, constipation, and urinary tract infection. Although this trial was not designed or sufficiently powered to detect antipsychotic effects in individual subtypes of dementia, pimavanserin effectively reduced frequency of psychosis relapse in broadly-defined dementia-related psychosis. Longer trials with larger numbers of patients are needed for determining the effects of pimavanserin in dementia-related psychosis.
Tariot PN et al. N Engl J Med 2021;385(4):309-19. Abstract
For more informationy: