Mortality Among Parkinson's Disease Patients Treated With Pimavanserin or Atypical Antipsychotics: An Observational Study in Medicare Beneficiaries

Am J Psychiatry. 2022 Aug;179(8):553-561. doi: 10.1176/appi.ajp.21090876. Epub 2022 Jun 15.


Objective: Pimavanserin, a serotonin 5-HT2 antagonist, is indicated for treatment of hallucinations and delusions associated with Parkinson's disease psychosis. In premarketing trials in patients with Parkinson's disease psychosis, 11% of patients died during open-label pimavanserin treatment. Antipsychotics, which are used off-label in Parkinson's disease psychosis, increase mortality in dementia patients. The authors compared mortality with pimavanserin and atypical antipsychotics in a large database.

Methods: This was a retrospective new-user cohort study of Medicare beneficiaries with Parkinson's disease initiating pimavanserin (N=3,227) or atypical antipsychotics (N=18,442) from April 2016 to March 2019. All-cause mortality hazard ratios and 95% confidence intervals were estimated for pimavanserin compared with atypical antipsychotics, using segmented proportional hazards regression over 1-180 and 181+ days of treatment. Potential confounding was addressed through inverse probability of treatment weighting (IPTW).

Results: Pimavanserin users had a mean age of approximately 78 years, and 45% were female. Before IPTW, some comorbidities were more prevalent in atypical antipsychotic users; after IPTW, comorbidities were well balanced between groups. In the first 180 days of treatment, mortality was approximately 35% lower with pimavanserin than with atypical antipsychotics (hazard ratio=0.65, 95% CI=0.53, 0.79), with approximately one excess death per 30 atypical antipsychotic-treated patients; however, during treatment beyond 180 days, there was no additional mortality advantage with pimavanserin (hazard ratio=1.05, 95% CI=0.82, 1.33). Pimavanserin showed no mortality advantage in nursing home patients.

Conclusions: Pimavanserin use was associated with lower mortality than atypical antipsychotic use during the first 180 days of treatment, but only in community-dwelling patients, not nursing home residents.

Keywords: Antipsychotics; Epidemiology; Neurology.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Antipsychotic Agents* / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Medicare
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • Piperidines
  • Psychotic Disorders* / complications
  • Psychotic Disorders* / drug therapy
  • Retrospective Studies
  • United States
  • Urea / analogs & derivatives


  • Antipsychotic Agents
  • Piperidines
  • Urea
  • pimavanserin