Impact of current antipsychotic medications on comparative mortality and adverse events in people with PD psychosis (PDP)

Abstract

Over 50% of people with PD will develop psychosis during the course of their disease. The symptoms of hallucinations and delusions are distressing and challenging for the individuals and their caregivers. PDP is commonly linked to institutionalization and increased risk of mortality. Atypical antipsychotics are frequently prescribed to address PDP despite limited evidence to support their efficacy and concerns about their safety in this generally elderly population. Limitations in the scope and design of published trials prevent a clear interpretation of mortality risk and adverse events, particularly for treatment periods exceeding 6 weeks. A post-hoc analysis was performed on data from 423 participants with PDP in an ongoing multicenter, open-label extension study of pimavanserin. Safety assessments were conducted at two weeks, one, three, six, nine and twelve months, and every six months thereafter, including comprehensive recording of adverse events and mortality. Data were analyzed according to whether participants received a concurrent antipsychotic drug (APD) versus those receiving pimavanserin alone. Participants who received a concurrent APD were significantly more likely to experience SAEs, including cognitive decline and infection. Increases in sedation, cardiovascular and stroke-related events, and thromboembolic events were also observed. In addition, there was a significant increase in mortality with concurrent APD use. These results highlight safety concerns with the use of current antipsychotics in PD, which appear similar to those reported previously in people with AD, and underscore the importance of identifying safer therapies for PDP that provide an effective alternative to current antipsychotic medications.