Clinical Implications of Pimavanserin Association With Mortality in Parkinson Disease Psychosis

It has been suggested that use of pimavanserin for the treatment of Parkinson disease (PD) psychosis symptoms is associated with higher mortality rates. The FDA found these rates unsimilar to that seen with other atypical antipsychotics, and both carry a black-box warning as a result. This has been controversial, in part because a single-center retrospective study (n=636) showed no difference in unadjusted mortality rates with vs without pimavanserin use in PD. 

However, a new retrospective cohort study (n=20,398) using data from records of people living in Medicare-certified long-term care facilities, has been published in Neurology. This new study showed people with PD treated with pimavanserin had adjusted mortality rates that were 20%, 28%, and 56% higher at 3, 6, and 12 months, respectively. Notably, people taking pimavanserin were also more likely to be taking atypical antipyschotics concomitantly.

An accompanying editorial by Farwa Ali, MBBS, of the Section of Movement Disorders, Department of Neurology, Mayo Clinic Rochester, explains that the study used propensity scoring to mathematically adjust comparisons of pimavanserin-treated vs nontreated individuals. Such analyses limit the effects of other differences among individuals in the cohort. Measures adjusted for include record-identified race, sex, age, regional location, symptom severity, comorbidities, concomitant medications, and more. Statistical E values were also used to limit the effect of unknown differences. 

Speaking to Practical Neurology, Dr. Ali said, "Although clinically speaking, no method is perfect at controlling for every possible confounder or clinical nuance we see in clinic every day, this is among the best analyses we could have to retrospectively control for possible differences within a cohort." 

Symptoms of psychosis in PD occur more often than not over the course of PD and are among the most distressing for families and patients. Onset of psychosis symptoms is associated with placement in long-term care and skilled nursing facilities.

Dr. Ali noted, "These symptoms are very challenging to manage, and it is important to prioritize and maximize benefits of nonpharmacologic treatment before proceeding to medications. When medications are used, it is important to have a frank discussion of risks and benefits, and follow patients closely, being vigilant for side effects and risks of polypharmacy."  

A limitation of this study is that all individuals were in long-term care, which may mean that these results may not be generalizable to people with PD living outside this setting.