Low Persistence of Antipsychotic Therapy in Parkinson Disease – Intolerance, Ineffectiveness, or Inertia?

Abstract

Background: Antipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and persistence of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the persistence to overall and initial antipsychotic therapy in individuals with PD and (2) determine whether persistence varies by drug dopamine receptor blocking activity.Methods: We conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001-2019. Adults age 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least six months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month persistence to overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation.Results: Overall, 38.6% of 3,566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within six months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for medications with dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40-2.20] for quetiapine, 2.15 [1.61-2.86] for aripiprazole, 2.12 [1.66-2.72] for risperidone, and 2.07 1.60-2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated greater dopamine-receptor blocking activity medication use – adjusted hazard ratios 1.57 (95% confidence interval 1.28-1.94), 1.88 (1.43-2.46), 2.00 (1.59-2.52) and 2.03 (1.60-2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses.Conclusions: Over one-third of individuals with PD stop antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population.