Low continuation 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 continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation 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 aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of 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 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known 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 with greater dopamine-receptor blocking activity medication use – adjusted hazard ratios 1.57 (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 discontinued 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.

Mortality in Patients with Parkinson’s Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study

“…Exposure information was based on pharmacy dispensing and prescription claims and may not reflect actual patient-level use if patients are nonadherent to prescribed treatments. Another limitation is that discontinuation of antipsychotics is common in patients with PD [ 41 ], and although we evaluated mortality over time, the majority of patients had been lost to follow-up by 1 year after treatment initiation, limiting sample sizes in longer periods of follow-up.…”

Long-term outcomes with pimavanserin for psychosis in clinical practice

“…A high discontinuation rate is not specific to pimavanserin. A retrospective cohort study of commercially-insured PD patients treated with antipsychotic medications found that the discontinuation rate after the first prescription was 39%, and after 6 months, the rate was highest for DRBDs and lowest for pimavanserin (23%) [8] . A retrospective chart review study reported a similar discontinuation rate of 36% for pimavanserin and 21% for quetiapine [9] .…”

Clozapine Use in a Movement Disorder Clinic

“…Haloperidol was the most commonly used drug (29%). More recently, a large database review in the United States, spanning 2001–2019, identified 3566 patients with PD treated with antipsychotics, 2452 were on quetiapine, 169 on aripiprazole, 462 on risperidone, and 304 olanzapine 33 . One hundred fifty-three had been treated with pimavanserin, which had become available in June 2016, and only 26 were treated with clozapine.…”

“…More recently, a large database review in the United States, spanning 2001-2019, identified 3566 patients with PD treated with antipsychotics, 2452 were on quetiapine, 169 on aripiprazole, 462 on risperidone, and 304 olanzapine. 33 One hundred fifty-three had been treated with pimavanserin, which had become available in June 2016, and only 26 were treated with clozapine. A review spanning 2016-2019 of electronic medical records at a university hospital, of all patients with idiopathic PD and no primary psychiatric disorders, identified 2994 patients of whom 40 were on pimavanserin, 188 on quetiapine, 74 on both, and 11 taking "clozapine monotherapy or other antipsychotics."…”