Pimavanserin and clozapine are superior to other atypical antipsychotics in treating Parkinson’s disease psychosis

Ismaeel Yunusa, PharmD, PhD

A recently published systematic review and network meta-analysis of atypical antipsychotics for the treatment of patients with Parkinson’s disease psychosis (PDP) found that pimavanserin (Nuplazid; Acadia) and clozapine had no effect on motor function. It has been shown to best improve symptoms. The researchers also suggested that quetiapine should be avoided in PDP patients with cognitive decline.

Nineteen independent studies involving a total of 1,242 PDP patients were used to compare the efficacy of each agent using the Clinical Global Impression Scale of Severity (GCI-S). After collecting data on pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone, the atypical antipsychotic pimavanserin (standardized mean difference) [SMD]–4.81; 95% CI, –5.39 to –4.24) and clozapine (SMD, –4.25; 95% CI, –5.24 to –3.26) showed significant ability to improve symptoms compared to placebo .

Led by Ismaeel Yunusa, PharmD, PhD, Assistant Professor, Department of Clinical Pharmacy, University of South Carolina, pimavanserin continues to significantly improve psychotic symptoms, as indicated by scores on the Parkinson’s Disease Psychosis/Hallucinations and Delusions Positive Symptom Rating Scale. Results of the study using the Unified Parkinson’s Disease Rating Scale showed that clozapine (SMD, –0.69; 95% CI, –1.35 to –0.02), pimavanserin (SMD, –0.01; 95% CI, –0.56 to 0.53), and quetiapine ( SMD, 0.00; 95% CI, –0.68 to 0.69) did not impair motor function.

SUCRA suggested that clozapine (78%) was most likely safe in avoiding impairment of motor function. Cognitive decline as assessed by the Mini-Mental State Examination was associated with quetiapine treatment (SMD, 0.60; 95% CI, 0.07-1.14). Although not significant, olanzapine (SMD, 0.28; 95% CI, -0.03 to 0.60) and ziprasidone (SMD, 0.18; 95% CI, -0.95 to 1.31) also showed higher cognitive deterioration compared to placebo. Reported MMSE score.

Quetiapine (SMD, 0.77; 95% CI, 0.12-1.42) significantly worsened cognitive function when compared with clozapine. In particular, clozapine was most likely to be safe in avoiding superficial cognitive impairment under the Cumulative Ranking Curve (SUCRA). It is the most used off-label AAP for the treatment of PDP, despite the lack of strong evidence to support a significant risk of certain AEs.Based on the findings from the current study, quetiapine is associated with excessive sleepiness and cognitive It significantly impairs performance and may need to be avoided in PD patients with sleep disturbances and significant cognitive decline.”

They continued, “Risperidone is the most acceptable AAP in terms of all-cause discontinuation and is ideal for patients with PDP, given the lack of supporting evidence of its effectiveness in improving psychosis and motor safety.” It was suggested that it was not an option.”

read more: Greater burden of care identified in caregivers of patients with advanced Parkinson’s disease

Compared with placebo, clozapine (OR, 4.64; 95% CI, 1.53-14.01) and quetiapine (OR, 2.38; 95% CI, 0.99-5.73) were associated with higher rates of somnolence. When compared with each other, pimavanserin had numerically lower odds of somnolence than clozapine (OR, 0.23; 95% CI, 0.04-1.53) and quetiapine (OR, 0.46; 95% CI, 0.08-2.63). Olanzapine was most likely safe (91.8%) in preventing somnolence in SUCRA.

With respect to discontinuations due to adverse events (AEs), the SUCRA rankings suggested that risperidone (73.8%) was the most acceptable, followed by placebo (71.4%) based on discontinuations due to any AE. A cluster ranking of the five antipsychotics for CGI-S (efficacy) and UPDRS (safety) found pimavanserin and clozapine to be the most effective and safest, and pimavanserin to be most likely to be effective. Olanzapine was the least effective, and placebo fell into the same cluster.

reference
1. Yunusa I, Rashid N, Rajagopalan K, et al. Comparing the efficacy, safety, and acceptability of pimavanserin and other atypical antipsychotics for psychosis in Parkinson’s disease: a systematic review and network meta-analysis. J Geriatr Psychiatry Neurol. Published online January 31, 2023. doi:10.1177/08919887231154933