Pimavanserin for Psychosis in Parkinson’s Disease-Related Disorders: A Retrospective Chart Review

Abstract

Background Psychosis is common in Parkinson’s disease-related disorders and is associated with significant morbidity. Pimavanserin is a newly approved treatment for Parkinson’s disease psychosis, but real-world experience with pimavanserin has been limited by small sample sizes and limited assessment of longitudinal outcomes. Objective The aim was to summarize the clinical experience with pimavanserin in a large cohort of patients with Parkinson’s disease-related psychosis. Methods We conducted a retrospective chart review of patients who were prescribed pimavanserin at Vanderbilt University Medical Center in the southeast United States between May 2016 and July 2018. We used Chi-squared analyses to compare efficacy and tolerability of pimavanserin, considering patient diagnosis, presence of dementia or delusions, use of deep brain stimulation, and prior antipsychotic failure. Additionally, we compared the clinical characteristics of patients who started treatment and those who did not, to evaluate safety outcomes. Results We identified 107 patients prescribed pimavanserin, and 91 began treatment. Clinical improvement in psychosis was documented in 76% of patients (69/91) and did not differ based on diagnosis, presence of dementia, delusions, use of deep brain stimulation, or prior antipsychotic failure. Adverse effects were reported in 20 patients (22%), the most common of which was worsening gait instability (5/91, 5%). Side effects led to cessation of therapy in 11 of the 91 patients (12%). At current follow-up, 50 (65%) of 77 living patients remain on treatment, with a mean treatment duration of 14.6 months. Although most of these patients are on pimavanserin monotherapy (33/50, 66%), 17 patients (34%) are on a dual-antipsychotic regimen. The living patients no longer on treatment stopped pimavanserin primarily because of a lack of perceived benefit (11/77, 14%), side effects (9/77, 12%), or both (1/77, 1%), though six patients (8%) stopped for reasons unrelated to medication effects, including the desire to reduce overall medication burden and negative media reporting on pimavanserin. Conclusions Study results emphasize long-term efficacy and tolerability of pimavanserin for psychosis in Parkinson’s disease-related disorders, including patients with dementia, delusions, deep brain stimulation use, or prior antipsychotic failure.

Pimavanserin Treatment for Parkinson’s Disease Psychosis in Clinical Practice

“…In addition, administering pimavanserin in the evening successfully averted daytime sedation. It is worth noting that sedation was not among the most frequent AEs reported in the pivotal phase 3 trial of pimavanserin (i.e., AEs occurring in ≥5% of patients in either treatment group) [ 38 ]; however, a medical center chart review of patients who received pimavanserin reported that “somnolence” was the second most common AE, occurring in 3 patients (3%) [ 43 ]. Among the other notable features in this case series, a nonpharmacological approach was applied that included alleviating life stresses and improving environmental factors such as lighting to reduce the risk of hallucinations; however, this approach must be balanced against the potentially more effective modality of antipsychotic therapy.…”

Systematic Review on Parkinson’s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson’s Symptoms

“…In a randomized trial and double-blind study, the efficacy of risperidone and clozapine in decreasing the symptoms of psychosis was similar while risperidone can aggravate extrapyramidal symptoms [ 51 ]. In addition, all 172 PD subjects in a retrospective study who were receiving an average daily dose of 1.5 mg risperidone had experienced aggravation of extrapyramidal symptoms [ 86 ].…”

“…Although pimavanserin was generally well-tolerated by many patients in several studies, some adverse reactions were reported. The most common adverse reactions reported for pimavanserin included confusional state, peripheral edema, and hallucinations [ 9 , 86 , 99 ]. Furthermore, QT-interval prolongation can be induced by pimavanserin and it may or may not cause serious cardiac outcomes [ 9 , 99 ].…”

“…Thus, it is not recommended for patients with pre-existing irregular heart rhythms or QT prolongation. Other problems include falls, instability, confusion, and edema [ 9 , 86 , 99 ]. Pimavanserin’s safety is unknown in pregnant and lactating women [ 9 ].…”

“…Moreover, some studies reported that pimavanserin may increase the risk of mortality in patients. Meanwhile, some studies claimed that increase mortality in pimavanserin is due to individuals requiring these medications having greater disease severity and are at higher risk of complications and death [ 86 ].…”