CHICAGO — The investigational agent pimavanserin appears to lessen psychosis in patients with Parkinson's disease without worsening motor function, according to a multicenter randomized phase II trial.
Pimavanserin is a potent, active 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor antagonist, said Dr. Stephen Revell of Acadia Pharmaceuticals Inc., which sponsored the study. However, it lacks the dopamine receptor (D2) and histamine receptor (H1) binding linked to the adverse effects of other antipsychotics.
Patients in the study had PD and psychosis and were given either pimavanserin (n = 29) or placebo (n = 31) on an outpatient basis for 28 days, starting at 20 mg daily on day 1, with dose escalations to 40 mg and 60 mg on day 8 and 15, respectively, depending on individual clinical response.
Pimavanserin patients demonstrated a 40% improvement in the Scale for the Assessment of Positive Symptoms (SAPS) combination score for hallucination and delusion, compared with an 11% improvement for placebo patients (P = .05), Dr. Revell reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.
Statistically significant improvements also were seen for patients treated with pimavanserin on the mentation, behavior, and mood part of the Unified Parkinson's Disease Rating Scale (UPDRS) (P = .05).
There was no clinically significant difference between patients treated with placebo vs. pimavanserin in the absolute mean change from baseline to day 28 in UPDRS motor scores (-3.05 vs. −1.24, P = .303) or activities of daily living scores (-2.51 vs. −0.70, P = .112).
No differences in the groups were seen on the Schwab and England Activities of Daily Living Scale part of the UPDRS, the Clinical Global Impression Scale severity of illness subscale, or the Epworth Sleepiness Scale daytime sleepiness subscale. The most common adverse events were somnolence, edema, and increased blood urea.
In a second poster, pimavanserin was well tolerated and did not worsen Parkinsonism symptoms in 39 patients (mean age 72) with PD and psychosis at doses up to 60 mg/day for up to 42 months (mean 14 months). Somnolence, fatigue, or dizziness were uncommon, said Dr. Roger Mills, also of Acadia, who led the industry-sponsored, open-label extension safety study.
A case of rhabdomyolysis was the only serious adverse event.
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