Pimavanserin for Treatment of Comorbid Depression in Patients With Parkinson’s Disease
Michael Guskey1, Gustavo Alva2, Jason Aldred3, Bruce Coate4, Victor Abler5, Marc Cantillon7, James Norton5, Daryl DeKarske6
1Medical Affairs, ACADIA Pharmaceuticals, 2Neuroscience, University of California at Riverside, 3Selkirk Neurology & Inland Northwest Research, 4Biostatistics, 5Medical Affairs, 6Regulatory Affairs, ACADIA Pharmaceuticals Inc., 7Psychiatry, Robert Wood Johnson Medical School
Objective:
To assess the utility of pimavanserin (PIM) for treatment of adults with Parkinson’s disease (PD) and depressive symptoms.
Background:
Depression occurs in ~50% of PD patients, increases in severity as the disease progresses, and is associated with increased morbidity.
Design/Methods:
This 8-week, open-label, single-arm study evaluated the safety and efficacy of PIM as an adjunct to SSRI or SNRI treatment or as monotherapy in adults with PD and depressive symptoms (baseline Hamilton Depression Scale 17-item version [HAMD-17] total score ≥15). The primary endpoint was change from Baseline to Week 8 in the HAMD-17.
Results:
Of the 47 patients in the safety population, 51.1% were male, and average age was 69.3 years, with 26 patients receiving PIM adjunctive therapy with SSRI/SNRI and 21 receiving PIM monotherapy. Patients in the efficacy population (N=45) had a Baseline mean(SD) HAMD-17 of 19.2(3.1). Change from Baseline to Week 8 (least squares mean(SE) in the HAMD-17 was –10.8(0.6) (95% CI; –12.0,–9.5; P<0.0001), with significant improvement seen as early as Week 2 (–7.3[0.9]; P<0.0001). HAMD-17 changes from Baseline to Week 8 were similar for adjunctive treatment and monotherapy: –10.2(0.8) and –11.2(1.0), respectively. Treatment responses (≥50% improvement on the HAMD-17) were seen in 60% of PIM-treated patients at Week 8, and 44.4% reached remission (HAMD-17 ≤7). Forty patients (85.1%) completed the study, and 7 (14.9%) terminated early (adverse event, n=3; protocol violation, n=2; lost to follow-up/other, n=1 each). Twenty-one patients reported adverse events, the most common being falls (8.5%), nausea (6.4%), diarrhea (4.3%), edema (4.3%), skin abrasion (4.3%), and urinary tract infection (4.3%).
Conclusions:
These data suggest that PIM treatment was associated with improvement of depressive symptoms as measured by HAMD-17  in patients with PD and well tolerated. Additional placebo-controlled data are needed to determine fully the efficacy of PIM in patients with comorbid PD and depression.