An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson's Disease and Depression.

backgroundMany patients with Parkinson's disease (PD) experience depression.

objectiveEvaluate pimavanserin treatment for depression in patients with PD.

methodsPimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale-17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose.

resultsEfficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was -10.8 (0.63) (95% CI, -12.0 to -9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, -11.2 [0.99]) and adjunctive therapy (week 8,-10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III.

conclusionIn this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.