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

Abstract

Background: Many patients with Parkinson's disease (PD) experience depression.

Objective: Evaluate pimavanserin treatment for depression in patients with PD.

Methods: Pimavanserin 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.

Results: Efficacy 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.

Conclusion: In 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.

Keywords: Parkinson’s disease; adjunctive therapy; dementia; depression; monotherapy; pimavanserin.

Fig. 1

Study design. PD, Parkinson’s disease; SNRI, serotonin/norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

Fig. 2

Change from baseline in HAMD-17 (A) total score over 8 weeks and (B) individual item scores at week 8 in all patients included in efficacy analyses. BL, baseline; HAMD-17, Hamilton Depression Scale–17-item version; LS, least squares; SE, standard error.

Fig. 3

Change in HAMD-17 from baseline by treatment with pimavanserin as (A) monotherapy and (B) adjunctive therapy. BL, baseline; HAMD-17, Hamilton Depression Scale–17-item version; LS, least squares; SE, standard error.

Fig. 4

Impact on (A) CGI-S and (B) CGI-I scores over 8 weeks in all patients included in efficacy analyses. BL, baseline; CGI-I, Clinical Global Impression–Improvement; CGI-S, Clinical Global Impression–Severity; LS, least squares; SE, standard error.

Fig. 5

Change from baseline to week 8 in (A) SCOPA-GS, (B) SCOPA-NS, and (C) SCOPA-DS in all patients included in efficacy analyses. BL, baseline; LS, least squares; SCOPA-DS, Scale for Outcomes in Parkinson’s Disease–daytime sleepiness; SCOPA-GS, Scale for Outcomes in Parkinson’s Disease–global sleep; SCOPA-NS, Scale for Outcomes in Parkinson’s Disease–nighttime sleep; SE, standard error.

Fig. 6

Change from baseline to week 8 in EQ-5D-5L-VAS in all patients included in efficacy analyses. BL, baseline; EQ-5D-5L-VAS, EuroQol-5 Dimensions-5 Levels version 1 visual analog scale; LS, least squares; SE, standard error.

Fig. 7

Change from baseline to week 8 in MDS-UPDRS Part III in all patients included in safety analysis. BL, baseline; LS, least squares; MDS-UPDRS Part III, Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III; SE, standard error.