Pimavanserin Effective for Depression in Parkinson Disease, Major Depressive Disorder

Pimavanserin, a selective 5-HT_2A receptor antagonist/inverse agonist, was reported to successfully treat depression among patients with Parkinson disease (PD) and major depressive disorder (MDD). These findings, from a pooled analysis of 2 trials, were presented during Psych Congress 2020 Virtual Experience, held online from September 11 to 13, 2020.

In an 8-week, open-label, single arm study, patients (N=47) with PD and depressive symptoms, as defined by a Hamilton Depression Rating Scale (HAMD-17) score ³15, were randomly assigned to receive pimavanserin 34 mg alone or in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Participants were assessed by the HAMD-17, Clinical Global Impression-Severity scale (CGI-S), CGI-Improvement scale (CGI-I), EuroQol-5 Dimensions-5 Levels Proxy (EQ-5D-5L), and the Movement Disorder Society Unified PD Rating Scale Part III (MDS-UPDRS III).

In a 2-stage, sequential, parallel comparison study, patients (N=155) with MDD, as defined by a CGI-S score ³4 and a Montgomery-Åsberg Depression Rating Scale score >20, who were being treated with an SSRI or SNRI were randomly assigned in a 3:1 ratio to receive pimavanserin 34 mg in addition to their current medication or a placebo for 5 weeks. At week 5, placebo recipients and nonresponders were reassigned in a 1:1 ratio to receive treatment or placebo for 5 additional weeks. Patients were again assessed using the HAMD-17, CGI-S, CGI-I, and the Sheehan Disability Scale (SDS).

At baseline, patients with PD had symptoms of moderate depression (HAMD-17, 19.2; standard deviation [SD], 3.1). Clinical improvement in their depression was observed as early as 2 weeks following treatment initiation. Throughout the study duration patients in the monotherapy and dual therapy groups showed similar responses. At 8 weeks, the participants exhibited an overall improvement (least squared difference [LS], -10.8; SD, 0.63; 95% CI, -12.0 to -9.5; P <.0001), and 44.4% of participants reached clinical remission of their depression symptoms. Patients exhibited significant improvement in their CGI-S (P <.0001), EQ-5D-5L (P =.0068), and MDS-UPDRS III (P =.007) scores.

At baseline, patients with MDD had HAMD-17 scores of 22.8 (SD, 4.6) among the treatment group and 22.0 (SD, 4.2) among the placebo group. Patients in the treatment group had greater decreases in HAMD-17 scores (LS, -11.5; SD, 0.94 vs LS, -7.5; SD, 0.55; P =.0003). Similar to the observation among patients with PD, after 5 weeks of treatment 23.5% of the treatment group reached clinical remission. Patients in the treatment group reported significantly greater improvement in CGI-S (P =.0001), CGI-I (P =.001), and function (P =.0036) scores.

A limitation of this study was the low sample sizes, especially among patients with PD. Further studies with larger sample sizes are needed to confirm these findings.

The study authors concluded that pimavanserin was well tolerated, did not incur adverse effects with regard to motor skills or function, and significantly improved symptoms of depression among patients with PD and MDD. The similar response of participants in the open-label and the placebo-controlled studies was a strong indicator that pimavanserin had the potential to treat symptoms of depression.

Disclosure: An author of the study declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Reference

DeKarske D, Jacobi L, Nunez R, et al. Depression in Parkinson’s disease: investigation of pimavanserin, a selective 5-HT2A receptor antagonist/inverse agonist. Presented at: Psych Congress 2020 Virtual Experience; September 10-13, 2020. Poster 131.