SAN FRANCISCO — Adjunctive pimavanserin appeared safe, effective and tolerable among patients with major depression disorder who responded inadequately to SSRI or SNRI therapy, according to results from a phase 2 study presented at the APA Annual Meeting.
“There is a tremendous need to develop new treatments for patients who suffer from depression and do not benefit from standard antidepressant therapies,” Maurizio Fava, MD, director of the division of clinical research of Massachusetts General Hospital Research Institute and executive vice chair of the hospital’s department of psychiatry, told Healio Psychiatry.
In a phase 2 double-blind, placebo-controlled study, the researchers examined the efficacy and safety of adjunctive pimavanserin, an atypical antipsychotic, among adults with MDD.
Fava and colleagues randomly assigned 207 adults (mean age, 46.2 years; 72.9% women) with inadequate response to ongoing antidepressant therapy to pimavanserin 34 mg/day or placebo added to their SSRI/SNRI treatment. The researchers used a sequential parallel comparison design, which consisted of two 5-week stages. Participants who did not response to placebo in the first stage were randomly reassigned to pimavanserin or placebo for the second stage. Then, the researchers evaluated the weighted average of stage 1 and stage 2 total scores of the Hamilton Depression Rating Scale (HAMD-17), which served as the primary efficacy measure.
During the first stage, 52 participants received pimavanserin and 155 received placebo.
The investigators found that pimavanserin reduced the weighted HAMD-17 total score in both stages compared with placebo (least-square means difference = –1.7; P = .04). Participants in the stage 1 pimavanserin group showed highly significant improvement on the HAMD-17 by week 5 (difference = –4.; P < .001), separating from placebo by the end of the first week (difference = –1.7; P = .04). Results from stage 2 showed no significant separation among stage 1 participants who did not respond to placebo.
Fava and colleagues found greater improvement with pimavanserin compared with placebo on the Sheehan Disability Scale (difference = –0.8; P = .004). They also observed positive results relative to responder rate (P = .007), Massachusetts General Hospital Sexual Functioning Index (P < .001), and Karolinska Sleepiness Scale for daytime sleepiness (P = .02) among those who received add-on pimavanserin vs. placebo, according to the poster.
Adjunctive pimavanserin was generally well-tolerated and appeared safe, with low discontinuation rates due to adverse events compared with placebo (1.2% vs. 3.2%).
“This study indicates that pimavanserin, a molecule with a relatively unique pharmacological activity as a selective inverse agonist of the serotonin 5-HT2A receptor, may show antidepressant activity and could be a novel adjunctive treatment for patients who do not adequately respond to standard antidepressant therapy with either an SSRI or SNRI,” Fava told Healio Psychiatry.
ACADIA plans to confirm these results in phase 3 studies beginning this year. – Savannah Demko
Fava M, et al. CLARITY: A phase 2 double-blind, placebo- controlled study to evaluate the efficacy and safety of adjunctive pimavanserin in major depressive disorder. Presented at: APA Annual Meeting; May 18-23, 2019; San Francisco.
Disclosures: Fava reports research funding from Acadia Pharmaceuticals at MGH and consulting on behalf of MGH to Acadia Pharmaceuticals.