Pimavanserin is effective in patients diagnosed with major depressive disorder (MDD) and is associated with few side effects, according to a recent randomized double-blind, placebo-controlled study published in the Journal of Clinical Psychiatry.
The investigators evaluated the efficacy and safety of adjunctive pimavanserin in patients with MDD and inadequate responses to antidepressant therapy in a study conducted from December 2016 to October 2018. The secondary goals of the study were to evaluate the side effects of pimavanserin. The patient population (n=207) consisted of adults at least 18 years old with a body mass index from 19 to 35 kg/m2 and a history of inadequate response to 1 or 2 antidepressants. The study quantified effects on disability, clinician’s global assessment, patient-reported quality of life, perception of treatment, sleepiness, sexual functioning, impulsivity, and irritability.
Following an 8- to 21-day screening period, there was a 10-week double-blind treatment period and a 30-day follow-up period. The treatment period consisted of 2 stages. In the first stage, a 3:1 ratio of placebo to treatment was established. Treatment consisted of adding pimavanserin to the patient’s current antidepressant medications. At the end of 5 weeks, placebo nonresponders were re-randomly assigned to placebo or pimavanserin at a 1:1 ratio for an additional 5 weeks, the second stage. Statistical differences between treatment and placebo were evaluated using least-square means after accounting for variation in relevant covariates. The effect size was quantified with Cohen d.
Pimavanserin treatment significantly lowered 17-item Hamilton Depression Rating Scale (HDRS-17) scores (effect size=.626, P =.0003), and Sheehan Disability Scale (SDS) scores at the end of stage 1 (effect size=.498, P =.0036). The differences between patients on continuous treatment with pimavanserin or placebo at the end of stage 2 were significant for both HDRS-17 (effect size=.497, P =.0076) and SDS (effect size=.469, P =.0094). By the end of stage 1, treatment-related adverse events occurred in 27.1% and 48.1% of placebo and treatment patients, respectively. During stage 2, 3.4% of placebo patients and 13.8% of treated patients experienced adverse events. The most common adverse events in the treatment group were dry mouth, nausea, and headache, all at less than 10% frequency.
The limitations of the study include the relatively short length of the treatment time and the small sample size, particularly for stage 2.
Researchers conclude that pimavanserin treatment consistently outperformed the placebo treatment for 10 weeks in patients diagnosed with MDD, noting that “Pimavanserin demonstrated robust and clinically meaningful efficacy in MDD patients with inadequate response to antidepressant therapy.”
Disclosure: Several study authors report affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Fava M, Dirks B, Freeman MP, et al. A phase 2, randomized double-blind, placebo-controlled study of adjunctive pimavanserin in patients with major depressive disorder and an inadequate response to therapy (CLARITY) [published online September 24, 2019]. J Clin Psychiatry. doi: 10.4088/JCP.19m12928