135 Use of Pimavanserin in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs)

Study ObjectivePsychosis is common in Parkinson’s disease (PD) and increases in both frequency and severity with disease duration. It is associated withincreased morbidity/mortality, complicates management of motor symptoms and often leads to long-term care placement. Pimavanserin is a selective 5-HT2A inverse agonist/antagonist approved in the U.S. for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Depression affects up to 60% ofPD patients and is frequently treated with SSRIs/SNRIs. Data suggest the potential for a synergistic effect between 5 HT2A receptor inverse agonist/antagonists and SSRIs insubjects with neuropsychiatric disease. This post-hoc analysis evaluated a subgroup of subjects from the pimavanserin clinical program to determine if there was any difference in antipsychotic response between the subjects receiving pimavanserin in combination with an SSRI versus those without.MethodA pooled analysis of two 6-week randomized, double-blind, placebo-controlled Phase 3 studies was conducted to assess the overall treatment effect of pimavanserin34 mg. The outside-North America region in Study 012 was not included due to a difference in methodology in the assessment of the primary endpoint. Subjects in both the 020 and 012 studies received 42 days of treatment. The mITT population included 268 subjects; with 135 in the pimavanserin group. The full safety dataset included 433 subjects; with 202 in the pimavanserin group. Of the 268 subjects in the mITT population, a total of 77 received concomitant therapy with SSRIs. A subgroup analysis was conducted to determine if there was any difference in response among the subjects receiving concomitant SSRIs.ResultsOverall, pimavanserin demonstrated a -6.21-point improvement in psychosis at Week 6 as measured by the PD-adapted Scale for Assessment of Positive Symptoms (primary change from baseline analysis [MMRM]). The treatment difference was 2.87 points over placebo (p