Pimavanserin for psychosis in patients with Parkinson’s disease

Pimavanserin is a potent 5-HT2A inverse agonist and 5-HT2C inverse agonist, with 5-fold greater affinity for the 5-HT2A receptor.1 Although antagonists block agonist actions at the receptor site, inverse agonists reduce the level of baseline constitutive activity seen in many G protein-coupled receptors. This medication is FDA approved for treating hallucinations and delusions associated with Parkinson’s disease (PD) psychosis (Table 1).1 In the pivotal 6-week clinical trial, pimavanserin significantly reduced positive symptoms seen in PD patients with psychosis (effect size = 0.50), with no evident impairment of motor function.2 Only 2 adverse effects occurred in ≥5% of pimavanserintreated patients and at ≥2 times the rate of placebo: peripheral edema (7% vs 3% for placebo) and confusion (6% vs 3% for placebo). There was a mean increase in the QTc of 7.3 milliseconds compared with placebo in the pivotal phase III study.