Pimavanserin is an atypical antipsychotic, which is meant to bind to the serotonin receptor 5-HT2A in the brain and thus avoid exacerbation of motor symptoms seen with older typical antipsychotics (1). Older antipsychotics are generally avoided and relatively contraindicated in PD due to blockade of dopamine receptors (the target of multiple drugs meant to improve motor symptoms). Pimavanserin exploits data that 5-HT2A serotonin receptors are specifically associated with visual hallucinations (2).
Phase II trial participants progressed to an average daily dose of 44.5 mg, and by day 28 revealed no impairment of motor function compared to placebo, nor did the drug cause sedation or hypotension (3). There were significant reductions in both hallucinations and delusions.
Phase III trial data showed an improvement in the quality of sleep and daytime wakefulness during a six-week period with 199 participants. The drug was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease. An open-label extension study presented at the 17th International Congress of Parkinson’s Disease and Movement Disorders reportedly showed that pimavanserin is safe and well-tolerated with long-term use.
Per the FDA press release (4), the most common side effects reported by participants taking Nuplazid were swelling, usually of the ankles, legs, and feet, nausea, and confusion. The FDA points out that “as with other atypical antipsychotic drugs, Nuplazid has a Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs to treat older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis.”
-Bill Stamey, M.D.
