Update on the treatment of Parkinson’s disease psychosis: role of pimavanserin

Parkinson’s disease (PD) has a prevalence of nearly 1 million people in the USA, with increasing incidence in the elderly population. Generally, the age of presentation is between 55 and 65 years, with the likelihood of diagnosis increasing as patients reach the age of 80 years or above. Some of the common treatments for PD increase dopamine levels in the brain. Dopaminergic therapy helps to improve motor and non-motor symptoms, but it is not without risks. Dopaminergic therapy can cause confusion, delirium, and psychotic-like behavior. It is recommended that these agents are used cautiously in patients with a history of psychosis due to the risk of exacerbation. It is unclear whether Parkinson’s disease psychosis (PDP) is due to the disease itself, the treatment, or a combination of both, but it is clear that a safe, effective treatment is necessary. Second-generation (atypical) antipsychotics are the current choice of therapy for PDP. All of these agents have a black box warning from the US Food and Drug Administration (FDA) for elevated risk of mortality in elderly patients with dementia-related psychosis. Pimavanserin (Nuplazid(®)) received its novel drug approval by the FDA on April 29, 2016, to treat hallucinations and delusions associated with psychosis experienced by some people with PD. We review in this article the new research that led to this approval as well as its potential place in therapy.