Antipsychotics to Treat Parkinson’s Psychosis Need Further Research, Report Says

The antipsychotics Clozaril (clozapine, or CLZ) and Nuplazid (pimavanserin, or PIM) are potential treatments for Parkinson’s disease psychosis (PDP) in patients with idiopathic Parkinson’s disease (iPD), whose cause is unknown. However, their use is currently limited and further research is necessary, according to a review of various trials.

Results of a meta-analysis of studies of antipsychotics used to treat PDP were shared in a letter titled, “Antipsychotics for the management of Parkinson’s disease psychosis,” published in the International Journal of Geriatric Psychiatry last April.

Up to 40% of patients with iPD develop PDP. Psychotic symptoms include visual hallucinations and delusions. PDP causes severe distress and agitation, which makes it harder for caregivers to provide care for these patients and often requires admission to nursing homes.

Antipsychotics are one of the options for treatment of PDP, but many antipsychotics cause deterioration in motor function. The letter reported on studies of antipsychotics that do not affect motor function in treating PDP.

Seroquel (quetiapine, or QTP) has often been used without demonstrated effectiveness, and over 50% of patients dropped out of trials because of adverse effects including somnolence and orthostatic hypotension, a drop in blood pressure when a person suddenly stands up from a lying or sitting position. Seroquel was not shown to reduce psychotic symptoms in PDP and neither was Zyprexa (olanzapine), even though they do not affect motor function.

Clozaril did reduce psychotic symptoms in these patients, but because it requires regular blood tests, it is inconvenient for elderly patients. Nuplazid, which is approved by the FDA in the U.S., but is not approved in the U.K., appears to be as effective as Clozaril in reducing psychotic symptoms, and neither therapy appears to cause deterioration in motor function.

In the U.K., Clozaril is recommended for managing PDP, but many neurologists have little experience with the drug, and collaboration between neurology and psychiatric services is required to make sure patients are safely treated.

“A standard therapy has yet to be determined for PDP. Despite its widespread use, QTP has not demonstrated efficacy or tolerability. CLZ and PIM are promising treatments; however, their use is currently limited. Further research, including adequately powered clinical trials and naturalistic cohort studies, with uniform outcome reporting are required to assess the efficacy, tolerability and access of these agents,” the letter stated. “These studies also need to investigate adherence issues, the impact of physical illness, quality of life measures and transition to nursing home placement.”