Question: In adults with Parkinson's disease, what is the most effective pharmacological intervention in reducing hallucinations?

Answer:

Plain language summary
Research suggests that clozapine and pimavanserin may be effective in reducing hallucinations in older adults with Parkinson's disease. However, more rigorous trials are needed to provide further clarification into the most effective pharmacological intervention.

Clinical and research implications
Evidence from two, generally well conducted, systematic reviews and two additional randomised controlled trials suggests that both clozapine and the 5-HT2A receptor modulator pimavanserin may be effective in treating hallucinations and other psychotic symptoms in older adults with Parkinson's disease. The observed effects were not associated with any increase in Parkinsonian symptoms.
No evidence was identified for any other negative modulators of 5-HT2A receptors and there were no studies comparing clozapine and pimavanserin.
The available evidence, from one systematic review and three additional randomised controlled trials suggests that the atypical antipsychotics quetiapine and olanzapine are ineffective in treating psychotic symptoms in people with Parkinson's disease.
Larger, high quality trials are needed to confirm the existing evidence and to assess the effectiveness of other negative modulators of 5-HT2A receptors and atypical antipsychotics. Evidence is particularly lacking about the effectiveness of treatments for psychosis in younger patients with Parkinson's disease.

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