Question: In adults with Parkinson’s disease and psychosis, how effective are anti-psychotics, compared to treatment as usual, for treating psychotic symptoms? Which is the most effective and most tolerable?


No definite clinical implications can be made from the available evidence. There are very few methodologically robust head-to-head studies, so that it is not possible to determine which antipsychotic is most effective. Several treatments were compared with placebo (olanzapine, clozapine, quetiapine, and pimavanserin); only two treatments reported significant findings. Clozapine showed significant improvement for some outcomes (mean scores on the CGI, and the positive subscore of PANSS), but somnolence was more frequent with treatment. A well-conducted study demonstrated that primavanserin significantly reduced psychotic symptoms in patients with moderate to severe Parkinson's disease. Although this treatment was well-tolerated, there was an increase in discontinuation in the treatment group compared with placebo. One RCT with a very small sample size compared risperidone with clozapine and found no significant differences in outcomes between the groups. Two open-label RCTs compared clozapine with quetiapine, but there were no differences between groups for any of the behavioural and motor function parameters evaluated, although in one of the studies, patients treated with clozapine experienced significantly fewer delusions. Studies of clozapine reported adverse effects including neutropenia and leukopenia. These findings are generally consistent with the systematic review results.

It is clear from the authors of the included studies that further research into new treatment alternatives for psychosis in PD is warranted. It has been suggested that RCTs are needed to evaluate newer atypical antipsychotics (i.e. zipasidone or aripiprazole) and other treatment strategies (e.g. rivastigmine or orondansetron). A well-conducted RCT also suggested that pimavanserin may be a viable alternative for the treatment of psychosis in Parkinson's disease, but further research is needed.

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