Table 6.
Interventions to treat psychosis in PD
| Drug | Efficacy | Safetya | Practice implications |
|---|---|---|---|
| Clozapine | Efficacious | Acceptable risk with specialized monitoring | Clinically useful |
| Olanzapine | Not efficacious | Unacceptable risk | Not useful |
| Quetiapine | Insufficient evidence | Acceptable risk without specialized monitoring | Possibly useful b |
| Pimavanserin | Efficacious | Acceptable risk without specialized monitoring c | Clinically useful |
RCTs, randomized controlled trials.
The FDA mandates that antipsychotic drug manufacturers add black box warnings to labels and prescribing information because of the link found between antipsychotics and an increased mortality risk in elderly dementia patients. Moreover, antipsychotic medication may be associated with QT interval prolongation.178
Although there is insufficient evidence for quetiapine to be rated for the treatment of psychosis in PD, the practice implication is “possibly useful.” There are no high‐quality RCTs available for the treatment of quetiapine for psychosis in PD, and quetiapine was similarly efficacious to clozapine in the clozapine‐controlled trials.
There is a lack of safety data regarding durability beyond 6 weeks. There were more serious adverse events in the pimavanserin arm (7.9%) when compared with the placebo arm (3.5%), but without a unifying pattern and as such it is difficult to interpret these as drug related.29 Nevertheless, the FDA has very recently conducted an evaluation of available information about pimavanserin after the publication of reports of postmarketing adverse events.90 Based on the analysis of all available data, the FDA did not identify any new or unexpected safety findings with pimavanserin. After a thorough review, the FDA's conclusion remains unchanged that the drug's benefits outweigh its risks for patients with hallucinations and delusions of PD psychosis.91 Although the FDA did not identify any new or unexpected safety risks, there should be awareness of the possible adverse effects of pimavanserin including QT prolongation (especially with the concomitant use of other antipsychotic drugs or drugs that can cause QT prolongation) and a potential to cause a paradoxical worsening of symptoms.142