Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.

To evaluate the long-term efficacy and tolerability of quetiapine for psychosis among parkinsonian patients, a retrospective analysis of all parkinsonian patients taking quetiapine for psychosis in a single movement disorders center was carried out. Demographic data, including type and severity of psychosis, presence of dementia, treatment response, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores and Hoehn and Yahr (H&Y) scale were obtained. One hundred six parkinsonian patients with a mean age of 76.6 years were on an average levodopa (L-dopa) dose of 415 mg/d. Seventy-eight of 106 (74%) remained on quetiapine for a mean duration of 15 months at an average dose of 60 mg per day. Eighty-seven (82%) patients had partial or complete resolution of their psychosis whereas 19 (18%) patients had no improvement on quetiapine. Motor worsening was noted in 34 (32%) patients but was uncommonly sufficient to warrant quetiapine discontinuation. More quetiapine non-responders were noted to be demented, delusional, and experienced threatening psychosis but only the presence of dementia remained significant on multivariate analysis (OR = 11.6; 95% CI = 1.4-92.9). Also, patients who developed motor worsening while on quetiapine tended to be more demented (P = 0.07).

Aripiprazole is the newest atypical antipsychotic (AA) drug to be released in the US. It is the only AA that is a partial agonist at the D2 and 5HT1a receptors and an antagonist at 5HT2a receptors. It also has a high 5HT2/D2 ratio and may therefore carry a low risk of extrapyramidal side effects and alleviate psychosis in Parkinson-vulnerable populations. We report our preliminary experience in 8 patients with probable Parkinson disease (PD) treated with aripiprazole for drug-induced psychosis. Two patients were neuroleptic-naive, 5 patients were "quetiapine failures", and 1 patient was switched from olanzapine to aripiprazole. Aripiprazole was started at 5 mg to 10 mg a day and slowly increased over 3 to 7 days until side effects or improvement of psychosis occurred. Only 2 out of 8 patients experienced near complete resolution of their psychosis using aripiprazole. The other six patients discontinued aripiprazole within 40 days, 2 of whom discontinued due to motor worsening. Our preliminary experience with aripiprazole is mixed but not very encouraging. Controlled studies are needed to evaluate aripiprazole in parkinsonian patients.