Which neuroleptic is the drug of choice in drug-induced psychosis in a patient with Parkinson´s dis

Fråga: Which neuroleptic is the drug of choice in drug-induced psychosis in a patient with Parkinson´s disease? Can the newer atypical neuroleptics olanzapine or risperidone be used? The question concerns a female patient with Parkinsons disease who is suffering from auditory hallucinations. She is currently being treated with ropinirol (Requip) in ordinary doses.

Sammanfattning: Neuroleptics are often used in Parkinson patients for drug-induced psychosis. Clozapine is the drug of choice but frequent monitoring of haematological status is required. In short term studies, olanzapine and risperidone appear to be effective in many Parkinson patients with psychosis. However, a significant portion of treated patients are at risk of aggravated parkinsonism.

Svar: Drug induced psychosis is a common adverse effect in patients with Parkinson´s disease treated with dopaminergic drugs and hence treatment with neuroleptics is often required.

Neuroleptic treatment of psychosis in patients with Parkinson´s disease has previously been discussed in a Drugline document (1). In summary, the atypical neuroleptic clozapine is recommended in Parkinson´s disease patients since it has been shown to be beneficial in the treatment of psychosis and lack extra pyramidal side effects that can worsen the parkinsonism (1). However, frequent monitoring of blood cell count is required since the drug has well-known haematological adverse effects such as agranulocytosis.

Several studies have been performed to evaluate whether the newer atypical neuroleptics olanzapine (2-4) or risperidone (2,5-6), which are not associated with blood dyscrasia, can be used instead of clozapine. The majority of the studies are open labelled comparing different atypical neuroleptic agents or a specific neuroleptic drug and focused on short-term treatment. None of the published studies was placebo-controlled.

A total of nine open labelled studies concerning olanzapine treatment in drug-induced psychosis in Parkinson´s disease are summarised in a review article (2). In short, among 130 patients, 91 showed improvement of psychosis although parkinsonism aggravated in 50 of these patients who were treated with doses ranging from 4.4-7.5 mg per day. In an 8-week open-label trial, 21 patients with Parkinson´s disease and psychosis were treated with olanzapine in doses of 2.5-10 mg daily (3). In 12 of the 15 subjects, who completed the study, the psychotic symptoms improved. In a randomised double blind parallel study, 7 patients received olanzapine and 8 patients clozapine for drug-induced psychosis (4). The patients showed no improvement in hallucinations or on overall behavioural assessment. In addition, with studied doses (2.5-15mg per day) olanzapine aggravated the parkinsonism.

The majority of the Parkinson´s disease patients (N=63) in 8 open label studies (N=82) on risperidone treatment (0.5-4mg/day) showed an improvement of drug induced psychosis (2). However, Parkinson´s disease worsened in 59 patients. Risperidone gave rise to slightly more extrapyramidal side effects than olanzapine. In a cohort study 39 patients were treated with risperidone (0.5-30mg daily) for drug-induced psychosis (5). A near complete resolution of hallucinations and delusions was observed in 23 of the patients and a 50-75% reduction of the symptoms in another four patients. In 11 of 27 Parkinson´s disease patients, with over 50% improvement, the drug was discontinued due to different adverse drug reactions, nursing home transfer or discontinuation of levodopa. Seventeen Parkinson´s disease patients were enrolled in a 12-week open pilot study to evaluate risperidone treatment for drug-induced psychosis (6). A significant improvement in psychosis was observed in 14 patients, who completed the study, treated with a median risperidone dose of 1.0 mg. Ten Parkinson´s disease patients with drug induced psychosis were randomised to risperidone (n=5) or clozapine (n=5) treatment (7). One patient on clozapine treatment dropped out of the study due to bowel infarction. A significant improvement in psychotic behaviour in the risperidone group was observed (mean dose 1.2mg per day) but not in the clozapine group (mean dose 62.5 per day).

Quetiapine is an atypical neuroleptic agent that is currently not an approved drug in Sweden. Three case reports (8,9) and four studies (10-13) indicate that this drug might be useful in drug-induced psychosis in Parkinson´s disease patients. Seventyeight patients out of 136 showed improvement in drug-induced psychosis. The doses ranged from 40.6-62.5mg daily. No exacerbation of Parkinson symptoms was observed.