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Trials on clozapine efficacy reported that most withdrawals were due to either treatment failure or adverse events. It may be precipitated by intercurrent illnesses eg infectionsaddition of new anti-parkinsonian medication or dementia.

Correspondingly, the initial treatment of psychosis should include general medical assessment and treatment of any potential causative factor. Consideration should be given to withdrawal of any recently added medication that may have triggered a psychotic reaction.

Drugs that are particularly prone to trigger psychosis, such as anti-cholinergics, selegiline and amantadine, should be withdrawn first. The patient should be evaluated for a fixed cognitive deficit that might suggest the development of dementia. For psychosis which does not respond to the above measures, no treatment may be required if psychotic features are not troublesome to the patient or their carers. In more severe psychosis, antipsychotic medication should be considered. Typical antipsychotics eg phenothiazines and butyrophenones are well known to exacerbate PD and should not be used.

Various atypical antipsychotics have been evaluated in PD, but only clozapine has a licence for this indication in England and Wales: Several randomised placebo -controlled trials have shown that clozapine can reduce psychotic symptoms in PD without exacerbating parkinsonian features. However, the use of clozapine requires intensive monitoring to detect the uncommon but potentially life-threatening complication of agranulocytosis. As a result, it is rarely used in PD. Limited trial evidence suggests that olanzapine is not effective against psychotic features and makes parkinsonian symptoms worse.


There are concerns about the safety of olanzapine and risperidone in elderly people with dementia and risk factors for stroke.

However, several trials are ongoing in this area. Quetiapine is thought to be relatively safe and does not require haematological monitoring. As a result, quetiapine has been widely used in PD psychosis. All people with PD and psychosis should receive a general medical evaluation and treatment for any precipitating condition. Consideration should be given to withdrawing gradually anti-parkinsonian medication that might have triggered psychosis in people with PD.

Mild psychotic symptoms in people with PD may not need to be actively treated if they are well tolerated by the patient and carer. Typical antipsychotic drugs such as phenothiazines and butyrophenones should not be used in people with PD because they exacerbate the motor features of the condition.

Atypical antipsychotics may be considered for treatment of psychotic symptoms in people with PDalthough the evidence base for their efficacy and safety is limited.

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