45 - Psychosis

Psychosis

Drug treatment of psychiatric symptoms in the context of other conditions CHAPTER 10 Psychosis Psychosis in PD is often characterised by visual hallucinations.28 Auditory hallucinations and delusions occur far less frequently,29 and usually in younger patients.30 Psychosis and dementia frequently coexist. Having one predicts the development of the other.31 Sleep disorders are also an established risk factor for the development of psychosis.32 The exact aetiology of PD psychosis is poorly understood. In the majority of patients, psychotic symptoms are thought to be secondary to dopaminergic medication rather than part of PD itself. Psychosis secondary to medication may be determined at least in part through polymorphisms of the ACE gene.33 From the limited data available, anticholinergics and dopamine agonists seem to be associated with a higher risk of inducing psychosis than levodopa or catechol-­O-­methyltransferase (COMT) inhibitors.29,34 Psychosis is a major contributor to caregiver distress and a risk factor for institutionalisation and early death.31 Suggested treatments are described in Table 10.14. Table 10.14  Recommendations for treatment of psychosis in Parkinson’s disease (PD). Step Intervention Exclude organic causes (delirium). Optimise the environment to maximise orientation and minimise problems due to poor caregiver–patient interactions. If the patient has insight and hallucinations are infrequent and not troubling, do not treat. Consider reducing or stopping anticholinergics and dopamine agonists. Monitor for signs of motor deterioration. Be prepared to restart/increase the dose of these drugs again to achieve the best balance between psychosis and mobility. Consider an atypical antipsychotic. The efficacy of clozapine (see step 7) is unequivocally supported by placebo-­controlled RCTs.28 In contrast, there are several negative placebo-­controlled trials for quetiapine and olanzapine.28 Low-­dose quetiapine (25–200mg a day) is the least badly tolerated and may have marginal efficacy.35 It is probably reasonable to try quetiapine36 before clozapine but the success rate is minimal. Olanzapine, ziprasidone and aripiprazole are likely to all have greater adverse effects on motor function than quetiapine and have no proven therapeutic effect. Risperidone and conventional antipsychotics should be avoided completely. All antipsychotics may be relatively less effective in managing psychotic symptoms in patients with dementia, and such patients may be more prone to developing motor and cognitive adverse effects.37 Antipsychotics have been associated with an increased risk of vascular events in the elderly. In PD all antipsychotics are linked to increased mortality38 although the effect of clozapine is not known. Consider a cholinesterase inhibitor, particularly if the patient has comorbid dementia.39 Cholinesterase inhibitors may also reduce the risk of falls.40 Early use of these drugs does not prevent or reduce episodes of psychosis although there is some benefit on cognition.41,42 Try clozapine. Clozapine is highly effective in PD psychosis but widely underused.43 It also has useful anti-­tremor properties equivalent to benztropine.44 A 2023 European study45 reported that only 1% of PD psychosis patients received clozapine (72% received quetiapine). Start at 6.25mg – usual dose 25–35mg/day.28,46 Usually safe but neuroleptic malignant syndrome has been reported.47 Monitor as for clozapine in schizophrenia. Older people are more prone to develop serious blood dyscrasia. A case of aplastic anaemia has been reported.48 Overall, clozapine is safer than other antipsychotics in PD psychosis.49 Consider ECT.50 Psychotic and motor symptoms usually respond well51 but the risk of inducing delirium is high,27 particularly in patients with pre-­existing cognitive impairment.