The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson’s Disease

Abstract

Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy.

Update on the treatment of Parkinson’s disease psychosis: role of pimavanserin

“…It has the potential to cause rare, but life-threatening, agranulocytosis 25. It is likely that clozapine is underutilized due to its many rare side effects and required blood monitoring.…”

“…Typically, no other atypical antipsychotics are used besides clozapine and quetiapine. Risperidone and olanzapine often result in worsening motor symptoms, in addition to multiple metabolic and cerebrovascular risks 25. Aripiprazole, an atypical antipsychotic that acts on serotonergic and dopaminergic receptors, has been shown to be effective in psychosis.…”

Successful management of persistent distressing neuropsychiatric symptoms by clozapine in a patient suffering from dementia with Lewy bodies

“…Antipsychotic use in patients with DLB is restricted due to their blockade of dopamine D2 receptors which can induce dyskinesia and other extrapyramidal side effects. Second generation antipsychotics such as clozapine and quetiapine are considered safer in these populations because of their lower affinity for D2 receptors 8. Many clinicians choose to use these without a clear evidence base.…”

Low dose clozapine controls adult-onset psychosis associated with the neurogenic ataxia-retinitis pigmentosa (NARP) mutation

“…Clozapine has strong affinity for several dopaminergic receptors and is also a serotonin antagonist with strong binding to 5-HT2A/2C receptors [4]. Efficacy and safety of low doses of clozapine have been previously shown in Parkinson's disease [5], [6], [7]. Further studies will hopefully confirm the interest of low dose of clozapine for psychotic symptoms in NARP syndrome, and maybe other mitochondrial disorders.…”