The effect of mirtazapine on dopaminergic psychosis and dyskinesia in the parkinsonian marmoset.

Abstract

Parkinson's disease (PD) psychosis is encountered in as many as 50% of patients with advanced disease. Treatment options for PD psychosis are few. In fact, only clozapine and pimavanserin have shown efficacy in randomised controlled trials. Clinicians are often reluctant to prescribe the former, due to the risk of agranulocytosis, while the latter is not widely available yet. Because it is already clinically available and exhibits high affinity for serotonin 2A receptors, a target with which both clozapine and pimavanserin interact, we hypothesised that the anti-depressant mirtazapine might be effective to alleviate PD psychosis. Here, we tested the anti-psychotic potential of mirtazapine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset. Five MPTP-lesioned marmosets exhibiting psychosis-like behaviours were administered L-3,4-dihydroxyphenylalanine (L-DOPA) in combination with mirtazapine (0.1, 1 and 10mg/kg) or vehicle. We also tested the effect of mirtazapine on L-DOPA-induced dyskinesia. The addition of mirtazapine 10 mg/kg to L-DOPA reduced psychosis-like behaviours by 50% (P < 0.05) and dyskinesia by 29% (P < 0.01), when compared to L-DOPA/vehicle. Importantly, the antipsychotic and antidyskinetic effects of mirtazapine were achieved without hindering L-DOPA anti-parkinsonian action. Our results suggest that mirtazapine may be effective to alleviate PD psychosis and, because the drug is clinically available, clinical trials that would assess its anti-psychotic efficacy in PD could be rapidly undertaken, hopefully leading to a new treatment option for this debilitating condition.