Parkinson's disease (PD) psychosis is a distressing condition that affects up to 60% of patients at the advanced stages of the disease. It significantly impairs patients' and caregivers' quality of life. Current therapeutic options are limited, with only 2 drugs, clozapine and pimavanserin, demonstrating efficacy in randomised controlled trials. These 2 drugs harbour significant affinity for serotonin 2A (5-HT2A) receptors, at which they act as antagonists. Mianserin is a non-selective, clinically-available, anti-depressant that blocks 5-HT2A receptors. Here, we hypothesised that mianserin would effectively alleviate PD psychosis.Methods:
We tested the anti-psychotic potential of mianserin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset. Six MPTP-lesioned marmosets exhibiting psychosis-like behaviours (PLBs) were administered l-3,4-dihydroxyphenylalanine (l-DOPA) in combination with mianserin (0.3, 1 and 3 mg/kg) or vehicle, after which the severity of PLBs was rated. We also assessed the effect of mianserin on l-DOPA-induced dyskinesia and parkinsonian disability.Results:
The addition of mianserin 3 mg/kg to l-DOPA led to a 23% reduction of PLBs (P < 0.05), when compared to l-DOPA/vehicle. Dyskinesia was reduced, by ≈41% (P < 0.01), when mianserin 3 mg/kg was added to l-DOPA, compared to l-DOPA/vehicle. However, mianserin 3 mg/kg reduced duration of l-DOPA anti-parkinsonian action, by ≈18% (P < 0.05), when compared to l-DOPA/vehicle.Conclusions:
Our results suggest that mianserin, a clinically-available anti-depressant, may be effective to alleviate both PD psychosis and dyskinesia, but may hinder l-DOPA anti-parkinsonian action, which limits its potential clinical usefulness.