Abstract
Background
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.
Methods
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 10 mg/kg) or vehicle. We also tested the effect of mirtazapine on L-DOPA-induced dyskinesia.
Results
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.
Conclusions
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.
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Acknowledgements
This work was supported by Université de Montréal, Centre Hospitalier de l’Université de Montréal, Parkinson Society Canada, Fonds de Recherche Québec – Santé and the Weston Brain Institute.We would like to thank Drs Jonathan Brotchie and Tom Johnston for their advice during MPTP administration.
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Animals were cared for in accordance with a protocol approved by McGill University Animal Care Committee in accordance with the regulations defined by the Canadian Council on Animal Care.
Conflict of Interest
PH has received payments from Philippe Huot MD Inc. The other authors declare that they have no conflicts of interest.
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Hamadjida, A., Nuara, S.G., Veyres, N. et al. The effect of mirtazapine on dopaminergic psychosis and dyskinesia in the parkinsonian marmoset. Psychopharmacology 234, 905–911 (2017). https://doi.org/10.1007/s00213-017-4530-z
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DOI: https://doi.org/10.1007/s00213-017-4530-z