Hamadjida Adjia, Nuara Stephen G, Veyres Nicolas, Frouni Imane, Kwan Cynthia, Sid-Otmane Lamia, Harraka Mery-Jane, Gourdon Jim C, Huot Philippe
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, R09.436, 900 Rue St-Denis, Montreal, QC, H2X 0A9, Canada.
Comparative Medicine and Animal Resources Centre, McGill University, Montreal, QC, Canada.
Psychopharmacology (Berl). 2017 Mar;234(6):905-911. doi: 10.1007/s00213-017-4530-z. Epub 2017 Jan 27.
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 10 mg/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.
在多达50%的晚期帕金森病（PD）患者中会出现帕金森病精神病。PD精神病的治疗选择很少。事实上，只有氯氮平和匹莫范色林在随机对照试验中显示出疗效。由于存在粒细胞缺乏症的风险，临床医生往往不愿开具前者，而后者尚未广泛供应。因为米氮平已在临床上可用，并且对5-羟色胺2A受体具有高亲和力，氯氮平和匹莫范色林都与该靶点相互作用，我们推测抗抑郁药米氮平可能有效缓解PD精神病。
在此，我们在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）损伤的普通狨猴中测试了米氮平的抗精神病潜力。对五只表现出精神病样行为的MPTP损伤狨猴给予左旋多巴（L-DOPA）联合米氮平（0.1、1和10mg/kg）或赋形剂。我们还测试了米氮平对L-DOPA诱导的运动障碍的影响。
与L-DOPA/赋形剂相比，在L-DOPA中添加10mg/kg米氮平可使精神病样行为减少50%（P<0.05），运动障碍减少29%（P<0.01）。重要的是，米氮平的抗精神病和抗运动障碍作用在不阻碍L-DOPA抗帕金森作用的情况下实现。
我们的结果表明米氮平可能有效缓解PD精神病，并且由于该药物在临床上可用，可以迅速开展评估其在PD中抗精神病疗效的临床试验，有望为这种使人衰弱的病症带来新的治疗选择。
