Yaw Tay Kay, Fox Susan H, Lang Anthony E
National Neuroscience Institute Singapore.
Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease Toronto Western Hospital University of Toronto Toronto Ontario Canada.
Mov Disord Clin Pract. 2015 Dec 30;3(2):116-124. doi: 10.1002/mdc3.12266. eCollection 2016 Mar-Apr.
The pathogenesis of rest tremor in Parkinson's disease (PD) is incompletely understood. This symptom can be resistant to typical anti-PD medications. Therefore, new treatments are needed given the concern that this symptom causes to patients and family. Limited experience suggests that clozapine can have an important antitremor effect in PD. The mechanism(s) underlying this effect is not well understood, but could provide insight and impetus to the development of more-effective and safer antitremor therapies.
Exemplifying the antitremor effects of clozapine, we describe a patient with tremor-predominant PD who obtained prominent reduction of rest tremor with clozapine treatment. We review the responses to this treatment in another 7 of our PD patients with treatment-resistant rest tremor. We also review the published literature on clozapine for tremor in PD and discuss its potential mechanisms of action and possible adverse effects. In our case series, there was a 64% reduction of tremor score after clozapine was initiated. The mechanism of tremor reduction remains unclear with possible involvement of anticholinergic, serotonergic, antihistaminergic, antiadrenergic, and antidopaminergic effects. Clozapine does have potential serious adverse effects.
Clozapine may be effective in controlling rest tremor in PD. Given the potential fatal side effects, if clozapine is to be initiated in PD patients, it has to be used cautiously with proper monitoring, preferably in specialized centers. We acknowledge that the number of patients in this case series is small. Further studies are needed to understand clozapine's mechanism of action in reducing tremor.
帕金森病（PD）静止性震颤的发病机制尚未完全明确。这种症状可能对典型的抗PD药物耐药。鉴于该症状给患者及其家属带来的困扰，需要新的治疗方法。有限的经验表明，氯氮平对PD可能具有重要的抗震颤作用。这种作用的潜在机制尚不清楚，但可能为开发更有效、更安全的抗震颤疗法提供思路和动力。
为了例证氯氮平的抗震颤作用，我们描述了一名以震颤为主的PD患者，其静止性震颤在氯氮平治疗后显著减轻。我们回顾了另外7例对治疗耐药的PD静止性震颤患者对该治疗的反应。我们还回顾了已发表的关于氯氮平治疗PD震颤的文献，并讨论了其潜在的作用机制和可能的不良反应。在我们的病例系列中，开始使用氯氮平后震颤评分降低了64%。震颤减轻的机制尚不清楚，可能涉及抗胆碱能、血清素能、抗组胺能、抗肾上腺素能和抗多巴胺能作用。氯氮平确实有潜在的严重不良反应。
氯氮平可能对控制PD的静止性震颤有效。鉴于其潜在的致命副作用，如果要在PD患者中使用氯氮平，必须谨慎使用并进行适当监测，最好在专业中心使用。我们承认该病例系列中的患者数量较少。需要进一步研究以了解氯氮平减轻震颤的作用机制。
