College of Pharmacy, The University of Texas, Austin, TX.
Ann Pharmacother. 2011 May;45(5):667-75. doi: 10.1345/aph.1P761. Epub 2011 May 3.
To provide an understanding of the underlying pathophysiology and current treatment options for clozapine-induced sialorrhea.
Literature was retrieved through MEDLINE (1977-February 2011) using the key search terms clozapine, sialorrhea, hypersalivation, drooling, and treatment. In addition, reference citations from identified publications were reviewed.
All articles published in English identified from the data source were evaluated and included in the review.
Sialorrhea is a common and disabling adverse effect of clozapine use. Current treatment options include topical and oral antimuscarinic medications and α-adrenergic agents. New areas of investigation include glycopyrrolate, botulinum toxin, and substitute benzamide derivatives. Thirteen clinical trials (2 retrospective, 5 open-label, 6 double-blind) and 13 case reports were reviewed. Overall, there are weak data on use of antimuscarinic agents, consisting mostly of small open-label or retrospective studies. Glycopyrrolate, however, demonstrated significant reduction of hypersalivation in a randomized controlled trial. Medications with activity at α-adrenergic receptors have shown positive results in case reports, retrospective evaluations, and an open-label trial, but have not been investigated in a double-blind, controlled fashion. Botulinum toxin also significantly improved sialorrhea in both a case report and double-blind study, although the trial included hypersalivation from other etiologies in addition to clozapine. Substitute benzamide derivatives have demonstrated significant improvements in randomized controlled trials; however, they are not available in the US. Overall, few treatment strategies have been evaluated in controlled settings, warranting further randomized controlled trials to identify more effective treatment options.
Current pharmacologic treatment options for clozapine-induced sialorrhea are limited in number and efficacy. Although few randomized controlled trials have been conducted, this review identifies potential treatment alternatives for this common and sometimes severe adverse effect.
了解氯氮平引起的流涎的潜在病理生理学和当前治疗选择。
通过 MEDLINE（1977 年至 2011 年 2 月）检索文献，使用的关键搜索词为氯氮平、流涎、唾液分泌过多、流口水和治疗。此外，还查阅了已确定出版物的参考文献。
从数据源中评估并纳入了发表的所有英文文章。
流涎是氯氮平使用的常见且使人丧失能力的不良作用。目前的治疗选择包括局部和口服抗毒蕈碱药物和α-肾上腺素能药物。新的研究领域包括格隆溴铵、肉毒杆菌毒素和替代苯甲酰胺衍生物。共回顾了 13 项临床试验（2 项回顾性、5 项开放性、6 项双盲）和 13 项病例报告。总体而言，使用抗毒蕈碱药物的数据较弱，主要是小样本开放性或回顾性研究。然而，格隆溴铵在一项随机对照试验中显示出显著减少唾液分泌过多的作用。具有α-肾上腺素能受体活性的药物在病例报告、回顾性评估和开放性试验中显示出积极的结果，但尚未以双盲、对照的方式进行研究。肉毒杆菌毒素也显著改善了流涎，在一项病例报告和双盲研究中均如此，尽管该试验除氯氮平外，还包括其他病因引起的唾液分泌过多。替代苯甲酰胺衍生物在随机对照试验中显示出显著改善；然而，它们在美国不可用。总体而言，很少有治疗策略在对照环境中得到评估，需要进一步的随机对照试验来确定更有效的治疗选择。
目前用于氯氮平引起的流涎的药物治疗选择数量有限，疗效也有限。虽然已经进行了少数随机对照试验，但本综述确定了这种常见且有时严重不良作用的潜在治疗替代方案。
