Kreinin Anatoly, Miodownik Chanoch, Mirkin Vitaly, Gaiduk Yulia, Yankovsky Yan, Bersudsky Yuly, Lerner Paul P, Bergman Joseph, Lerner Vladimir
From the *Mental Health Center Ma'ale Carmel, Bruce Rapaport Faculty of Medicine Technion, Haifa; †Be'er-Sheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva; and ‡Faculty of Medicine, Bar-Ilan University, Safed, Israel.
J Clin Psychopharmacol. 2016 Jun;36(3):200-5. doi: 10.1097/JCP.0000000000000493.
Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.
流涎过多是氯氮平治疗常见、令人困扰且不适的不良反应，常导致患者不依从治疗。本研究旨在探讨甲氧氯普胺（多巴胺D2拮抗剂，一种止吐药物）治疗氯氮平相关性流涎过多（HAC）的疗效。2012年1月至2014年5月，在大学研究诊所进行了一项为期3周的双盲、安慰剂对照试验，纳入58例接受氯氮平治疗且出现流涎过多的住院患者。受试者被随机分为安慰剂组和甲氧氯普胺组。起始剂量为10mg/d。无反应的参与者每周增加剂量10mg/d，至第三周时总量达30mg/d。安慰剂胶囊数量相应增加至每日3粒。主要结局是采用夜间流涎过多评定量表和流口水严重程度量表测量的从基线到研究结束时流涎过多严重程度的变化。次要结局包括临床总体印象改善量表和不良反应量表。甲氧氯普胺组在第二周结束时夜间流涎过多评定量表显示有显著改善（P<0.004），第三周时流口水严重程度量表有显著改善（P<0.02）。临床总体印象改善量表评分显示有显著改善。与接受安慰剂的8例患者（28.6%）相比，20例接受甲氧氯普胺治疗的患者（66.7%）报告HAC显著减轻或完全消失（P=0.031）。未报告甲氧氯普胺的不良反应。甲氧氯普胺被发现对治疗HAC安全有效。
