title: Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.
abstract: 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.
authors.affiliation: 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.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Kreinin
authors.forename: Chanoch
authors.initials: C
authors.lastname: Miodownik
authors.forename: Vitaly
authors.initials: V
authors.lastname: Mirkin
authors.forename: Yulia
authors.initials: Y
authors.lastname: Gaiduk
authors.forename: Yan
authors.initials: Y
authors.lastname: Yankovsky
authors.forename: Yuly
authors.initials: Y
authors.lastname: Bersudsky
authors.forename: Paul P
authors.initials: PP
authors.lastname: Lerner
authors.forename: Joseph
authors.initials: J
authors.lastname: Bergman
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lerner
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D065127:Dopamine D2 Receptor Antagonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D008787:Metoclopramide / Q000627:therapeutic use*; D008875:Middle Aged; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy; D012798:Sialorrhea / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D003024:Clozapine; D008787:Metoclopramide