title: An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder.
abstract: Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent α2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted.
authors.affiliation: Dartmouth Geisel School of Medicine, Department of Psychiatry, Hanover, NH, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Brunette
authors.affiliation: Dartmouth Geisel School of Medicine, Department of Psychiatry, Hanover, NH, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Akerman
authors.affiliation: Frontier Science and Technology Research Foundation, Boston, MA, USA.
authors.forename: Ree
authors.initials: R
authors.lastname: Dawson
authors.affiliation: Dartmouth Geisel School of Medicine, Department of Psychiatry, Hanover, NH, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: O'Keefe
authors.affiliation: Dartmouth Geisel School of Medicine, Department of Psychiatry, Hanover, NH, USA; Dartmouth Clinical and Translational Research Institute, Dartmouth College, Hanover, NH, USA. Electronic address: alan.i.green@dartmouth.edu.
authors.forename: Alan I
authors.initials: AI
authors.lastname: Green
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000639:trends; D019973:Alcohol-Related Disorders / Q000175:diagnosis* / Q000188:drug therapy*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D000078785:Mirtazapine; D010865:Pilot Projects; D000069348:Quetiapine Fumarate / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D008803:Mianserin; D000069348:Quetiapine Fumarate; D000078785:Mirtazapine
keywords: Alcohol dependence; Alcohol use disorder; Mirtazapine; Quetiapine