title: Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation.
abstract: High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol.
authors.affiliation: Department of Addiction Medicine, CHU Lille, F-59037 Lille, France; Department of Pharmacology, INSERM U 1171, Univ Lille, F-59045 Lille, France. Electronic address: benjamin.rolland@chru-lille.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rolland
authors.affiliation: Department of Biostatistics, CHU Lille, F-59037 Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.affiliation: Department of Biostatistics, CHU Lille, F-59037 Lille, France; CERIM, EA 2694, Univ Lille, F-59045 Lille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.affiliation: CEIP, CHU Lille, F-59037 Lille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Deheul
authors.affiliation: Department of Pharmacology, INSERM U 1171, Univ Lille, F-59045 Lille, France; Department of Pharmacovigilance, F-59037 Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
authors.affiliation: Department of Pharmacovigilance, F-59037 Lille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Auffret
authors.affiliation: Department of Addiction Medicine, CHU Lille, F-59037 Lille, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Pignon
authors.affiliation: Department of Psychiatry, CH Douai F-59507, Douai, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Valin
authors.affiliation: Department of Pharmacology, INSERM U 1171, Univ Lille, F-59045 Lille, France; CEIP, CHU Lille, F-59037 Lille, France; Department of Pharmacovigilance, F-59037 Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: Department of Addiction Medicine, CHU Lille, F-59037 Lille, France; SCALAB UMR CNRS 9193, Univ Lille, F-59045 Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cottencin
mesh_terms: D000427:Alcohol Deterrents / Q000008:administration & dosage* / Q000009:adverse effects*; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D000437:Alcoholism / Q000188:drug therapy* / Q000453:epidemiology; D001418:Baclofen / Q000008:administration & dosage* / Q000009:adverse effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012306:Risk
chemical_list: D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D001418:Baclofen
keywords: Alcohol-related disorders; Alcoholism; Baclofen; Drug-related side effects and adverse reactions; Ethanol; GABA agonists