Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation Benjamin Rolland a,b,n , Julien Labreuche c , Alain Duhamel c,d , Sylvie Deheul e , Sophie Gautier b,f , Marine Auffret f , Baptiste Pignon a , Thomas Valin g , Régis Bordet b,e,f , Olivier Cottencin a,h a Department of Addiction Medicine, CHU Lille, F-59037 Lille, France b Department of Pharmacology, INSERM U 1171, Univ Lille, F-59045 Lille, France c Department of Biostatistics, CHU Lille, F-59037 Lille, France d CERIM, EA 2694, Univ Lille, F-59045 Lille, France e CEIP, CHU Lille, F-59037 Lille, France f Department of Pharmacovigilance, F-59037 Lille, France g Department of Psychiatry, CH Douai F-59507, Douai, France h SCALAB UMR CNRS 9193, Univ Lille, F-59045 Lille, France Received 24 March 2015; received in revised form 29 April 2015; accepted 25 May 2015 KEYWORDS Baclofen; Alcoholism; Drug-related side effects and adverse reactions; GABA agonists; Ethanol; Alcohol-related disorders 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 Z7. 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 demon- strated that the rate of patient-month to EMS increased gradually with AWAC (po0.001), from 0.9% for AWAC = 0 to 9.4% for AWAC 435. There was also a significant gradual risk for EMS associated with DDB (o0.001). Multivariate analysis demonstrated a significant interaction www.elsevier.com/locate/euroneuro http://dx.doi.org/10.1016/j.euroneuro.2015.05.008 0924-977X/& 2015 Elsevier B.V. and ECNP. All rights reserved. n Correspondence to: Service d’Addictologie, Hôpital Fontan2, CS 70001, CHU Lille, F-59037 Lille, France. Tel.: + 33 320 445 838. E-mail address: benjamin.rolland@chru-lille.fr (B. Rolland). European Neuropsychopharmacology (]]]]) ], ]]]–]]] Please cite this article as: Rolland, B., et al., Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation. European Neuropsychopharmacology (2015), http://dx.doi.org/10.1016/j.euroneuro.2015.05.008