BACLOFEN EFFICACY IN REDUCING ALCOHOL CRAVING AND INTAKE: A PRELIMINARY DOUBLE-BLIND RANDOMIZED CONTROLLED STUDY

Alcohol & Alcoholism Vol. 37, No. 5, pp. 504–508, 2002 BACLOFEN EFFICACY IN REDUCING ALCOHOL CRAVING AND INTAKE: A PRELIMINARY DOUBLE-BLIND RANDOMIZED CONTROLLED STUDY GIOVANNI ADDOLORATO*, FABIO CAPUTO2, ESMERALDA CAPRISTO, MARCO DOMENICALI2, MAURO BERNARDI2, LUIGI JANIRI1, ROBERTA AGABIO3, GIANCARLO COLOMBO4, GIAN LUIGI GESSA3–5 and GIOVANNI GASBARRINI Institute of Internal Medicine and 1Institute of Psychiatry, Catholic University of Rome, Rome, 2‘G. Fontana’ Centre for the Study and Treatment of the Alcohol Addiction, University of Bologna, Bologna, 3‘Bernard B. Brodie’ Department of Neuroscience, University of Cagliari, 4 C.N.R. Institute of Neurogenetics and Neuropharmacology, Cagliari and 5Neuroscienze S.c.a r.l., Cagliari, Italy (Received 15 March 2002; in revised form 19 April 2002; accepted 22 April 2002) Abstract — Aims: The γ-aminobutyric acid (GABAB) receptor agonist, baclofen, has recently been shown to reduce alcohol intake in alcohol-preferring rats and alcohol consumption and craving for alcohol in an open study in humans. The present study was aimed at providing a first evaluation of the efficacy of baclofen in inducing and maintaining abstinence and reducing craving for alcohol in alcohol-dependent patients in a double-blind placebo-controlled design. Methods: A total of 39 alcohol-dependent patients were consecutively enrolled in the study. After 12–24 h of abstinence from alcohol, patients were randomly divided into two groups. Twenty patients were treated with baclofen and 19 with placebo. Drug and placebo were orally administered for 30 consecutive days. Baclofen was administered at the dose of 15 mg/day for the first 3 days and 30 mg/day for the subsequent 27 days, divided into three daily doses. Patients were monitored as out-patients on a weekly basis. At each visit alcohol intake, abstinence from alcohol, alcohol craving and changes in affective disorders were evaluated. Results: A higher percentage of subjects totally abstinent from alcohol and a higher number of cumulative abstinence days throughout the study period were found in the baclofen, compared to the placebo, group. A decrease in the obsessive and compulsive components of craving was found in the baclofen compared to the placebo group; likewise, alcohol intake was reduced in the baclofen group. A decrease in state anxiety was found in the baclofen compared to the placebo group. No significant difference was found between the two groups in terms of current depressive symptoms. Baclofen proved to be easily manageable and no patient discontinued treatment due to the presence of side-effects. No patient was affected by craving for the drug and/or drug abuse. Conclusions: Baclofen proved to be effective in inducing abstinence from alcohol and reducing alcohol craving and consumption in alcoholics. With the limits posed by the small number of subjects involved, the results of this preliminary double-blind study suggest that baclofen may represent a potentially useful drug in the treatment of alcohol-dependent patients and thus merits further investigations. INTRODUCTION The present double-blind randomized placebo-controlled study was performed in order to determine the efficacy of short-term baclofen administration on craving for alcohol, alcohol intake and abstinence from alcohol in patients affected by alcoholism. In recent years, the use of pharmacotherapy together with psychosocial interventions (including Alcoholics Anonymous and various counselling approaches) has enhanced the percentage of success in maintaining alcoholic patients in remission and assisting the development of a lifestyle compatible with long-term alcohol abstinence. However, to date, drugs with proven efficacy are very few (see Garbutt et al., 1999; Swift, 1999; Kranzler, 2000) and the discovery of new medications capable of positively affecting the components of alcohol dependence syndrome, such as craving and loss of control on drinking or protracted abstinence symptoms, would represent an important step forward in the treatment of patients with alcohol problems (see Garbutt et al., 1999). Baclofen is a potent and stereoselective γ-aminobutyric acid (GABAB) receptor agonist used clinically to control spasticity (Davidoff, 1985). Recent preclinical experiments have demonstrated the efficacy of baclofen in suppressing both alcohol withdrawal signs in rats made physically dependent on alcohol and voluntary alcohol intake in alcohol-preferring rats (Colombo et al., 2000, 2002). Moreover, preliminary clinical open studies have confirmed the ability of baclofen to reduce alcohol craving and intake (Addolorato et al., 2000b) and alcohol withdrawal symptoms (Addolorato et al., 2002) in alcohol-dependent patients. PATIENTS AND METHODS A total of 39 alcohol-dependent patients (mean age ± SD: 47.3 ± 10.5 years; mean daily drinks: 14.2 ± 7.9; mean years of addiction: 11.8 ± 4.2) were consecutively admitted to the study. Inclusion criteria were: (1) age ranging from 18 to 70 years; (2) diagnosis of current alcohol dependence according to DSM-IV criteria (American Psychiatric Association, 1994); (3) last alcohol intake reported to have taken place in the 24 h preceding observation; (4) presence of a referred family member. Exclusion criteria were the presence of: (1) severe liver, kidney, heart or lung diseases; (2) psychopathological illness undergoing treatment with psychoactive drugs, epilepsy or epileptiform convulsion; (3) addiction to drugs other than nicotine. Each patient was required to provide his/her informed consent after having received information on the characteristics, dosing rate and possible side-effects of the drug, as well as on the possibility of dropping out of the study at any time. The study protocol fully complied with the guidelines of the Ethics Committees of the Università Cattolica in Rome and of the University of Bologna, where the study was performed. Patients were randomized in two groups; 20 patients were treated with baclofen (mean age: 45.8 ± 10.6 years; mean daily drinks: 17.6 ± 7.5; mean years of addiction: 12.6 ± 4.8) *Author to whom correspondence should be addressed at: Institute of Internal Medicine, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, I-00168 Rome, Italy. 504 © 2002 Medical Council on Alcohol EFFICACY OF BACLOFEN IN ALCOHOLISM and 19 patients with placebo (mean age: 48.8 ± 10.4 years; mean daily drinks: 10.7 ± 6.7; mean years of addiction: 11.0 ± 3.4). Patients were recruited among those contacting our Alcohol Treatment Units. Randomization was performed as follows: the 39 consecutive patients received either baclofen or placebo in a double-blind fashion. Baclofen and placebo were entrusted to a referred family member. Placebo tablets were identical in size, colour, shape and taste to baclofen tablets. Baclofen or placebo was orally administered for 4 consecutive weeks. For the first 3 days, baclofen was administered at a dose of 15 mg/day refracted in (...truncated)