Low-dose topiramate in alcohol dependence: a randomized, double-blind, placebo-controlled trial

The anticonvulsivant topiramate could be useful in the treatment of Alcohol Withdrawal Syndrome since it has the ability to suppress glutamatergic input, to facilitate GABAA-mediated inhibitory impulse, to block sodium and calcium channels, and to facilitate potassium conductance [1]. Several studies have demonstrated the safety and efficacy of topiramate in promoting abstinence and relapse prevention [2]. Purpose of the study: The aim of this randomized, doubleblind, placebo-controlled trial was to compare topiramate at low dosage with placebo on alcohol drinking indices and craving in detoxified alcohol dependent subjects. Psychiatric symptomatology, quality of life and clinical global improvement have also been investigated. Methods: 52 detoxified Alcohol Dependent (DSM-IV-TR) outpatients (M/F 2/1, mean age 46.1±11.1; mean daily drinks 8.3±3.2; mean years of addiction 6.8±3.7) were recruited and subsequently randomized into two groups, respectively receiving topiramate (100 mg/die) (n = 26) or placebo (n = 26). The level of craving for alcohol was evaluated through a 10-cm Visual Analogue Scale (VASc) and the Italian version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated through the Symptom Check List 90 Revised (SCL-90-R), withdrawal symptoms through the Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar), quality of life through the Quality of Life Index 74 (QL-INDEX-74) and clinical global improvement using the Clinical Global Impression (CGI). Subjects were assessed at the beginning of the treatment (T0) and after 30 (T1), 90 (T2) and 180 (T3) days. Results: The survival function showed that patients treated with topiramate remained abstinent from any alcohol amount for a longer time with respect to placebo (Z = −2.197; p<0.05). The improvement of alcohol drinking indices and craving scores was significant in both groups but higher in the topiramate than in the placebo one (OCDS: p<0.05; VASc: p<0.05). Withdrawal total scores as measured by the CIWA-Ar were significantly reduced in the topiramate group (F = 3.8; p<0.025) and in the placebo group (F = 3.2; p<0.025). Significant improvements (p<0.05) for both groups were seen at the CGI and the QL-INDEX-74. The SCL-90-R general index of ‘Positive Symptom Total’ was significantly reduced only in the topiramate group (F = 3.41, p <0.05). The number of patients dropped-out from the study for adverse events was not different between groups. No clinically relevant differences between groups were seen in the mean change from baseline for any vital signs, ECGs, haematological, or clinical chemistry parameters. Conclusions: Topiramate resulted to be more efficacious than placebo for both the improvement of withdrawal symptomatology and the reduction of relapses. Furthermore, it showed efficacy in reducing craving, obsession and compulsion connected with alcohol intake, the severity of global psychopathology and in improving the quality of life. Moreover, the use of topiramate at low dosage could increase the number of subjects remaining in treatment, given the reduced possibility of adverse events. In conclusion, our results continue to provide evidence that topiramate is a safe and effective treatment, which could represent an alternative option beyond the already approved agents for the treatment of Alcohol Dependence.