We agree with Baltieri et al. that there are few well-researched and approved medications to manage alcohol dependence on a long-term basis. Topiramate is one of the drugs that have attracted attention for its use in pharmacoprophylactic management of alcohol-dependent patients [2,3].
The work by Baltieri et al. is commendable as the first published double-blind, placebo-controlled, randomized clinical trial with a head-to-head comparison of the efficacy of topiramate with an already approved drug, i.e. naltrexone, in the treatment of alcohol dependence. The authors have further verified the integrity of the double-blind procedure, something which is reported only rarely in clinical trials. The study has several other strengths. The research has not been sponsored by any pharmaceutical industry and this is extremely important today, in an era when industry-driven research is predominant. Also, this study comes from a developing nation as opposed to most of the previous studies.
There is an interesting observation in their findings, with potentially important clinical implications. Topiramate was significantly superior to placebo with regard to the percentage of patients remaining continuously abstinent at the 4th and 8th weeks but not at 12 weeks. Thus, the statistically significant difference appeared as early as 4 weeks when the dose of topiramate was merely 100 mg/day, whereas the difference ceased to be significant at 12 weeks when the patients were receiving 300 mg/day. In addition, it had a shorter study period when compared to other studies, e.g. the study by Rubio et al., which compared two active drugs (naltrexone and acamprosate) over a period of 1 year.
Nevertheless, this observation raises an important question: whether a small dose of 100 mg/day of topiramate is as good as or even better than a dose of 300 mg/day? This can have several implications. If it can be shown that topiramate is at least equally efficacious at a dose of 100 mg/day when compared to higher doses, then the dose-related side effects would be fewer (it may be recalled that the dose of topiramate as an adjunct anti-epileptic drug is actually in the range of 100–200 mg/day). Moreover, the treatment would certainly become cost-effective. This can be highly advantageous in the treatment of alcohol dependence, especially in the developing world. Most of the randomized controlled trials [2,3] have compared placebo to topiramate at doses of 300 mg/day. Inevitably, further well-designed studies with larger sample sizes are needed to answer these questions. The research should compare (1) topiramate at 100 mg/day to a placebo and (2) topiramate at 100 mg/day to topiramate at the more researched dose of 300 mg/day through well-designed trials. Thus, studies with three parallel arms should be ideal.