Topiramate or Quetiapine for Alcohol Dependence?

Summary and Comment |
October 15, 2007

Topiramate or Quetiapine for Alcohol Dependence?

  1. Peter Roy-Byrne, MD

Early results are promising, especially for patients with difficult-to-treat Type B alcoholism.

  1. Peter Roy-Byrne, MD

Alcohol dependence remains difficult to treat pharmacologically. Disulfiram requires regular compliance, and acamprosate and naltrexone have only small-to-medium effect sizes. Two research groups examined other pharmacologic agents added to brief behavioral interventions.

In 2003, researchers conducting a randomized controlled trial established the efficacy of topiramate for alcohol dependence. Now, the same group has conducted a longer and larger (14 vs. 8 weeks; n=371 vs. 150), multisite, randomized, placebo-controlled, manufacturer-funded trial of topiramate. Topiramate (dose, ≤300 mg/day, titrated over 6 weeks [titration lasted 8 weeks in the previous study]), was superior to placebo in reducing the percentage of heavy drinking days, reducing drinks per drinking day, and increasing abstinent days. Still, effect sizes were smaller and topiramate was less well tolerated than in the initial study, with paresthesia, anorexia, and poor concentration commonly reported. Only 63% of topiramate recipients versus 78% of placebo recipients completed the trial.

In a pilot, randomized, placebo-controlled, 12-week study, researchers examined the efficacy of the atypical antipsychotic quetiapine in 61 subjects with alcohol dependence (33 with Type A and 28 with Type B alcoholism). Patients with Type B alcoholism are particularly difficult to treat, as it has an early onset and is associated with antisocial behavior, other psychopathology, and more severe polysubstance abuse. Patients with current severe psychiatric symptoms were excluded. Fewer Type B (64%) than Type A (90%) patients completed the trial, but placebo and quetiapine groups had similar completion rates. Rates of abstinence were significantly higher with quetiapine (31%) than with placebo (6%). Compared with placebo, quetiapine significantly reduced drinking days and heavy drinking days in Type B patients; these effects were not significant in Type A patients. Quetiapine had no significant effects on time to drinking relapse.


The topiramate study replicates positive findings from a smaller study (although with smaller effect sizes) and suggests that medications with anticonvulsant and GABAA agonist properties may be useful. However, it also highlights important adverse effects, possibly uncovered in this study not because of its faster titration, but because of its larger sample size.

The promising findings for quetiapine, while preliminary, suggest that it has some efficacy in treating alcohol dependence, particularly in patients with Type B alcoholism. Dopaminergic blocking effects of quetiapine might reduce the rewarding properties of alcohol, or the general psychotropic effects of quetiapine — which has been shown to have antidepressant, antimanic, and antipsychotic effects — might play a role. Clearly, this agent should be tested in larger trials.


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