Research findings on the efficacy of medical treatments for alcohol dependence are generally mixed. While overall treatment effects for these medications have been quite modest, it is clear that some alcohol dependent patients will benefit from pharmacotherapy. Unfortunately for clinical practice, objective clinical predictors of individual treatment response to specific medications are currently unavailable.
Nevertheless, our review found several evidence-based results that support a role for alcohol dependence treatment in medical settings. First, the one study with the highest Jadad score, showed no advantage for disulfiram over placebo using an unsupervised disulfiram protocol. However, the majority of studies found that supervised disulfiram is more effective than placebo, with some evidence that it may be more efficacious than naltrexone, acamprosate, and topiramate. Compliance is a major problem with disulfiram and daily supervision of ingestion appears to be an essential key to clinical success. Second, evidence suggests that topiramate is an efficacious treatment for alcohol dependence, although the number of studies is small. Third, there is little evidence to support the use of antidepressants (either SSRIs or tricyclics) for alcohol dependence although one recent RCT found the combination of sertraline and naltrexone more effective with depressed alcoholics than naltrexone alone. Fourth, acamprosate may increase abstinence, although studies show mixed results, with some larger multisite studies in the US (e.g., the Combine Study) showing no advantage over placebo and European studies showing more favorable results (possibly due to differences in subject populations). However, taken as a whole, this review as well as a recent Cochrane review97
, suggests modest efficacy with abstinent alcoholics (i.e., those who were able to abstain for at least a few days prior to initiating medication). Fifth, a majority of studies support the efficacy of oral naltrexone over placebo. Injectable naltrexone shows efficacy but the number of studies are limited. Sixth, while some studies suggest that patients do better with extensive psychosocial treatments added to medications, others show that brief support (as would be appropriate in most medical settings) can be equally effective.
In medical settings, current research suggests either oral naltrexone, , topiramate (used off-label), or acamprosate (with abstinent patients) as the initial pharmacotherapy consideration in patients without contraindications to their use. Disulfiram can be considered with motivated, abstinent patients if daily supervision of ingestion is feasible. Brief compliance-oriented support should accompany medication treatment although some patients may require more extensive adjunctive psychosocial treatment. Systematic evidence on specific populations that may or may not require more extensive psychosocial interventions is lacking. There is evidence to suggest, however, that, in the absence of the availability of intensive psychological help, medication plus brief support from a medical provider can lead to clinical improvement.
While these conclusions are based on a comprehensive search of the literature, it should be noted that non-English language articles and unpublished papers were excluded. Also, article screening, data abstraction, and Jadad ratings were not blinded, which may introduce a potential bias. However, there is evidence that blinding does not alter reviews of this nature.98
The challenge in producing conclusions from a review of this nature is the heterogeneity of the patient populations under study. Variations in severity of dependence, genetic polymorphisms, gender, psychiatric comorbidites, and history of alcohol dependence may influence treatment response. Indeed, recent evidence indicates that genetic factors may predict treatment response to naltrexone.99
Another major difficulty in comparing studies is the lack of uniformity of drinking outcome measures. In addition, definitions for outcomes such as “heavy drinking days” or “relapse” vary from study to study. The need for consensus on the most clinically relevant drinking outcome measures and a standardized format for reporting these data is essential.. In addition, a potential limitation of published clinical trials on treatment of alcohol dependence is the limited length of follow-up (refer to – ). Follow-up of all these studies is problematic since many are of only a three to six month duration. In particular, longer-term effects on morbidity and mortality should be investigated in future studies but, as yet, have not been quantified.
Most studies include some type of psychosocial treatment along with medications but often such treatments are not described in detail, with little information on frequency and duration of treatment. Too few studies are available that examine the separate effects of these treatments on medication efficacy. Overall, pharmacotherapy for alcohol dependence in primary and specialty care settings appears to be feasible and has the potential to improve patient outcomes. Unfortunately, while alcohol medications with brief interventions have demonstrated efficacy, few trials have been conducted in primary care. Issues that require further study include the identification of patients who are most likely to respond to certain medications, whether medication alone (i.e., without even brief psychosocial interventions) can be effective, compliance problems, and adoption and implementation issues in busy medical practice settings.