Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate. 
Palpacuer, C., Duprez, R., Huneau, A., Locher, C., Boussageon, R., Laviolle, B., and Naudet, F. (2018) Addiction, 113: 220–237. doi: click here to read paper.

This paper reviews 32 double-blind randomised controlled trials assessing the efficacy of a range of medications for reducing alcohol use in non-abstinent patients with alcohol dependence or an alcohol use disorder. With the exception of two studies, all patients also received ‘a psychological co-intervention’, though this was not clearly defined.

While the authors found that nalmefene, baclofen and topiramate showed superiority over placebo on total alcohol consumption, no efficacy was observed for naltrexone and acamprosate. They concluded that there is no high-grade evidence for pharmacologically controlled drinking using the above medications. Many of the studies included had a risk of selective outcome reporting and a high risk of attrition bias. Furthermore, none of the studies demonstrated that pharmacologically controlled drinking showed any benefit on health outcomes.

Commentary: Acamprosate and naltrexone are widely prescribed for the treatment of cravings in abstinent patients. This systematic review aimed to consolidate the evidence for the pharmacological treatment of alcohol misuse in patients who are still drinking. 

Whilst the review might appear to be a fairly damning critique of two widely recommended treatments for alcohol cravings, it should be understood that the paper does not review the evidence for this indication. Thus, professionals working with alcohol misuse in clinical practice should not lose faith in these NICE-recommended, evidence-based treatments.

In practice, we work with an ageing population with a high level of comorbidity. Unfortunately, this review excluded studies involving patients with physical or psychological comorbidity. If trial participants are not representative of the patients we see in daily practice, the applicability of findings to real world scenarios must be considered.

The authors conclude that the evidence for pharmacological approaches to harm reduction in alcohol use is currently lacking. A clearer strategy for future research is required, as well as more trials which focus on measuring long-term health outcomes. More trials are also needed which directly compare the efficacy of different drugs. Additionally, the role of psychosocial co-interventions cannot be understated, and should be standardised and controlled for in future studies.

Clinicians must be cautious prescribing these medications to control drinking, taking into account their individual safety profiles and the risks for the patient. Medication as an alcohol harm reduction strategy is somewhat of a paradigm shift, however the poor quality research driving guidelines and policy formation may not be fully transparent about the risks involved. It has been demonstrated, for example, that baclofen has a withdrawal state of its own. Furthermore it has CNS depressant qualities which are additive when taken with alcohol, increasing the risk of respiratory depression. Whilst it has been widely prescribed in France under a ‘temporary recommendation for use’ since 2014 the authors found the evidence for its use to be inconsistent. Topiramate, found in this review to potentially be considered the most effective treatment, is also known to have negative cognitive side effects. 

In summary, while the use of these medications may eventually prove a useful adjunct to the treatment of alcohol misuse in clinical populations, as it stands the current evidence is clearly lacking. We should not be seduced by the idea of a quick fix - there is still no ‘magic pill’ to cure alcohol dependence.

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