Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers

Abstract

Background and aimsNalmefene has been approved in Europe for the treatment of alcohol dependence and subsequently recommended by the UK National Institute for Health and Care Excellence (NICE). This study examines critically the evidence base underpinning both decisions and the issues arising.MethodsPublished studies of nalmefene were identified through a systematic search, with documents from the European Medicines Agency, the NICE appraisal and public clinical trial registries also examined to identify methodological issues.ResultsEfficacy data used to support the licensing of nalmefene suffer from risk of bias due to lack of specification of a priori outcome measures and sensitivity analyses, use of post‐hoc sample refinement and the use of inappropriate comparators. Despite this, evidence for the efficacy of nalmefene in reducing alcohol consumption in those with alcohol dependence is, at best, modest, and of uncertain significance to individual patients. The relevance of existing trial data to routine primary care practice is doubtful.ConclusionsProblems with the registration, design, analysis and reporting of clinical trials of nalmefene did not prevent it being licensed and recommended for treating alcohol dependence. This creates dilemmas for primary care clinicians and commissioning organisations where nalmefene has been heavily promoted, and poses wider questions about the effectiveness of the medicines regulation system and how to develop the alcohol treatment evidence base.

Reduced Drinking in Alcohol Dependence Treatment, What Is the Evidence?

“…Despite the efficacy in reducing heavy drinking among high-risk drinking level patients with AD, there is an ongoing debate in the field about the efficacy of nalmefene and on the process of approval [94]. Given the large number of heavy drinkers with AD who are not seeking treatment because they do not want to pursue an abstinence goal [30,31], we feel the nalmefene debate needs to be considered within the larger context of a public health approach to the treatment of AD [95].…”

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

“…Nevertheless, the evidence for its approval was contested . As no difference was observed on health outcomes, which is the aim of a harm reduction strategy, the approval was based on small differences versus placebo on alcohol consumption outcomes, only observed in a subgroup defined a posteriori in studies with a possible attrition bias (nalmefene tolerance was poor) . In addition, nalmefene has not been compared with other active treatments, in particular naltrexone , another opioid antagonist that has previous approval in maintaining abstinence and that has already been used off‐label in reducing consumption, with some evidence suggesting a possible interest for this indication .…”

Treatment options for alcohol use disorders

“…26 Although supported by NICE for use "within its marketing authorisation", 27 recent reviews have expressed concern about the evidence base supporting its use. [28][29][30] Shared care prescribing of drugs to support alcohol abstinence Following a suitable period in specialist care, specialist prescribers may ask their primary care colleagues to take over the prescribing of acamprosate, naltrexone and disulfiram. This supports holistic care and the re-integration of patients into primary care as they move towards recovery.…”