Pam Harrison

October 13, 2016

WASHINGTON, DC ― Nalmefene (Selincro, H. Lundbeck A/S), a competitive opioid antagonist that is approved in Europe to help individuals reduce alcohol consumption, appears to limit the number of heavy drinking days and total alcohol consumed over time, a new literature review suggests.

However, some experts are skeptical.

Meelie Bordoloi, MD, psychiatry resident, University of Missouri, Columbia, and coauthor Vivek Agarwal, MBBS, consultant psychiatrist, Norwich, United Kingdom, found that of the four randomized controlled trials in which nalmefene was compared to placebo, individuals who took the drug 1 to 2 hours before drinking alcohol consumed significantly less alcohol and had significantly fewer heavy drinking days at 6 months compared to baseline than those who received placebo.

The main side effects associated with nalmefene included headache, nausea, and dizziness, but they tended to lessen with continued treatment, Dr Bordoloi noted.

"People say the drug decreases craving, but it really causes extinction of the reinforcing behavior which makes a person drink more," Dr Bordoloi told Medscape Medical News.

"So the goal is not to achieve complete alcohol abstinence, because that's something a lot of people find very difficult to do. The goal is to decrease alcohol consumption, and in our systematic review of randomized controlled trials of the drug, we found that there was a significant reduction in the number of heavy drinking days and a decrease in total alcohol consumption compared with placebo, so we feel that nalmefene constitutes a new pharmacological treatment paradigm for alcohol-dependent patients who are unable to reduce alcohol consumption on their own."

The study was presented here at the Institute of Psychiatric Services (IPS): The Mental Health Services 2016 Conference.

Randomized-Controlled Trials

Researchers identified four randomized controlled trials in which nalmefene was compared with placebo over a treatment interval of generally 6 months.

The number of patients included in the four trials varied, but all four trials included at least several hundred individuals overall.

Results for most of the studies were reported as both the number of heavy drinking days (HDD) and total alcohol consumed (TAC). TAC was defined as more than 60 g a day for men and 40 g a day for women. Study participants took 18 mg of nalmefene 1 to 2 hours before they expected to begin drinking.

One of the studies in the review did not report a change in TAC at 6 months' follow-up, and another looked at treatment effects at the end of 12 months instead of 6 months.

Table. Change From Baseline in HDD and TAC for Nalmefene (N) and Placebo (P) at Follow-up

  HDD, Baseline HDD, Follow-up Total Alcohol Consumption, Baseline (in grams) Total Alcohol Consumption, Follow-up (in grams)
Study 1 N: 15.5 P: 16.2 N: 9.3 P: 11.7    
Study 2 N: 19.5 P: 19.5 8.3 10.6 N: 84.8 P: 84.1 N: 34.1 P: 44.4
Study 3 N: 19.7 P: 18.4 N: 7.4 P: 7.8 N: 92.9 P: 88.8 N: 33.2 P: 34.8
Study 4 N: 14.1 P: 13.7 N: 4.3* P: 4.8* N: 68.6 P: 68.0 N: 19.6* P: 22.4*

An asterisk (*) indicates 12-month follow-up.

 

Dr Bordoloi noted that control patients who received placebo also showed a decrease in the number of heavy drinking days and TAC during the study period.

This may be explained by the fact that when people are screened at the time of enrollment into these trials, "screening itself serves as a motivation to reduce drinking, so people reduced their alcohol consumption even before randomization started," she said.

Limited Efficacy "At Best"

Commenting on the findings for Medscape Medical News, Niamh Fitzgerald, PharmD, University of Stirling, United Kingdom, pointed out that a systematic review and meta-analysis published last year in PLOS Medicine concluded that at best, nalmefene had limited efficacy in reducing alcohol consumption.

"There have been no comparisons between nalmefene and naltrexone, but there would be no reason to prescribe a new and more expensive drug that is clinically identical to a cheaper generic drug," Dr Fitzgerald said.

"So there is no economic argument to bring nalmefene here, because it is not clinically different from naltrexone," she added.

Dr Fitzgerald noted that the manufacturers of nalmefene have argued that the drug has fewer adverse effects than naltrexone, including toxic effects on the liver.

"But the current evidence that I've seen would suggest that at the doses we use clinically, there's no significant difference between the two drugs in terms of adverse effects on the liver," she said.

"And there is no reason to think naltrexone works any differently than nalmefene in the brain."

Furthermore, a study published by Dr Fitzgerald and colleagues in June, which was reported by Medscape Medical News at that time, suggested that its efficacy in the treatment of alcohol dependence is weak.

Nalmefene was approved in Europe in 2013 to help people curb their drinking. It was subsequently recommended by the UK National Institute for Health and Care Excellence for use in conjunction with psychosocial support to reduce alcohol consumption in adults.

A 2014 letter published in the BMJ describes nalmefene's European approval for alcohol misuse as "bad medicine."

In the United States, nalmefene is approved for the treatment of opioid overdose but not for alcohol dependence.

Dr Bordoloi and Dr Fitzgerald have disclosed no relevant financial relationships.

Institute of Psychiatric Services (IPS): The Mental Health Services 2016 Conference. Abstract 18. Presented October 8, 2016.

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