Nalmefene – an Opioid Receptor Antagonist for the Treatment of Alcohol Dependence

A few days ago, the European Medicines Agency EMA has approved the opioid receptor antagonist nalmefene for the treatment of alcohol dependence. The substance will be marketed as Selincro® in Germany, manufacturer is the Danish company Lundbeck.

Nalmefene is not the first opioid receptor antagonist available for the treatment of alcohol dependence. Unlike treatment with naltrexone – approved as Adepent® in Germany since 2010 – which has the goal of abstinence, nalmefene is supposed to reduce alcohol consumption in patients with persistent heavy alcohol intake. Complete abstinence is no longer the goal of therapy. Nalmefene is indicated in patients with alcohol dependence with a continuously high level of alcohol consumption (> 60 g of alcohol per day for men and > 40 g alcohol per day for women). There is no need for long-term therapy, patients can use the drug if they feel a strong desire for alcohol. Treatment with nalmefene should be embedded in an overall psychosocial treatment plan.

Nalmefene is a non-receptor-specific opioid receptor antagonist, i.e. μ-, δ-and κ-receptors are equally antagonized. However, there is evidence for partial agonist effects at the κ-receptor. The substance binds with higher affinity than naltrexone to opioid receptors and has a longer elimination half-life of about 10-12 hours. The liver toxicity is less pronounced than with naltrexone. Both drugs are structurally related.

Nalmefene is not a new compound. It was clinically tested in part already in the 90s (Mason et al., 1999). There are several double-blind, randomized, placebo-controlled studies. Low doses (20 mg daily) were as effective as high doses (80 mg daily), the lower doses, however, are better tolerated. In a Scandinavian study (Karhuvaara et al., 2007) nalmefene reduced the number of days of heavy alcohol consumption of 15.5 before treatment to 8.6 to 9.3 during treatment. In the placebo-treated group, the number of days of heavy drinking decreased from 16.2 before treatment to 10.6 to 12.0 during treatment (p = 0.0065). The liver enzymes were significantly more reduced in the  group treated with nalmefene.

Adverse effects include nausea, insomnia, fatigue, dizziness and malaise. In a methodologically well-designed study conducted in healthy volunteers Lundbeck recently showed that nalmefene has no effect on the QTc interval in the ECG (Matz et al., 2011).

This post is also available in: German

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