Alcohol dependence is a major public health problem. Even in countries where free healthcare is available universally, proportion that receive treatment is miniscule. Abstinence oriented treatment may not be acceptable to many. Treatments that aim at reducing drinking have a special place in dealing with this problem.
Nalmefene is an opioid modulator . It is licensed to treat dependent individuals with continued high drinking risk. Previous studies ( lasting up to 6 months) have shown that it is well tolerated and safe . SENSE study group ( Amsterdam University) who carried out those studies report the long term efficacy , tolerability and safety of Nalmefene in this report.
This RCT recruited 675 alcohol dependent patients ( from 60 sites across europe). Those with ALT/AST more than 3 times normal were excluded. Patients in withdrawal or those with less than 6 heavy drinking days in last month or abstinent for 14 days in last month were excluded.Patients with a stable comorbid psychiatric disorder were eligible for inclusion.Patients were followed up for 52 weeks.
Patients took the medicine on an AS NEEDED Basis ( i.e. if they thought they might drink, 1-2 hrs prior to the anticipated drinking) up to once daily.
Two randomised groups were similar to start with. Majority met medium drinking level with (on average ) 1 4 heavy drinking days in last month. Majority were not treated for dependence or withdrawal previously. 32% of placebo treated and 38% of Nalmefene treated patients dropped out during the study.
Change in heavy drinking days were not statistically significant at 6 months.
At month 13 Nalmefene was more effective both in the reduction of heavy drinking days (group difference: − 1.6 days/month [95% CI – 2.9; − 0.3]; p = 0.017) and total alcohol consumption (group difference: − 6.5 g/day last month [95% CI – 12.5; − 0.4]; p = 0.036).
Almost 40% of the patients in the full-analysis set substantially decreased their alcohol consumption already in the period between screening and randomisation, i.e. prior to taking any study medication. Once these subjects were excluded , the rest of the participants ( i.e. Target efficacy population: 33% of full group) showed an effect of Nalmefene compared to placebo, both for the number of heavy drinking days and total alcohol consumption.effect is more on total alcohol consumption.
63% of placebo group and 75% of Nalmefene group had adverse effects.These were transient and mild/moderate in intensity. 5% of placebo group and 11% of Nalmefene group dropped out due to side effects. Nausea, insomnia and loss of appetite were the common side effects. Disorientation episode was reported in two Nalmefene treated patients.
62% of the nalmefene-treated patients in the total population completed the 1-year study which is quite good in this condition.
Limitations: levels of psychiatric comorbidity were lower as compared to usual subjects with this condition treated in psychiatric settings. The fact that 40% of participants significantly reduced their drinking between randomisation and study initiation is worth noting.
Nalmefene is an effective treatment for alcohol-dependent patients who continue to have high/very high risk drinking levels 1–2 weeks after an assessment of their alcohol use.
Comments: The significant reduction in alcohol use before the start of study medication points towards the efficacy of brief interventions.
Summary of the article:
van den Brink W, Sørensen P, Torup L, Mann K, Gual A; for the SENSE Study Group.
J Psychopharmacol. Aug, 2014. 733-744.