Background
Nalmefene
is a recent option in alcohol dependence treatment. Its approval was
controversial. We conducted a systematic review and meta-analysis of the
aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the
harm/benefit of nalmefene versus placebo or active comparator in this
indication.
Methods and Findings
Three
reviewers searched for published and unpublished studies in Medline, the
Cochrane Library, Embase, ClinicalTrials.gov,
Current Controlled Trials, and bibliographies and by mailing pharmaceutical
companies, the European Medicines Agency (EMA), and the US Food and Drug
Administration. Double-blind randomized clinical trials evaluating nalmefene to
treat adult alcohol dependence, irrespective of the comparator, were included
if they reported (1) health outcomes (mortality, accidents/injuries, quality of
life, somatic complications), (2) alcohol consumption outcomes, (3) biological
outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors
independently screened the titles and abstracts of the trials identified.
Relevant trials were evaluated in full text. The reviewers independently
assessed the included trials for methodological quality using the Cochrane
Collaboration tool for assessing risk of bias. On the basis of the I2 index or
the Cochrane’s Q test, fixed or random effect models were used to estimate risk
ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs)
with 95% CIs. In sensitivity analyses, outcomes for participants who were lost
to follow-up were included using baseline observation carried forward (BOCF);
for binary measures, patients lost to follow-up were considered equal to
failures (i.e., non-assessed patients were recorded as not having responded in
both groups). Five randomized controlled trials (RCTs) versus placebo, with a
total of 2,567 randomized participants, were included in the main analysis.
None of these studies was performed in the specific population defined by the
EMA approval of nalmefene, i.e., adults with alcohol dependence who consume
more than 60 g of alcohol per day (for men) or more than 40 g per day (for
women). No RCT compared nalmefene with another medication. Mortality at 6 mo
(RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and
quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95%
CI [−0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI
[−1.33; 3.34]) were not different across groups. Other health outcomes were not
reported. Differences were encountered for alcohol consumption outcomes such as
monthly number of heavy drinking days at 6 mo (MD = −1.65, 95% CI [−2.41; −0.89])
and at 1 y (MD = −1.60, 95% CI [−2.85; −0.35]) and total alcohol consumption at
6 mo (SMD = −0.20, 95% CI [−0.30; −0.10]). An attrition bias could not be
excluded, with more withdrawals for nalmefene than for placebo, including more
withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63])
and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no
differences for alcohol consumption outcomes between nalmefene and placebo, but
the weight of these results should not be overestimated, as the BOCF approach
to managing withdrawals was used.
Conclusions
The value of nalmefene for treatment of alcohol addiction
is not established. At best, nalmefene has limited efficacy in reducing alcohol
consumption.
Below: Forest plots for health outcomes at 6 mo
Full article at: http://goo.gl/39dTbp
By:
Clément Palpacuer, Bruno Laviolle, Jean Michel Reymann, Eric
Bellissant, Florian Naudet
INSERM Centre d’Investigation
Clinique 1414, Centre Hospitalier Universitaire de Rennes, Rennes, France
Bruno Laviolle, Jean Michel Reymann, Eric Bellissant,
Florian Naudet
Laboratoire de Pharmacologie
Expérimentale et Clinique, Faculté de Médecine, Université de Rennes 1, Rennes,
France
Rémy Boussageon
Département de Médecine
Générale, Faculté de Médecine et de Pharmacie, Université de Poitiers,
Poitiers, France
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