a comprehensive systematic review and meta-analysis of studies looking at pharmacotherapy for alcohol use disorders (which are associated with 3x increase in early mortality, only 30% of patients receive treatment, and <10% are prescribed meds to decrease alcohol consumption) – see doi.org/10.1001/jama.2014.3628. Reviewed 123 studies, almost all RCTs, with 22.8K participants. Mean age in 40’s. studies from 12-52 weeks long. Mostly enrolled patients after detox or at least 3 days off alcohol. Results (significant findings only):
–acamprosate tid (a glutamine antagonist and γ-aminobutyric acid agonist): NNT (# needed to treat) to prevent return to any drinking=12;
–naltrexone 50mg/d: NNT to prevent any drinking =20; NNT to prevent return to heavy drinking=12.
–In trials comparing these 2 drugs – no signif difference
–injectable naltrexone: no effect on return to drinking or heavy drinking, but 4.6% reduction in heavy drinking days
–nalmefene (one tab daily, off-label): decrease of 2 heavy drinking days/month
–topiramate (off-label): 9% fewer heavy drinking days
–adverse effects: naltrexone and nalmefene – withdrawal from trials higher, esp for dizziness and gi effects (# needed to harm=48). No signif adverse effects for acamprosate or topiramate
–they did look at studies of other off-label meds (aripiprazole, atomoxetine, desipramine, fluvoxamine, gabapentin, imipramine, olanzapine, ondansetron, and paroxetine – all with only one trial. Multiple trials for baclofen, buspirone, citalopram, fluoxetine, quetiapine, sertraline, valproic acid and varenicline), insufficient evidence to support their use.
–No significant benefit of disulfuram in the 4 studies found (data inconsistent. Some found that fewer drinking days in those returning to drinking. Also small numbers of patients).
–Nalmefene and topiramate considered “somewhat effective”, but disulfiram is not.
–in many of these meds, improved results when combined with psychosocial intervention, esp studies with acamprosate and oral naltrexone.
So, pretty striking how little we are using meds, some of which have pretty good results for a very difficult, chronic, debilitating condition for many patients. Acamprosate and oral naltrexone are the best, with acomprosate being a t.i.d. med (less convenient) and contraindicated with severe renal impairment. Naltrexone being more convenient (once a day), but contraindicated if acute hepatitis, liver failure, concurrent opioid use, and with more adverse effects. The potential benefit of increasing treatment coverage to 40%, as per the authors, would reduce alcohol-attributable mortality by 13% in the European Union. Cost of a month supply of acamprosate or naltrexone is $140. ?cost of nalmefene (prescribed as one pill daily, but i am unable to get a price for it). best if meds supplemented with psychosocial intervention.
geoff