Therapeutics 3. Panaretto K, Craig JC, Knight JF, et al. Risk factors for recurrent urinary tract infection in preschool children. J Paediatr Child Health 1999;35:454–9. 4. Toffolo A, Ammenti A, Montini G. Long-term clinical consequences of urinary tract infections during childhood: a review. Acta Paediatrica 2012;101:1018–31.

Systematic review and meta-analysis

If pharmacotherapies for alcohol use disorders are effective, why are they underutilised? 10.1136/ebmed-2014-110050 Elizabeth M Oliva,1 Alex H S Harris2 1 VA Palo Alto Heath Care System, Center for Innovation to Implementation (Ci2i), Menlo Park, California, USA; 2VA Palo Alto Heath Care System, Center for Innovation to Implementation (Ci2i), VA Substance Use Disorder Quality Enhancement Research Initiative, Menlo Park, California, USA

Correspondence to: Dr Elizabeth M Oliva, VA Palo Alto Heath Care System, Center for Innovation to Implementation, 795 Willow Road (152 MPD), Menlo Park, CA 94025, USA; [email protected]

Commentary on: Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 2014;311:1889–900.

Context Although alcohol use disorders (AUDs) are highly prevalent and often disabling, effective pharmacological treatments are underutilised, due partly to clinicians’ lack of knowledge and misperceptions about effectiveness.1 2 This systematic review and meta-analysis examined research literature on the efficacy of pharmacotherapies for AUDs in outpatient settings, providing an updated synthesis of effect sizes for a variety of outcomes.

Methods The study reviewed pharmacotherapy studies for AUDs from January 1970 through March 2014, including randomised clinical trials (RCTs) of at least 12 weeks duration in an outpatient setting with alcohol outcomes (eg, return to any drinking, return to heavy drinking), and head-to-head prospective cohort studies with health or adverse effect outcomes. Studies using FDA-approved medications (ie, naltrexone, acamprosate and disulfiram) were included, as were studies evaluating a total of 23 off-label medications (eg, topiramate and nalmfefene). Numbers needed to treat for benefit (NNT) or harm (NNH) were reported, as were weighted mean differences (WMD). The review adhered to a standard meta-analytic protocol and included graded strength of evidence, assessment for risk of publication bias and tests of statistical heterogeneity.

Findings One hundred and twenty-two RCTs and one cohort study (n=22 803) met inclusion criteria. Most studies involved naltrexone and/or

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5. Craig JC, Williams GJ. Denominators do matter: it’s a myth—urinary tract infection does not cause chronic kidney disease. Pediatrics 2011;128:984–5. 6. Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 2009;361:1748–59.

acamprosate and a psychosocial co-intervention, and included participants in their 40s who met criteria for alcohol dependence and were enrolled after a period of sobriety. Compared to placebo, significant differences were found for prevention of return to any drinking (NNT=12 for acamprosate and 20 for oral naltrexone), to heavy drinking (NNT=12 for oral naltrexone) and for reductions in drinking days (WMD=−6.5% for topiramate), heavy drinking days (WMD=−4.6% for injectable naltrexone and −9% for topiramate), heavy drinking days per month (WMD=−2.0 for nalmefene) and drinks per drinking day (WMD=−1.02 for nalmafene and −1.0 for topiramate). Meta-analysis of RCTs comparing acamprosate with naltrexone found no significant differences in alcohol outcomes. Compared to placebo, patients treated with naltrexone and nalmefene had higher risk of trial withdrawal due to adverse events (NNH=48 and 12, respectively); there were no significant differences between placebo and acamprosate or topiramate.

Commentary This study updates and synthesises the evidence-base supporting pharmacotherapy for AUDs, including medications—topiramate and nalmfefene—currently used off-label, providing more precision and confidence in current recommendations. Despite strong evidence supporting pharmacotherapy for AUDs, use of these medications is low, with

If pharmacotherapies for alcohol use disorders are effective, why are they underutilised?

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