1. www.aodhealth.org1 Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2014

2. Featured Article Acamprosate and Naltrexone: Similar Efficacy for Reducing Return to Drinking Jonas DE, et al. JAMA. 2014;311:1889–1900.

3. www.aodhealth.org3 Study Objective To determine the harms and benefits of medications for the treatment of alcohol use disorder in adults.

4. www.aodhealth.org4 Study Design Systematic review and meta-analysis. Studies were double-blind randomized controlled trials (RCTs) ≥12 weeks’ duration (n = 122) AND one head-to-head prospective cohort study. –Total participants = 22,803. Reviewers used random-effects models and calculated numbers needed to treat (NNT) and numbers needed to harm (NNH).

5. www.aodhealth.org5 Assessing an Overview Article (Systematic Reviews and Meta-Analyses) Are the results of the study valid? What are the results? Will the results help me in caring for my patients?

6. www.aodhealth.org6 Are the Results of the Study Valid? Did the overview address a focused clinical question? Were the criteria used to select articles for inclusion appropriate? Is it unlikely that important, relevant studies were missed? Was the validity of the included studies appraised? Were assessments of studies reproducible? Were the results similar from study to study?

7. www.aodhealth.org7 Did the overview address a focused clinical question? Yes Main outcomes and measures: –Alcohol consumption, motor vehicle crashes, injuries, quality of life, function, mortality, and harms.

8. www.aodhealth.org8 Were the criteria used to select articles for inclusion appropriate? Yes The authors included randomized controlled trials of at least 12 weeks' duration that: –enrolled adults outpatients with alcohol use disorders. –evaluated an FDA-approved medication or any of 23 off- label medications. Studies were required to assess one of the following outcomes: –Consumption: return to any drinking, return to heavy drinking, drinking days, heavy drinking days (≥4 drinks in a day for women;≥5 for men), drinks per drinking day. –Health outcomes: accidents (ie, motor vehicle crashes), injuries, quality of life, function, and mortality. –Adverse effects.

9. www.aodhealth.org9 Is it unlikely that important, relevant studies were missed?  No  The authors searched PubMed, the Cochrane Library, PsycINFO, CINAHL, and EMBASE from January 1, 1970 through March 1, 2014, for this article.  They also searched for unpublished studies using ClinicalTrials.gov, the World Health Organization International Clinical TrialsRegistry Platform, and the FDA website. The Scientific Resource Center of the Agency for Healthcare Research and Quality requested unpublished data and studies from manufacturers.

10. www.aodhealth.org10 Was the validity of the included studies appraised? Yes. –The authors graded the strength of evidence as high, moderate, low, or insufficient covering 4 domains: Risk of bias, consistency, directness, and precision.

11. www.aodhealth.org11 Were assessments of studies reproducible? Yes. The authors state that: –Two reviewers assessed each domain for every outcome and determined an overall grade. –Differences were resolved by consensus.

12. www.aodhealth.org12 Were the results similar from study to study? No Study results were heterogeneous

13. www.aodhealth.org13 What Are the Results?  What are the overall results of the review?  How precise were the results?

14. www.aodhealth.org14 What are the overall results of the review? Acamprosate and naltrexone both reduced return to any drinking (numbers needed to treat, 12 and 20, respectively), and there were no differences in head to head comparisons. Naltrexone reduced heavy drinking. Acamprosate studies with the lowest risk of bias found no efficacy for the medication. Topiramate and nalmefene both reduced several drinking outcomes. There was insufficient evidence for improvements in health outcomes for any medication.

15. www.aodhealth.org15 What are the overall results of the review? (cont ’ d) –Harms included: Naltrexone was associated with dizziness, nausea, and vomiting (number needed to harm [NNH], 16, 9, and 24, respectively). Acamprosate was associated with anxiety, diarrhea, and vomiting (NNH, 7, 11, and 42, respectively). Topiramate was associated with cognitive dysfunction, paresthesias, and taste abnormalities (NNH, 12, 4, and 7, respectively). Nalmefene was associated with dizziness, headache, insomnia, nausea, and vomiting (NNH, 7, 26, 10, 7, and 17, respectively).

16. www.aodhealth.org16 How precise were the results? Summary of Findings Comparing the Effects of Acamprosate and Naltrexone (Negative effect sizes favor acamprosate over naltrexone) OutcomeResults effect size (95% CI) Strength of evidence Return to any drinkingRisk difference: 0.02 (−0.03 to 0.08)Moderate Return to heavy drinkingRisk difference: 0.01 (−0.05 to 0.06)Moderate Percent drinking daysWeighted mean difference: −2.98 (−13.4 to 7.5) Low

17. www.aodhealth.org17 Will the Results Help Me in Caring for My Patients? Can the results be applied to my patient care? Were all clinically important outcomes considered?

18. www.aodhealth.org18 Can the results be applied to my patient care? Yes. –Study participants with moderate to severe alcohol use disorders tended to reduce alcohol consumption while in treatment with these medications. –Participants had a mean age around 40 years and the majority met criteria for DSM-IV alcohol dependence. Nearly all studies required that participants go through detoxification or have a period of abstinence prior to the initiation of pharmacotherapy.

19. www.aodhealth.org19 Were all clinically important outcomes considered? Yes.