Journal Club

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Journal Club

Alcohol, Other Drugs, and Health: Current Evidence

July–August 2014

Featured Article

Acamprosate and Naltrexone: Similar

Efficacy for Reducing Return to Drinking

Jonas DE, et al. JAMA. 2014;311:1889–1900.

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Study Objective

• To determine the harms and benefits of medications for the treatment of alcohol use disorder in adults.

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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).

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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?

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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?

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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.

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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.

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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.

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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.


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.


Were the results similar from study to study?

• No• Study results were heterogeneous


What Are the Results?

What are the overall results of the review?

How precise were the results?


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.


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).


How precise were the results?

Summary of Findings Comparing the Effects of Acamprosate and Naltrexone(Negative effect sizes favor acamprosate over naltrexone)

Outcome Results effect size (95% CI) Strength of evidence

Return to any drinking

Risk difference: 0.02 (−0.03 to 0.08) Moderate

Return to heavy drinking

Risk difference: 0.01 (−0.05 to 0.06) Moderate

Percent drinking days Weighted mean difference: −2.98 (−13.4 to 7.5)

Low


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?


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.


Were all clinically important outcomes considered?

• Yes.

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