Transcript Related Journal Club Presentation

Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
July–August 2014
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Featured Article
Acamprosate and
Naltrexone: Similar Efficacy
for Reducing Return to
Drinking
Jonas DE, et al. JAMA. 2014;311:1889–1900.
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 offlabel 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
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manufacturers.
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.
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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.
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Were the results similar from
study to study?
• No
• Study results were heterogeneous
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What Are the Results?
 What are the overall results of the
review?
 How precise were the results?
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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.
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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).
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How precise were the results?
Summary of Findings Comparing the Effects of Acamprosate and Naltrexone
(Negative effect sizes favor acamprosate over naltrexone)
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
Weighted mean difference:
−2.98 (−13.4 to 7.5)
Low
Outcome
Percent drinking days
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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?
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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.
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Were all clinically important
outcomes considered?
• Yes.
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