acamprosate

Pharmacotherapy for Adults With Alcohol Use Disorder in Outpatient Settings: Systematic Review

Author/s: 
Melissa McPheeters, Elizabeth A. O’Connor, Sean Riley, Sara M. Kennedy, Christiane Voisin, Kaitlin Kuznacic, Cory P. Coffey, Mark Edlund, Georgiy Bobashev, Daniel E. Jonas

Pharmacotherapy for Adults With Alcohol Use Disorder in Outpatient Settings: Systematic Review
Background. Unhealthy alcohol use is the third leading preventable cause of death in the United States, accounting for more than 140,000 deaths annually. Only 0.9 percent of Americans who reported having alcohol use disorder (AUD) in the past year indicated they received medication-assisted AUD treatment.

Methods. We updated a 2014 Agency for Healthcare Research and Quality (AHRQ) report on pharmacotherapy for AUD treatment, following AHRQ Evidence-based Practice Center Guidance. We assessed efficacy and comparative effectiveness of specific medications for improving consumption outcomes (Key Question [KQ] 1) and health outcomes (KQ 2). We assessed harms (KQ 3) and sought to identify evidence for the use of pharmacotherapy to treat AUD in primary care (KQ 4) and among subgroups (KQ 5). When possible, we conducted quantitative analyses using random-effects models to estimate pooled effects. When quantitative analyses could not be conducted, we used qualitative approaches.

Results. We included 118 studies (156 articles) in our review, which included 81 studies (106 articles) from the 2014 review and 37 studies (50 articles) published since then. Studies generally included counseling co-interventions in all study groups, and the benefits observed reflect the added benefit of medications beyond those of counseling and placebo. Oral naltrexone at the 50 mg dosage had moderate strength of evidence (SOE) for reducing return to any drinking, return to heavy drinking, percent drinking days, and percent heavy drinking days. The addition of a new randomized controlled trial of injectable naltrexone conducted in a population experiencing homelessness resulted in positive outcomes for a reduction in drinking days and heavy drinking days with low SOE. Acamprosate had moderate SOE for a significant reduction in return to any drinking and reduction in drinking days. Topiramate had moderate SOE for several outcomes as well, but with greater side effects. Two other medications demonstrated low SOE for benefit in at least one consumption outcome—baclofen (reduced return to any drinking) and gabapentin (reduced return to drinking and to heavy drinking). With no new studies on disulfiram, there remains inadequate evidence for efficacy compared to placebo for preventing return to any drinking or for other alcohol consumption outcomes. No new eligible studies provided head-to-head comparisons.

Conclusions. Oral naltrexone at the 50 mg dose had moderate strength of evidence across multiple outcomes and relative ease of use as a once-daily oral medication. Acamprosate and topiramate also have moderate evidence of benefit with a less desirable side effect profile (topiramate) and a higher pill burden (acamprosate). Clinicians and patients may want to consider which treatment outcomes are most important when choosing among the medications. Current data are largely insufficient for understanding health outcomes. Finally, there is relatively little research to assess the use of medications for AUD among subgroups (9 studies) or in primary care settings (1 study).

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

Author/s: 
Fairbanks, J, Umbreit, A, Kolla, BP, Karpyak, VM, Schneekloth, TD, Loukianova, LL, Sinha, S

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Acamprosate for alcohol dependence

Author/s: 
Rösner, Susanne, Hack-Herrwerth, Andrea, Leucht, Stefan, Lehert, Philippe, Vecchi, Simona, Soyka, Michael

BACKGROUND:

Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.

OBJECTIVES:

To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents.

SEARCH STRATEGY:

We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.

SELECTION CRITERIA:

All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes.

DATA COLLECTION AND ANALYSIS:

Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes.

MAIN RESULTS:

24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).

AUTHORS' CONCLUSIONS:

Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.

Keywords 
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