Therapeutics
Gabapentin increased complete abstinence in alcohol-dependent patients seeking treatment
Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174: 70-7.
Clinical impact ratings: F ★★★★★★✩ Question
Conclusion
In alcohol-dependent patients who seek treatment, what is the efficacy of gabapentin for increasing abstinence?
In alcohol-dependent patients who seek treatment, gabapentin increased rates of complete abstinence and no heavy drinking.
Methods
*See Glossary.
Design: Randomized placebo-controlled trial. ClinicalTrials.gov NCT00391716.
†Information provided by author.
Allocation: Concealed.*
Source of funding: National Institute on Alcohol Abuse and Alcoholism. Study drug was provided by Pfizer.
Blinding: Blinded* (patients, clinicians, {data collectors, outcome adjudicators, and data analysts}†). Follow-up period: 12 weeks. Setting: The Scripps Research Institute, California, USA. Patients: 150 patients > 18 years of age (mean age 45 y, 57% men) who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence and were abstinent for 3 days to 1 month. Exclusion criteria included risk for significant withdrawal; dependence on drugs other than alcohol or nicotine; urine drug screen positive for benzodiazepines, cocaine, methamphetamine, tetrahydrocannabinol, methadone, or opiates; use of medications that could affect study outcomes; clinically significant medical or psychiatric disorders; or legally mandated treatment. Intervention: Gabapentin, 900 mg (n = 54) or 1800 mg (n = 47), or placebo (n = 49). Each group took 2 identical capsules 3 times/d; in the gabapentin groups, placebo capsules were gradually replaced by gabapentin capsules, 300 mg, until the appropriate daily dose was achieved (by day 4 for the 900-mg group and day 6 for the 1800-mg dose). Beginning at week 11, gabapentin groups were titrated off active medication by gradually replacing active capsules with placebo capsules over 1 week. Outcomes: Complete abstinence (self-report validated by weekly breathalyzer tests, monthly measurement of γ-glutamyltransferase values, and collateral informant reports) and no heavy drinking. Patient follow-up: 97% (intention-to-treat analysis) {for both abstinence and no heavy drinking}†.
Main results There were linear dose effects of increasing rate of complete abstinence (P = 0.02) and of no heavy drinking (P = 0.04). Compared with placebo, gabapentin, 1800 mg, increased the relative benefit for complete abstinence and for no heavy drinking (Table). Gabapentin, 1800 mg, vs placebo at 12 wk in alcoholdependent patients who seek treatment‡ Outcomes
Event rates Gabapentin Placebo
Complete abstinence
17%
No heavy drinking
45%
4.1% 23%
RBI (95% CI)
NNT (CI)
317% (7 to 1584)
8 (4 to 134)
99% (11 to 269)
5 (3 to 31)
‡Abbreviations defined in Glossary. RBI, NNT, and CI calculated from event rates in article.
JC10
© 2014 American College of Physicians
For correspondence: Dr. B.J. Mason, The Scripps Research Institute, La Jolla, CA, USA. E-mail [email protected]. ■
Commentary Gabapentin might be effective for treating alcohol use disorder because of its effects on the γ-aminobutyric acid system. Mason and colleagues concluded that their trial showed that gabapentin was effective in treating alcohol dependence, a conclusion broadcast by a National Institutes of Health press release (1) and an editorial (2). What were the findings, and what do they mean? There was a significant dose–response effect for abstinence, but confidence intervals for the 1800-mg dose and placebo overlapped. Results for the co-primary outcome of no heavy drinking (45% vs 23%, respectively) also showed a linear dose effect but had overlapping confidence intervals. Patients who entered the trial did so under the best possible circumstances for finding a medication effect— they were treatment-seeking volunteers who responded to advertisements, had no other drug use or comorbid conditions, and achieved abstinence before starting the study treatment. Naltrexone and acamprosate, which are approved by the U.S. Food and Drug Administration, have proven efficacy based on statistically significant differences in abstinence or heavy drinking between medication and placebo (3, 4). In the study by Mason and colleagues, gabapentin showed a significant dose–response effect, and estimates of effect sizes were larger than those seen for naltrexone and acamprosate. This would be clinically important if these effect sizes were replicated and found to be statistically significant in a larger trial, particularly when comparing a particular dose directly with placebo. Until then, decisions about where gabapentin fits into practice await further proof of efficacy in another, probably larger, trial. Richard Saitz, MD, MPH Boston University Boston, Massachusetts, USA References 1. NIH-funded study finds that gabapentin may treat alcohol dependence. www.niaaa.nih.gov/news-events/news-releases/gabapentin-alcoholdependence. (accessed 26 Nov 2013). 2. Nunes EV. Gabapentin: a new addition to the armamentarium for alcohol dependence? JAMA Intern Med. 2014;174:78-9. 3. Rösner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010;(9):CD004332. 4. Rösner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010;(12):CD001867. 18 February 2014 | ACP Journal Club | Volume 160 • Number 4
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929769/ by a Tufts University User on 07/19/2017
Gabapentin increased complete abstinence in alcohol-dependent patients seeking treatment
Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174: 70-7.
Clinical impact ratings: F ★★★★★★✩ Question
Conclusion
In alcohol-dependent patients who seek treatment, what is the efficacy of gabapentin for increasing abstinence?
In alcohol-dependent patients who seek treatment, gabapentin increased rates of complete abstinence and no heavy drinking.
Methods
*See Glossary.
Design: Randomized placebo-controlled trial. ClinicalTrials.gov NCT00391716.
†Information provided by author.
Allocation: Concealed.*
Source of funding: National Institute on Alcohol Abuse and Alcoholism. Study drug was provided by Pfizer.
Blinding: Blinded* (patients, clinicians, {data collectors, outcome adjudicators, and data analysts}†). Follow-up period: 12 weeks. Setting: The Scripps Research Institute, California, USA. Patients: 150 patients > 18 years of age (mean age 45 y, 57% men) who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence and were abstinent for 3 days to 1 month. Exclusion criteria included risk for significant withdrawal; dependence on drugs other than alcohol or nicotine; urine drug screen positive for benzodiazepines, cocaine, methamphetamine, tetrahydrocannabinol, methadone, or opiates; use of medications that could affect study outcomes; clinically significant medical or psychiatric disorders; or legally mandated treatment. Intervention: Gabapentin, 900 mg (n = 54) or 1800 mg (n = 47), or placebo (n = 49). Each group took 2 identical capsules 3 times/d; in the gabapentin groups, placebo capsules were gradually replaced by gabapentin capsules, 300 mg, until the appropriate daily dose was achieved (by day 4 for the 900-mg group and day 6 for the 1800-mg dose). Beginning at week 11, gabapentin groups were titrated off active medication by gradually replacing active capsules with placebo capsules over 1 week. Outcomes: Complete abstinence (self-report validated by weekly breathalyzer tests, monthly measurement of γ-glutamyltransferase values, and collateral informant reports) and no heavy drinking. Patient follow-up: 97% (intention-to-treat analysis) {for both abstinence and no heavy drinking}†.
Main results There were linear dose effects of increasing rate of complete abstinence (P = 0.02) and of no heavy drinking (P = 0.04). Compared with placebo, gabapentin, 1800 mg, increased the relative benefit for complete abstinence and for no heavy drinking (Table). Gabapentin, 1800 mg, vs placebo at 12 wk in alcoholdependent patients who seek treatment‡ Outcomes
Event rates Gabapentin Placebo
Complete abstinence
17%
No heavy drinking
45%
4.1% 23%
RBI (95% CI)
NNT (CI)
317% (7 to 1584)
8 (4 to 134)
99% (11 to 269)
5 (3 to 31)
‡Abbreviations defined in Glossary. RBI, NNT, and CI calculated from event rates in article.
JC10
© 2014 American College of Physicians
For correspondence: Dr. B.J. Mason, The Scripps Research Institute, La Jolla, CA, USA. E-mail [email protected]. ■
Commentary Gabapentin might be effective for treating alcohol use disorder because of its effects on the γ-aminobutyric acid system. Mason and colleagues concluded that their trial showed that gabapentin was effective in treating alcohol dependence, a conclusion broadcast by a National Institutes of Health press release (1) and an editorial (2). What were the findings, and what do they mean? There was a significant dose–response effect for abstinence, but confidence intervals for the 1800-mg dose and placebo overlapped. Results for the co-primary outcome of no heavy drinking (45% vs 23%, respectively) also showed a linear dose effect but had overlapping confidence intervals. Patients who entered the trial did so under the best possible circumstances for finding a medication effect— they were treatment-seeking volunteers who responded to advertisements, had no other drug use or comorbid conditions, and achieved abstinence before starting the study treatment. Naltrexone and acamprosate, which are approved by the U.S. Food and Drug Administration, have proven efficacy based on statistically significant differences in abstinence or heavy drinking between medication and placebo (3, 4). In the study by Mason and colleagues, gabapentin showed a significant dose–response effect, and estimates of effect sizes were larger than those seen for naltrexone and acamprosate. This would be clinically important if these effect sizes were replicated and found to be statistically significant in a larger trial, particularly when comparing a particular dose directly with placebo. Until then, decisions about where gabapentin fits into practice await further proof of efficacy in another, probably larger, trial. Richard Saitz, MD, MPH Boston University Boston, Massachusetts, USA References 1. NIH-funded study finds that gabapentin may treat alcohol dependence. www.niaaa.nih.gov/news-events/news-releases/gabapentin-alcoholdependence. (accessed 26 Nov 2013). 2. Nunes EV. Gabapentin: a new addition to the armamentarium for alcohol dependence? JAMA Intern Med. 2014;174:78-9. 3. Rösner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010;(9):CD004332. 4. Rösner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010;(12):CD001867. 18 February 2014 | ACP Journal Club | Volume 160 • Number 4
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929769/ by a Tufts University User on 07/19/2017
