Journal Club Alcohol, Other Drugs, and Health: Current Evidence March–April 2014

Featured Article Gabapentin Can Decrease Heavy Drinking and Increase Abstinence for Patients with Alcohol Dependence Mason BJ, et al. JAMA Intern Med. 2014;174(1):70–77.

Study Objective To determine whether gabapentin can increase rates of sustained abstinence and decrease rates of heavy drinking.

4 Study Design A 12-week, double-blind, placebo-controlled randomized dose-ranging trial comparing three groups (N = 150 adults with current alcohol dependence). All groups received counseling. The three groups received: –Gabapentin 900 mg/day –Gabapentin 1800 mg/day –Gabapentin 0 mg/day (control)

5 Assessing Validity of an Article about Therapy Are the results valid? What are the results? How can I apply the results to patient care?

Are the Results Valid? Were patients randomized? Was randomization concealed? Were patients analyzed in the groups to which they were randomized? Were patients in the treatment and control groups similar with respect to known prognostic variables?

Are the Results Valid? (cont‘d) Were patients aware of group allocation? Were clinicians aware of group allocation? Were outcome assessors aware of group allocation? Was follow-up complete?

Were patients randomized? Yes. –Patients were randomized using a computer- generated randomization code. –Patients were randomized in a 1:1:1 ratio.

Was randomization concealed? Yes. –The randomization code was kept by the study pharmacist who administered the medication.

Were patients analyzed in the groups to which they were randomized? Yes.

Were the patients in the treatment and control groups similar? Yes.

Were patients aware of group allocation? No. –Patients were blinded to group allocation.

Were clinicians aware of group allocation? No. –Only the study pharmacist was aware of group allocation. Other researchers or clinicians were not.

Were outcome assessors aware of group allocation? No.

Was follow-up complete? No. –The trial was 12 weeks long and patients were administered medication weekly. –Number of patients who provided 12-week data for analysis: Gabapentin 900 mg group: 27 of 54 initially enrolled Gabapentin 1800 mg group: 28 of 47 initially enrolled Control group: 30 of 49 initially enrolled

What Are the Results? How large was the treatment effect? How precise was the estimate of the treatment effect?

How large was the treatment effect? Gabapentin had a significant linear dose effect in increasing rates of abstinence (P = 0.04). The rate of 12-week abstinence was: –Gabapentin 900 mg group: 11.1% (95% CI, 5.2%–22.2%) –Gabapentin 1800 mg group: 17% (95% CI, 8.9%–30.1%; NNT = 8; OR = 4.8) –Control: 4.1% (95% CI, 1.1%–13.7%) The rate of no heavy drinking at 12 weeks was: –Gabapentin 900 mg group: 29.6% (95% CI, 19.1%–42.8%) –Gabapentin 1800 mg group: 44.7% (95% CI, 31.4%–58.8%; NNT = 5; OR = 2.8) –Control: 22.5% (95% CI, 13.6%–37.2%)

How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Were all clinically important outcomes considered? Are the likely treatment benefits worth the potential harm and costs?

Were the study patients similar to those in my practice? The patients were treatment-seeking adult volunteers. All were people with current DSM-IV alcohol dependence; the majority had moderate dependence. They were excluded if urine toxicology screens revealed the use of any other substances besides alcohol or nicotine. They could not have significant medical or psychiatric disorders.

Were all clinically important outcomes considered? Yes.

Are the likely treatment benefits worth the potential harm and costs? Possibly. –There were no differences in the rate of termination due to adverse events by study arm. Costs were not considered. –Due to the loss to follow-up, further studies into acceptability and efficacy of gabapentin for treating alcohol use disorders are needed. –Results may not be generalizable since it was a single-site study. –The overlapping confidence intervals across the study groups suggest that widespread use of the treatment for dependence should await a larger effectiveness trial.