1. Alcohol, Other Drugs, and Health: Current Evidence May-June, 2018
Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
May-June, 2018

2. Featured Articles
A: Effect of varenicline combined with medical management on alcohol use disorder with comorbid cigarette smoking: a randomized clinical trial
O’Malley SS, et al. JAMA Psychiatry. 2018;75(2):129–138.
B: Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: a randomized controlled trial
Hurt RT, et al. Drug Alcohol Depend. 2018;184:12–17.

3. Study Objectives
A: “To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence.”
B: “To evaluate the efficacy of 12 weeks of varenicline for increasing smoking abstinence rates” among people with smoking and alcohol use disorder.

4. Study Design
A: Randomized, double-blind, parallel group, placebo-controlled trial at 2 outpatient clinics from 2012 to 2015.
Participants had DSM-IV alcohol dependence and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) ≥2 times/week and smoking ≥2 times/week.
131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were intention-to-treat.
B: Participants were ≥18 years, smoked ≥10 cigarettes/day for at least 6 months, had DSM-IV alcohol abuse or dependence, and were interested in quitting smoking.
“Participants were randomly assigned to receive 12 weeks of varenicline 1 mg twice daily or matching placebo.
The primary end point was 7-day point prevalence smoking abstinence at week 12.”

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?

6. Are the Results Valid? Were participants randomized?
Was randomization concealed?
Were participants analyzed in the groups to which they were randomized?
Were participants in the intervention and control groups similar?

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

8. Were participants randomized?
Yes.
In both studies, patients were randomized.

9. Was randomization concealed?
Yes.

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

11. Were the participants in the intervention and control groups similar?
A: Yes. Randomization to varenicline or placebo was stratified by site and sex.
B: Yes.

12. Were participants aware of group allocation?
No. In both trials, participants, investigators, and study staff were blinded to group allocation.

13. Were outcome assessors aware of group allocation?
No.

14. Was follow-up complete?
A: Mostly. Of 131 randomized, 101 completed treatment.
B: No. Of 33 randomized, 14 completed the study.

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

16. How large and precise was the treatment effect?
The primary outcomes—percentage of heavy drinking days (PHDD) and no heavy drinking days (NHDD) during weeks 9–16—were not significantly different between the two groups.
Varenicline did result in significantly greater abstinence from smoking during the last 28 days of treatment (13% versus 0%, respectively).
In secondary analyses, varenicline was associated with a significantly greater decrease in PHDD among men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, to 1.18; P = .09; Cohen d = 0.45), but not among women (LS mean difference, -0.69; 95% CI, to 0.25; P = .15; Cohen d = -0.53). 16

17. How large and precise was the treatment effect? cntd.B:
Seven-day smoking abstinence was more common in the varenicline group at 12 weeks (44% versus 6% in the placebo group, P = .01).
Participants in the varenicline group reported 2.8 fewer drinks per drinking day on average at 12 weeks (5.7 [3.9] vs 9.0 [5.3] drinks; treatment effect estimate, -2.8 [90% CI, -6.6 to -1.0]).
There were no significant differences between groups in drinks per day, drinking days, or heavy drinking days. 17

18. How Can I Apply the Results to Patient Care?
Were all clinically important outcomes considered?
Are the likely treatment benefits worth the potential harm and costs?

19. Were all clinically important outcomes considered?
Yes.

20. Are the likely treatment benefits worth the potential harm and costs?
Probably. These trials suggest that varenicline is effective for tobacco cessation, even among those with alcohol use disorder not seeking treatment for smoking. The effects on alcohol use appear to be smaller and inconclusive.
Costs were not considered in these studies.