1. www.aodhealth.org1 Journal Club Alcohol, Other Drugs, and Health: Current Evidence September–October 2008

2. www.aodhealth.org2 Featured Article Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo- controlled trial Schottenfeld RS, et al. Lancet. 2008;371(9631):2192–2200.

3. www.aodhealth.org3 Study Objective To compare the efficacy of naltrexone versus buprenorphine for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviors

4. www.aodhealth.org4 Study Design A randomized, double-blind, placebo-controlled trial of 126 patients who: –completed a 14-day residential detoxification for heroin dependence and –received weekly manual-guided drug counseling. Patients were assigned to either… –placebo (n=39) –oral naltrexone (n=43), or –sublingual buprenorphine (n=44).

5. www.aodhealth.org5 Study Design - II Primary outcomes, assessed by urine testing 3 times per week, were: –days to first heroin use –days to heroin relapse –3 consecutive opioid-positive urine tests –maximum consecutive days of heroin abstinence –reductions in HIV risk behaviors

6. www.aodhealth.org6 Assessing Validity of an Article about Therapy Are the results valid? What are the results? How can I apply the results to patient care?

7. www.aodhealth.org7 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?

8. www.aodhealth.org8 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?

9. www.aodhealth.org9 Were patients randomized? Yes. –The patients were randomized to either oral naltrexone, sublingual buprenorphine, or placebo.

10. www.aodhealth.org10 Was randomization concealed? Yes. –Randomization was concealed.

11. www.aodhealth.org11 Were patients analyzed in the groups to which they were randomized? Yes. –Patients were analyzed in the groups to which they were randomized (intention to treat).

12. www.aodhealth.org12 Were the patients in the treatment and control groups similar? Yes. –Baseline clinical and demographic characteristics were similar across the 3 treatment groups.

13. www.aodhealth.org13 Were patients aware of group allocation? No. –Patients were unaware of group allocation. –All patients ingested oral capsules (containing either naltrexone or placebo) and dissolved sublingual tablets (containing either buprenorphine or placebo), under direct observation. –Patients gargled with a mentholated antiseptic mouthwash before taking the sublingual tablets to mask taste differences between active and placebo buprenorphine tablets.

14. www.aodhealth.org14 Were clinicians aware of group allocation? No. –Clinicians were unaware of group allocation.

15. www.aodhealth.org15 Were outcome assessors aware of group allocation? No. –Outcome assessors were unaware of group allocation.

16. www.aodhealth.org16 Was follow-up complete? Six month follow-up was obtained in: –36 of 44 patients randomized to buprenorphine. –29 of 42 patients randomized to naltrexone. –23 of 39 patients randomized to placebo. Urine tests on patients not available for follow-up were presumed to be positive for opiates given the high likelihood of relapse to drug use. The study was halted early due to an interim safety analysis. At the time the study was halted, researchers had complete follow-up on 103 of an anticipated sample size of 180 patients.

17. www.aodhealth.org17 What Are the Results? How large was the treatment effect? How precise was the estimate of the treatment effect?

18. www.aodhealth.org18 How large was the treatment effect? Buprenorphine was associated with greater time to first heroin use than naltrexone (hazard ratio [HR], 1.9) or placebo (HR, 2.0). Compared with placebo, buprenorphine was associated with greater time to heroin relapse (HR, 2.2) and more consecutive days abstinent (59 versus 24 days). Retention, time to first heroin use, and time to relapse did not differ significantly between naltrexone and placebo. HIV risk behaviors did not differ between any of the groups.

19. www.aodhealth.org19 How precise was the estimate of the treatment effect? The 95% confidence intervals were narrow, indicating a precise estimate of the treatment effect. Buprenorphine was associated with greater time to first heroin use than: –Naltrexone (HR, 1.9 [95% CI, 1.21–2.88]) –Placebo (HR, 2.0 [95% CI, 1.29–3.16]) Compared with placebo only, buprenorphine was associated with greater time to heroin relapse, (HR, 2.2 [95% CI, 1.38–3.42]).

20. www.aodhealth.org20 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?

21. www.aodhealth.org21 Were the study patients similar to those in my practice? Patients were recruited from an urban community in Malaysia. Sixty-eight percent were of Malay ethnic origin. The majority were in their late 30s and had been using heroin for approximately 15 years. Gender is not specified.

22. www.aodhealth.org22 Were all clinically important outcomes considered? Yes. –The primary and secondary outcomes included heroin use, relapse, and HIV risk behaviors.

23. www.aodhealth.org23 Are the likely treatment benefits worth the potential harm and costs? No substantive harms were noted with buprenorphine treatment. Patients receiving buprenorphine were more likely to report constipation, drowsiness, urinary hesitancy, or sweating, but these reports were only present in 1–2.5% of encounters. Costs were not considered in this analysis. Prior evaluations have found buprenorphine to be cost-effective.