1. www.aodhealth.org1 Update on Alcohol, Other Drugs, and Health April 2008

2. www.aodhealth.org2 Studies on Interventions and Assessments

3. www.aodhealth.org3 Baclofen for Alcohol Dependence in Patients with Cirrhosis Addolorato G, et al. Lancet. 2007;370(9603):1915–1922. Summary by Richard Saitz, MD, MPH

4. www.aodhealth.org4 Objectives/Methods Some medications used to treat alcohol dependence are potentially hepatotoxic. Some medications used to treat alcohol dependence are potentially hepatotoxic. This study measured the effectiveness and safety of baclofen in achieving and maintaining alcohol abstinence in patients with cirrhosis. This study measured the effectiveness and safety of baclofen in achieving and maintaining alcohol abstinence in patients with cirrhosis. 84 patients were randomly allocated TO either oral baclofen or placebo for 12 weeks. 84 patients were randomly allocated TO either oral baclofen or placebo for 12 weeks. A family member administered medication and monitored adherence, side effects, and alcohol use. A family member administered medication and monitored adherence, side effects, and alcohol use. Analysis was by intention to treat. Analysis was by intention to treat.

5. www.aodhealth.org5 Results At the end of the study period, those patients who received baclofen… At the end of the study period, those patients who received baclofen… were much more likely to be abstinent than patients who received placebo (71% versus 29%). were much more likely to be abstinent than patients who received placebo (71% versus 29%). had greater improvements in liver-related blood tests. had greater improvements in liver-related blood tests. had side effects similar to the placebo group, none of which led to discontinuation of the medication. had side effects similar to the placebo group, none of which led to discontinuation of the medication.

6. www.aodhealth.org6 Comments Although acamprosate poses no risk of liver toxicity and naltrexone poses little risk at standard doses, another nonhepatotoxic medication option to treat alcohol dependence would be useful. Although acamprosate poses no risk of liver toxicity and naltrexone poses little risk at standard doses, another nonhepatotoxic medication option to treat alcohol dependence would be useful. The effect of baclofen on abstinence in these patients was impressive; however, the sample was small and the study short. Results should be confirmed by future studies. The effect of baclofen on abstinence in these patients was impressive; however, the sample was small and the study short. Results should be confirmed by future studies.

7. www.aodhealth.org7 Grant K, et al. Alcohol. 2007;41(5):381–391. Summary by Julia H. Arnsten, MD, MPH Bupropion Added to Nicotine Replacement for Patients in Alcohol Treatment

8. www.aodhealth.org8 Objectives/Methods Bupropion aids in smoking cessation, however, its effect on smoking in patients being treated for alcohol dependence is not known. Bupropion aids in smoking cessation, however, its effect on smoking in patients being treated for alcohol dependence is not known. This double-blind, placebo-controlled study of 58 patients undergoing treatment for alcohol dependence examined the effect of bupropion on smoking in this group. This double-blind, placebo-controlled study of 58 patients undergoing treatment for alcohol dependence examined the effect of bupropion on smoking in this group. Medication was combined with nicotine replacement in all cases, and optional counseling was offered. Medication was combined with nicotine replacement in all cases, and optional counseling was offered. Criteria for inclusion were… Criteria for inclusion were… smoking ≥20 cigarettes per day. smoking ≥20 cigarettes per day. willingness to quit. willingness to quit. absence of a psychiatric condition or contraindication to bupropion. absence of a psychiatric condition or contraindication to bupropion.

9. www.aodhealth.org9 Results Thirty-three percent of patients in the bupropion group and 11% in the placebo group discontinued medication by week 4. Thirty-three percent of patients in the bupropion group and 11% in the placebo group discontinued medication by week 4. Smoking decreased significantly in both the bupropion and placebo groups: Smoking decreased significantly in both the bupropion and placebo groups: 30% and 18%, respectively, at week 4; and 30% and 18%, respectively, at week 4; and 17% and 29%, respectively, at 6 months. 17% and 29%, respectively, at 6 months. Despite the decrease, no significant difference in smoking abstinence was observed between the groups. Despite the decrease, no significant difference in smoking abstinence was observed between the groups.

10. www.aodhealth.org10 Comments People with alcohol or other drug use disorders have a high prevalence of smoking and much difficulty quitting. People with alcohol or other drug use disorders have a high prevalence of smoking and much difficulty quitting. Bupropion, when added to nicotine patch, did not improve smoking outcomes in this study. Bupropion, when added to nicotine patch, did not improve smoking outcomes in this study. Results do suggest that nicotine replacement in patients undergoing treatment for alcoholism may help them quit smoking. Results do suggest that nicotine replacement in patients undergoing treatment for alcoholism may help them quit smoking.

11. www.aodhealth.org11 Wedam EF, et al. Arch Intern Med. 2007;167(22):2469-2475. Summary by David A. Fiellin, MD Effect of Opioid Dependence Medications on Cardiac QT Intervals

12. www.aodhealth.org12 Objectives/Methods Levomethadyl (LAMM), methadone, and buprenorphine are effective treatments for opioid dependence. Levomethadyl (LAMM), methadone, and buprenorphine are effective treatments for opioid dependence. All 3 block hERG*-channel activity, which may prolong the corrected QT interval (QTc). Both LAMM and methadone have been associated with severe cardiac arrhythmias. All 3 block hERG*-channel activity, which may prolong the corrected QT interval (QTc). Both LAMM and methadone have been associated with severe cardiac arrhythmias. In a recent randomized, controlled trial, researchers compared the effects of the 3 medications on the QTc in 154 opioid addicted patients. In a recent randomized, controlled trial, researchers compared the effects of the 3 medications on the QTc in 154 opioid addicted patients. * *human ether-a-go-go–related gene

13. www.aodhealth.org13 Results Baseline QTc was similar in the 3 groups. Baseline QTc was similar in the 3 groups. During treatment, QTc was prolonged in 28% of subjects in the LAAM group and in 23% of subjects in the methadone group, but in no subjects in the buprenorphine group. During treatment, QTc was prolonged in 28% of subjects in the LAAM group and in 23% of subjects in the methadone group, but in no subjects in the buprenorphine group. In the LAMM group, 21% of patients had an increase in QTc >60 milliseconds above baseline compared with 12% in the methadone group and 2% in the buprenorphine group. In the LAMM group, 21% of patients had an increase in QTc >60 milliseconds above baseline compared with 12% in the methadone group and 2% in the buprenorphine group.

14. www.aodhealth.org14 Comments Results of this study indicate that buprenorphine is less likely than LAAM or methadone to prolong the QTc. Results of this study indicate that buprenorphine is less likely than LAAM or methadone to prolong the QTc. Limitations of this study include… Limitations of this study include… administration of buprenorphine 3 times per week rather than 1 time per day, as is standard practice. administration of buprenorphine 3 times per week rather than 1 time per day, as is standard practice. a short treatment period. a short treatment period. lack of a placebo arm due to ethical concerns. lack of a placebo arm due to ethical concerns. LAAM is no longer available in the United States. Physicians prescribing methadone should consider checking a baseline ECG and monitoring QTc intervals periodically. LAAM is no longer available in the United States. Physicians prescribing methadone should consider checking a baseline ECG and monitoring QTc intervals periodically.

15. www.aodhealth.org15 A Brief Screen for Classifying Pain Severity in Patients with Opioid Dependence Potter JS, et al. Am J Drug Alcohol Abuse. 2008;34(1):101–107. Summary by Marc N. Gourevitch, MD, MPH

16. www.aodhealth.org16 Objectives/Methods Pain is prevalent in people with opioid dependence. Its association with psychosocial stressors may threaten clinical gains achieved through substance abuse treatment. Pain is prevalent in people with opioid dependence. Its association with psychosocial stressors may threaten clinical gains achieved through substance abuse treatment. This study explored the benefit of rapid screening for pain in opioid-dependent patients seeking treatment. This study explored the benefit of rapid screening for pain in opioid-dependent patients seeking treatment. 110 opioid-dependent adults admitted for OPIOID? detoxification completed a brief questionnaire, including the Brief Pain Inventory–Short Form, to assess physical pain. 110 opioid-dependent adults admitted for OPIOID? detoxification completed a brief questionnaire, including the Brief Pain Inventory–Short Form, to assess physical pain.

17. www.aodhealth.org17 Results 91% of patients reported some pain during the previous week. 91% of patients reported some pain during the previous week. 43% reported chronic pain (lasting ≥6 months), and 70% of those with chronic pain rated their pain as “severe” (≥7on a scale of 1 to 10). 43% reported chronic pain (lasting ≥6 months), and 70% of those with chronic pain rated their pain as “severe” (≥7on a scale of 1 to 10). Patients with severe chronic pain had worse depressive symptoms and were more likely to be receiving occupational disability benefits than patients with less severe or no pain. Patients with severe chronic pain had worse depressive symptoms and were more likely to be receiving occupational disability benefits than patients with less severe or no pain.

18. www.aodhealth.org18 Comments Severe chronic pain was common among patients seeking treatment for opioid dependence and was associated with functional impairment that could potentially complicate recovery. Severe chronic pain was common among patients seeking treatment for opioid dependence and was associated with functional impairment that could potentially complicate recovery. Limitations of this study included… Limitations of this study included… a high-acuity patient population (seeking inpatient treatment). a high-acuity patient population (seeking inpatient treatment). lack of detail about the timing of pain assessment. lack of detail about the timing of pain assessment. insufficient data on the sequence of screening steps. insufficient data on the sequence of screening steps. acknowledgment of the potential for withdrawal symptoms to be reported as pain. acknowledgment of the potential for withdrawal symptoms to be reported as pain.

19. www.aodhealth.org19 Comments (cont.) Nonetheless, results suggest that assessing pain severity in patients undergoing treatment for opioid dependence may help clinicians identify those who might benefit from pain-related interventions. Nonetheless, results suggest that assessing pain severity in patients undergoing treatment for opioid dependence may help clinicians identify those who might benefit from pain-related interventions. Additional research is needed to assess the impact of pain screening algorithms on clinical outcomes among people in treatment for opioid dependence. Additional research is needed to assess the impact of pain screening algorithms on clinical outcomes among people in treatment for opioid dependence.

20. www.aodhealth.org20 Studies of Health Outcomes

21. www.aodhealth.org21 Death Before, During, and After Opioid Maintenance Treatment Clausen T, et al. Drug Alcohol Depend. 2008;94(1-3):151-157. Summary by Jeffrey A. Samet, MD, MA, MPH

22. www.aodhealth.org22 Objectives/Methods This Norwegian study sought to determine the extent to which opioid maintenance therapy (OMT) reduced mortality in patients with opioid dependence. This Norwegian study sought to determine the extent to which opioid maintenance therapy (OMT) reduced mortality in patients with opioid dependence. Researchers linked data from a national death registry to a national database of people either on a waiting list for OMT, receiving OMT (predominantly methadone), or who had discontinued OMT. Researchers linked data from a national death registry to a national database of people either on a waiting list for OMT, receiving OMT (predominantly methadone), or who had discontinued OMT. In the 3789 patients identified, risk of death during treatment was compared with risk before and after treatment. In the 3789 patients identified, risk of death during treatment was compared with risk before and after treatment.

23. www.aodhealth.org23 Results Over 7 years, 213 patients died. Over 7 years, 213 patients died. 79% of deaths in the waiting-list group, 27% of deaths in the treatment group, and 61% of deaths in the discontinued-treatment group were attributed to overdose. 79% of deaths in the waiting-list group, 27% of deaths in the treatment group, and 61% of deaths in the discontinued-treatment group were attributed to overdose. Mortality risk was significantly lower in patients receiving treatment than in patients on the waiting list (relative risk [RR], 0.5; death rates of 1.4 versus 2.4 per 100 person years, respectively). Mortality risk was significantly lower in patients receiving treatment than in patients on the waiting list (relative risk [RR], 0.5; death rates of 1.4 versus 2.4 per 100 person years, respectively). Risk was highest among men who discontinued treat- ment (RR, 1.8 compared with men on the waiting list). Risk was highest among men who discontinued treat- ment (RR, 1.8 compared with men on the waiting list).

24. www.aodhealth.org24 Comments This rigorous investigation provides further strong evidence that OMT lowers mortality risk in opioid- dependent patients. This rigorous investigation provides further strong evidence that OMT lowers mortality risk in opioid- dependent patients. Increasing cases of overdose death attributed to physician-prescribed methadone for pain have increased the potential for negative public backlash against methadone. Increasing cases of overdose death attributed to physician-prescribed methadone for pain have increased the potential for negative public backlash against methadone. Therefore, these results may play an important role in policy efforts supporting the continued use of OMT to treat patients with opioid dependence. Therefore, these results may play an important role in policy efforts supporting the continued use of OMT to treat patients with opioid dependence.

25. www.aodhealth.org25 Dawson DA, et al. Alcohol Clin Exp Res. 2007;31(12):2036–2045. Summary by Kevin L. Kraemer, MD, MSc Relapse Risk in People with Remitted Alcohol Dependence

26. www.aodhealth.org26 Objectives/Methods The rate of relapse among people in remission from alcohol dependence has not been extensively studied. The rate of relapse among people in remission from alcohol dependence has not been extensively studied. Researchers assessed alcohol use and alcohol use disorder (AUD) symptoms over 3 years among 1772 adults currently in remission from alcohol dependence. Researchers assessed alcohol use and alcohol use disorder (AUD) symptoms over 3 years among 1772 adults currently in remission from alcohol dependence. Analysis was based on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Analysis was based on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

27. www.aodhealth.org27 Results At baseline, 25% of subjects reported risky drinking, * 38% reported lower risk drinking, ** and 37% reported abstinence. At baseline, 25% of subjects reported risky drinking, * 38% reported lower risk drinking, ** and 37% reported abstinence. At follow-up, 51% of subjects who drank risky amounts, 27% who drank lower risk amounts, and 7% who abstained reported a recurrence of AUD symptoms. At follow-up, 51% of subjects who drank risky amounts, 27% who drank lower risk amounts, and 7% who abstained reported a recurrence of AUD symptoms. 10%, 4%, and 3% of subjects, respectively, met criteria for a recurrence of alcohol dependence. 10%, 4%, and 3% of subjects, respectively, met criteria for a recurrence of alcohol dependence. *Greater than 14 drinks per week (>7 for women) or >4 drinks on any day (>3 for women). **Subjects did not meet criteria for risky drinking.

28. www.aodhealth.org28 Results (cont.) Recurrence of AUD symptoms or alcohol dependence was more likely in younger subjects. Recurrence of AUD symptoms or alcohol dependence was more likely in younger subjects. Recurrence was less likely among patients with a longer duration of remission at baseline. Recurrence was less likely among patients with a longer duration of remission at baseline. In adjusted analyses, subjects who drank risky or lower risk amounts were more likely than subjects who abstained to report recurrent AUD symptoms (odds ratios [ORs], 14.6 and 5.8, respectively) and alcohol dependence (ORs, 7.0 and 3.0, respectively) at follow- up. In adjusted analyses, subjects who drank risky or lower risk amounts were more likely than subjects who abstained to report recurrent AUD symptoms (odds ratios [ORs], 14.6 and 5.8, respectively) and alcohol dependence (ORs, 7.0 and 3.0, respectively) at follow- up.

29. www.aodhealth.org29 Comments Results of this large longitudinal study show that relapse is common among people in remission from alcohol dependence and much more likely if they are drinking risky amounts. Results of this large longitudinal study show that relapse is common among people in remission from alcohol dependence and much more likely if they are drinking risky amounts. Clinicians need to carefully monitor and support abstinence in people with remitted alcohol dependence. Clinicians need to carefully monitor and support abstinence in people with remitted alcohol dependence.

30. www.aodhealth.org30 Bell J, et al. Addiction. 2007;102(12):1899–1907. Summary by Peter D. Friedmann, MD, MPH Similar Outcomes from Observed and Unobserved Dosing of Buprenorphine-Naloxone

31. www.aodhealth.org31 Objectives/Methods Few studies have compared the effects of observed (in clinic) dosing of opioid maintenance treatment with unobserved dosing (medication taken at home). Few studies have compared the effects of observed (in clinic) dosing of opioid maintenance treatment with unobserved dosing (medication taken at home). In this Australian study, 119 adults (>18 years) seeking maintenance treatment for heroin dependence were randomized to receive either observed dosing or unobserved dosing of buprenorphine-naloxone for 3 months. In this Australian study, 119 adults (>18 years) seeking maintenance treatment for heroin dependence were randomized to receive either observed dosing or unobserved dosing of buprenorphine-naloxone for 3 months. Monitoring consisted of a weekly interview relating to heroin and other drug use, with submission of a urine sample at each interview. Monitoring consisted of a weekly interview relating to heroin and other drug use, with submission of a urine sample at each interview.

32. www.aodhealth.org32 Results At 3 months, retention in treatment was similar in each group (61% in the observed dosing group and 57% in the unobserved dosing group). At 3 months, retention in treatment was similar in each group (61% in the observed dosing group and 57% in the unobserved dosing group). Reduction in days of heroin use in the past month was also similar (22-day reduction for the observed dosing group versus 18.5 days for the unobserved dosing group). Reduction in days of heroin use in the past month was also similar (22-day reduction for the observed dosing group versus 18.5 days for the unobserved dosing group). Treatment cost was significantly higher for the observed dosing group (US $1858 versus $1445). Treatment cost was significantly higher for the observed dosing group (US $1858 versus $1445).

33. www.aodhealth.org33 Comments Some opioid treatment providers believe observed dosing leads to better outcomes, while investigators in this study hypothesized that the attendance required would hinder retention and lead to worse outcomes. Some opioid treatment providers believe observed dosing leads to better outcomes, while investigators in this study hypothesized that the attendance required would hinder retention and lead to worse outcomes. Overall findings support neither assertion and indicate that unobserved dosing is more cost-effective on average. Overall findings support neither assertion and indicate that unobserved dosing is more cost-effective on average. The patient factors that would help determine which patients would benefit from observed dosing has yet to be established. The patient factors that would help determine which patients would benefit from observed dosing has yet to be established.

34. www.aodhealth.org34 Currie SL, et al. Drug Alcohol Depend. 2008:93:(1-2):148–154. Summary by Alexander Y. Walley, MD, MSc Persistent Hepatitis C Reinfection in Injection Drug Users Who Have Cleared the Virus

35. www.aodhealth.org35 Objectives/Methods The rate of persistent hepatitis C virus (HCV) reinfection—i.e., more than one consecutive positive HCV test in patients whose infection had previously been resolved—has not been measured prospectively. The rate of persistent hepatitis C virus (HCV) reinfection—i.e., more than one consecutive positive HCV test in patients whose infection had previously been resolved—has not been measured prospectively. To determine this rate, researchers prospectively examined 224 people with HCV infection, a history of injection drug use, and serial hepatitis C viral loads. To determine this rate, researchers prospectively examined 224 people with HCV infection, a history of injection drug use, and serial hepatitis C viral loads.

36. www.aodhealth.org36 Results Of 224 subjects followed for 1391 person-years, 38 resolved their infection (29 spontaneously and 9 after receiving HCV treatment). Of 224 subjects followed for 1391 person-years, 38 resolved their infection (29 spontaneously and 9 after receiving HCV treatment). Fourteen of those with an infection that resolved spontaneously and 2 of those whose resolution followed treatment continued to inject drugs during follow-up. Fourteen of those with an infection that resolved spontaneously and 2 of those whose resolution followed treatment continued to inject drugs during follow-up. Only 1 of the 38 subjects with a resolved infection (a subject who had spontaneous resolution, continued to inject drugs, and was also infected with HIV) had persistent HCV reinfection. Only 1 of the 38 subjects with a resolved infection (a subject who had spontaneous resolution, continued to inject drugs, and was also infected with HIV) had persistent HCV reinfection.

37. www.aodhealth.org37 Comments Results of this study indicate that persistent HCV reinfection in people with resolved HCV, even in those with ongoing injection drug use, is much less common than previous reports suggest. Results of this study indicate that persistent HCV reinfection in people with resolved HCV, even in those with ongoing injection drug use, is much less common than previous reports suggest. Determining reliable rates of hepatitis C reinfection among injection drug users will require larger studies. Determining reliable rates of hepatitis C reinfection among injection drug users will require larger studies.