www.aodhealth.org1 update on alcohol, other drugs, and health april 2008

www.aodhealth.orgwww.aodhealth.org 11

Update on Update on Alcohol, Other Alcohol, Other

Drugs, and HealthDrugs, and Health

April 2008April 2008


Studies on Studies on Interventions and Interventions and

AssessmentsAssessments


Baclofen for Alcohol Baclofen for Alcohol Dependence in Patients Dependence in Patients

with Cirrhosiswith Cirrhosis

Addolorato G, et al. Addolorato G, et al. Lancet.Lancet. 2007;370(9603):1915–1922. 2007;370(9603):1915–1922.

Summary by Richard Saitz, MD, MPH Summary by Richard Saitz, MD, MPH


Objectives/MethodsObjectives/Methods Some medications used to treat alcohol Some medications used to treat alcohol

dependence are potentially hepatotoxic.dependence are potentially hepatotoxic.

This study measured the effectiveness and This study measured the effectiveness and safety of baclofen in achieving and maintaining safety of baclofen in achieving and maintaining alcohol abstinence in patients with cirrhosis.alcohol abstinence in patients with cirrhosis.

84 patients were randomly allocated TO either 84 patients were randomly allocated TO either oral baclofen or placebo for 12 weeks.oral baclofen or placebo for 12 weeks.

A family member administered medication and A family member administered medication and monitored adherence, side effects, and alcohol monitored adherence, side effects, and alcohol use.use.

Analysis was by intention to treat. Analysis was by intention to treat.


ResultsResults At the end of the study period, those patients At the end of the study period, those patients

who received baclofen… who received baclofen…

were much more likely to be abstinent than were much more likely to be abstinent than patients who received placebo (71% versus patients who received placebo (71% versus 29%).29%).

had greater improvements in liver-related had greater improvements in liver-related blood tests.blood tests.

had side effects similar to the placebo group, had side effects similar to the placebo group, none of which led to discontinuation of the none of which led to discontinuation of the medication.medication.


CommentsComments

Although acamprosate poses no risk of liver Although acamprosate poses no risk of liver toxicity and naltrexone poses little risk at toxicity and naltrexone poses little risk at standard doses, another nonhepatotoxic standard doses, another nonhepatotoxic medication option to treat alcohol medication option to treat alcohol dependence would be useful.dependence would be useful.

The effect of baclofen on abstinence in these The effect of baclofen on abstinence in these patients was impressive; however, the sample patients was impressive; however, the sample was small and the study short. Results should was small and the study short. Results should be confirmed by future studies.be confirmed by future studies.


Grant K, et al. Alcohol. 2007;41(5):381–391.Summary by Julia H. Arnsten, MD, MPH

Bupropion Added to Bupropion Added to Nicotine Replacement Nicotine Replacement for Patients in Alcohol for Patients in Alcohol

TreatmentTreatment


Objectives/MethodsObjectives/Methods Bupropion aids in smoking cessation, however, its Bupropion aids in smoking cessation, however, its

effect on smoking in patients being treated for effect on smoking in patients being treated for alcohol dependence is not known.alcohol dependence is not known.

This double-blind, placebo-controlled study of 58 This double-blind, placebo-controlled study of 58 patients undergoing treatment for alcohol patients undergoing treatment for alcohol dependence examined the effect of bupropion on dependence examined the effect of bupropion on smoking in this group.smoking in this group.

Medication was combined with nicotine replacement Medication was combined with nicotine replacement in all cases, and optional counseling was offered.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 absence of a psychiatric condition or contraindication to

bupropion.bupropion.


ResultsResults Thirty-three percent of patients in the bupropion Thirty-three percent of patients in the bupropion

group and 11% in the placebo group group and 11% in the placebo group discontinued medication by week 4.discontinued medication by week 4.

Smoking decreased significantly in both the Smoking decreased significantly in both the bupropion and placebo groups:bupropion and placebo groups:

30% and 18%, respectively, at week 4; and30% 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 Despite the decrease, no significant difference in smoking abstinence was observed between in smoking abstinence was observed between the groups.the groups.


CommentsComments

People with alcohol or other drug use disorders People with alcohol or other drug use disorders have a high prevalence of smoking and much have a high prevalence of smoking and much difficulty quitting. difficulty quitting.

Bupropion, when added to nicotine patch, did Bupropion, when added to nicotine patch, did not improve smoking outcomes in this study.not improve smoking outcomes in this study.

Results do suggest that nicotine replacement Results do suggest that nicotine replacement in patients undergoing treatment for in patients undergoing treatment for alcoholism may help them quit smoking.alcoholism may help them quit smoking.


Wedam EF, et al. Wedam EF, et al. Arch Intern Med.Arch Intern Med. 2007;167(22):2469- 2007;167(22):2469-2475.2475.

Summary by David A. Fiellin, MDSummary by David A. Fiellin, MD

Effect of Opioid Effect of Opioid Dependence Medications Dependence Medications on Cardiac QT Intervalson Cardiac QT Intervals


Objectives/MethodsObjectives/Methods Levomethadyl (LAMM), methadone, and Levomethadyl (LAMM), methadone, and

buprenorphine are effective treatments for buprenorphine are effective treatments for opioid dependence.opioid dependence.

All 3 block hERG*-channel activity, which may All 3 block hERG*-channel activity, which may prolong the corrected QT interval (QTc). Both prolong the corrected QT interval (QTc). Both LAMM and methadone have been associated LAMM and methadone have been associated with severe cardiac arrhythmias.with severe cardiac arrhythmias.

In a recent randomized, controlled trial, In a recent randomized, controlled trial, researchers compared the effects of the 3 researchers compared the effects of the 3 medications on the QTc in 154 opioid addicted medications on the QTc in 154 opioid addicted patients.patients.

**human ether-a-go-go–related gene


ResultsResults Baseline QTc was similar in the 3 groups.Baseline QTc was similar in the 3 groups.

During treatment, QTc was prolonged in 28% During treatment, QTc was prolonged in 28% of subjects in the LAAM group and in 23% of of subjects in the LAAM group and in 23% of subjects in the methadone group, but in no subjects in the methadone group, but in no subjects in the buprenorphine group.subjects in the buprenorphine group.

In the LAMM group, 21% of patients had an In the LAMM group, 21% of patients had an increase in QTc >60 milliseconds above increase in QTc >60 milliseconds above baseline compared with 12% in the baseline compared with 12% in the methadone group and 2% in the methadone group and 2% in the buprenorphine group.buprenorphine group.


CommentsComments Results of this study indicate that buprenorphine Results of this study indicate that buprenorphine

is less likely than LAAM or methadone to prolong is less likely than LAAM or methadone to prolong the QTc.the QTc.

Limitations of this study include…Limitations of this study include… administration of buprenorphine 3 times per week administration of buprenorphine 3 times per week

rather than 1 time per day, as is standard practice.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. LAAM is no longer available in the United States. Physicians prescribing methadone should Physicians prescribing methadone should consider checking a baseline ECG and monitoring consider checking a baseline ECG and monitoring QTc intervals periodically.QTc intervals periodically.


A Brief Screen for A Brief Screen for Classifying Pain Severity Classifying Pain Severity in Patients with Opioid in Patients with Opioid

DependenceDependence

Potter JS, et al. Potter JS, et al. Am J Drug Alcohol Abuse.Am J Drug Alcohol Abuse. 2008;34(1):101–107. 2008;34(1):101–107.Summary by Marc N. Gourevitch, MD, MPHSummary by Marc N. Gourevitch, MD, MPH


Objectives/MethodsObjectives/Methods Pain is prevalent in people with opioid Pain is prevalent in people with opioid

dependence. Its association with psychosocial dependence. Its association with psychosocial stressors may threaten clinical gains achieved stressors may threaten clinical gains achieved through substance abuse treatment. through substance abuse treatment.

This study explored the benefit of rapid This study explored the benefit of rapid screening for pain in opioid-dependent patients screening for pain in opioid-dependent patients seeking treatment.seeking treatment.

110 opioid-dependent adults admitted for 110 opioid-dependent adults admitted for OPIOID? detoxification completed a brief OPIOID? detoxification completed a brief questionnaire, including the Brief Pain questionnaire, including the Brief Pain Inventory–Short Form, to assess physical pain.Inventory–Short Form, to assess physical pain.


Results Results 91% of patients reported some pain during 91% of patients reported some pain during

the previous week.the previous week.

43% reported chronic pain (lasting ≥6 43% reported chronic pain (lasting ≥6 months), and 70% of those with chronic pain months), and 70% of those with chronic pain rated their pain as “severe” (≥7on a scale of rated their pain as “severe” (≥7on a scale of 1 to 10).1 to 10).

Patients with severe chronic pain had worse Patients with severe chronic pain had worse depressive symptoms and were more likely depressive symptoms and were more likely to be receiving occupational disability to be receiving occupational disability benefits than patients with less severe or no benefits than patients with less severe or no pain.pain.


CommentsComments Severe chronic pain was common among patients Severe chronic pain was common among patients

seeking treatment for opioid dependence and was seeking treatment for opioid dependence and was associated with functional impairment that could associated with functional impairment that could potentially complicate recovery.potentially complicate recovery.

Limitations of this study included…Limitations of this study included…

a high-acuity patient population (seeking inpatient a high-acuity patient population (seeking inpatient treatment).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 acknowledgment of the potential for withdrawal

symptoms to be reported as pain.symptoms to be reported as pain.


Comments (cont.)Comments (cont.)

Nonetheless, results suggest that assessing Nonetheless, results suggest that assessing pain severity in patients undergoing pain severity in patients undergoing treatment for opioid dependence may help treatment for opioid dependence may help clinicians identify those who might benefit clinicians identify those who might benefit from pain-related interventions.from pain-related interventions.

Additional research is needed to assess the Additional research is needed to assess the impact of pain screening algorithms on impact of pain screening algorithms on clinical outcomes among people in treatment clinical outcomes among people in treatment for opioid dependence.for opioid dependence.


Studies of Studies of Health OutcomesHealth Outcomes


Death Before, During, Death Before, During, and After Opioid and After Opioid

Maintenance TreatmentMaintenance Treatment

Clausen T, et al. Clausen T, et al. Drug Alcohol Depend.Drug Alcohol Depend. 2008;94(1-3):151- 2008;94(1-3):151-157.157.

Summary by Jeffrey A. Samet, MD, MA, MPHSummary by Jeffrey A. Samet, MD, MA, MPH


Objectives/MethodsObjectives/Methods This Norwegian study sought to determine the This Norwegian study sought to determine the

extent to which opioid maintenance therapy extent to which opioid maintenance therapy (OMT) reduced mortality in patients with opioid (OMT) reduced mortality in patients with opioid dependence.dependence.

Researchers linked data from a national death Researchers linked data from a national death registry to a national database of people either registry to a national database of people either on a waiting list for OMT, receiving OMT on a waiting list for OMT, receiving OMT (predominantly methadone), or who had (predominantly methadone), or who had discontinued OMT.discontinued OMT.

In the 3789 patients identified, risk of death In the 3789 patients identified, risk of death during treatment was compared with risk before during treatment was compared with risk before and after treatment.and after treatment.


ResultsResults Over 7 years, 213 patients died.Over 7 years, 213 patients died.

79% of deaths in the waiting-list group, 27% of 79% of deaths in the waiting-list group, 27% of deaths in the treatment group, and 61% of deaths in the treatment group, and 61% of deaths in the discontinued-treatment group deaths in the discontinued-treatment group were attributed to overdose.were attributed to overdose.

Mortality risk was significantly lower in patients Mortality risk was significantly lower in patients receiving treatment than in patients on the receiving treatment than in patients on the waiting list (relative risk [RR], 0.5; death rates of waiting list (relative risk [RR], 0.5; death rates of 1.4 versus 2.4 per 100 person years, 1.4 versus 2.4 per 100 person years, respectively).respectively).

Risk was highest among men who discontinued Risk was highest among men who discontinued treat-ment (RR, 1.8 compared with men on the treat-ment (RR, 1.8 compared with men on the waiting list).waiting list).


CommentsComments This rigorous investigation provides further This rigorous investigation provides further

strong evidence that OMT lowers mortality risk strong evidence that OMT lowers mortality risk in opioid-dependent patients.in opioid-dependent patients.

Increasing cases of overdose death attributed Increasing cases of overdose death attributed to physician-prescribed methadone for pain to physician-prescribed methadone for pain have increased the potential for negative have increased the potential for negative public backlash against methadone.public backlash against methadone.

Therefore, these results may play an important Therefore, these results may play an important role in policy efforts supporting the continued role in policy efforts supporting the continued use of OMT to treat patients with opioid use of OMT to treat patients with opioid dependence.dependence.


Dawson DA, et al. Dawson DA, et al. Alcohol Clin Exp Res.Alcohol Clin Exp Res. 2007;31(12):2036– 2007;31(12):2036–2045.2045.

Summary by Summary by Kevin L. Kraemer, MD, MScKevin L. Kraemer, MD, MSc

Relapse Risk in People with Relapse Risk in People with Remitted Alcohol Remitted Alcohol

DependenceDependence


Objectives/MethodsObjectives/Methods

The rate of relapse among people in remission from The rate of relapse among people in remission from alcohol dependence has not been extensively alcohol dependence has not been extensively studied. studied.

Researchers assessed alcohol use and alcohol use Researchers assessed alcohol use and alcohol use disorder (AUD) symptoms over 3 years among 1772 disorder (AUD) symptoms over 3 years among 1772 adults currently in remission from alcohol adults currently in remission from alcohol dependence.dependence.

Analysis was based on data from the National Analysis was based on data from the National Epidemiologic Survey on Alcohol and Related Epidemiologic Survey on Alcohol and Related Conditions (NESARC).Conditions (NESARC).


ResultsResults At baseline, 25% of subjects reported risky At baseline, 25% of subjects reported risky

drinking,drinking,* * 38% reported lower risk drinking,38% reported lower risk drinking,**** and and 37% reported abstinence.37% reported abstinence.

At follow-up, 51% of subjects who drank risky At follow-up, 51% of subjects who drank risky amounts, 27% who drank lower risk amounts, amounts, 27% who drank lower risk amounts, and 7% who abstained reported a recurrence of and 7% who abstained reported a recurrence of AUD symptoms.AUD symptoms.

10%, 4%, and 3% of subjects, respectively, met 10%, 4%, and 3% of subjects, respectively, met criteria for a recurrence of alcohol dependence.criteria for a recurrence of alcohol dependence.

*Greater than 14 drinks per week (>7 for women) or >4 drinks on any day *Greater than 14 drinks per week (>7 for women) or >4 drinks on any day (>3 for women).(>3 for women).

**Subjects did not meet criteria for risky drinking.**Subjects did not meet criteria for risky drinking.


Results (cont.)Results (cont.)

Recurrence of AUD symptoms or alcohol Recurrence of AUD symptoms or alcohol dependence was more likely in younger subjects.dependence was more likely in younger subjects.

Recurrence was less likely among patients with a Recurrence was less likely among patients with a longer duration of remission at baseline.longer duration of remission at baseline.

In adjusted analyses, subjects who drank risky or In adjusted analyses, subjects who drank risky or lower risk amounts were more likely than lower risk amounts were more likely than subjects who abstained to report recurrent AUD subjects who abstained to report recurrent AUD symptoms (odds ratios [ORs], 14.6 and 5.8, symptoms (odds ratios [ORs], 14.6 and 5.8, respectively) and alcohol dependence (ORs, 7.0 respectively) and alcohol dependence (ORs, 7.0 and 3.0, respectively) at follow-up.and 3.0, respectively) at follow-up.


CommentsComments

Results of this large longitudinal study show Results of this large longitudinal study show that relapse is common among people in that relapse is common among people in remission from alcohol dependence and remission from alcohol dependence and much more likely if they are drinking risky much more likely if they are drinking risky amounts.amounts.

Clinicians need to carefully monitor and Clinicians need to carefully monitor and support abstinence in people with remitted support abstinence in people with remitted alcohol dependence.alcohol dependence.


Bell J, et al. Bell J, et al. Addiction.Addiction. 2007;102(12):1899–1907. 2007;102(12):1899–1907.Summary by Summary by Peter D. Friedmann, MD, MPHPeter D. Friedmann, MD, MPH

Similar Outcomes from Similar Outcomes from Observed and Unobserved Observed and Unobserved Dosing of Buprenorphine-Dosing of Buprenorphine-

NaloxoneNaloxone


Objectives/MethodsObjectives/Methods Few studies have compared the effects of Few studies have compared the effects of

observed (in clinic) dosing of opioid observed (in clinic) dosing of opioid maintenance treatment with unobserved dosing maintenance treatment with unobserved dosing (medication taken at home).(medication taken at home).

In this Australian study, 119 adults (>18 years) In this Australian study, 119 adults (>18 years) seeking maintenance treatment for heroin seeking maintenance treatment for heroin dependence were randomized to receive either dependence were randomized to receive either observed dosing or unobserved dosing of observed dosing or unobserved dosing of buprenorphine-naloxone for 3 months.buprenorphine-naloxone for 3 months.

Monitoring consisted of a weekly interview Monitoring consisted of a weekly interview relating to heroin and other drug use, with relating to heroin and other drug use, with submission of a urine sample at each interview.submission of a urine sample at each interview.


ResultsResults

At 3 months, retention in treatment was similar At 3 months, retention in treatment was similar in each group (61% in the observed dosing in each group (61% in the observed dosing group and 57% in the unobserved dosing group).group and 57% in the unobserved dosing group).

Reduction in days of heroin use in the past Reduction in days of heroin use in the past month was also similar (22-day reduction for the month was also similar (22-day reduction for the observed dosing group versus 18.5 days for the observed dosing group versus 18.5 days for the unobserved dosing group). unobserved dosing group).

Treatment cost was significantly higher for the Treatment cost was significantly higher for the observed dosing group (US $1858 versus observed dosing group (US $1858 versus $1445).$1445).


CommentsComments Some opioid treatment providers believe Some opioid treatment providers believe

observed dosing leads to better outcomes, observed dosing leads to better outcomes, while investigators in this study hypothesized while investigators in this study hypothesized that the attendance required would hinder that the attendance required would hinder retention and lead to worse outcomes.retention and lead to worse outcomes.

Overall findings support neither assertion and Overall findings support neither assertion and indicate that unobserved dosing is more cost-indicate that unobserved dosing is more cost-effective on average. effective on average.

The patient factors that would help determine The patient factors that would help determine which patients would benefit from observed which patients would benefit from observed dosing has yet to be established.dosing has yet to be established.


Currie SL, et al. Currie SL, et al. Drug Alcohol Depend.Drug Alcohol Depend. 2008:93:(1-2):148– 2008:93:(1-2):148–154. Summary by Alexander Y. Walley, MD, MSc154. Summary by Alexander Y. Walley, MD, MSc

Persistent Hepatitis C Persistent Hepatitis C Reinfection in Injection Reinfection in Injection Drug Users Who Have Drug Users Who Have

Cleared the VirusCleared the Virus


Objectives/MethodsObjectives/Methods

The rate of persistent hepatitis C virus (HCV) The rate of persistent hepatitis C virus (HCV) reinfection—i.e., more than one consecutive reinfection—i.e., more than one consecutive positive HCV test in patients whose infection positive HCV test in patients whose infection had previously been resolved—has not been had previously been resolved—has not been measured prospectively.measured prospectively.

To determine this rate, researchers To determine this rate, researchers prospectively examined 224 people with HCV prospectively examined 224 people with HCV infection, a history of injection drug use, and infection, a history of injection drug use, and serial hepatitis C viral loads.serial hepatitis C viral loads.


ResultsResults Of 224 subjects followed for 1391 person-years, Of 224 subjects followed for 1391 person-years,

38 resolved their infection (29 spontaneously 38 resolved their infection (29 spontaneously and 9 after receiving HCV treatment).and 9 after receiving HCV treatment).

Fourteen of those with an infection that resolved Fourteen of those with an infection that resolved spontaneously and 2 of those whose resolution spontaneously and 2 of those whose resolution followed treatment continued to inject drugs followed treatment continued to inject drugs during follow-up.during follow-up.

Only 1 of the 38 subjects with a resolved Only 1 of the 38 subjects with a resolved infection (a subject who had spontaneous infection (a subject who had spontaneous resolution, continued to inject drugs, and was resolution, continued to inject drugs, and was also infected with HIV) had persistent HCV also infected with HIV) had persistent HCV reinfection.reinfection.


CommentsComments

Results of this study indicate that persistent Results of this study indicate that persistent HCV reinfection in people with resolved HCV, HCV reinfection in people with resolved HCV, even in those with ongoing injection drug use, even in those with ongoing injection drug use, is much less common than previous reports is much less common than previous reports suggest.suggest.

Determining reliable rates of hepatitis C Determining reliable rates of hepatitis C reinfection among injection drug users will reinfection among injection drug users will require larger studies. require larger studies.

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