Transcript Update on Alcohol and Health

Update on
Alcohol, Other Drugs,
and Health
April 2008
www.aodhealth.org
1
Studies on
Interventions and
Assessments
www.aodhealth.org
2
Baclofen for Alcohol
Dependence in Patients with
Cirrhosis
Addolorato G, et al. Lancet. 2007;370(9603):1915–1922.
Summary by Richard Saitz, MD, MPH
www.aodhealth.org
3
Objectives/Methods


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.

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.

Analysis was by intention to treat.
www.aodhealth.org
4
Results

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%).
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.
www.aodhealth.org
5
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.
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.
www.aodhealth.org
6
Bupropion Added to
Nicotine Replacement for
Patients in Alcohol
Treatment
Grant K, et al. Alcohol. 2007;41(5):381–391.
Summary by Julia H. Arnsten, MD, MPH
www.aodhealth.org
7
Objectives/Methods




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.
Medication was combined with nicotine replacement in all
cases, and optional counseling was offered.
Criteria for inclusion were…



smoking ≥20 cigarettes per day.
willingness to quit.
absence of a psychiatric condition or contraindication to bupropion.
www.aodhealth.org
8
Results



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:

30% and 18%, respectively, at week 4; and

17% and 29%, respectively, at 6 months.
Despite the decrease, no significant difference in
smoking abstinence was observed between the groups.
www.aodhealth.org
9
Comments



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.
Results do suggest that nicotine replacement in
patients undergoing treatment for alcoholism may
help them quit smoking.
www.aodhealth.org
10
Effect of Opioid Dependence
Medications on Cardiac QT
Intervals
Wedam EF, et al. Arch Intern Med. 2007;167(22):2469-2475.
Summary by David A. Fiellin, MD
www.aodhealth.org
11
Objectives/Methods



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.
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
www.aodhealth.org
12
Results



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.
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.
www.aodhealth.org
13
Comments


Results of this study indicate that buprenorphine is less
likely than LAAM or methadone to prolong the QTc.
Limitations of this study include…




administration of buprenorphine 3 times per week rather than
1 time per day, as is standard practice.
a short treatment period.
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.
www.aodhealth.org
14
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
www.aodhealth.org
15
Objectives/Methods



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.
110 opioid-dependent adults admitted for OPIOID?
detoxification completed a brief questionnaire,
including the Brief Pain Inventory–Short Form, to
assess physical pain.
www.aodhealth.org
16
Results



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).
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.
www.aodhealth.org
17
Comments


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…




a high-acuity patient population (seeking inpatient
treatment).
lack of detail about the timing of pain assessment.
insufficient data on the sequence of screening steps.
acknowledgment of the potential for withdrawal
symptoms to be reported as pain.
www.aodhealth.org
18
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.
Additional research is needed to assess the impact
of pain screening algorithms on clinical outcomes
among people in treatment for opioid dependence.
www.aodhealth.org
19
Studies of
Health Outcomes
www.aodhealth.org
20
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
www.aodhealth.org
21
Objectives/Methods



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.
In the 3789 patients identified, risk of death during
treatment was compared with risk before and after
treatment.
www.aodhealth.org
22
Results




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.
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 treatment (RR, 1.8 compared with men on the waiting list).
www.aodhealth.org
23
Comments



This rigorous investigation provides further strong
evidence that OMT lowers mortality risk in opioiddependent patients.
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.
www.aodhealth.org
24
Relapse Risk in People with
Remitted Alcohol
Dependence
Dawson DA, et al. Alcohol Clin Exp Res. 2007;31(12):2036–2045.
Summary by Kevin L. Kraemer, MD, MSc
www.aodhealth.org
25
Objectives/Methods



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.
Analysis was based on data from the National
Epidemiologic Survey on Alcohol and Related
Conditions (NESARC).
www.aodhealth.org
26
Results



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.
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.
www.aodhealth.org
27
Results (cont.)



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.
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 followup.
www.aodhealth.org
28
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.
Clinicians need to carefully monitor and support
abstinence in people with remitted alcohol
dependence.
www.aodhealth.org
29
Similar Outcomes from Observed
and Unobserved Dosing of
Buprenorphine-Naloxone
Bell J, et al. Addiction. 2007;102(12):1899–1907.
Summary by Peter D. Friedmann, MD, MPH
www.aodhealth.org
30
Objectives/Methods



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.
Monitoring consisted of a weekly interview relating to
heroin and other drug use, with submission of a urine
sample at each interview.
www.aodhealth.org
31
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).
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).
www.aodhealth.org
32
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.
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.
www.aodhealth.org
33
Persistent Hepatitis C
Reinfection in Injection Drug
Users Who Have Cleared the
Virus
Currie SL, et al. Drug Alcohol Depend. 2008:93:(1-2):148–154.
Summary by Alexander Y. Walley, MD, MSc
www.aodhealth.org
34
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.
To determine this rate, researchers prospectively
examined 224 people with HCV infection, a history of
injection drug use, and serial hepatitis C viral loads.
www.aodhealth.org
35
Results



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.
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.
www.aodhealth.org
36
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.
Determining reliable rates of hepatitis C reinfection
among injection drug users will require larger studies.
www.aodhealth.org
37