Transcript Update on Alcohol, Other Drugs, and Health

Update on
Alcohol, Other Drugs,
and Health
September–October 2008
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1
Studies on
Interventions
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2
Brief Intervention for Illicit Drug
Use in Primary Health Care
Settings: Does It Work?
Humeniuk R, et al. Technical Report of Phase III Findings of the
WHO ASSIST Randomized Controlled Trial. Geneva, Switzerland:
WHO, 2008.
Summary by Richard Saitz MD, MPH
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3
Objectives/Methods



World Health Organization researchers conducted the
first randomized trial on the efficacy of brief
intervention (BI) to decrease illicit drug use.
Patients (N=731) with current drug use identified
using the Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST) were recruited
from sexually transmitted disease clinics, walk-in
clinics, a dental clinic, and community medical care
sites in 4 countries.
Patients scoring in the moderate-risk range were
randomly assigned to BI or no BI (until after the
study). Patients who scored in the low- or high-risk
range were excluded.
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4
Results


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Brief intervention was associated with a 3-point
greater decrease (compared with no BI) in a
substance use score with a maximum of 336
points.
Cannabis and stimulant scores also decreased
more for BI subjects (by about 2–3 points on
scales with a maximum of 39 points); opioid
scores did not.
Substance use was not significantly impacted by
BI in the US.
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5
Comments

Brief intervention for drugs may have some benefit in
general health settings. However, the clinical
significance in this study is unclear.

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The use of the same interviewers for the BI and followup assessments could introduce a bias favoring BI.
Patients were not recruited from what is usually
considered primary care.
The clinical meaning of small differences in substance
use scores has not been established.
Screening and BI for illicit drug use is more complex
than it is for alcohol. Whether BI will have important
clinical benefits in primary care remains unknown.
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6
Buprenorphine with Drug
Counseling Is Superior to
Oral Naltrexone with
Counseling or Counseling
Alone for Heroin
Dependence
Schottenfeld RS, et al. Lancet. 2008;371(9631): 2192–2200.
Summary by Peter D. Friedmann, MD, MPH
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7
Objectives/Methods



Opiate dependence and injection drug use are major
vectors for HIV transmission across the globe, yet
many nations prohibit opioid agonist treatment (OAT).
Researchers conducted a randomized, double-blind,
placebo-controlled trial of OAT in patients who had
completed standardized 14-day residential
detoxification and begun group drug counseling.
Patients were assigned to either placebo (n=39), oral
naltrexone (n=43), or sublingual buprenorphine
(n=44).
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Results

Over 24 weeks of follow-up,

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treatment retention was significantly higher for
buprenorphine compared with naltrexone.
time to first heroin use was significantly higher for
buprenorphine compared with naltrexone or
placebo.
time to heroin relapse was significantly higher for
buprenorphine compared with naltrexone or
placebo.
no differences were detected between oral
naltrexone and placebo.
HIV risk behaviors did not differ between groups.
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Comments

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
Studies from around the world have demonstrated
that OAT with counseling is superior both to
counseling alone and to oral naltrexone with or
without counseling.
Nonetheless, significant barriers to OAT remain
both within the US and internationally.
Policy initiatives are needed to change regulations
about these evidence-based treatments for opiate
dependence.
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10
Topiramate, Physical Health, and
Psychosocial Function in Adults
with Alcohol Dependence
Johnson BA, et al. Arch Intern Med. 2008;168(11):1188–1199.
Summary by Kevin L. Kraemer, MD, MSc
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Objectives/Methods

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Topiramate combined with adherence
enhancement counseling can decrease alcohol
use in some alcohol-dependent individuals.
To assess whether topiramate also improves
physical health and psychosocial function,
researchers analyzed data from 364 patients in a
14-week multisite double-blind trial.
Patients were randomized to receive either
topiramate (up to 300 mg/day) or placebo.
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Objectives/Methods (cont’d)

Eligibility criteria included:
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diagnosis of alcohol dependence per DSM-IV.
consumption of ≥35 drinks per week (men) and
≥28 drinks per week (women).
negative screens for opioids, cocaine,
amphetamines, antidepressants, propoxyphene,
and barbiturates.
No additional psychiatric diagnosis (e.g.,
depression).
No clinically significant withdrawal symptoms.
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Results

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Sixty-three percent (112 of 179 patients) receiving
topiramate completed the trial. More than half of those
who withdrew (34 of 67 patients) did so due to side
effects.
Seventy-eight percent (144 of 185 patients) receiving
placebo completed the trial. Three percent (6 of 185
patients) withdrew due to side effects.
Patients who received topiramate had significantly
greater decreases in…
 liver enzymes
 body mass index
 harmful consequences of
drinking
 blood pressure
 cholesterol
 obsessional thoughts about
alcohol
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Results (cont’d)

These physical health findings were similar
whether excluding or using multiple imputation
for patients who did not complete the study.
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Comments

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
These findings suggest topiramate can improve
physical health and psychosocial function in people
with alcohol dependence.
Some physical health improvements may have been
due to the weight loss associated with topiramate.
The generalizability of the findings is uncertain
because:

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The study eligibility criteria were restrictive.
Sixty-seven patients (nearly 40%) in the topiramate
group did not finish the trial despite weekly adherence
counseling.
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16
Drug-related HIV Risk
Behaviors Decrease during
Treatment with
Buprenorphine/Naloxone
in Primary Care
Sullivan LE, et al. J Subst Abuse Treat. 2008;35(1):87–92.
Alexander Y. Walley, MD, MSc
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Objectives/Methods

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The impact of primary-care based buprenorphine/
naloxone maintenance treatment on HIV risk
behaviors has not been examined.
Researchers studied changes in HIV risk behaviors
among 155 opioid dependent subjects receiving
buprenorphine/naloxone maintenance treatment
in a primary care setting.
Subjects were enrolled in a randomized controlled
trial of 2 levels of psychosocial counseling.
Neither counseling arm received HIV-specific risk
reduction counseling.
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Results
HIV risk behaviors at baseline and at 12 and 24 weeks
Risk behavior
(% of patients)
Baseline
(n=155)
12 weeks 24 weeks
(n=91)
(n=75)
Intravenous drug use
37
12
7
Needle sharing
8
4
1
64
13
15
Sex while under the influence of
drugs or alcohol
Other sex-related HIV risk behaviors
(e.g., nonuse of condoms)

No significant changes
No changes in HIV risk behaviors were detected by
counseling group assignment.
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Comments


This secondary analysis of a randomized controlled trial demonstrates that drug-related HIV
risk behaviors decrease during buprenorphine/
naloxone maintenance in primary care.
Additional risk-reduction counseling interventions
are needed to increase condom use and
decrease non-drug–related sexual risk behaviors
among buprenorphine/ naloxone maintenance
patients.
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20
Levetiracetam (Keppra)
Shows Promise in Treating
Alcohol Dependence
Sarid-Segal O, et al. Am J Drug Alcohol Abuse. 2008;34(4):441–447.
Summary by Marc N. Gourevitch, MD, MPH
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Objectives/Methods

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Preliminary evidence suggests that levetiracetam
(Keppra), used in treating partial onset seizures,
diminishes symptoms of alcohol withdrawal.
In an open label study, investigators assessed the
impact of a 10-week course of levetiracetam
(1000 mg twice daily) on alcohol consumption in
20 alcohol dependent persons.
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Results
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Mean daily drinks consumed diminished from >5 per
day at baseline to <2 per day during weeks 5–10
(p=.0005).
Significant improvements were also observed in
alcohol craving and alcohol composite scores (but not
other composite scores) on the ASI-Lite.*
Alcohol withdrawal scores (CIWA-Ar**) were low at
baseline and remained low during the course of the
study.
Side effects, including irritability and sedation, were
reported in 4 of the 20 participants.
*Addiction Severity Index, Lite version; **Clinical Institute Withdrawal Assessment for
Alcohol, Revised version.
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Comments
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Although levetiracetam significantly diminished
alcohol consumption in this study, the proportion
of patients achieving abstinence was not
reported.
Open-label studies cannot distinguish the impact
of the medication from that of participants’
motivation to drink less.
Nonetheless, because of its potential to treat
alcohol dependence, levetiracetam should be
studied in a double-blind randomized controlled
trial.
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24
Effectiveness of a Smoking
Cessation Intervention in
Substance Abuse
Treatment Programs
Reid MS, et al. J Subst Abuse Treat. 2008;35(1):68–77.
Summary by Julia H. Arnsten, MD, MPH
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Objectives/Methods

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Although patients with substance abuse disorders often
smoke, treating nicotine dependence in substance
abuse treatment (SAT) settings is uncommon.
Researchers conducted a randomized trial to evaluate
the effectiveness of a smoking cessation intervention in
SAT programs.
They compared nicotine replacement therapy plus 9
weekly cognitive-behavioral group counseling sessions
with treatment-as-usual (TAU) in 225 smokers from 5
methadone maintenance programs and 2 drug- and
alcohol-dependence treatment programs.
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Results
Smoking Abstinence Rates
Intervention
arm (%)
TAU arm
(%)
p
10-11
<1
<.01
Week 13 follow-up
5.5
0
.065
Week 26 follow-up
5.7
5.2
.963
Weeks 2–7 (treatment period)

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Intervention-arm participants also had significantly greater
reductions in cigarettes smoked, cigarette craving, and
nicotine withdrawal during treatment.
No differences in SAT retention, abstinence from primary
substance of abuse, or craving for primary substance of
abuse was observed between groups.
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Comments


Combining nicotine replacement therapy and
counseling can be effective in reducing smoking,
although the effect was diminished at follow-up.
Results of this study indicate that SAT programs
offer a unique means of integrating nicotine
dependence treatment with treatment for
substance abuse.
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28
Studies of
Health Outcomes
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29
Universal Screening, Assessment,
and Treatment of Substance Use
at Prenatal Visits Improves
Obstetric Outcomes
Goler NC, et al. J Perinatol. 2008;28(9):597–603.
Summary by Peter D. Friedmann, MD, MPH
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Objectives/Methods
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
This retrospective cohort study examined whether
Early Start, a coordinated program of prenatal
substance abuse screening, treatment, and patient/
provider education, including a licensed substanceuse treatment specialist onsite in the obstetric clinic,
improved perinatal outcomes.
Investigators compared obstetric outcomes for:
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2073 women treated by Early Start.
1203 women who screened positive for alcohol or drug use
and were assessed by Early Start, but did not receive
treatment.
156 women who screened positive but were never assessed
or treated.
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Results

Adjusting for maternal age, ethnicity, and
number of prenatal visits, women who screened
positive for substance use but were not treated
had more:
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preterm deliveries (odds ratio [OR], 2.1)
placental abruption (OR, 6.8)
intrauterine fetal demise (OR, 16.2)
compared with women treated by Early Start.
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Comments
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
This study suggests that screening and treatment
of substance-involved pregnant women during
prenatal visits improves obstetric outcomes.
The study design cannot eliminate the possibility
that greater motivation, not the intervention,
improved outcomes in the treatment group.
Nonetheless, these results add to growing
evidence that onsite screening and treatment for
alcohol and drug use can improves obstetrical
outcomes in pregnant women.
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33
Adolescent Cannabis Use Has a
Dose-Response Association
with Adverse Social Outcomes
in Adulthood
Fergusson DM, et al. Addiction. 2008;103(6):969–976.
Summary by Alexander Y. Walley, MD, MSc
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Objectives/Methods

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Investigators in New Zealand studied a birth cohort
of 1003 subjects to determine whether cannabis use
at age 14–21 had an adverse effect on education,
income, employment, relationship quality, and life
satisfaction at age 25.
Subjects were divided into 6 groups based on selfreported cannabis use ranging from no use to use on
greater than 400 occasions.
Potential confounding factors, (e.g., socioeconomic
status, family functioning, and comorbid mental
health and substance use disorders) were adjusted
for in the final analyses.
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Results

Subjects with increased adolescent cannabis use
showed significant linear trends for:
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decreased university degree attainment
decreased income
increased welfare dependence
increased unemployment
decreased relationship satisfaction
decreased life satisfaction
This dose-response relationship was consistent for
all outcomes in unadjusted and adjusted analyses.
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Comments
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These findings may be subject to reporting bias
and may not be immune to residual confounding.
However, a consistent dose-response association
between adolescent cannabis use and subsequent
adverse social outcomes is demonstrated.
Supporting evidence for a causation will require:
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similarly findings in other populations of different ages.
studies with more direct measures of cannabis use and
consequences than self-reports.
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37
Moderate Wine Drinking Is
Associated with Decreased
Prevalence of Nonalcoholic
Fatty Liver Disease
Dunn W, et al. Hepatology. 2008;47(6):1947–1954.
Summary by R. Curtis Ellison, MD
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Objectives/Methods

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Researchers sought to determine the relationship between moderate alcohol consumption and
nonalcoholic fatty liver disease (NAFLD) .
Data were analyzed from the 3rd National Health
and Nutrition Examination Survey (NHANES III).
Subjects included 7211 nondrinkers and 4543
moderate drinkers of wine (n=945), beer
(n=2237), liquor (n=688), and mixed drinks
(n=673).
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Objectives/Methods (cont’d)

Suspected NAFLD was based on unexplained
serum alanine aminotransferase (ALT) elevation
using:
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the NHANES III reference laboratory cut point
(ALT>43), and
the 95th percentile of healthy subjects cut point
(ALT>30 for men and >19 for women).
Analyses were adjusted for age, gender, race,
income, neighborhood, education, caffeine
intake, and physical activity.
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Results

Using the reference-laboratory cut point, suspected
NAFLD was observed in…
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Using the healthy-subject cut point, suspected
NAFLD was observed in…

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3.2% of nondrinkers
0.4% of moderate wine drinkers (adjusted odds ratio
[OR], 0.15).
14.3% of nondrinkers
8.6% of moderate wine drinkers (OR, 0.51).
No significant associations were seen for moderate
consumers of beer or spirits.
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Comments
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Moderate wine consumption may have a
protective effect against NAFLD.
Although the authors adjusted for many
factors that relate to beverage preference in
the US, other lifestyle habits of wine drinkers
could explain these findings.
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42
College-Student Drinking
Patterns during the First 4
Years
Johnsson KO, et al. Eur Addict Res. 2008;14(1):11–18.
Summary by Nicolas Bertholet, MD, MSc
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Objectives/Methods
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To identify drinking trajectories in college students,
researchers in Sweden examined AUDIT* scores in
a cohort of 359 students each year over their first
4 college years.
Trajectories of students with risky drinking at
college admission (AUDIT scores ≥11 for men and
≥7 for women) and a random sample of those with
lower risk scores were analyzed.
Prevalence of risky drinking at baseline was 27%.
*Alcohol Use Disorders Identification Test.
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Results
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Sixteen percent of students consistently reported risky
drinking and 13% increased consumption from lower
risk to risky drinking over the study period.
Among students with risky drinking at admission, the
majority (59%) continued risky drinking.
41% reported a decrease in drinking.
Among those with lower risk drinking at baseline, most
continued lower risk drinking (83%).
Gender differences influenced trajectories. Men were
more likely to report consistent risky drinking, while
women were more likely to report a decrease.
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Comments
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Students with risky drinking do not appear to
reduce this risk behavior on their own.
Risky drinking may increase during this period for
young adults.
Periodic reassessment and interventions
regarding drinking and consequences over the
course of the college years are needed.
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46
Crack Cocaine’s Effect on
HIV Disease Progression in
Women: What Are the
Major Outcomes?
Cook JA, et al. AIDS. 2008;22(11):1355–1363.
Summary by Jeffrey H. Samet, MD, MA, MPH
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Objectives/Methods

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To assess the impact of crack cocaine on HIV
disease progression in women, investigators
analyzed data from 1686 HIV-positive participants
in the Women’s Interagency Cohort Study
between 1996–2004.
Analyses were based on patterns of crack cocaine
use:
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1203 women (71%) were nonusers.
429 (25%) were intermittent users (use reported
previously with abstinence reported at current visit).
54 (3%) were persistent users (use reported at every
visit).
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Objectives/Methods (cont’d)
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Outcomes examined included death, AIDS-defining
illness, CD4 count, and HIV viral load.
Potential confounders controlled for in multivariable analyses included:

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Age
Race/ethnicity
Education
Income
Baseline HIV viral load
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Baseline CD4 cell count
Year of diagnosis
Study site
HAART adherence
Problem drinking
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Results
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Persistent use was significantly associated with
increased death, AIDS-defining illness, and HIV
viral load and with a decrease in CD4 count
compared with nonusers.
Intermittent users had an increase in AIDSdefining illnesses compared with nonusers and
had intermediate CD4 counts and HIV viral loads.
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Comments
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This study provides good evidence on the
impact of crack cocaine use on HIV outcomes.
The extent to which this work translates to use
of other forms of cocaine is not clear.
Despite minor methodological deficiencies, the
HIV clinical progression puzzle as it relates to
crack cocaine use in women has been notably
elucidated.
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51
Does Moderate Alcohol Use
Protect against Low Bone
Density and Osteoporotic
Fractures?
Berg KM, et al. Am J Med. 2008;121(5):406–418.
Summary by Kevin L. Kraemer, MD, MSc
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52
Objectives/Methods
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To assess the association of moderate alcohol
use with bone density, osteoporotic fracture,
and bone changes over time, researchers
conducted a systematic review and metaanalysis of the literature published before May
2007.
Thirty-three studies met content and quality
criteria for inclusion in at least 1 of the analyses.
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Results
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In 4 studies assessing the relationship between
alcohol consumption and bone density, femoral
neck bone density increased 0.045 g/cm2 for
each drink per day over the range of 0–3 drinks
per day.
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Results (cont’d)

Compared with abstainers, risk of hip fracture
decreased for individuals consuming:

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>0–0.5 drinks per day (5 studies; pooled relative
risk [RR], 0.84*)
>0.5–1 drinks per day (11 studies; RR, 0.80)
>1–2 drinks per day (10 studies; RR, 0.91*).
Risk of hip fracture increased for individuals
consuming:

>2 drinks per day (6 studies; RR, 1.39).
* Not significant.
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Results (cont’d)

Several studies indicated that, compared with
abstainers, moderate alcohol use was
associated with decreased bone loss over
time.
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Comments
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
These data suggest moderate alcohol use is
associated with increased bone density at the hip
and decreased risk for osteoporotic hip fractures.
Although the exact range of alcohol use to
improve bone outcomes cannot be determined
from existing data, the levels of alcohol use noted
to be beneficial in this study are similar to current
low-risk drinking recommendations.
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Differing Health Effects
Related to Quantity and
Frequency of Drinking
Breslow RA, et al. Alcohol Clin Exp Res. 2008; 32(3):513–521.
Summary by R. Curtis Ellison, MD
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Objectives/Methods

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To assess the relationship between quantity and
frequency of alcohol consumption and mortality,
investigators linked data from the 1988 National
Health Interview Survey with the National Death
Index through 2002.
The cohort included 20,765 current drinkers age
≥18 years.
At 14-year follow up, 2547 had died.
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Results

Men who consumed ≥5 drinks (compared with 1
drink) on drinking days had a relative risk (RR) of
mortality of…
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1.30 for cardiovascular disease (nonsignificant)
1.53 for cancer
1.42 for other causes
Women who consumed ≥5 drinks on drinking
days had an RR of mortality from other causes of
2.88.
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Results (cont’d)

Men with the highest consumption frequency
(compared with the lowest) had a RR of…
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0.79 for cardiovascular disease
1.23 for cancer
1.30 for other causes (nonsignificant)
Relative risk for cancer in women with the highest
consumption frequency (≥3 days per week) was
1.65.
Increasing frequency of drinking had no significant
effect on total mortality for either men or women.
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Comments
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
The numbers of deaths in some of the higher
alcohol-intake categories were small, especially for
women, leading to less precise estimates of effect.
Two of the findings are particularly interesting and
noteworthy:


Quantity and frequency effects trended in opposite
directions for cardiovascular disease in men.
Increased frequency of drinking was associated
with risk for cancer death. Other studies have not
demonstrated an increase in cancer risk with more
frequent drinking when adjusted for total intake.
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