PHARMACOLOGIC TREATMENT FOR SUBSTANCE ABUSE DISORDERS
From Advances in Pharmacology Throughout the Lifespan, presented by the University of California, San Diego,
School of Medicine
Marc Schuckit, MD, Professor of Psychiatry, University of California, San Diego, School of Medicine
| Introduction: seeking out undesirable substances often begins in teen years; severe problems can occur
when individual continues to use substances despite consequences; substance use responsible for ≈22,000
deaths per year in United States, ≈5000 of them adolescents; substance use disorders may mimic major
psychiatric syndromes, at least temporarily, and make preexisting psychiatric syndromes worse and more
difficult to treat
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| Applying adult treatments to adolescents: young people resilient, lowering probability that they will experience
withdrawal from substances, so “you’ll have teenagers with very severe problems in multiple
life areas, but no evidence of withdrawal”; tolerance also more difficult to identify in adolescents because
to develop tolerance, substance must be used almost daily, and few adolescents have resources
available to do that; among dependence criteria most frequently seen in adolescents are using substance
for longer periods than intended and inability to cut down on use
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 | Diagnostic “orphans”: people who do not meet enough criteria to be classified as “dependent” in Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) but do have repetitive problems in at
least one major life area; prognosis generally falls between that for abuse and that for dependence; most
diagnostic orphans in literature adolescents; 5% to 10% of adults (ie, those >20 yr of age) who develop
abuse go on to develop dependence; percentage in adolescents unknown, but thought to be greater
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| Diagnostic criteria for substance use disorders: same in adolescents as in adults, with caveats that in adolescents,
withdrawal less common, tolerance more difficult to identify, and inability to control use greater
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| Substance use common in adolescents: Monitoring the Future study shows that 77% of students have consumed
at least full glass of alcohol by end of high school, 40% by 8th grade, and 12% by 12 yr of age; in
addition, by end of high school, 50% have used marijuana, 15% amphetamines, 8% cocaine, and 50% ≥1
illicit substances; speaker advises that when seeing adolescent for any condition, consider possibility that
he or she also uses drugs or alcohol
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| Predicting which users might progress to dependence: best predictor of elevated risk, especially for alcohol
dependence, is family history of dependence on any substance (alcohol dependence ≈60% genetic and
40% environmental; genetic influence probably lower for other substances); second major predictor is
conduct disorder in childhood with antisocial personality disorder in adulthood; in some studies, child who
has full drink prior to 13 yr of age has 4-fold increased risk of developing substance abuse or dependence
later in life (controversial); impact of family history and conduct disorder moderated or mediated by heavy
drinking in peers and by problems in school; active religious practice can be fairly protective; expecting
alcohol to “do wonderful things for you” has negative influence; attention-deficit/hyperactivity disorder
(ADHD) appears not to increase risk in adolescents who do not have conduct disorder; oppositional defiant
disorder probably increases risk
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| Course of substance use in teenagers: teens generally have fewer problems than adults; teens have decreased
incidence of withdrawal, decreased probability of medical problems, and increased social problems;
data suggest there may be some impairment in memory and executive functioning in some
individuals; effect of substances on sex hormones and development of sexuality unknown
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| Outcomes: several studies of treatment of substance use disorders in teens show rates of doing well similar
to those in adults
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| Treatment of alcohol dependence: treatment algorithm considers substance abuse and dependence as
chronic relapsing disorders that tend to wax and wane; core of treatment to “get the attention of your patients,
get them motivated, help them to implement changes in their lives; and if you choose to use medications,
help them to be compliant with the medications”
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| Psychologic treatment: cognitive behavioral therapy to help change how patients think about disorder and
how they think about their responsibility for their disorder, help them to implement changes and to recognize
possibility that they will revert to previous behavior, and help them to stay abstinent and to rebuild
their lives around abstinence; teenagers as likely as adults to participate in and benefit from 12-step
programs, as long as there are other teens in group; motivational interviewing—promotes abstinence; directive
and builds trust; helps patient to rebuild life; encourages patient to identify changes to which he or
she resistant; emphasizes that patient, not therapist, is one who must make decisions about changes; brief
physician advice—technique in which physician counsels patient about substance use, including doing
brief assessment, giving feedback, addressing ambivalence and/or resistance to change, helping to set
goals, using worksheets, and providing reinforcement
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| Medications: in treating substance use, medications alone not enough, but they do have role in rehabilitation;
disulfiram (Antabuse)—avoid; difficult to prove it works better than placebo; has many side effects,
including optic neuritis, major neuroplexus neuritides, peripheral neuropathy, and depression; no
data available on its use in adolescents; lithium—no better than placebo in treatment of alcohol use disorder
in patients who do not have bipolar disorder (in those with bipolar disorder, treats mania but not
alcohol dependence); antidepressants—in controlled studies, helped depression but not alcohol dependence
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| Opioid inhibitors: naltrexone—50 mg/day orally or 150 mg 3 times per week increases days of abstinence,
but studies “relatively small and relatively short”; adolescents less likely to have contraindications;
do not use if patient has chronic pain syndrome or needs pain medications; Vivitrex—depot form
of naltrexone given once monthly; injectable form shown better than placebo in adults, but no studies in
adolescents; other opioid blockers—theoretically should work, but no data; acamprosate (Campral)—
new to United States but used in Europe for last decade; inhibits glutamate N-methyl-D-aspartate
(NMDA) receptors; not useful in acute withdrawal, but shown to help in protracted withdrawal when
adults have sleep disturbance, anxiety, or moodiness; no data on adolescents; statistically significant
increase in suicidal ideation seen in 1 adult study; moderate-size trial in Germany showed combination
of naltrexone (50 mg/day) and acamprosate (2 g/day) better than either alone
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| Future treatments for alcohol dependence: ondansetron—decreases nausea in people having chemotherapy;
some chemotherapy patients noticed decrease in desire to drink, so small trial done; ≈50% dropped out
due to side effects; results showed ondansetron no better than placebo for most patients, but showed promise
for those with conduct disorder and antisocial personality disorder; more trials needed; rimonabant—
used in Europe, not yet approved in United States; cannabinol-1 (CB1) receptor antagonist; tested extensively
as appetite suppressant, but so far, no studies have looked specifically at decrease in alcohol or marijuana
consumption; topiramate (Topamax)—associated with decrease in alcohol use in adults, but trials
few; has many side effects; baclofen—“don’t use it”; has many sedative side effects; 1 small trial suggested
it might be useful in alcohol withdrawal; kudzu—plant widely distributed in Far East and used for centuries in
Chinese medicine; 1 small trial showed less drinking in nonalcoholic subjects, compared to placebo, but no
tests yet on alcohol-dependent subjects
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| Other substances of abuse: lifetime risk for dependence on substances other than alcohol much lower than
for alcohol (“in the general population, alcohol is the grandaddy regarding the dependencies”)
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| Opioids: methadone—has most data; no data on teenagers per se, but in adults, optimal dose 80 mg/day; long
acting, so need be taken only once daily; data show significant decrease in amount of opioid used; special license
required to prescribe methadone; buprenorphine (Buprenex)—usual dose 8 to 20 mg/day; requires
special training but not special license, as long as clinician has <30 patients on buprenorphine; easier than
methadone to build up to optimal dosage because of fewer side effects and less likelihood of inadvertent
overdose with buprenorphine; however, in head-to-head comparisons, methadone “does better”;
naltrexone—50 to 150 mg/day or 150 mg 3 times per week; not only decreases craving, but blocks “high”
that results from opioid; no data for adolescents; stimulants, antidepressants, and dopamine agonists—in
controlled trials, no better than placebo; disulfiram (Antabuse)—1 trial appeared to show it was better than
placebo, but results have not been replicated; antipsychotics—no good data to support their efficacy
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| Cocaine vaccine: most trials to date done in animals (human data limited), but “immunization may have
some important use for us in the future”
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| Cannabinoids: hardest dependence to treat because marijuana decreases motivation and “it’s really hard to
get [the users’] attention”; speaker thinks rimonabant may be useful, but no trials with cannabinoids to
date
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| Summary: substance abuse causes ≈5000 adolescent deaths per year in United States; DSM-IV criteria same
for adolescents as for adults; best predictor of future behavior is past behavior, so someone with severe repetitive
problems in multiple life areas will have difficulty controlling use for any extended period in future;
unknown how many adolescent substance abusers continue on to dependence; core of treatment is
cognitive behavioral therapy, with medications as possible adjunct; only drugs that appear to be moderately
safe and significantly better than placebo for treating alcohol dependence in adults are acamprosate and
naltrexone, and probably most efficacious is combination of those; little data to address their use in adolescents;
most data on treatment of opioid dependence addresses adults, but may be applicable to adolescents
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| Nicotine dependence: “well worthy of people’s attention”; nicotine patch and bupropion (Zyban) better
than placebo; other antidepressants may also work, but no data available
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Educational Objectives
| The goal of this program is to educate the listener about pharmacologic treatment for substance abuse disorders,
especially in adolescents. After hearing and assimilating this program, the clinician will be better able
to:
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| 1. Apply adult data about treating substance abuse disorders to adolescents.
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| 2. Describe the differences between diagnostic criteria for substance abuse disorders in adults and in adolescents.
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| 3. State the pharmacologic treatment available for treatment of alcohol dependence in adolescents.
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| 4. Describe some investigational treatments for alcohol dependence.
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| 5. Discuss available treatments for use of or dependence on substances other than alcohol in adolescents.
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Discussed on This Program
Acamprosate calcium [Campral]
Baclofen [Kemstro, Lioresal, Lioresal Intrathecal]
Bromocriptine mesylate [Parlodel, Parlodel Snap Tabs]
Buprenorphine hydrochloride [Buprenex, Subutex]
Bupropion hydrochloride [Zyban]
Buspirone hydrochloride [BuSpar]
Disulfiram [Antabuse]
Kudzu (Pueraria montana var. lobata )
Methadone hydrochloride [Dolophine HCl, Methadone HCl Diskets, Methadone HCl Intensol, Methadose]
Naltrexone hydrochloride [ReVia, Vivitrex]
Ondansetron hydrochloride [Zofran, Zofran ODT]
Rimonabant (investigational) [Acomplia]
Topiramate [Topamax]
Suggested Reading
Addolorato G et al: Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam.
Am J Med 119:276, 2006; Ameisen O: Naltrexone treatment for alcohol dependency. JAMA 294:899,
2005; Anton RF et al: COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions
for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295:2003,
2006; Buydens-Branchey L, Branchey M, Reel-Brander C: Efficacy of buspirone in the treatment of opioid
withdrawal. J Clin Psychopharmacol 25:230, 2005; Carai MA, Colombo G, Gessa GL: Rimonabant: the
first therapeutically relevant cannabinoid antagonist. Life Sci 77:2339, 2005; Cofta-Woerpel L, Wright KL,
Wetter DW: Smoking cessation 1: pharmacological treatments. Behav Med 32:47, 2006; Collins GB, McAllister
MS, Adury K: Drug adjuncts for treating alcohol dependence. Cleve Clin J Med 73:641, 2006; Dawes
MA et al: A prospective, open-label trial of ondansetron in adolescents with alcohol dependence. Addict Behav
30:1077, 2005; Fiellin DA et al: Counseling plus buprenorphine-naloxone maintenance therapy for opioid
dependence. N Engl J Med 355:365, 2006; Frishman WH et al: Nicotine and non-nicotine smoking cessation
pharmacotherapies. Cardiol Rev 14:57, 2006; Gorelick DA, Wilkins JN: Bromocriptine treatment for cocaine
addiction: association with plasma prolactin levels. Drug Alcohol Depend 81:189, 2006; Gossop M,
Carroll KM: Disulfiram, cocaine, and alcohol: two outcomes for the price of one? Alcohol Alcohol 41:119,
2006; Heading CE: Vivitrex (Alkermes/Cephalon). Curr Opin Investig Drugs 7:81, 2006; Johansson BA,
Berglund M, Lindgren A: Efficacy of maintenance treatment with naltrexone for opioid dependence: a
meta-analytical review. Addiction 101:491, 2006; Johnson BA, Schuckit MA et al: Understanding and treating
alcohol dependence. Alcohol Clin Exp Res 30:567, 2006; Klein JD: Adolescents and smoking: the first
puff may be the worst. CMAJ 175:262, 2006; Licanin I, Redzic A, Ibrahimagic E: Alcoholism during adolescence.
Med Arh 60:225, 2006; Lichtman AH, Martin BR: Cannabinoid tolerance and dependence. Handb
Exp Pharmacol (168):691, 2005; Mason BJ: Rationale for combining acamprosate and naltrexone for treating
alcohol dependence. J Stud Alcohol Suppl Jul; 148, 2005; Methadone treatment preserving, saving lives. W V
Med J 102:336, 2006; Rose JS et al: Effects of buspirone in withdrawal from opiates. Am J Addict 12:253,
2003; Srivastava A, Kahan M: Buprenorphine: a potential new treatment option for opioid dependence.
CMAJ 174:1835, 2006; Suh JJ et al: The status of disulfiram: a half of a century later. J Clin Psychopharmacol
26:290, 2006; Williams SH: Medications for treating alcohol dependence. Am Fam Physician 72:1775, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed.
For this issue, Dr. Schuckit reported attending an Advisory Board meeting at Forest Pharmaceuticals.
Dr. Schuckit was recorded at Advances in Pharmacology Throughout the Lifespan, held April 6-8, 2006, in San
Diego, CA, and sponsored by the University of California, San Diego, School of Medicine. The Audio-Digest
Foundation thanks Dr. Schuckit and UCSD for their cooperation in the production of this program.
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