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Why Provide Treatment?
 

Good for addicted individual
Good for society
Addiction impacts on health care, crime, AIDS

Role of Pharmacologic Treatment

"Cure" of withdrawal or overdose
Create "window of opportunity"
Long term maintenance agents

Treatment of Alcohol Dependence

Treatment of withdrawal: relief of symptoms; prevention of arrhythymias,
seizures; minimize dependence or risk of toxicity related to drug therapy
Antidipsotropic agents: disulfiram, naltrexone

Use of naltrexone: 50 mg each day, diminishes hedonic value of alcohol,
keep lapse from becoming a relapse, supervised intake preferable,
additional supportive/relapse prevention therapy

Treatment of comorbid disorders

Treatment of Opiate Dependence

Opiates: Rise in Use

Cost down, purity up
Why is heroin popular? Rapid onset, highly euphoric, rush is not as intense with slower routes, thus i.v. route is preferable

Heroin pharmacology

Average heroin dependent individual uses 2-4 per day
Tolerance develops within few weeks
Withdrawal begins within 12 hours, lasts 1-3 days, usually over within 5-7 days
Protracted withdrawal can last for months

Treatment of Opiate Withdrawal

Use the drug the individual is addicted to
Other drugs that produce cross tolerance
Medications for symptomatic relief
Drugs affecting mechanisms by which withdrawal is expressed

Pharmacologic Treatments for Opiate Withdrawal

Methadone
Buprenorphine
Clonidine
Clonidine/Naltrexone-rapid detoxification.
Anesthesia-ultra rapid detoxification

Methadone Substitution

Requires special license
Completion rates ranges from less than 20% for outpatient, 70-80% inpatient
May have rebound withdrawal symptoms after last dose of methadone
Adjunctive use of benzodiazepines, NSAIDS, or clonidine

Clonidine

Alpha-2 adrenergic agonist
Doses range 0.3-2.0 mg/day, need to monitor blood pressure
Reduces autonomic withdrawal components but may not reduce craving,
insomnia, and muscle aches
Approximately 50% complete outpatient withdrawal
Use of benzodiazepines and NSAIDS

Clonidine/Naltrexone Rapid Detoxification
Day 1: 9:00 a.m.: Clonidine 0.2-0.4 mg/day orally

Oxazepam 30-60 mg

Clonidine 0. 1-0.2 mg every 4 hours up to 1.2 mg/day
Oxazepam 15-30 mg every 6 hours as needed
Patient in clinic until 5 p.m.

Day 2:
9:00 a.m.: Clonidine 0.1-0.2 mg orally and then every 4 hours up to 1.2 mg/day

Oxazepam 15-30 mg every 6 hours as needed
10:00 a.m.: Naltrexone 25 mg
Patient may leave 2 hours after naltrexone

9:00 a.m.: Clonidine 0. 1-0.2 mg orally and then q4 hrs, tapering total dose by 0.2
Oxazepam 15-30 mg every 6 hours as needed
10:00 a.m.: Naltrexone 50 mg

Patient may leave 1 hour after naltrexone
Continue clonidine 0.1-0.2 mg every 4 hours as needed over next 2-3 days
Continue oxazepam 15-30 mg every 6 hours as needed over next 2-3 days
Adjunctive medication as needed; nonnarcotic analgesics, antiemetics
Continue naltrexone 50 mg/day

Anesthesia-Assisted Detoxification
            Why is it popular?

Magic bullet
Detoxification fear
Previous experience of discomfort
Shorten length of withdrawal for occupational or potential reasons
Difficulty in withdrawing from methadone

Anesthesia-Assisted Rapid Detoxification

Withdrawal precipitated by iv naloxone followed by NG naloxone
Withdrawal ameliorated by iv clonidine
Use of propofol anesthesia or midazolam

Opiate Detoxifications:Pros and Cons

Methadone taper:

Pros:Simple to use, few side effects but requires special license
Cons: Longest duration of withdrawal, rebound withdrawal

Clonidine substitution:

Pros: No special license, shortens withdrawal from Methadone but not heroin.
Cons: harder to use, more side effects, need to monitor blood pressure, not fully
relieve withdrawal symptoms

Ultra-rapid clonidine/naltrexone technique:

Pros: No special license, no rebound withdrawal, cuts withdrawal from methadone or
heroin to 2-3 days
Cons: more difficult to use, more side effects, first day need to be day or inpatient
setting

Anesthesia-aided ultra-rapid antagonist detoxification:

Pros: Shortens time for withdrawal, useful for patients afraid of withdrawal discomfort,
use for withdrawal from high dose methadone.
Con: No adequate published studies, risk of anesthesia, aspiration if intubation not
used is possible, expensive

Treatment of Opiate Dependence: Maintenance Agents

Agonists: Methadone, Levo-alpha-acetyl-methadol (LAAM)
Partial agonists: buprenorphine
Antagonists: naltrexone

Characteristics of Ideal Maintenance Agent for Opiate Dependence

Low diversion potential
Long duration of action
Low potential for increasing concomitant use of other drugs
Low toxicity of overdose
Detoxification should be short, simple, and minimal rebound withdrawal
Facilitate abstinence from illicit opiates
Good acceptance by patients

Methadone Maintenance Programs

Best studied, but controversial
Methadone is orally effective, 24-hour opioid drug
110,000 slots nationwide
Patients maintained usually 1-3 years, minority may need long term
maintenance
Relapse high when stop methadone
Increased services, better treatment outcome

LAAM- Levo alpha acetyl methadol

Slow onset, low reinforcement
Smooth onset, less abuse potential
Long duration, less withdrawal problems
Take home, compliance

Buprenophine- partial agonist

Reduced opiate agonist effect, less respiratory depression
Withdrawal easier
May be used as transition from methadone to naltrexone
Use for treating heroin addiction
May be used in office-based practice in the future
Buprenorphine-naloxone formulation

Naloxone 100x more potent intravenously compared to oral route
Small amount of oral naloxone will not antagonize buprenorphine
May limit street use

50 mg daily or 100 mg/100 mg/150 mg taken 3x/week
Generally use for relapse prevention
High drop-out rate
Beneficial for patients who are motivated, family support, legitimate career

What is the target?

Cocaine withdrawal symptoms
Prolonged cocaine craving
Block cocaine's effects but not dopamine
Rapidly inactivate cocaine's actions

Many pharmacologic treatments tried, none proven effective

Best studied medication is desipramine, although some trials negative
Must include appropriate psychosocial support
If successful, continue 3-6 months
Heterogeneity of population increases difficulty of determining what
Works. Targeting psychiatric subpopulations

Need for Treatment Medications

Effective behavioral interventions for some cocaine addicts have been
developed.
However, better approaches needed and an effective medication could
markedly improve treatment outcome
Both the human and financial cost of cocaine addiction suggest such a
medication would be cost-effective for the country
Some addicts will need habilitation regardless of a medication

Conclusion

Detoxification is simply the first step
Some patients benefit from pharmacologic interventions
No one treatment is universally effective given heterogeneity of population
Medications may provide "window of opportunity" such that other
nonpharmacologic interventions are enhanced

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