Management of Withdrawal Syndromes and Relapse Prevention in Drug and Alcohol Dependence



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The primary care physician is in a good position to diagnose, manage and intervene with patients who are undergoing the process of treatment and recovery from alcohol and drug disorders. Medications such as benzodiazepines are effective in the treatment of withdrawal syndromes, and naltrexone and disulfiram can be used to augment relapse prevention. Patients may also participate in psychosocial methods of addiction treatment that can reduce the risk of relapse and improve their psychosocial, health, legal and employment status.

Nearly one half of the patients who visit a family practice have an alcohol or drug disorder. Primary care physicians have an opportunity to intervene at all stages during the course of addictive illness. Each stage can be characterized by types and severity of withdrawal and relapse prevention.13 Management of alcohol and drug disorders includes assessment, intervention, prescription of medications, participation in specific addiction treatment strategies and monitoring of recovery.

Pharmacotherapy for Withdrawal Syndromes

Detoxification

Pharmacologic therapies are indicated for use in patients with addictive disorders to prevent life-threatening withdrawal complications such as seizures and delirium tremens, and to increase compliance with psychosocial forms of addiction treatment. Laboratory testing is indicated to assess the type and timing of drugs used addictively and to guide management of withdrawal and recovery.4

Alcohol

Management of alcohol withdrawal is based on the patient's history and current clinical status. The single best predictor of the likelihood of future withdrawal symptoms when alcohol is concerned is the patient's previous history, e.g., the presence or absence of seizures or delirium tremens (Table 1).

TABLE 1

Signs and Symptoms of Alcohol and Drug Withdrawal

Drug Peak period Duration Signs Symptoms

Alcohol

1 to 3 days

5 to 7 days

Elevated blood pressure, pulse and temperature, hyperarousal, agitation, restlessness, cutaneous flushing, tremors, diaphoresis, dilated pupils, ataxia, clouding of consciousness, disorientation

Anxiety, panic, paranoid delusions, illusions, visual and auditory hallucinations (often derogatory and intimidating)

Benzodiazepines and other sedative/hypnotics

Short-acting: 2 to 4 days Long-acting: 4 to 7 days

Short-acting: 4 to 7 days Long-acting: 7 to 14 days

Increased psychomotor activity, agitation, muscular weakness, tremulousness, hyperpyrexia, diaphoresis, delirium, convulsions, elevated blood pressure, pulse and temperature, tremor of eyelids, tongue and hands

Anxiety, depression, euphoria, incoherent thoughts, hostility, grandiosity, disorientation, tactile, auditory and visual hallucinations, suicidal thoughts

Stimulants (cocaine, amphetamines and derivatives)

1 to 3 days

5 to 7 days

Social withdrawal, psychomotor retardation, hypersomnia, hyperphagia

Depression, anhedonia, suicidal thoughts and behavior, paranoid delusions

Opiates (heroin)

1 to 3 days

5 to 7 days

Drug seeking, mydriasis, piloerection, diaphoresis, rhinorrhea, lacrimation, diarrhea, insomnia, elevated blood pressure and pulse (mild)

Intense desire for drugs, muscle cramps, arthralgia, anxiety, nausea, vomiting, malaise

PCP/psychedelics

Days to weeks

Days to weeks

Hyperactivity, increased pain threshold, nystagmus, hyperreflexia, hypertension and tachycardia, eyelid retraction (stare), agitation and hyperarousal, dry and erythematous skin, violent and self-destructive behaviors

Anxiety, depression, delusions, auditory and visual hallucinations, memory loss, irritable and angry mood and affect, suicidal thoughts


PCP = phencyclidine.

TABLE 1   Signs and Symptoms of Alcohol and Drug Withdrawal

View Table

TABLE 1

Signs and Symptoms of Alcohol and Drug Withdrawal

Drug Peak period Duration Signs Symptoms

Alcohol

1 to 3 days

5 to 7 days

Elevated blood pressure, pulse and temperature, hyperarousal, agitation, restlessness, cutaneous flushing, tremors, diaphoresis, dilated pupils, ataxia, clouding of consciousness, disorientation

Anxiety, panic, paranoid delusions, illusions, visual and auditory hallucinations (often derogatory and intimidating)

Benzodiazepines and other sedative/hypnotics

Short-acting: 2 to 4 days Long-acting: 4 to 7 days

Short-acting: 4 to 7 days Long-acting: 7 to 14 days

Increased psychomotor activity, agitation, muscular weakness, tremulousness, hyperpyrexia, diaphoresis, delirium, convulsions, elevated blood pressure, pulse and temperature, tremor of eyelids, tongue and hands

Anxiety, depression, euphoria, incoherent thoughts, hostility, grandiosity, disorientation, tactile, auditory and visual hallucinations, suicidal thoughts

Stimulants (cocaine, amphetamines and derivatives)

1 to 3 days

5 to 7 days

Social withdrawal, psychomotor retardation, hypersomnia, hyperphagia

Depression, anhedonia, suicidal thoughts and behavior, paranoid delusions

Opiates (heroin)

1 to 3 days

5 to 7 days

Drug seeking, mydriasis, piloerection, diaphoresis, rhinorrhea, lacrimation, diarrhea, insomnia, elevated blood pressure and pulse (mild)

Intense desire for drugs, muscle cramps, arthralgia, anxiety, nausea, vomiting, malaise

PCP/psychedelics

Days to weeks

Days to weeks

Hyperactivity, increased pain threshold, nystagmus, hyperreflexia, hypertension and tachycardia, eyelid retraction (stare), agitation and hyperarousal, dry and erythematous skin, violent and self-destructive behaviors

Anxiety, depression, delusions, auditory and visual hallucinations, memory loss, irritable and angry mood and affect, suicidal thoughts


PCP = phencyclidine.

Alcohol withdrawal may be treated with a pharmacologic agent that exhibits cross-tolerance with alcohol. Agents that are commonly recommended include diazepam (Valium), lorazepam (Ativan), chlordiazepoxide (Librium), clorazepate (Tranxeme) and phenobarbital. The usual initial dosage of diazepam or lorazepam is titrated according to elevations of blood pressure, pulse rate, degree of agitation and presence of delirium. In general, longer-acting preparations such as diazepam or chlordiazepoxide provide a smoother and safer withdrawal than other preparations. Shorter-acting preparations such as lorazepam are indicated when elimination time for benzodiazepines is prolonged, such as in patients with significant liver disease.

A loading dose of a long-acting benzodiazepine such as diazepam or chlordiazepoxide may be given initially, and the dosage may then be tapered. This method is often used in conjunction with a scale for detoxification. It is also used frequently in an inpatient setting. The physician should screen the patient for the presence of other sedating drugs to avoid untoward drug interactions, particularly oversedation. Initial loading doses for diazepam are in the range of 30 to 50 mg. Suggested parameters and dosages are presented in Table 2.

TABLE 2

Medications for Alcohol Detoxification

Mild withdrawalModerate withdrawalSevere withdrawal (delirium tremens)*Loading-dose method

Diazepam (Valium), 5 to 10 mg orally as needed or Lorazepam (Ativan), 1 to 2 mg orally every 4 to 6 hours as needed for 1 to 3 days

Diazepam: 15 to 20 mg orally four times daily on day 1 10 to 20 mg orally four times daily on day 2 5 to 15 mg orally four times daily on day 3 10 mg orally four times daily on day 4 5 mg orally four times daily on day 5 or Lorazepam: 2 to 4 mg orally four times daily on days 1 and 2 1 to 2 mg orally four times daily on days 3 and 4 1 mg orally twice daily on day 5

Diazepam, 10 to 25 mg orally as needed every hour while awake until sedation occurs Lorazepam, 1 to 2 mg intravenously as needed every hour while awake for 3 to 5 days (to sedate)

Diazepam, 10 mg, or chlordiazepoxide (Librium), 25 mg, orally every hour Diazepam may be given intravenously

Administer medication when:

Systolic blood pressure: > 150 mm Hg

Systolic blood pressure: 150 to 200 mm Hg

Systolic blood pressure: > 200 mm Hg

Diastolic blood pressure: > 90 mm Hg

Diastolic blood pressure: 100 to 140 mm Hg

Diastolic blood pressure: > 140 mm Hg

Pulse: > 100

Pulse: 110 to 140

Pulse: > 140

Temperature: > 37.7°C (100°F)

Temperature: 37.7°C to 38.3°C (100°F to 101°F)

Temperature: > 38.3°C (101°F)

Tremulousness, insomnia, agitation are present

Tremulousness, insomnia, agitation are present

Tremulousness, insomnia, agitation are present


*—Monitoring in an intensive care unit is recommended for cardiac and respiratory function, fluid and nutrition replacement, vital signs and mental status. Restraints are indicated in patients who are confused or agitated to protect the patient from self and others (delirium tremens can be a terrifying and life-threatening state). Thiamine, 100 mg intramuscularly or orally every day for 3 to 7 days, hydration and magnesium replacement may be indicated, according to the severity of the withdrawal state. 5,6,10,21

TABLE 2   Medications for Alcohol Detoxification

View Table

TABLE 2

Medications for Alcohol Detoxification

Mild withdrawalModerate withdrawalSevere withdrawal (delirium tremens)*Loading-dose method

Diazepam (Valium), 5 to 10 mg orally as needed or Lorazepam (Ativan), 1 to 2 mg orally every 4 to 6 hours as needed for 1 to 3 days

Diazepam: 15 to 20 mg orally four times daily on day 1 10 to 20 mg orally four times daily on day 2 5 to 15 mg orally four times daily on day 3 10 mg orally four times daily on day 4 5 mg orally four times daily on day 5 or Lorazepam: 2 to 4 mg orally four times daily on days 1 and 2 1 to 2 mg orally four times daily on days 3 and 4 1 mg orally twice daily on day 5

Diazepam, 10 to 25 mg orally as needed every hour while awake until sedation occurs Lorazepam, 1 to 2 mg intravenously as needed every hour while awake for 3 to 5 days (to sedate)

Diazepam, 10 mg, or chlordiazepoxide (Librium), 25 mg, orally every hour Diazepam may be given intravenously

Administer medication when:

Systolic blood pressure: > 150 mm Hg

Systolic blood pressure: 150 to 200 mm Hg

Systolic blood pressure: > 200 mm Hg

Diastolic blood pressure: > 90 mm Hg

Diastolic blood pressure: 100 to 140 mm Hg

Diastolic blood pressure: > 140 mm Hg

Pulse: > 100

Pulse: 110 to 140

Pulse: > 140

Temperature: > 37.7°C (100°F)

Temperature: 37.7°C to 38.3°C (100°F to 101°F)

Temperature: > 38.3°C (101°F)

Tremulousness, insomnia, agitation are present

Tremulousness, insomnia, agitation are present

Tremulousness, insomnia, agitation are present


*—Monitoring in an intensive care unit is recommended for cardiac and respiratory function, fluid and nutrition replacement, vital signs and mental status. Restraints are indicated in patients who are confused or agitated to protect the patient from self and others (delirium tremens can be a terrifying and life-threatening state). Thiamine, 100 mg intramuscularly or orally every day for 3 to 7 days, hydration and magnesium replacement may be indicated, according to the severity of the withdrawal state. 5,6,10,21

Benzodiazepines and Other Sedative/Hypnotics

The signs and symptoms of benzodiazepine withdrawal are similar to those for withdrawal of other sedative/hypnotics (barbiturates, ethchylorvynol [Placidyl], glutethimide and meprobamate [Equanil]) (Table 1). The management of withdrawal for sedative/hypnotics (barbiturates) is similar to that for benzodiazepines (Table 3).

TABLE 3

Benzodiazepine (Barbiturate) Withdrawal

Short-acting detoxification Long-acting detoxification

7- to 10-day taper:

10- to 14-day taper:

On day 1, give diazepam (Valium), 10 to 20 mg orally four times daily, and taper until the dosage is 5 to 10 mg orally on last day. Avoid giving the drug “as needed.” Adjustments in dosage according to the patient's clinical state may be indicated.

On day 1, give diazepam, 10 to 20 mg orally four times daily, and taper until the dosage is 5 to 10 mg orally on last day. Avoid giving the drug “as needed”. Adjustments in dosage according to the patient's clinical state may be indicated.

or

or

7- to 10-day taper:

10- to 14-day taper:

Calculate barbiturate or benzodiazepine equivalence and give 50 percent of the original dosage; taper (if actual dosage is known before detoxification). Avoid giving the drug “as needed.”

Calculate barbiturate or benzodiazepine equivalence and give 50 percent of the original dosage; taper (if actual dosage is known before detoxification). Avoid giving the drug “as needed.”


Information from references 5 through 8.

TABLE 3   Benzodiazepine (Barbiturate) Withdrawal

View Table

TABLE 3

Benzodiazepine (Barbiturate) Withdrawal

Short-acting detoxification Long-acting detoxification

7- to 10-day taper:

10- to 14-day taper:

On day 1, give diazepam (Valium), 10 to 20 mg orally four times daily, and taper until the dosage is 5 to 10 mg orally on last day. Avoid giving the drug “as needed.” Adjustments in dosage according to the patient's clinical state may be indicated.

On day 1, give diazepam, 10 to 20 mg orally four times daily, and taper until the dosage is 5 to 10 mg orally on last day. Avoid giving the drug “as needed”. Adjustments in dosage according to the patient's clinical state may be indicated.

or

or

7- to 10-day taper:

10- to 14-day taper:

Calculate barbiturate or benzodiazepine equivalence and give 50 percent of the original dosage; taper (if actual dosage is known before detoxification). Avoid giving the drug “as needed.”

Calculate barbiturate or benzodiazepine equivalence and give 50 percent of the original dosage; taper (if actual dosage is known before detoxification). Avoid giving the drug “as needed.”


Information from references 5 through 8.

Withdrawal from benzodiazepines is not usually marked by significant elevations in blood pressure and pulse as commonly occur in patients undergoing alcohol withdrawal. Furthermore, supplemental doses of sedatives taken as needed are usually not required for changes in vital signs58  (Table 3). Since benzodiazepines have cross-tolerance within that drug class as well as with other sedative/hypnotic drugs, benzodiazepines can be substituted for other sedative/hypnotics and vice versa. Equivalent doses can be calculated if the actual doses are known before beginning the tapering process (Table 4).

TABLE 4

Drug Dose Conversion* (Equivalent to 60 mg of Diazepam [Valium] and 180 mg of Phenobarbital)

Drug Dose (mg) Diazepam (60 mg) conversion factor Phenobarbital (180 mg) conversion factor

Benzodiazepines

Alprazolam (Xanax)

6

10.0

30.0

Chlordiazepoxide (Librium) [corrected]

150

0.4

1.2

Clonazepam (Klonopin)

24

2.5

7.5

Flurazepam (Dalmane)

90

0.6

2.0

Halazepam (Paxipam)

240

0.25

0.75

Lorazepam (Ativan)

12

5.0

15.0

Oxazepam (Serax)

60

1.0

3.0

Temazepam (Restoril)

60

1.0

3.0

Barbiturates

Butabarbital (Butisol)

600

0.1

0.3

Pentobarbital (Nembutal)

600

0.1

0.3

Secobarbital (Seconal)

600

0.1

0.3

Phenobarbital

180

0.33

1.0

Glycerol

Meprobamate (Equanil)

2,400

0.025

0.075

Piperideinedione

Glutethimide (Doriden)

1,500

0.04

0.12

Quinazoline

Methaqualone

1,800

0.03

0.1


NOTE: To find the dose of chlordiazepoxide equivalent to that of diazepam, multiply by 0.4. A dose of 150 mg of chlordiazepoxide is equivalent to a dose of 60 mg of diazepam. A dose of 100 mg is equivalent to a dose of 40 mg, etc.

*—Conversion factor × dose = diazepam or phenobarbital dose equivalent. Divide this amount in half to determine starting dosage.

TABLE 4   Drug Dose Conversion* (Equivalent to 60 mg of Diazepam [Valium] and 180 mg of Phenobarbital)

View Table

TABLE 4

Drug Dose Conversion* (Equivalent to 60 mg of Diazepam [Valium] and 180 mg of Phenobarbital)

Drug Dose (mg) Diazepam (60 mg) conversion factor Phenobarbital (180 mg) conversion factor

Benzodiazepines

Alprazolam (Xanax)

6

10.0

30.0

Chlordiazepoxide (Librium) [corrected]

150

0.4

1.2

Clonazepam (Klonopin)

24

2.5

7.5

Flurazepam (Dalmane)

90

0.6

2.0

Halazepam (Paxipam)

240

0.25

0.75

Lorazepam (Ativan)

12

5.0

15.0

Oxazepam (Serax)

60

1.0

3.0

Temazepam (Restoril)

60

1.0

3.0

Barbiturates

Butabarbital (Butisol)

600

0.1

0.3

Pentobarbital (Nembutal)

600

0.1

0.3

Secobarbital (Seconal)

600

0.1

0.3

Phenobarbital

180

0.33

1.0

Glycerol

Meprobamate (Equanil)

2,400

0.025

0.075

Piperideinedione

Glutethimide (Doriden)

1,500

0.04

0.12

Quinazoline

Methaqualone

1,800

0.03

0.1


NOTE: To find the dose of chlordiazepoxide equivalent to that of diazepam, multiply by 0.4. A dose of 150 mg of chlordiazepoxide is equivalent to a dose of 60 mg of diazepam. A dose of 100 mg is equivalent to a dose of 40 mg, etc.

*—Conversion factor × dose = diazepam or phenobarbital dose equivalent. Divide this amount in half to determine starting dosage.

A long-acting benzodiazepine is more effective than short-acting preparations in suppressing withdrawal symptoms and in producing a gradual and smooth transition to the abstinent state. In general, greater patient compliance and lower morbidity can be expected with the use of the longer-acting benzodiazepines, since withdrawal symptoms are less intense.

A taper over eight to 12 weeks or longer may be indicated in patients who have been taking benzodiazepines for several years (Table 5). The rate of taper can be adjusted according to patient tolerance. The rate of taper is a reduction in dosage of approximately 25 percent per quarter of the withdrawal period (e.g., 25 percent per week for one month).

TABLE 5

Benzodiazepine Taper

Day Dosage per day (mg)

1

10 mg three times daily = 30 mg

2

10 mg three times daily = 30 mg

3

10 mg three times daily = 30 mg

4

5 mg four times daily = 20 mg

5

5 mg four times daily = 20 mg

6

5 mg four times daily = 20 mg

7

5 mg three times daily = 15 mg

8

5 mg three times daily = 15 mg

9

5 mg three times daily = 15 mg

10

5 mg twice daily = 10 mg

11

5 mg twice daily = 10 mg

12

5 mg twice daily = 10 mg

13

5 mg every day = 5 mg

14

5 mg every day = 5 mg

15

5 mg every day = 5 mg


Example: Patient taking 12 mg of lorazepam (Ativan) per day = 60 mg diazepam (Valium) ×(50 percent reduction) = 30 mg.

TABLE 5   Benzodiazepine Taper

View Table

TABLE 5

Benzodiazepine Taper

Day Dosage per day (mg)

1

10 mg three times daily = 30 mg

2

10 mg three times daily = 30 mg

3

10 mg three times daily = 30 mg

4

5 mg four times daily = 20 mg

5

5 mg four times daily = 20 mg

6

5 mg four times daily = 20 mg

7

5 mg three times daily = 15 mg

8

5 mg three times daily = 15 mg

9

5 mg three times daily = 15 mg

10

5 mg twice daily = 10 mg

11

5 mg twice daily = 10 mg

12

5 mg twice daily = 10 mg

13

5 mg every day = 5 mg

14

5 mg every day = 5 mg

15

5 mg every day = 5 mg


Example: Patient taking 12 mg of lorazepam (Ativan) per day = 60 mg diazepam (Valium) ×(50 percent reduction) = 30 mg.

Stimulants (Cocaine, Amphetamines and Derivatives)

Supportive rather than specific treatment is indicated in patients who are undergoing withdrawal from stimulants. Observation and monitoring for depression and suicidal ideation are advised (Table 1). Since stimulant withdrawal may cause significant irritability, a dosage of 5 to 10 mg of diazepam given orally every six hours on a fixed schedule or as needed for two to three days is recommended in patients with mild to moderate withdrawal symptoms. For severe withdrawal symptoms with persistent depression, therapy may be initiated with antidepressants such as desipramine (Norpramin), at a dosage of 50 mg per day, titrated upward every other day in 50-mg increments until a dosage of 150 to 250 mg per day is attained. The dosage is maintained for three to six months and discontinued by gradually tapering the drug over two weeks.4,9 However, desipramine is not recommended routinely for management of withdrawal.

Opiates

Withdrawal symptoms from heroin addiction are predictable and identifiable (Table 1). Management of withdrawal can be accomplished with clonidine (Catapres) or methadone. Patients for whom clonidine is indicated include intranasal heroin users, outpatients and those who are motivated to achieve abstinency. Patients for whom methadone is indicated include intravenous users, inpatients, those who have medical and psychiatric complications and patients with a history of poor compliance when withdrawing from opiates5,9,10  (Table 6). Federal regulations do not allow the use of methadone for detoxification if opiate withdrawal is the primary diagnosis. However, methadone may be used if the primary diagnosis is a medical condition and the secondary condition is withdrawal from opiates.

TABLE 6

Opiate Detoxification (Heroin/Morphine Withdrawal)

Clonidine (Catapres) substitution Methadone substitution

Clonidine, 0.1 or 0.2 mg orally, given every 4 to 6 hours as needed for signs and symptoms of withdrawal for 5 to 7 days. (Peak dosages are given between 2 and 4 days.) Check blood pressure before each dose and do not give medication if patient is hypotensive.

Methadone test dose of 10 mg given orally in liquid or crushed tablet. Additional 10- to 20-mg doses are given for signs and symptoms of withdrawal every 4 to 6 hours for 24 hours after initial dose. Range for daily dose is 15 to 30 mg in 24 hours. Repeat total first day dose in a single dose or two divided doses (stabilization dose) for 2 to 3 days, then reduce dosage by 5 to 10 mg per day until medication is completely withdrawn. Methadone cannot be given for detoxification from other opiates unless licensed by the federal government or a medical comorbidity is the condition of primary treatment.


Information from references 5, 9 and 10.

TABLE 6   Opiate Detoxification (Heroin/Morphine Withdrawal)

View Table

TABLE 6

Opiate Detoxification (Heroin/Morphine Withdrawal)

Clonidine (Catapres) substitution Methadone substitution

Clonidine, 0.1 or 0.2 mg orally, given every 4 to 6 hours as needed for signs and symptoms of withdrawal for 5 to 7 days. (Peak dosages are given between 2 and 4 days.) Check blood pressure before each dose and do not give medication if patient is hypotensive.

Methadone test dose of 10 mg given orally in liquid or crushed tablet. Additional 10- to 20-mg doses are given for signs and symptoms of withdrawal every 4 to 6 hours for 24 hours after initial dose. Range for daily dose is 15 to 30 mg in 24 hours. Repeat total first day dose in a single dose or two divided doses (stabilization dose) for 2 to 3 days, then reduce dosage by 5 to 10 mg per day until medication is completely withdrawn. Methadone cannot be given for detoxification from other opiates unless licensed by the federal government or a medical comorbidity is the condition of primary treatment.


Information from references 5, 9 and 10.

Phencyclidine and Other Psychedelic Agents

Acute symptoms of withdrawal from psychedelic agents may be diminished or reversed by using therapy with haloperidol (Haldol), 5 to 10 mg intramuscularly or orally every three to six hours as tolerated and needed for behavior control. Lorazepam, 1 to 2 mg intravenously, or diazepam, 5 to 10 mg orally every three to six hours, can also be given as needed. Behavior control may also be indicated (e.g., isolation and restraints).5,9,11

Medications for Relapse Prevention

Disulfiram

Disulfiram is a major aversive agent. It has been shown in a randomized, double-blind, placebo-controlled multisite trial12 to be effective as an adjunct to other forms of addiction treatment.

The key components to effective use of disulfiram are overall patient motivation for abstinence and expectation of adverse reactions. Selected patients who have a commitment to working with other treatments for alcoholism may benefit from the addition of disulfiram therapy. The usual dosage of disulfiram is 250 mg per day, or 125 mg per day in patients who experience side effects such as sedation, sexual dysfunction and elevated liver enzymes.12,13

Disulfiram inhibits acetaldehyde dehydrogenase, an enzyme that catalyzes the degradation of acetaldehyde (formed by the action of alcohol dehydrogenase on alcohol). An accumulation of acetaldehyde produces an unpleasant reaction when alcohol is consumed that is similar to a severe hangover. It is potentially lethal, although only a small number of fatalities have been reported. The reaction to disulfiram is characterized by headache, diaphoresis, tachycardia, nausea and vomiting, cardiovascular collapse, delirium, seizures and, occasionally, death. Before using disulfiram, patients must have a blood alcohol level of zero and must be able to comprehend the risks and benefits of treatment.12,13

Methadone

Methadone maintenance is a form of pharmacologic management of opiate addiction. Methadone maintenance is performed in programs that are in compliance with federal regulations. Patients must meet admission requirements and must conform to clinic standards to participate in the program. Typically, methadone is given daily in oral doses ranging from 30 to 100 mg or greater. Methadone is administered under the supervision of a physician. Studies of methadone maintenance show initial efficacy following entrance to the program, and the medication remains effective in conjunction with other psychosocial forms of addiction treatment. Moreover, some studies show a reduction in intravenous drug use as well as in the rate of tests positive for human immunodeficiency virus infection.5,9,14 Methadone is an opiate agonist that acts competitively at opiate receptor sites to produce effects similar to those of other forms of opioids, such as heroin. Methadone is itself addicting, and patients commonly relapse to use of other drugs such as cocaine, alcohol, benzodiazepines and heroin. Nonetheless, methadone maintenance can be an alternative for patients who are addicted to intravenous heroin, particularly those who cannot or will not accept an abstinence-based addiction treatment program.5,9,14

Naltrexone

Naltrexone (ReVia) is an opioid antagonist that acts at opiate receptors to competitively inhibit effects of opiate agonists. It has no analgesic activity of its own. Preliminary controlled double-blind studies suggest that naltrexone is effective in decreasing the mean number of drinking days per relapse and in reducing the subjective craving for alcohol. Study subjects who relapsed tended to drink less alcohol and had shorter relapse periods than control subjects. Naltrexone was considered to be an adjunctive treatment, since all study subjects also were undergoing psychosocial forms of treatment for alcoholism.1517

While interest in developing these agents appears warranted, caution is urged because of disappointment in the clinical efficacy of naltrexone in previous studies of patients addicted to opiates (except those who are most highly motivated).

Use of Psychosocial Addiction Treatment to Prevent Relapse

Medical management of alcohol and drug withdrawal often is not sufficient to produce sustained abstinence from recurrent use. Therefore, other types of addiction treatment are indicated to prevent relapse to alcohol and drug use following treatment of withdrawal.18

Cost Benefits of Treatment

Historically, addiction treatment has not been integrated within the mainstream of the health care system, even though such treatment is effective and reduces health care costs. More accurate data on treatment outcomes and costs are needed so that informed and rational decisions about addiction treatment can be formulated by consumers, insurers, physicians and policy makers. Fortunately, the results of several recent health services research studies unequivocally demonstrate the cost effectiveness of addiction treatment.1922

Treatment Approaches and Effectiveness

The abstinence-based method is commonly used to treat alcohol/drug addiction (95 percent of programs surveyed). This method utilizes cognitive behavior techniques and referral to 12-step recovery programs, such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA).23

One-year abstinence rates of 80 to 90 percent were achieved when patients participated in weekly continuing care and/or AA meetings after discharge from the treatment program (Table 7). Also, one-year abstinence rates were associated with reduced rates of medical and psychiatric utilization18  (Table 8).

TABLE 7

One-Year Abstinence by Continuum of Care and Self-Help Support

Care criteria Inpatients (N = 6,508) Outpatients (N = 1,572)
Attending (%) Abstinent (%) Attending (%) Abstinent (%)

Months of continuing care attended in one year

0

42

53

34

48

1 to 5

32

55

33

61

6 to 11

19

71

18

68

12

8

88

14

89

AA attendance

Non-attender

54

47

43

49

Regular attender

46

74

57

80


AA = Alcoholics Anonymous.

Information from reference 23.

TABLE 7   One-Year Abstinence by Continuum of Care and Self-Help Support

View Table

TABLE 7

One-Year Abstinence by Continuum of Care and Self-Help Support

Care criteria Inpatients (N = 6,508) Outpatients (N = 1,572)
Attending (%) Abstinent (%) Attending (%) Abstinent (%)

Months of continuing care attended in one year

0

42

53

34

48

1 to 5

32

55

33

61

6 to 11

19

71

18

68

12

8

88

14

89

AA attendance

Non-attender

54

47

43

49

Regular attender

46

74

57

80


AA = Alcoholics Anonymous.

Information from reference 23.

TABLE 8

Medical Care Utilization One Year Before and After Treatment

Care criteria Inpatients (N = 6,508) Outpatients (N = 1,572)
Attending (%) Abstinent (%) Attending (%) Abstinent (%)

Hospitalizations

Medical

23

10

16

7

Psychiatric

5

2

4

1

Detoxification

16

4

9

2

Any admission

28

14

21

9

Emergency department use

Medical

31

22

29

22

Psychiatric

3

1

3

1

Any emergency department use

30

24

29

23


Information from references 18 and 23.

TABLE 8   Medical Care Utilization One Year Before and After Treatment

View Table

TABLE 8

Medical Care Utilization One Year Before and After Treatment

Care criteria Inpatients (N = 6,508) Outpatients (N = 1,572)
Attending (%) Abstinent (%) Attending (%) Abstinent (%)

Hospitalizations

Medical

23

10

16

7

Psychiatric

5

2

4

1

Detoxification

16

4

9

2

Any admission

28

14

21

9

Emergency department use

Medical

31

22

29

22

Psychiatric

3

1

3

1

Any emergency department use

30

24

29

23


Information from references 18 and 23.

Recovery in Alcoholics Anonymous

According to results of a 1992 survey conducted by AA, the following recovery rates were achieved. (1) Of those members sober in AA less than one year, 41 percent will attend AA another year. (2) Of those members sober more than one year and less than five years, 83 percent will attend AA another year. (3) Of those members sober five years or more, 91 percent will attend AA another year.23

Attendance in an abstinence-based treatment program such as AA can increase recovery rates from 41 to 80 percent in patients with alcoholism.18,23 For this reason, patients with alcoholism should be referred to AA following withdrawal treatment and during maintenance therapy.

The Authors

NORMAN S. MILLER, M.D., is associate professor of psychiatry and neurology and chief of the division of addiction programs at the University of Illinois School of Medicine, Chicago. He received a medical degree from Howard University, Washington, D.C., and completed a residency in psychiatry at Johns Hopkins Hospital, Baltimore, and a residency in neurology at the University of Minnesota, Minneapolis.

MARK S. GOLD, M.D., is professor of psychiatry at the University of Florida Brain Institute, Gainesville. He received a medical degree from the University of Florida College of Medicine, Gainesville, and served a residency in psychiatry at Yale University, New Haven, Conn.

Address correspondence to Norman S. Miller, M.D., University of Illinois at Chicago Department of Psychiatry (MC 913), 912 S. Wood Street, Chicago, IL 60612–7327. Reprints are not available from the authors.

REFERENCES

1. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. Epidemiology of alcohol use and alcoholrelated consequences. In: Alcohol and health. Eighth special report to the U.S. Congress from the Secretary of Health and Human Services. September 1993:1–35.

2. Bennett JC, Plum F, eds. Cecil textbook of medicine. 20th ed. Philadelphia: Saunders, 1996.

3. Adams RD, Victor M, Ropper AH. Principles of neurology. 6th ed. New York: McGraw-Hill, Health Professions Division, 1997.

4. Miller NS, Gold MS, Smith DE, eds. Manual of therapeutics for addictions. New York: Wiley-Liss, 1997.

5. American Society of Addiction Medicine. Principles of addiction medicine. Washington, D.C.: The Society, 1994.

6. Miller NS, Gold MS. Abuse, addiction, tolerance, and dependence to benzodiazepines in medical and nonmedical populations. Am J Drug Alcohol Abuse. 1991;17:27–37.

7. Rickels K, Schweizer E, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Arch Gen Psychiatry. 1990;47:899–907 [Published erratum appears in Arch Gen Psychiatry 1991;48:51]

8. Schweizer E, Rickels K, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry. 1990;47:908–15.

9. Gorelick DA. Overview of pharmacologic treatment approaches for alcohol and other drug addiction. Intoxication, withdrawal, and relapse prevention. Psychiatr Clin North Am. 1993;16:141–56.

10. Gold MS. Pharmacological therapies of opiate addiction. In: Miller NS, Gold MS, eds. Pharmacologic therapies for drug and alcohol addictions. New York: Marcel Dekker, 1995.

11. Giannini AT. Phencyclidine. In: Miller NS, ed. Comprehensive handbook of drug and alcohol addiction. New York: Dekker, 1991:383–94.

12. Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, et al. Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. JAMA. 1986;256:1449–55.

13. Banys P. The clinical use of disulfiram (Antabuse): a review. J Psychoactive Drugs. 1988;20:243–61.

14. Weddington WW. Methadone maintenance for opioid addiction. In: Miller NS, Gold MS, eds. Pharmacological therapies for drug and alcohol addictions. New York: Dekker, 1995:411–18.

15. Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992;49:876–80.

16. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry. 1992;49:881–7.

17. O'Malley SS. Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse. Alcohol Alcohol. 1996;31(Suppl 1):77–82.

18. Miller NS. Treatment of the addictions: applications of outcome research for clinical management. New York: Haworth, 1995.

19. Gerstein DR, Johnson RA, Harwood H, Fountain D, Suter N, Malloy K. Evaluating recovery services: the California Drug and Alcohol Treatment Assessment (CALDATA). Sacramento, Calif.: State of California Department of Drug and Alcohol Programs, 1994.

20. Iglehart JK. The American health care system. Managed care. N Engl J Med. 1992;327:742–7.

21. Holder HD, Blose JO. The reduction of health care costs associated with alcoholism treatment: a 14-year longitudinal study. J Stud Alcohol. 1992;53:293–302.

22. Turnure C. Minnesota Consolidated Fund, annual cost offsets. Minnesota Department of Human Services, 1993.

23. Chappel JN. Long-term recovery from alcoholism. Psychiatr Clin North Am. 1993;16:177–87.



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