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.1–3 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
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
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).
|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|
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.
|Mild withdrawal||Moderate withdrawal||Severe withdrawal (delirium tremens)*||Loading-dose method|
|Diazepam (Valium), 5 to 10 mg orally as needed|
Lorazepam (Ativan), 1 to 2 mg orally every 4 to 6 hours as needed for 1 to 3 days
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
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
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).
|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.|
|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.”|
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 signs5–8 (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).
|Drug||Dose (mg)||Diazepam (60 mg) conversion factor||Phenobarbital (180 mg) conversion factor|
|Chlordiazepoxide (Librium) [ corrected]||150||0.4||1.2|
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).
|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|
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.
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.
|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.|
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 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 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 (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.15–17
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.19–22
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).
|Care criteria||Inpatients (N = 6,508)||Outpatients (N = 1,572)|
|Attending (%)||Abstinent (%)||Attending (%)||Abstinent (%)|
|Months of continuing care attended in one year|
|1 to 5||32||55||33||61|
|6 to 11||19||71||18||68|
|Care criteria||Inpatients (N = 6,508)||Outpatients (N = 1,572)|
|Attending (%)||Abstinent (%)||Attending (%)||Abstinent (%)|
|Emergency department use|
|Any emergency department use||30||24||29||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