Few diseases have as significant an impact on patients and their families as addiction disorders. Each year in the United States, 30,000 deaths occur because of illegal drug use, and more than 100,000 deaths are attributed to alcoholism.1 The lifetime prevalence of drug addiction is estimated at 6 percent of the general population.2 Although a reported 15 million Americans have alcohol problems, fewer than 5 percent receive formal treatment.3
Substance abuse occurs among persons of all ages. Recent studies on the daily use of addictive substances by high school seniors report prevalence rates of 4 percent for alcohol, 2 percent for marijuana and 9 percent for cocaine.4,5 In the geriatric population, alcohol and benzodiazepine withdrawal is a significant source of morbidity and mortality,6 and 10 to 15 percent of senior citizens reportedly are drinking in excess of recommended limits.7
Given the current shift to outpatient treatment of alcohol and other drug addiction, family physicians are increasingly being called on to address issues related to substance abuse. Except for situations involving severe or complicated withdrawal, alcohol and drug rehabilitation is now almost exclusively an outpatient process.10
Identification of Substance Abuse
Although many physicians routinely ask about alcohol and drug use, few do so in a structured manner.8 Several tools are available to help physicians assess a patient's history of alcohol and drug use. Regardless of the tool selected, screening for substance abuse needs to become part of every physician's practice routine.
The CAGE questionnaire, which consists of only four questions, is one common screening tool (Table 1).11 Given its brevity and utility, the CAGE questionnaire could be included as part of every new patient assessment, every annual health promotion visit and every hospital admission. One drawback to the CAGE questionnaire is its narrow focus on alcohol abuse. Adding a fifth question focusing on substance tolerance may make the questionnaire a more effective screening tool for drug abuse.12
The 10-item Alcohol Use Identification Test (AUDIT) is another commonly used screening tool (Figure 1).13 Although this questionnaire requires more administration time than the CAGE questionnaire, it may be more effective in identifying alcohol abuse in the general population, particularly among women.14
Other screening techniques may be used. For example, a single-question screening tool has recently been shown to be quite effective in identifying problem drinking. The physician simply asks, “On any single occasion during the past three months have you had more than five drinks containing alcohol?”15
The tendency for addicted patients to deny that they have a problem is a major barrier to treatment intervention. Effective strategies for breaking through this denial include reviewing the family history, including family members in the treatment process, involving employers or law enforcement agents, and stressing the social consequences of continued substance abuse. Explanations of the biologic and physical effects of abuse can also be potentially sobering reminders of the consequences of a patient's actions. Although confronting patients about substance use may sometimes appear to be a waste of time and effort, physician confrontation has been shown to increase the likelihood of subsequent recovery in patients who abuse alcohol or other drugs.16
The use of substitution medication is the most common approach to detoxification. However, this approach is only useful in patients with addictions to sedative-hypnotics, alcohol, opioids and nicotine. Withdrawal from opioids or nicotine is unlikely to cause morbidity or mortality, although it often is very uncomfortable.17 On the other hand, unsupervised withdrawal from sedative-hypnotic drugs or alcohol can result in significant morbidity and mortality.
The appropriateness of outpatient treatment depends on the stage of withdrawal (Table 2).17 All patients in stage III withdrawal must be treated in an inpatient intensive care setting, whereas patients in stage II withdrawal can be managed in an outpatient setting. It should be noted, however, that stage II withdrawal can be difficult to identify, because patients may be reluctant to volunteer information about hallucinations unless they are reassured that hallucinating is an expected aspect of the withdrawal process. In general, patients can undergo detoxification in an outpatient setting as long as they do not progress to a higher withdrawal stage or present in stage III withdrawal.17
Certain guidelines must be observed when managing patients who are entering withdrawal. First, adequate dosages of medications with long half-lives are helpful in preventing breakthrough irritability and seizures.18 One of the most frequent mistakes that primary care physicians make during detoxification is failing to provide adequate medication to control withdrawal symptoms.
Patient monitoring is also important. In the outpatient setting, the patient who is undergoing withdrawal must be monitored by a person who is committed to staying with the patient throughout the detoxification process. In addition, daily physician visits are necessary until detoxification has been completed and the patient is medically stable.
Special attention needs to be given to the patient with previous withdrawal seizures or a history of delirium tremens. If close monitoring or inpatient treatment is an option, a flexible detoxification schedule that allows for adequate sedation can be used.19 When close monitoring is not available, a rigid schedule of medication is appropriate to ensure that the patient receives adequate sedation. If a patient progresses to stage III withdrawal, immediate admission to an inpatient unit is required.20
SUBSTITUTION MEDICATIONS FOR ALCOHOL WITHDRAWAL
Several detoxification medication regimens are appropriate for use in outpatient alcohol withdrawal. Chlordiazepoxide (Librium), one of the most frequently used medications, has a well-documented efficacy profile.21,22 This drug has a wide therapeutic window and is “self-tapering” because of its long half-life. Thus, chlordiazepoxide is an ideal drug for use in outpatient detoxification.19 One treatment option is to “front load” the patient to provide adequate sedation (Table 3). Then small amounts of the drug are added as needed during the detoxification period.20
|Schedule||Day 1||Day 2||Day 3||Day 4|
|Rigid||50 to 100 mg four times daily||50 to 100 mg three times daily||50 to 100 mg twice daily||50 to 100 mg at bedtime|
|Flexible||50 to 100 mg every 4 to 6 hours as needed based on symptoms*||50 to 100 mg every 6 to 8 hours as needed||50 to 100 mg every 12 hours as needed||50 to 100 mg at bedtime as needed|
|Front loading†||100 to 200 mg every 2 to 4 hours until sedation is achieved; then 50 to 100 mg every 4 to 6 hours as needed||50 to 100 mg every 4 to 6 hours as needed||50 to 100 mg every 4 to 6 hours as needed||None|
Chlordiazepoxide therapy should be stopped if a patient does not respond as expected to an adequate dosage of the medication. Failure to respond may reflect complete down-regulation of the γ-aminobutyric acid–neuron benzodiazepine receptors, which renders the medication ineffective.23 In this situation, a barbiturate may be necessary to induce sedation.24
Pregnant women should not be treated with chlordiazepoxide. The drug also should not be given to patients with liver failure. Because the liver's ability to oxidize substances declines before its ability to conjugate substances, medications conjugated by the liver, such as lorazepam (Ativan), oxazepam (Serax) and phenobarbital, should be used in place of chlordiazepoxide.19 Treatment regimens for these drugs are provided in Table 4.
|Lorazepam (Ativan)||1 to 4 mg every 3 or 4 hours for 3 to 5 days|
|Oxazepam (Serax)||20 to 40 mg every 3 or 4 hours for 3 to 5 days|
|Phenobarbital||60 to 120 mg initially, followed by 60 to 120 mg four times daily for day 1, three times daily for day 2, twice daily for day 3 and then once daily at bedtime|
Except in patients with liver failure, short-acting benzodiazepines such as lorazepam and oxazepam generally should not be used in the outpatient setting because of the potential for breakthrough seizures.19 Intravenous administration of lorazepam is an acceptable option in hospitalized patients who are in stage III withdrawal. These patients can be given an initial loading dose of 2 to 4 mg of lorazepam, with subsequent doses titrated until adequate sedation is achieved. The use of lorazepam in this setting allows more precise titration than can be obtained with longer acting medications.
Long-acting benzodiazepines such as clorazepate (Tranzene), diazepam (Valium) and clonazepam (Klonopin) appear to have no advantages over chlordiazepoxide and may be more expensive.19 Thus, when alternative treatment regimens are indicated, oxazepam, lorazepam and phenobarbital are appropriate choices.
Barbiturates can be used as first-line medications for substitution in alcohol withdrawal.25 A disadvantage to this protocol, however, is that the narrow therapeutic window increases the possibility of toxicity. Barbiturates also interfere with the clearance of many drugs that are metabolized by the liver. Selected drug interactions with phenobarbital are listed in Table 5.
|Anticoagulants, corticosteroids, doxycycline (Vibramycin) and steroidal hormones||Phenobarbital increases the metabolism of these drugs and decreases their effectiveness.|
|Griseofulvin (Grisactin)||Phenobarbital decreases the absorption and effectiveness of griseofulvin.|
|Phenytoin (Dilantin)||Phenobarbital may increase or decrease the metabolism of phenytoin.|
|Valproic acid (Depakene)||Valproic acid increases phenobarbital blood levels.|
|Monoamine oxidase inhibitors||These drugs prolong the action of phenobarbital.|
|Central nervous system depressants||Phenobarbital may produce additive depressant effects.|
SUBSTITUTION MEDICATIONS FOR SEDATIVE-HYPNOTIC WITHDRAWAL
As opposed to alcohol, withdrawal from the long-term use of sedative-hypnotics requires prolonged administration of substitution medications to reduce symptoms. Pretreatment anxiety levels may recur for several weeks after withdrawal. A protracted abstinence syndrome marked by chronic, fluctuating anxiety occasionally occurs during discontinuation of a chronic, low-dose benzodiazepine.26 This state can persist more than a year and becomes most evident during withdrawal of the last 10 to 25 percent of the original maintenance dosage.26
Anxiety can be reduced by using a low dosage of carbamazepine (Tegretol; 400 to 1,200 mg per day) or valproic acid (Depakene; 500 to 1,500 mg per day) while slowly tapering the sedative-hypnotic drug at the rate of one half of the daily dosage each week.27
The use of supportive medications should be considered in patients who are undergoing alcohol withdrawal. Thiamine supplementation can counteract the thiamine deficiencies that are common in chronic alcohol abusers. This measure can help prevent the development of Wernicke-Korsakoff syndrome, which may present with confusion, apathy, drowsiness, amnesia and polyneuropathies. Symptoms of the syndrome typically last several weeks to several months in untreated patients, but they can be permanent. The recommended regimen is 100 mg of thiamine per day for three days. If a dextrose infusion is being given, thiamine supplementation should be continued until the infusion has been completed.17
Clonidine (Catapres) can be helpful in reducing the increased noradrenergic output that persists in some patients after the completion of detoxification. This drug should not be used during detoxification, because it can mask the changes in heart rate and blood pressure that are used to titrate sedation.18,19 Beta blockers may be used in place of clonidine, but these drugs can aggravate delirium and precipitate psychosis in the early withdrawal period.19
Phenytoin (Dilantin), carbamazepine and valproic acid are highly effective in treating comorbid seizure disorders. However, these medications should not be used to treat acute alcohol withdrawal because they do not prevent withdrawal seizures or progression of the withdrawal syndrome.23
Hallucinations without insight resulting from stage III alcohol withdrawal signify an acute medical emergency. In this situation, neuroleptic drugs (antipsychotic agents) should not be used alone, because they do not prevent progression of the withdrawal syndrome, and they may lower the seizure threshold.19 When used in conjunction with adequate sedation, haloperidol (Haldol) is preferable because it has only a minimal effect on the seizure threshold.19
Following successful completion of withdrawal, a patient's primary challenge is to maintain sobriety. To assist with this lifelong process, the physician needs to diagnose and treat comorbid psychiatric, personality and medical disorders, and address social and environmental impediments to continuing recovery.
A significant number of alcoholics and drug abusers also have a depressive disorder or other mood or anxiety disorder.28 Treatment of these comorbid psychiatric disorders is crucial, because patients with untreated anxiety, depression or bipolar disorder frequently resume drinking alcohol or using drugs in an attempt to self-medicate their mood disorder.
Adequate relief of periodic pain is also important to reduce the potential for self-medication with alcohol or other substances.28 In treating acute pain, selective use of short-term narcotic therapy is acceptable. Severe pain rarely lasts more than a few days, at which time it is appropriate to change to a nonnarcotic medication for pain control. When possible, it is best to use nonnarcotic medications in patients with chronic pain.
Family physicians must always be alert for symptoms of relapse. Monitoring patients with routine liver function tests and red blood cell indexes may be helpful in assessing ongoing treatment compliance. Routine contact with family members is also important.
Most communities offer a variety of adjunctive long-term support systems, including Alcoholics Anonymous (AA), outpatient involvement with professionals experienced in addiction counseling and participation in religious organizations. These treatment options all have similar one- to two-year recovery rates, but AA and other 12-step programs have the best long-term recovery rates.29 Narcotics Anonymous (NA) uses a structure similar to that of AA to encourage abstinence among narcotic abusers, and Ala-Non and Ala-Teen provide 12-step support for the families of substance abusers.25
Patients who require more intensive ongoing treatment may need to be referred to physicians and other health care professionals who are accredited in substance abuse treatment through the American Society of Addiction Medicine or the American Academy of Addiction Psychiatry. Alternatively, these patients may need to be managed in an inpatient program staffed with a multidisciplinary team.
Family physicians with a supportive, non-judgmental, yet assertive attitude can be a great asset in confronting and treating patients with alcohol and other substance abuse problems. With the right attitude and the right tools, primary care physicians can manage most patients through the withdrawal phase of their illness and be a powerful influence in their ongoing struggle for recovery