Treatment of alcohol withdrawal

An important initial intervention for a minority of alcohol-dependent patients is the management of alcohol withdrawal through detoxification. The objectives in treating alcohol withdrawal are relief of discomfort, prevention or treatment of complications, and preparation for rehabilitation. Successful management of the alcohol withdrawal syndrome is generally necessary for subsequent efforts at rehabilitation to be successful treatment of withdrawal alone is usually not sufficient, because relapse occurs commonly. 

The identification of co-occurring medical problems is an important element in detoxification (Naranjo and Sellers 1986). Good supportive care and treatment of concurrent illness, including fluid and electrolyte repletion, are essential (Naranjo and Sellers 1986). Administration of thiamine (50—100 mg/day po or im) and multivitamins is a low-cost, low-risk intervention for the prophylaxis and treatment of alcohol-related neurological disturbances. 

Social detoxification, which involves the nonpharmacological treatment of alcohol withdrawal, has been shown to be effective (see Naranjo et al. 1983). It consists of frequent reassurance, reality orientation, monitoring of vital signs, personal attention, and general nursing care (Naranjo and Sellers 1986). Social detoxification is most appropriate for patients in mild-to-mod-erate withdrawal. The medical problems commonly associated with alcoholism (Sullivan and O Connor 2004) may substantially complicate therapy, so that care must be taken to refer patients whose condition requires medical management. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Increasingly, detoxification is being done on an ambulatory basis, which is much less costly than inpatient detoxification (Hayashida et al. 1989). Inpatient detoxification is indicated for patients with serious medical or surgical illness and for those with a past history of adverse withdrawal reactions or with current evidence of more serious withdrawal reactions (e.g., dehrium tremens) (Feldman et al. 1975). 

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Some of these drugp may have additional uses as sedatives, muscle relaxants, anticonvulsants, and in the treatment of alcohol withdrawal. For example, clo-razepate (Tranxene) and diazepam (Valium) are used as anticonvulsants (see Chap. 28). Additional uses of the individual antianxiety drugp are given in the Summary Drug Table Antianxiety Drugp. 

In general, with the exception of the central role that benzodiazepines play in the treatment of alcohol withdrawal, the use of medications that have been approved for alcoholism rehabilitation remains very limited. A survey of nearly 1,400 addiction physicians showed that they prescribed disulfiram to only 9% of their alcoholic patients and that naltrexone was prescribed for only slightly higher proportion of patients (13%) (Market al. 2003). These tesults contrast with findings for antidepressants, which were prescribed to 44% of alcoholic patients. Although neatly all of these physicians had heatd of both disulfiram and naltrexone, their self-reported level of knowledge of these medications was much lowet than that of antidepressants. 

Malcolm R, Ballenger JC, Sturgis ET, et ah Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Am J Psychiatry 146 617-621, 1989... 

Another potential chnical use of GHB is in the treatment of alcohol withdrawal and alcohol dependence. In prechnical studies, GHB inhibited voluntary ethanol consumption in ethanol-preferring rats and suppressed the... 

GHB treatment in mice, tolerance develops to both the hypolocomotion and cataleptic effects of the drug (Itzhak and Ali 2002). There is also preclinical evidence of cross-tolerance and cross-dependence of GHB with alcohol (Colombo et al. 1995 Fadda et al. 1989). As described in the earlier section on clinical pharmacology, GHB and its analogues have been used in humans in the treatment of alcohol withdrawal. Nicholson and Balster (2001) reviewed the evidence for cross-tolerance and cross-dependence of GHB with alcohol. 

Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, et al Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol 37 67—73, 2002... 

Sellers EM, Naranjo CA, Harrison M, et al Diazepam loading simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 34 822-826, 1983 Sharp CW Introduction to inhalant Abuse, in Inhalant Abuse A Volatile Research Agenda (NIDA Research Monograph 129). Edited by Sharp CW, Beuvais F, Spence R. Rockville, MD, National Institute on Drug Abuse, 1992, pp 1-10 Smelson DA, Losonczy MF, Davis CW, et al Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence. Can J Psychiatry 47 671-675, 2002... 

Most clinicians agree that the BZs are the drugs of choice in treatment of alcohol withdrawal. 

Pharmacologic Agents Used in the Treatment of Alcohol Withdrawal... 

Historically, the treatment of alcohol use disorders with medication has focused on the management of withdrawal from the alcohol. In recent years, medication has also been used in an attempt to prevent relapse in alcohol-dependent patients. The treatment of alcohol withdrawal, known as detoxification, by definition uses replacement medications that, like alcohol, act on the GABA receptor. These medications (i.e., barbiturates and benzodiazepines) are cross-tolerant with alcohol and therefore are useful for detoxification. By contrast, a wide variety of theoretical approaches have been used to reduce the likelihood of relapse. This includes aversion therapy and anticraving therapies using reward substitutes and interference approaches. Finally, medications to treat comorbid psychiatric illness, in particular, depression, have also been used in attempts to reduce the likelihood of relapse. 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

Unlabeled Uses Treatment of alcohol withdrawal, diabetes insipidus, neurogenic pain, psychotic disorders... 

Uniabeied Uses Treatment of alcohol withdrawal, panic disorders, skeletal muscle spasms, chemotherapy-induced nausea orvomiting, tension headache, tremors adjunctive treatment before endoscopic procedures (diminishes patient recall)... 

The treatment of alcohol withdrawal incorporates general supportive measures, as well as management of specific symptoms. Supportive measures include abstinence from alcohol, ample rest, adequate general nutrition, and reality orientation. It is important to treat the syndrome vigorously and, when appropriate, to prevent it by using sufficient doses of medication. 

Propranolol reduces the frequency and intensity of migraine headache. Other 13-receptor antagonists with preventive efficacy include metoprolol and probably also atenolol, timolol, and nadolol. The mechanism is not known. Since sympathetic activity may enhance skeletal muscle tremor, it is not surprising that 13 antagonists have been found to reduce certain tremors (see Chapter 28). The somatic manifestations of anxiety may respond dramatically to low doses of propranolol, particularly when taken prophylactically. For example, benefit has been found in musicians with performance anxiety ("stage fright"). Propranolol may contribute to the symptomatic treatment of alcohol withdrawal in some patients. 

Seizures Clonazepam [kloe NA ze pam] is useful in the chronic treatment of epilepsy, whereas diazepam is the drug of choice in terminating grand mal epileptic seizures and status epilepticus (see p. 149). Chlordiazepoxide [klor di az e POX ide], clorazepate [klor AZ e pate], diazepam, and oxazepam [ox A ze pam] are useful in the acute treatment of alcohol withdrawal. 

S. D. Ferrara, F. Fadda, and G. L. Gessa. Gamma-hydroxybutyric Acid for Treatment of Alcohol Withdrawal Syndrome. Lancet2 (8666) (1989) 787-789 Beghe, F., and M. T. Carpanini. Safety and Tolerability of Gamma-hydroxybutyric Acid in the Treatment of Alcohol-dependant Patients. Alcohol 20... 

F. Fadda, and G. L. Gessa. Gamma-hydroxybutyric Acid for Treatment of Alcohol Withdrawal Syndrome. Lancet 2 (8666) (1989) 787-789. 

Social detoxification Treatment of alcohol withdrawal without the use of medicine (Chapter 9). 

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