Alcohol Withdrawal Syndrome
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The spectrum of alcohol withdrawal symptoms ranges from such minor symptoms as insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens. Although the history and physical examination usually are sufficient to diagnose alcohol withdrawal syndrome, other conditions may present with similar symptoms. Most patients undergoing alcohol withdrawal can be treated safely and effectively as outpatients. Pharmacologic treatment involves the use of medications that are cross-tolerant with alcohol. Benzodiazepines, the agents of choice, may be administered on a fixed or symptom-triggered schedule. Carbamazepine is an appropriate alternative to a benzodiazepine in the outpatient treatment of patients with mild to moderate alcohol withdrawal symptoms. Medications such as haloperidol, beta blockers, clonidine, and phenytoin may be used as adjuncts to a benzodiazepine in the treatment of complications of withdrawal. Treatment of alcohol withdrawal should be followed by treatment for alcohol dependence. (Am Fam Physician 2004;69:1443-50. Copyright© 2004 American Academy of Family Physicians) |
In 1992, approximately 13.8 million Americans (7.4 percent of the U.S. adult population)1 met the criteria for alcohol abuse or dependence as specified in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR).2 In 2000, 226,000 patients were discharged from short-stay hospitals (excluding Veteran's Affairs and other federal hospitals) with one of the following diagnoses: alcohol withdrawal (Table 1),2 alcohol withdrawal delirium, or alcohol withdrawal hallucinosis.3 It is estimated that only 10 to 20 percent of patients undergoing alcohol withdrawal are treated as inpatients,4 so it is possible that as many as 2 million Americans may experience symptoms of alcohol withdrawal conditions each year.
Pathophysiology
Alcohol withdrawal syndrome is mediated by a variety of mechanisms. The brain maintains neurochemical balance through inhibitory and excitatory neurotransmitters. The main inhibitory neurotransmitter is gamma-aminobutyric acid (GABA), which acts through the GABA-alpha (GABA-A) neuroreceptor. One of the major excitatory neurotransmitters is glutamate, which acts through the N-methyl-D-aspartate (NMDA) neuroreceptor.
Alcohol enhances the effect of GABA on GABA-A neuroreceptors, resulting in decreased overall brain excitability. Chronic exposure to alcohol results in a compensatory decrease of GABA-A neuroreceptor response to GABA, evidenced by increasing tolerance of the effects of alcohol.
Alcohol inhibits NMDA neuroreceptors, and chronic alcohol exposure results in up-regulation of these receptors. Abrupt cessation of alcohol exposure results in brain hyperexcitability, because receptors previously inhibited by alcohol are no longer inhibited. Brain hyperexcitability manifests clinically as anxiety, irritability, agitation, and tremors. Severe manifestations include alcohol withdrawal seizures and delirium tremens.
An important concept in both alcohol craving and alcohol withdrawal is the "kindling" phenomenon; the term refers to long-term changes that occur in neurons after repeated detoxifications. Recurrent detoxifications are postulated to increase obsessive thoughts or alcohol craving.5 Kindling explains the observation that subsequent episodes of alcohol withdrawal tend to progressively worsen.
Although the significance of kindling in alcohol withdrawal is debated, this phenomenon may be important in the selection of medications to treat withdrawal. If certain medications decrease the kindling effect, they may become preferred agents.
Withdrawal Symptoms
The spectrum of withdrawal symptoms and the time range for the appearance of these symptoms after cessation of alcohol use are listed in Table 2. Generally, the symptoms of alcohol withdrawal relate proportionately to the amount of alcoholic intake and the duration of a patient's recent drinking habit. Most patients have a similar spectrum of symptoms with each episode of alcohol withdrawal