Withdrawal from Sedatives (Alcohol and Benzodiazepines)

The clinical history often suggests alcohol problems, which are seen in 15 to 20 percent of patients in primary care and hospitalized patients. Since alcohol withdrawal can be complicated by seizures and delirium and is more severe in persons with more previous episodes of withdrawal or other illnesses, careful evaluation is essential. Such evaluation should include assessment for anemia, thrombocytopenia, and elevated liver-enzyme levels. Specific symptoms during sedative or alcohol withdrawal that may dictate pharmacotherapy include auditory and tactile disturbances and seizures.

Significant components of the withdrawal syndrome after chronic alcohol use reflect reduced neurotransmission in type A γ-aminobutyric acid pathways and enhanced neurotransmission in glutamate (N-methyl-D-aspartate) pathways. Seizures during withdrawal probably result from this altered neurobiology, but the anticonvulsant medication phenytoin is not an effective treatment for alcohol withdrawal. Benzodiazepines are effective, probably owing to cross-tolerance with ethanol at the type A γ-aminobutyric acid receptor, where carbamazepine and divalproate are also believed to have their main actions.

On the basis of this neurobiology, antagonism at the N-methyl-D-aspartate receptor is another potential mechanism for relieving symptoms of alcohol and sedative withdrawal and may be important for reducing the toxic effects from repeated episodes of alcohol withdrawal.

Withdrawal symptoms can be quantified to allow symptom-triggered therapy, in which the patient receives medication only when symptoms exceed a threshold of severity, rather than on a fixed schedule. This approach is as effective as fixed-dose therapy but requires significantly less medication and leads to a more rapid detoxification. It does, however, require careful and frequent monitoring with a validated withdrawal-symptom scale such as the Clinical Institute Withdrawal Assessment for Alcohol. The categories on this scale are sweating, anxiety, tremor, auditory or visual disturbances, agitation, nausea and vomiting, tactile disturbances, headache, and orientation. Total symptom scores of more than 15 on this scale or a history of withdrawal seizures indicates that medications should be started at presentation.

Without medication, alcohol-withdrawal symptoms might be expected to peak about 72 hours after the last use of alcohol, but medications can reduce symptoms within hours. In patients with delirium tremens, management with medication requires high doses of benzodiazepines (e.g., 5 to 10 mg of diazepam by intravenous injection, repeated in two to four hours if seizures occur). Unless delirium is present, medication is typically needed for no more than seven days after the last use of alcohol, although some patients will report withdrawal symptoms, including sleep problems, for several more weeks. Protracted symptoms may precipitate relapse.

Withdrawal from benzodiazepines and other sedatives produces more psychomotor and autonomic nervous system signs than does withdrawal from alcohol, and these signs start between 2 and 10 days after abrupt discontinuation. If medications are used, treatment with anticonvulsant drugs such as carbamazepine will need to be continued for about two weeks, and the dose of benzodiazepines gradually tapered.