Alcohol Withdrawal

Pathophysiology. Alcohol tolerance occurs with neuroadaptations to chronic alcohol exposure. Alcohol is a sedative; chronic exposure leads to compensatory changes with reduced neurotransmission at inhibitory type A gamma-aminobutyric acid (GABA) receptors and enhanced neurotransmission at excitatory N-methyl-D-aspartate (NMDA) glutamatergic receptors. During abrupt abstinence episodes, the unopposed activity of these compensatory changes results in central hyperexcitability responsible for objective and subjective AWS symptoms.

Presentation. AWS onset typically peaks within 48 to 72 hours of the last ethyl alcohol intake. Clinical signs of AWS include diaphoresis, tachycardia, hypertension, fever, vomiting, insomnia, anxiety, tremor, hyperreflexia, delirium, and grand mal seizures. Delirium tremens (“DTs”) is a very severe withdrawal syndrome, with a fatal potential if not recognized or if undertreated. This involves autonomic instability, agitation, altered mental state, hallucinations, and tremor. Risk factors include advanced age, advanced alcohol dependence, prior episodes of DTs, and medical illness. Clinical symptoms of AWS include anxiety, irritability, dysphoria, nausea, anorexia, alcohol craving, headache, fatigue, and auditory, visual and/or tactile hallucinations. AWS is measured using a standardized instrument, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA). This measures 10 AWS symptoms categories with a 0 to 7 scoring range for each. Moderate scores (8 to 15) reflect autonomic hyperactivity, and high scores (>15) predict seizures and delirium; these scores warrant immediate initiation of medical treatment.

Persistent AWS may endure 1 to 6 months and consists of anxiety or dysphoria, insomnia, and restlessness as well as frequent cravings for alcohol. Some medical treatments assisting recovery and promoting abstinence are hypothesized to address persistent central hyperexcitability. These include acamprosate, naltrexone, disulfiram, and topiramate (see Plate 4-14). These medications must be combined with complete alcohol abstinence and active attendance at Alcoholics Anonymous or similar support groups. This will reduce symptoms that frequently lead to alcohol relapse.

Treatment. Benzodiazepines are the gold standard AWS treatment due to their cross-reactivity with alcohol at type A GABA receptors. Symptom-triggered detoxification protocols are used because these prevent medical morbidity, and even a very occasional death, while minimizing dosing requirements for benzodiazepines and thus adverse effects. Typical protocols initiate treatment with either short-acting (lorazepam) or longer-acting (diazepam, chlordiazepoxide) benzodiazepines once autonomic arousal is recognized; this is followed by repeated dosing during the first 24 hours, based on resolution of autonomic arousal and patient comfort. Chlordiazepoxide may be administered at 25- to 50-mg doses every 2 hours PRN during the first 24 hours; subsequently, a continuing taper protocol follows, reducing the total 24-hour requirement by not more than 25% per day. These protocols are guidelines because ongoing clinical assessment is required for safety; doses should be held if increasing sedation or gait instability develops. Treatment must include nutritional repletion of thiamine, folate, and multivitamins.

Carbamazepine and valproate are anticonvulsants that may be useful AWS therapeutic adjuncts. However, the very favorable efficacy and safety of benzodiazepines does not support their use with their weaker evidence for efficacy as primary treatments.

Medical stabilization of the acute AWS must always be paired with appropriate referral to maintenance treatment to prevent alcohol use relapse. This includes medication management per Plate 4-13, treatment of co-occurring psychiatric and medical illnesses, and referral to ongoing care for substance abuse. Level of care determinations may be assisted by evidence-based Patient Placement Criteria developed by clinical researchers in the American Society of Addiction Medicine. Six domains influencing probability of good outcome are assessed to help determine the appropriate level of care; these include (1) severity of intoxication and withdrawal, (2) medical comorbidity, (3) psychiatric illness and psychosocial stability, (4) patient readiness to participate actively in treatment, (5) history of past treatment outcomes, and (6) recovery environment. Levels of care range from least restrictive outpatient to increasing medical and psychiatric outpatient supervision (intensive outpatient, partial hospital) to residential treatment. The highest level of care is inpatient hospitalization with both intensive medical and psychiatric stabilization of life-threatening symptoms.

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