Alcohol withdrawal syndrome is a set of symptoms that can occur when an individual reduces or stops alcoholic consumption after long periods of use. Prolonged and excessive use of alcohol leads to tolerance and physical dependence. The withdrawal syndrome is largely a hyper-excitable response of the central nervous system to lack of alcohol. Symptoms typical of withdrawal include agitation, seizures, and delirium tremens.
Sedative-hypnotics, such as alcohol, are well known for their propensity to induce physiological dependence. This dependence is due to alcohol-induced neuro-adaptation. Withdrawal is characterized by neuropsychiatric excitability and autonomic disturbances. Dependence on other sedative-hypnotics can increase the severity of the withdrawal syndrome.
Signs and symptoms
Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as sleep disturbances and anxiety to severe and life-threatening symptoms such as delirium, hallucinations, and autonomic instability.
Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, tonic-clonic seizures, and autonomic instability.
The severity of symptoms is dictated by a number of factors, the most important of which is degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified:
- Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear.
- Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures.
- Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations. This usually occurs 24 to 72 hours after alcohol cessation. Delirium tremens is the most severe form of withdrawal and occurs in 5 to 20% of patients experiencing detoxification and 1/3 of patients experiencing withdrawal seizures.
Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required. In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider.
Benzodiazepines are the most commonly used medication for the treatment of alcohol withdrawal and are generally safe and effective in suppressing symptoms of alcohol withdrawal. This class of medications are generally effective in symptoms control, but need to be used carefully. Although benzodiazepines have a long history of successfully treating and preventing withdrawal, there is no consensus on the ideal one to use. The most commonly used agents are long-acting benzodiazepines, such as chlordiazepoxide and diazepam. These are believed to be superior to other benzodiazepines for treatment of delirium and allow for longer periods between dosing. However, benzodiazepines with intermediate half-lives like lorazepam may be safer in people with liver problems.
The primary debate between use of long-acting benzodiazepines and short-acting is that of ease of use. Longer-acting drugs, such as diazepam, can be dosed less frequently. However, evidence does exist that “symptom-triggered regimens” such as those used when treating with lorazepam, are as safe and effective, but have decreased treatment durations and medication quantity used.
Although benzodiazepines are very effective at treating alcohol withdrawal, they should be carefully used. Benzodiazepines should only be used for brief periods in alcoholics who are not already dependent on them, as they share cross tolerance with alcohol. There is a risk of replacing an alcohol addiction with benzodiazepine dependence or adding an additional addiction. Furthermore, disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects. The combination of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal.
The prophylactic administration of thiamine intravenously is recommended before starting any carbohydrate containing fluids or food. Alcoholics are often deficient in various nutrients which can cause severe complications during alcohol withdrawal such as the development of Wernicke syndrome. The vitamins of most importance in alcohol withdrawal are thiamine and folic acid. To help to prevent Wernicke syndrome alcoholics should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. Vitamins should always be administered before any glucose is administered otherwise Wernicke syndrome can be precipitated. These vitamins are often combined into banana bag which is given intravenously to patients.
Some evidence indicates that topiramate carbamazepine and other anticonvulsants are effective in the treatment of alcohol withdrawal however, research is limited. A Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not significant and noted weaknesses in the studies available. The Cochrane review did note however, that paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and also noted that carbamazapine may have advantages for certain symptoms.
Clonidine may be used in combination with benzodiazepines to help some of the symptoms. There is insufficient evidence to support the use of baclofen for AWS.
Antipsychotics, such as haloperidol, are sometimes in addition to benzodiazepines to control agitation or psychosis. Antipsychotics may potentially worsen alcohol withdrawal as they lower the seizure threshold. Clozapine, olanzapine or low potency phenothiazines(e.g. chlorpromazine) are particularly risky; if used, extreme caution is required.
While intravenous ethanol could theoretically be used, evidence to support this use, at least in those who are very sick is insufficient.
Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death. It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists. The NMDA antagonist acamprosate reduces excessive glutamate rebound thereby suppressing excitotoxicity and potential withdrawal related neurotoxicity.
Substances impairing recovery
Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol. Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.