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Alcohol Withdrawal Syndrome

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From Wikipedia, the free encyclopedia

 

Alcohol withdrawal syndrome is the set of symptoms seen when an individual reduces or stops alcohol consumption after prolonged periods of excessive alcohol intake. Excessive abuse of alcohol leads to tolerance, physical dependence, and an alcohol withdrawal syndrome. Unlike most withdrawals from drugs, alcohol withdrawal can be deadly.

Neurochemistry

Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptions occur such as changes in gene expression and down regulation of GABAa receptors. During acute alcohol withdrawal changes also occur such as upregulation of alpha4 containing GABAa receptors and down regulation of alpha1 and alpha3 containing GABAa receptors. Neurochemical changes occurring during alcohol can be minimised with drugs which are used for acute detoxification. With abstinence from alcohol and cross tolerant drugs these changes in neurochemistry gradually return towards normal.[1][2]

Presentation

The severity of the alcohol withdrawal syndrome can vary from mild symptoms such as mild sleep disturbances and mild anxiety to very severe and life threatening including delirium, particularly visual hallucinations in severe cases and convulsions (which may result in death).[3] The severity of alcohol withdrawal depends on various factors including age, genetics and most importantly degree of alcohol intake and length of time the individual has been misusing alcohol for and number of previous detoxifications.[4][5]

Withdrawal symptoms

Protracted withdrawal

A protracted alcohol withdrawal syndrome occurs in many alcoholics where withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is also sometimes referred to as the post acute withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (also known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.[14] Insomnia is also a common protracted withdrawal symptom which persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in alcoholics because many of the traditional sleep aids eg benzodiazepine receptor agonists and barbiturate receptor agonists work via a GABAA receptor mechanism and are cross tolerant with alcohol. However, trazodone is not cross tolerant with alcohol.[15][16][17] The acute phase of the alcohol withdrawal syndrome can also occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal.[18]

Kindling

Kindling is the phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example binge drinkers may initially experience no withdrawal symptoms but with each period of resumption of drinking followed by abstinence their withdrawal symptoms intensify in severity and may eventually result in full blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during hospital detoxification have been found to be much more likely to have had experienced more previous detoxifications from alcohol than alcoholics who did not have seizures and are more likely to have a more medically complicated alcohol withdrawal syndrome. Kindling can cause complications and may increase the risk of relapse, alcohol related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alerations in the GABA<AA receptors.[19] The mechanism behind kindling is sensitisation of some neuronal systems and desensitisation of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.[5]


Treatment

Treatment of alcohol withdrawal syndrome can be managed with various pharmaceutical medications including barbiturates, benzodiazepines and clonidine. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome.

Baclofen

Baclofen has been shown to be as effective as diazepam in uncomplicated alcohol withdrawal syndrome.[20]

Barbiturates

Barbiturates are superior to diazepam in the treatment of severe alcohol withdrawal syndromes such as delirium tremens but equally effective in milder cases of alcohol withdrawal.[21]

Benzodiazepines

Benzodiazepines are the most commonly used drug for the treatment of alcohol withdrawal and are safe and effective in suppressing alcohol withdrawal signs. Chlordiazepoxide and diazepam are the benzodiazepines most commonly used in alcohol detoxification.[22] Benzodiazepines can be life saving, particularly if delerium tremens appears during alcohol withdrawal.[23] Benzodiazepines should only be used short term in alcoholics who aren't already dependent on benzodiazepines as benzodiazepines share cross tolerance with ethanol and there is a risk of replacing the addiction with a benzodiazepine dependence or worse still 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.[24][25] Benzodiazepines have the problem of increasing cravings for alcohol in problem alcohol consumers and they also increase the volume of alcohol consumed by problem drinkers.[26] The combindation 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.[27]

Carbamazepine

Some evidence indicates that carbamazepine may be effective in the treatment of alcohol withdrawal but more research is needed.[28] It has the advantage of not causing rebound withdrawal symptoms and appears to have a higher success rate compared with lorazepam.[29]

Clonidine

Clonidine has demonstrated superior clinical effects in the suppression of alcohol withdrawal symptoms in a head to head comparison study with the benzodiazepine drug chlordiazepoxide.[30][31][32]

Ethanol

Alcohol (ethanol) itself at low doses has been found to be superior to chlordiazepoxide in the detoxification of alcohol dependent patients. Low dose ethanol as a means of weaning alcoholics off of alcohol was found to produce less profound sleep disturbances during withdrawal.[33] Low dose ethanol has been found to reduce treatment time, improve the failure rate from 20% down to 7% and increase retention in treatment centres with an increased rate of alcoholics attending substance misuse clinics after detoxification.[34]

Flumazenil

Flumazenil, which has shown some promise in the management of the benzodiazepine withdrawal syndrome has also demonstrated benefit in a research study in reducing anxiety withdrawal related symptomatology during alcohol withdrawal.[35]

Trazodone

Trazodone has demonstrated efficacy in the treatment of the alcohol withdrawal syndrome. It may have particular use in withdrawal symptoms, especially insomnia, persisting beyond the acute withdrawal phase.[36][16][17]

Vitamins

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.[37]

Smoking

Smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.[38]

See also


References

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