Limited evidence supports the use of gabapentin or carbamazepine for the treatment of mild or moderate alcohol withdrawal as the sole treatment or as combination therapy with other medications; however, gabapentin does not appear to be effective for treatment of severe alcohol withdrawal and is therefore not recommended for use in this setting. A 2010 Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not supported. Paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and carbamazepine may have advantages for certain symptoms. Long term anticonvulsant medications are not usually recommended in those who have had prior seizures due to withdrawal. Prevention of further drinking
There are three medications used to help prevent a return to drinking: naltrexone, acamprosate, and disulfiram. They are used after withdrawal has occurred. Other
Clonidine may be used in combination with benzodiazepines to help some of the symptoms. No conclusions can be drawn concerning the efficacy or safety of baclofen for alcohol withdrawal syndrome due to the insufficiency and low quality of the evidence.Antipsychotics, such as haloperidol, are sometimes used 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 (such as 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.
Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in these individuals because many of the traditional sleep aids (e.g., 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. The acute phase of the alcohol withdrawal syndrome can occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal. Pathophysiology
Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations 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 downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross-tolerant drugs these changes in neurochemistry may gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity.