Withdrawal alcohol

The abstinence syndrome (synonym, withdrawal symptom) is observed after withdrawal of a dtug to which a person is addicted. For example, the abstinence syndrome after alcohol withdrawal is characterized by tremor, nausea, tachycardia, sweating and sometimes hallucinations. 

Cessation of prolonged heavy alcohol abuse may be followed by alcohol withdrawal or life-threatening alcohol withdrawal delirium. Typical withdrawal symptoms are autonomic hyperactivity, increased hand tremor, insomnia and anxiety, and are treated with benzodizepines and thiamine. Alcoholism is the most common cause of thiamine deficiency and can lead in its extreme form to the Wernicke s syndrome that can be effectively treated by high doses of thiamine. 

These findings were unexpected because previous studies had demonstrated that the y2 subunit is required for potentiation of GABAa receptor function by low concentrations of ethanol [2]. The y2 subunit gene is located within a definitely mapped quantitative trait locus (QTL) for acute alcohol withdrawal on mouse chromosome 11 [1]. Allelic variation was genetically... 

Buck KJ, Metten P, Belknap JK et al (1997) Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J Neurosci 17 3946-3955... 

Some of these drugp may have additional uses as sedatives, muscle relaxants, anticonvulsants, and in the treatment of alcohol withdrawal. For example, clo-razepate (Tranxene) and diazepam (Valium) are used as anticonvulsants (see Chap. 28). Additional uses of the individual antianxiety drugp are given in the Summary Drug Table Antianxiety Drugp. 

Ethanol also reduces the activity of the noradrenergic system in the locus coeruleus, and alterations in norepinephrine activity may account for some aspects of intoxication and the abstinence syndrome. The 0.2 antagonist clon-idine and the P-receptor antagonist propranolol reduce some symptoms of alcohol withdrawal (Bailly et al. 1992 Carlsson and Fasth 1976 Dobrydnjov et al. 2004 Kahkonen 2003 Petty et al. 1997 Wong et al. 2003). 

The two main settings in which medications are used for alcohol treatment are to control the symptoms of alcohol withdrawal (i.e., detoxification) and to reduce or prevent alcohol consumption (i.e., rehabilitation). In the sections that follow, we will first discuss pharmacological approaches to detoxification... 

An important initial intervention for a minority of alcohol-dependent patients is the management of alcohol withdrawal through detoxification. The objectives in treating alcohol withdrawal are relief of discomfort, prevention or treatment of complications, and preparation for rehabilitation. Successful management of the alcohol withdrawal syndrome is generally necessary for subsequent efforts at rehabilitation to be successful treatment of withdrawal alone is usually not sufficient, because relapse occurs commonly. 

Social detoxification, which involves the nonpharmacological treatment of alcohol withdrawal, has been shown to be effective (see Naranjo et al. 1983). It consists of frequent reassurance, reality orientation, monitoring of vital signs, personal attention, and general nursing care (Naranjo and Sellers 1986). Social detoxification is most appropriate for patients in mild-to-mod-erate withdrawal. The medical problems commonly associated with alcoholism (Sullivan and O Connor 2004) may substantially complicate therapy, so that care must be taken to refer patients whose condition requires medical management. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Antipsychotics are not indicated for the treatment of withdrawal, except when hallucinations or severe agitation are present (Naranjo and Sellers 1986), in which case they should be added to a benzodiazepine. In addition to their potential to produce extrapyramidal side effects, antipsychotics lower the threshold for seizures, which is particularly problematic during alcohol withdrawal. 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

In general, with the exception of the central role that benzodiazepines play in the treatment of alcohol withdrawal, the use of medications that have been approved for alcoholism rehabilitation remains very limited. A survey of nearly 1,400 addiction physicians showed that they prescribed disulfiram to only 9% of their alcoholic patients and that naltrexone was prescribed for only slightly higher proportion of patients (13%) (Market al. 2003). These tesults contrast with findings for antidepressants, which were prescribed to 44% of alcoholic patients. Although neatly all of these physicians had heatd of both disulfiram and naltrexone, their self-reported level of knowledge of these medications was much lowet than that of antidepressants. 

Bailly D, Servant D, Blandin N, et al Effects of beta-blocking drugs in alcohol withdrawal a double-blind comparative study with propranolol and diazepam. Bio-med Pharmacother 46 419—424, 1992... 

Bonnet U, Banger M, Leweke FM, et al Treatment of acute alcohol withdrawal with gabapentin results from a controlled two-center trial. J Clin Psychopharmacol 23 514-519, 2003... 

Dobrydnjov I, Axelsson K, Berggren L, et al Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome a randomized double-blinded study. Anesth Analg 98 738—744, 2004... 

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

KahkonenS, Bondarenko BB L-typeCa2+ channels mediate cardiovascular symptoms of alcohol withdrawal in humans. Prog Neuropsychopharmacol Biol Psychiatry 28 45 8, 2004... 

Kahkonen S Alcohol withdrawal changes cardiovascular responses to propranolol challenge. Neuropsychobiology 47 192—197, 2003 Kessler RC, McGonagle KA, Zhao S, et al Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry 51 8-19,1994... 

Malcolm R, Ballenger JC, Sturgis ET, et ah Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Am J Psychiatry 146 617-621, 1989... 

Malcolm R, Myrick H, Roberts J, et al The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 17 349—355, 2002... 

Myers RD, Melchior CL Differential actions on voluntary alcohol intake of tetra-hydroisoquinolines or a beta-carboline infused chronically in the ventricle of the rat. Pharmacol Biochem Behav 7 381-392, 1977 Naranjo CA, Sellers EM Clinical assessment and pharmacotherapy of the alcohol withdrawal syndrome, in Recent Developments in Alcoholism, Vol 4. Edited hy Galanter M. New York, Plenum, 1986... 

Naranjo CA, Sellers EM, Chater K, et al Non-pharmacological interventions in acute alcohol withdrawal. Clin Pharmacol Ther 34 214—219, 1983 Naranjo CA, Sellers EM, Roach CA, et al Zimelidine-induced variations in alcohol intake hy nondeptessed heavy drinkers. Clin Pharmacol Ther 35 374-381, 1984 Naranjo CA, Sellers EM, Sullivan ]T, et al The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clin Pharmacol Ther 41 266-274, 1987 Naranjo CA, Sullivan ]T, Kadlec KE, et al Differential effects of viqualine on alcohol intake and other consummatory behaviors. Clin Pharmacol Ther 46 301 -309,1989 Naranjo CA, Kadlec KE, Sanhueza P, et al Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers. Clin Pharmacol Ther 47 490 98, 1990... 

Reoux JP, Saxon AJ, Malte CA, et al Divalproex sodium in alcohol withdrawal a randomized douhle-hlind placeho-controlled clinical trial. Alcohol Clin Exp Res 25 1324-1329,2001... 

Lejoyeux et al. 1998). Similar to opioid-dependent persons, these patients reported that they use benzodiazepines to self-medicate anxiety, insomnia, and alcohol withdrawal and, less commonly, to enhance the effects of ethanol. Approximately l6%-25% of patients presenting for treatment of anxiety disorders abuse alcohol (Kushner et al. 1990 Otto et al. 1992). Controversy exists concerning appropriate benzodiazepine prescribing in this population (Cir-aulo and Nace 2000 Posternak and Mueller 2001). 

Pentobarbital withdrawal may involve a distal region of the chromosome 1 in the mouse (Buck et al. 1999), a site that may be identical to that associated with alcohol withdrawal. This finding suggests that common genes may be involved in both ethanol and pentobarbital dependence. 

Buck K, Metten P, Belknap J, et al Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and... 

Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Another potential chnical use of GHB is in the treatment of alcohol withdrawal and alcohol dependence. In prechnical studies, GHB inhibited voluntary ethanol consumption in ethanol-preferring rats and suppressed the... 

GHB treatment in mice, tolerance develops to both the hypolocomotion and cataleptic effects of the drug (Itzhak and Ali 2002). There is also preclinical evidence of cross-tolerance and cross-dependence of GHB with alcohol (Colombo et al. 1995 Fadda et al. 1989). As described in the earlier section on clinical pharmacology, GHB and its analogues have been used in humans in the treatment of alcohol withdrawal. Nicholson and Balster (2001) reviewed the evidence for cross-tolerance and cross-dependence of GHB with alcohol. 

Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, et al Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol 37 67—73, 2002... 

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