III. The Alcohol Withdrawal Syndrome. Alfonso Paredes, Section Editor

Transcription

1 III The Alcohol Withdrawal Syndrome Alfonso Paredes, Section Editor

2 Overview Alfonso Paredes The physiological and behavioral events that follow the cessation of drinking in an alcohol-dependent person deserve careful examination. Justifiably much interest has been focused on those clinical manifestations that appear within the first 7-10 days after drinking has ceased and in particular on the symptoms that constitute the acute withdrawal syndrome. Three categories of symptoms have attracted the interest of clinicians: Clouding of sensorium, tremor, and diaphoresis; hallucinations; and, in general, hyperexcitability of the central nervous system. It must be pointed out that most alcoholics experience only mild symptoms such as slight tremor and malaise and irritability following the cessation of drinking. Many do not report serious discomfort and only 1-15% exhibit severe symptoms such as delirium tremens. 1,2 Considering the fact that alcohol has marked effects on most organ systems we must postulate the existence of significant changes with long-lasting consequences. Changes may be expected at the molecular, neuroendocrine, and neuropharmacologicallevels. Several other physiological systems are also involved. Furthermore, there is the possibility that a protracted withdrawal period exists, characterized by physiological and behavioral disturbances that may last weeks and even months. The alterations during this period may have an impact on the clinical course of alcohol dependence. The chapters included in this section were designed with this perspective in mind. It is possible that a better understanding of the mechanisms affected during the period indicated, as well as improved methods of management, may impact favorably on aspects such as risk or relapse. A good knowledge of the mechanisms should be of importance even in the management of those alcohol-dependent individuals who do not give signs of serious discomfort or who appear relatively asymptomatic. The chapters that constitute this section address the several levels affected during withdrawal. In Chapter 10, Goldstein reviews the withdrawal phenomena at the molecular level and examines some of the animal models. She indicates that after the development of tolerance and dependence, CNS hy- Alfonso Paredes. Department of Psychiatry, The Neuropsychiatric Institute, Alcohol Research Center, University of California, Los Angeles, California M. Galanter et al. (eds.), Recent Developments in Alcoholism Springer Science+Business Media New York

3 226 III Alcohol Withdrawal Syndrome perexcitability follow the withdrawal from alcohol. This state of increased responsiveness may be conditioned by cell membrane changes. Spectrometric techniques such as electron spin resonance and fluorescence polarization reveal that cell membranes of ethanol-withdrawn animals are often abnormally rigid and resistant to ethanol-induced disorder. Chemical changes may also account for the altered physical properties of membranes. Perhaps there is an increase in cholesterol or changes in the ratio of saturated to unsaturated fatty acids in the phospholipid components of the membrane. Some of the alterations in neurotransmitter metabolism and release and in the characteristics of neuronal receptors during the alcohol withdrawal period may be related to the physical properties of the neuronal membranes. Wilkins and Gorelick examine in Chapter 11 the neuropharmacologic and neuroendocrine mechanisms underlying the process of withdrawal. Among the neuropharmacologic aspects, a most interesting GABA-benzodiazepine-barbiturate complex interaction with alcohol is discussed. The ubiquity of systems affected by alcohol is illustrated by the studies of endocrine systems reviewed by Wilkins and Gorelick. The two most important systems implicated are the hypothalamic-pituitary-adrenal (HP A) axis and the endogenous opiates (endorphines). These systems are affected by the acute and chronic exposure to alcohol and significant alterations following the discontinuance of the drug. Along these lines, increases have been observed in plasma cortisol and ACTH levels. Alcoholics during acute withdrawal show a blunted rise in plasma cortisol following insulin-induced hypoglycemia. Interestingly, this response may remain abnormal for 3 to 6 weeks after cessation of alcohol intake. Persistent dysfunction of the HP A axis has been further demonstrated in cases of alcohol induced pseudo-cushing's syndrome. The levels in the brain of the endogenous opiates [3-endorphin and metenkephalin are lowered during withdrawal from alcohol. The broad neuroendocrine changes taking place in alcoholics are illustrated by a recent study showing blunted TSH response to TRA stimulation in a group of alcoholics without depression or hepatic disease. Serum prolactin is initially decreased and then returns to normal in patients undergoing alcohol withdrawal. High vasopressin levels have been found in alcoholics with clinical symptoms of withdrawal. During alcohol ingestion vasopressin release is inhibited and a rebound effect is observed during withdrawal. Dose-response relationships between CNS amine metabolism and the severity of alcohol withdrawal has been reported in experimental animals. This phenomenon explains the CNS hyperirritability. In humans there is a close relationship between the signs and symptoms of autonomic nervous system disturbance and increased central norepinephrine turnover. It is possible that changes in biogenic amines and their metabolites during acute withdrawal and the recovery phase may be related to the severity of the withdrawal syndrome. Other interesting effects reviewed by Wilkins and Gorelick are a decrease in [3

4 III Overview 227 receptor binding activity during withdrawal. Also, a probable relationship has been found to exist between alcohol withdrawal syndrome delirium and decreased CNS dopaminergic activity. Finally it has been demonstrated that decreases in brain cyclic AMP levels occur during withdrawal. In Chapter 12, Naranjo and Sellers review recent developments in the clinical assessment and nonpharmacologic and pharmacologic treatment of the alcohol withdrawal syndrome. This progress makes possible a more effective treatment of the syndrome. The objectives of therapy, the authors contend, should be the relief of subjective symptoms, prevention and treatment of the more severe complications, such as seizures, hallucinations, and delirium, and preparation of the patient for long-term rehabilitation. Within this scheme it is important to minimize the hazards of creating a new drug dependence or exposing the patient to direct drug-induced toxicity. Treatment of alcohol withdrawal syndrome should be standardized, humane and as economical as possible. It should be based in a sound pharmacokinetic and pharmacodynamic rationale and meet good standards of safety and efficacy. This needs to be established by studies conducted with sound methodology. The authors indicate that in the management of over two thirds of the uncomplicated cases of alcohol withdrawal, monitoring of signs and symptoms, personal attention, and general nursing care suffice. The treatment recommended includes the administration of vitamins particularly thiamine. The use of benzodiazepines is favored since these drugs have a cross-tolerance with alcohol and do not cause enzyme induction. A novel procedure is recommended for the detoxification process: the authors suggest loading doses of diazepam 20 mg administered hourly until the patient shows clinical improvements or becomes mildly sedated. In Chapter 13, Gorelick and Wilkins have addressed issues of considerable clinical importance seldom considered in the literature. Among these included are the management of withdrawal in patients who have concurrent psychiatric illness or mixed substance dependence. Concurrent illness may precipitate withdrawal in most patients. Certain complications are of particular importance. In many patients, elevated blood pressure during acute withdrawal is a manifestation triggered by the cessation of drinking rather than a direct result of primary hypertension. Thus the diagnosis of primary hypertension and the initiation of antihypertensive medication may be unwarranted in many of these cases. If medication is used, it might be more appropriate to use an adrenergic agent such as clonidine or propanolol rather than a thiazide diuretic. Drug pharmacokinetics may be altered during withdrawal; changes in drug plasma protein binding have been found in patients who experience acute withdrawal. For example warfarin and propanolol binding are decreased while diazepam binding is increased. Psychiatric symptoms complicate the clinical picture observed during withdrawal. Significant depression has been observed in as many of 98% of

5 228 III Alcohol Withdrawal Syndrome the alcoholic patients who appear for treatment. Depression may be misdiagnosed for primary disorder; however, the depressive pictures in alcoholics resolve spontaneously in most cases. Important aspects of management have to be considered in patients who show dependence on alcohol and another (cross-tolerant) hypnotic drug and in cases of dependence on alcohol plus another (non-cross-tolerant) drug such as an opiate or a stimulant. In the first situation, the course of the withdrawal symptoms may be prolonged and resemble the course of alcohol withdrawal alone. A bimodal course may also be observed. In the case of combined alcohol-nonsedative withdrawal the clinical picture may be a mixture of alcohol and opiate or stimulant withdrawal syndromes. Valuable suggestions for the management of these syndromes are included. An important possibility discussed is the existence of the protracted withdrawal mentioned earlier and its likely clinical implications. Lastly, the need for more studies on the influence of withdrawal and its management on the outcome of alcohol dependence is presented. There is already some evidence that suggests that patients who receive medically oriented treatment during withdrawal are more likely to remain in treatment for their addiction. A final comment on an area not fully covered in the chapters following deserves mention. Cessation of drinking in an alcohol-dependent individual may have been precipitated by the discomfort caused by symptoms associated with drinking, by the threat to health, or by the social consequences of drinking excessively. Whatever the reasons might be, this is a period of crisis during which the patient becomes aware of his or her psychological vulnerability and of the social consequences of drinking. It is a time when the person with a relatively clear mind has an opportunity to decide to accept help and more importantly assess the decision to discontinue or change their drinking behavior. Several options may be considered at this time. A decision to discontinue drinking has many implications for the patient's pattern of social relationships. The need to accept many responsibilities that in the past may have been neglected may also become apparent. Appreciation of serious interpersonal problems are evident and major changes in life style will have to be considered. It is therefore not surprising that patients experience considerable stress and anxiety during this phase. There may be feelings of guilt, bewilderment, and fear. Patients may describe feelings such as "feeling torn apart inside," "want badly to scream," or manifest psychological and conflict through somatizations. For these patients alcohol has been a steady and reliable companion that will not be given up without a sense of loss or grief. The period of withdrawal therefore provides an opportunity to encourage the patient to accept help with the behavioral aspects of the dependence on alcohol and to structure a long-term rehabilitative plan. The concern, therefore, with the demands created by the physiological disturbances should not overlook the fact that the withdrawal phase is a critical point in the psychological treatment of alcohol dependence.

6 III Overview 229 References 1. Gross MM, Lewis E, Hastey J: Acute alcohol withdrawal syndrome, in Kissin and Begleiter (eds): Biology of Alcoholism, vol 3, Clinical Pathology. New York, Plenum Press, 1978, p Gross MM, Lewis E, Best S, et al: Quantitative changes of signs and symptoms associated with alcohol withdrawal: Incidence severity and circadian effects in experimental studies in alcoholics. Adv Exp Bioi Med 59: , 1975.