Info alkoholism

The yearly cost of alcohol-related problems in the United States is as much as $300 billion, including accidents, health problems, lost productivity, crime, and treatment

Marc A. Schuckit

The yearly cost of alcohol-related problems in the United States is as much as $300 billion, including accidents, health problems, lost productivity, crime, and treatment. There are more than 22,000 deaths from alcohol-related auto accidents per year, as well as almost 2 million nonfatal injuries and damage to almost 5 million vehicles. In addition, alcohol is responsible for almost 5% of missed work time, with a 25% decrease in work performance among heavy drinkers. Men and women who fulfill criteria for alcohol use disorders decrease their life span by approximately 15 years, with abuse and dependence responsible for almost 25% of premature deaths in men and 15% in women, figures that represent a three- to sixfold odds ratio of early death even among people with higher levels of education and socioeconomic functioning.


Ethanol is a weakly charged molecule that moves easily through cell membranes, rapidly equilibrating between blood and tissues. The effects of drinking depend in part on the amount of ethanol consumed per unit of body weight; the level of alcohol in the blood is expressed as milligrams or grams of ethanol per deciliter (e.g., 100 mg/dL or 0.10 g/dL). A level of 0.02 to 0.03 results from the ingestion of one to two typical drinks. In round figures, 340 mL (12 oz) of beer, 115 mL (4 oz) of nonfortified wine, and 43 mL (1.5 oz) (a shot) of 80-proof beverage each contain approximately 10 g of ethanol; 0.5 L (1 pint) of 86-proof beverage contains approximately 160 g, and 1 L of wine contains approximately 80 g of ethanol. Congeners found in alcoholic beverages may contribute to body damage with heavy drinking; these include low-molecular-weight alcohols (e.g., methanol and butanol), aldehydes, esters, histamine, phenols, tannins, iron, lead, and cobalt.

Ethanol is a central nervous system (CNS) depressant that decreases activity of neurons, although some behavioral stimulation is observed at low blood levels. This drug has cross-tolerance and shares a similar pattern of behavioral problems with other brain depressants, including the benzodiazepines and barbiturates. Alcohol is absorbed from mucous membranes of the mouth and esophagus (in small amounts), from the stomach and large bowel (in modest amounts), and from the proximal portion of the small intestine (the major site). The rate of absorption is increased by rapid gastric emptying; by the absence of proteins, fats, or carbohydrates (which interfere with absorption); by the absence of congeners; by dilution to a modest percentage of ethanol (maximum at about 20% by volume); and by carbonation (e.g., champagne).

Between 2% (at low blood alcohol concentrations) and about 10% (at high blood alcohol concentrations) of ethanol is excreted directly through the lungs, urine, or sweat, but the greater part is metabolized to acetaldehyde, primarily in the liver. At least two metabolic routes, each with different optimal concentrations of ethanol (Km), result in the metabolism of approximately one drink per hour. The most important pathway occurs in the cell cytosol where alcohol dehydrogenase (ADH) produces acetaldehyde, which is then rapidly destroyed by aldehyde dehydrogenase (ALDH) in the cytosol and mitochondria. Each of these steps requires nicotinamide adenine dinucleotide (NAD) as a cofactor, and it is the increased ratio of the reduced cofactor (NADH) to NAD (NADH:NAD) that is responsible for many of the metabolic derangements observed after drinking. A second pathway occurs in the microsomes of the smooth endoplasmic reticulum (the microsomal ethanol-oxidizing system, or MEOS), which is responsible for 10% or more of ethanol oxidation at high blood alcohol concentrations.

One gram of ethanol has approximately 29.7 kJ (7.1 kcal) of energy, and a drink contains between 293.0 and 418.6 kJ (70 and 100 kcal) from ethanol and other carbohydrates. However, these are “empty” of nutrients such as minerals, proteins, and vitamins. In addition, alcohol interferes with absorption of vitamins in the small intestine and decreases their storage in the liver. These actions affect folate (folacin or folic acid), pyridoxine (B6), thiamine (B1), nicotinic acid (niacin, B3), and vitamin A. Heavy drinking can also produce low blood levels of potassium, magnesium, calcium, zinc, and phosphorus as a consequence of dietary deficiency and acid-base imbalances during excess alcohol ingestion or withdrawal.

An ethanol load in a fasting, healthy individual is likely to produce transient hypoglycemia within 6 to 36 h, secondary to the acute actions of ethanol on gluconeogenesis. This can result in glucose intolerance until the alcoholic has abstained for 2 to 4 weeks. Alcohol ketoacidosis, probably reflecting a decrease in fatty acid oxidation coupled with poor diet or recurrent vomiting, should not be misdiagnosed as diabetic ketosis. With the former, patients show an increase in serum ketones along with a mild increase in glucose but a large anion gap, a mild to moderate increase in serum lactate, and a b-hydroxybutyrate/lactate ratio of between 2:1 and 9:1 (with normal being 1:1).


The effects of any drug depend on the dose, the rate of increase in plasma, the concomitant presence of other drugs, and the past experience with the agent. With alcohol, an additional factor is whether blood alcohol levels are rising or falling; the effects are more intense during the former period.

Even though “legal intoxication” requires a blood alcohol concentration of at least 80 to 100 mg/dL, behavioral, psychomotor, and cognitive changes are seen at levels as low as 20 to 30 mg/dL (i.e., after one to two drinks). Deep but disturbed sleep can be seen at twice the legal intoxication level, and death can occur with levels between 300 and 400 mg/dL. Beverage alcohol is probably responsible for more overdose deaths than any other drug.

The intoxicating effects of alcohol appear to be due to actions at specific neurotransmitter receptors and transporters. Alcohol enhances g-aminobutyric acid A (GABAA) receptors, and inhibits N-methyl-D-asparate (NMDA) receptors (Chap. 386). In vitro studies suggest that additional effects involve inhibition of adenosine uptake and a translocation of the cyclic AMP-dependent protein kinase catalytic subunit from the cytoplasm to the nucleus. Neurons adapt quickly to these actions, and thus different effects may be present during chronic administration and withdrawal.

At least three types of compensation develop after repeated exposure to the drug, producing tolerance of higher ethanol levels. First, after 1 to 2 weeks of daily drinking, metabolic or pharmacokinetic tolerance develops, with a 30% increase in the rate of hepatic ethanol metabolism. This alteration disappears almost as rapidly as it develops. Second, cellular or pharmacodynamic tolerance develops through neurochemical changes that may also contribute to physical dependence. Third, individuals can learn to adapt their behavior so that they can function better than expected under drug influence (behavioral tolerance).

The cellular changes caused by chronic ethanol exposure may not resolve for several weeks or longer following cessation of drinking. In the interim, the neurons require ethanol to function optimally, and the individual can be said to be physically dependent. This physical condition is distinct from psychological dependence, a concept indicating that the person is psychologically uncomfortable without the drug.


While one to two drinks per day in an otherwise healthy and nonpregnant individual can have some beneficial effects, at higher doses alcohol is toxic to most body systems. Knowledge about the deleterious effects of alcohol helps the practicing physician to identify alcoholic patients. Signs and symptoms of ethanol abuse can be used to help motivate the patient to abstain. It is important to remember that the typical white- or blue-collar alcoholic functions at a fairly high level for years, and that not everyone develops each problem.


Approximately 35% of drinkers may experience a blackout, an episode of temporary anterograde amnesia, in which the person forgets all or part of what occurred during a drinking evening. Another common problem, one seen after as few as one or two drinks, is that while alcohol can help someone to fall asleep, it also “fragments” the sleep pattern causing alterations between sleep stages and a deficiency in deep sleep. At the same time, alcohol diminishes rapid eye movement (REM) or dream sleep early in the evening, with resulting prominent and sometimes disturbing dreams later in the night. Finally, alcohol relaxes muscles in the pharynx, which can cause snoring and exacerbate sleep apnea, with symptoms of the latter in 75% of alcoholic men over age 60.

An additional problem related to the acute effects of alcohol on most drinkers is the impairment in judgment, balance, and motor coordination that contributes to the high incidence and severity of accidents. At least half of individuals who experience severe physical trauma in an accident have evidence of substance-related impairment, a finding that is consistent with the fact that 40% of drinkers in the United States have at some time driven while intoxicated with alcohol and that 15% of flight crews have evidence of repeated heavy drinking. Regarding the latter, at least one study noted that pilot performance is still impaired 14 h after a blood alcohol concentration of 100 mg/dL, despite subsequent abstinence.

The effect of alcohol on the nervous system is even more pronounced among alcohol-dependent individuals. Chronic intake of high doses of ethanol causes peripheral neuropathy in 5 to 15% of alcoholics, which is possibly related to thiamine deficiency. Patients complain of bilateral limb numbness, tingling, and paresthesias; symptoms are more pronounced distally than proximally. The treatment is abstinence and thiamine supplementation.

Wernicke’s syndrome (ophthalmoparesis, ataxia, and encephalopathy) and Korsakoff’s syndrome (alcohol-induced persisting amnestic disorder), are seen in the United States at a rate of approximately 50 per million people per year. These disorders are the result of thiamine deficiency in vulnerable individuals, possibly owing to interaction with a genetic transketolase deficiency. Korsakoff’s syndrome presents as profound and persistent anterograde amnesia (inability to learn new material) and a milder retrograde amnesia. Additional symptoms can include impairment in visuospatial, abstract, and conceptual reasoning but with a normal intelligence quotient (IQ). Some patients demonstrate an acute onset of Korsakoff’s syndrome in association with the neurologic stigmata seen with Wernicke’s syndrome (e.g., sixth nerve palsy and ataxia), whereas others have a more gradual onset. With oral thiamine replacement (50 to 100 mg/d), only one-quarter of Korsakoff’s patients achieve full recovery, one-half experience partial improvement, and one-quarter show no improvement, even after many months of supplementation. ®Wernicke’s syndrome is discussed in detail in Chap. 376.

About 1% of alcoholics develop cerebellar degeneration, a syndrome of progressive unsteady stance and gait often accompanied by mild nystagmus. Atrophy of the cerebellar vermis is seen on brain computed tomography and magnetic resonance imaging scans, but the cerebrospinal fluid is usually normal. Treatment consists of abstinence and multiple vitamin supplementation, although improvement is often minimal.

Alcoholics can show severe cognitive problems and impairment in recent and remote memory for weeks to months after an alcoholic binge. Increased size of the brain ventricles and cerebral sulci are seen in 50% or more of chronic alcoholics, but these changes are often reversible, returning toward normal after a year or more of abstinence. Permanent CNS impairment (alcohol-induced persisting dementia) can develop and accounts for up to 20% of chronically demented patients. There is no single alcoholic dementia syndrome; rather, this label is used to describe patients who have apparently irreversible cognitive changes (possibly from diverse causes) in the midst of chronic alcoholism.

Finally, almost every psychiatric syndrome can be seen temporarily during heavy drinking or subsequent withdrawal. These include intense sadness lasting for days to weeks in the midst of heavy drinking in 40% of alcoholics, which is classified as an alcohol-induced mood disorder in the Fourth Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV); severe anxiety in 10 to 30% of alcoholics, often beginning during alcohol withdrawal and which can persist for many months after cessation of drinking (alcohol-induced anxiety disorder); and auditory hallucinations and/or paranoid delusions in the absence of any obvious signs of withdrawal¾a state now called alcohol-induced psychotic disorder¾and reported at sometime in 1 to 10% of alcoholics. Treatment of all forms of alcohol-induced psychopathology includes abstinence and supportive care, with the likelihood of full recovery within several days to 6 weeks. A history of alcohol intake is an important consideration in any patient with one of these psychiatric symptoms.


Esophagus and Stomach  Acute alcohol intake can result in inflammation of the esophagus (possibly secondary to reflux of gastric contents) and stomach (resulting from both an increase in acid production and damage to the gastric mucosal barrier). Esophagitis can cause epigastric distress, and gastritis, the most frequent cause of gastrointestinal bleeding in heavy drinkers, can present as anorexia and/or abdominal pain. Chronic heavy drinking, if associated with violent vomiting, can produce a longitudinal tear in the mucosa at the gastroesophageal junction¾a Mallory-Weiss lesion. Although many gastrointestinal problems are reversible, two complications of chronic alcoholism, esophageal varices secondary to cirrhosis-induced portal hypertension and atrophy of the gastric mucosa, may be irreversible.

Pancreas  The incidence of acute pancreatitis in alcoholics (about 25 per 1000 per year) is almost threefold higher than in the general population, accounting for an estimated 10% or more of the cases of this disorder (Chap. 304).

Liver  Ethanol absorbed from the small bowel is carried directly to the liver, where it becomes the preferred fuel; NADH accumulates and oxygen utilization escalates; gluconeogenesis is impaired (with a resulting fall in the amount of glucose produced from glycogen); lactate production increases; and there is a decreased oxidation of fatty acids in the citric acid cycle with an increase in fat accumulation within liver cells. In the healthy individual taking no medications, these changes are reversible, but with repeated exposure to ethanol, more severe changes in liver functioning are likely to occur. These include, in overlapping stages, fatty accumulation, alcohol-induced hepatitis, perivenular sclerosis, and cirrhosis, with the latter observed in an estimated 15 to 20% of alcoholics (Chap. 298).


As discussed briefly below, the leading cause of death in alcoholics is cardiovascular disease, but cancer occupies a solid second place. Women drinking as few as 1.5 drinks per day increase their risk of breast cancer 1.4-fold. For both genders, four drinks per day increases the risk for oral and esophageal cancers by approximately threefold and rectal cancers by a factor of 1.5, whereas seven to eight or more drinks per day enhances the risks for many of these cancers by a factor of five. Overall, it has been estimated that alcoholics have a rate of carcinoma 10 times higher than the general population.


Ethanol exerts multiple reversible acute and chronic effects on all blood cells. The impact on red blood cells (RBC) is an increase in  size (mean corpuscular volume, MCV), usually without anemia. This change appears to reflect the effect of alcohol on stem cells. If heavy drinking is accompanied by folic acid deficiency, there can also be hypersegmented neutrophils, reticulocytopenia, and hyperplastic bone marrow; if malnutrition is present, sideroblastic changes can also be observed. Chronic heavy drinking can also decrease production of most white blood cells (WBCs), decrease granulocyte mobility and adherence, and impair the delayed-hypersensitivity response to new antigens (with a possible false-negative tuberculin skin test). Finally, many alcoholics present with mild thrombocytopenia. When due to repeated intoxication, the low platelet count usually resolves within a week of abstinence. Thrombocytopenia can also occur secondary to hepatic cirrhosis and congestive splenomegaly (increased destruction) or to folic acid deficiency (decreased production). Ethanol itself might not have a major effect on platelet function, but polyphenols and other constituents of some alcoholic beverages, particularly wine, may interfere with platelet aggregation.


Acutely, ethanol decreases myocardial contractility and causes peripheral vasodilation, with a resulting mild decrease in blood pressure and a compensatory increase in cardiac output. Exercise-induced increases in cardiac oxygen consumption are higher after alcohol intake. These acute effects have little clinical importance for the average healthy drinker but can produce problems in men and women with cardiac disease.

Chronic intake of even modest doses of alcohol can have both deleterious and beneficial effects. Regarding the latter, a maximum of one to two drinks per day over long periods may decrease the risk for cardiovascular death, perhaps through an increase in high-density lipoprotein (HDL) cholesterol or changes in clotting mechanisms. In one large national study, cardiovascular mortality was reduced by 30 to 40% among individuals reporting one or more drinks daily compared to nondrinkers, with overall mortality lowest among those consuming approximately one drink per day. Recent data have also corroborated the decreased risk for ischemic, but not hemorrhagic, stroke associated with regular light drinking.

The consumption of three or more drinks per day results in a dose-dependent increase in blood pressure, which returns to normal within weeks of abstinence. As a result, heavy drinking is an important contributor to mild to moderate hypertension. Chronic heavy drinking can cause cardiomyopathy, with symptoms ranging from unexplained arrhythmias in the presence of left ventricular impairment to heart failure with dilation of all four heart chambers and hypocontractility of heart muscle. Perhaps one-third of cases of cardiomyopathy are alcohol-induced. Mural thrombi can form in the left atrium or ventricle, while heart enlargement exceeding 25% can cause mitral regurgitation. Atrial or ventricular arrhythmias, especially paroxysmal tachycardia, can also occur after a drinking binge in individuals showing no other evidence of heart disease¾a syndrome known as the “holiday heart.”


Acutely, modest ethanol doses (e.g., blood alcohol concentrations of 100 mg/dL or even less) can both increase sexual drive and decrease erectile capacity in men. Even in the absence of liver impairment, a significant minority of chronic alcoholic men may show irreversible testicular atrophy with concomitant shrinkage of the seminiferous tubules, decreases in ejaculate volume, and a lower sperm count (Chap. 335).

The repeated ingestion of high doses of ethanol by women can result in amenorrhea, a decrease in ovarian size, absence of corpora lutea with associated infertility, and spontaneous abortions. Heavy drinking during pregnancy results in the rapid placental transfer of both ethanol and acetaldehyde, which may have serious consequences for fetal development. The fetal alcohol syndrome can include any of the following: facial changes with epicanthal eye folds, poorly formed concha, and small teeth with faulty enamel; cardiac atrial or ventricular septal defects; an aberrant palmar crease and limitation in joint movement; and microcephaly with mental retardation. The specific amount of ethanol and/or specific time of vulnerability during pregnancy have not been defined, making it advisable for pregnant women to abstain completely.


Between one-half and two-thirds of alcoholics have evidence of decreased skeletal muscle strength caused by acute alcoholic myopathy, a condition that improves but which might not disappear with abstinence. Effects of repeated heavy drinking on the skeletal system include alterations in calcium metabolism, lower bone density, and less growth in the epiphyses, with an increased risk for fractures and osteonecrosis of the femoral head. Hormonal changes include an increase in cortisol levels, which can remain elevated during heavy drinking; inhibition of vasopressin secretion at rising blood alcohol concentrations and the opposite effect at falling blood alcohol concentrations (with the final result that most alcoholics are likely to be slightly overhydrated); a modest and reversible decrease in serum thyroxine (T4); and a more marked decrease in serum triiodothyronine (T3).


Because many drinkers occasionally imbibe to excess, temporary alcohol-related pathology is common in nonalcoholics. The period of heaviest drinking is usually the late teens to the late twenties. This is also a time of high risk for temporary alcohol-related social, occupational, or driving difficulties. These phenomena are often isolated events or self-limited, but when repeated problems in multiple life areas develop, the person is likely to meet criteria for alcohol abuse or dependence.


DSM-IV defines alcohol dependence as repeated alcohol-related difficulties in at least three of seven areas of functioning that cluster together over any 12-month period. These problems include any combination of tolerance, withdrawal, taking larger amounts of alcohol over longer periods than intended, an inability to control use, spending a great deal of time associated with alcohol use, giving up important activities to drink, and continued use of alcohol despite physical or psychological consequences. In this diagnosis a special emphasis is placed on evidence of tolerance and/or withdrawal, a condition referred to as “dependence with a physiological component” and which is associated wtih a more severe clinical course. Dependence occurs in both men and women, in individuals from all socioeconomic strata, and in people of all racial backgrounds. The diagnosis predicts a course of recurrent problems with the use of alcohol and the consequent shortening of the life span by a decade or more. In the absence of alcohol dependence, an individual can be given a diagnosis of alcohol abuse if he or she demonstrates repetitive problems with alcohol in any one of four life areas: an inability to fulfill major obligations, use in hazardous situations such as driving, legal problems, or use despite social or interpersonal difficulties.

The clinical diagnosis of alcohol abuse or dependence rests on the documentation of a pattern of difficulties associated with alcohol use; the definition is not based on the quantity and frequency of alcohol consumption. Thus, in screening for alcohol abuse or dependence, it is important to probe for life problems and then attempt to tie in use of alcohol or another substance. Information regarding marital or job problems, legal difficulties, histories of accidents, medical problems, evidence of tolerance, etc., is an important component of all evaluations and yields data that are of use even for nonalcoholic individuals.

The lifetime risk for alcohol dependence in most western countries is about 10 to 15% for men and 5% for women. When alcohol abuse is also considered, the rates are even higher. The typical alcoholic is a blue- or white-collar worker or homemaker and thus does not fit the common stereotype.


Alcoholism is a multifactorial disorder in which both environmental and biologic factors contribute. The importance of genetic influences in alcoholism is supported by the higher risk for this disorder in the identical versus fraternal twin of an alcoholic and the fourfold increased risk for children of alcoholics even if adopted at birth and raised without knowledge of the problems of their biologic parents.

The evidence supporting genetic influences in alcoholism has stimulated a search for trait markers of a vulnerability toward the disorder. A 15-year follow-up of 453 men originally studied at age 20 has shown that subjects with alcoholic fathers demonstrated relatively lower levels of response to alcohol, including less intense subjective feelings of intoxication, less alcohol-related impairment in cognitive and psychomotor tests, and less intense alcohol-related changes in prolactin and cortisol secretion. This low level of response to alcohol at around age 20 was a powerful predictor of later alcoholism, explaining most of the relationship between a family history of this disorder and later alcohol problems. Additional genetically influenced characteristics that contribute to the risk of alcoholism appear to include some personality traits such as higher levels of impulsivity and sensation seeking, and several electrophysiologic measures such as the P300 wave of the event-related potential (Chap. 357), which might relate to cognitive styles or evidence of CNS disinhibition. All the genetic factors combined appear to explain up to 60% of the risk, with environmental influences contributing at least 40%.


For the “average” alcoholic, the age of first drink and first minor problems (e.g., an argument with a friend while drunk or an alcoholic blackout) are similar to those in the general population. However, by the early to mid-twenties, most men and women moderate their drinking (perhaps learning from minor problems), whereas difficulties for alcoholics are likely to escalate, with the first major life problem from alcohol appearing in the mid-twenties to early forties. Once established, the course of alcoholism is likely to be one of exacerbations and remissions. As a rule, there is remarkably little difficulty in stopping alcohol use when problems develop, and this step is often followed by days to months of carefully controlled drinking. Unfortunately, these periods are almost inevitably followed by escalations in alcohol intake and subsequent problems. The course is not hopeless, because between half and two-thirds of alcoholics maintain abstinence for extended periods after treatment. Even without formal treatment or self-help groups there is at least a 20% chance of long-term abstinence. However, should the alcoholic continue to drink, the life span is shortened by an average of 15 years, with the leading causes of death, in decreasing order, being heart disease, cancer, accidents, and suicide.


Physicians even in affluent areas should recognize that approximately 20% of patients have alcoholism. Therefore, it is important to pay attention to the alcohol-related symptoms and signs described above as well as laboratory tests that are likely to be abnormal in the context of regular consumption of 6 to 8 or more drinks per day. These include a high-normal or slightly elevated MCV (e.g., ³91 fL), g-glutamyl transferase (GGT) (³30 units), serum uric acid [>416 umol/L (7 mg/dL)], carbohydrate-deficient transferrin (CDT) (³20 g/L), and triglycerides [³2.0 mmol/L (180 mg/dL)]. Mild and fluctuating hypertension (e.g., 140/95), repeated infections such as pneumonia, and otherwise unexplained cardiac arrhythmias should also raise the possibility that the patient is an alcoholic. Other disorders suggestive of alcoholism include cancer of the head and neck, esophagus, or stomach as well as cirrhosis, unexplained hepatitis, pancreatitis, bilateral parotid gland swelling, and peripheral neuropathy.

Once the likelihood of alcoholism is established, only a few moments are needed to gather the history of alcohol-related life problems. The patient and the spouse or another close family member should be asked about patterns of accidents, relationship difficulties, problems on the job, and driving-related difficulties, after which the role played by alcohol should be identified. All physicians should be able to take the time needed to gather such information. In addition, a simple 25-item form to be answered by the patient, the Michigan Alcohol Screening Test (MAST), is available to aid in identifying alcoholics. However, this is only a screening tool, and a careful face-to-face interview is still required for a meaningful diagnosis. The CAGE, which consists of asking about alcohol-related trouble cutting down on intake, being annoyed by criticisms, guilt, or use of an “eye-opener,” can also be helpful as an initial screen.

After alcoholism is identified, the diagnosis must be shared with the patient. The presenting complaint can be used as an entree to the alcohol problem. For instance, the patient complaining of insomnia or hypertension could be told that these are clinically important symptoms and that physical findings and laboratory tests indicate that alcohol appears to have contributed to the complaints and is increasing the risk for further medical and psychological problems. The physician should share information about the course of alcoholism and explore possible avenues of attacking the problem. Some patients and family members will benefit from the opportunity to read additional material (see “Bibliography”).

The process of intervention is rarely accomplished in one session. For the person who refuses to stop drinking at the first intervention, a logical step is to “keep the door open,” establishing future meetings so that help is available as problems escalate. In the meantime the family may benefit from counseling or referral to self-help groups such as Al-Anon (the Alcoholics Anonymous group for family members) and Alateen (for teenage children of alcoholics). The patient should be reminded that driving while intoxicated is dangerous and illegal.


Once the brain has been repeatedly exposed to high doses of alcohol, any sudden decrease in intake can produce symptoms of withdrawal. As with all CNS depressants, the symptoms are generally the opposite of those produced by intoxication. Features include tremor of the hands (shakes or jitters); agitation and anxiety; autonomic nervous system overactivity such as an increase in pulse, respiratory rate, and body temperature; insomnia, possibly accompanied by bad dreams; and gastrointestinal upset. These withdrawal symptoms generally begin within 5 to 10 h of decreasing ethanol intake, peak in intensity on day 2 or 3, and improve by day 4 or 5. Anxiety, insomnia, and mild levels of autonomic dysfunction may persist at decreasing levels for 6 months or more as a protracted abstinence syndrome, which may contribute to the tendency to return to drinking.

At some point in their lives, between 2 and 5% of alcoholics experience withdrawal seizures (“rum fits”), usually within 48 h of stopping drinking. These are usually generalized (unless there is an underlying focal lesion), and any electroencephalographic abnormalities are mild and generally return to normal within several days.

The term delirium tremens (DTs) refers to delirium (mental confusion with fluctuating levels of consciousness) along with a tremor, severe agitation, and autonomic overactivity (e.g., marked increases in pulse, blood pressure, and respirations). Fortunately, this serious and potentially life-threatening complication of alcohol withdrawal is rare. Only 5 to 10% of alcohol-dependent individuals ever experience DTs; the chance of DTs during any single withdrawal is less than 1% but is higher if there has been a withdrawal seizure. DTs are most likely to develop in patients with concomitant severe medical disorders or evidence of underlying brain damage, and thus can usually be avoided if the underlying medical problems can be identified and treated.


Acute Intoxication  The first priority is to be certain that the vital signs are relatively stable without evidence of respiratory depression, cardiac arrhythmia, or potentially dangerous changes in blood pressure. Life-threatening problems require appropriate emergency care and hospitalization. The clinician must recognize that a variety of causes may produce obtundation or coma in the alcoholic patient. The possibility of intoxication with other drugs should be considered, and a blood or urine sample is indicated to screen for opioids or other CNS depressants such as benzodiazepines or barbiturates. A coexisting seizure disorder, head injury, meningitis, brain abscess, or other potentially life-threatening neurologic disorder may be present. Other medical conditions that must be considered include hypoglycemia, hepatic failure, or diabetic ketoacidosis.

Patients who are medically stable should be placed in a quiet environment and asked to lie on their side if fatigued in order to minimize the risk of aspiration. When the behavior indicates an increased likelihood of violence, hospital procedures should be followed, including planning for the possibility of a show of force with an intervention team. In the context of aggressiveness, patients should be clearly reminded in a nonthreatening way that it is the goal of the staff to help them to feel better and to avoid problems. If the aggressive behavior continues, relatively low doses of a short-acting benzodiazepine such as lorazepam (e.g., 1 mg by mouth) may be used and can be repeated as needed, but care must be taken so that the addition of this second CNS depressant does not destabilize vital signs or worsen confusion. An alternative approach is to use an antipsychotic medication (e.g., 5 mg of haloperidol liquid), but this has the potential danger of lowering the seizure threshold. If aggression escalates, the patient might require a short-term admission to a locked ward, where medications can be used more safely and vital signs more closely monitored.

Withdrawal  The first, and most important, step is to perform a thorough physical examination in all alcoholics who are considering stopping drinking. It is necessary to evaluate organ systems likely to be impaired, including a search for evidence of liver failure, gastrointestinal bleeding, cardiac arrhythmia, and glucose or electrolyte imbalance.

The second step in treating withdrawal for even the typical well-nourished alcoholic is to give patients adequate nutrition and rest. All patients should be given oral multiple B vitamins, including 50 to 100 mg of thiamine daily for a week or more. Most patients enter withdrawal with normal levels of body water or mild overhydration, and intravenous fluids should be avoided unless there is evidence of significant recent bleeding, vomiting, or diarrhea. Medications can usually be administered orally.

The third step in treatment is to recognize that most withdrawal symptoms are caused by the rapid removal of a CNS depressant. Therefore, patients can be weaned by administering any drug of this class and gradually decreasing the levels over 3 to 5 days. While many CNS depressants are effective, the benzodiazepines have the highest margin of safety and are, therefore, the preferred class of drugs in the treatment of alcohol withdrawal. Benzodiazepines with short half-lives (Chap. 385) are especially useful for patients with serious liver impairment or evidence of preexisting encephalopathy or brain damage. On the other hand, short-half-life benzodiazepines, e.g., oxazepam or lorazepam, result in rapidly changing drug blood levels and must be given every 4 h to avoid abrupt fluctuations in blood levels that may increase the risk for seizures. Therefore, most clinicians use drugs with longer half-lives, such as diazepam or chlordiazepoxide. The goal is to administer enough drug on day 1 to alleviate most of the symptoms of withdrawal (e.g., the tremor and elevated pulse), and then to decrease the dose by 20% on successive days over a period of 3 to 5 days. The approach is flexible; the dose is increased if signs of withdrawal escalate, and the medication is withheld if the patient is sleeping or shows signs of increasing orthostatic hypotension. The average patient requires 25 to 50 mg of chlordiazepoxide or 10 mg of diazepam given orally every 4 to 6 h on the first day.

For the patient with DTs, treatment can be difficult and the condition is likely to run a course of 3 to 5 days regardless of the therapy employed. The focus of care is to identify medical problems and correct them and to control behavior and prevent injuries. Many clinicians recommend the use of high doses of benzodiazepine (doses as high as 800 mg/day of chlordiazepoxide have been reported), a treatment that will decrease the agitation and raise the seizure threshold but probably does little to improve the confusion. Other clinicians recommend the use of antipsychotic medications, such as 20 mg or more per day of haloperidol, an approach less likely to exacerbate confusion but which may increase the risk of seizures. Antipsychotic drugs have no place in the treatment of mild withdrawal symptoms.

Generalized wtihdrawal seizures rarely require aggressive pharmacologic intervention beyond that given to the usual patient undergoing withdrawal, i.e., adequate doses of benzodiazepines. There is little evidence that anticonvulsants such as phenytoin are effective in drug-withdrawal seizures, and the risk of seizures has usually passed by the time effective drug levels are reached. ®The rare patient with status epilepticus must be treated aggressively, as outlined in Chap. 361, initially with intravenous lorazepam.

While alcohol withdrawal is often treated in a hospital, efforts at reducing costs have resulted in the development of outpatient detoxification for relatively mild abstinence syndromes. This is appropriate for patients in good physical condition who demonstrate mild signs of withdrawal despite low blood alcohol concentrations and for those without prior history of DTs or withdrawal seizures. Such individuals still require a careful physical examination, evaluation of blood tests, and vitamin supplementation. Benzodiazepines can be given in a 1- to 2-day supply to be administered to the patient by a spouse or other family member four times a day. Patients are asked to return daily for evaluation of vital signs and to come to the emergency room if signs and symptoms of withdrawal escalate.

Rehabilitation of Alcoholics  After completing alcoholic rehabilitation, 60% or more of middle-class alcoholics maintain abstinence for at least a year, and many for a lifetime. As is true for any long-term disorder for which treatment requires changes in life-style (e.g., diabetes or hypertension), therapeutic approaches include general supports that meet commonsense guidelines. Considering the lack of evidence for the superiority of any specific treatment type, it is best to keep interventions simple.

Maneuvers in rehabilitation fall into two general categories. First are attempts to help the alcoholic achieve and maintain a high level of motivation toward abstinence. These include education about alcoholism and instructing family and/or friends to stop protecting the person from the problems caused by alcohol. The second step is to help the patient to readjust to life without alcohol and to reestablish a functional lifestyle through counseling, vocational rehabilitation, and self-help groups such as Alcoholics Anonymous. The third component, called relapse prevention, helps the person to identify situations in which a return to drinking is likely, formulate ways of managing these risks, and develop coping strategies that increase the chances of a return to abstinence if a slip occurs.

There is no convincing evidence that inpatient rehabilitation is always more effective for the average alcoholic than is outpatient care. However, more intense interventions work better than those that are less intensive, and some alcoholics do not respond to outpatient care. The decision to hospitalize can be made if (1) the patient has medical problems that are difficult to treat outside a hospital; (2) depression, confusion, or psychosis interferes with outpatient care; (3) the patient has such a severe life crisis that it is difficult to get his or her attention as an outpatient; (4) outpatient treatment has failed; or (5) the patient lives far from the treatment center. In any setting, the best predictors of continued abstinence include evidence of higher levels of life stability (e.g., supportive family and friends) and higher levels of functioning (e.g., job skills, higher levels of education, and absence of crimes unrelated to alcohol).

Whether the treatment begins in an inpatient or an outpatient setting, subsequent outpatient contact should be maintained for a minimum of 6 months and preferably a full year after abstinence is achieved. Counseling with an individual physician or through groups focuses on day-to-day living¾emphasizing areas of improved functioning in the absence of alcohol (i.e., why it is a good idea to continue to abstain) and helping the patient to manage free time without alcohol, develop a nondrinking peer group, and handle stresses on the job without alcohol.

The physician serves an important role in identifying the alcoholic, treating associated medical or psychiatric syndromes, overseeing detoxification, referring the patient to rehabilitation programs, and providing counseling. The physician is also responsible for selecting which (if any) medication might be appropriate during alcoholism rehabilitation. Patients often complain of continuing sleep problems or anxiety when acute withdrawal treatment is over, problems that may be a component of protracted withdrawal. Unfortunately, there is no place for hypnotics or antianxiety drugs in the treatment of most alcoholics after acute withdrawal has been completed. Regarding insomnia, patients should be reassured that the trouble in sleeping is normal after alcohol withdrawal and will improve over the subsequent weeks and months. They should then follow a rigid bedtime and awakening schedule and avoid any naps or the use of caffeine in the evenings. The sleep pattern will improve rapidly. Anxiety can be approached by helping the person to gain insight into the temporary nature of the symptoms and to develop strategies to achieve relaxation as well as using forms of cognitive therapy.

In addition, while the mainstay of alcoholic rehabilitation involves counseling, education, and cognitive techniques, several interesting medications are under active evaluation and might prove to be useful. The first is the opioid-antagonist drug naltrexone, which has been reported in several small-scale, short-term studies to decrease the probability of a return to drinking and to shorten periods of relapse. While this medication looks promising, longer-term large-scale trials in more diverse clinical settings will be required before the cost-effectiveness of naltrexone can be established. A second medication, acamprosate, has been tested in over 5000 patients in Europe, with results that appear similar to those reported for naltrexone. Currently, acamprosate is not available in the United States, although a long-term, trial of naltrexone, acamprosate, and their combination is in progress. A third medication, which has historically been used in the treatment of alcoholism, is the ALDH inhibitor disulfiram. Taken in doses of 250 mg/day, this drug produces an unpleasant (and potentially dangerous) reaction in the presence of alcohol, a phenomenon related to rapidly rising blood levels of the first metabolite of alcohol, acetaldehyde. However, few adequate double-blind controlled trials have demonstrated the superiority of disulfiram over placebo. Disulfiram has many side effects, and the reaction with alcohol can be dangerous, especially for patients with heart disease, stroke, diabetes mellitus, and hypertension. Thus, most clinicians reserve this medication for patients who have a clear history of longer-term abstinence associated with prior use of disulfiram and for those who might take the drug under the supervision of another individual (such as a spouse), especially during discrete periods that they have identified as representing high-risk drinking situations for them (such as the Christmas holiday).

More data are required before any medication can be recommended for routine use in alcohol rehabilitation. However, additional support for alcoholics is available through Alcoholics Anonymous in almost every community. Alcoholics Anonymous is a self-help group of recovering alcoholics (men and women who have stopped drinking, perhaps many years ago) that offers an effective model of abstinence, provides a sober peer group, and makes crisis intervention available when the urge to drink escalates. No matter what type of rehabilitation program is planned, the alcoholic should be offered the option of joining Alcoholics Anonymous.^


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Copyright© 2001 McGraw-Hill. All rights reserved.


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