Leave a comment

Approach to the problem of alcohol abuse and dependence

Incidence and Epidemiology
Clinical Findings
Optimal Treatment

The use of ethyl alcohol as a beverage began before recorded history, and most persons in Western societies at least experiment with this substance at some time in their lives. Alcohol is a sedative drug, and a high proportion of users find its effects to be quite pleasant. The attractiveness of this beverage leads to excessive use and severe medical problems in about 14% of consumers. Alcohol abuse and alcohol dependence (i.e., alcoholism) are behavioral syndromes that exist along a continuum from minimal use to abuse to addictive use. Alcoholism is a pattern of alcohol use that continues despite significant problems produced by alcohol. There is no specific quantity that is diagnostic of alcoholism, and some alcoholics use ethanol episodically rather than daily. There is no source of alcohol that is more or less toxic than others. One beer (12 ounces) equals approximately one glass of wine (5 ounces), which equals 1.5 ounces of 80-proof liquor (Table 34.1).


As with other sedating drugs, drinkers acquire tolerance to the effects of alcohol. This reduced sensitivity to alcohol is the consequence of an adaptive process that occurs when homeostatic mechanisms are repeatedly perturbed by the stress of alcohol. If alcohol use is discontinued, a rebound occurs as the homeostatic mechanisms adapt to the absence of alcohol. This rebound is seen with many drugs and results in symptoms that are opposite in direction to the effects of the drug itself. This rebound is called a withdrawal syndrome. The state of adaptation to the repeated effects of a drug is called physical dependence, and its presence is determined by the appearance of withdrawal symptoms when the drug is abruptly stopped.
Evidence of increased tolerance and symptoms of withdrawal are frequently found in alcoholics, but neither tolerance nor withdrawal is necessary or sufficient for a diagnosis of alcoholism. Early diagnosis is important, because early treatment is more effective. Unfortunately, at an early stage, alcoholics convincingly deny their excessive drinking, and the physician must obtain a history from family members and look for physical and laboratory evidence to support a clinical suspicion of alcoholism.
An active alcoholic may appear to be a normal and productive person. Too often, physicians fail to recognize alcoholism in prosperous, employed individuals because of the stereotype of the homeless alcoholic who has been unemployed for years. A skilled diagnostician can recognize the signs of early alcoholism and make a referral to a treatment expert. Untreated alcoholism is a progressive disorder, with a downhill course that varies in rate.
Approximately 70% of American adults consume alcohol occasionally. A US probability sample of noninstitutionalized adults (15 to 54 years of age) conducted from 1990 to 1991 found that about 14% had experienced alcohol dependence at some time in their lives, and approximately 7% met criteria for alcoholism in the past year. This disorder is seen in all socioeconomic groups, including persons who are still gainfully employed.
The development of alcohol abuse and dependence is influenced by a combination of hereditary and environmental factors. Children of alcoholics show an increased likelihood of becoming alcoholics, even when they are adopted at birth and raised by nonalcoholic parents. The studies of genetic influences in this disorder show only an increased risk of alcoholism, not 100% determinism, and this is consistent with the features of a polygenic disorder that has multiple determinants. Even identical twins, who share the same genetic endowment, do not have 100% concordance when one twin is alcoholic. The concordance rate for identical twins, however, is much higher than that of fraternal twins, who share the same environment but have a different genotype.
One of the inherited factors that seems to influence the development of alcoholism is tolerance to alcohol. Although tolerance can be acquired by repeated experience with alcohol, persons vary in the innate tolerance manifested when they first consume alcohol. The sons of alcoholics have reduced sensitivity (i.e., more tolerance) to alcohol than other young men of the same age (22 years) and drinking histories. When reexamined 10 years later, those who tolerated alcohol as young men were the most likely to have become alcoholics during the time since they were first tested. These data suggest that tolerance is partly inherited and that inherited tolerance can increase the probability of developing alcoholism. Having an innate tolerance to alcohol does not make a person an alcoholic, but it seems to enhance significantly the probability that alcoholism will develop.
The opposite influence, a kind of “antialcoholism,” also can be inherited. Ethanol is metabolized by alcohol dehydrogenase, producing acetaldehyde, which is itself metabolized by a mitochondrial aldehyde dehydrogenase known as ALDH2. A common mutation occurs in the gene for ALDH2, resulting in a less effective aldehyde dehydrogenase. This allele has a high prevalence in Asian populations and results in excess production of acetaldehyde after the ingestion of alcohol. A person with this allele experiences a very unpleasant facial flushing reaction 5 to 10 minutes after ingesting alcohol. The probability of becoming alcohol dependent is reduced for persons with this heredity pattern, but the risk is not eliminated. Those who are strongly motivated to consume alcoholic beverages can endure the flushing to achieve the other effects of alcohol. There are likely multiple genetic factors that can influence the probability of becoming an alcoholic, but no single factor is determinant. Those who inherit a tolerance to alcohol may avoid alcohol and never become alcoholic. Conversely, those who inherit the gene for a less effective aldehyde dehydrogenase may drink excessively despite the flushing reaction.
Ethanol is classed as a depressant because it produces sedation and sleep. Nonetheless, the initial effects of alcohol, particularly at lower doses, are often perceived as stimulation and are thought to result from suppression of brain inhibitory systems. The course of alcohol intoxication varies. Early in the drinking period, when blood alcohol levels are rising, reports of expansive mood, increased verbalization, and more assertiveness are common, but the sedative symptoms are dominant for some individuals even at an early stage. Some impairment of psychomotor function is measurable at levels as low as 35 to 50 mg per deciliter, well below the level considered to be legal intoxication in this country. This impairment is not perceptible to the average drinker. With increasing dose, the individual is likely to become progressively more depressed, withdrawn, and cognitively impaired. At very high blood alcohol levels (200 to 300 mg per deciliter), a nontolerant individual is likely to fall asleep and enter the first stage of anesthesia. Higher blood alcohol levels (in excess of 300 to 400 mg per deciliter) can inhibit respiration and pulse and can cause death in nontolerant individuals.
The duration of intoxication depends on how much alcohol was consumed over a given period. In general, the body is able to metabolize approximately one drink per hour, and the blood alcohol level generally declines at a rate of 15 to 20 mg per deciliter per hour. Experience with alcohol can produce greater tolerance (i.e., acquired tolerance) such that extremely high blood levels (300 to 400 mg per deciliter) can be found in alcoholics who do not appear to be grossly sedated. In these cases, the lethal dose does not increase proportionate to the sedating dose, and the margin of safety (i.e., therapeutic index) is dangerously low.
Heavy consumers of alcohol acquire tolerance, and they inevitably develop a state of physical dependence on alcohol. This often leads to drinking in the morning to restore alcohol blood levels diminished during the night. Eventually, alcoholics may awaken during the night and take a drink to avoid the restlessness produced by falling alcohol levels. The withdrawal syndrome generally depends on the size of the average daily dose, and it is usually “treated” by resumption of alcohol ingestion. Withdrawal symptoms are experienced frequently, but they are usually not severe or life-threatening until they occur in conjunction with other medical problems.
Depending on its concentration in tissues, alcohol has effects on brain physiology, varying from specific receptor actions to nonspecific membrane changes. Ethanol enhances the actions of the inhibitory neurotransmitter g-aminobutyric acid (GABA) at a subpopulation of GABA receptors. One of the effects of ethanol is increased activity of the dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). This activation can be mediated by the effect on GABA receptors through suppression of inhibitory interneurons, but VTA activation results in an increase in extracellular dopamine in the NAc region. This effect can be learned; rats trained to self-administer alcohol begin to show an increase in NAc dopamine levels as soon as they are placed in the chamber where they have previously obtained alcohol. Other drugs of abuse, such as cocaine and heroin, also raise levels of the neurotransmitter dopamine in this brain area.
There is evidence from animal studies that the endogenous opioid system plays a part in alcohol reinforcement, because alcohol self-administration in animals is diminished by opiate receptor antagonists. In human volunteers, alcohol ingestion in the laboratory produced significant increases in peripheral b-endorphin levels in those with a family history of alcoholism, but the levels were not raised in those without such a family history. For alcoholics, data show that the opiate receptor antagonist naltrexone reduces or blocks the ability of alcohol to produce euphoria. Double-blind, placebo-controlled studies have shown that the relapse rate is lower when alcoholics are given naltrexone (50 mg daily) during the rehabilitation process.
Taking an adequate history from a suspected alcoholic requires diligence and experience. Alcohol abusers typically underestimate the quantity of alcohol they have ingested, but they more often respond truthfully to indirect questions about the effects of their drinking. The CAGE questionnaire (Table 34.2) has been found to be a useful addition to the standard medical history.


Alcohol impairs recent memory and, in high doses, produces the phenomenon of blackouts, after which the drinker has no memory of his or her behavior while intoxicated. The mechanism of the acute memory effects is unclear, but the evidence suggests that reports from patients about their reasons for drinking and their behavior during a binge are not reliable. Alcohol-dependent persons often say that they drink to relieve anxiety or depression. When allowed to drink under observation, however, alcoholics typically become more dysphoric as drinking continues, contradicting the explanation that they drink to relieve tension. The long-term use of alcohol and other sedatives is associated with the development of depression, and the risk of suicide among alcoholics is one of the highest of any diagnostic category.
Cognitive deficits have been reported in alcoholics tested while sober. These usually improve after weeks to months of abstinence. More severe recent memory impairment is associated with specific brain damage caused by nutritional deficiencies common in alcoholics (see later discussion of Wernicke–Korsakoff syndrome). Contrary to the notions of many physicians, alcohol is not a good treatment for insomnia. Physicians should not recommend a bedtime alcoholic drink as a treatment for complaints of insomnia, because drinking alcohol in the late evening actually impairs sleep. Alcohol ingestion can result in stimulation or sedation, depending on the dose and the experience and metabolism of the individual. When sleep is induced, it tends to be a deep, drugged sleep with disruption of sleep stages and suppression of rapid eye movement sleep. Later in the night, a rebound produces lighter sleep and potential awakenings.
Alcohol is toxic to many organ systems, including the liver, pancreas, hematopoietic system, nervous system, heart, gastrointestinal tract, endocrine glands, and bone. Alcohol may produce mild, otherwise unexplained abnormalities that are noticed on routine laboratory testing. Common findings include signs of hepatotoxicity and hematologic abnormalities (Table 34.3). Although none of these findings is diagnostic of alcoholism, they should alert the clinician to take a more careful history of alcohol intake and look for other signs that would support this diagnosis.


Alcohol is an important cause of treatable hypertension. Physicians should always take a careful history of alcohol intake when evaluating a hypertensive patient. Drinking does not have to be heavy enough to qualify as alcohol abuse or dependence in order to increase blood pressure. Often simply reducing or stopping alcohol will bring the blood pressure of a person with mild hypertension into the normal range, obviating the need for antihypertensive medication.
The gastrointestinal effects of alcohol, including hepatic toxicity, are covered in Chapter 121. Alcoholism also has been associated with an increased rate of cancer of the esophagus, stomach, and other parts of the gastrointestinal tract. Many of the symptoms and physical findings associated with alcoholism are a consequence of the multiorgan toxicity of this drug. Examples are the dyspepsia, nausea, and bloating that accompany gastritis and the hepatomegaly, esophageal varices, and hemorrhoids associated with alcohol-induced changes in the liver. Other physical signs include tremor, unsteady gait, insomnia, and erectile dysfunction. Individuals with chronic alcoholism may exhibit decreased testicular size and feminizing effects, such as the gynecomastia associated with reduced testosterone levels caused by the endocrine effects of alcohol.
Severe, repeated alcohol intoxication may also suppress immune mechanisms and increase the risk of infections. Meningitis, especially tuberculous meningitis, is greatly overrepresented among alcoholics. Alcohol also impairs judgment and increases the likelihood of unprotected sex. Sexually transmitted infections, such as human immunodeficiency virus infection, syphilis, and gonorrhea, are linked to alcohol use. Spontaneous abortion and fetal alcohol syndrome have been associated with heavy drinking during pregnancy. Alcohol drinking during pregnancy is one of the most common preventable causes of mental retardation. Although the data show a correlation between heavy drinking and fetal alcohol syndrome, it is not clear whether small amounts of alcohol produce any increased risk. Because data from animal models and clinical studies are ambiguous on this point, many physicians advocate complete abstinence from alcohol during pregnancy.
Alcohol Overdose
Coma due to an overdose of alcohol is a medical emergency. It can occur in someone who rapidly drinks large quantities of alcohol, resulting in a high blood alcohol level. In most overdoses, alcohol is combined with another drug, such as a benzodiazepine. Benzodiazepines are widely prescribed for anxiety, insomnia, and muscle relaxation. Although this class of medication is not dangerous when taken alone, when combined with alcohol, accidental overdoses are common. Blood levels of alcohol and commonly used medications should be obtained when evaluating a comatose patient in the emergency room. For recent ingestion, gastric aspiration can prevent further absorption of toxic agents. Treatment consists mainly of support of vital functions. If opiates are involved, the opiate receptor antagonist naloxone can block opiate effects, but it has no effect on overdose from alcohol or other drugs.
The potential for violence and antisocial behavior is increased by alcohol. Intoxicated individuals tend to get into fights and commit crimes. Family violence, including spouse abuse and child abuse, is strongly linked to alcohol use.
Alcohol is associated with about 50% of all traffic fatalities in the United States each year. Alcohol intoxication may result in falls and accidents that can cause fractures, subdural hematomas, and other forms of brain trauma. Individuals with histories of epilepsy or severe head trauma are more likely to experience alcohol-related seizures.
Alcoholic Blackouts
Alcohol intoxication seriously impairs the storage of memories, and it is not surprising that alcohol abusers and alcoholics frequently have periods of amnesia concerning events that occurred during bouts of heavy drinking. This amnesia facilitates the denial of drinking problems expressed by most alcoholics when confronted by a physician or family member. Even when the patient exhibited outrageous behavior that ordinarily would have been embarrassing, there is no memory of the events, and denial by the patient is facilitated.
Severe Alcoholism and Nutritional Deficiencies
The neurotoxic role of alcohol itself in directly producing chronic neurologic dysfunction is unclear. The neurologic syndromes of alcoholism are seen in a context of chronic nutritional deficiency in heavy drinkers who consume empty calories in the form of ethyl alcohol.
Wernicke–Korsakoff Syndrome
The Wernicke–Korsakoff syndrome is produced by severe nutritional deficiency, especially a lack of thiamine. It consists of a persistent inability to encode new memories and specific neurologic signs, including nystagmus, ophthalmoplegia, and ataxia. Wernicke–Korsakoff syndrome usually develops over days and weeks and then suddenly becomes dramatically apparent during a period of stress caused by infection or trauma. The lack of memory often produces confabulation, as patients try to “fill in the gaps.” This disorder was called Korsakoff’s psychosis, but it was discovered later that confabulation was a behavioral response to the underlying neurologic deficit, known as Wernicke’s syndrome. Hemorrhagic lesions of the mamillary bodies, a part of the brain known to be involved in the encoding of recent memories, have been described in cases examined at autopsy. High doses of thiamine partially reverse these deficits, and thiamine should always be given during the acute treatment of alcoholism. Although the Wernicke–Korsakoff syndrome is most often seen in alcoholics, it can be produced by severe nutritional deficiency in the absence of alcohol, as in cases of gastric carcinoma.
Peripheral Neuropathy
Alcoholics have many problems that can lead to peripheral nerve damage, and this is confirmed by reports of a 45% incidence in some alcoholic populations. Pressure palsies, especially affecting the radial or peroneal nerves and sometimes even the brachial plexus (called park bench neuropathy), arise when alcohol produces a deep sleep without the normal position shifts that protect peripheral nerves. Malnutrition probably accounts for most of the neuropathies seen in alcoholics, including those affecting sensorimotor and autonomic nerves. Rare neurologic complications of alcoholism that stem from extreme malnutrition have been described. These include Marchiafava–Bignami syndrome, a primary degeneration of the corpus callosum, and central pontine myelinolysis, which is associated with chronic hyponatremia.
A patient who is seen in a medical setting with an alcohol withdrawal syndrome should be considered to have a potentially lethal condition. Although most mild cases of alcohol withdrawal never come to medical attention, severe cases require general evaluation; attention to hydration and electrolytes; vitamin supplementation, especially high-dose thiamine (100 mg, given intramuscularly daily for 7 days); and a sedating medication that has cross-tolerance with alcohol. Because of the likelihood of liver impairment, a short-acting benzodiazepine, such as oxazepam, can be given at doses sufficient to block or diminish the alcohol withdrawal symptoms described in Table 34.4. A typical alcoholic requires 15 to 30 mg every 6 hours for 48 hours, decreasing the dose by 10% to 20% per day over the next several days. After medical evaluation, uncomplicated alcohol withdrawal can be effectively treated on an outpatient basis. Hospitalization is required for all unstable patients or when there is a history of seizures. The likelihood of alcohol withdrawal seizures is increased by repeated attempts at withdrawal. Adequate treatment of withdrawal symptoms is important for preventing the development of seizures in the current episode of withdrawal and reducing the potential for seizures in the future.


Detoxification is only the first step of treatment. Complete abstinence is the objective of long-term treatment, and this is accomplished mainly by behavioral approaches. Self-help groups, such as Alcoholics Anonymous (AA), are a mainstay of the rehabilitation of alcoholics. Physicians should learn about the AA groups in their community and make appropriate referrals. AA is a movement rather than an institution, and each group is different, though they all follow a similar set of principles, called the twelve steps. AA can be an important ally of the physician in the care of alcoholics.
Medications that aid in the rehabilitation process are being sought. Disulfiram blocks the metabolism of alcohol, resulting in the accumulation of acetaldehyde, which produces an unpleasant flushing reaction when alcohol is ingested. This drug has been useful in some programs that focus on behavioral efforts to ensure that the patient ingests the medication. Knowledge of this unpleasant reaction helps the patient resist taking a drink. Although it is pharmacologically quite effective, disulfiram has not been found to be practical in controlled clinical trials, because so many patients have failed to ingest the medication regularly.
Naltrexone is another medication used as an adjunct in the treatment of alcoholism. This opiate antagonist appears to block some of the reinforcing properties of alcohol and has resulted in a decreased rate of relapse to alcohol drinking in double-blind clinical trials. Naltrexone was approved by the Food and Drug Administration for the treatment of opiate dependence in 1983, and in 1995 it received approval for the treatment of alcoholism. Naltrexone has not been shown to be effective when given alone, but in the context of a comprehensive treatment program for alcoholism, it increases the probability of a successful outcome.
Alcoholism is a chronic, recurring disorder that requires long-term care. Physicians tend to see treatment of addictive disorders as unsuccessful because of their chronic nature. In reality, the course of alcoholism and other addictions is similar to that of hypertension, diabetes, asthma, and other chronic medical conditions. The patient initially responds to fairly intensive intervention, but some type of maintenance treatment is necessary to deal with recurrences and prevent their becoming severe. In this context, the prognosis for alcoholics in treatment is good because their function improves, but complete “cures” are unlikely.
Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: basic findings from the National Comorbidity Survey. Exp Clin Psychopharmacol 1994;2:244–268.
Hayashida M, Alterman A, McLellan AT, et al. Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild to moderate alcohol withdrawal syndrome. N Engl J Med 1989;320:358–365.
O’Brien CP, McLellan AT. Myths about the treatment of addiction. Lancet 1996;347:237–240.
Schuckit MA. Advances in understanding the vulnerability to alcoholism. In: O’Brien CP, Jaffe J, eds. Addictive states. New York: Raven Press, 1992:93–108.
Schuckit MA. Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 1994;151:184–189
Volpicelli JR, Rhines KC, Rhines JS, et al. Naltrexone and alcohol dependence. Role of subject compliance. Arch Gen Psychiatry 1997;54:737–742.
Weiss F, Lorang MT, Bloom FE, et al. Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants. J Pharmacol Exp Ther 1993;267:250–258.


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: