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The Diseases of Addiction: Disorders Relating to Alcohol

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Mind-altering substances all yield four basic types of disorders: Substance Dependence; Abuse; Intoxication, and Withdrawal. The etiology and pathophysiology of addictive behavior has been somewhat a mystery to the primary care physician. As such, patients with addiction issues are a particularly difficult group to treat in a coherent and comprehensive manner. The common pathways in reward circuitry that affect memory and learning, motivation, control, and decision making are also involved in the addictive process. With the more global understanding of addiction come more treatment strategies, such as meditation and mindfulness training, psychosocial interventions, and pharmacologic approaches. Interestingly, our growing understanding of addiction as a disease has not diminished the value of the spiritually driven approaches, such 12-step-oriented treatments by Alcoholic Anonymous (AA).

The purpose of this document is to give a comprehensive overview of alcohol-related disorders. It is hoped through these publications; the cycle of addiction can be better understood and managed. Citizens of this century have an ever-widening variety of mind-altering substances to use, but doing so still leads to a few basic sorts of problems with behavior, cognition, and physiological symptoms. These behaviors and alcohol abuse are discussed in this chapter.

Introduction:

All drugs of abuse affect the brain's reward pathways. The effects of alcohol appear to be related to complex multiple interactions with the dopamine, gamma-aminobutyric acid (GABA), serotonin, opioid, and N-methyl-D aspartate (NMDA) neurotransmitter systems. New data suggest that the reinforcing effect of alcohol is partially mediated through nicotinic receptors in the ventral tegmental area, which when combined with nicotine may be a factor in the high incidence of smoking among those who are alcohol dependent. Alcohol, food, and drug abuse have similar effects on dopamine receptors. There are several theories of addiction, one of which is that dependence risk is inherited and influenced by alterations in the rewarding chemicals released per dose. Substances of abuse are often put into categories based on their effects. Alcohol has effects similar to other depressants.

As many as 90% of adults in the United States have had some experience with alcohol. Approximately one-half (50.9%) of all Americans older than 12 years of age reported being current consumers of alcohol in the 2006 National Survey on Drug Use and Health. This translates to an estimated 121 million people. More than one-fifth (23%) of Americans participated in binge drinking at least once in the 30 days prior to the survey (1). This represents approximately 45% of all current drinkers. Heavy drinking was reported by 6.9% of the population 12 years of age and older (17 million people). These 2006 estimates are very similar to the 2002 and 2003 estimates. About 40% of people who drink have experienced an alcohol related problem. Between 3% and 8% of women and 10% to 15% of men will be alcohol dependent at some point in their lives. Research suggests that some violent behavior may be preventable. The results of one study suggest that a 10% increase in the beer tax could reduce murder by 0.3%, rape by 1.32%, and robbery by 0.9%. it is reported estimates of the percentages of violent offenders who were drinking when the offense was committed as follows: up to 86% of people committing homicide, 60% of sex offenders, almost 60% of men and more than 25% of women involved in domestic violence, 37% of those committing assault, and 13% of child abusers (4)(5).

Costs of Alcohol Abuse and Dependence:

The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) estimated that the economic cost of alcohol and drug abuse was $246 billion in 1992. This estimate represents $965 for every man, woman, and child living in the United States in 1992. Alcohol abuse and alcohol dependence generated about 60% of the estimated costs ($148 billion) in 1992, while drug abuse and dependence accounted for the remaining 40% ($98 billion). The estimated cost of alcohol abuse for 1998 alone was $184.6 billion. Two-thirds of the costs of alcohol abuse are related to lost productivity, either due to alcohol-related illness (47.5%) or premature death (19.8%). Most of the remaining costs of alcohol abuse were in the form of healthcare expenditures to treat alcohol use disorders and the medical consequences of alcohol consumption (14.2%), property and administrative costs of alcohol-related motor vehicle crashes (8.5%), and various additional costs of alcohol-related crime (8.9%). Alcohol dependence generally reduces the lifespan by 15 years (2). Approximately 45% of the costs of alcohol abuse are borne by those who abuse alcohol and members of their households; 38% by federal, state, and local governments; 10% by private insurance; and 6% by victims of alcohol abusers. When both direct and indirect costs are included, the estimated annual cost of alcohol related problems may be a high as $300 billion.

Definitions:

Tolerance: Either a need for markedly increased amounts of the substance to achieve intoxication or desired effect; or a markedly diminished effect with continued use of the same amount of the substance.

Withdrawal: Either the characteristic withdrawal syndrome for the substance; or the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.

A Standard Drink: A shot of liquor, a glass of wine, or a can of beer (1.5 ounces of 80-proof distilled spirits, 5 ounces of table wine, or 12 ounces of beer).

Alcohol Intoxication: Maladaptive behaviors or psychological changes (e.g., inappropriate sexual or aggressive behavior, mood changes, impaired judgment, and impaired social or work behavior) that result from recent alcohol consumption. Changes include slurred speech, loss of coordination, unsteady walking or running, impairment of attention or memory, nystagmus, stupor, or coma (3).

Alcohol Withdrawal: The presence of certain symptoms after stopping or reducing heavy and prolonged alcohol use. The symptoms of alcohol withdrawal may develop within a few hours to a few days after stopping or reducing use and symptoms cause significant physical and emotional distress in social, work, or other important areas of functioning. Symptoms include increased hand tremor, sweating, increased pulse rate, nausea, vomiting, insomnia, temporary hallucinations or illusions, anxiety, psychomotor agitation, and grand mal seizures. Fewer than 5% of persons who develop alcohol withdrawal experience severe symptoms such as seizures and death.

Blood Alcohol Concentration (BAC): The percentage of alcohol present in the bloodstream. The BAC is usually what is measured by police officers to determine legal intoxication. It can be measured directly from a blood sample or a breath sample collected by a "Breathalyzer."

Binge Drinking: Consuming five or more drinks on the same occasion.

Moderate Drinking: No more than one drink a day for women and no more than two drinks a day for men.

Alcohol and Genetics:

Research has shown that genetic factors play a strong role in whether a person becomes an alcoholic, accounting for 40% to 60% of the risk (4). In fact, family transmission of alcohol dependence has been well established. Individuals who have alcoholic relatives are at three to five times greater risk of developing alcohol dependence than the general population. The presence of alcohol dependence in one or both biological parents is more important than the presence of alcohol dependence in one or both adoptive parents. The genetic risk of alcohol dependence increases with the number of alcoholic relatives and the closeness of the genetic relationship. However, most children of alcoholics do not become alcoholics themselves, and some children from families where alcohol is not a problem develop alcohol dependence when they get older. Alcohol dependence is seen in twins from alcoholic parents, even when they are raised in environments where there is little or no drinking. Identical twins adopted into households with an alcoholic stepfather do not show more alcohol dependence than the general population. Children with close biological relatives who are alcoholics, who are adopted into a never drinking, even religiously opposed family, can readily develop alcohol problems.

As mentioned previously, genetic factors are thought to account for 40% to 60% of the risk of developing alcohol dependence. Animal studies have shown that genetic factors may be responsible for enhanced brain reward produced by alcohol, decreased initial impairment, or even altered metabolism of alcohol. Genetic factors appear to influence the level of response (LR) to alcohol, as measured by the intensity with which one reacts to a given quantity. The level of response to alcohol varies from individual to individual depending on the tolerance. Low LR at an early age contributes to the risk of alcohol dependence later in life (4). Genetic differences in metabolic or other biological processes may play a role in the development of alcohol dependence in specific individuals. Studies using a self-rated scale have shown consistent results in sons of alcoholic fathers scoring themselves lower than sons of non-alcoholic fathers on feelings of drunkenness, dizziness, drug effect, and sleepiness following alcohol consumption. This suggests that sons of alcoholic fathers have a less intense reaction to alcohol than sons of nonalcoholic fathers. Low reaction to alcohol suggests tolerance, an indicator of tendency towards dependence. High alcohol sensitivity in men is associated with substantially decreased risk of alcohol dependence. Understanding reactions to alcohol could establish a better understanding of future risk of developing alcohol dependence in these men.

Studies have found similar results of higher tolerance for alcohol among daughters of alcoholics. One study examined the drinking patterns of 38 daughters of alcoholics compared with 75 family-history-positive men from the same families and 68 men with no family history of alcohol dependence (5). Family-history-positive men and women both displayed low reaction to alcohol. This indicates that the degree of genetic influence on alcohol-related behavior is similar for both men and women with family history of alcohol dependence. In a study of adolescent and young adult offspring from families where alcohol dependence is prevalent, researchers found both neurophysiological and neuroanatomical differences, such as reduced right amygdala volume, when comparing these offspring to controls. American Indians have a lower level of response and an increased risk of alcohol dependence. The alcohol metabolizing enzymes are another important genetic influence, especially for persons of Asian decent. About 50% of Japanese, Chinese, and Korean persons flush and have a more intense response to alcohol because they have a form of alcohol dehydrogenase (ADH) that causes high levels of acetaldehyde. Forms of ADH and aldehyde dehydronase (ALDH) (e.g., homozygous or heterozygous) contribute to a higher rate of alcohol metabolism, intensify the response to alcohol, and lower the risk of alcohol dependence. High levels of impulsivity/sensations seeking/disinhibition are also genetically influenced and may impact alcohol dependence risk.

Fetal Alcohol Syndrome (FAS): Recognition & Prevention

Known Risk Factors for Alcohol Dependence:

A review of some of the research findings on genetic and psychosocial risk factors may provide a better understanding of the factors leading to alcohol dependence (6).

Temperament: Moodiness, negativity, and provocative behavior may lead to a child being criticized by teachers and parents. These strained parent-child interactions may increase the chances that a child will drink.

Hyperactivity: Hyperactivity in childhood is a risk factor for the development of adult alcohol dependence. Children with attention deficit hyperactivity disorder (ADHD) and conduct disorders have increased risk of developing an alcohol use disorder. Childhood aggression also may predict adult alcohol abuse.

Parents: The most compelling and largest body of research shows parents to be the most important factor in an adolescent's decision to drink.

Gender: Among adults, heavy alcohol use is almost three times more common among men than women and also more common among males in middle or high school than among females. Males with ADHD and/or conduct disorders are more likely to use alcohol than males without these disorders, while females who experience more depression, anxiety, and social avoidance as children are more likely to begin using alcohol as teens than females who do not experience these negative states.

Other Psychiatric Disorders:Bipolar disorder, schizophrenia, antisocial personality disorder, and panic disorder all also increase the risk of a future alcohol use disorder. Abuse and Adverse Conditions in the Home: Childhood abuse is a significant risk factor for later alcohol and substance abuse. Women who were physically abused are 1.5 to 2 times more likely to abuse alcohol than non-abused adults. Children from crowded, noisy, and disorderly homes without rules or religion are more likely to abuse alcohol as teens. Children who are quick to anger, who perceive themselves to be highly stressed, who are resentful of parents' absences, or who have repeated conflicts at home are more likely to abuse alcohol as teens.

Elevated Laboratory Findings:

Most common laboratory findings are elevated - serum glutamic oxaloacetic transaminase (SGOT); lactic acid dehydrogenase (LDH); cholesterol; gamma glutamyl transferase (GGT); mean corpuscular volume (MCV); alkaline phosphatase; triglycerides; blood alcohol concentration; serum transferring; and uric acid.

Alcohol and Liver Disease:

The liver is a particularly vulnerable organ to alcohol consumption, in large part because it is where alcohol is metabolized prior to elimination from the body. As little as six drinks a day for men have been found to be associated with liver damage. The most common manifestation among alcoholics is called "fatty liver." Among heavy drinkers, the incidence of fatty liver is almost universal. For some alcoholics, a fatty liver may precede the onset of alcoholic cirrhosis. Fatty deposits have been associated with men who have six or more drinks a day and women who have only one or two drinks daily. Alcoholic hepatitis is a condition that, when severe, is characterized by jaundice, fever, anorexia, and right upper-quadrant pain. Between 10% and 35% of heavy drinkers (those drinking five or six standard drinks a day or more) develop alcoholic hepatitis, and 10% to 20% develop cirrhosis (7). More than 60% of persons who develop both alcoholic hepatitis and cirrhosis will die within four years. Drinking 12 beers a day for 20 years has been associated with a 50% incidence of cirrhosis. It is not known which individuals will develop cirrhosis. Studies have shown that women develop liver disease faster and at lower levels of alcohol consumption than men. Women also have a higher incidence of alcoholic hepatitis and higher mortality rate from cirrhosis.

Alcohol and Cardiovascular Disorders:

Alcohol can have a detrimental effect on the heart, including a decrease in myocardial contractility, hypertension, atrial and ventricular arrhythmias, and secondary non-ischemic dilated cardiomyopathy. A common complication in alcohol dependence is elevated pulse and blood pressure, often in the hypertension range. Younger alcoholics and those without existing hypertension are less likely to have an elevation than those who are older and predisposed to some hypertension. When drinking stops, the blood pressure often returns to normal over a period of a few days. One study found that people who had six or more drinks a day were twice as likely to suffer from hypertension than moderate drinkers (two or less drinks a day) or nondrinkers (8). Increased serum GGT levels may be an indicator of an individual's susceptibility to the hypertensive effect of alcohol. Aside from hypertension, chronic heavy drinking can adversely affect the heart primarily through direct toxicity to striated muscle, leading to a form of cardiomyopathy. Alcoholic cardiomyopathy is probably more common than is currently thought because of under diagnosis of alcohol dependence in general. The association between heavy alcohol consumption and rhythm disturbances, particularly supraventricular tachyarrhythmias in apparently healthy people, is called "holiday heart syndrome". The syndrome was first described in persons with heavy alcohol consumption, who typically presented on weekends or after holidays, but it may also occur in patients who usually drink little or no alcohol. The most common rhythm disorder is atrial fibrillation, which usually converts to normal sinus rhythm within 24 hours. The incidence of holiday heart syndrome depends on the drinking habits of the studied population. Holiday heart syndrome should be considered as a diagnosis particularly in patients without overt heart disease presenting with new onset atrial fibrillation. Though recurrences occur, the clinical course is benign and specific antiarrhythmic therapy is usually not warranted.

Vitamin Deficiency, Alcohol, and Cardiovascular Disease:

Abnormally high plasma levels of the amino acid homocysteine have been shown in studies to increase the risk for cardiac and other vascular diseases. Even small increases in homocysteine appear to increase the risk of heart disease. Vitamins like folate, B12, and B6 are required for homocysteine disposal within cells. The lower the concentration of these and other vitamins, the greater the concentration of homocysteines (9). A number of nutritional problems have been reported in people with alcohol dependence. Malnourished alcoholics with liver diseases have been found to have B6 and folate deficiencies. In addition, average homocysteine levels are twice as high in chronic alcoholics when compared to nondrinking controls. Thus, homocysteine may contribute to the cardiovascular complications experienced by many chronic alcoholics. Lowering homocysteine with B vitamin supplementation may reduce cardiovascular risk (8). Further research is necessary to determine whether joining a treatment program or abstinence reverses the risk of cardiovascular disease, and whether folate and vitamins B12 and B6 should be considered as appropriate nutritional supplements for patients with alcohol dependence.

Alcohol and Cancer:

Heavy drinking increases the risk of cancer of the upper gastrointestinal and respiratory tracts. Almost 50% of cancers of the mouth, pharynx, and larynx and approximately 75% of esophageal cancers in the U.S. are associated with chronic, excessive alcohol consumption. When alcohol consumption is combined with tobacco use, the risk of esophageal cancer increases markedly, as much as 130-fold in one study. Alcohol increases production of estradiol, and increased levels of estradiol have been linked to an increased risk of breast cancer in women who drink.

Alcohol and Gastrointestinal Disorders:

Alcohol produces irritation and inflammation of the mucosal lining of the gastrointestinal tract and influences the motility in the esophagus, stomach, and small bowel. Frank ulceration may occur with chronic excessive alcohol use. This well-known alcohol related "heartburn" is due to esophageal reflux with esophagitis that commonly occurs with irritation and inflammation of the gastroesophageal junction. Severe vomiting from alcohol gastritis may result in mucosal tears at the gastroesophageal junction, resulting in frank, usually transient pain in the upper gastrointestinal tract. Short-term and long-term alcohol ingestion are associated with gastritis, erosive gastritis, gastric ulceration, atrophic gastritis, and gastric hemorrhage. Furthermore, duodenitis and duodenal ulcerations are a direct result of chronic excessive alcohol irritation and inflammation. Patients who have undergone gastric bypass surgery for obesity have higher breath-alcohol levels after drinking the same amount as other people. Findings from a small study suggest that it takes much longer for their levels to return to zero.

Alcohol and Chronic Pancreatitis:

Alcohol consumption is the leading cause of chronic pancreatitis, accounting for approximately 70% of cases in the United States; however, fewer than 10% of heavy alcohol drinkers develop the disease. While there are many theories regarding the pathophysiology of chronic pancreatitis, the most prevalent for alcohol-induced chronic pancreatitis involves the effect of toxic metabolites on the pancreas. This theory suggests that inflammation and fibrotic changes in the pancreas are the direct result of premature activation of enzymes due to ethanol's effect on the Golgi complex. Another theory suggests that pancreatic hypoxia results from decreased blood flow to the pancreas. Alcohol-induced acinar injury may reduce capillary flow and result in edema and capillary compression. Alcoholics may develop diabetes mellitus or hyperglycemia as a result of chronic pancreatitis, when the islet cells in the pancreas are eventually destroyed.

Alcohol and Body Weight:

Although alcohol has a relatively high caloric value, 7.1 calories per gram (1 gram of fat contains 9 calories), alcohol consumption does not generally result in increased body weight. Moderate doses of alcohol added to the diets of lean men and women do not seem to lead to weight gain. However, obese patients in some studies have gained weight when alcohol is added to their diets. An analysis of data collected from the first National Health and Nutrition Examination Survey (NHANES I) found that although drinkers had significantly higher intakes of total calories than non-drinkers, drinkers were not more obese than non-drinkers. In fact, women drinkers had significantly lower body weight than non-drinkers. As alcohol intake among men increased, their body weight decreased. An analysis of data from the second National Health and Nutrition Examination Survey (NHANES II) and other large U.S. studies found similar results for women. When chronic heavy drinkers substitute alcohol for carbohydrates in their diets, they lose weight and weigh less than their non-drinking counterparts. Furthermore, when chronic heavy drinkers add alcohol to an otherwise normal diet, they do not gain weight. This is generally attributed to alcoholics using alcohol as a main calorie source.

Alcohol and Malnutrition:

Excessive drinking may interfere with the absorption, digestion, metabolism, and utilization of nutrients, particularly vitamins. Alcoholics often use alcohol as a source of calories to the exclusion of other food sources, which may also lead to a nutrient deficiency and malnutrition. Alcoholics in the late stage of the disease may develop anorexia or severe loss of appetite, and refuse to eat. Alcoholics account for a significant proportion of patients hospitalized for malnutrition. Direct toxic effects of alcohol on the small bowel causes a decrease in the absorption of water-soluble vitamins (e.g., thiamine, folate, and B6). Studies have suggested that alcoholism is the most common cause of vitamin and trace-element deficiency in adults in the United States. Alcohol's effects are dose dependent and the result of malnutrition, malabsorption, and ethanol toxicity (9). Vitamins A, C, D, E, K, and the B vitamins are deficient in some alcoholics. All of these vitamins are involved in wound healing and cell maintenance. Because vitamin K is necessary for blood clotting, deficiencies can cause delayed clotting and result in excess bleeding. Vitamin A deficiency can be associated with night blindness, and vitamin D deficiency is associated with softening of the bones. Deficiencies of other vitamins involved in brain function can cause severe neurological damage (e.g., deficiencies of folic acid, pyridoxine, thiamine, iron, and zinc). Thiamine deficiency from chronic heavy alcohol consumption can lead to devastating neurological complications, including Wernicke-Korsakoff syndrome, cerebellar degeneration, dementia, and peripheral neuropathy. Thiamine deficiency in alcoholics who are suffering from Wernicke-Korsakoff syndrome leads to lesions and increased microhemorrhages in the mammillary bodies, thalamus, and brainstem. This syndrome can also be associated with diseases of the gastrointestinal tract when there is inadequate thiamine absorption.

Alcohol and Infectious Diseases:

Alcohol abuse is a major risk factor for many infectious diseases, especially pulmonary infections. Pulmonary infections, pneumonia, and tuberculosis are frequent causes of illness and death among alcoholics. Other infectious diseases that are over-represented among alcohol dependent individuals are bacterial meningitis, peritonitis, and ascending cholangitis. Less serious infections are chronic sinusitis, pharyngitis, and other minor infections. The consumption of alcohol alters T-lymphocyte functions, immunoglobulin production by B cells, NK cell function, and neutrophil and macrophage activities. Studies have shown that animals given ethanol are unable to suppress infections that can ultimately result in progressive organ damage and death.

Alcohol and Sleep Disorders:

Although some people believe that alcohol helps them sleep, chronic excessive drinking can induce sleep disorders by disrupting the sequence and duration of sleep states and by altering total sleep time, as well as the time required to fall asleep. Specifically, drinking within an hour of bedtime appears to disrupt the second half of the sleep period. The person may sleep poorly during the second half of sleep, awakening from dreams and returning to sleep with difficulty, resulting in daytime fatigue and sleepiness (10). Individuals who are alcohol dependent may be at increased risk for sleep apnea, a disorder in which the upper air passage narrows or closes during sleep. The combination of alcohol, obstructive sleep apnea, and snoring increases a person's risk for heart attack, arrhythmia, stroke, and sudden death.

Alcohol Dependence and Nervous System:

The most common neurologic abnormality among alcohol dependent patients is dementia syndrome, which manifests primarily as impairment in recent memory, and more subtle fluctuations in abstractions, calculations, and other aspects of cognitive functions. As previously stated, one specific neurological complication resulting from thiamine deficiency is Wernicke-Korsakoff syndrome, which involves delirium, clouded sensorium and confusion, ophthalmoplegia, nystagmus, and ataxia. Immediate administration of thiamine is usually successful in treating the symptoms, but in some cases permanent memory loss occurs. Once delirium and confusion resolve, there is sometimes a profound loss in recent memory out of proportion to the other cognitive deficits, and alcoholic peripheral neuropathy, which results in diminished sensitivity to touch, pinprick, and vibration objectively, and paraesthesias subjectively (10). The acute effects of alcohol on the nervous system are signs people commonly think of when they envision an intoxicated person, such as slurred speech, loss of coordination, unsteady gait, impairment of attention or memory, nystagmus, stupor, or coma. The degree to which the central nervous system is impaired is directly proportional to the behavioral and cognitive impairment.

Alcohol and the Brain:

Alcohol affects most neurochemical systems including N-methyl-D aspartate (NMDA), gamma-aminobutyric acid (GABA), serotonin, dopamine (DA), and opioid systems. Alcohol inhibits NMDA systems, which may contribute to feeling intoxicated. NMDA receptors change as tolerance develops. These receptor systems are overactive during withdrawal. Alcohol also enhances the action of the GABA system, producing some of the symptoms of acute intoxication. GABA receptors are especially sensitive to alcohol. The GABA system is underactive during withdrawal, and the genes that control these receptors may have an impact on the risk of alcohol dependence. Alcohol causes the release of 5-HT, or serotonin. Lower 5-HT levels in the brain are associated with increased alcohol intake in animals and humans, while higher 5-HT levels are associated with slightly reduced alcohol intake. Several 5-HT genes may be related to the genetic risk of alcohol dependence. Alcohol activates DA in the reward system in the ventral tegmental area of the brain. Alcohol also causes the release of DA. Several DA receptors may be related to the genetic risk of alcohol dependence (10).

Finally, alcohol causes the release of endogenous opioids. Opioid receptors change with tolerance and withdrawal. Some receptors may affect genetic predisposition for alcohol dependence and opioid antagonists can decrease voluntary alcohol consumption. Alcohol may also affect acetylcholine, norepinephrine and steroids. Most people who drink do not develop brain damage. However, studies do indicate that impaired cognition and motor abilities occur in some individuals who are heavy drinkers. Older persons with alcohol dependence exhibit more brain tissue loss than both older and younger persons without alcohol dependence. These results suggest that aging may render a person more susceptible to the effects of chronic excessive alcohol. Most studies suggest that, following long-term abstinence, most brain changes resolve. Magnetic resonance imaging (MRI) has been used to measure changes in the brain structure and volume in alcoholics at three weeks after abstinence from alcohol. The results indicated that the brain volume in alcohol dependent men and women was significantly reduced as compared to non-alcohol dependent men and women. The differences, however, were much more significant in women than in men. These results indicate that alcohol inflicts worse neurotoxic effects in alcohol dependent women than alcohol dependent men, but again, these brain changes may resolve with long-term abstinence.

Alcohol and Child Abuse:

Living with a non-recovering alcoholic in the family can contribute to stress for all members of the family. Alcohol dependence usually has strong negative effects on marital relationships. Separated and divorced men and women were three times as likely as married men and women to say they had been married to an alcoholic or problem drinker. The majority of studies suggest an increased prevalence of alcohol dependence among parents who abuse children. Existing research suggests that alcoholism is more strongly related to child abuse than are other disorders, such as parental depression, but the most important factor is whether the abusive parent was abused themselves or witnessed a parent or sibling being abused. Although several studies report very high rates of alcoholism among the parents of incest victims, much additional research in this area is needed.

Alcohol and Depressive Disorders:

Alcohol is both a stimulant and a depressant, depending on the levels and time after drinking. Alcoholics are often misdiagnosed as depressed because of the many symptoms of alcohol dependence that mimic depression. Insomnia, reduced appetite, and decreased energy are just a few of the symptoms that can occur in both diseases. Alcohol can cause temporary depressive symptoms, even in persons who have no history of depression. In fact, as many as 80% of alcoholic men and women complain of depressive symptoms, and at least one-third meet the criteria for a major depressive disorder. Depression is often a comorbid disorder but can also be solely due to alcohol. This is very important because the depression must also be treated along with the alcohol dependence. Alcohol intoxication, especially binge drinking, can also cause mood swings that mimic the "highs" of people with manic depression/bipolar disorder. Thirty to fifty percent of alcoholics suffer from major depression at the same time. How alcohol dependence is related to depression is not clear (9). Some studies have suggested that both conditions may share common risk factors. For example, both problems may run in families.

Co-occurrence is very common, but thought by some to be independent in etiology. Treatment professionals have found that after two to three weeks of abstinence from alcohol and with good nutrition, the temporary depressive effects of alcohol dissipate. However, there are subgroups of alcoholics who have true depression or manic depression, and it is critically important to treat these illnesses during alcohol treatment (15). If true depression is left untreated, many alcoholics will drop out of treatment and relapse to drinking. Alcohol abuse, alcohol dependence, and depression are important risk factors for suicidal thinking or actions. Because alcohol can make depression worse, even intolerable, alcohol is often a factor in suicides.

Alcohol and Suicide:

Suicide is the eleventh leading cause of death overall and the third leading cause among persons 15 to 34 years of age. Most people who attempt suicide and 90% of suicide victims have a diagnosable psychiatric disorder. Alcohol is the number one drug of abuse associated with suicide. In 2005, 32,637 people in the United States committed suicide and an estimated 816,000 attempted suicide. Among people who attempt suicide, alcohol dependence is a common diagnosis. Major depression and alcohol dependence, respectively, are the most commonly diagnosed psychiatric disorders in patients who commit suicide. Next to age, alcohol dependence and drug addictions are the second most important risk factors in suicide. As many as 85% of individuals who commit suicide suffer from depression or alcohol dependence, and 70% of alcoholics with comorbid depression report that they have made a suicide attempt at some point in their lives. It is reported the likelihood of suicide in diagnosed alcoholism is between 60 and 120 times that of persons without mental illness (11). Alcohol intoxication can exaggerate depression and increase the likelihood of an impulsive act like suicide or other forms of violence. Alcohol use is frequently detected in suicide methods involving driving a vehicle or overdosing. Alcohol impairs judgment and lowers the threshold to commit suicide, explaining its association with suicide methods that involve a high level of pain. In a case-control study, researchers examined the relationship between near fatal suicide attempts and aspects of alcohol consumption, such as amount and frequency of drinking, alcoholism, binge drinking, and drinking within three hours of a suicide attempt, and found a J-shaped relationship between alcohol exposure and near lethal attempts for all measures (11).

It is estimated that the lifetime suicide risk among alcohol dependent individuals is 10%, a figure 5 to 10 times greater than seen in the general population. Between 15% and 20% of alcohol dependent persons will attempt suicide, and of those who have attempted in the past, 15% to 20% will attempt suicide again in the next five years. One study conducted in Japan showed that, among drinkers, the risk of suicide increased with the amount of alcohol consumed. An unusual finding of this study was a U-shaped relationship between alcohol and suicide. Abstainers also have a significantly increased risk, similar to heavy drinkers. Among middle-aged males, moderate drinkers had the lowest risk for suicide. In order to be most effective at the prevention of suicide, healthcare providers must be adept at eliciting both a substance use history and a psychiatric history. Risk factors associated with completed suicide with alcohol dependence include comorbid major depression, active drinking, serious medical illness, living alone, and interpersonal loss and conflict.

Treatment of Depressed Alcohol Dependent Patients:

Male, alcoholic, and depressed are the most common descriptors for suicide attempters. Always evaluate depressed alcoholics for depression, suicide, and possible referral to a psychiatrist or psychologist. Depression and alcohol dependence are common problems in the United States. Both are at the top of the list of problems that commonly require psychiatric treatment. Treating one problem but not the other is also very common. In order to successfully treat alcohol dependence and depression it is important that healthcare providers diagnose and treat both problems (15). Treatment of alcohol dependence begins with intervention or some type of treatment-based approach, which may include a 12-step program. Adding an antidepressant and treating the depression requires a number of subtle changes in thinking.

The next issue is determining which antidepressant to use. Lithium and tricyclics used to treat depression alone may not be effective or could have serious side effects when used in depressed alcoholics. Another class of antidepressants, selective serotonin reuptake inhibitors (SSRIs), have been studied to treat depression after failing to treat alcohol dependence. SSRIs generally cause less serious side effects than tricyclics, but some, like fluoxetine, work slowly and cause sexual performance side effects. SSRIs, such as fluoxetine, sertraline, and paroxetine, and herbal remedies such as St. John's Wort have been tried in a variety of studies and are generally able to alleviate depression, but did not appear to help with drinking outcomes. Venlafaxine and bupropion appear to be especially effective in treating depressed patients with alcohol dependence. Venlafaxine is well suited to treat alcohol dependence with depression and even depression with anxiety. Venlafaxine is effective in mild and severe depression with anhedonia. Bupropion is effective as well, but it has seizure risks in this population. Alcohol-using depressed males appear very sensitive to the sexual side effects of the SSRIs and may discontinue their use and drop out of treatment (15). Patients with major depression and alcohol dependence are generally treated with venlafaxine and, when necessary, are augmented with bupropion or mirtazapine.

Alcohol and Bipolar Disorder:

A 2000 study analyzed the substance/alcohol abuse patterns of 89 patients with a confirmed diagnosis of bipolar disorder (71 with bipolar I and 18 with bipolar II). The diagnosis was confirmed by a structured clinical interview for DSM-IV axis I, an attending psychiatrist, a medical records review, and family members. The age of the patients ranged from 18 to 65 years. Among those with bipolar disorder I, 41 patients (57.8%) abused or were dependent on one or more substances (including alcohol), 28.2% abused or were dependent on two substances, and 11.3% abused or were dependent on three or more substances. Among those with bipolar disorder II, 39% of patients abused or were dependent on one or more substances, 17% were dependent on two or more substances, and 11% were dependent on three or more substances (12). The risk for substance or alcohol abuse was higher among patients with bipolar I disorder than with bipolar disorder II. Patients with both bipolar disorders I and II abused alcohol more often than any other substances.

Alcohol and Anxiety:

Alcohol withdrawal causes many of the signs and symptoms of anxiety and can even mimic panic attacks. Alcohol works much like a benzodiazepine; many people who abuse and are dependent on alcohol have learned to drink to temporarily relieve anxious feelings. Special problems exist for people who drink to self-medicate the symptoms of a true generalized anxiety disorder, social phobia, or panic disorder. Alcohol may provide temporary relief, but it is not a good treatment for shyness or an anxiety disorder. The price a person may pay for self-medication are two diseases: anxiety and alcohol dependence.

TREATMENT

Treatment works. People who make the decision to stop drinking will be able to find the treatment and support they need to quit, remain sober, and regain their lives. However, as with treatment for any other disease, it is important to have a good idea of the options available in order to make informed choices.

Phases of Treatment: To understand treatment and make the right treatment choices, it helps to have an overview. Treatment is often seen as having four general phases (13).

  1. Getting started: Assessment and evaluation of disease symptoms and accompanying life problems, making treatment choices, and developing a plan
  2. Detoxification: Stopping use
  3. Active treatment: Residential treatment or therapeutic communities, intensive and regular outpatient treatment, medications to help with alcohol craving and to discourage alcohol use, medications to treat concurrent psychiatric illnesses, 12-step programs, other self-help and mutual-help groups
  4. Maintaining sobriety and relapse prevention: Outpatient treatment as needed, 12-step programs, other self-help and mutual-help groups

Withdrawal Symptoms and Medical Management:

Abrupt discontinuation or even cutting down on the amount of drinking by persons who are physiologically dependent on alcohol produces a characteristic withdrawal syndrome with sweating, rapid heartbeat, hypertension, tremors, anorexia, insomnia, agitation, anxiety, nausea, and vomiting. In some ways, alcohol withdrawal resembles withdrawal from opiates. However, alcohol withdrawal is strikingly different from opiate withdrawal in that as many as 15% of alcoholics progress from the autonomic hyperactivity and agitation common to withdrawal from other drugs to seizures and, for some, even death. In some cases, delirium tremens (DTs) may occur within the first 96 hours and can include disorientation, confusion, auditory or visual hallucinations, and psychomotor hyperactivity. The Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) is a symptom-triggered, 10-item scale that quantifies the risk and severity of alcohol withdrawal. However, in order to be most useful, it requires patient input, which may not be feasible in patients undergoing severe DTs. If the patient is able, the assessment takes only minutes and aids in identification of patients who may need immediate pharmacological treatment to prevent further complications. Mild withdrawal usually corresponds with a score of 8 or less, moderate withdrawal with a score between 9 and 15, and scores greater than 15 indicate severe withdrawal. Patients scoring less than 9 may not require pharmacological intervention. However, reassessment of symptoms should be performed every 1 to 2 hours until withdrawal is resolved.

Pharmacological management of acute alcohol withdrawal generally involves the use of benzodiazepines, which reduce related anxiety, restlessness, insomnia, tremors, DTs, and withdrawal seizures. Benzodiazepines are the most widely used, and while they may have abuse liability in some patients, they have been safely used for years. These medications may be administered either on a fixed interval or symptom-triggered schedule. However, both short-acting and long-acting benzodiazepines have their problems. The long-acting benzodiazepines can decrease rebound symptoms and work for long periods of time, but intramuscular absorption can be very erratic. Short-acting benzodiazepines have less risk of oversedation, no active metabolites, and considerable utility in patients with liver problems or disease. Yet, breakthrough symptoms can and do occur, and risk of seizure is imminent.

Patients with withdrawal symptoms are generally treated with diazepam or chlordiazepoxide until withdrawal subsides. These medications are preferred due to their long action, which decreases the risk of rebound symptoms. If intramuscular administration is necessary, lorazepam is the drug of choice. More severe withdrawal is generally treated in a hospital setting. Other medications may be used in conjunction with benzodiazepines for the treatment of withdrawal. Anticonvulsants are used safely to treat withdrawal. They do not have abuse liability and have anticonvulsant and antikindling effects. Nevertheless, they also have problems. They do not reduce delirium and can have liver toxicity. Alpha-adrenergic agonists like clonidine can reverse many of the behavioral symptoms of withdrawal but do not prevent seizure and can cause hypotension (14). However, for those patients with coronary artery disease, use of an alpha-adrenergic agonist or beta blocker may be indicated. More research is necessary regarding the efficacy of calcium channel antagonists in the treatment of alcohol withdrawal. Studies have shown that those who have withdrawal seizures may have a worse prognosis than those who do not. Detoxification is only the first step in the treatment process, and the beginning of a lifelong process.

Medications Used to Treat Alcohol Dependence:

Several medications are available to help treat alcohol dependence. Some are used for detoxification and others are used to prevent relapse. Research has shown that medications are most effective when used in conjunction with other therapies (13)(14).

Disulfiram

Disulfiram, commonly known as Antabuse, was the first drug to be made available for the treatment of alcohol dependence. It was approved for treatment of alcohol dependence by the FDA in 1951 and has been used safely and effectively for more than half a century. It works by blocking an enzyme, aldehyde dehydrogenase that helps metabolize alcohol. Taking even one drink while on disulfiram causes the alcohol at the acetaldehyde stage to accumulate in the blood. This produces nausea, vomiting, sweating, and even difficulty breathing. Patients must also be mindful of consuming even minute amounts of alcohol in foods, over-the-counter medications, mouthwash, and even topical lotions. The American College of Physicians concluded that disulfiram can be effective for people who are committed to staying sober. Due to more modern and improved medication modalities, many clinicians prescribe disulfiram as a last resort intervention. Although widely used, it is less clearly supported by clinical trial evidence. The recommended dose for disulfiram is 250 mg/day, which can be increased to 500 mg based upon whether a patient experiences the disulfiram-ethanol reaction. Due to the physiological changes that occur with use, use of disulfiram is not recommended in patients with diabetes, cardiovascular or cerebrovascular disease, or kidney or liver failure.

Naltrexone

Naltrexone (ReVia) is an opioid antagonist that interferes with the rewarding or pleasurable effects of alcohol and reduces alcohol craving. The FDA approved the use of naltrexone in alcohol dependence in December 1994. Naltrexone, which has long been used to treat heroin addicts, was not known as a treatment that could reduce alcohol relapse until the 1980s. In 1980, researchers reported reductions in monkey ethanol self-administration when they were pretreated with naltrexone. By 1992, Volpicelli and colleagues reported a six-week, double-blind placebo-controlled outpatient naltrexone trial with 70 alcohol dependent individuals. They found that the naltrexone-treated patients had a lower relapse rate, fewer drinking episodes, longer time to relapse, and reduced tendency for a slip to become a relapse. These and other data suggested that endogenous opioids were important in alcohol reinforcement.

Also in 1992, O'Malley and associates compared naltrexone with placebo and found that naltrexone-treated patients had lower rates of relapse to heavy drinking, consumed fewer drinks per drinking day, and had lower dropout rates than placebo-treated alcohol dependent patients. These results have since been supported by other studies. Research suggests that naltrexone may be most effective for alcohol dependent individuals with a family history of alcohol dependence. After a complete history, physical exam, and laboratory testing, most patients are started on 50 mg orally per day. For most patients, this is the safe and effective dose of naltrexone. However, in a 4-month study period, the COMBINE study demonstrated efficacy of naltrexone at a dose of 100 mg daily. Some treatment providers give patients a naltrexone identification card or ask them to order a MedicAlert bracelet that clearly indicates that they are maintained on an opioid antagonist, so if they need an opiate drug or medication for pain relief, the dose of the pain medication can be adjusted higher.

The most common side effects of naltrexone are light-headedness, diarrhea, dizziness, and nausea. These tend to disappear quickly in most patients. Naltrexone is not recommended for patients with acute hepatitis or liver failure, for adolescents, or for pregnant or breastfeeding women. Weight loss and increased interest in sex have been reported by some patients. In general, patients maintained on opioid antagonists should be treated with nonopioid cough, antidiarrheal, headache, and pain medications. The patient's family or physician should call the treating physician if questions arise about opioid blockade or analgesia. It is important to realize that naltrexone is not disulfiram; drinking while maintained on naltrexone does not produce side effects or symptoms. Naltrexone works best when it is used in the context of a full spectrum of treatment services, possibly including traditional 12-step fellowship-based treatments. Studies show also that naltrexone is effective when coupled with cognitive behavioral therapies (CBT). Patients receiving medical management with naltrexone, CBT, or both fared better on drinking outcomes. Nalmefene hydrochloride (Revex) is newer opioid antagonist given intravenously. It may be advantageous to use in place of naltrexone as it has not shown signs of liver toxicity and may bind to more opiate receptors. In a study of 105 alcohol dependent patients randomly assigned to weekly CBT and 10 mg nalmefene twice daily, 40 mg nalmefene twice daily, or placebo, both doses of nalmefene were found to be effective.

Acamprosate

Acamprosate (Campral) is a synthetic compound that has a chemical structure similar to that of the naturally occurring amino acid neurotransmitters homotaurine and GABA. Because chronic alcohol use is associated with decreased GABA and glutamate activity, a hyperexcitable glutamate system is one possible alcohol withdrawal mechanism. Glutamate systems may become unstable for 12 months after a person stops drinking. The effect on abstinence, combined with an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol dependence. A dose of 2,000 mg/day is associated with the greatest efficacy regardless of body weight. It is important to note that medication in combination with therapies can improve outcomes. In July 2004, after many years of safe use in Europe and around the world, the FDA approved the use of acamprosate for the maintenance of alcohol abstinence. As in the case of naltrexone, acamprosate reduces the reinforcing (pleasurable) effects of alcohol to reduce craving. Common side effects include diarrhea, anxiety, insomnia, nausea, dizziness, and weakness. Some research indicates that acamprosate may worsen depression and/or suicidal ideation; so, patients with a history of major depression should be monitored closely or prescribed a different medication. An analysis of many studies of acamprosate published in 2006 showed a benefit in maintaining abstinence when coupled with CBT.

Baclofen

Baclofen is a GABA agonist that may prove to be a unique therapeutic alternative to reduce alcohol craving and consumption. In a small, 12-week trial, alcohol-dependent patients were given 10 mg of baclofen 3 times daily paired with motivational enhancement therapy. Patients experienced a reduction in number of drinks, drinking days, anxiety, and craving. In a study of alcohol-dependent patients with liver cirrhosis, baclofen was also found to work favorably in maintenance of alcohol abstinence. Seventy-one percent of baclofen-treated patients maintained abstinence as compared with 29% of the placebo group.

Anticonvulsants

Research has demonstrated that topiramate is efficacious in decreasing heavy drinking among individuals with alcohol dependence. In a controlled study, topiramate produced significant and meaningful improvement in a wide variety of drinking outcomes. Topiramate may suppress the craving and rewarding effects of alcohol. In a double-blind, controlled trial, 150 alcohol dependent patients were randomized to escalating doses of topiramate (25-300 mg/day) or placebo. Those on topiramate had a reduction in self-reported drinking (number of drinks and drinking days), alcohol craving, and plasma y-glutamyl transferase (an indicator of alcohol consumption). Side effects of topiramate include numbness in the extremities, fatigue, confusion, paresthesias, depression, change in taste, and weight loss. Carbamazepine has proven effective for treating acute alcohol withdrawal. Its side effects include nausea, vomiting, drowsiness, dizziness, chest pain, headache, trouble urinating, numbness in extremities, liver damage, and allergic reaction. In a 12-month, double-blind, placebo-controlled trial, 29 patients were assigned to carbamazepine 3 times daily (to reach an average blood level of 6 mg/liter) or placebo. Those treated with carbamazepine showed a delay in time to first drink and a decrease in number of drinks and drinking days (14). Oxcarbazepine is a carbamazepine derivative, with fewer side effects and contraindications, used to prevent relapse in alcohol-dependent patients by blocking alcohol withdrawal. A group of 84 detoxified alcohol dependent patients were randomized to 50 mg naltrexone, 1500-1800 mg oxcarbazepine, or 600-900 mg oxcarbazepine for 90 days. Approximately 58.6% of the high-dose oxcarbazepine patients remained alcohol free, a significantly larger number as compared to the low-dose (42.8%) and naltrexone groups (40.7%).

Summary:

Addiction constitutes a major health problem, yet so many addicts are left untreated. With the mounting evidence that verifies addiction as a disease, it is the hope that these individuals will be less harshly judged and have more access to treatment. Today, it is understood that addiction is a disease that impacts reward, memory and learning, motivation, and decision making. An essential element in the recovery for chemical dependency is the use of 12-step recovery. It is understood, however, that recovery is remission from the disease, that there is no cure. Because addicts are individuals, individualized treatment plans based on personality profiles assist in this process, as does extended aftercare and monitoring.

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Published: 22 December 2009

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