Definition

Amphetamines are a group of powerful and highly addictive substances that dramatically affect the central nervous system. They induce a feeling of well-being and improve alertness, attention, and performance on various cognitive and motor tasks. Closely related are the socalled “designer amphetamines,” the most well known of which is the “club drug” MDMA, best known as “ecstasy.” Finally, some over-the-counter drugs used as appetite suppressants also have amphetamine-like action. Amphetamine-related disorders refer to the effects of abuse, dependence, and acute intoxication stemming from inappropriate amphetamine and amphetamine-related drug usage.

Description

Several amphetamines are currently available in the United States. These include dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and methylphenidate (Ritalin). These Schedule II stimulants, known to be highly addictive, require a triplicate prescription that cannot be refilled. Amphetamines are also known as sympathomimetics, stimulants, and psychostimulants. Methamphetamine, the most common illegally produced amphetamine, goes by the street name of “speed,” “meth,” and “chalk.” When it is smoked, it is called “ice,” “crystal,” “crank,” and “glass.” Methamphetamine is a white, odorless, bitter-tasting crystalline powder that dissolves in water or alcohol.

The leaves of the East African bush Catha edulis can be chewed for their stimulant effects. This drug, cathinone or Khat, has an effect on most of the central nervous system, in addition providing the other properties of amphetamines. Illegal laboratories have begun making methcathinone, which has effects similar to cathinone. Methcathinone, also known as “crank,” is easily synthesized from ephedrine or pseudoephedrine.

Amphetamines were initially produced for medical use, and were first used in nasal decongestants and bronchial inhalers. Early in the 1900s, they were also used to treat several medical and psychiatric conditions, including narcolepsy (a rare condition in which an individuals falls asleep at dangerous and inappropriate moments and cannot maintain normal alertness), attention-deficit disorders, obesity, and depression. They are still used to treat these disorders today.

Amphetamine-like substances called ephedrine and propranolamine are available over the counter in the United States and are used as nasal decongestants. Phenylpropanolamine is also used as an appetite suppressant, and is available over the counter as well. These are less potent than the classic amphetamines, but are still subject to abuse, partly because of their ready availability and low price.

In the 1970s, governmental agencies initiated restrictions increasing the difficulty of obtaining amphetamines legally through prescription. During this same time period, a drug chemically related to the amphetamines began to be produced. This so-called designer drug, best known as “ecstasy,” but also as MDMA, XTC, and Adam, has behavioral effects that combine amphetamine-like and hallucinogen-like properties.

The structure of amphetamines differs significantly from that of cocaine, even though both are stimulants with similar behavioral and physiological effects. Like cocaine, amphetamine results in an accumulation of the neurotransmitter dopamine. It is this excessive dopamine concentration that appears to produce the stimulation and feelings of euphoria experienced by the user. Cocaine is much more quickly metabolized and removed from the body, whereas amphetamines have a much longer duration of action. A large percentage of the drug remains unchanged in the body, leading to prolonged stimulant effects.

The handbook that mental health professionals use to diagnose mental disorders is the Diagnostic and Statistical Manual of Mental Disorders, also known as the DSM. The 2000 edition of this manual (the Fourth Edition Text Revision, also known as DSM-IV-TR) describes four separate amphetamine-related disorders. These are:

• Amphetamine dependence, which refers to chronic or episodic binges (known as “speed runs”), with brief drug-free periods of time in between use.
• Amphetamine abuse, which is less severe than dependence. Individuals diagnosed with amphetamine abuse have milder but nevertheless still substantial problems due to their drug usage.
• Amphetamine intoxication, which refers to serious maladaptive behavioral or psychological changes that develop during, or shortly after, use of an amphetamine or related substance.
• Amphetamine withdrawal, which refers to symptoms that develop within a few hours to several days after reducing or stopping heavy and prolonged amphetamine use. Withdrawal symptoms are, in general, opposite to those seen during intoxication and include fatigue, vivid and unpleasant dreams, insomnia or hypersomnia (too much sleep), increased appetite and agitation or slowing down.

Causes and symptoms

Causes

All amphetamines are rapidly absorbed when taken orally, and even more rapidly absorbed when smoked, snorted, or injected. Tolerance develops with both standard and designer amphetamines, leading to the need for increasing doses by the user.

The classic amphetamines, dextroamphetamine, methamphetamine, and methylphenidate, produce their primary effects by causing the release of catecholamines, especially dopamine, in the brain. These effects are particularly strong in areas of the brain associated with pleasure, specifically, the cerebral cortex and the limbic system, known as the “reward pathway.” The effect on this pathway is probably responsible for the addicting quality of the amphetamines. Catecholamines are any of several compounds found naturally in the body and act as hormones or neurotransmitters in the sympathetic nervous system. Dopamine, an intermediate substance that emerges from the biosynthesis of ephinephrine and norepinephrine, is one of those compounds.

Designer amphetamines, most notably MDMA, causes the release of catecholamines, dopamine and norepinephrine; and in addition, releases serotonin. Serotonin, also a neurotransmitter, produces hallucinogenic effects. The clinical effects of designer amphetamines blend the effects of classic amphetamines with those of hallucinogenic drugs, such as LSD.

Symptoms

CLASSIC AMPHETAMINES. According to the DSM-IVTR, symptoms of heavy, chronic, or episodic use of amphetamine, known as amphetamine dependence, can be very serious. Amphetamine dependence is characterized by compulsive drug-seeking and drug use leading to functional and molecular changes in the brain. Aggressive or violent behavior may occur, especially when high doses are ingested. The individual may develop anxiety or paranoid ideas, also with the possibility of experiencing terrifying psychotic episodes that resemble schizophrenia, with visual or auditory hallucinations, delusions such as the sensation of insects creeping on the skin, known as “formication.” hyperactivity, hypersexuality, confusion, and incoherence. Amphetamine-induced psychosis differs from true psychosis in that despite other symptoms, the disorganized thinking that is a hallmark of schizophrenia tends to be absent. Amphetamine dependence consistently affects relationships at home, school and/or work.

Amphetamine abuse is less serious than dependence, but can cause milder versions of the symptoms described above, as well as problems with family, school, and work. Legal problems may stem from aggressive behavior while using, or from obtaining drugs illegally. Individuals may continue to use despite the awareness that usage negatively impacts all areas of their lives.

Acute amphetamine intoxication begins with a “high” feeling which may be followed by feelings of euphoria. The user experiences enhanced energy, becoming more outgoing and talkative, and more alert. Other symptoms include anxiety, tension, grandiosity, repetitive behavior, anger, fighting, and impaired judgment.

In both acute and chronic intoxication, the individual may experience dulled feelings, along with fatigue or sadness, and social withdrawal. These behavioral and psychological changes are accompanied by other signs and symptoms including increased or irregular heartbeat, dilation of the pupils, elevated or lowered blood pressure, heavy perspiring or chills, nausea and/or vomiting, motor agitation or retardation, muscle weakness, respiratory depression, chest pain, and eventually confusion, seizures, coma, or a variety of cardiovascular problems, including stroke. With amphetamine overdoses, death can result if treatment is not received immediately. Long-term abuse can lead to memory loss as well, and contributes to increased transmission of hepatitis and HIV/AIDs. Impaired social and work functioning is another hallmark of both acute and chronic intoxication.

Following amphetamine intoxication, a “crash” occurs with symptoms of anxiety, shakiness, depressed mood, lethargy, fatigue, nightmares, headache, perspiring, muscle cramps, stomach cramps, and increased appetite. Withdrawal symptoms usually peak in two to four days and are gone within one week. The most serious withdrawal symptom is depression, possibly very severe and leading to suicidal thoughts.

DESIGNER AMPHETAMINES. Use of so-called designer amphetamines, the best-known of which is MDMA, leads to symptoms of classic amphetamine use. Users report a sense of feeling unusual closeness with other people and enhanced personal comfort. They describe seeing an increased luminescence of objects in the environment, although these hallucinogenic effects are less than those caused by other hallucinogens, such as LSD. Some psychotherapists have suggested further research into the possible use of designer amphetamines in conjunction with psychotherapy. This idea is highly controversial, however.

Like classic amphetamines, use of MDMA produces cardiovascular effects of increased blood pressure, heart rate, and heart oxygen consumption. People with preexisting heart disease are at increased risk of cardiovascular catastrophe resulting from MDMA use. MDMA is not processed and removed from the body quickly, and remains active for a long period of time. As a result, toxicity may rise dramatically when users take multiple doses over brief time periods, leading to harmful reactions such as dehydration, hyperthermia, and seizures.

MDMA tablets often contain other drugs, such as ephedrine, a stimulant, and dextromethorphan, a cough suppressant with PCP-like effects at high doses. These additives increase the harmful effects of MDMA. It appears also to have toxic effects on the brain’s serotonin system. In tests of learning and memory, MDMA users perform more poorly than nonusers. Research with primates show that MDMA can cause long-lasting brain damage. Exposure to MDMA during the period of pregnancy in which the fetal brain is developing is associated with learning deficits that last into adulthood.

Demographics

Classic amphetamines

Amphetamine dependence and abuse occur at all levels of society, most commonly among 18- to 30-year-olds. Intravenous use is more common among individuals from lower socioeconomic groups, and has a male-to-female ratio of three or four to one. Among non-intravenous users, males and females are relatively equally divided.

An annual study known as the Monitoring the Future Study, or MTF, examines drug use and attitudes related to drugs held by American teenagers. It focuses primarily on teens in the eighth, 10th, and 12th grades, but also on young adults across the country. Recent data on methamphetamine use showed that in 1997, 4.4% of 12th graders had tried crystal methamphetamine at least once in their lifetime. This represented an increase from 2.7% in 1990. Also in 1997, 2.3% of seniors reported having used crystal methamphetamine at least once during the past year. This represented an increase from 1.3% in 1990.

According to the 2000 National Household Survey on Drug Abuse, approximately 8.8 million Americans have tried methamphetamine at some time during their lives. Data from the 2000 Drug Abuse Warning Network (DAWN), which collects information on drug usage problems from emergency room departments in 21 metropolitan areas found that methamphetamine-related problems increased from 10,400 in 1999 to 13,500 in 2000, an increase of 30%.

Treatment admissions reports by the National Institute of Drug Abuse (NIDA) Community Epidemiology Work Group, or CEWG, showed that as of June 2001, methamphetamine usage continued to be the leading drug of abuse among clients in treatment in the San Diego area and Hawaii. Methamphetamine is the most prevalent illegal drug in San Diego. Both San Francisco and Honolulu also reported substantial methamphetamine use problems during the late 1990s. Increased use was also reported in Denver, Los Angeles, Minneapolis/St.Paul, Phoenix, Seattle, and Tucson.

Definition

Amphetamines are a group of drugs that stimulate the central nervous system. Some of the brand names of amphetamines sold in the United States are Dexedrine, Biphetamine, Das, Dexampex, Ferndex, Oxydess II, Spancap No 1, Desoxyn, and Methampex. Some generic names of amphetamines include amphetamine, dextroamphetamine, and methamphetamine.

Purpose

Amphetamines stimulate the nervous system and are used in the treatment of depression, attention-deficit disorder, obesity, and narcolepsy, a disorder that causes individuals to fall asleep at inappropriate times during the day. Amphetamines produce considerable side effects and are especially toxic in large quantities. Amphetamines are commonly abused recreational drugs and are highly addictive.

Description

Amphetamines are usually given orally and their effects can last for hours. Amphetamines produce their effects by altering chemicals that transmit nerve messages in the body.

Recommended dosage

The typical dose for amphetamines in the treatment of narcolepsy in adults ranges from 5 mg to 60 mg per day. These daily doses are usually divided into at least two small doses taken during the day. Doses usually start on the low end of the range and are increased until the desired effects occur. Children over the age of 12 years with narcolepsy receive 10 mg per day initially. Children between the ages of six and 12 years start with 5 mg per day. The typical dose for adults with obesity ranges from 5 mg to 30 mg per day given in divided doses. The medication is usually given about one-half hour to one hour before meals.

The typical starting dose of amphetamines given to children with attention-deficit disorder over the age of six years is 5 mg per day. This is increased by 5 mg per day over a period of time until the desired effect is achieved. Children under the age of six years with this condition are usually started at 2.5 mg per day.

Precautions

People who are taking amphetamines should not stop taking these drugs suddenly. The dose should be lowered gradually and then discontinued. Amphetamines should only be used while under the supervision of a physician. People should generally take the drug early in the day so that it does not interfere with sleep at night. Hazardous activities should be avoided until the person’s condition has been stabilized with medication. The effects of amphetamine can last up to 20 hours after the medication has last been taken. Amphetamine therapy given to women for medical reasons does not present a significant risk to the developing fetus for congenital disorders. In such cases, there may be mild withdrawal in the newborn. However, illicit use of amphetamines for non-medical reasons presents a significant risk to the fetus and the newborn because of uncontrolled doses.

Amphetamines are highly addictive and should be used only if alternative approaches have failed. They should be used with great caution in children under three years of age, anyone with a history of slightly elevated blood pressure, people with neurological tics, and in individuals with Tourette’s syndrome. Amphetamines should not be taken by individuals with a history of an overactive thyroid, those with moderate-to-severe high blood pressure, those with the eye disease called glaucoma, those who have severe arteriosclerosis (hardening of the arteries), or anyone with psychotic symptoms (hallucinations and delusions). Individuals with a history of drug abuse, psychological agitation, or cardiovascular system disease should also not receive amphetamine therapy. In addition, patients who have taken MAO inhibitors, a type of antidepressant, within the last 14 days should not receive amphetamines. MAO inhibitors include phenelzine (Nardil), and tranylcypromine (Parnate).

Side effects

The most common side effects that are associated with amphetamines include the development of an irregular heartbeat, increased heart rate, increased blood pressure, dizziness, insomnia, restlessness, headache, shakiness, dry mouth, metallic taste, diarrhea, constipation, and weight loss. Other side effects can include changes in sexual drive, nausea, vomiting, allergic reactions, chills, depression, irritability, and other problems involving the digestive system. High doses, whether for medical purposes or illicit ones, can cause addiction, dependence, increased aggression, and, in some cases, psychotic episodes.

Interactions

Patients taking amphetamines should always tell their physicians and dentists that they are using this medication. Patients should consult their physician before taking any over-the-counter medication while taking amphetamines. The interaction between over-the-counter cold medications with amphetamine, for instance, is particularly dangerous because this combination can significantly increase blood pressure. Such cold medications should be avoided when using amphetamine unless a physician has carefully analyzed the combination.

The combination of amphetamines and antacids slows down the ability of the body to eliminate the amphetamine. Furazolidone (Furoxone) combined with amphetamine can significantly increase blood pressure. Sodium bicarbonate can reduce the amount of amphetamine eliminated from the body and dangerously increase amphetamine levels in the body. Certain medications taken to control high blood pressure, including guanadrel (Hylorel) and guanethidine (Ismelin), MAO inhibitors, and selegiline (Eldepryl) should not be used in conjunction with amphetamines. In addition, tricyclic antidepressants [including desipramine (Norpramin) and imipramine (Tofranil)], antihistamines, and anticonvulsant drugs should not be combined with amphetamines.

Definition

Amoxapine is an oral tricyclic antidepressant. Formerly sold in the United States under the brand name Asendin, it is now manufactured and sold only under its generic name.

Purpose

Amoxapine is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, amoxapine has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, enuresis (bed-wetting), eating disorders such as bulimia nervosa, cocaine dependency, and the depressive phase of bipolar (manic-depressive) disorder. It has also been used to support smoking cessation programs.

Description

Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Amoxapine acts primarily by increasing the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, by blocking the action of another brain chemical, acetylcholine. Amoxapine shares most of the properties of other tricyclic antidepressants, such as amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, and trimipramine. Studies comparing amoxapine with these other drugs have shown that amoxapine is no more or less effective than other antidepressants of its type. Its choice for treatment is as much a function of physician preference as any other factor.

The therapeutic effects of amoxapine, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking amoxapine should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.

Recommended dosage

As with any antidepressant, amoxapine must be adjusted by the physician to produce the desired therapeutic effect. Amoxapine is available as 25-mg, 50-mg, 100-mg, and 150-mg oral tablets. Therapy is usually started at 100 to 150 mg per day and increased to 200 to 300 mg daily by the end of the first week. If no improvement is seen at this dose after two weeks, the physician may increase the dose up to 400 mg per day in outpatients and up to 600 mg per day in hospitalized patients. Doses up to 300 mg may be given in single or divided doses. Doses of more than 300 mg per day should be divided in two or three doses daily.

Because of changes in drug metabolism of older patients, starting at about age 60, the initial dose of amoxapine should be adjusted downward to 50 to 75 mg per day and increased to 100 to 150 mg daily by the end of the first week. Some older patients may require up to 300 mg daily, but doses should never be increased beyond that.

Precautions

Like all tricyclic antidepressants, amoxapine should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if amoxapine is the right antidepressant for them.

A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then patients taking amoxapine should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when amoxapine is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take amoxapine in combination with these substances. Amoxapine may increase the possibility of having seizures. Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use amoxapine only with caution and be closely monitored by their physician.

Amoxapine may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must receive amoxapine, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.

Side effects

Amoxapine shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.

Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.

Men with prostate enlargement who take amoxapine may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.

Interactions

Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as amoxapine, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, amoxapine should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil (phenelzine sulfate) or Parmate (tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting amoxapine or any other tricyclic antidepressant. The same holds true when discontinuing amoxapine and starting an MAO inhibitor.

Amoxapine may decrease the blood pressure–lowering effects of clonidine. Patients who take both drugs should be monitored for loss of blood-pressure control and the dose of clonidine may be increased as needed.

The sedative effects of amoxapine are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia. The anticholinergic effects of amoxapine are additive with other anticholinergic drugs such as benztropine, biperiden, trihexyphenidyl, and antihistamines.

Definition

Amnesia is a partial or total loss of memory.

Description

There are numerous causes of amnesia, including stroke, injury to the brain, surgery, alcoholism, encephalitis (inflammation of the brain), and electroconvulsive therapy (ECT, a treatment for various mental disorders in which electricity is sent to the brain through electrodes).

Contrary to the popular notion of amnesia—in which a person suffers a severe blow to the head, for example, and cannot recall his or her past life and experiences—the principal symptom of amnesia is the inability to retain new information, beginning at the point at which the amnesia began. The capacity to recall past experiences may vary, depending on the severity of the amnesia.

There are two types of amnesia: retrograde and anterograde. Retrograde amnesia refers to the loss of memory of one’s past, and can vary from person to person. Some retain virtually full recall of things that happened prior to the onset of amnesia; others forget only their recent past, and still others lose all memory of their past lives. Anterograde amnesia refers to the inability to recall events or facts introduced since the amnesia began.

Amnesia is not always obvious to the casual observer—motor skills such as tying shoelaces and bike riding are retained, as is the ability to read and comprehend the meaning of words. Because of this phenomenon, researchers have suggested that there is more than one area of the brain used to store memory. General knowledge and perceptual skills may be stored in a memory separate from the one used to store personal facts.

Childhood amnesia, a term coined by Anna Freud in the late 1940s, refers to the fact that most people cannot recall childhood experiences during the first three to five years of life. It has been suggested that this type of amnesia occurs because children and adults organize memories in different ways based on their brain’s physical development. Others believe children begin remembering facts and events once they have accumulated enough experience to be able to relate experiences to each other.

Definition

The amnestic disorders are a group of disorders that involve loss of memories previously established, loss of the ability to create new memories, or loss of the ability to learn new information. As defined by the mental health professional’s handbook, the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (2000), also known as DSM-IV-TR, the amnestic disorders result from two basic causes: general medical conditions that produce memory disturbances; and exposure to a chemical (drug of abuse, medication, or environmental toxin). An amnestic disorder whose cause cannot be definitely established may be given the diagnosis of amnestic disorder not otherwise specified.

Description

The amnestic disorders are characterized by problems with memory function. There is a range of symptoms associated with the amnestic disorders, as well as differences in the severity of symptoms. Some people experience difficulty recalling events that happened or facts that they learned before the onset of the amnestic disorder. This type of

amnesia is called retrograde amnesia. Other people experience the inability to learn new facts or retain new memories, which is called anterograde amnesia. People with amnestic disorders do not usually forget all of their personal history and their identity, although memory loss of this degree of severity occurs in rare instances in patients with dissociative disorders.

Causes and symptoms

Causes

In general, amnestic disorders are caused by structural or chemical damage to parts of the brain. Problems remembering previously learned information vary widely according to the location and the severity of brain damage. The ability to learn and remember new information, however, is always affected in an amnestic disorder.

Amnestic disorder due to a general medical condition can be caused by head trauma, tumors, stroke, or cerebrovascular disease (disease affecting the blood vessels in the brain). Substance-induced amnestic disorder can be caused by alcoholism, long-term heavy drug use, or exposure to such toxins as lead, mercury, carbon monoxide, and certain insecticides. In cases of amnestic disorder caused by alcoholism, it is thought that the root of the disorder is a vitamin deficiency that is commonly associated with alcoholism, known as Korsakoff’s syndrome. The causes of transient global amnesia, or TGA, are unclear.

Symptoms

In addition to problems with information recall and the formation of new memories, people with amnestic disorders are often disoriented with respect to time and space, which means that they are unable to tell an examiner where they are or what day of the week it is. Most patients with amnestic disorders lack insight into their loss of memory, which means that they will deny that there is anything wrong with their memory in spite of evidence to the contrary. Others will admit that they have a memory problem but have no apparent emotional reaction to their condition. Some persons with amnestic disorders undergo a personality change; they may appear apathetic or bland, as if the distinctive features of their personality have been washed out of them.

Some people experiencing amnestic disorders confabulate, which means that they fill in memory gaps with false information that they believe to be true. Confabulation should not be confused with intentional lying. It is much more common in patients with temporary amnestic disorders than it is in people with long-term amnestic disorders.

Transient global amnesia (TGA) is characterized by episodes during which the patient is unable to create new memories or learn new information, and sometimes is unable to recall past memories. The episodes occur suddenly and are generally short. Patients with TGA often appear confused or bewildered.

Demographics

The overall incidence of the amnestic disorders is difficult to estimate. Amnestic disorders related to head injuries may affect people in any age group. Alcohol-induced amnestic disorder is most common in people over the age of 40 with histories of prolonged heavy alcohol use. Amnestic disorders resulting from the abuse of drugs other than alcohol are most common in people between the ages of 20 and 40. Transient global amnesia usually appears in people over 50. Only 3% of people who experience transient global amnesia have symptoms that recur within a year.

Diagnosis

Amnestic disorders may be self-reported, if the patient has retained insight into his or her memory problems. More often, however, the disorder is diagnosed because a friend, relative, employer, or acquaintance of the patient has become concerned about the memory loss or recognizes that the patient is confabulating, and takes the patient to a doctor for evaluation. Patients who are disoriented, or whose amnesia is associated with head trauma or substance abuse, may be taken to a hospital emergency room.

The doctor will first examine the patient for signs or symptoms of traumatic injury, substance abuse, or a general medical condition. He or she may order imaging studies to identify specific areas of brain injury, or laboratory tests of blood and urine samples to determine exposure to environmental toxins or recent consumption of alcohol or drugs of abuse. If general medical conditions and substance abuse are ruled out, the doctor may administer a brief test of the patient’s cognitive status, such as the mini-mental state examination or MMSE. The MMSE is often used to evaluate a patient for dementia, which is characterized by several disturbances in cognitive functioning (speech problems, problems in recognizing a person’s face, etc.) that are not present in amnestic disorders. The doctor may also test the patient’s ability to repeat a string of numbers (the so called digit span test) in order to rule out delirium. Patients with an amnestic disorder can usually pay attention well enough to repeat a sequence of numbers where as patients with delirium have difficulty focusing or shifting their attention. In some cases the patient may also be examined by a neurologist (a doctor who specializes in disorders of the central nervous system)

If there is no evidence of a medical condition or substance use that would explain the patient’s memory problems, the doctor may test the patient’s memory several times in order to rule out malingering or a factitious disorder. Patients who are faking the symptoms of an amnestic disorder will usually give inconsistent answers to memory tests if they are tested more than once.

DSM-IV-TR specifies three general categories of amnestic disorders. These are: amnestic disorder due to a general medical condition, substance-induced persisting amnestic disorder, and amnestic disorder not otherwise specified. The basic criterion for diagnosing an amnestic disorder is the development of problems remembering information or events that the patient previously knew, or inability to learn new information or remember new events. In addition, the memory disturbance must be sufficiently severe to affect the patient’s social and occupational functioning, and to represent a noticeable decline from the patient’s previous level of functioning. DSM-IV-TR also specifies that the memory problems cannot occur only during delirium, dementia, substance use or withdrawal.

Treatments

There are no treatments that have been proved effective in most cases of amnestic disorder, as of 2002. Many patients recover slowly over time, and sometimes recover memories that were formed before the onset of the amnestic disorder. Patients generally recover from transient global amnesia without treatment. In people judged to have the signs that often lead to alcohol-induced persisting amnestic disorder, treatment with thiamin may stop the disorder from developing.

Prognosis

Amnestic disorders caused by alcoholism do not generally improve significantly over time, although in a small number of cases the patient’s condition improves completely. In many cases the symptoms are severe, and in some cases warrant long-term care for the patient to make sure his or her daily needs are met. Other substance induced amnestic disorders have a variable rate of recovery, although in many cases full recovery does eventually occur. Transient global amnesia usually resolves fully.

Prevention

Amnestic disorders resulting from trauma are not generally considered preventable. Avoiding exposure to environmental toxins, refraining from abuse of alcohol or other substances, and maintaining a balanced diet may help to prevent some forms of amnestic disorders.

Definition

Amitriptyline is a medication used to treat various forms of depression, pain associated with the nerves (neuropathic pain), and to prevent migraine headaches. It is sold in the United States under the brand names Elavil and Endep.

Purpose

Amitriptyline helps relieve depression and pain. This medication, usually given at bedtime, also helps patients sleep better.

Description

This medication is one of several tricyclic antidepressants, so-called because of the three-ring chemical structure common to these drugs. Amitriptyline acts to block reabsorption of neurotransmitters (chemicals that transmit nerve messages in the brain). Amitriptyline and the other tricyclic antidepressants are primarily used to treat mental depression but are increasingly being replaced by a newer and more effective group of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs). Amitriptyline is sometimes prescribed to help treat pain associated with cancer. In addition, it is sometimes prescribed for various types of chronic pain. Tablets are available in 10, 25, 50, 70, and 150 mg.

Recommended dosage

The usual adult dose for pain management ranges from 10 mg to 150 mg at bedtime. Patients are generally started on a low dose and the amount may be increased as needed. Side effects, such as a dry mouth and drowsiness, may make it difficult to increase the dose in older adults. Bedtime dosing helps the patient sleep. Doctors generally prescribe 75–150 mg for depression. It is given at bedtime or in divided doses during the day. It may take 30 days for the patient to feel less depressed. Pain relief is usually noticed sooner than the mood change. Teens and older adults usually receive a lower dose. If the nightly dose is missed, it should not be taken the next morning. Taking amitriptyline during waking hours could result in noticeable side effects. Patients should check with their doctor if the daily dose is missed. Those on more than one dose per day should take a missed dose as soon as it is remembered but should not take two doses at the same time. While amitriptyline is usually administered orally, injectable amitriptyline is available. It should not be used in this form long-term; patients should switch to tablets as soon as possible.

Precautions

Patients should not stop taking this medication suddenly. The dose should gradually be decreased, then discontinued. If the drug is stopped abruptly, the patient may experience headache, nausea, or discomfort throughout the body, and a worsening of original symptoms. The effects of the medication last for three to seven days after it has been stopped, and older patients usually are more prone to some side effects such as drowsiness, dizziness, mental confusion, blurry vision, dry mouth, difficulty urinating, and constipation. Taking a lower dose may help resolve these problems. Patients may need to stop this medication before surgery.

Amitriptyline should not be given to anyone with allergies to the drug or to patients recovering from a heart attack. Patients taking the monoamine oxidase inhibitors (MAOIs) Parnate (tranylcypromine) and Nardil (phenelzine) —different types of antidepressants—should not use amitriptyline in combination. It should be administered with caution to patients with glaucoma, seizures, urinary retention, overactive thyroid, poor liver or kidney function, alcoholism, asthma, digestive disorders, enlarged prostate, seizures, or heart disease. This medication should not be given to children under 12 years of age. Pregnant women should discuss the risks and benefits of this medication with their doctor as fetal deformities have been associated with taking this drug during pregnancy. Women should not breast feed while using amitriptyline.

Side effects

Common side effects include dry mouth, drowsiness, constipation, and dizziness or lightheadedness when standing. Patients can suck on ice cubes or sugarless hard candy to combat the dry mouth. Increased fiber in the diet and additional fluids may help relieve constipation. Dizziness is usually caused by a drop in blood pressure when suddenly changing position. Patients should slowly rise from a sitting or lying position if dizziness is noticed. Amitriptyline may increase the risk of falls in older adults. Patients should not drive or operate machinery or appliances while under the influence of this drug. Alcohol and other central nervous system depressants can increase drowsiness. Amitriptyline may also produce blurry vision, irregular or fast heartbeat, high or low blood pressure, palpitations, and an increase or decrease in a diabetic patient’s blood sugar levels. Patients’ skin may become more sensitive to the sun and thus direct sunlight should be avoided by wearing protective clothing and the application of sunscreen with a protective factor of 15 or higher.

Amitriptyline may increase appetite, cause weight gain, or produce an unpleasant taste in the mouth. It may also cause diarrhea, vomiting, or heartburn. Taking this medication with food may decrease digestive side effects. Other less likely side effects include muscle tremors, nervousness, impaired sexual function, sweating, rash, itching, hair loss, ringing in the ears, or changes in the makeup of the patient’s blood. Patients with schizophrenia may develop an increase in psychiatric symptoms.

Interactions

Patients should always tell all doctors and dentists that they are taking this medication. It may decrease the effectiveness of some drugs used to treat high blood pressure and should not be taken with other antidepressants, epinephrine and other adrenaline-type drugs, or methylphenidate. Patients should not take over-thecounter medications without checking with their doctor. For instance, amitriptyline should not be taken with Tagamet (cimetidine) or Neosynephrine. Patients taking this drug should avoid the dietary supplements St. John’s wort, belladonna, henbane, and scopolia. Black tea may decrease the absorption of this drug. Patients should ingest the drug and tea at least two hours apart.

Definition

Amantadine is a synthetic antiviral agent that also has strong antiparkinsonian properties. It is sold in the United States under the brand name Symmetrel, and is also available under its generic name.

Purpose

Amantadine is used to treat a group of side effects (called parkinsonian side effects) that include tremors, difficulty walking, and slack muscle tone. These side effects may occur in patients who are taking antipsychotic medications used to treat mental disorders such as schizophrenia. An unrelated use of amantadine is in the treatment of viral infections of some strains of influenza A.

Description

Some medicines, called antipsychotic drugs, that are used to treat schizophrenia and other mental disorders can cause side effects similar to the symptoms of Parkinson’s disease. The patient does not have Parkinson’s disease, but he or she may experience shaking in muscles while at rest, difficulty with voluntary movements, and poor muscle tone. These symptoms are similar to the symptoms of Parkinson’s disease.

One way to eliminate these undesirable side effects is to stop taking the antipsychotic medicine. Unfortunately, the symptoms of the original mental disorder usually come back, so in most cases simply stopping the antipsychotic medication is not a reasonable option. Some drugs such as amantadine that control the symptoms of Parkinson’s disease also control the parkinsonian side effects of antipsychotic medicines.

Amantadine works by restoring the chemical balance between dopamine and acetylcholine, two neuro-transmitter chemicals in the brain. Taking amantadine along with the antipsychotic medicine helps to control symptoms of the mental disorder, while reducing parkinsonian side effects. Amantadine is in the same family of drugs (commonly known as anticholinergic drugs) as biperiden and trihexyphenidyl.

Recommended dosage

Amantadine is available in 100-mg tablets and capsules, as well as a syrup containing 50 mg of amantadine in each teaspoonful. For the treatment of drug-induced parkinsonian side effects, amantadine is usually given in a dose of 100 mg orally twice a day. Some patients may need a total daily dose as high as 300 mg. Patients who are taking other antiparkinsonian drugs at the same time may require lower daily doses of amantadine (100 mg daily, for example).

People with kidney disease or who are on hemodialysis must have their doses lowered. In these patients, doses may range from 100 mg daily to as little as 200 mg every seven days.

Precautions

Amantadine increases the amount of the neurotransmitter dopamine (a central nervous system stimulant) in the brain. Because of this, patients with a history of epilepsy or other seizure disorders should be carefully monitored while taking this drug. This is especially true in the elderly and in patients with kidney disease. Amantadine may cause visual disturbances and affect mental alertness and coordination. People should not operate dangerous machinery or motor vehicles while taking this drug.

Side effects

Five to ten percent of patients taking amantadine may experience the following nervous system side effects:

• dizziness or lightheadedness
• insomnia
• nervousness or anxiety
• impaired concentration

One to five percent of patients taking amantadine may experience the following nervous system side effects:

• irritability or agitation
• depression
• confusion
• lack of coordination
• sleepiness or nightmares
• fatigue
• headache

In addition, up to 1% of patients may experience hallucinations, euphoria (excitement), extreme forgetfulness, aggressive behavior, personality changes, or seizures. Seizures are the most serious of all the side effects associated with amantadine.

Gastrointestinal side effects may also occur in patients taking amantadine. Five to ten percent of people taking this drug experience nausea and up to 5% have dry mouth, loss of appetite, constipation, and vomiting. In most situations, amantadine may be continued and these side effects treated symptomatically.

One to five percent of patients taking amantadine have also reported a bluish coloring of their skin (usually on the legs) that is associated with enlargement of the blood vessels (called livedo reticularis). This side effect usually appears within one month to one year of starting the drug and subsides within weeks to months after the drug is discontinued. People who think they may be experiencing this or other side effects from any medication should tell their physician.

Interactions

Taking amantadine along with other drugs used to treat parkinsonian side effects may cause increased confusion or even hallucinations. The combination of amantadine and central nervous system stimulants (such as amphetamines or decongestants) may cause increased central nervous stimulation or increase the likelihood of seizures.

Definition

Alzheimer’s disease, or AD, is a progressive, incurable disease of the brain caused by the degeneration and eventual death of neurons (nerve cells) in several areas of the brain.

Description

Patients with AD first lose such mental functions as short-term memory and the ability to learn new things. In the later stages of AD they gradually lose control over their sense of orientation, their emotions, and other aspects of behavior. End-stage AD is characterized by loss of control of body functions, an increased likelihood of seizures, loss of the ability to eat or swallow, and eventual death from infection or malnutrition. Alzheimer’s disease is the most common cause of dementia (loss of cognitive abilities) in the elderly; it is thought to be responsible for 50%–70% of cases of dementia in the United States.

Alzheimer’s disease was first identified in 1906 by a German psychiatrist and neuroanatomist named Alois Alzheimer. He was studying slides prepared from the brain of a fifty-one-year-old woman, known as Frau D., who had died after several years of dementia with symptoms that did not fit the definition of any brain disorder known at the time. Alzheimer was the first to describe the plaques and neurofibrillary tangles that are now used to identify AD at autopsy. Plaques are clumps or clusters of dead or dying nerve cells and other cellular debris found in the brains of patients with Alzheimer’s disease. Neurofibrillary tangles are the accumulations of twisted protein fragments found inside the nerve cells in the brains of Alzheimer’s patients. Because dementia had been associated with elderly people and Frau D. had been middle-aged, AD was first known as presenile dementia and was thought to be a very rare disorder. It was not until the early 1950s that researchers at St. Elizabeth’s Hospital in Washington, DC, came to recognize that AD is the single most common cause of dementia in adults.

Alzheimer’s disease is now considered a very serious public health problem because of the growing numbers of people who are affected by it, the increasing length of their lives, and the direct and indirect costs of their care. It is estimated that four million people in the United States had AD as of 2000, with 360,000–400,000 new cases identified every year. One person in ten over the age of 65 has AD, and nearly 50% of those over 85 have the disease. Unless a cure or preventive treatment is discovered, 14 million Americans will have Alzheimer’s by 2050. Very few people are wealthy enough to cover the cost of caring for an Alzheimer’s patient in the seven–10 years that typically extend between the beginning of the person’s dependency and death. The average lifetime cost of caring for one patient with AD is estimated at $174,000. The costs of laboratory tests, physicians’ visits, medications, nursing services, home care, and adult day care come to $114.4 billion per year in the United States alone. This sum is greater than the combined annual budgets of six Federal departments (Commerce, Education, Justice, Labor, Energy, and Interior).

The problem is expected to be complicated in future years by the fact that the so-called “baby boomer” generation is better nourished and better educated than the generation now at risk for AD. When the baby boomers are old enough to be at risk for late-onset Alzheimer’s, they are expected to live longer than the average Alzheimer’s patient does in 2002. Public health researchers who are making future projections about the impact of AD in the mid-twenty-first century point out that a treatment that would delay the onset of the disease would reduce the overall prevalence of AD. One study estimates that a therapy that would delay the onset of Alzheimer’s by only one year would save the United States $9 billion by 2007. The second approach, that of discovering a treatment for people who already have Alzheimer’s, would alter the proportion of mild cases to those considered moderate or severe. The researchers conclude by stating: “None of our models predicts less than a threefold rise in the total number of persons with Alzheimer’s disease between 2000 and 2050.”

Types of Alzheimer’s disease

As of 2002, some researchers think that Alzheimer’s may be more accurately described as a group or family of diseases rather than a single disease. Moreover, more recent research is helping to differentiate Alzheimer’s disease from other less common causes of dementia. In particular, some cases of dementia that were formerly thought to have been related to AD are now known to have been caused by Pick’s disease or Lewy body dementia. Pick’s disease is a rare type of dementia that affects certain areas of the brain and is characterized by a progressive loss of social skills, language, and memory. Lewy body dementia is a type of dementia in which the brain has characteristic Lewy bodies—areas of injury found on damaged nerve cells in certain parts of the brain.

Physicians now recognize three different forms of Alzheimer’s disease.

EARLY-ONSET AD. Early-onset AD is a rare form of Alzheimer’s found in fewer than 10% of AD patients. This group of patients, however, develops more of the brain abnormalities associated with AD than patients with the late-onset form. In addition, patients with early-onset Alzheimer’s are more likely to develop myoclonus (a condition in which a muscle or group of muscles has sudden spasms or twitching).

LATE-ONSET AD. Late-onset AD is the most common form of the disease; its symptoms usually begin to appear after age 65. Late-onset Alzheimer’s, which may or may not be affected by genetic variables, is also called sporadic Alzheimer’s disease because it does not necessarily run in families.

FAMILIAL ALZHEIMER’S DISEASE (FAD). Familial Alzheimer’s disease, or FAD, is a rare form that is entirely inherited. FAD accounts for fewer than 5% of all cases of AD. It has a very early onset, often in the patient’s 40s, and there is a clear family history of the disease.

Stages

Health care professionals use the term “insidious” to describe Alzheimer’s, which means that it is very gradual in onset. Many times people recognize the first symptoms of the disorder in a friend or family member only in hindsight. In addition, the present generation of people old enough to be at risk for Alzheimer’s is the first generation in history to know what the diagnosis means; there are therefore very powerful emotional reasons for attributing the early signs of AD to normal aging, job stress, adjusting to retirement, and other less troubling factors. The insidious onset of Alzheimer’s is a characteristic, however, that allows doctors to distinguish it from other causes of dementia, including vascular dementia.

EARLY-STAGE ALZHEIMER’S. Early-stage Alzheimer’s may begin almost imperceptibly. The first symptoms usually include short-term memory loss, temporary episodes of spatial disorientation, groping for words while one is speaking, minor problems with arithmetic, and small errors of judgment. For example, the person may light a stove burner under a saucepan before noticing that he has forgotten to put the food or water in the pan first, or he may have difficulty balancing a checkbook as quickly as he used to. At this stage in the disease, however, the patient can usually keep up with most activities of daily life. Although some persons at this point can still operate a motor vehicle safely, it is advisable to consult a physician about possible impairment behind the wheel. Many patients with early-stage AD voluntarily give up their driver’s licenses for their own safety and that of other drivers on the roads.

MIDDLE-STAGE ALZHEIMER’S. In the middle stage, which typically begins two to three years after onset, the person begins to lose awareness of his or her cognitive deficits. Memory lapses are more frequent and the person begins to have more severe problems with language. Unlike early-stage AD, the problems caused by loss of cognitive functioning are impossible to ignore. The middle stage of AD is the point at which the behavioral and psychiatric symptoms that are so stressful to caregivers often begin— the agitation, wandering, temper outbursts, depression, and disorientation. The patient is at high risk for falls and similar accidents. In addition, the patient becomes increasingly unable to understand simple instructions or to follow a conversation, and begins to lose his or her basic sense of personal identity.

END-STAGE ALZHEIMER’S. End-stage Alzheimer’s is marked by the loss of the ability to walk and eventually even to sit up. Patients may be able to use a wheelchair for awhile but eventually become completely bedridden. They lose bladder and bowel control. When the disease begins to affect the patient’s brain stem, the basic processes of digestion, respiration, and excretion shut down. Patients usually stop eating at this point and sleep most of the time. The hands and feet begin to feel cold, the breathing becomes shallow, and the patient is generally unresponsive to caregivers. Eventually the patient’s breathing simply stops.

Causes and symptoms

Causes

Evidence has accumulated that Alzheimer’s disease is multifactorial— that is, it is caused by a combination of several genetic and environmental factors.

GENETIC. Early-onset AD is caused by a defect in one of three genes known as APP, presenilin-1, and presenilin-2, found on human chromosomes 21, 14, and 1, respectively. Early-onset AD is also associated with Down syndrome, in that people with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop this form of Alzheimer’s. The brains of people with Down syndrome age prematurely, so that those who develop early-onset AD are often only in their late 40s or early 50s when the symptoms of the disease first appear.

Genetic research indicates that late-onset Alzheimer’s disease is a polygenic disorder; that is, its development is influenced by more than one gene. It has been known since 1993 that a specific form of a gene for apolipoprotein E (apoE4) on human chromosome 19 is a genetic risk factor for late-onset AD. People who have the apoE4 gene from one parent have a 50% chance of developing AD; a 90% chance if they inherited the gene from both parents. They are also likely to develop AD earlier in life. One of the remaining puzzles about this particular gene, however, is that it is not a consistent marker for AD. In other words, some people who have the apoE4 gene do not develop Alzheimer’s, and some who do not have the gene do develop the disorder. In 1998 another gene on chromosome 12 that controls the production of bleomycin hydrolase (BH, an enzyme involved in the body’s processing of amyloid precursor protein) was identified as a second genetic risk factor that acts independently of the APOE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of a particular protein is also involved in the development of late-onset AD.

Familial Alzheimer’s disease appears to be related to abnormal genes on human chromosomes 21 and 14.

NEUROBIOLOGICAL. Investigators since Alois Alzheimer’s time have studied the abnormalities found at autopsy in the brains of patients with AD. One abnormality is plaques, or clumps, of a starchy protein called beta amyloid. Beta amyloid is formed when a substance called amyloid precursor protein, or APP, fails to be metabolized properly in the body. APP is a substance found in many parts of the body, but its precise function is not yet known. Following the formation of beta amyloid, pieces of it then stick to one another and gradually build up into plaques. The other abnormal finding is neurofibrillary tangles, which are twisted threads formed from parts of the dying nerve cell called the tau protein, which was discovered in 1986. If the tau protein is damaged by the addition of molecules of phosphorus, a process called hyperphosphorylation, it forms filaments that twist around each other to form the neurofibrillary tangles. As the plaques and tangles accumulate in the brain, they cause the nerve cells to wither and eventually die. As the nerve cells die, the affected parts of the brain start to shrink in size. It is not known as of 2002, however, whether the plaques and tangles are causes of AD or results of it. The relationship between the plaques and the tangles is another question that has not yet been answered. Although the plaques usually appear in brain tissue before the tangles, it is not clear that they cause the tangles. There are other brain disorders, such as Pick’s disease, in which tangles appear in the brain cells without plaques.

Another nervous system abnormality in AD is the lowered level of neurotransmitters produced by the cells in the brain. Neurotransmitters are chemicals that carry nerve impulses across the small gaps (synapses) between nerve cells. The neurotransmitters whose production is affected by Alzheimer’s include serotonin, norepinephrine, and acetylcholine. Many of the behavioral and psychiatric problems associated with AD are thought to result from the inadequate supply of these neurotransmitters.

ENVIRONMENTAL. Researchers have been studying the possibility that certain chemicals or other toxins in the environment may have a role in causing or triggering AD. The environmental factors that have been considered include aluminum, zinc, toxins in contaminated food, and viruses. Although there is little evidence as of 2002 that AD is caused by a virus or other infectious agent, the possibility cannot be completely excluded.

Other hypotheses about the causes of Alzheimer’s include damage caused by oxidation, estrogen deficiency, and inflammation. All of these possibilities are presently under investigation.

RISK FACTORS. A number of factors have been identified that increase a person’s risk of developing Alzheimer’s:

• Age. The risk of developing AD rises after age 65, and rises sharply after age 75. While 1% of the population has AD at age 65, almost 50% of those over 85 have it.
• Sex. Women are more likely to develop AD than men. As of 2002, however, it is not known whether women are more susceptible to the disorder, or more likely to develop it because they live longer than men, on average.
• Family history of AD.
• Having Down syndrome.
• History of head injury.
• Substances in the environment. Higher-than-average amounts of aluminum have been found in the brains of patients with Alzheimer’s. Some researchers in the late 1990s thought that exposure to aluminum might be a risk factor for the disorder. It now appears that the levels of aluminum in the brains of patients are a result rather than a cause of AD.
• Low occupational attainment and education level. Studies have found a clear correlation between employment in jobs that are not mentally challenging and an increased risk of AD. In addition, taking less rather than more challenging jobs as one grows older is associated with a higher risk of AD.
• High systolic blood pressure.
• High blood cholesterol levels. When both high systolic blood pressure and high cholesterol are present, the risk of developing AD increases by a factor of 3.5.
• Mild cognitive impairment (MCI). Mild cognitive impairment is a transitional decline in cognitive functioning that precedes the onset of AD. MCI is characterized primarily by memory loss while other cognitive functions remain intact. People with MCI are at higher risk for AD than people who do not develop the condition; 12% of people with mild cognitive impairment develop Alzheimer’s disease each year, compared with 1–2% per year of people without MCI. After four years, 40% of people diagnosed with mild cognitive impairment have clear symptoms of Alzheimer’s disease.

• Amnesia. Amnesia refers to memory impairment; however, loss of short-term memory also means that the patient loses his or her sense of time as well.
• Aphasia. Aphasia refers to loss of language function. The person may not remember the names of objects and may use words like “thing” or “it” instead; they may echo what other people say or repeat a word or phrase over and over. On occasion the person may lose the ability to speak except for curse words.
• Apraxia. Apraxia is the loss of the ability to perform voluntary movements in the absence of paralysis. A person with apraxia, for example, may have trouble putting on a hospital gown or brushing his or her teeth.
• Agnosia. Agnosia comes from a Latin word that means “to not know”, and refers to inability to recognize familiar places and people. Patients with agnosia may even fail to recognize their own face in a mirror.

Definition

Alcoholism is defined as alcohol seeking and consumption behavior that is harmful. Long-term and uncontrollable harmful consumption can cause alcohol-related disorders that include: antisocial personality disorder, mood disorders (bipolar and major depression) and anxiety disorders.

Description

Alcoholism is the popular term for the disorder recognized by the American Psychiatric Association (APA) as alcohol dependence. The hallmarks of this disorder are addiction to alcohol, inability to stop drinking, and repeated interpersonal, school- or work-related problems that can be directly attributed to the use of alcohol. Alcoholism can have serious consequences, affecting an individual’s health and personal life, as well as impacting society at large.

Alcohol dependence is a complex disorder that includes the social and interpersonal issues mentioned above, and also includes biological elements, as well. These elements are related to tolerance and withdrawal, cognitive (thinking) problems that include craving, and behavioral abnormalities including the impaired ability to stop drinking. Withdrawal is a term that refers to the symptoms that occur when a person dependent on a substance stops taking that substance for a period of time; withdrawal symptoms vary in type and severity depending on the substance, but alcohol withdrawal symptoms can include shaking, irritability, and nausea. Tolerance is a reduced response to the alcohol consumed and can be acute or chronic. Acute tolerance occurs during a single episode of drinking and is greater when blood alcohol concentration rises. Chronic tolerance occurs over the long term when there is greater resistance to the intoxicating effects of alcohol, and, as a result, the affected person has to drink more to achieve desired effect.

The APA also recognizes another alcohol use disorder called alcohol abuse. Alcohol abuse is similar to dependence in that the use of alcohol is impairing the affected person’s ability to achieve goals and fulfill responsibilities, and his or her interpersonal relationships are affected by the alcohol abuse. However, unlike a person with dependence, a person diagnosed with alcohol abuse does not experience tolerance or, when not drinking, withdrawal symptoms. People who abuse alcohol can become dependent on the substance over time.

Alcohol-related disorders are groups of disorders that can result in persons who are long-term users of alcohol. These disorders can affect the person’s metabolism, gastrointestinal tract, nervous system, bone marrow (the matter in bones that forms essential blood cells) and can cause endocrine (hormone) problems. Additionally, alcoholism can result in nutritional deficiencies. Some common alcohol-related medical disorders include vitamin deficiencies, alterations in sugar and fat levels in blood, hepatitis, fatty liver, cirrhosis, esophagitis (inflammation of the esophagus), gastritis (inflammation of the lining of the stomach), dementia, abnormal heart rates and rhythms, lowered platelets (cells important for forming a clot), leukopenia (decrease in the number of white blood cells that are important for body defenses and immunity), and testicular atrophy (shrinking of the testicles). People with anxiety, depression, or bipolar disorder may consume alcohol for temporary relief from their symptoms. Others, such as people with antisocial personality disorder, may use alcohol as part of a dual diagnosis of criminality and substance dependence.

Causes and symptoms

Causes

The cause of alcoholism is related to behavioral, biological, and genetic factors.

Behaviorally, alcohol consumption is related to internal or external feedback. Internal feedback is the internal state a person experiences during and after alcohol consumption. External feedback is made up of the cues that other people send the person when he or she drinks. Internal states pertaining to alcohol can include shame or hangover. Alcohol-related external cues can include reprimands, criticism, or encouragement. People may drink to the point of dependence because of peer pressure, acceptance in a peer group, or because drinking is related to specific moods (easygoing, relaxed, calm, sociable) that are related to the formation of intimate relationships.

Biologically, repeated use of alcohol can impair the brain levels of a “pleasure” neurotransmitter called dopamine. Neurotransmitters are chemicals in the brain that pass impulses from one nerve cell to the next. When a person is dependent on alcohol, his or her brain areas that produce dopamine become depleted and the individual can no longer enjoy the pleasures of everyday life— his or her brain chemistry is rearranged to depend on alcohol for transient euphoria (state of happiness).

Genetic studies have isolated a gene that causes alcohol dependence and that is usually transmitted from affected fathers to sons. Other genetic studies have demonstrated that close relatives of an alcoholic are four times more likely to become alcoholics themselves. Furthermore, this risk holds true even for children who were adopted away from their biological families at birth and raised in a nonalcoholic adoptive family, with no knowledge of their biological family’s difficulties with alcohol.

Symptoms

ALCOHOL DEPENDENCE. Individuals who are alcohol-dependent compulsively drink ethanol (the chemical name for alcohol) to the level of intoxication. Intoxication occurs at blood alcohol levels of 50 to 150 mg/dl and is characterized by euphoria at first, and then if blood concentrations of alcohol continue to rise, a person can become explosively combative. Neurologically, acute intoxication causes impaired thinking, incoordination, slow or irregular eye movements, and impaired vision. As the person repeatedly drinks, the body develops a reduced response to ethanol called tolerance.

People with chronic tolerance may apparently be sober (not intoxicated) even after consumption of alcohol that could cause death in non-drinkers. People with alcohol dependence may also develop alcoholic blackouts after large amounts of ethanol consumption. These blackouts are typically characterized by amnesia (loss of memory) lasting several hours without impaired consciousness. In other words, people experiencing blackouts appear to be conscious, but will not remember their actions during the blackouts after the intoxication has worn off.

People with alcohol dependence also develop alcohol withdrawal (a state of non-drinking) syndrome. The nervous system adapts to chronic ethanol exposure by increasing the activity of nerve cell mechanisms that counteract alcohol’s depressant effects. Therefore, when drinking is abruptly reduced, the affected person develops disordered perceptions, seizures, tremor (often accompanied by irritability, nausea, and vomiting). Tremor of the hands called “morning shakes,” usually occurs in the morning due to overnight abstinence. The most serious manifestation of alcohol withdrawal syndrome is delirium tremens, which occurs in approximately 5% of people dependent on alcohol. Delirium tremens consists of agitation, disorientation, insomnia, hallucinations, delusions, intense sweating, fever, and increased heart rate (tachycardia). This state is a medical emergency because it can be fatal, and affected persons must be immediately hospitalized and treated with medications that control vital physiological functions.

The APA publishes a manual for mental health professionals called the Diagnostic and Statistical Manual of Mental Disorders, also known as the DSM. This manual lists criteria that each disorder must meet for diagnosis. The criteria are symptoms that must be present so that the diagnosis can be made. Alcohol dependence can be diagnosed if three or more of the following symptoms are present:

• tolerance
• withdrawal
• denial of problem
• preoccupation with seeking alcohol
• drinking is the focal point of person’s life (using takes up most of the person’s time)
• continued use despite problems

ALCOHOL ABUSE. In order for a person to be diagnosed with alcohol abuse, one of the following four criteria must be met. Because of drinking, a person repeatedly:

• fails to live up to his or her most important responsibilities
• physically endangers him- or herself, or others (for example, by drinking when driving)
• gets into trouble with the law
• experiences difficulties in relationships or jobs

Demographics

The lifetime prevalence in the general population for alcoholism is between 9.4% and 14.1%. The disorder occurs twice as often in males than in females. Alcoholism and alcohol abuse affect 20% or more of hospitalized and ambulatory patients (those receiving care on an outpatient basis). Alcoholism can develop in all people of all races and socioeconomic classes. Approximately two-thirds of Americans older than 14 years drink alcohol. People who drink excessive amounts of alcohol account for about half of the total alcohol consumed, and account for almost all the socioeconomic and medical complications of alcoholism at an annual cost of $100 billion. Alcoholism ranks third in the United States as a preventable disease and accounts for 5% of the total deaths in the U.S. amounting to about 100,000 people dying annually.

Diagnosis

The diagnosis of alcoholism can either be based on medical and/or psychological conditions. With a long-term history of abusive drinking, medical conditions can result, and these could lead the physician to suspect a patient’s alcoholism. These medical conditions may include organ complications such as: cirrhosis (liver), hepatitis (liver), pancreatitis (pancreas), peripheral neuropathy (nervous system) or cardiomyopathy (heart). Additionally, recurrent trauma, resulting in bone fractures, fatigue, depression, sexual dysfunction, fluctuating blood pressure, and sleep disorders may prompt the clinician to further assess for alcoholism.

Psychological diagnosis can be accomplished through a clinical interview and history (biopsychosocial assessment), and from a choice of many standardized alcohol use tests. The biopsychosocial assessment is an extensive interview conducted by the clinician. During the interview, the clinician will ask the patient about many areas of life, including childhood, education, and medical history. One very simple tool for beginning the diagnosis of alcoholism is called the CAGE questionnaire. It consists of four questions, with the first letters of each key word spelling out the word CAGE:

• Have you ever tried to Cut down on your drinking?
• Have you ever been Annoyed by anyone’s comments about your drinking?
• Have you ever felt Guilty about your drinking?
• Do you ever need an Eye-opener (a morning drink of alcohol) to start the day?

Other, longer lists of questions exist to help determine the severity and effects of a person’s alcohol use. Given the recent research pointing to a genetic basis for alcoholism, the doctor will also attempt to ascertain whether anyone else in the person’s family has ever suffered from alcoholism.

Diagnosis is sometimes facilitated when family members call the attention of a physician to a loved one’s difficulties with alcohol.

Treatments

Comprehensive treatment for alcohol dependence has two components: detoxification and rehabilitation.

Detoxification

The goal of detoxification is to rid the patient’s body of the toxic effects of alcohol. Because the person’s body has become accustomed to alcohol, the person will need to be supported as he or she goes through withdrawal. Withdrawal will be different for different patients, depending on the severity of the alcoholism, as measured by the quantity of alcohol ingested daily and the length of time the patient has been dependent on alcohol. Withdrawal symptoms can range from mild to life-threatening. Mild withdrawal symptoms include nausea, achiness, diarrhea, difficulty sleeping, sweatiness, anxiety, and trembling. This phase is usually over in about three to five days. More severe effects of withdrawal can include hallucinations (in which a patient sees, hears, or feels something that is not actually real), seizures, a strong craving for alcohol, confusion, fever, fast heart rate, high blood pressure, and delirium (a fluctuating level of consciousness). Patients at highest risk for delirium tremens are those with other medical problems, including malnutrition, liver disease, or Wernicke’s syndrome. Delirium tremens usually begins about three to five days after the patient’s last drink, progressing from the more mild symptoms to the more severe, and may last a number of days.

Patients going through mild withdrawal are simply monitored carefully to make sure that more severe symptoms do not develop. No medications are necessary, however. Treatment of a patient suffering the more severe effects of withdrawal may require the use of sedative medications to relieve the discomfort of withdrawal and to avoid the potentially life-threatening complications of high blood pressure, fast heart rate, and seizures. Benzodiazepines are medications that ease tension by slowing down the central nervous system and may be helpful in those patients suffering from hallucinations. Because of the patient’s nausea, fluids may need to be given through a vein (intravenously), along with some necessary sugars and salts. It is crucial that thiamin be included in the fluids, because thiamin is usually quite low in patients with alcohol dependence, and deficiency of thiamin is responsible for Wernicke-Korsakoff syndrome.

Rehabilitation

After cessation of drinking has been accomplished, the next steps involve helping the patient stay healthy and avoid relapsing. (Relapse occurs when a patient returns to old behaviors that he or she was trying to change.) This phase of treatment is referred to as rehabilitation. The best programs incorporate the family into the therapy, because the family has undoubtedly been severely affected by the patient’s drinking. Some therapists believe that family members, in an effort to deal with their loved one’s drinking problem, sometimes develop patterns of behavior that accidentally support or “enable” the patient’s drinking. This situation is referred to as “co-dependence,” and must be addressed in order to treat a person’s alcoholism successfully.

PSYCHOLOGICAL THERAPIES.Psychotherapy helps affected individuals to anticipate, understand, recognize, and prevent relapse. Behavioral therapy approaches typically include community-centered support groups, meetings such as Alcoholics Anonymous (AA), cognitive-behavioral therapy (CBT), and Motivated Enhancement Therapy (MET). CBT focuses on teaching alcoholics recognition and coping skills for craving states and high-risk situations that precipitate or trigger relapsing behaviors. MET can motivate patients to use their personal resources to initiate changes in behavior. Many people recovering from substance dependence find peerled support groups helpful in helping them avoid relapse.

MEDICATIONS. Two medications called naltrexone (Revia) and acamprosate can help decrease craving states in alcoholics. In combination with psychotherapy, these medications can help reduce relapse. Another medication called disulfiram (Antabuse) affects the metabolism of alcohol and causes unpleasant effects in patients who consume alcohol while taking the medication. Antabuse should only be taken by people who are committed to recovery and understand that they are to avoid all contact with alcohol or alcohol-containing products. People who have alcohol dependence along with other disorders, such as depression, can work with their physician to determine if medication might be a feasible treatment option for them.

ADDITIONAL TREATMENTS. Alternative treatments can be a helpful adjunct for the alcoholic patient, once the medical danger of withdrawal has passed. Because many alcoholics have very stressful lives (whether because of or leading to the alcoholism is sometimes a matter of debate), many of the treatments for alcoholism involve managing and relieving stress. These include massage, meditation, and hypnotherapy. The malnutrition of long-term alcohol use is addressed by nutrition-oriented practitioners and dietitians with careful attention to a healthy diet and the use of nutritional supplements such as vitamins A, B complex, and C, as well as certain fatty acids, amino acids, zinc, magnesium, and selenium. Acupuncture is believed to decrease both withdrawal symptoms and to help improve a patient’s chances for continued recovery from alcoholism.

Prognosis

Most people who use alcohol start to drink during adolescence or early adulthood. Approximately 50% of male drinkers have alcohol-related problems such as fighting, blackouts, or legal problems during their early drinking years, usually late teens or early twenties. People who cannot control their drinking behaviors will tend to accumulate drinking-related problems and become dependent on alcohol. Approximately 30% to 60% of alcoholics maintain about one year of sobriety with psychotherapeutic interventions alone. About 20% of alcoholics can achieve long-term abstinence without any type of active treatment.

Prevention

Good prevention includes education and a knowledge of family (genetic) propensity. If alcohol dependence is present in a close family member, then relatives should know and be discouraged to drink alcohol-containing beverages. Education of older children and young teenagers concerning the negative effects and consequences of drinking alcohol may help to decrease or recognize problems before start or worsen.

Definition

Agoraphobia is an anxiety disorder characterized by intense fear related to being in situations from which escape might be difficult or embarrassing (i.e., being on a bus or train), or in which help might not be available in the event of a panic attack or panic symptoms. Panic is defined as extreme and unreasonable fear and anxiety.

According to the handbook used by mental health professionals to diagnose mental disorders, the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, also known as the DSM-IV-TR, patients with agoraphobia are typically afraid of such symptoms as feeling dizzy, having an attack of diarrhea, fainting, or “going crazy.”

The word “agoraphobia” comes from two Greek words that mean “fear” and “marketplace.” The anxiety associated with agoraphobia leads to avoidance of situations that involve being outside one’s home alone, being in crowds, being on a bridge, or traveling by car or public transportation. Agoraphobia may intensify to the point that it interferes with a person’s ability to take a job outside the home or to carry out such ordinary errands and activities as picking up groceries or going out to a movie.

Description

The close association in agoraphobia between fear of being outside one’s home and fear of having panic symptoms is reflected in DSM-IV-TR classification of two separate disorders: panic disorder (PD) with agoraphobia, and agoraphobia without PD. PD is essentially characterized by sudden attacks of fear and panic. There may be no known reason for the occurrence of panic attacks; they are frequently triggered by fear-producing events or thoughts, such as driving, or being in an elevator. PD is believed due to an abnormal activation of the body’s hormonal system, causing a sudden “fight-or-flight” response.

The chief distinction between PD with agoraphobia and agoraphobia without PD is that patients who are diagnosed with PD with agoraphobia meet all criteria for PD; in agoraphobia without PD, patients are afraid of panic-like symptoms in public places, rather than full-blown panic attacks.

People with agoraphobia appear to suffer from two distinct types of anxiety— panic, and the anticipatory anxiety related to fear of future panic attacks. Patients with agoraphobia are sometimes able to endure being in the situations they fear by “gritting their teeth,” or by having a friend or relative accompany them.

In the United States’ diagnostic system, the symptoms of agoraphobia can be similar to those of specific phobia and social phobia. In agoraphobia and specific phobia, the focus is fear itself; with social phobia, the person’s focus is on how others are perceiving him/her. Patients diagnosed with agoraphobia tend to be more afraid of their own internal physical sensations and similar cues than of the reactions of others per se. In cases of specific phobia, the person fears very specific situations, whereas in agoraphobia, the person generally fears a variety of situations (being outside of the home alone, or traveling on public transportation including a bus, train, or automobile, for example). An example of a patient diagnosed with a specific phobia rather than agoraphobia would be the person whose fear is triggered only by being in a bus, rather than a car or taxi. The fear of the bus is more specific than the agoraphobic’s fear of traveling on public transportation in general. The DSM-IVTR remarks that the differential diagnosis of agoraphobia “can be difficult because all of these conditions are characterized by avoidance of specific situations.”

Causes and symptoms

Causes

GENETIC. As of 2002, the causes of agoraphobia are complex and not completely understood. It has been known for some years that anxiety disorders tend to run in families. Recent research has confirmed earlier hypotheses that there is a genetic component to agoraphobia, and that it can be separated from susceptibility to PD. In 2001 a team of Yale geneticists reported the discovery of a genetic locus on human chomosome 3 that governs a person’s risk of developing agoraphobia. PD was found to be associated with two loci: one on human chromosome 1 and the other on chromosome 11q. The researchers concluded that agoraphobia and PD are common; they are both inheritable anxiety disorders that share some, but not all, of their genetic loci for susceptibility.

INNATE TEMPERAMENT. A number of researchers have pointed to inborn temperament as a broad vulnerability factor in the development of anxiety and mood disorders. In other words, a person’s natural disposition or temperament may become a factor in developing a number of mood or anxiety disorders. Some people seem more sensitive throughout their lives to events, but upbringing and life history are also important factors in determining who will develop these disorders. Children who manifest what is known as “behavioral inhibition” in early infancy are at increased risk for developing more than one anxiety disorder in adult life—particularly if the inhibition remains over time. (Behavioral inhibition refers to a group of behaviors that are displayed when the child is confronted with a new situation or unfamiliar people.) These behaviors include moving around, crying, and general irritability, followed by withdrawing, seeking comfort from a familiar person, and stopping what one is doing when one notices the new person or situation. Children of depressed or anxious parents are more likely to develop behavioral inhibition.

PHYSIOLOGICAL REACTIONS TO ILLNESS. Another factor in the development of PD and agoraphobia appears to be a history of respiratory disease. Some researchers have hypothesized that repeated episodes of respiratory disease would predispose a child to PD by making breathing difficult and lowering the threshold for feeling suffocated. It is also possible that respiratory diseases could generate fearful beliefs in the child’s mind that would lead him or her to exaggerate the significance of respiratory symptoms.

LIFE EVENTS. About 42% of patients diagnosed with agoraphobia report histories of real or feared separation from their parents or other caretakers in childhood. This statistic has been interpreted to mean that agoraphobia in adults is the aftermath of unresolved childhoo