36.11 - Buspirone

Authors: Sadock, Benjamin James; Sadock, Virginia Alcott

Title: Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition

Copyright ©2007 Lippincott Williams & Wilkins

> Table of Contents > 12 - Substance-Related Disorders > 12.6 - Cocaine-Related Disorders

12.6

Cocaine-Related Disorders

Few public health issues attracted as much media attention in the United States during the 1980s and early 1990s as the problems resulting from the use of cocaine and crack, a highly potent form of cocaine. Although the intranasal use of cocaine hydrochloride during that time was associated with high-income, “jet-set” users, since the beginning of the 21st century, smokable crack cocaine has become an endemic drug problem in the inner cities across the United States and around the world.

Cocaine is an alkaloid derived from the shrub Erythroxylon coca, which is indigenous to South America, where the leaves of the shrub are chewed by local inhabitants to obtain the stimulating effects (Fig. 12.6-1). The cocaine alkaloid was first isolated in 1860 and first used as a local anesthetic in 1880. It is still used as a local anesthetic, especially for eye, nose, and throat surgery, for which its vasoconstrictive and analgesic effects are helpful. In 1884, Sigmund Freud made a study of cocaine's general pharmacological effects and, for a period of time, according to his biographers, was addicted to the drug. In the 1880s and 1890s, cocaine was widely touted as a cure for many ills and was listed in the 1899 Merck Manual. It was the active ingredient in the beverage Coca-Cola until 1902. In 1914, however, once its addictive and adverse effects had been recognized, cocaine was classified as a narcotic, along with morphine and heroin.

Definitions

Substance use can be associated with a number of distinct disorders of which dependence and abuse are but two; the text revision of the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) describes ten others for cocaine. Cocaine dependence is defined in DSM-IV-TR as a cluster of physiological, behavioral, and cognitive symptoms that, taken together, indicate that the person continues to use cocaine despite significant problems related to such use. It is defined in the 10th revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) as a cluster of physiological, behavioral, and cognitive phenomena in which a person gives much higher priority to cocaine use than to other

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behaviors that once had a greater value. Central to these definitions is the emphasis placed on the drug-using behavior, its maladaptive nature, and how over time the voluntary choice to engage in that behavior shifts and becomes constrained as a result of interactions with the drug.

FIGURE 12.6-1 Cocaine is an alkaloid obtained from coca leaves.

The ICD-10 and DSM-IV-TR differ in their classification of what is called substance abuse. ICD-10 does not use the term abuse and includes instead the category of harmful use, which differs substantially from the concept of abuse used in DSM-IV-TR. Moreover, the concept of harm is limited to physical and mental health (e.g., hepatitis, cardiac damage, episodes of depression, or toxic psychosis). It specifically excludes social impairments, as follows: Harmful patterns of use are often criticized by others and frequently associated with adverse social consequences of various kinds. That a pattern of use of a particular substance is disapproved of by another person or by the culture, or may have led to socially negative consequences, such as arrest or marital arguments, is not in itself evidence of harmful use.

Epidemiology

Cocaine Use

In 2002 and 2003, 5.9 million (2.5 percent) persons aged 12 years or older used cocaine in the past year, and more than 2.1 million (0.9 percent) persons used cocaine in the past month. Persons aged 18 to 25 (6.7 percent) had a higher rate of past year cocaine use than persons aged 26 or older (1.9 percent) and youths aged 12 to 17 (1.9 percent). Males (3.4 percent) were more than twice as likely as females (1.6 percent) to have used cocaine in the past year. Asians had the lowest rate of past year cocaine use (0.7 percent) compared with other racial or ethnic groups.

Cocaine Abuse and Dependence

In 2002 and 2003, more than 1.5 million (0.6 percent) persons aged 12 or older met the criteria for abuse of, or dependence on, cocaine in the past year. Persons aged 18 to 25 (1.2 percent) had the highest rate of past year cocaine abuse or dependence, followed by persons aged 26 or older (0.6 percent) and youths aged 12 to 17 (0.4 percent). Males (0.9 percent) were more than twice as likely as females (0.4 percent) to have met the criteria for cocaine abuse or dependence. Blacks (1.1 percent) and Hispanics (0.9 percent) had higher rates of cocaine abuse or dependence than whites (0.5 percent), and the rate for Asians (0.1 percent) was lower than that for blacks, Hispanics, whites, American Indians or Alaskan Natives (1.2 percent), and non-Hispanic persons who identified themselves with two or more races (0.9 percent).

Crack Cocaine

An estimated 1.5 million (0.6 percent) persons aged 12 or older used crack cocaine in the past year, and 586,000 (0.2 percent) persons used crack cocaine in the past month. Persons aged 18 to 25 (0.9 percent) had the highest rate of past year crack use, followed by persons aged 26 or older (0.6 percent) and youths aged 12 to 17 (0.4 percent). Males (0.9 percent) were more than twice as likely as females (0.4 percent) to have used crack cocaine in the past year. Asians had the lowest rate of past year crack cocaine use (0.1 percent) compared with other racial or ethnic groups. Blacks (1.6 percent), American Indians or Alaska Natives (1.3 percent), Native Hawaiians or Other Pacific Islanders (1.2 percent), and persons who identified themselves with two or more non-Hispanic races (1.5 percent) had higher rates of past year crack cocaine use than whites (0.5 percent) and Hispanics or Latinos (0.5 percent).

Current cocaine use is on the decline, primarily because of increased awareness of cocaine's risks as well as a comprehensive public campaign about cocaine and its effects. The societal effects of the decrease in cocaine use, however, have been somewhat offset by the frequent use over the past years of crack.

Comorbidity

As with other substance-related disorders, cocaine-related disorders are often accompanied by additional psychiatric disorders. The development of mood disorders and alcohol-related disorders usually follows the onset of cocaine-related disorders, whereas anxiety disorders, antisocial personality disorder, and attention-deficit/hyperactivity disorder (ADHD) are thought to precede the development of cocaine-related disorders. Most studies of comorbidity in patients with cocaine-related disorders have shown that major depressive disorder, bipolar II disorder, cyclothymic disorder, anxiety disorders, and antisocial personality disorder are the most commonly associated psychiatric

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diagnoses. The percentages of comorbidity in cocaine users are presented in Table 12.6-1.

Table 12.6-1 Additional Psychiatric Diagnoses among Cocaine Users Seeking Treatment (New Haven Cocaine Diagnostic Study Results, Percentages)

Psychiatric Diagnosis Current Disorder Lifetime Disorder
Major depression 4.7 30.5
Cyclothymia/hyperthymia 19.9 19.9
Mania 0.0 3.7
Hypomania 2.0 7.4
Panic disorder 0.3 1.7
Generalized anxiety disorder 3.7 7.0
Phobia 11.7 13.4
Schizophrenia 0.0 0.3
Schizoaffective disorder 0.3 1.0
Alcoholism 28.9 61.7
Antisocial personality disorder—RDC 7.7 7.7
Antisocial personality disorder—DSM-III 32.9 32.9
Attention-deficit disorder   34.9
(Adapted from Rounsaville BJ, Anton SI, Caroll K, et al. Psychiatric diagnoses of treatment-seeking cocaine abusers. Arch Gen Psychiatry. 1991;48:43, with permission.)

Etiology

Genetic Factors

The most convincing evidence to date of a genetic influence on cocaine dependence comes from studies of twins. Monozygotic twins have higher concordance rates for stimulant dependence (cocaine, amphetamines, and amphetamine-like drugs) than dizygotic twins. The analyses indicate that genetic factors and unique (unshared) environmental factors contribute about equally to the development of stimulant dependence.

Sociocultural Factors

Social, cultural, and economic factors are powerful determinants of initial use, continuing use, and relapse. Excessive use is far more likely in countries where cocaine is readily available. Different economic opportunities may influence certain groups more than others to engage in selling illicit drugs, and selling is more likely to be carried out in familiar communities than in those where the seller runs a high risk of arrest.

Learning and Conditioning

Learning and conditioning are also considered important in perpetuating cocaine use. Each inhalation or injection of cocaine yields a “rush” and a euphoric experience that reinforce the antecedent drug-taking behavior. In addition, the environmental cues associated with substance use become associated with the euphoric state so that long after a period of cessation, such cues (e.g., white powder and paraphernalia) can elicit memories of the euphoric state and reawaken craving for cocaine.

In cocaine abusers (but not in normal controls), cocaine-related stimuli activate brain regions subserving episodic and working memory and produce electroencephalographic (EEG) arousal (desynchronization). Increased metabolic activity in the limbic-related regions, such as the amygdala, parahippocampal gyrus, and dorsolateral prefrontal cortex, reportedly correlates with reports of craving for cocaine, but the degree of EEG arousal does not.

Pharmacological Factors

As a result of actions in the central nervous system (CNS), cocaine can produce a sense of alertness, euphoria, and well-being. Users may experience decreased hunger and less need for sleep. Performance impaired by fatigue is usually improved. Some users believe that cocaine enhances sexual performance.

Neuropharmacology

Cocaine's primary pharmacodynamic action related to its behavioral effects is competitive blockade of dopamine reuptake by the dopamine transporter. This blockade increases the concentration of dopamine in the synaptic cleft and results in increased activation of both dopamine type 1 (D1) and type 2 (D2) receptors. The effects of cocaine on the activity mediated by D3, D4, and D5 receptors are not yet well understood, but at least one preclinical study has implicated the D3 receptor. Although the behavioral effects are attributed primarily to the blockade of dopamine reuptake, cocaine also blocks the reuptake of norepinephrine and serotonin. The behavioral effects related to these activities are receiving increased attention in the scientific literature. The effects of cocaine on cerebral blood flow and cerebral glucose use have also been studied. Results in most studies generally showed that cocaine is associated with decreased cerebral blood flow and possibly with the development of patchy areas of decreased glucose use.

The behavioral effects of cocaine are felt almost immediately and last for a relatively brief time (30 to 60 minutes); thus, users require repeated doses of the drug to maintain the feelings of intoxication. Despite the short-lived behavioral effects, metabolites of cocaine can be present in the blood and urine for up to 10 days.

Cocaine has powerful addictive qualities. Because of its potency as a positive reinforcer of behavior, psychological dependence on cocaine can develop after a single use. With repeated administration, both tolerance and sensitivity to various effects of cocaine can arise, although the development of tolerance or sensitivity is apparently caused by many factors and is not easily predicted. Physiological dependence on cocaine does occur, although cocaine withdrawal is mild compared with withdrawal from opiates and opioids.

Researchers recently reported that positron emission tomography (PET) scans of the brains of patients being treated for cocaine addiction show high activation in the mesolimbic dopamine system when addicts profoundly crave a drug. Researchers exposed patients to cues that had previously caused them to crave cocaine, and patients described feelings of intense cravings for the drug while PET scans showed activation in areas from the amygdala and the anterior cingulate to the tip of both temporal lobes. Some researchers claim that the mesolimbic dopamine system is also active in patients with nicotine addiction, and the same system has been linked to cravings for heroin, morphine, amphetamines, marijuana, and alcohol.

The D2 receptors in the mesolimbic dopamine system have been held responsible for the heightened activity during periods of craving. PET scans of patients recovering from cocaine addiction are reported to show a drop in neuronal activity consistent with a lessened ability to receive dopamine, and the reduction in this ability, although it decreases over time, is apparent as long as a year and a half after withdrawal. The pattern of reduced brain activity reflects the course of the craving; between the third and fourth weeks of withdrawal, the activity is at its lowest level, and the risk of patient relapse is highest. After about 1 year,

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the brains of former addicts are almost back to normal, although whether the dopamine cells ever return to a completely normal state is debatable.

Methods of Use

Because drug dealers often dilute cocaine powder with sugar or procaine, street cocaine varies greatly in purity. Cocaine is sometimes cut with amphetamine. The most common method of using cocaine is inhaling the finely chopped powder into the nose, a practice referred to as “snorting” or “tooting.” Other methods of ingesting cocaine are subcutaneous or intravenous (IV) injection and smoking (freebasing). Freebasing involves mixing street cocaine with chemically extracted pure cocaine alkaloid (the freebase) to get an increased effect. Smoking is also the method used to ingest crack cocaine. Inhaling is the least dangerous method of cocaine use; IV injection and smoking are the most dangerous. The most direct methods of ingestion are often associated with cerebrovascular diseases, cardiac abnormalities, and death. Although cocaine can be taken orally, it is rarely ingested via this, the least effective, route.

Crack

Crack, a freebase form of cocaine, is extremely potent. It is sold in small, ready-to-smoke amounts, often called “rocks.” Crack cocaine is highly addictive; even one or two experiences with the drug can cause intense craving for more. Users have been known to resort to extremes of behavior to obtain the money to buy more crack. Reports from urban emergency rooms have also associated extremes of violence with crack abuse.

Diagnosis and Clinical Features

The DSM-IV-TR lists many cocaine-related disorders (Table 12.6-2), but only specifies the diagnostic criteria for cocaine intoxication (Table 12.6-3) and cocaine withdrawal (Table 12.6-4) within the cocaine-related disorders section. The diagnostic criteria for the other cocaine-related disorders are in the DSM-IV-TR sections that focus on the principal symptom—for example, cocaine-induced mood disorder in the mood disorders section (see Table 15.3-10).

Cocaine Dependence and Abuse

The DSM-IV-TR uses the general guidelines for substance dependence and substance abuse to diagnose cocaine dependence and cocaine abuse (see Tables 12.1-3, 12.1-4, and 12.1-5). Clinically and practically, cocaine dependence or cocaine abuse can be suspected in patients who evidence unexplained changes in personality. Common changes associated with cocaine use are irritability, impaired ability to concentrate, compulsive behavior, severe insomnia, and weight loss. Colleagues at work and family members may notice a person's general and increasing inability to perform the expected tasks associated with work and family life. The patient may show new evidence of increased debt or inability to pay bills on time because of the large sums used to buy cocaine. Cocaine abusers often excuse themselves from work or social situations every 30 to 60 minutes to find a secluded place to inhale more cocaine. Because of the vasoconstricting effects of cocaine, users almost always develop nasal congestion, which they may attempt to self-medicate with decongestant sprays.

Table 12.6-2 DSM-IV-TR Cocaine-Related Disorders

Cocaine use disorders
Cocaine dependence
Cocaine abuse
Cocaine-induced disorders
Cocaine intoxication
   Specify if:
      With perceptual disturbances
Cocaine withdrawal
Cocaine intoxication delirium
Cocaine-induced psychotic disorder, with delusions
   Specify if:
      With onset during intoxication
Cocaine-induced psychotic disorder, with hallucinations
   Specify if:
      With onset during intoxication
Cocaine-induced mood disorder
   Specify if:
      With onset during intoxication
      With onset during withdrawal
Cocaine-induced anxiety disorder
   Specify if:
      With onset during intoxication
      With onset during withdrawal
Cocaine-induced sexual dysfunction
   Specify if:
      With onset during intoxication
Cocaine-induced sleep disorder
   Specify if:
      With onset during intoxication
      With onset during withdrawal
Cocaine-related disorder not otherwise specified
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

T. Taylor was a separated, 39-year-old African American man who was admitted to a psychiatric day program in the shelter where he lived when he complained of sudden impulses to stab other residents. The staff in the shelter described him variously as “manipulative” and “charming.” He gives a long history of abuse of alcohol, heroin, and cocaine, but says he has been “clean” for 3 weeks. He reports several arrests for felonies, including armed robbery and kidnapping, for which he always seems to have an explanation that minimizes his own responsibility.

Mr. Taylor entered the city shelter system 2 years earlier when the woman he was living with threw him out because she couldn't tolerate his temper and substance abuse. During his marriage to another woman 20 years ago, he was able to work briefly in blue-collar jobs in between prison and hospital stays. He has not worked for the past 7 years and has never paid child support to his wife.

Life did not begin easily for Mr. Taylor. His father left home before he was born, leaving behind a family scandal. The family story is that his father impregnated his wife's sister, causing Mr. Taylor to be treated like an outcast by the family. His mother had nine children, each with a different father. She had chronic depression and had received extensive psychiatric treatment. All of her children have psychiatric or substance abuse problems.

When Mr. Taylor was 3, his mother turned him over to a succession of reluctant caregivers on both sides of the family. He was physically abused by some of his mother's boyfriends, being whipped with belts and electric cords. He dropped out of school in seventh grade because “a teacher embarrassed me.” He began drinking when he entered the Job Corps at age 16. In his late teens and early 20s, he used nasal cocaine and heroin, then intravenous heroin for about a year. He stopped using drugs in his mid-20s, but continued to binge on alcohol every few weeks.

At age 19, after an argument with his wife, he cut his wrists and was hospitalized for 6 months. He was given an antidepressant, an unknown tranquilizer, and psychotherapy following his discharge, but stopped treatment when he felt better. Over the ensuing 20 years there were multiple hospitalizations when he was suicidal or had violent impulses. At one point he jumped off a bridge, sustaining multiple fractures. He has never exhibited manic symptoms, nor has he ever had delusions or hallucinations.

The one psychiatric chart that was available outlined an extensive criminal record and gives the patient the diagnosis of Antisocial Personality Disorder. His criminal history included charges for multiple armed robberies, desertion and neglect of a minor, and kidnapping of a 20-year-old man. With reference to the last crime, he said that he held the man at bay with a machete while his friends stole the man's car.

Follow-Up

Over a 10-month treatment period, Mr. Taylor exhibited an intense attachment to his female caseworker. He often demanded immediate attention. When frustrated, he would occasionally become intoxicated and verbally abusive. This was especially the case when his caseworker left the program for another job. However, he did refrain from violent behavior and enrolled in a group for drug abusers who also have other psychiatric problems. An anticonvulsant drug helped him control his aggressive impulses. He also received individual and group counseling and social skills training and took part in a work and money-management program.

Mr. Taylor was accepted into a community residence and has been able to maintain his housing and his outpatient treatment in a day program during a 9-month period. He is monitored closely by his shelter caseworker, who intervenes when problems arise. (From DSM-IV-TR Casebook.)

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Table 12.6-3 DSM-IV-TR Diagnostic Criteria for Cocaine Intoxication

  1. Recent use of cocaine.
  2. Clinically significant maladaptive behavioral or psychological changes (e.g., euphoria or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors; impaired judgment; or impaired social or occupational functioning) that developed during, or shortly after, use of cocaine.
  3. Two (or more) of the following, developing during, or shortly after, cocaine use:
    1. tachycardia or bradycardia
    2. pupillary dilation
    3. elevated or lowered blood pressure
    4. perspiration or chills
    5. nausea or vomiting
    6. evidence of weight loss
    7. psychomotor agitation or retardation
    8. muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias
    9. confusion, seizures, dyskinesias, dystonias, or coma
  4. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.
Specify if:
   With perceptual disturbances
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Table 12.6-4 DSM-IV-TR Diagnostic Criteria for Cocaine Withdrawal

  1. Cessation of (or reduction in) cocaine use that has been heavy and prolonged.
  2. Dysphoric mood and two (or more) of the following physiological changes, developing within a few hours to several days after Criterion A:
    1. fatigue
    2. vivid, unpleasant dreams
    3. insomnia or hypersomnia
    4. increased appetite
    5. psychomotor retardation or agitation
  3. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  4. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Cocaine Intoxication

The DSM-IV-TR specifies the diagnostic criteria for cocaine intoxication (Table 12.6-3), which emphasizes the behavioral and physical signs and symptoms of cocaine use. The DSM-IV-TR diagnostic criteria allow for specification of the presence of perceptual disturbances. If hallucinations are present in the absence of intact reality testing, the appropriate diagnosis is cocaine-induced psychotic disorder, with hallucinations.

Persons use cocaine for its characteristic effects of elation, euphoria, heightened self-esteem, and perceived improvement on mental and physical tasks. Some studies have indicated that low doses of cocaine can actually be associated with improved performance on some cognitive tasks. With high doses, however, the symptoms of intoxication include agitation, irritability, impaired judgment, impulsive and potentially dangerous sexual behavior, aggression, a generalized increase in psychomotor activity, and, potentially, symptoms of mania. The major associated physical symptoms are tachycardia, hypertension, and mydriasis.

Cocaine Withdrawal

After cessation of cocaine use or after acute intoxication, postintoxication depression (“crash”) may be associated with

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symptoms of dysphoria, anhedonia, anxiety, irritability, fatigue, hypersomnolence, and sometimes agitation. With mild to moderate cocaine use, these withdrawal symptoms end within 18 hours. With heavy use, as in cocaine dependence, withdrawal symptoms can last up to a week, but usually peak in 2 to 4 days. Some patients and some anecdotal reports have described cocaine withdrawal syndromes that have lasted for weeks or months. The withdrawal symptoms can also be associated with suicidal ideation in affected persons. A person in the state of withdrawal can experience powerful and intense cravings for cocaine, especially because taking cocaine can eliminate the unpleasant withdrawal symptoms. Persons experiencing cocaine withdrawal often attempt to self-medicate with alcohol, sedatives, hypnotics, or antianxiety agents such as diazepam (Valium). The DSM-IV-TR diagnostic criteria for cocaine withdrawal are listed in Table 12.6-4.

Cocaine Intoxication Delirium

The DSM-IV-TR has specified a diagnosis for cocaine intoxication delirium (see Table 10.2-6). Cocaine intoxication delirium is most common when high doses of cocaine are used; when cocaine has been used over a short time, so that cocaine blood concentrations rapidly increase; or when cocaine is mixed with other psychoactive substances (e.g., amphetamine, opiates, opioids, and alcohol). Persons with preexisting brain damage (often resulting from previous episodes of cocaine intoxication) are also at increased risk for cocaine intoxication delirium.

Cocaine-Induced Psychotic Disorder

Paranoid delusions and hallucinations can occur in up to 50 percent of all persons who use cocaine. The occurrence of these psychotic symptoms depends on the dose, the duration of use, and the individual user's sensitivity to the substance. Cocaine-induced psychotic disorders are most common with IV and crack users. Men are much more likely to have psychotic symptoms than are women. Paranoid delusions are the most frequent psychotic symptoms. Auditory hallucinations are also common, but visual and tactile hallucinations may be less common than paranoid delusions. The sensation of bugs crawling just beneath the skin (formication) has been reported to be associated with cocaine use. Psychotic disorders can develop with grossly inappropriate sexual and generally bizarre behavior and homicidal or other violent actions related to the content of the paranoid delusions or hallucinations. The DSM-IV-TR diagnostic criteria of cocaine-induced psychotic disorders are listed in Table 14.4-7. Clinicians can further specify whether delusions or hallucinations are the predominant symptom.

Cocaine-Induced Mood Disorder

The DSM-IV-TR allows for the diagnosis of cocaine-induced mood disorder (see Table 15.3-10), which can begin during either intoxication or withdrawal. Classically, the mood disorder symptoms associated with intoxication are hypomanic or manic; the mood disorder symptoms associated with withdrawal are characteristic of depression.

Cocaine-Induced Anxiety Disorder

The DSM-IV-TR also allows for the diagnosis of cocaine-induced anxiety disorder (see Table 16.7-3). Common anxiety disorder symptoms associated with cocaine intoxication or withdrawal are those of obsessive–compulsive disorder, panic disorders, and phobias.

Cocaine-Induced Sexual Dysfunction

The DSM-IV-TR allows for the diagnosis of cocaine-induced sexual dysfunction (see Table 21.2-17), which can begin when a person is intoxicated with cocaine. Although cocaine is used as an aphrodisiac and as a way to delay orgasm, its repeated use can result in impotence.

Cocaine-Induced Sleep Disorder

Cocaine-induced sleep disorder, which can begin during either intoxication or withdrawal, is described under substance-induced sleep disorders (see Table 24.2-21). Cocaine intoxication is associated with the inability to sleep; cocaine withdrawal is associated with disrupted sleep or hypersomnolence.

Cocaine-Related Disorder Not Otherwise Specified

The DSM-IV-TR provides a diagnosis of cocaine-related disorder not otherwise specified for cocaine-related disorders that cannot be classified into one of the previously discussed diagnoses (Table 12.6-5).

Adverse Effects

A common adverse effect associated with cocaine use is nasal congestion; serious inflammation, swelling, bleeding, and ulceration of the nasal mucosa can also occur. Long-term use of cocaine can also lead to perforation of the nasal septa. Freebasing and smoking crack can damage the bronchial passages and the lungs. The IV use of cocaine can result in infection, embolisms, and the transmission of human immunodeficiency virus (HIV). Minor neurological complications with cocaine use include the development of acute dystonia, tics, and migraine-like headaches. The major complications of cocaine use, however, are cerebrovascular, epileptic, and cardiac. About two thirds of

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these acute toxic effects occur within 1 hour of intoxication, about one fifth occur in 1 to 3 hours, and the remainder occurs up to several days later.

Table 12.6-5 DSM-IV-TR Diagnostic Criteria for Cocaine- Related Disorder Not Otherwise Specified

The cocaine-related disorder not otherwise specified category is for disorders associated with the use of cocaine that are not classifiable as cocaine dependence, cocaine abuse, cocaine intoxication, cocaine withdrawal, cocaine intoxication delirium, cocaine-induced psychotic disorder, cocaine-induced mood disorder, cocaine-induced anxiety disorder, cocaine-induced sexual dysfunction, or cocaine-induced sleep disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Cerebrovascular Effects

The most common cerebrovascular diseases associated with cocaine use are nonhemorrhagic cerebral infarctions. When hemorrhagic infarctions do occur, they can include subarachnoid, intraparenchymal, and intraventricular hemorrhages. Transient ischemic attacks have also been associated with cocaine use. Although these vascular disorders usually affect the brain, spinal cord hemorrhages have also been reported. The obvious pathophysiological mechanism for these vascular disorders is vasoconstriction, but other pathophysiological mechanisms have also been proposed.

Seizures

Seizures have been reported to account for 3 to 8 percent of cocaine-related emergency room visits. Cocaine is the substance of abuse most commonly associated with seizures; the second most common substance is amphetamine. Cocaine-induced seizures are usually single events, although multiple seizures and status epilepticus are also possible. A rare and easily misdiagnosed complication of cocaine use is partial complex status epilepticus, which should be considered as a diagnosis in a patient who seems to have cocaine-induced psychotic disorder with an unusually fluctuating course. The risk of having cocaine-induced seizures is highest in patients with a history of epilepsy who use high doses of cocaine as well as crack.

Cardiac Effects

Myocardial infarctions and arrhythmias are perhaps the most common cocaine-induced cardiac abnormalities. Cardiomyopathies can develop with long-term use of cocaine, and cardioembolic cerebral infarctions can be a further complication of cocaine-induced myocardial dysfunction.

Death

High doses of cocaine are associated with seizures, respiratory depression, cerebrovascular diseases, and myocardial infarctions—all of which can lead to death in persons who use cocaine. Users may experience warning signs of syncope or chest pain but may ignore these signs because of the irrepressible desire to take more cocaine. Deaths have also been reported with the ingestion of “speedballs,” which are combinations of opioids and cocaine.

Treatment and Rehabilitation

Detoxification

The cocaine withdrawal syndrome is distinct from that of opioids, alcohol, or sedative-hypnotic agents, because no physiological disturbances necessitate inpatient or residential drug withdrawal. Thus, it is generally possible to engage in a therapeutic trial of outpatient withdrawal before deciding whether a more intensive or controlled setting is required for patients unable to stop without help in limiting their access to cocaine. Patients withdrawing from cocaine typically experience fatigue, dysphoria, disturbed sleep, and some craving; some may experience depression. No pharmacological agents reliably reduce the intensity of withdrawal, but recovery over a week or two is generally uneventful. It may take longer, however, for sleep, mood, and cognitive function to recover fully.

Most cocaine users do not come to treatment voluntarily. Their experience with the substance is too positive, and the negative effects are perceived as too minimal, to warrant seeking treatment. Those who do not seek treatment often have polysubstance-related disorder, fewer negative consequences associated with cocaine use, fewer work- or family-related obligations, and increased contact with the legal system and with illegal activities.

The major hurdle to overcome in the treatment of cocaine-related disorders is the user's intense craving for the drug. Although animal studies have shown that cocaine is a powerful inducer of self-administration, these studies have also shown that animals limit their use of cocaine when negative reinforcers are experimentally linked to the cocaine intake. In humans, negative reinforcers may take the form of work and family-related problems brought on by cocaine use. Therefore, clinicians must take a broad treatment approach and include social, psychological, and perhaps biological strategies in the treatment program.

Attaining abstinence from cocaine in patients may require complete or partial hospitalization to remove them from the usual social settings in which they had obtained or used cocaine. Frequent, unscheduled urine testing is almost always necessary to monitor patients' continued abstinence, especially in the first weeks and months of treatment. Relapse prevention therapy (RPT) relies on cognitive and behavioral techniques in addition to hospitalization and outpatient therapy to achieve the goal of abstinence.

Psychosocial Therapies

Psychological intervention usually involves individual, group, and family modalities. In individual therapy, therapists should focus on the dynamics leading to cocaine use, the perceived positive effects of the cocaine, and other ways to achieve these effects. Group therapy and support groups, such as Narcotics Anonymous, often focus on discussions with other persons who use cocaine and on sharing experiences and effective coping methods. Family therapy is often an essential component of the treatment strategy. Common issues discussed in family therapy are the ways the patient's past behavior has harmed the family and the responses of family members to these behaviors. Therapy should also focus, however, on the future and on changes in the family's activities that may help the patient stay off the drug and direct energies in different directions. This approach can be used on an outpatient basis.

Network Therapy

Network therapy was developed as a specialized type of combined individual and group therapy to ensure greater success in the office-based treatment of addicted patients. Network therapy uses both psychodynamic and cognitive-behavioral approaches to individual therapy while engaging the patient in a group support network. The group, composed of the patient's family and peers, is used as a therapeutic network joining the patient and therapist at intervals in therapy sessions. The approach promotes group cohesiveness as a vehicle for engaging patients in this treatment. This network is managed by the therapist to provide cohesiveness and support and to

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promote compliance with treatment. Although network therapy has not received systematic controlled evaluation, it is frequently applied in the psychiatric practice because it is one of the few manualized approaches that has been designed for use by individual practitioners in an office setting.

Pharmacological Adjuncts

Presently, no pharmacological treatments produce decreases in cocaine use comparable to the decreases in opioid use seen when heroin users are treated with methadone, levomethadyl acetate (ORLAAM) (commonly called L-a-acetylmethadol [LAAM]) or buprenorphine (Buprenex). A variety of pharmacological agents, most of which are approved for other uses, have been, and are being, tested clinically for the treatment of cocaine dependence and relapse.

Cocaine users presumed to have preexisting ADHD or mood disorders have been treated with methylphenidate (Ritalin) and lithium (Eskalith), respectively. Those drugs are of little or no benefit in patients without the disorders, and clinicians should adhere strictly to maximal diagnostic criteria before using either of them in the treatment of cocaine dependence. In patients with ADHD, slow-release forms of methylphenidate may be less likely to trigger cocaine craving, but the impact of such pharmacotherapy on cocaine use remains to be demonstrated.

Many pharmacological agents have been explored on the premise that chronic cocaine use alters the function of multiple neurotransmitter systems, especially the dopaminergic and serotonergic transmitters regulating hedonic tone, and that cocaine induces a state of relative dopaminergic deficiency. Although the evidence for such alterations in dopaminergic function has been growing, it has been difficult to demonstrate that agents theoretically capable of modifying dopamine function can alter the course of treatment.

Tricyclic antidepressant drugs yielded some positive results when used early in treatment with minimally drug-dependent patients; however, they are of little or no use inducing abstinence in moderate or severe cases.

Also tried but not confirmed effective in controlled studies are other antidepressants, such as bupropion, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), antipsychotics, lithium, several different calcium channel inhibitors, and anticonvulsants. One study found that 300 mg a day of phenytoin (Dilantin) reduced cocaine use; this study requires further replication.

Several agents are being developed that have not been tried in human studies. These include agents that would selectively block or stimulate dopamine receptor subtypes (e.g., selective D1 agonists) and drugs that can selectively block the access of cocaine to the dopamine transporters but still permit the transporters to remove cocaine from the synapse. Another approach is aimed at preventing cocaine from reaching the brain by using antibodies to bind cocaine in the bloodstream (a so-called “cocaine vaccine”). Such cocaine-binding antibodies do reduce the reinforcing effects of cocaine in animal models. Also under study are catalytic antibodies that accelerate the hydrolysis of cocaine, and butyrylcholinesterase (pseudocholinesterase), which appears to hydrolyze cocaine selectively and is normally present in the body.

Vigabatrin is a drug that has been used as a treatment for refractory pediatric epilepsy, that appears to function by significantly elevating brain GABA levels. In animals, it was also noted to attenuate cocaine, nicotine, heroin, alcohol, and methamphetamine-induced increases in extracellular nucleus accumbens dopamine as well as drug-seeking behaviors associated with these biochemical changes. Preliminary clinical studies suggest efficacy for the treatment of cocaine and methamphetamine dependence. Large scale clinical trials for this indication are underway.

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