Michael I. Fingerhood
Definitions
Drugs with abuse liability modify mood, feeling, thinking, and perception. Many are commonly prescribed and are useful therapeutic agents. The use and abuse of such substances date back thousands of years. Plant alkaloids, alcohol, and an ever-increasing array of newly synthesized chemicals have also been used in illicit endeavors. Patterns of use and the social acceptance of use of these agents have differed from time to time and from place to place. Successive generations of the same society have held discordant views about which substance to use, at what age, in what amount, and under which circumstances (e.g., attitudes regarding alcohol use in the pre-Prohibition and post-Prohibition eras in the United States). There are two forms of less problematic use of illicit substances (experimental and social–recreational) and two defined patterns of abnormal use (substance abuse and substance dependence).
Experimental Use
The experimental use of illicit substances is sporadic; the initial trial and experience are usually associated with adolescence. These experiments usually have little impact on mental health. They are potentially dangerous because of possible overdose, because unsterile methods of exposure may occur, because of behaviors that may endanger the user or other people, and because some people may find the drug experience extraordinarily rewarding leading to repeated use. Incorrect labeling of illicit drugs (a common problem) increases the risk of untoward consequences.
Social–Recreational Use
Social and recreational use of illicit substances suggests that they have been used repetitively but that control has been exerted over the dosage and the frequency of use. The risks of unintended overdose and improper exposure are increased by the frequency of use. Recreational use may not be psychologically disabling even though adverse consequences may occur. Adequate social and behavioral function is maintained. Most use of alcohol and marijuana conforms to this pattern of social–recreational use.
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Substance Abuse and Substance Dependence
The Diagnostic and Statistical Manual of the American Psychiatric Association, 4th Edition (DSM-IV) delineates two diagnostic categories for substance-related disorders (1). The diagnostic criteria are the same for all psychoactive substances, including alcohol.
The Diagnostic and Statistical Manual, 4th Edition, Criteria for Substance Abuse
The Diagnostic and Statistical Manual, 4th Edition, Criteria for Substance Dependence
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three or more of the following occurring at any time in the same 12-month period:
Classification by Pharmacologic Effect
Later sections of this chapter describe the manifestations and the principles of management for selected substances of abuse common in the United States (Chapters 27 and 28 describe tobacco and alcohol abuse/dependence, respectively). A list of all drugs that have abuse potential would be extremely long. However, it is possible to group the various substances into broad classes, the members of which share common characteristics and are readily distinguishable from other classes (Table 29.1). Psychoactive substances may be classified as depressants, opioids, stimulants, and drugs that alter perception (including hallucinogens).
Tolerance and Physical Dependence
Most drugs of abuse share the capacity to induce tolerance. Tolerance is defined as the phenomenon whereby with repeated use an increased amount of drug is required to
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produce a given effect. Alternatively, the same amount of drug produces a lesser effect with repeated administration. The time required for the induction of tolerance ranges from days after repeated use of opioids by injection to weeks or months after repeated oral administration of opioids, barbiturates, alcohol, and other sedatives.
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TABLE 29.1 Categories of Psychoactive Drugs |
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TABLE 29.2 Characteristics of Dependence on Drugs of Abuse |
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Physical dependence is defined as the phenomenon whereby abrupt cessation of a drug results in withdrawal symptoms and signs (the abstinence state). Withdrawal symptoms and signs are often the opposite of the biologic effects exerted by the drug in question (Table 29.2). Physical dependence is not synonymous with addiction. People who are prescribed benzodiazepines may exhibit physical dependence (sometimes called therapeutic dependence) but do not fulfill criteria for substance dependence (see DSM-IV criteria above). Similarly, many people exhibit a withdrawal syndrome for caffeine but do not fulfill criteria for substance dependence.
Primary Care Practitioner's Role
Background
Since the 1920s, with the exception of small numbers of psychiatrists and substance abuse specialists from other disciplines, practitioners in the United States have been reluctant to become involved in problems of substance abuse and dependence. The passage of the Harrison Narcotic Act in 1914, prohibited physicians from prescribing opiates for the treatment of opiate dependence. From 1920 to 1940, health care providers who prescribed or dispensed narcotics in violation of the Harrison Act were prosecuted and imprisoned. This campaign led to avoidance of the problems of addiction by physicians and other health care providers. Providers are still reluctant to become involved in problems with addiction because of a lack of knowledge of how to deal with these patients, their own attitudes toward substance abuse, and the understandable response to the difficult behaviors these patients often exhibit. In recent years, substance abuse has been recognized as a major cause of morbidity seen in medical practice—usually a mix of physical, mental, and social consequences—and the responsibility of primary care practitioners to care for the patient with substance abuse has been emphasized. This role was expanded with recent federal legislation allowing primary care physicians to prescribe buprenorphine as opioid replacement therapy.
Specific Roles
For the patient with substance abuse, the role of the primary care practitioner is recognition of the problem, motivation of the patient to accept treatment, referral to a treatment program, ongoing care for the patient's other medical problems, and continued motivation to help the patient remain in recovery. By prescribing controlled substances wisely, the primary care practitioner can also play an important role in preventing prescription drug abuse.
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Recognition/Diagnosis
Discovery of a substance abuse problem starts with a suspicion of the diagnosis if signs, symptoms, and elements of the history suggest the possibility, even in the most unlikely subjects. People from all walks of life abuse drugs. The stereotype of the drug abuser is of a young antisocial male who uses drugs for their euphoric effect. Although this may be true, the abuse of illicit drugs such as marijuana and cocaine also occurs commonly among middle and upper class Americans, and the misuse and abuse of prescription analgesics and sedatives by people who are in the mainstream of American society have been recognized for many years. Patients with chronic anxiety, insomnia, or pain are at risk of abusing medications used to treat those conditions. In some instances, escalated use (and sometimes abuse) develops not because the patient is primarily seeking drug-induced euphoria or intoxication but because the tolerance that develops during continued use leads the patient to increase the dosage to inappropriate levels. Elderly patients are at particular risk because they are more likely to be given medications. Changes in the pharmacokinetics of drugs secondary to the aging process also make the elderly more vulnerable to normally prescribed dosages.
Advice on history taking includes: ask questions about drug use in the context of general medical history, develop a nonjudgmental approach, use direct questions, learn to recognize qualified answers, be persistent and friendly, and do not discuss rationalizations. It is often helpful to obtain information from a family member or close friend, with the patient's consent.
Chapter 28 describes interviewing techniques helpful in screening for alcoholism and motivating the alcoholic to accept treatment. Techniques such as the CAGE questionnaire, as shown in Fig. 28.1, can be adapted to screen patients for the abuse of other drugs and substances.
Urine Testing
Urine testing to establish drug abuse seems a tempting and objective means of cutting through the problems of denial, unreliable histories, and the less than clear-cut signs and symptoms presented to arrive at a diagnosis. In the primary care practitioner's office, however, testing for drug abuse can prove problematic. The patient already knows whether he or she is abusing drugs. The question is whether the patient is willing to share that information with the practitioner.
Drug testing requires informed voluntary consent of any person 18 years of age or older, except in true emergencies. Faced with this requirement, laboratory testing yields no more information than the patient is willing to provide by history. Testing at the request of an employer or school authority, in particular, is fraught with ethical questions. Nevertheless, many employers now require drug testing (which is legal).
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TABLE 29.3 Medications That May Give False Positive Results on Drug Screen |
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There are problems of sensitivity and specificity in using urine-screening tests. False-negative results occur because of deception in collection and insensitive testing. False-positive results occur because of innocent confounding substances (Table 29.3), errors in processing samples, and the normal frequency of testing error. Experimental, social, and recreational use of illicit substances is so widely practiced that a positive test by no means establishes abuse or dependency. It also does not provide evidence of intoxication or impairment.
The testing of minors younger than age 18 years, which theoretically can be authorized by parents and legal guardians regardless of the wishes of the patient, raises issues of patient trust, ethics, and legality if contested. Possible drug use can be explored most productively in the context of the total family relationship, without the referring practitioner appearing to have to take sides.
In most instances, the drug treatment program should perform drug testing. Avoiding urine testing in the primary care setting also helps facilitate the doctor–patient relationship. It is hoped that people who relapse will be open and honest and will be more likely to show up for medical visits if they do not have to worry about urine testing.
Prescribing Controlled Drugs
Prescription drug abuse can be best avoided by careful and thoughtful prescribing of medications. Office-based practitioners prescribe large amounts of controlled drugs. Table 29.4 shows a summary description of the various schedules under the Controlled Substances Act. When prescribing these drugs, it is important to realize that chronic pain, anxiety, and insomnia treated with controlled drugs on a long-term basis will result in physiologic dependence.
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TABLE 29.4 Controlled Substances Act |
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Practitioners must be vigilant to avoid being “duped,” acquiescing to patient demands by prescribing inappropriately. To avoid possible abuse, medications with abuse liability should be prescribed on a fixed schedule. This strategy improves control of symptoms, minimizes the development of symptoms (rather than reacting to symptoms after they occur), and avoids patient focus on immediate relief. Medications should be prescribed for short periods during treatment of acute problems. Patients should be seen for reassessment at frequent intervals and telephone refills should be avoided.
There is a definite risk of theft of prescription blanks or alteration of a prescription. All prescription pads should be safeguarded and, ideally, marked “not for scheduled drugs.” Prescription blanks for scheduled drugs should be kept locked separately. Prescriptions should be written clearly, and the number of pills to be dispensed and the number of refills should be written out (not just a number). For some medications, such as sustained release oxycodone, the milligram dose should be spelled out, as a 10 can easily be altered to a 40. If no refills are to be given, “no refill” should be noted. All prescribing of scheduled drugs should be documented clearly in the chart.
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TABLE 29.5 Generally Inappropriate Prescribing Practices |
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Practitioners should be suspicious of patients who: 1) lose prescriptions or medications, 2) obtain prescriptions from multiple practitioners, 3) run out of medication before the time that would be expected, 4) demand one specific drug as the only one that will work, 5) have a sudden deterioration in work, school, or relationships, 6) have a history of substance abuse, 7) have a history of violent behavior, or 8) have slurred speech or unexplained cognitive impairment. Table 29.5 lists prescribing practices that may be illegal, dangerous, or inappropriate or indicate drug abuse.
Two classes of controlled drugs, benzodiazepines and narcotics, are the most commonly abused prescription drugs (2). Long-term use of these drugs is sometimes appropriate (see Chapter 22 and Chronic Pain Management, below). However, intermittent use is required to avoid physical dependence. Nonpharmacologic modalities should always be used to increase the interval between doses, decrease the required dosage, and permit intermittent use of these drugs if possible.
Nonscheduled drugs with abuse liability include muscle relaxants (especially carisoprodol—Soma), clonidine, Phenergan, and amitriptyline. Clonidine, prescribed for hypertension, commonly finds its way onto the streets, where it is sold to opiate addicts to alleviate opiate withdrawal. Muscle relaxants are abused commonly as sleeping pills.
Social and Epidemiologic Aspects
Social Aspects
Drug abuse has been a dominant public health concern for the past 30 years. Quite apart from toxic effects that may
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represent specific health threats to the individual abuser (discussed at greater length below under each substance), there are major societal consequences. The loss of impulse control directly associated with drug abuse, especially that caused by depressant intoxication is clearly recognized as conducive to acts of violence (assault, rape, murder, and suicide). Impaired judgment and performance secondary to intoxication are associated with greatly increased rates of vehicular and workplace accidents and trauma, as well as impaired work performance and attendant economic loss.
Finally, not as a result of pharmacologic effects but as an unintended byproduct of illicit status, substances of abuse are closely linked to crime (3). Illegal status raises the cost of such substances and creates an economic stimulus to hook and then supply consumers. Tens of billions of dollars annually in property crime and robberies are committed by addicts to pay the hugely inflated price of their addiction. Thousands of homicides annually are linked to drug abuse, many by dealers to acquire and police their turf. Many more billions of dollars are spent in the criminal justice system in the apprehension, trial, and imprisonment of addicts and dealers.
Epidemiology
Although survey data show changes in the use of some illicit substances among important segments of the U.S. population, drug abuse continues to be one of the most serious problems faced by public health and law enforcement authorities. Overall, in 2003 there were an estimated 19.5 million Americans who were current users of an illicit drug (4). This represents 8.3% of the population older than age 12 years. Marijuana was the most commonly used illicit drug with 14.6 million users, followed by cocaine, with 3.5 million current users. In the past 5 years, there has been a tremendous surge in the use of the so-called “rave” drugs—methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), gamma-hydroxybutyrate (GHB, liquid Ecstasy), and Rohypnol. Additionally, in rural areas where heroin is not readily available, illicit OxyContin is commonly snorted or injected.
Drug use and abuse are not evenly distributed throughout various segments of society. The incidence and prevalence of regular use and abuse are greater among inner city populations characterized by low levels of employment and educational achievement. Minorities are overrepresented in this population. Women are at lower risk of drug abuse than men but still make up about a third of the treatment population. They also are more likely than men to abuse illicit drugs by smoking or snorting rather than injecting. Particular problems include prostitution and consequent high rates of sexually transmitted diseases (STDs) as well as pregnancy, child care problems, and single-parent status.
The elderly are not at high risk for illicit drug use. Addiction to illicit drugs tends to wane over the years in those who survive beyond their fifties or sixties. Most drug problems in the elderly occur with alcohol, tobacco, and prescription drugs (opioids for analgesia and benzodiazepines for insomnia).
Polydrug use, abuse, and dependence are extremely common. For example, more than 80% of alcoholics are cigarette smokers. Many younger alcoholics also abuse cocaine. Alcoholics, in general, are at greater risk of abusing benzodiazepines when compared with non-drug abusing populations. People in methadone maintenance programs often abuse cocaine, benzodiazepines, and alcohol, and more than 90% are cigarette smokers. Heroin and cocaine are frequently injected together as a “speedball.” Use of a particular drug can be a function of price and availability, as illustrated by geographic differences in the patterns of drug abuse. Sometimes a drug interaction is desired (e.g., anxiolytic effects of alcohol counteract stimulant effects of cocaine). Generally, people who find one drug of abuse particularly rewarding are likely to find other drugs of abuse also to be rewarding.
Psychiatric disorders are more common among substance abusers than in the population as a whole. These both precede onset of substance abuse and result from substance abuse. Consequences of substance abuse also mimic psychiatric disorders. For example, patients with anxiety disorders may self-medicate with alcohol or benzodiazepines. Withdrawal from these substances produces anxiety regardless of whether the patient has an anxiety disorder. Stimulants acutely produce psychotic reactions, and depression is seen during withdrawal. Substance abusers are often given personality disorder diagnoses (especially the antisocial type).
Causes
Predisposing Factors
The causes of substance abuse are clearly complex. Some of the factors involved are:
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to drug abuse. Those with mood or anxiety disorders may find that certain drugs of abuse normalize these states.
Models for Understanding and Managing Substance Abuse
These causes do not speak to possible legal consequences or to therapeutic maneuvers. Four models, described here, have been proposed to encompass these concerns. The models, although distinct, are not mutually exclusive, and most people fit into more than one model, illustrating the complexity of their disease.
Moral Failure Model
This view attributes substance abuse to a failure by parents or parental surrogates (e.g., religious training, schools, movies, television, and music) to inculcate values, with resultant lack of morality that would prevent the use and abuse of drugs. From a public health viewpoint the model has utility. When applied to the person already dependent on drugs and with a long criminal record, it is not useful unless there is some religious conversion experience or complete acceptance of a 12-step program (e.g., Alcoholics Anonymous or Narcotics Anonymous).
Legal Model
Proponents define behavior as aberrant only when specific acts violate existing law and then recommend existing legal remedies such as trial, fines, and imprisonment to deal with these infractions. This model counters the disease or illness concept of addiction.
Disease Model
The disease model hypothesizes a host susceptibility to drugs of abuse that is lifelong, progressive, and incapable of modification and hence can be coped with only by total abstinence. It takes as its substrate only those meeting the definitions of substance abuse or dependence and does not concern itself with social or experimental use. The disease model partially encompasses research advances in psychopharmacology.
The disease model was originally proposed to counter adverse societal attitudes and judgmental views toward alcohol and drug abuse. This model also offers a nonstigmatizing explanation of substance abuse to organizations such as Alcoholics Anonymous and Narcotics Anonymous. These organizations have helped unleash a vast movement for self-improvement that has helped a significant number of abusers. The disease model is the paradigm for methadone maintenance, developed in the 1960s, for the treatment of heroin dependence. Heroin abuse was seen as a biologic modification of the brain that required supplementation by a narcotic substitute that does not lead to significant dysfunction.
Psychosocial Model
The psychosocial model views chemical dependency as the inadvertent effect of repeated self-medication by a vulnerable individual intent on relieving overwhelming anxiety or psychic pain related to hopelessness, boredom, depression, or fear. Drugs of abuse are potent and effective, albeit short-term, chemical alleviators of these symptoms. Vulnerability in this model is not a function of genetic constitution (although this may define an enhanced susceptibility). Rather it is because of membership in at-risk populations who, because of immaturity, socioeconomic disability, and the lack of responsible familial or peer support systems, have not developed the behaviors that the greater part of society uses to cope with adversity. This model has the virtue of defining an at-risk population from among the young, the dropouts, and the socially and economically disadvantaged that best fits most abusers in our current epidemic. The model helps explain the potential for endemic abuse by people who, although they may be socially and economically advantaged, may also turn to repetitive self-medication in the face of losses or situational anxiety, demoralization, or physical pain. The psychosocial model avoids a simplistic expectation of cure by mere detoxification or by enforced abstinence if release back into the same environment occurs without change in the conditions of vulnerability. The model also relies on support systems and self-help as a condition of remission.
Selected Drugs of Abuse
Opioid (Narcotic) Analgesics
Opioids are commonly prescribed drugs and play an essential role in the care of patients. The fear of causing opioid addiction has led some practitioners to under-medicate in the management of acute pain. Less commonly, there has been a tendency in treating patients with chronic pain to continue the use of opioid analgesics when the development of tolerance has rendered them less effective. Patients who have been taking opioid analgesics for long periods may experience little pain relief and may, in fact, confuse incipient withdrawal toward the end of a dosing interval with the onset of pain. An understanding of tolerance, physical dependence, and addiction can ensure more rational prescribing patterns.
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The opiate-dependent patient is not generally seen in office practice seeking treatment for drug dependence. Patients often appear in office practice settings attempting to obtain prescription drugs when they experience difficulty in obtaining heroin. Morphine, hydromorphone (Dilaudid), oxycodone, and meperidine (Demerol) are the drugs most preferred by addicts, but they will readily use the whole range of less potent opioid analgesics if preferred drugs are unavailable. The term opioid refers both to drugs derived from opium (opiates) and to synthetic drugs with similar actions. Alcohol, benzodiazepines, and promethazine (Phenergan) are often abused by opioid dependent patients because of their tendency to potentiate the effects of opiates.
Usual Effects and Therapeutic Use
Opiates are the prototype for managing patients with pain. To prevent abuse, they should be prescribed on a fixed schedule. For a comparison of the different opioids, see Chapter 13. Used for short intervals after an acute pain syndrome, opioids are safe and effective. Abuse liability increases with potency. Heroin, the most commonly abused illicit opioid, is usually injected intravenously but can also be injected subcutaneously (skin-popping), smoked, or sniffed (snorting). Heroin crosses the blood–brain barrier more effectively than other opioids. The effects after use consist of a brief and intense period of euphoria followed by several hours of a pleasant dreamy state in which the user may slowly nod as if falling asleep. Areas of pain feel numbed. The skin may itch (because of histamine release), which leads to characteristic scratching. Other effects include increased talkativeness (soap boxing), increased activity, and conjunctival suffusion (red eye). Stomach turning and vomiting (pleasant sick) occur. Physiologic effects include miosis and respiratory depression.
Acute Adverse Effects
Depressed consciousness and respiration characterize opioid overdose. Pulmonary edema, a common complication of opioid overdose, contributes to hypoxia and may cause death. Some opioids, such as propoxyphene (Darvon) and meperidine (Demerol), cause convulsions at high dosages. The latter has a proconvulsive metabolite (normeperidine) that accumulates in the setting of renal failure.
Chronic Adverse Effects
The adverse effects of chronic heroin abuse result from use of dirty needles (see Complications of Injecting Drugs, below), the adulterants mixed with the heroin, and the associated life-style (poor nutrition, lack of health care, and criminal activity) rather than from the drug itself. Heroin is usually mixed with lactose and quinine under unsterile conditions. Other more dangerous adulterants may also be included to mask the dilution of the heroin.
Tolerance to heroin develops quickly and can be demonstrated to some degree after only a few days of administration of the drug. The degree of tolerance and the consequent severity of withdrawal symptoms depend primarily on dosage levels and the frequency and duration of use. As outlined in Table 29.2, anxiety, nausea, yawning, diarrhea, sweating, rhinorrhea, dilated pupils, and piloerection (gooseflesh) characterize opioid withdrawal. In the advanced stages of withdrawal, the patient experiences vomiting and muscle spasms. Although the untreated addict experiences significant anxiety and discomfort during withdrawal, the process itself presents no serious medical risks.
Treatment
Opioid overdose must be treated in an emergency room. Emergency treatment requires cardiorespiratory monitoring and support. The opioid antagonist naloxone (Narcan) is safe and effective in countering the central nervous system (CNS) depression caused by opioid overdose but may precipitate withdrawal. The initial dose is 0.4 mg intravenously. This may need to be repeated because naloxone has a shorter duration of action than most opioid agonists.
Any patient who has been abusing heroin or other opioids and is willing to accept help should be referred for treatment. Few addicts voluntarily seek treatment before being faced with the destructive consequences of their drug use.
Detoxification from opiate dependence involves the administration of an opiate agonist (methadone), the nonopiate clonidine, or a partial agonist (buprenorphine). Substitution and slow tapering of methadone effectively reduces the severity of opiate withdrawal (5). It has a long duration of action and is conveniently administered orally. However, federal regulations limit the use of methadone to specially licensed centers. Detoxification may be accomplished by substituting methadone for the opioid previously used by the patient and then gradually reducing the dosage over time (usually at least 7 days). The initial dose should be sufficient to suppress withdrawal symptoms without causing sedation. Methadone detoxification is normally done on an ambulatory basis by specially licensed drug treatment programs.
Clonidine is a nonopioid medication demonstrated effective in suppressing symptoms of opiate withdrawal. A centrally acting α-adrenergic agonist, clonidine reduces sympathetic nervous system related effects of opiate withdrawal. It is more effective in suppressing signs than in relieving symptoms of withdrawal (6). Clonidine is dosed at 0.1 mg every 4 to 6 hours for the first day, followed by 0.1 mg every 8 hours the second day, and 0.1 mg every 12 hours on the third day. Dosages are held for systolic
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blood pressure less than 100 mm Hg. Transdermal clonidine may be an effective adjunct in outpatient treatment. However, it has a delayed onset of action, not crossing the dermis for at least 24 hours after placement. Recent cases of oral ingestion of the clonidine patch resulting in profound hypotension and bradycardia may limit its use. Outpatient use of clonidine is also impacted by diversion for illicit use. Other pharmacologic aids (dicyclomine for abdominal cramps, ibuprofen for bone pain, and loperamide for diarrhea) provide additional treatment for symptoms of opiate withdrawal.
Buprenorphine is a partial µ-opiate receptor agonist with a long duration of action. It is more effective than clonidine and equally effective to methadone for the management of opiate withdrawal (7). The parenteral formulation has been used to treat opiate withdrawal symptoms in hospitalized medically ill opiate-dependent patients (8). Experimental studies have demonstrated the efficacy of a sublingual preparation of buprenorphine as a maintenance therapy for opiate dependence (9,10). This preparation has recently become available for use in the United States and has become the drug of choice for outpatient treatment of opiate withdrawal. Only physicians who complete an approved eight-hour course and subsequently obtain a special Drug Enforcement Agency (DEA) number may prescribe buprenorphine. For detoxification, sublingual buprenorphine is administered once withdrawal symptoms are present, with typical treatment of 3 to 7 days.
Except for physicians licensed to prescribe buprenorphine, it is illegal for a care provider to prescribe an opiate for the treatment of opiate withdrawal. As with detoxification from any substance, the patient should be engaged in a program of outpatient chemical dependency counseling during and after detoxification (see sections on detoxification and rehabilitation, below). Even short-term detoxification has been shown to impact positively on future outcomes related to opiate dependence (11).
Cocaine and Other Stimulants
Cocaine, the amphetamines (especially methamphetamine), and methylphenidate are the most commonly abused stimulant drugs (nicotine is discussed in Chapter 27). Cocaine is used in several forms. The route for cocaine intake depends on the form used. As the natural water-soluble powder, cocaine hydrochloride, it is either sniffed (snorted) and absorbed through the nasal mucosa or injected intravenously. Forms of cocaine that can be smoked (using a water pipe or in cigarette form) are produced by extracting or freeing the cocaine alkaloid from the hydrochloride salt. When ether is used as the reagent in this process, the resulting product is referred to as freebase. When baking soda and water are used as reagents, the resulting product is crack, so named because of the crackling sound that is produced when the drug is smoked. Although they may differ in appearance and concentration, freebase and crack are pharmacologically the same.
Cocaine use appears in variable patterns. In the early stages, sessions of cocaine use typically last 2 to 4 hours, with intervals of days or weeks between sessions. Some users are able to maintain this pattern of use without progressing further. However, many users follow a pattern of rapidly escalating use in which both the length of sessions and the rate of consumption increase; users of freebase and crack may be more likely to succumb to this pattern than users who snort cocaine powder.
Chronic abusers typically engage in runs or periods of intensive cocaine use that can last anywhere from a few hours to several days. A run is terminated when the user runs out of cocaine or money, or is too physically exhausted to continue.
Methamphetamine, a synthetic stimulant, is sold as a white powder that is taken orally, intranasally, or intravenously or as a clear “rock” that is heated and smoked. It is known on the street as ice, speed, crystal meth, crank, tina, or glass. It is easily synthesized from the over-the-counter cold remedy pseudoephedrine by illegal small-time laboratories that quickly change location. Methamphetamine is especially popular in nonurban areas that have less influx of cocaine.
Methylphenidate (Ritalin) mimics the effects of naturally occurring stimulants such as cocaine and can be taken orally or intravenously. Legitimately used for the treatment of attention deficit disorder, methylphenidate is sometimes obtained by diversion from family members with the disorder or by seeking refills for reportedly affected family members from unsuspecting practitioners.
Abusers of stimulants develop some tolerance to the euphoric effects of the drugs but may become more sensitive to other effects such as irritability, restlessness, hypervigilance, and paranoia. Users report that in any given session of cocaine use, the duration and intensity of the euphoric effect seem to recede with successive doses, a phenomenon called “chasing the dragon's tail.”
Usual Effects and Therapeutic Use
CNS stimulants produce euphoria, increased confidence and energy, increased heart rate and blood pressure, dilated pupils, constriction of peripheral blood vessels, and increased body temperature. Effects are caused by sympathetic stimulation centrally and peripherally. The duration and intensity of effect depend on the dosage and the route of administration. Single oral doses of amphetamines produce effects lasting 2 to 4 hours. The effects of cocaine, when snorted, are rapid in onset but short in duration. Smoking freebase or crack produces an intense short-duration effect (peak effect in 2 to 3 minutes, duration about 10 minutes) because smoking is an extremely
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efficient method of drug administration. Intravenous use produces similar (or greater) intensity and longer duration of effects. Smoking and intravenous use of methamphetamine results in a pleasurable rush that lasts a few minutes. Oral use results in a muted longer duration effect.
Its capacity to produce euphoria gives cocaine a high abuse potential. In animals, cocaine produces reinforcing responses that exceed those of other drugs of abuse. The administration of cocaine in humans is associated with an increased desire for more cocaine (i.e., the presence of the drug itself in the body increases desire for cocaine). Users often delay entry into treatment until they are physically and emotionally exhausted or are faced with serious financial, legal, or medical problems.
Acute Adverse Effects
Very large doses of all stimulants may cause hyperpyrexia, arrhythmias, hypertension, and coronary and cerebral artery vasospasm, leading to myocardial infarction, stroke, seizures, cardiovascular collapse, and death (12). Large doses of cocaine may also cause respiratory depression with a fatal outcome. A reversible organic delusional disorder that resembles paranoid schizophrenia is occasionally seen. This syndrome may occur in normal subjects with no previous psychiatric history.
Chronic Adverse Effects
The chronic abuser of cocaine, amphetamines, and other long-acting stimulants is typically hyperactive, jittery, and irritable while using and depressed, exhausted, or lethargic afterward. Previously stable individuals may develop unexplained financial problems or uncharacteristic overnight disappearances. With chronic heavy use there is usually a history of sleep disturbance and weight loss. The patient may be emotionally labile, and periods of irritability, depression, and fatigue may alternate with periods of elation and mania. Cases of persistent psychotic disorders have been reported. Intravenous abusers of methylphenidate develop talc lung because talc is contained as filler in the tablet.
Physical examination may reveal needle marks; rhinitis; teeth worn from bruxism (grinding of teeth); ulcers on the lips, tongue, or nose; nasal septum perforation; tremor; flushing; and excessive sweating. Although cocaine may initially enhance sexual functioning, chronic use often interferes with sexual performance. Extremely heavy users may exhibit rapid, repetitious, and ritualistic body movements.
Stimulant withdrawal as outlined in Table 29.3 is characterized by a “crash” with symptoms of fatigue, drowsiness, dysthymia and drug craving. Orthostatic hypotension may accompany amphetamine withdrawal.
Treatment
Stimulant-abusing patients are generally treated in the outpatient setting, except for patients who present a risk of suicide. Treatment preferably involves daily counseling sessions during the first few weeks of abstinence. Necessary external supports include stable employment, a drug-free home environment, and active involvement in Narcotics Anonymous. No specific pharmacologic treatment is indicated for cocaine withdrawal because symptoms are mild. Currently, no drugs have been convincingly demonstrated to be efficacious in maintaining abstinence. A variety of drugs, including fluoxetine, desipramine, topiramate, and ondansetron, has been studied for their effects in reducing the reinforcing responses to cocaine in humans. To date, none has become clinically useful.
Sedative-Hypnotics and Benzodiazepines
The most commonly abused sedatives are alprazolam (Xanax), clonazepam (Klonopin), and diazepam (Valium). Rohypnol (flunitrazepam) has recently gained attention for abuse as “the date rape drug.” It is not licensed in the United States but is sold illicitly on the street. Rohypnol may cause paradoxical agitation and is not detectable by routine urine toxicology.
Usual Effects and Therapeutic Use
Sedatives cause intoxication similar to that seen with alcohol. Sufficient amounts are often taken to produce a depression of cortical function and to relax social and personal inhibitions. A high, or a state in which mood is elevated and anxiety is reduced, occurs. Normal individuals and those with anxiety disorders do not necessarily find these effects pleasurable or reinforcing. Because of their safety profile, benzodiazepines have become the only sedative-hypnotics prescribed for anxiolytic or sedating purposes. Chapter 22 discusses the proper prescribing of benzodiazepines for this purpose. This class of medicine should be avoided in all patients with a history of substance abuse. Phenobarbital should be the only prescribed barbiturate, with its indication being a second- to third-line drug for seizure prevention (seeChapter 88). Shorter acting barbiturates are contained in migraine medicines such as Fiorinal. These medications have a high abuse potential and should be avoided.
Acute Adverse Effects
Overdose may lead to slurred speech, impaired judgment, and unsteady gait. Even greater overdose may lead to stupor, coma, respiratory depression, vasomotor collapse, and death. Benzodiazepines (compared with barbiturates) cause less loss of motor coordination and almost never
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cause death when taken alone in large doses (unless given rapidly intravenously, e.g., midazolam or diazepam). However, the combination of alcohol and benzodiazepines can be lethal.
Chronic Adverse Effects
Benzodiazepine use may increase the risk of accidental injury and in a study of older adults, an elevated rate of automobile accident was found in benzodiazepine users (13). Several epidemiologic studies have shown benzodiazepines increase the risk of falls (14,15) and hip fractures in the elderly (16,17). One study has shown an increased risk of suicide attempt in benzodiazepine users with borderline personality disorder (18).
Almost no organ toxicity is associated with chronic administration of these drugs. From this standpoint, they are safer than alcohol. If prescribed for insomnia, benzodiazepines should be prescribed for short-term treatment (19,20). Otherwise, if patients use the medications on a regular basis, they will induce tolerance and increase the dosage. Chronic use of benzodiazepines may go undetected until confusion, irritability, slurred speech, or ataxia is recognized as a sign of sedative intoxication.
Physical examination may include ecchymoses from injuries sustained during an intoxicated state. Sedative-hypnotics can also produce anterograde amnesia. This is mostly dosage related and has been most often described with flunitrazepam (Rohypnol) and diazepam (Valium).
Physical dependence on benzodiazepines and the potential for major withdrawal symptoms may occur in as little as 2 months if dosages substantially above therapeutic levels are used. Most patients who abuse and have significant physical dependence on benzodiazepines abuse other drugs concurrently. Withdrawal symptoms (outlined in Table 29.2) occur in patients taking therapeutic dosages daily for 6 months or more (21). Tapering the dosage can reduce the risk of withdrawal. Although chronic use may create the risk of withdrawal symptoms, there is evidence that patients may use benzodiazepines on a chronic basis without developing tolerance to the anxiolytic effects of the medication (22,23).
Treatment
Nonbenzodiazepine sedative overdose is a life-threatening occurrence that should be treated in an emergency department. Because of physical dependence, patients who use excessive dosages of sedative drugs are at risk of serious withdrawal reactions, including life-threatening seizures. Outpatient treatment for therapeutic dependence can often be managed by tapering the prescribed benzodiazepine or switching to a benzodiazepine with a longer half-life and tapering it over several weeks (24). Onset time of withdrawal symptoms is inversely related to the half-life of the benzodiazepine of use. Inpatient treatment is often required for high-dose abuse and can be managed using phenobarbital, which has a long half-life (80 to 100 hours) and provides the pharmacokinetic umbrella to prevent withdrawal symptoms (25).
Marijuana and Hashish
Marijuana consists of the dried leaves of the Cannabis sativa plant, which are usually smoked in pipes or cigarettes (joints). Hashish is a concentrated resin of cannabis and contains approximately 5 to 10 times the concentration of the principal psychoactive ingredient—9-tetrahydrocannabinol—as compared with marijuana. The discussion that follows applies to both marijuana and hashish. Cannabis can also be added to foods such as brownies, but when it is eaten, effects appear less rapidly and are less under control of the user.
Usual Effects and Therapeutic Use
The effects of marijuana from usual smoked doses last from 3 to 6 hours. The more common effects are elation or high, an increased tendency to laughter and silliness, tachycardia, reddening of the eyes, and a later stage of relaxation. At higher dosages these effects are enhanced. The user may misjudge the effects of time, and perception of sound, color, and other sensations may be distorted or sharpened. Short-term memory and logical thinking are impaired, as is the ability to drive a car or perform other complex tasks. Additive effects occur with alcohol or other CNS depressants. Dosages three to five times higher than those producing relaxation and mild euphoria can result in effects similar to those of lysergic acid diethylamide (LSD) and other hallucinogenic substances (depersonalization, auditory, and visual hallucinations). Some of the usual effects of marijuana that might be enjoyable to the experienced user, as well as the more alarming effects associated with high dosage, can be frightening to the inexperienced user. The setting is important in determining the effects of the drug. When smoked in a pleasant and familiar setting, marijuana is less likely to produce a negative response than when used in unfamiliar or threatening surroundings.
Cannabis has effects that are potentially useful for therapeutic purposes (e.g., decreased intraocular pressure, anti-emetic properties). However, other currently approved drugs are of similar or superior efficacy for these indications and have fewer side effects. The principal psychoactive substance in cannabis is marketed in oral preparations; dronabinol (Marinol) is a schedule II drug in the United States and nabilone is available in Canada, where they are approved for use as appetite stimulants.
Acute Adverse Effects
Considering the large number of regular users in the United States, it is clear that adverse reactions to
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marijuana requiring medical treatment are rare. The most common adverse response is an acute anxiety reaction, which may include paranoid ideation. These reactions are most likely to occur in novice users or in users who unexpectedly receive a much larger than usual dose. Most reactions last only the few hours it takes for the effects of the drug to wear off. Some patients experience persistent anxiety for several days after the initial panic subsides.
There have also been reports of delirium induced by marijuana. A dysphoric reaction characterized by disorientation, catatonic immobility, acute panic, and heavy sedation has also been reported. These conditions tend to remit within 2 to 4 hours as the effects of the marijuana diminish. Reports of enduring psychotic reactions after heavy marijuana use have appeared, largely in countries where marijuana is used at much higher dosages than in the United States. Reports of confirmed psychotic reactions to marijuana in this country are rare.
Chronic Adverse Effects
There is substantial evidence that marijuana at dosage levels associated with common social usage results in loss of energy and drive, impaired memory, and apathy. This is sometimes called the amotivational syndrome.
Smoking marijuana alone does not appear to cause a decline in pulmonary function (26). However, heavy cannabis users tend to be heavy tobacco smokers. The tar content of cannabis smoke is 50% higher than that of tobacco. Accordingly, users may develop chronic bronchitis and other respiratory diseases. Marijuana smoke contains 70% more carcinogens than does tobacco smoke (27). There have been conflicting findings concerning possible adverse effects of marijuana on the immune system. Some studies report changes in immunologic responsiveness, but the clinical implications of these changes are currently unknown. There is evidence that marijuana reduces testosterone levels in men, although generally, the testosterone level in users remains within normal limits (28).
Regular use induces moderate tolerance. High dosages followed by sudden cessation produces a mild withdrawal syndrome in both animals and humans. Regular users of marijuana often exhibit restlessness, sleep disturbance, loss of appetite, and irritability when they stopped using marijuana. For social use, neither tolerance nor physical dependence is a major issue.
Treatment
Because they must be closely observed and may take several hours to recover, patients with panic reactions are best managed in a setting such as a drug abuse program, mental health center, or emergency department where continuing observation and supportive contact can be provided. Generally, these patients require simple reassurance and an explanation that they are experiencing a drug reaction that will dissipate as the drug is eliminated from their bodies.
Delusional or delirious patients should be seen in an emergency department because they present more complicated management problems and may require sedation or hospitalization. Furthermore, other causes of delirium should be ruled out. Restraints should be used only when absolutely necessary for the safety of the patient or others. Medications should not be used unless the patient is extremely agitated and difficult to control.
Treatment for chronic use should involve the support necessary for abstinence: a drug-free environment, active participation in 12-step meetings of Alcoholics Anonymous or Narcotics Anonymous, and, in some circumstances, group counseling.
3,4-Methylenedioxymethamphetamine (Ecstasy)
MDMA is a synthetic drug that is both a stimulant and hallucinogen (LSD-like). It was originally synthesized as a drug to facilitate communication during psychotherapy (29). Street names for MDMA include Ecstasy, Adam, XTC, hug, beans, and love drug. Most MDMA sold on the street has MDMA in combination with other drugs, including LSD, amphetamine, caffeine, heroin, and lactose. Using MDMA with LSD is termed “candyflipping.” MDMA comes in the form of a white powder that is usually pressed into pills, but other routes, such as snorting, injecting, and use as a rectal suppository, have been reported.
Usual Effects
When taken on an empty stomach, oral ingestion of MDMA results in a “rush” within minutes. The rush, consisting of euphoria and an intensification of perceptions, lasts 25 to 30 minutes. Individuals crave the effect and take additional doses. However, repeated doses have diminished effect. After the initial intense phase, a plateau phase occurs during which users report a trance-like feeling that lasts a few hours. A down phase, accompanied by feelings of dysphoria and anxiety, occurs 3 to 6 hours after initial ingestion. Despite feelings of exhaustion, users are unable to fall asleep.
Acute and Chronic Adverse Effects
MDMA is neurotoxic, damaging dopamine and serotonin producing neurons in the brain. Acute use of MDMA results in muscle rigidity, involuntary teeth clenching, nausea, blurred vision, faintness, and cold sweats. Cases of acute rhabdomyolysis have been reported. Heart rate and blood pressure increases may be dose dependent. MDMA can cause confusion, depression, sleep problems, severe anxiety, and paranoia. These effects may linger weeks after
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use. Hepatotoxicity and an acneform rash occur in many individuals after chronic use. Long-term users of MDMA may suffer permanent deficits in thought and memory (30). Motor disturbances may occur resulting in a syndrome resembling Parkinson disease.
Treatment
The acute toxic effects of MDMA are short lived. It is metabolized in the liver and excreted in the urine. Management of overdose is supportive care in a quiet dark setting. For individuals who are agitated and paranoid, treatment with benzodiazepines will ameliorate symptoms. Intravenous hydration is indicated in cases of overdose accompanied by rhabdomyolysis. Dantrolene may be useful if severe persistent muscle spasms occur.
Long-term treatment for abuse of MDMA is similar to other drugs of abuse, consisting of counseling and 12-step groups. Most users of MDMA are young and should seek treatment centers that have programs specific for adolescents and young adults.
γ-Hydroxybutyrate
γ-Hydroxybutyrate (GHB) is a precursor of the neurotransmitter gamma aminobutyric acid. It was developed as an adjunct to anesthesia and is used clinically for narcolepsy. It is sold in small bottles as a salty clear liquid and goes by the street names liquid ecstasy, easy lay, cherry meth, soap, liquid X, liquid G, and liquid E. After ingestion, the onset of action is within 15 to 30 minutes with effects lasting up to 3 hours. The drug's half-life is about 30 minutes with elimination by expiration as carbon dioxide.
Usual Effects
Acting on the central dopaminergic system, GHB produces euphoria and disinhibition without a subsequent dysphoria.
Adverse Effects
Idiosyncratic responses to GHB occur. These include delusions, aggressive behavior, altered mental status, seizures, nausea, vertigo, ataxia, nystagmus, amnesia, somnolence, and coma. Recovery from somnolence and coma is often characterized by myoclonic jerks and confusion. During intoxication, individuals are at risk for aspiration. In severe cases of intoxication, bradycardia and myoclonus may accompany coma. Adverse effects are potentiated by CNS depressants, including alcohol, benzodiazepines, and opiates. Use of GHB with methamphetamine increases the risk of seizures.
Treatment
Management of acute overdose is supportive. Comatose patients may require intubation for airway protection. Atropine should be prescribed in the presence of symptomatic bradycardia. Because many patients ingest GHB with other drugs, a screen for other drugs should be performed with treatment for toxicity from other drugs as indicated.
Long-term treatment for abuse of GHB is similar to other drugs of abuse, consisting of counseling and 12-step groups. GHB users are at high risk of developing dependence to other drugs. Most users of GHB are young and should seek treatment centers that have programs specific for adolescents and young adults.
Phencyclidine
Phencyclidine (PCP) is a barbiturate-like anesthetic and derivative of ketamine. However, PCP exhibits selective action as an anesthetic, appearing to depress sensory tracts—including proprioception, pain, touch, and temperature—to a greater degree than it depresses cortical function. The resultant state of sensory deprivation and relative cortical wakefulness makes for a peculiar sense of detachment, disembodiment, and weightlessness. These sensations are intensely pleasurable for some, whereas for others they induce intense anxiety and even panic. PCP was developed as an anesthetic but was abandoned for this purpose when it was found to cause disturbing side effects. It continues to be used by veterinarians as an animal tranquilizer or immobilizing agent. Pure PCP is a white powder that dissolves in water. It is usually sprinkled on marijuana, dried parsley flakes, or other organic material and smoked. Less often, it is obtained in powder or tablet form and ingested or snorted. Street names for the drug vary considerably from region to region, but it is most commonly known as angel dust, flakes, crystal, greens, hog, or sheets.
Usual Effects
The effects of PCP are dose-related, although both individual responses vary. People who take PCP in the dosages normally associated with street use may experience exhilaration, euphoria, inebriation, tranquilization, and perceptual disturbances. Some unpleasant effects commonly reported include disorientation, hallucinations, anxiety, paranoia, excitability, and irritability. At usual street dosages, most users reach peak intoxication in 5 to 30 minutes and remain high for 4 to 6 hours. It may take 24 hours or more before the user feels completely normal again.
Acute Adverse Effects
Even at low dosages, PCP is capable of occasionally causing severe reactions that may precipitate extreme agitation
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and acts of violence toward the user and to others. With higher dosages, users are more likely to exhibit delirium, which may include hallucinations. Users may also develop PCP psychosis, a disorder closely resembling schizophrenia that persists for 24 hours or more. Such psychoses may develop out of the original intoxication or may occur days after the intoxication has cleared.
Ataxia, nystagmus, slurred speech, and ptosis are common features of acute PCP toxicity. Very high dosages of PCP, which are normally the result of oral ingestion rather than smoking, can result in coma, severe respiratory depression, seizures, and death.
Chronic Adverse Effects
Chronic use of PCP may produce persistent changes in personal habits (hygiene or dress), problems with memory or speech, sleep disturbances, mood changes (depression, irritability), delusional thinking, and unusual excitability or lethargy. Little is known about long-term physical effects.
Treatment
Consistent correlation has been found between the patient's initial level of consciousness and the time course of improvement. Patients who are delirious at presentation can be treated in an emergency department and do not necessarily require hospitalization. Repeated mental status examinations should be performed to ensure that the patient is in a state of clear consciousness for at least 4 hours before discharge. Members of the family should be cautioned that the patient should stay in the company of family members or reliable friends for several days. Patients can have the onset of severe depression or a PCP psychosis for several days after the acute effects of the drug have subsided. PCP abuse usually occurs in the setting of polysubstance abuse, and long-term treatment should include traditional 12-step meetings.
Lysergic Acid Diethylamide
LSD is the prototype of a number of alkaloid substances of high potency that cause hallucinations. Others include psilocybin, dimethyltryptamine, and mescaline. All are classified as hallucinogens and are CNS depressants at higher dosages. LSD (acid) is sold illicitly in the form of powder, tablets, or capsules. Sugar cubes, small squares of gelatin (window panes), or paper (blotter acid) that have been impregnated with the drug are also available. LSD is usually ingested orally and its effects appear within 30 to 40 minutes, reaching a peak at about 90 minutes, with physiologic effects gone by 6 hours but subjective effects persisting for 8 to 12 hours.
Usual Effects
Subjective effects produced by LSD include depersonalization, altered time perception, labile mood, perceptual distortions (usually visual), body image distortion, and feelings of increased insight. Physiologic effects include slight rises in blood pressure and heart rate, fever, lack of coordination, dilated pupils, increased salivation and lacrimation, hyperreflexia, and occasionally vomiting.
Acute Adverse Effects
Inexperienced users may have an acute panic reaction that occurs because the normal effects of the drug are unfamiliar or unexpected. In more severe reactions, users of LSD may experience hallucinations (usually visual) and delusions that may persist beyond the time when the drug is circulating in the blood.
Flashbacks, spontaneous recurrences of the original LSD experience, occur in some users, often days to years later. They are more likely to occur in chronic users (and can occur after the use of any hallucinogenic drug). There have also been reports of prolonged psychotic reactions after the use of LSD, although these are rare.
Patients with acute LSD toxicity can be differentiated from those with PCP toxicity or schizophrenia in several ways. LSD causes dilation of the pupils, which is absent in PCP toxicity and schizophrenia. PCP toxicity usually is characterized by clouding of consciousness and the patient often exhibits ataxia, nystagmus, and ptosis, which are not features of LSD toxicity or of schizophrenia.
Chronic Adverse Effects
Some degree of tolerance develops with repeated use of LSD, but no chronic effects or withdrawal syndrome has been observed.
Treatment
Adverse reactions to LSD usually remit in 8 to 24 hours, and hospitalization is usually unnecessary. However, the patient should be observed until symptoms clear. Referral to an emergency room or to a drug abuse program that can provide this type of support will usually be necessary. The same supportive measures described earlier for the treatment of adverse reactions to marijuana are appropriate. Extremely agitated patients should be treated with diazepam or lorazepam.
Inhalants: Solvents
The inhalation of solvents is a form of substance abuse that is most commonly found among children and adolescents. Because solvents are easily obtainable and inexpensive,
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they are likely to be preferred by people who lack the money or other resources needed to obtain more desirable drugs. A partial list of specific substances subject to this type of abuse includes gasoline, ignition spray, airplane glue, paint thinner, spray paint, lighter fluid, nail polish remover, cleaning fluid, and shoe polish. Inhalation is typically accomplished by saturating a rag with the substance and holding it directly over the face or placing it in a bag that is then placed over the nose and the mouth.
Usual Effects
The effects of solvents are immediate and of short duration, usually dissipating in a few hours or less (depending on the dosage). Acute intoxication is similar to alcohol intoxication except for the shorter duration.
Acute Adverse Effects
A hangover, with symptoms of headache and nausea that is similar but perhaps milder than the hangover produced by alcohol has been observed. Some users experience apparent delirium characterized by tactile hallucinations, spatial distortions, and body image distortions. Sudden sniffing deaths have been described when inhalants were used during strenuous activity or under conditions in which blood oxygen is reduced. Such deaths apparently occur as a result of cardiac arrhythmias. Other deaths have been caused by suffocation when the user loses consciousness with the bag containing the solvent covering the nose and mouth.
Chronic Adverse Effects
The effects of solvents on the CNS, liver, kidneys, and bone marrow are not well understood. Cerebellar damage (which is partially reversible with abstinence) and peripheral neuropathy occur with long-term use. Numerous studies have demonstrated organ damage from long-term exposure to low concentrations of industrial solvents, but it is less clear to what extent these findings can be generalized to the short-term high-concentration exposures experienced by inhalant abusers.
There is evidence that tolerance develops with chronic solvent abuse, but withdrawal symptoms and signs are uncommon, probably because the concentration of the substance in neurons is not sustained.
Treatment
Because the acute effects of solvents are usually of short duration, abusers rarely present for medical treatment. On rare occasions, a patient may be brought in for treatment of a solvent-induced delirium. Chronic solvent abuse requires the same type of intense counseling and rehabilitative intervention indicated for other forms of substance abuse.
Anabolic Androgenic Steroids
These drugs are used to enhance athletic performance and improve physique. They are derivatives of testosterone and promote growth of skeletal muscle and may increase lean body mass. Use is widespread but data are limited. Anabolic steroids are mostly used in cycles of weeks or months. Stacking (use of more than one preparation) and pyramiding (dosages gradually increased and then tapered) are common patterns of administration. Dosages used are much greater than those administered for therapeutic purposes.
Usual Effects and Therapeutic Use
Anabolic steroids are prescribed routinely to individuals with hypogonadism. Acute experimental administration of testosterone to eugonadal individuals produces no acute psychoactive effect (31). Total body weight increases in less than a week, partly because of salt and water retention and also because of a true increase in lean body mass. Anabolic steroids contribute to an increase in strength in trained individuals (32).
Anabolic steroids have therapeutic benefit in people with weight loss related to human immunodeficiency virus (HIV) infection. Both oxandrolone, an oral synthetic anabolic steroid, and testosterone are prescribed for involuntary weight loss and wasting related to medical illness. In these settings they are safe to prescribe, with low abuse potential.
Chronic Adverse Effects
Although it is not clear whether there are any acute adverse effects, there are chronic adverse effects if these drugs are taken in excess. Adverse chronic effects include decrease in sperm count, testicular atrophy, masculinization in women (hoarse voice and clitoral hypertrophy), premature fusion of epiphyses in adolescents, decreased glucose tolerance, an unfavorable lipid profile (increased low-density lipoprotein, decreased high-density lipoprotein), acne, alopecia, hirsuteness, hepatitis, and complications of injection drug use (see above). There is a tenuous link with malignancy and case reports of MI and other vascular events. The most reported psychological effect is an increase in aggression. Some users fulfill DSM-IV criteria for psychoactive substance abuse and dependence as defined at the beginning of this chapter (33).
Atropinic Drugs
Atropine (the alkaloid produced by nightshade Atropa belladonna and by jimsonweed) and scopolamine are
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acetylcholine antagonists that at high dosages produce hallucinations, delirium, and varying states of excitement, insomnia, or amnesia. CNS depression and coma may follow these effects. The undesired pharmacologic effects of these drugs—dryness of the mouth, blurred vision, anhidrosis, and tachycardia—limit their appeal as psychoactive agents. Thus, the rare instances of abuse are mostly by teenagers experimenting with jimsonweed in rural areas or, in the past, by use of over-the-counter soporifics that contained scopolamine until the Food and Drug Administration (FDA) banned this. Treatment of toxic overdose is a medical emergency requiring gastric lavage and ingestion of activated charcoal to limit intestinal absorption, maintenance of vital signs, administration of physostigmine, and lowering of body temperature.
Arecoline (Betel/Areca Nuts)
Arecoline is a parasympathomimetic alkaloid somewhat similar in structure to nicotine. It is used for its psychoactive effects by about a billion people, mostly in Southeast Asia and the Indian subcontinent. It is the world's fourth most popular psychoactive drug (after caffeine, alcohol, and nicotine). It is a cholinergic drug, exerting effects similar to acetylcholine, including sweating, salivation, and increase in bladder tone. At low dosages it produces general arousal and is usually classified as a stimulant. However, at higher doses there may be sedating effects. The nuts have a bitter taste and produce reddened saliva and stained teeth, and chronic use commonly leads to grinding of the teeth and cancer of the oral cavity. They are usually chewed with lime to enhance absorption. Treatment of arecoline poisoning consists of administration of atropine and cardiorespiratory support.
Complications Of Injecting Drugs
Cutaneous complications in injection drug users include needle marks or scars, usually in the antecubital fossae of both arms, on the forearms and wrists, or on the backs of the hands. The presence of old abscess scars and of bluish phlebitis scars from past injections also indicates chronic use. Long-time users are usually forced to seek new injection sites as old sites become unusable because of scarring, and they may exhibit fresh needle marks on the legs and neck.
Skin and soft tissue infections are extremely common. Staphylococcus aureus is the most common pathogen (staphylococcal colonization is universal among injecting drug users). Streptococci (groups A and G) are the next most common pathogens. However, almost every common pathogen (as well as some uncommon ones) is seen. The types of infections include cellulitis, abscess, multiple chronic ulcerations, necrotizing fasciitis, pyomyositis, septic phlebitis, and infected aneurysms. Regional lymphangitis and lymphadenitis are common with all of these conditions. Unusual infections introduced at the site of injection include wound botulism, candidiasis, and tetanus.
When needles are shared, there is a high risk of acquiring viral hepatitis. Seroprevalence surveys among injecting drug users reveal positive hepatitis C serology in up to 86% of users (34). Many individuals have chronically elevated aminotransferase levels. Although the natural history of hepatitis C in this population is not yet well described, injecting drug users infected with hepatitis C may be more likely to die from drug overdose or homicide than from hepatitis C (35). Hepatitis B virus (HBV) is also common among injecting drug users with carrier (antigen positive) rates of 4% and previous infection (antibody positive) rates ranging from 30% to 94% (34,36). People who have been infected with HBV are at risk for infection with hepatitis D virus (HDV) (delta virus). Hepatitis B vaccine should be given to seronegative injecting drug users. Chapters 18 and 47 describe hepatitis vaccines and hepatitis in detail.
Approximately 30% of recent cases of acquired immunodeficiency syndrome (AIDS) in the United States relate to injecting drug use (37). Injecting drug users are the main sources of heterosexual, and subsequent perinatal, transmission of HIV. Compared with homosexuals who are HIV-positive, injecting drug users who are HIV-positive are more likely to have morbidity related to bacterial infections (endocarditis, pneumonia, and abscesses). Generally, studies have found that modest behavior change among injecting drug users has occurred as a result of concern about AIDS. This relates mostly to risk reduction rather than to elimination (smoking or snorting rather than injecting drugs). Multiple simultaneous interventions appear to be needed. These include access to drug abuse treatment (including methadone), education, counseling, social support, and needle and syringe exchange/availability (38). Even with these interventions, many individuals (especially those with antisocial personality) do not significantly change their behavior. Chapter 39 describes HIV infection in detail.
Endocarditis usually is caused by bacteria at injection sites and most often affects the tricuspid valve. S. aureus is the most common causative organism. Mitral and aortic valves are not uncommonly involved and are more likely to be affected if there is pre-existing pathology. Streptococci (enterococcus, viridans, and α-hemolytic) are next most common and are more likely to affect left-sided valves. Other offending organisms include gram-negative organisms (Pseudomonas) and fungi (Candida). Polymicrobial and culture-negative endocarditis also occur. Prognosis is related to size of vegetations and to complications such as heart failure and embolic events. Treatment should be in a controlled inpatient setting. Chapter 40 describes the posthospital management of endocarditis.
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Skeletal infections account for a significant number of admissions of injecting drug abusers. Osteomyelitis and septic arthritis occur, mainly by hematogenous, but occasionally from contiguous, spread. The lumbar spine, sternoarticular structures, and the pelvis and its articular structures are commonly involved. Synovial joints (most commonly the knee) and occasionally the appendicular skeleton can be involved. Tuberculosis and fungal infections are also encountered. Gonococcal arthritis is commonly seen among drug-abusing women who prostitute.Chapter 40 describes the ambulatory aspects of diagnosis and management of osteomyelitis.
Pulmonary complications, other than septic emboli, are mostly related to obtundation and drug intoxication with consequent aspiration pneumonia (or pulmonary edema from opiates), lung abscess, and empyema. Microembolization, talc granulomas, pulmonary fibrosis, and, uncommonly, pulmonary hypertension are sometimes seen. Pneumothorax may occur as a complication of attempted injection in the neck.
Defects in host defense mechanisms (independent of HIV-induced problems) are present in injecting drug users. Cell-mediated immunity is depressed, but the mechanisms involved are not clearly understood. Other factors such as malnutrition and concurrent alcohol abuse complicate the study of this problem. The humoral immune response is not diminished. Polyclonal increases in immunoglobulin, probably related to repeated antigenic exposure, result in elevated total protein levels. Thrombocytopenia commonly occurs as a result of circulating immune complexes reacting with platelets. Up to 25% of drug users have a biological false positive serologic test result for syphilis. Usually, the positive titer is 1:4 or less, and the more specific fluorescent treponemal antibody test is negative.
Pharmacologic Approaches to the Treatment of Substance Abuse
As mentioned above, the roles of the primary care practitioner are to recognize substance abuse, discuss the problem nonjudgmentally, motivate patients to accept treatment and to refer patients for treatment. Pharmacologic treatment and rehabilitation are generally managed by specialists in substance abuse in the context of a treatment program.
Detoxification
With the exception of opioid-addicted patients who enter methadone maintenance treatment, rehabilitation usually begins with detoxification. This is the process or set of procedures involved in readjusting the patient to a lower or absent tissue level of the substance of abuse. Where they are available, the specific pharmacologic approaches to detoxification have been described above under descriptions of individual drugs of abuse.
Detoxification is the first and easiest task for the recovering addict. Patients tend to attach too much significance to the task of physiologic withdrawal and too little significance to the behavioral changes that are required to prevent relapse (see Rehabilitation, below).
With proper support, many chemically dependent patients can be detoxified on an outpatient basis. Such patients should be seen on a daily basis throughout the detoxification and should be participating concurrently in an intensive program of counseling and education. Medications should be administered on a daily basis so that the patient has only the dosages needed between visits. Clearly many patients do not have the social support and accessibility to appropriate programs for this to occur. Chapter 28 describes the other conditions needed for successful outpatient detoxification.
In general, inpatient detoxification is necessary when (a) the patient is unable to discontinue use of illicit substances on an outpatient basis; (b) the patient has concurrent medical problems that require hospitalization or significant medical problems that would be exacerbated by detoxification (e.g., symptomatic coronary artery disease); (c) the patient has developed an extremely high tolerance and has a history of major withdrawal symptoms such as seizures and delirium tremens; (d) the patient presents a clear risk of suicide or, because of chronic intoxication and impaired judgment, is a danger to self or others; or (e) the patient is dependent on multiple drugs.
For most patients, it is not physical dependence that presents the major obstacle to recovery. Rather, it is the propensity to relapse, and the factors that influence this, that determine the success of the patient's efforts to become drug free.
Methadone Maintenance
Methadone maintenance is the most widely used chemotherapeutic approach to the treatment of opioid addiction. Methadone is a long half-life opioid that is taken orally in a single daily dose. Methadone is substituted for the opioid previously used by the patient at a dosage that prevents withdrawal but causes less sedation or intoxication. The starting dose is usually 30 mg. The methadone dosage is gradually increased, thereby increasing the patient's tolerance for all opioids to a level where the user is less able to experience a significant effect, even from large dosages of illicit narcotics. Although this methadone blockade can be overridden by a sufficiently large dose of another narcotic, the payoff for doing so is small in relation to the cost. Patients taking methadone are partially tolerant to its euphoric–sedative effects and are thus able to function normally in home and work settings.
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Numerous studies have shown methadone maintenance to be a cost-effective approach in treating opioid addiction (39). Methadone maintenance reduces heroin use (40). It may reduce crime and increases economic productivity of patients in treatment (41). It has also taken on a new significance because of its potential for reducing the spread of AIDS.
Contingency management treatment has been most often applied to methadone maintenance programs. Attempts are made to change behavior by manipulating consequences. Rewards or punishments are provided as incentives for desirable behavior. For example, take-home privileges are linked to the provision of clean urine tests.
Although cost effective, methadone treatment has limitations. As with other forms of chemical dependency treatment, there is a high turnover and rate of relapse. Patients are required to take methadone under observation at a clinic at least three times a week, and this requirement sometimes conflicts with work and family commitments. Although methadone is effective in suppressing the use of opioids, it has no such effect on alcohol or other drugs, and many methadone-maintained patients develop problems with other substances. Methadone-maintained patients become both physically and psychologically dependent on the drug, and many patients experience considerable difficulty in making the transition from methadone to abstinence. Some treatment professionals believe that opioid addicts have a biochemical abnormality that is corrected by methadone so that it may be necessary for them to remain on methadone for life. No scientific evidence supports this view at this time. However, it is likely that genetic studies will reveal a biologic predisposition to opioid use, as has been demonstrated with alcohol and tobacco. Some patients who make appropriate changes in life-style and develop good social and emotional support systems are able to detoxify successfully from methadone.
Buprenorphine Maintenance
A combination sublingual tablet buprenorphine/naloxone (Suboxone) and a buprenorphine mono-tablet (Subutex) are available in the United States for treatment of opioid dependence in office-based practice. The interaction of buprenorphine at the µ-opioid receptor results in buprenorphine having a good safety profile, low physical dependence, and convenient dosing. The buprenorphine plus naloxone combination product is safer for use than plain buprenorphine with decreased risk of diversion. Only physicians who complete an approved 8-hour course and apply for a special DEA number may prescribe buprenorphine. Courses and information are listed on the Web site athttp://www.buprenorphine.samhsa.gov. Buprenorphine, is as effective as methadone in treating opiate addiction (9,10).
Naltrexone
Naltrexone is an orally administered opioid receptor antagonist that is highly effective in blocking the effects of opioids. It is a long-acting drug that can effectively block the effects of opioids when administered three times a week. Because naltrexone causes an acute withdrawal reaction, candidates for naltrexone treatment must first be detoxified from the opioid to which they are addicted. Unlike methadone, which works by increasing the patient's tolerance for opioids, naltrexone competes with opioids at the receptor site. Another important difference is that naltrexone is not addicting, and patients can discontinue use without difficulty. The major disadvantage of naltrexone is that few patients are willing to use the drug and stay on it for an appropriate length of time. Its effectiveness is thus limited to highly motivated patients or patients who can be required to take the drug. Its effectiveness as maintenance therapy is less certain (42) than is that of methadone (40) or buprenorphine (10). Like methadone, naltrexone is not effective in blocking the use of other substances of abuse. A patch preparation of naltrexone is under development. Equivalents of methadone and naltrexone have not been developed that would allow for the pharmacologic management of other forms of drug abuse, such as cocaine.
Rehabilitation
All forms of drug abuse optimally require both acute and long-term intervention. Acute interventions include the management of overdose, toxicity, and withdrawal under medical supervision (if this is indicated). However, when the immediate physical consequences of drug abuse have been successfully treated, there remains a need to identify and treat, if possible, any underlying conditions that motivated drug misuse in the first place. Many drug abusers have significant problems of psychological and social adjustment and may benefit from counseling and rehabilitation over extended periods. As described above, the primary care practitioner's major role in dealing with long-term rehabilitation is to motivate patients to cease drug abuse and to enter and continue in rehabilitation programs.
Effective rehabilitation programs stress the development of practical social and vocational skills and the avoidance of social environments conducive to drug use. Unfortunately, many employers are reluctant to hire someone with a history of substance abuse. However, employment is a key aspect of recovery. In recent years, there has been an increasing recognition that families may actually enable drug abuse by one or more members. Family therapy has been used successfully with opiate addicts and appears to be the treatment of choice with drug-abusing teenagers who are still living with their parents.
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Because many drug abusers have important deficits in education and vocational preparation, lack basic social and recreational skills, and are handicapped by problems of poor impulse control and low self-esteem, the process of rehabilitation often takes considerable time. Some treatment programs serve as therapeutic workplaces, integrating drug treatment and vocational training.
There is evidence that existing treatment modalities improve the course of substance abuse disorders and reduce the amount of injury to both the individual and the community. There is evidence that treatment reduces the economic costs that result from drug abuse and that these cost reductions substantially exceed the actual cost of providing care (43). However, it must also be acknowledged that definitive treatment methods that result in lasting abstinence from drugs in a significant proportion of patients do not currently exist.
Principal Types of Rehabilitation Programs
Residential Treatment Programs
Two types of residential treatment programs are commonly encountered in the United States. Therapeutic communities typically require patients to commit themselves to 6 months or more of treatment. Patients are subjected to an intense aggressively confrontational form of group therapy that is intended to facilitate change by stripping away antisocial drug-oriented beliefs and values and replacing them with socially adaptive beliefs and values. Therapeutic communities tend to have high dropout rates in the first few weeks of treatment because many patients are not willing to make the commitment required by this form of treatment. Patients who remain for the duration of treatment, however, often achieve an enduring drug-free adjustment.
A more common form of residential treatment is the intermediate-term residential program. These programs are typically 4 weeks in duration and were originally designed to treat alcoholism. Over the last two decades, they have evolved into chemical dependence programs that accept patients with a wide range of substance abuse problems. Intermediate-term residential programs use a more traditional group therapy approach that is less aggressive than the approach used by therapeutic communities. They also place a strong emphasis on education. In most facilities, patients attend lectures and films designed to increase their understanding of the disease of chemical dependency and the nature of the recovery process.
Traditionally, intermediate-term residential programs have been viewed as the treatment of choice for chemical dependency, but in recent years they have come under pressure from a variety of groups concerned about the rising cost of health care benefits. Residential treatment is considerably more expensive than outpatient care, and comparisons of the two approaches for one form of drug abuse—alcoholism—show little difference in outcome for comparable patients (43). There are few data for other drugs of abuse. In response to the demand for more cost-effective treatment approaches, intermediate-term residential facilities now offer flexible lengths of stay rather than admitting all patients for the same 28- or 30-day program.
Intensive Outpatient Treatment Programs
Demands for more cost-effective forms of treatment have led to a greater emphasis on the use of outpatient approaches. Intensive outpatient programs offer a combination of education and group counseling similar to that found in the intermediate-term residential programs, but they provide treatment in the evenings so patients do not have to be absent from home or work. Intensive outpatient programs have patients attend treatment sessions four to six times a week and offer 12 to 20 hours of therapeutic activities each week for 4 to 6 weeks or longer. Traditional individual psychotherapy (rather than counseling) has not proved particularly effective in treating drug dependence.
Self-Help Groups
Self-help groups such as Alcoholics Anonymous (see Chapter 28) and Narcotics Anonymous (http://www.na.org/) provide another valuable resource for people seeking help for a substance abuse problem. These 12-step programs provide a clearly defined sequence of steps that the addict must take to recover. They also provide immediate access to the emotional support and encouragement of others who have successfully coped with similar problems. Alcoholics Anonymous and Narcotics Anonymous both maintain hotlines that are listed in the telephone directories of every major community in the United States and Canada. Chapter 28 describes the Narcotics Anonymous process, which is identical to the process of Alcoholics Anonymous. Most drug-free treatment programs incorporate the tenets of Narcotics Anonymous into their approach and encourage patients to get actively involved with a 12-step program.
Nar-anon (http://www.naranon.com/home.html) provides support for members of the addict's family using 12 steps modeled on the 12 steps of Al-Anon (see Chapter 28). Even if the patient refuses to accept treatment or try self-help groups, family members (who may be codependents) can be referred to Nar-anon. Codependents may experience a wide range of physical and emotional stresses as a result of another family member's addiction. Codependents often experience guilt, shame, loss of self-esteem, diminished self-confidence, and social isolation. They often believe that they are in some way to blame for the substance abuser's problems, a belief that is often fostered
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by the substance abuser, who is more than happy to shift responsibility to others. Codependents often engage in enabling behaviors—actions that are intended to help the substance abuser but only shield the substance abuser from the consequences of his or her behavior and therefore delay serious efforts at recovery. Codependents often resort to a variety of strategies intended to control or prevent access to drugs by the substance abuser. Such efforts are usually unsuccessful. Recovery usually occurs when the substance abuser feels the need for change and is willing to accept full responsibility for making change occur. Substance abusers who recover are motivated to change in large part by the unpleasant and painful consequences of their drug use. Nar-anon helps family members recognize and discontinue enabling behaviors and helps them cope with the physical and emotional stresses that result from living with a substance abuser.
Common Obstacles to Recovery
Many patients, particularly those in the early stages of addiction, have difficulty accepting the requirement of total abstinence. Although they might not admit it, many patients enter treatment with the unstated agenda of gaining control of their drug use rather than stopping it. They are reluctant to give up the pleasurable effects of drugs or they doubt their ability to cope with emotional distress without the relief afforded by drugs. They secretly hope to learn how to enjoy the benefits of drugs while avoiding the problems that have accompanied their drug use in the past. This is part of the process of denial. Other patients enter treatment believing that they have a problem with one type of drug but not with others. Cocaine addicts, for example, often believe that they do not have a problem with alcohol or marijuana and see no reason to give up the use of those drugs. Experience has shown, however, that continued use of non–problem drugs tends to predispose patients to relapse with their problem drug. Furthermore, patients who continue to use other drugs are less likely to make the changes in life-style that are important in maintaining recovery over the longer term.
One of the most important tasks for the patient in early recovery is to sever ties with drug users and to develop new relationships with nonusers, or at least with nonabusers. The relationships with other abusers tend to be superficial and based mainly on the shared activity of getting high. In addition to forming new relationships, the recovering addict must learn to form a new type of relationship, one that involves a level of trust, honesty, and intimacy that may seem alien to some. Such relationships are fundamental to recovery because they are the primary source of support for the addict struggling with the physical and emotional demands of recovery. During their addiction, most addicts learn to use drugs as a quick and effective, though ultimately destructive, method of dealing with physical or emotional distress. In recovery, the addict must learn other strategies to cope with distress.
The active abuse of drugs during adolescence and early adulthood seems to interfere with the development of basic social skills. Additionally, addicts are often hampered by diminished self-esteem and self-confidence and by the expectation that they will be rejected by society. Meeting people for the first time and attempting to initiate new relationships generate anxiety for most people under the best circumstances. When normal social anxiety is compounded by the social and emotional deficits that characterize most addicts in early recovery, the task of forming new relationships can become so intimidating that it may be avoided altogether. The recovering addict who feels lonely or isolated is tempted to resume contact with old friends who are still using drugs.
Another important life-style change has to do with the use of leisure time. Drug use is, among other things, a recreational activity. Getting and using drugs provides a daily routine that fills time and provides stimulation and challenge. For some addicts, the enjoyment of certain aspects of the drug-oriented life-style is as important as the reinforcing effects of drug use in maintaining drug involvement. For other users, being high makes it possible to tolerate what would otherwise be a tedious daily routine. It is important for the addict in early recovery to identify new activities that will provide a reasonable amount of stimulation and satisfaction. Boredom greatly increases the risk of relapse, and the recovering addict who fails to find employment that is in some way rewarding or to develop satisfying leisure activities is in danger of relapse.
Self-help groups are an invaluable resource for people in early recovery. In addition to providing emotional support and guidance, they are the best available forums for meeting nonusers and developing new friendships. They also sponsor social and recreational activities and provide opportunities for addicts in early recovery to learn new ways of managing leisure time from people who are further along in recovery.
In summary, recovery from chemical dependency requires a multitude of changes in beliefs, relationships, and life-style. Some of the required changes are difficult to accomplish, and the need for them is not immediately apparent to many addicts. In early episodes of treatment, most addicts make some of the needed changes but not enough to avoid relapse over the long term. As a result, relapse rates among patients successfully completing treatment run as high as 80% in the year after treatment. Of course, results highly depend on how the population is selected. Socially stable higher socioeconomic groups have a better prognosis. With successive treatment episodes, however, one can hope to see a changing pattern in which periods of abstinence grow longer and periods of active drug use grow shorter. Perhaps it is best to view relapse as an indication that the patient has so far failed to make all the necessary
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changes needed to support an enduring recovery. Instead of regarding relapse as an indication that the patient's case is hopeless, the patient's practitioner can encourage the patient to identify the reasons for the current relapse and to make changes that will help the patient avoid a recurrence. The approach should not be very different from that of other chronic diseases such as hypertension or diabetes, in which complete cure is uncommon.
Chronic Pain Management
Chronic pain of nonmalignant origin is not a single entity. It has a variety of causes and contributing factors. Treatment may vary from behavioral and physical therapy approaches to medications, including opioids. Pain is one of the most common reasons patients consult a practitioner, yet it is often inadequately treated. There is much controversy over the long-term use of opioids for nonmalignant pain. Opioids can clearly be of benefit in some patients with chronic pain who have not responded to other pharmacologic therapies, including nonsteroidal anti-inflammatory drugs (NSAIDs), and have no history of substance abuse. Success or benefit should be measured by improvement in quality of life, as measured by greater ability to perform activities of daily life. Side effects such as respiratory depression and sedation tend to be rare in patients with chronic pain and should not prevent the proper prescribing of opioids.
Evaluation of a patient with chronic pain should include the following: (a) a pain history with specific details of the impact of pain on the patient, (b) an assessment of pain in a typical day (worst score, best score, average score, and response of pain score to pharmacologic and nonpharmacologic interventions—use of a visual analog scale, as illustrated in Chapter 13, Fig. 13.1, can be helpful), (c) a directed physical examination, (d) a review of previous diagnostic studies, (e) a review of previous interventions, (f) an alcohol and drug history, and (g) an assessment of coexisting diseases or conditions. Treatment should be based on the findings in this evaluation and the presenting cause of pain.
Patients with chronic pain require frequent visits and phone calls. Many providers view such patients as time-consuming and frustrating and as a result look to refer them to pain centers. However, referral to pain centers is often limited by insurance as a result of their cost. Most studies of the effectiveness of pain centers focus on patients with chronic back pain. A meta-analytic review of 65 studies of pain centers in the management of chronic back pain tended to show beneficial effects of pain treatment centers, but many studies were poorly designed (44). One randomized controlled study in Denmark of 189 patients with chronic pain of nonmalignant origin showed that the patient group treated at a multidisciplinary pain center had better pain relief and quality of life than the comparison group treated by a general practitioner after initial consultation by a pain specialist (45). No time or cost analysis was performed.
Nonpharmacologic therapies, including acupuncture (see Chapter 5), acupressure, exercise, hydrotherapy, biofeedback, relaxation techniques, massage, and physical therapy, should all be considered and prescribed, if appropriate, as adjuncts to the management of chronic pain (46). They provide an opportunity for patients to be active in their approach to overcoming chronic pain. Psychosocial stress and mood have an impact on pain perception and the ability to cope with pain. Patients should not lose their “identity” to their diagnosis of chronic pain, and these nonpharmacologic modalities often contribute to a better sense of well being.
The relationship between pain and depression is complex because many patients with depression have a history of chronic pain and vice versa. Depression does lower pain tolerance and increase analgesic requirements. There have been a variety of trials using tricyclic antidepressants as adjuncts for pain control (47,48). Additionally, when given at bedtime, they enable sleep, which may have a positive impact on pain during the day. Pain improvement may occur at lower than therapeutic blood levels. Nortriptyline at a dosage of 10 or 25 mg at bedtime is a usual starting point, with gradual increase of dosage depending on effect. Other antidepressants have also been found to be useful as pain management adjuncts, with paroxetine (Paxil) deserving particular mention, especially when coupled with a tricyclic antidepressant (49). Chapter 24 gives details regarding antidepressants.
Other drugs to be considered as adjuncts for pain management include the anticonvulsants gabapentin, phenytoin, and carbamazepine. A recent meta-analysis provides some evidence from randomized controlled trials supporting the efficacy of these agents but recommends that they be withheld until other interventions have been tried (50). Gabapentin in escalating doses up to 3,600 mg/day may be particularly effective for chronic pain of neuropathic origin (51). It may be better tolerated than the other anticonvulsants and can be titrated up in dose with little side effect other than sedation. The above cited meta-analysis, however, found no statistically significant difference in toxicity (numbers needed to harm) among the three agents (50). Capsaicin, a topical substance P inhibitor, is available without prescription and is often useful as an adjunct for treatment of postherpetic neuralgia, arthritis, diabetic neuropathy, and reflex sympathetic dystrophy. Topical lidocaine is also useful for postherpetic neuralgia.
If a trial of opioids is deemed appropriate, the provider should ensure that the patient is informed of the risks and benefits of opioid use. Most patients should have already been tried on a course of NSAIDs. The provider may choose
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to continue an NSAID while initiating opioid therapy. Specific conditions under which opioids will be prescribed should be agreed upon (e.g., strict adherence with directions, no telephone refills, and patient responsibility for the prescription and all pills). Only one provider should be responsible for all prescriptions related to chronic pain. A written agreement specifying these conditions may be useful (Fig. 29.1).
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FIGURE 29.1. Sample pain contract. |
Generally, long-acting opioids should be used for chronic pain because they reduce the need for frequent dosing, have reduced abuse liability, and alleviate pain while preventing the re-emergence of pain. Both morphine and oxycodone are available as long-acting twice a day preparations for the treatment of pain. Fentanyl is available in a transdermal patch formulation that lasts for 3 days. Transdermal fentanyl should be prescribed only to patients who are already opioid experienced. A recent multicenter controlled study found transdermal fentanyl to be superior to sustain release oral morphine in the treatment of chronic nonmalignant pain (52). Chapter 13 gives details regarding opioid analgesics. In most patients, the effective opiate analgesic dose for chronic pain will stabilize at a set dose, without need for escalation over time and with sustained pain relief.
Review of treatment efficacy should be an ongoing process. Patients should keep a pain diary with a record of daily activity and pain scores during a typical day. Monthly followup visits should include a review of the pain diary, an assessment of functional status, efficacy of analgesia, drug side effects, quality of life, and any sign of medication misuse. All this information should be documented in the patient chart on each visit.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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