Approach to Drug Use Disorders
E. Nalan Ward
The person suffering from a drug use disorder poses diagnostic and management challenges to the primary care clinician and represents one of the foremost public health problems in the United States. Illicit drug abuse and dependence lead to high-risk dysfunctional behavior that disrupts interpersonal relationships and destroys lives, playing major roles in accidents, crime, domestic violence, and lost productivity. Intravenous (IV) drug use strongly contributes to the spread of AIDS and other infectious diseases such as hepatitis C. The comorbidity of substance abuse and psychiatric illness is particularly devastating. About half of individuals with a dependence on an illicit drug have another psychiatric illness.
Use of illicit drugs represents a major societal and medical problem, but even more pervasive, though less appreciated, is drug abuse or dependence associated with prescription pain relievers. The Centers for Disease Control and Prevention report that annually, more people die from prescription painkiller overdoses than from heroin and cocaine combined.
According to 2011 National Survey on Drug Use and Health (NSDUH), an estimated 22.5 million Americans aged 12 or older (8.7% of the population) are current illicit drug users, meaning they had used an illicit drug during the month prior to the survey interview (see Fig. 235-1).
Marijuana continues to be the most commonly used illicit drug in the United States (18.1 million). That is an increase in number of users from 14.5 million in 2007. In 2011, 4.5 million individuals reported current nonmedical use of pain relievers. Marijuana and prescription analgesics are the most commonly initiated drugs and therefore are considered to be the entry point into drug use disorders (Fig. 235-2).
The physicians should be aware that more than half of all illicit pain reliever users obtain them from family or friends for free and an additional 16.6% buy or take it from family and friends. In majority, the source of the pain relievers is one doctor (Fig. 235-3).
The Centers for Disease Control and Prevention report that annually, more people die from prescription painkiller overdoses than from heroin and cocaine combined (Fig. 235-4).
Illicit drug use effects mostly young adult population. The highest rate of use is 23.8% for 18- to 20-year-olds and 19.9% for 21- to 25-year-olds (Fig. 235-5).
The other group that requires special attention is the adults aged 50 to 59. Between 2002 and 2011, the rate of current illicit drug use in this group has increased from 2.7% to 6.3%. This trend partially reflects the aging of baby boom cohort whose rates of illicit drug use have been higher than those of older cohorts.
Illicit drug use is higher in males (11.1%) than for females (6.5%). It is important to note that the gender difference in illicit drug use among adolescents aged 12 to 17 is much lower (10.8% for males vs. 9.3% for females). The illicit drug use is estimated to be 5.0% among pregnant women aged 15 to 44.
Illicit drug use varies between different regions of the United States. Higher rates of methamphetamine use are seen in the West and the Midwest, whereas opioid abuse is more common in the Northeast. Access to treatment remains to be a major issue for the persons who suffer from illicit drug use problems. In 2011, about 7.2 million persons reported being in need of treatment for an illicit drug use. Of these, 1.4 millions received substance abuse treatment at a specialty facility.
Specifically, the significant increase in illicit pain reliever use has led to a dramatic rise (430%) in the rate of treatment admissions for the abuse of prescription pain relievers from 1999 to 2009. The numbers who received treatment for the use of pain relievers have risen from 360,000 to 754,000.
DEFINITIONS (4)
Consensus psychiatric definitions, as expressed in the Diagnostic and Statistical Manual of Mental Disorders 5th edition, (DSM-5), defines substance use disorders as a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues using the substance despite significant substancerelated problems. Once considered separate diagnostic entities, substance abuse (illegal, maladaptive or dangerous use of a substance) and substance dependence (compulsive, out of control, and persistent drug-seeking and drug taking behavior despite serious medical, psychological and social consequences) are now viewed as manifestations of a substance use disorder.
Addiction is a term that is used interchangeably with substance dependence. Physical dependence is the development of physical tolerance and a physical withdrawal and does not necessarily mean addiction or substance dependence. Example: A patient taking prescribed narcotic pain relievers for a medical condition develops tolerance and shows signs and symptoms of withdrawal if the pain medication is abruptly stopped.
 Figure 235-1 Past month use of selected illicit drugs among persons aged 12 or older: 2002-2011. Findings from National Survey on Drug Use and Health, SAMHSA. |
Drug use disorders are complex disorders caused by biopsychosocial factors. Addiction affects the brain reward and inhibitory control centers that normally insure the survival of species. With prolonged drug exposure in vulnerable persons, neurons in key circuits undergo molecular adaptations. The mesolimbic dopamine system provides powerful reinforcement behaviors with important survival value (e.g., sexual activity) by producing a sense of euphoria on stimulation. The most addictive of drugs (e.g., cocaine, amphetamines, opiates, alcohol, and nicotine) are believed to tap into the “brain reward” system by mimicking or enhancing the action of endogenous neurotransmitters such as dopamine or endorphins. It has been hypothesized that the drugs that produce these adaptive responses in the mesolimbic dopamine system cause the core symptoms of substance use disorders.
A subset of these responses also produces adaptive changes in other neurons that lead to physical dependence. When the drug is stopped, the person feels that the world is intolerable without it. In this model, the pathologic behaviors (e.g., denial, manipulations) of the person with a substance use disorder become more understandable. The key motivational system in the person’s brain has been usurped by drugs. Without the drug, the person experiences strong negative emotions, an inability to feel pleasure, and an intense craving for the drug. In addition, drugs dysregulate the brain inhibitory control systems such that despite serious consequences, individuals show diminished inhibitory control over drug use-related decision making. Overtime with repeated drug use, people with addictions stop experiencing any pleasure from what most people would find pleasure in and lose control over intense urges to use.
 Figure 235-2 Past year initiates of specific illicit drugs among persons aged 12 or older: 2011. Findings from National Survey on Drug Use and Health, SAMHSA. |
 Figure 235-3 Source where pain relievers were obtained for most recent nonmedical use among past year users aged 12 or older: 2010-2011. Findings from National Survey on Drug Use and Health, SAMHSA. |
Why some people become addicted during the course of drug use and others do not and why some people recover and some do not are not fully understood. Individual vulnerability appears in part genetic, such as the linkage of the dopamine receptor gene to multiple substance dependences. Developmental experiences, chronic pain, current levels of distress, and complex social factors, including family and peer relationships and the availability of valued behavioral alternatives, are all contributors to individual vulnerability. Psychiatric disorders are a significant risk factor in substance use disorders and complicate diagnosis and treatment (Table 235-2).
Cocaine, Amphetamines, and Other Central Nervous System Stimulants
These agents show their effect mainly by increasing synaptic dopamine in the mesocorticolimbic system (dopamine neurons in the ventral tegmental area and its projections in the nucleus accumbens and prefrontal cortex). Animal studies show that natural rewards such as food, sex, and success increase levels of the brain dopamine, thereby increasing neural activity in the nucleus accumbens. Increase in dopamine levels yields to feelings of euphoria and high. The enhancement of the effects of serotonin and norepinephrine by these drugs likely contributes to their sympathomimetic effects. Cocaine specifically binds to dopamine transporter and inhibits the reuptake of dopamine in the synapse causing in accumulation of dopamine in the synapse and also blocks the reuptake of norepinephrine and serotonin. Amphetamine acts predominantly by promoting dopamine release; it also decreases dopamine reuptake, resulting in increased dopamine in the synapse.
 Figure 235-4 Rates of opioid pain reliever (OPR) overdose death, OPR treatment admissions, and kilograms of OPR sold—United States, 1999-2010. The Centers for Disease Control and Prevention Report. |
The repeated use of stimulants causes neuronal changes that lead to compulsive use as well as to tolerance and withdrawal symptoms when the drug use is stopped abruptly. Chronic abuse is associated with low D2-receptor availability.
Cocaine
Cocaine is derived from coca leaves. It can be snorted, injected, or smoked. Street names for cocaine include “coke,” “snow,” “flake,” and “blow.” Crack is cocaine hydrochloride powder that has been processed to form a rock crystal that is then usually smoked.
Clinical Effects and Patterns of Abuse.
Higher brain levels are achieved more rapidly with IV administration and smoking and therefore considered more addictive than intranasal “snorting.” Faster absorption results in shorter duration of action. High from snorting may last 15 to 30 minutes, and smoking may cause a more intense and rapid high lasting from 5 to 10 minutes. Due to short duration of action, addicted persons develop binge use patterns, meaning they use in large amounts and repeatedly in a short period of time to maintain the high feeling.
It is estimated that in the United States, there are 1.0 million persons with cocaine dependence or abuse. In the 1980s and 1990s, the drug was very popular and was extensively abused. The rate and the number of those with cocaine use disorders declined between 2002 and 2009 from 0.6% (1.5 million) to 0.4% (1.0 million), respectively.
Stimulants (Amphetamines, Methamphetamine, Methylphenidate)
These agents are commonly abused, but some are also prescribed therapeutically (e.g., to treat attention deficit disorder).
When abused, these medications are taken orally, crushed, and snorted or used intravenously.
When abused, these medications are taken orally, crushed, and snorted or used intravenously.
 Figure 235-5 Past month illicit drug use among persons aged 12 or older, by age: 2010 and 2011. Findings from National Survey on Drug Use and Health, SAMHSA. |
Methamphetamine is another very addictive stimulant that is closely related to amphetamine. It is a white, odorless, bittertasting powder taken orally or by snorting or injecting or a rock “crystal” that is heated and smoked. Other street names are speed, meth, chalk, ice, crystal, and glass. Methamphetamine has a longer duration of action than does cocaine and causes toxicity at the dopamine nerve terminals in the central nervous system (CNS).
The number of current methamphetamine users decreased between 2006 and 2010, from 731,000 (0.3%) to 353,000 (0.1%), but due to its potent addiction liability and destructive health and social consequences, it is still considered one of the most dangerous drugs of abuse.
Clinical Effects and Patterns of Abuse.
CNS stimulants are highly addictive substances that affect many organ systems. Cocaine’s effects appear almost immediately after a single dose and disappear within a few minutes to an hour. Cocaine initially constricts blood vessels, dilates pupils, and causes tachycardia, hypertension, fever, and tremor and produces euphoria, increased energy, and confidence followed by restlessness, anxiety, hostility, hypersexuality, and paranoia.
Prescription stimulants are abused to enhance performance and to get “high.” They can also be abused as a weight loss agent, to increase wakefulness, and to increase focus and attention. When abused, these medications are usually crushed and then snorted or injected. At low doses, it increases wakefulness and physical activity and causes euphoria and hypersexuality. At higher doses, it can cause anxiety, irritability, insomnia, and paranoia.
Due to longer duration of action, the clinical side effects of methamphetamine are related to its toxic effects on nerve terminals. Specifically chronic users of crystal meth develop psychotic symptoms, including paranoia, visual and auditory hallucinations, and delusions, sometimes irreversible changes in brain function and structure, memory loss, aggressive or violent behavior, and severe dental problems (“meth mouth”).
With chronic use resulting in dependence, patients with cocaine and stimulant use exhibit jitteriness, loss of appetite, weight loss, depression, a lack of energy, and malnourishment. Repeatedly snorting cocaine can cause loss of sense of smell, nosebleeds, swallowing problems, hoarseness, and irritation of the nasal septum.
Intravenous cocaine users are subject to developing infections, abscesses, and sepsis. They present with “track marks,” and IV users of cocaine are at increased risk for contracting infectious diseases such as human immunodeficiency virus (HIV) and viral hepatitis. This risk stems not only from sharing contaminated needles and drug paraphernalia but also from engaging in risky sexual behaviors as a result of intoxication.
Persons with stimulant dependence are at high risk for the development of a paranoid psychosis.
Withdrawal from cocaine is called “crash.” It is characterized by severe dysphoria, depression, anhedonia, fatigue, hypersomnia, and a craving for cocaine. Crystal meth and prescription stimulant withdrawal present similarly, and the long-term withdrawal symptoms can be significant and quite disabling. Patients present with anhedonia, hypersomnia, lack of energy and motivation, and inability to deal with demands of daily life routines.
Overdosing with cocaine or amphetamine produces tachyarrhythmias, perspiration or chills, nausea or vomiting, hypertension, high fever, seizures, delirium, paranoia, psychosis, coma, and cardiovascular collapse. Stroke and myocardial infarction have been reported with crack use. Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest.
Opioids
The term “opioid” encompasses the opiates (natural alkaloids and semisynthetic opioids derived from the resin of the opium poppy) and the nonopiate opioids (wholly synthetic agents originally developed to provide opiate-like analgesic effect without some of the adverse effects). Most opioid abuse in the United States involves prescription opioids. Leading examples include morphine, hydrocodone, and oxycodone. The synthetic opioids such as methadone, fentanyl, and meperidine are also widely used (see Chapter 236) and may be abused. The opiates bind to endogenous opiate receptors, producing analgesia and sense
of euphoria. They affect breathing, blood pressure, and arousal and also have antitussive and antidiarrheal properties.
of euphoria. They affect breathing, blood pressure, and arousal and also have antitussive and antidiarrheal properties.
TABLE 235-1 The Population at Increased Risk of Developing Drug Use Disorders | ||
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Patterns of Abuse
Heroin, Hydrocodone, and Oxycodone.
These frequently abused opiates interact predominantly with µ-type opiate receptors. Neurons in the locus caeruleus appear to adapt to prolonged opiate exposure and fire at abnormally high rates when opiates are abruptly withdrawn, thereby triggering much of the physical withdrawal syndrome.
TABLE 235-2 Diagnostic Criteria for Substance Use Disorders* | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Heroin derives from the seed of poppy plants, appearing as a white or brown powder or as a black, sticky substance. It is injected, snorted, or smoked. Street names for heroin include “smack,” “H,” “ska,” and “junk.” In 2010, it was estimated that 359,000 persons had heroin dependence or abuse in the United States.
Hydrocodone and oxycodone are examples of prescription opiates taken for nonmedical purposes, often in the form of popularly prescribed combination preparations with acetaminophen (e.g., Vicodin) or as a slow-release preparation (e.g., OxyContin). Their use is a serious public health problem. National Institute on Drug Abuse’s (NIDA) Monitoring the Future (MTF) survey found that about 1 in 12 high school seniors reported past year nonmedical use of the prescription pain reliever Vicodin in 2010 and 1 in 20 reported abusing OxyContin—making these medications among the most commonly abused drugs by adolescents.
Opioid Use Among Patients with Chronic Noncancerous Pain.
Chronic noncancer pain is a risk factor to develop opioid abuse/dependence. Addictive disorders develop in up to 32% of patients with chronic noncancer pain. Patients who misuse or abuse their prescribed medications and lose control over their use can become addicted and present with behaviors that raise concern. Such aberrant drug-related behaviors (ADRBs) include more interest in immediate-release and brand-name opioids than in other medications or in any other aspect of treatment. It encompasses taking excessive doses and increasing dosage without consulting the clinician, insisting that higher doses are needed. Making multiple phone calls about prescriptions and attempting unscheduled visits (typically after office hours or when the clinician is unavailable) are also characteristic, as is appearing sedated or obtaining medications illegally (e.g., from multiple clinicians, street dealers, family members, the Internet, forged prescriptions).
Contributing factors include poor response to opioid pain relievers (medication failure), development of tolerance, and withdrawal. Other reasons for nonadherence and escalating behavior to obtain prescription pain medications are diversion of medications and untreated mental illness such as depression, anxiety, and insomnia.
Prescription opioid abuse is considered to be an epidemic problem in the United States. Unintentional overdose deaths involving opioid pain relievers have quadrupled since 1999 and, by 2007, outnumbered those involving heroin and cocaine. The perception that prescription drugs are less harmful than illicit drugs is likely a contributing factor to unintentional overdoses. In 2010, an estimated number of 1.9 million persons had pain reliever dependence or abuse. According to 2009 Drug Abuse Warning Network (DAWN), which monitors emergency department (ED) visits, roughly 343,000 ED visits involved prescription opioid pain relievers, a rate more than double that of 5 years prior.
There is significant increase in use of methadone for chronic noncancer pain in recent years as well as methadone-linked death reports (Fig. 235-6). Data show most of these deaths are linked to methadone prescribed for pain management.
Clinical Effects and Patterns of Abuse
Prescribed pain relievers when abused can be taken orally, crushed, snorted, or used intravenously. Especially controlledrelease oxycodone HCl, when crushed, becomes a rapid-release drug with the same abuse potential.
Opiates produce an initial sense of euphoria (a “rush”), especially after IV injection, smoking, or crushing, which is followed by a sense of tranquility and then sleepiness and mental clouding. Respiratory depression, sedation, and loss of motor control occur when large amounts are abused. When tolerance and dependence develop
with repeated consumption, increasing doses are required to achieve the desired euphoria. Tolerance to the respiratory depressant effects of opiates develops approximately in parallel. Tolerance to opiate-induced pupillary constriction does not develop.
with repeated consumption, increasing doses are required to achieve the desired euphoria. Tolerance to the respiratory depressant effects of opiates develops approximately in parallel. Tolerance to opiate-induced pupillary constriction does not develop.
 Figure 235-6 From 2010 SAMHSA/CSAT Methadone Mortality Meeting, July 2010. |
Unlike alcohol, opiates do not directly produce serious organ pathology. Constipation is the major side effect and may represent a significant problem. Other effects of opioids are sensation of urinary urgency, miosis, hypotension, and infertility.
Dependence.
As opiates produce high levels of physiologic dependence, repeated use of the drug is needed to prevent withdrawal symptoms. IV injection of the drug is a widely used method of administration and commonly involves sharing needles. This results in hepatitis C, HIV infection, endocarditis, infection of the local injection site, and other complications of unsterile self-injection. Heroin dependence increases mortality and morbidity risks. A recent study followed 581 men with heroin addiction from 1962 to 1997. By 1997, 282 of the men had died, at an average age of 47. Heroin overdose and chronic liver disease, which is associated with hepatitis B, hepatitis C, and alcohol abuse, caused 17% and 15% of deaths, respectively.
Withdrawal.
In general, clinically significant withdrawal symptoms do not occur with less than 2 weeks of opioid use, unless the person has a previous opioid dependence. Withdrawal from opiates is quite uncomfortable, both physically and psychologically, but not lethal. Various factors influence the severity of withdrawal symptoms, such as specific drug used (long acting vs. short acting), total daily amount used, duration and regularity of use, and psychological and individual factors.
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