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Substance use disorder is a chronic disease with progressive
deterioration of psychological and physiologic activity secondary to the
habitual use of a drug. This complex disease disrupts many if not all
aspects of an individual’s life; therefore, multimodal treatment is
Opioid misuse includes illicit drugs, such as heroin, and the nonmedical
use of prescription pain relievers. Opioid withdrawal is characterized as
a flu-like syndrome, involving nausea, vomiting, sweats, diarrhea, pain,
and elevations in pulse and blood pressure. The full agonist methadone,
partial agonist buprenorphine, and antagonist naltrexone all can be used
as maintenance therapy to reduce relapses. Treatment considerations
during pregnancy consist of fetal risks if the mother goes into opiate
withdrawal or if the mother relapses into addictive behavior. Neonatal
abstinence syndrome occurs in the newborn if the mother has been
maintained on methadone or buprenorphine.
Sedative-hypnotic drugs of abuse include benzodiazepines, barbiturates,
alcohol withdrawal, may include tremors, insomnia, anxiety, elevations in
pulse and blood pressure, seizures, and hallucinations, and may be
potentially life-threatening. In clinical practice, three general medication
strategies are used for withdrawing patients from sedative-hypnotics:
gradual tapering of the drug of abuse, substituting and gradually tapering
phenobarbital, and substituting and gradually tapering a long-acting
Major central nervous system (CNS) stimulants of abuse include cocaine
and amphetamines. These drugs are associated with serious acute and
chronic adverse effects, such as hyperthermia, paranoia, psychosis,
hypertension, arrhythmias, myocardial infarction, seizures, and strokes.
Withdrawal from stimulants is not associated with severe symptoms.
Primarily, withdrawal consists of fatigue and hypersomnolence. There is
currently no US Food and Drug Administration (FDA)-approved
treatment for withdrawal or maintenance treatment of stimulant use
The use of hallucinogens, including LSD, psilocybin, mescaline, and Case 90-8 (Questions 1–3)
MDMA, may result in psychological, but not physical, dependency.
Adverse reactions during intoxication, such as anxiety, paranoia, and
fear, may necessitate benzodiazepine or antipsychotic therapy, but are
best managed using a “talk-down” method.
Marijuana is a widely used substance. The withdrawalsyndrome is
generally mild, characterized by anxiety, depression, irritability, and
insomnia, and does not require treatment. Chronic use has been shown
to result in increased risks of car accidents, pulmonary complications,
Alcohol use disorder is defined by acute and chronic alcohol use. It can
result in toxicity, withdrawal, and addiction. Alcohol toxicity is an acute,
life-threatening condition that requires aggressive medical attention.
Symptoms include a strong smell of alcohol, risk of aspiration, depressed
and shallow respiration, and cardiac arrest. Management generally
consists of respiratory support and a thorough diagnostic evaluation to
rule out coingestion of other drugs or other underlying medical
conditions that may also need attention.
Alcohol withdrawal is the neurobiologicalsyndrome associated with
increased tolerance or physical dependence resulting from chronic
alcohol consumption. This syndrome results in a continuum of signs or
symptoms including paresthesias, headache, nausea, anxiety, shaking,
important since untreated withdrawal can result in death. Treatment
may be complicated not only by the physical or cognitive deterioration
that can occur but also by the lack of attention to other serious medical
or psychological conditions that could be contributing to, or resulting
from, chronic alcohol use. Adjunctive treatments including fluid (e.g.,
normalsaline solution), nutritional (e.g., thiamine, folic acid,
multivitamins), and electrolyte (e.g., magnesium, potassium)
replacement should also be initiated to address the physiological
consequences of chronic alcohol use.
Chronic alcohol use disorder (alcohol dependence) is a life-long relapsing
disorder that consists of signs of alcohol abuse (continued drinking
despite alcohol-related physical, social, psychological, or occupational
problems, or drinking in dangerous situations, such as while driving) to
the extent that the person also experiences at least three of the
following seven symptoms: neglect of other activities, excessive use of
alcohol, impaired control of alcohol consumption, persistence of alcohol
use, large amounts of time spent in alcohol-related activities, withdrawal
symptoms, and tolerance of alcohol. Approved pharmacotherapies
include disulfiram, naltrexone (tablets and injection), and acamprosate.
Which option is best is determined by many factors such as home
support, medical comorbidities, and concomitant medications.
Physical dependence occurs when repeated administration of a drug causes an
altered physiologic state (neuroadaptation). After neuroadaptation, a characteristic
set of withdrawal symptoms occurs when the drug is abruptly discontinued.
Psychological addiction or psychological dependence refers to a “maladaptive
pattern of substance use leading to clinically significant impairment or distress.”
Habituation is a state of either chronic or periodic drug use characterized by a desire
(but not a compulsion) to continue using the drug, no tendency to increase the dose,
and an absence of physical symptoms despite some degree of psychological
dependence. A different clinical syndrome is associated with each drug, but all
involve a chronic process with progressive deterioration of psychological and
physiologic activity secondary to the habitual use of a drug. Addiction is not a
diagnosis but is defined by the American Society of Addiction Medicine as a chronic
disease of brain reward, motivation, memory, and related circuitry. Dysfunction in
these circuits has biological, psychological, social, and spiritual effects. There is a
pathologic pursuit of the substance with an inability to abstain, loss of control,
craving, and diminished recognition of the intensity of the problem. It is cyclical with
periods of relapse and remission. Without treatment, it is significantly disabling and
will result in premature death. Addiction is frequently used as a descriptor of the
most disabling and intense form of a substance use disorder.
neurochemistry of the addictive process is possibly the same for all drugs, the
psychosocial and pharmacokinetic aspects vary from drug to drug. Evidence,
consistent with models established for alcoholism, indicates that genetically inherited
traits may result in expression of addictive disease when the person is exposed to
certain drugs and other habituating psychic stimuli.
QUESTION 1: R.L., age 26, was recently arrested for possession and driving under the influence (DUI)
weekly use. Does R.L. meet the criteria for a diagnosis of a substance use disorder?
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
cites criteria for substance-related disorders and divides them into two groups: the
substance use disorders Table 90-1) and the substance-induced disorders
(intoxication, withdrawal, and others).
In 2014, an estimated 27 million persons age
12 or older were classified as current illicit drug users.
Pharmacologic treatment is only one aspect of the management of substance use
disorders. Treatment of withdrawal (when needed depending on the chemical of
abuse) is the first step in management and should be followed by individualized,
psychosocial treatment that is effective in the least restrictive and most cost-effective
manner. A strong therapeutic alliance between care provider and patient based on a
supportive, empathic, nonjudgmental, clinically appropriate relationship is
predictive of successful therapy outcomes. Substance use disorder is a complex
disease that disrupts many if not all aspects of an individual’s life. Therefore,
multimodal treatment is necessary. Psychosocial therapies that may or may not
include pharmacologic agents consist of individual as well as group counseling,
cognitive-behavioral therapies (learning triggers for use, new coping mechanisms,
and relapse prevention), motivational enhancement therapies, family counseling, and
voucher-based reinforcement therapy among others. These therapies are often
augmented with involvement in support groups, such as 12-step programs.
American Psychiatric Association, Diagnostic and Statistical Manual of Mental
Disorders, Criteria for Substance Use Disorders
The patient must display 2 of the following in the last 12 months
Consuming larger amounts of the substance
a or over a longer period of time than was intended
Persistent desire to reduce substance use or unsuccessful efforts to cut down or control use
Craving or a strong urge to use the substance
Recurrent use results in failures to fulfill obligations at work, school, or home
Recurrent substance use in situations that are physically hazardous
problems caused or worsened by the substance
Tolerance defined by either of the following:
A need for increased amounts of the substance to achieve intoxication or desired effects
A markedly diminished effect with continued use of the same amount of the substance
Withdrawal as defined by either of the following:
The characteristic withdrawalsyndrome for the substance
aSubstance is defined as any drug, including alcohol.
ed. Washington, DC: American Psychiatric Publishing; 2013.
R.L. has a pattern of oxycodone use in situations in which it is physically
hazardous, as well as two arrests in the last year for DUI. R.L. meets the DSM-5
criteria for substance use disorder.
Abuse of opioids includes illicit drugs, such as heroin, and the nonmedical use of
prescription pain relievers. According to the Drug Enforcement Administration
(DEA), prescription pain relievers appear to be increasingly diverted from
legitimate and illegitimate sources of supply via the internet.
Survey on Drug Use and Health reports, among persons age 12 years or older, that
there are 4.3 million nonmedical use of pain relievers.
opiate heroin is produced in four major source areas, South America, Mexico,
Southeast Asia, and Southwest Asia. Mexico has been the predominant supplier to
the west coast of the United States and is expanding distribution in eastern US
markets as South American production has decreased.
potent, 40% to 80% pure, but contains more plant impurities than the white powder
refined heroin fromAsia or South America.
7 The purity of available heroin enables a
new, younger user population, who can smoke or snort this high purity heroin and
avoid the stigma and hazards associated with needle use. As the substance use
disorder intensifies and the user’s “habit” (amount used daily) increases, the user
will often begin injecting the drug. The Centers for Disease and Prevention (CDC)
estimates there are roughly 900,000 persons who have used heroin in the last year in
the United States. The 2014 National Survey on Drug Use and Health found that usage
of heroin has increased since the early 2000s mostly driven by the 18- to 25-year age
4 Some prescription opioid abusers will eventually switch to using heroin,
Physical dependence occurs in any patient after a few days of continuous
administration of an opioid. In the management of acute pain, opioid dependence is
generally not clinically significant because the patient is tapered off opioid
analgesics naturally because the pain condition resolves. If the opioid is abruptly
stopped, the patient may experience withdrawal symptoms; however, the intensity of
those symptoms varies depending on the individual’s physiology, as well as the dose
and duration of use of the opioid. Although the exact dose and duration of opioid
administration required to produce clinically significant physical dependence is not
known, higher doses and longer times of administration correlate with more severe
symptoms of withdrawal on cessation of opioid use.
Physical dependence is defined as a neurobiological adaptation that occurs with
chronic exposure and occurs with many drug classes regardless if they have an abuse
potential (e.g., β-blockers, steroids, SSRIs). Physical dependence and tolerance (the
need for increasing doses to achieve the initial effects of the drug) can occur in the
setting of substance use disorder, but are also expected, nonpathological sequelae of
Most studies evaluating the occurrence of opioid use disorder resulting from the
therapeutic treatment of pain have concluded the risk is low.
greater problem has been the undertreatment of pain. Yet, people at risk
environmentally or predisposed genetically for substance use disorder may have their
first exposure through a legitimate, therapeutically dosed prescription of an opiate for
an acute pain syndrome. This then progresses to an inappropriate use of the opiate
and resultant substance use disorder. Thus, pain management with opiates needs
careful monitoring (see Pain Management Chapter 55).
Certain pharmacologic properties, such as high potency, rapid onset and shorter
duration of action, and water solubility, may increase the likelihood of abuse of that
medication. Although all opioids have some abuse liability, some are intrinsically
more abusable than others. For example, the controlled-release formulations have
been promoted as less likely to cause substance use disorder than immediate-release
products, because some of the reinforcing properties, like multiple peaks and troughs,
of the opioid are reduced. When tablets, such as OxyContin, are crushed, however,
the drug’s controlled-release properties are compromised, and the result is much
higher dosages than what is available in the immediate-release formulation tablets.
Despite the manufacturer’s attempts at altering the formulation of OxyContin to make
it harder to tamper with, this product can still be abused. Mixed agonist–antagonist
opioids (pentazocine, nalbuphine, butorphanol, buprenorphine) have less potential
for misuse than the pure mu agonists (e.g., morphine, hydromorphone, oxycodone);
however, misuse to all has been observed.
8 Other options to reduce diversion and
misuse are formulary management strategies that help the clinician limit opiate
In total, the best method of reducing this problem is a combination
of psychosocial therapy, pharmacotherapy, and policy.
The term “pseudoaddiction” has been coined to describe the inaccurate
interpretation of certain “drug-seeking behaviors” in patients who are inadequately
actually reflects a need for pain relief, but is erroneously interpreted as a severe
substance use disorder (addiction).
The common practice of sharing needles and syringes between friends has resulted in
transmission of various infectious diseases. Chief among those is viral hepatitis,
specifically the hepatitis C virus (HCV). According to the CDC, in the United States,
human immunodeficiency virus (HIV) infection caused by injection drug use had an
overall prevalence of 6% in 2015.
11 Other infectious diseases such as syphilis,
tetanus, botulism, and malaria can be transmitted in a similar manner and should be
considered when evaluating these patients. When heroin is prepared for self-
administration, cotton is used as a filter to trap adulterants; thus, some of the drug
remains trapped in the cotton. These crude filters are saved, and when money or drug
availability is poor, water or other solvents are added to the “old cottons” to extract
any remaining drug for intravenous (IV) use. “Cotton fever” is an acute febrile
reaction. The onset is within 30 minutes of injection, with shaking chills, diaphoresis,
postural hypotension, tachycardia, and low-grade fever. These symptoms are initially
suggestive of sepsis, but most of the symptoms resolve without treatment in 2 to 4
hours, with complete recovery in 1 day. The causal agent is probably Pantoea
(formerly Enterobacter) agglomerans, via a heat-stable endotoxin.
plants are heavily colonized with P. agglomerans.
IV drug users will often use the
term cotton fever to describe any short-term illness characterized by fever, chills,
Immediate treatment includes airway management, cardiorespiratory support, and
opioid reversal with naloxone. Naloxone is a full opioid competitive antagonist that
rapidly reverses the respiratory depression and hypotension associated with
overdose. The preferred route of administration is IV; if access cannot be gained, it
may be given intramuscularly (IM), subcutaneously (SC), intranasally, or by
endotracheal tube. Intranasal use by first responders and friends or family members
of those who have overdosed has shown to have saved lives.
Initial IV administration of 0.2 to 0.4 mg naloxone should be slow and should be
discontinued if T.F. responds. It is not necessary to precipitate opioid withdrawal
symptoms; the end point of naloxone therapy is a relative stabilization of the patient’s
vital signs. A naloxone-precipitated, sudden-onset withdrawal syndrome is more
severe than the symptoms produced by abstinence alone. Repetitive doses should be
given if the patient remains unresponsive, up to a maximal dose of 10 mg of
If the patient still has not responded, the diagnosis of opioid overdose
The duration of action of naloxone ranges from 20 to 60 minutes, depending on the
dose and route of administration. Treatment of the methadone-overdosed patient will
require serial dosing of naloxone every 20 to 60 minutes because the toxic effects of
this long-acting opiate recur.
15 The patient must be carefully observed after the
termination of naloxone therapy to detect any reappearance of opioid intoxication. An
IV infusion of naloxone may be appropriate if high doses are needed or if the patient
has recurrent respiratory depression.
Treatment of Opioid Withdrawal Syndrome
withdrawalsymptoms and what treatment options there are available for detoxification.
Abstinence precipitated a withdrawal syndrome in D.J.; therefore, he is physically
dependent on heroin. The powerful ability of the drug to rapidly alleviate withdrawal
symptoms results in reinforcement to continue using the drug. D.J.’s ongoing desire to
continue using heroin despite his inability to afford it and his all-day hustling
constitutes a psychological dependence on heroin. Noticeable opioid physical
dependence is highly variable, but it is assumed that the potential for an abstinence
syndrome exists after repeated administration for only a few days.
Six to twelve hours after the last dose of morphine or heroin (diacetylmorphine),
patients physically dependent will experience symptoms of anxiety, hyperactivity,
restlessness, and insomnia with yawning, sialorrhea, rhinorrhea, and lacrimation.
There may also be profuse diaphoresis with concurrent shaking chills and pilomotor
activity resulting in waves of gooseflesh of the skin (thus, the term cold turkey).
Anorexia, nausea, vomiting, abdominal cramps, and diarrhea may occur. Severe back
pain may accompany muscle spasms that cause kicking movements (“kicking the
habit”). These symptoms are most severe 48 to 72 hours after the last opioid dose.
D.J. is exhibiting typical heroin withdrawal symptoms, and supportive therapy would
During withdrawal, the heart rate and blood pressure may be elevated. Inadequate
nutrition and hydration, combined with vomiting, sweating, and diarrhea, can result in
marked weight loss, dehydration, ketosis, and acid–base imbalance. Rarely,
cardiovascular collapse has occurred during the peak phase of opiate withdrawal.
The more dramatic symptoms of heroin withdrawal subside after 7 to 14 days of
abstinence even without treatment; however, a return to complete physiologic
equilibrium may require months or longer.
The character, severity, and time course of withdrawal symptoms that appear when
an opioid drug is discontinued depend on many factors, including the particular
opioid, total daily dose, interval between doses, duration of use, and the health and
personality of the user. Unlike the withdrawal symptoms from sedative-hypnotic
drugs, opioid withdrawal symptoms are seldom life-threatening.
Physiologic withdrawal symptoms from all opioid drugs are qualitatively similar
but quantitatively different in onset, duration, and severity. Opioids with shorter
durations of action tend to produce brief, intense abstinence syndromes, whereas
eliminated from the body at much slower rates produce prolonged but milder
Treatment options for detoxification usually involve either an abrupt cessation of
the opioid with supportive nonopioid pharmacotherapeutic options or opioid
substitution. Currently, methadone and buprenorphine are FDA-approved for the
opiate substitution indications. The nonopiate approach involves symptomatic
treatment of withdrawal. The mainstay of this approach is the α2
third approach uses rapid detoxification precipitated by an opioid antagonist under
Methadone is a synthetic oral opiate agonist with a prolonged duration of action of
12 to 24 hours. Pharmacologically, it is qualitatively identical to morphine and other
opioid analgesics. Methadone detoxification involves stabilizing the patient on a
daily methadone dose that is determined by the patient’s response based on objective
symptoms of withdrawal. This may involve the use of standard rating scales for
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