Recognition of intoxication and withdrawal states is critical for the appropriate management of individuals with substance use disorders. In addition to being able to recognize the unique intoxication and withdrawal states of particular substances of abuse, the treatment of patients who are under the influence of, or experiencing withdrawal from, substances of abuse requires an understanding of many variables. These variables include an appreciation of the natural history and variants of such syndromes, a complete assessment of the patient’s individual medical, psychiatric, and social issues, and knowledge of the uses and limitations of a variety of behavioral and pharmacologic interventions. All therapies must be individualized to each patient’s needs and adjusted to reflect the patient’s response to treatment.
The number of referrals due to complications from acute intoxication or withdrawal from substances to emergency departments (EDs) are at all-time highs. Data from the Drug Abuse Warning Network revealed that the total number of drug-related ED visits increased 81% from 2004 (2.5 million) to 2009 (4.6 million). ED visits involving nonmedical use of pharmaceuticals increased 98.4% over the same period, from 627,291 visits to 1,244,679 (1). The largest pharmaceutical increases were observed for oxy-codone products (242.2% increase), alprazolam (148.3% increase), and hydrocodone products (124.5%). Among ED visits involving illicit drugs, only those involving ecstasy increased more than 100% from 2004 to 2009 (123.2% increase) (1). For patients aged 20 or younger, ED visits resulting from nonmedical use of pharmaceuticals increased 45.4% between 2004 and 2009 (116,644 and 169,589 visits, respectively). Among patients aged 21 or older, there was an increase of 111.0% (1).
This chapter serves as an introduction to the identification and management of intoxication and withdrawal states, with the management of specific substances to be reviewed in subsequent chapters in this section.
Intoxication is the result of being under the influence of, and responding to, the acute effects of alcohol or another drug of abuse. It typically includes feelings of pleasure, altered emotional responsiveness, altered perception, and impaired judgment and performance. The recognition of intoxication states is of paramount importance in the appropriate treatment of substance-abusing patients. Intoxication states can range from euphoria or sedation to life-threatening emergencies when overdose occurs. Typically, each substance of abuse has a set of signs and symptoms that are seen during intoxication. Identification and treatment of intoxication can lead to appropriate management of the withdrawal phenomenon and provide an avenue for entry into treatment. The initial challenge to the clinician, however, is diagnosis, because intoxication can mimic many psychiatric and medical conditions.
Identification and Management of Intoxication
The identification of intoxication begins with the collection of patient data through a patient history, physical examination, and laboratory screening. Of immediate concern is life-threatening intoxication or overdose. Thus, the first priority is general supportive care and resuscitative actions. It is important to determine not only the severity of the substance ingestion but also the patient’s level of consciousness, the substances involved, and any complicating medical disorders. Often, more than one substance of abuse is involved, and it is critical to know what substances have been ingested, as well as how much of each substance.
Historical information regarding substance use usually can be obtained from the patient. Questions regarding the quantity and frequency of substance use provide valuable information to the clinician. Discovering chronic patterns of substance use may aid in subsequent referral to addiction treatment. Acute intoxication may impede an individual’s ability to provide such information. In these cases, the patient’s companions or family may be able to provide important information.
Standardized questionnaires for self-administration by the patient or for use by the physician are designed to elicit answers related to alcohol use. Toxicology screens provide valuable information regarding the type or types of substances used. As discussed below, the rise in the use of “designer drugs” can make identification of the causative substance(s) more difficult by routine toxicology screening. When screening for substances of abuse, urine is the most widely used specimen because of the ease with which a sample is obtained, the relatively high concentrations of drugs and metabolites present in urine, and the stability of metabolites when frozen (2). Drug screens can aid in the differential diagnosis when atypical symptoms are present. Such screening can be particularly helpful in cases where little clinical history is available. Having knowledge of the particular sensitivities, specificities, and cross-reactivities of the particular urine drug screen being used is of vital importance to the appropriate interpretation of the urine drug screen. In addition, one must have an understanding of the usual duration of detectability of particular substances. However, the duration of detectability can be significantly impacted by the amount of substance ingested, individual rates of metabolism and excretion, as well as fluid ingestion of the individual.
Screening for alcohol is most frequently accomplished by breathalyzer or blood alcohol levels; however, urine tests are also available that detect metabolites of alcohol. Laboratory assays that measure increases in liver enzymes—such as gamma-glutamyl transpeptidase, aspartate aminotransfer-ase, and alanine aminotransferase—can be helpful in identifying alcohol use. Although alcohol is not the only cause of an increase in gamma-glutamyl transpeptidase (GGT), and GGT frequently does not increase in younger drinkers, this assay is a reliable predictor of drinking behavior. A biologic assay to monitor alcohol intake involves percent carbohydrate-deficient transferrin (%CDT), which is a more sensitive and specific indicator of heavy alcohol consumption (3,4). The conjugated ethanol metabolites ethyl gluc-uronide (EtG) and ethyl sulfate (EtS) are other measures used to confirm or rule out recent drinking. Although EtG and EtS account for only less than 0.1% of the ingested ethanol dose, they remain detectable in urine for several hours up to some days longer than ethanol, the time lag largely depending on the amount consumed (5).
RISE IN DESIGNER DRUGS NOT READILY DETECTED THROUGH ROUTINE TOXICOLOGY SCREENING
The rise in the use of “designer drugs” or “synthetic legal intoxicating drugs” is contributing to escalation of ED visits because of the severity of physical and behavioral hazards associated with acute intoxication. This is especially dangerous as these substances are not detected in routine drug screen, and overdose can be lethal. The psychoactive “designer drug” methylenedioxypyrovalerone, the primary ingredient in “bath salts,” is a synthetic, cathinone-derivative, central nervous system stimulant that is taken to produce a cocaine-or methamphetamine-like high. The intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, with physical manifestations ranging from tachycardia, hypertension, arrhyth-mias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure prevention measures, intravenous fluids, close monitoring, and restraints to prevent harm to self or others. The clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach (6).
“Spice” refers to a wide variety of herbal mixtures that produce experiences similar to marijuana and that are marketed as “safe,” legal alternatives to that drug. They are sold under names such as K2, fake weed, Yucatan Fire, Skunk, and Moon Rocks, and others. They are labeled “not for human consumption.” While they do contain plant material, synthetic cannabinoid compounds are responsible for their psychoactive effects. These products are popular among young people; of the illicit drugs most used by high school seniors, they are second only to marijuana. Contributing to their popularity is the misperception that they are “natural” and therefore safe, and they are not detected in routine urine drug screening. Spice users report experiences similar to those produced by marijuana (elevated mood, relaxation, and altered perception); however, the effects can be even stronger than those of marijuana. Some users report psychotic effects like extreme anxiety, paranoia, and hallucinations. Physical and neuro-logic manifestations of acute intoxication can include tachycardia, vomiting, agitation, and confusion. It has also been associated with myocardial ischemia, and in a few cases, it has been associated with myocardial infarction (7).
Salvia (Salvia divinorum) is an herb common to southern Mexico and Central and South America. The main active ingredient in Salvia, salvinorin A, is a potent activator of kappa opioid receptors in the brain. Traditionally, S. divino-rum has been ingested by chewing fresh leaves or by drinking their extracted juices. Its dried leaves can also be smoked as a joint, consumed in water pipes, or vaporized and inhaled. Users typically experience hallucinations or transient psychotic episodes. Subjective effects have been described as intense but short lived, appearing in less than 1 minute and lasting less than 30 minutes. They include psychedelic-like changes in visual perception, mood and body sensations, emotional swings, feelings of detachment, and a highly modified perception of external reality and the self, leading to a decreased ability to interact with one’s surroundings (8).
Substance withdrawal has been defined by the American Psychiatric Association as “the development of a substance-specific maladaptive behavioral change, usually with uncomfortable physiological and cognitive consequences, that is the result of a cessation of, or reduction in, heavy and prolonged substance use.” (9) The signs and symptoms of withdrawal usually are the opposite of a substance’s direct pharmacologic effects. Substances in a given pharmacologic class produce similar withdrawal syndromes; however, the onset, duration, and intensity are variable, depending on the particular agent used, the duration of use, and the degree of neuroadaptation.
Evidence for the cessation of or reduction in use of a substance may be obtained by history or toxicology. Additionally, the clinical picture should not correspond to any of the organic mental syndromes, such as organic hallu-cinosis (9). Withdrawal may, however, be superimposed on any organic mental syndrome. Therefore, a thorough physical examination is necessary, including appropriate laboratory analysis of basic organ functions.
The term detoxification implies a clearing of toxins. However, for individuals with physiologic substance dependence, detoxification is defined as the management of the withdrawal syndrome.
Goals of Detoxification
Detoxification includes a set of interventions by which a substance an individual is physically dependent on is eliminated from the body. Detoxification seeks to minimize the physical harm caused by the abuse of substances. The American Society of Addiction Medicine (ASAM) lists three immediate goals for detoxification of alcohol and other substances: (a) “to provide a safe withdrawal from the drug(s) of dependence and enable the patient to become drug-free”; (b) “to provide a withdrawal that is humane and thus protects the patient’s dignity”; and (c) “to prepare the patient for ongoing treatment of his or her dependence on alcohol or other drugs” (10). Furthermore, it comprises three essential and sequential steps: evaluation, stabilization, and fostering patient readiness for and entry into treatment (11). It is important to distinguish detoxification from substance use disorder treatment. Substance use disorder treatment/rehabilitation involves a constellation of ongoing therapeutic services ultimately intended to promote recovery for substance use disorder patients (11). Detoxification may be the first step in this process.
Many risks are associated with withdrawal, some of which are influenced by the setting in which detoxification occurs. For example, in persons who are severely dependent on alcohol, an abrupt, untreated cessation of drinking may result in marked hyperautonomic signs, seizures (which may be recurrent), withdrawal delirium, or even death. Other sedative–hypnotics also can produce life-threatening withdrawal syndromes. Withdrawal from opioids and stimulants produces severe discomfort, but generally is not life threatening. It may, however, present a danger to those who are debilitated by advanced HIV disease, medical sequelae of addiction, advanced age, coronary artery disease, and other medical problems. Moreover, risks to the patient and society are not limited to the severity of the patient’s physical disturbance, particularly when the detoxification is conducted in an outpatient setting. Outpatients experiencing withdrawal symptoms may self-medicate with alcohol or other drugs that can interact with withdrawal medications in an additive fashion or precipitate overdose.
A caring staff, a supportive environment, sensitivity to cultural issues, confidentiality, and the selection of appropriate detoxification medications (as needed) are important components of a humane withdrawal. However, staff must be clear in their treatment goals and set firm boundaries, as well as be sympathetic and have experience in dealing with difficult behaviors that often accompany detoxification. Supportive others (family members, friends, or employers) should be enlisted whenever possible to assist in the care of the patient during outpatient detoxification.
During detoxification, patients may form therapeutic relationships with treatment staff and other patients, providing an opportunity to explore alternatives to an alcohol-or drug-using lifestyle. Detoxification is therefore an opportunity to offer patients information and to motivate them for longer-term treatment. Unfortunately, managed care organizations and other third-party payers often regard detoxification as separate from other phases of alcohol and other drug treatment, as though detoxification occurs in isolation from such treatment. In clinical practice, this separation cannot exist; detoxification is but one component of a comprehensive treatment strategy.
General Principles of Management
Some detoxification procedures are specific to particular drugs, whereas others are based on general principles of treatment and are not drug specific. The general principles are presented here; subsequent chapters address specific treatment protocols for each class of drugs.
There is a risk of serious adverse consequences for some patients who undergo withdrawal. As such, an initial medical assessment is important to determine the need for medication and medical management. Such an assessment should include evaluation of predicted withdrawal severity and medical or psychiatric comorbidity. Although the severity of a given patient’s withdrawal cannot always be predicted with accuracy, helpful information includes the amount and duration of alcohol or other drug use, the severity of the patient’s prior withdrawal experiences (if any), and the patient’s medical and psychiatric history. Past complicated withdrawal should alert the practitioner to the likely possibility of future complicated withdrawals. The kindling hypothesis has been well supported in alcohol research, such that past alcohol withdrawal seizures are a strong indicator of future alcohol withdrawal seizures (12). A widely used instrument in clinical and research settings for the initial assessment and ongoing monitoring of alcohol withdrawal is the Clinical Institute Withdrawal Assessment of Alcohol–revised. The Clinical Institute Withdrawal Assessment of Alcohol–revised is a short test that rates the severity of withdrawal, as observed by the clinician. In general, low scores (<8) suggest that pharmacotherapy may not be required, whereas high scores (>10) indicate a greater risk of seizures and delirium tremens.
Every means possible should be used to ameliorate the patient’s withdrawal signs and symptoms. Medication should not be the only component of treatment, because psychological support is extremely important in reducing the patient’s distress during detoxification.
The duration of detoxification is not a clearly defined, discrete period. Because detoxification often requires a greater intensity of services than other types of treatment, there is a practical value in defining a period during which a person is “in detoxification.” The detoxification period usually is defined as the time during which the patient receives detoxification medications, even though some signs and symptoms may persist for a much longer period. Another way of defining the detoxification period is by measuring the duration of withdrawal signs or symptoms. However, the duration of these symptoms may be difficult to determine in a correctly medicated patient, because symptoms of withdrawal are largely suppressed by the medication.
Another problem in defining the duration of detoxification is the fact that many patients may have prolonged withdrawal signs or symptoms, or “protracted withdrawal syndrome.” Symptoms of the syndrome include disturbances of sleep, anxiety, irritability, mood instability, and craving. The very existence of the protracted abstinence syndrome has been the subject of considerable controversy; however, there is increasing evidence in the literature supporting its existence. The protracted withdrawal syndrome is hypothesized to be a period when individuals are at a heightened risk of relapse (13,14).