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Substance-Related and Addictive Disorders

Substance use disorders are a significant cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status, especially among adolescents and young adults. A substance-related (addictive disorder) is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. There are several individual substance use disorders, and they are linked by their chronicity and the significant impairment they cause. Most substance use disorders have associated intoxication and withdrawal symptoms. Treatment options include pharmacotherapy and behavioral interventions; however, individuals with substance use disorders have frequent relapse Relapse Relapsing Fever/ remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches as well as low compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology with treatment.

Last updated: Mar 29, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Introduction

The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) Work Group revisions combined abuse and dependence criteria from previous classifications into a single substance use disorder.

  • Lack of agreement on the terms “addiction “and “dependence” among the DSM-5 Substance-Related Disorders Work Group
  • Added the title “Substance-Related and Addictive Disorders” to include the diagnosis of “gambling addiction” (moved from “Impulse-Control Disorders”); now in the same chapter as substance use disorders 
  • New section on “Conditions for further study”:
    • Internet gaming disorder 
    • Caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants use disorder 
  • Cannabis withdrawal Cannabis withdrawal Cannabis Use Disorder disorder was added as a substance-specific diagnosis. 
  • Since DSM-5 combines dependence and abuse, nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants use disorder was examined with regard to the substance use disorders criteria for research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest and clinical assessment. “Tobacco use disorder” was aligned with the criteria for other substance use disorders.
  • Disorders involving sexual behaviors or eating are not listed under addictive disorders; they are included elsewhere in the DSM-5.

Definition

A substance-related (addictive disorder) is the continued use of a substance despite harmful consequences, including significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home due to substance use.

Epidemiology

  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: approximately 7.2% of individuals > age 12 in the United States:
    • 5.3% with alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder
    • 2.8% with illicit drug use disorder
    • Total > 7.2% because the 2 disorders may coexist.
  • Clinical assessment of substance use:
    • Unhealthy use of 1 substance ↑ likelihood of unhealthy use of other substances.
    • Start with “socially accepted” substances:
      • Caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants
      • Tobacco/ nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants
      • Alcohol
    • Prescription medication misuse:
      • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
      • Sedative/hypnotics
      • Stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants
    • Marijuana
    • Illicit drugs Illicit Drugs Drugs that are manufactured, obtained, or sold illegally. They include prescription drugs obtained or sold without prescription and non-prescription drugs. Illicit drugs are widely distributed, tend to be grossly impure and may cause unexpected toxicity. Delirium:
      • Stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants (e.g., methamphetamine Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Stimulants, cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics)
      • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics (e.g., heroin Heroin A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of federal regulations, title 21 parts 329. 1, 1308. 11 (1987). Sale is forbidden in the United States by federal statute. Nephrotic Syndrome)
      • Hallucinogens
      • Inhalants

Etiology

  • Combination of multiple factors 
  • Biologic factors:
    • Feedback cycle of drug use or dangerous behavior
    • Dependence/escalation
    • Withdrawal/ relapse Relapse Relapsing Fever
    • Enhanced effect of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS at the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles accumbens 
    • Drugs of abuse replace reinforcement 
  • Genetic factors:
    • Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder: correlated with biologic parents
    • No specific genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure have been identified with other substance use disorders. 
  • Environmental factors:
    • Low socioeconomic status
    • Pressure from substance-using peers 
  • Personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders (especially cluster B):
    • Borderline 
    • Histrionic 
    • Narcissistic
    • Antisocial
Cycle of substance-related and addictive disorders

Cycle of substance-related and addictive disorders

Image by Lecturio.

Clinical Presentation and Management

Substance use disorder assessments should establish the type of substance(s) used as well as the frequency, amount, and whether other mental health disorders (mood disorders, schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia, personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders) or past history of substance use disorder are present.

Effect of substances on pupils

Substances causing pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities dilation:

  • Opioid withdrawal Opioid withdrawal Opioid Use Disorder
  • Amphetamine
  • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Lysergic acid diethylamide (LSD)
  • Anticholinergics Anticholinergics Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs ( atropine Atropine An alkaloid, originally from atropa belladonna, but found in other plants, mainly solanaceae. Hyoscyamine is the 3(s)-endo isomer of atropine. Anticholinergic Drugs, tropicamide Tropicamide One of the muscarinic antagonists with pharmacologic action similar to atropine and used mainly as an ophthalmic parasympatholytic or mydriatic. Anticholinergic Drugs, scopolamine Scopolamine An alkaloid from solanaceae, especially datura and scopolia. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Its many uses include an anesthetic premedication, the treatment of urinary incontinence and motion sickness, an antispasmodic, and a mydriatic and cycloplegic. Antiemetics)
  • Medications with anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs activity ( tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants, antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines)
  • Sympathomimetics Sympathomimetics Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs

Substances causing pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities constriction:

  • Opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation intoxication
  • Heroin Heroin A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of federal regulations, title 21 parts 329. 1, 1308. 11 (1987). Sale is forbidden in the United States by federal statute. Nephrotic Syndrome
  • Sympatholytics (alpha-2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs, decongestants)
  • Parasympathomimetics Parasympathomimetics Cholinomimetic drugs, also known as parasympathomimetics or cholinergic agonists, increase acetylcholine (Ach), which acts on cholinergic muscarinic and nicotinic receptors. Other cholinomimetic drugs result in a net cholinergic effect by inhibiting the cholinesterase enzyme. Cholinomimetic Drugs ( pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs), organophosphates

Summary of intoxication findings and their management: stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants

Table: Summary of intoxication findings and their management: stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants
Substance Intoxication findings Management
Nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants/tobacco
  • Restlessness, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
  • Increase GI motility GI Motility The primary functions of the GI tract are digestion and absorption, which require coordinated contractions of the smooth muscles present in the GI tract. Peristaltic waves, segmentation contractions, and the migrating motor complex are all important contraction patterns that help to mix contents, get them in contact with the intestinal walls, and propel material down the tract at appropriate times and in appropriate amounts. Gastrointestinal Motility
Supportive treatment
Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, diaphoresis
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy, psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, or depression
  • Dilated pupils
  • Elevated blood pressure, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Hyperthermia
  • Psychosis, paranoia, hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • May present with MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
  • Intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage or stroke (due to vasoconstrictive effect)
  • Reassurance Reassurance Clinician–Patient Relationship
  • Antipsychotics and benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for severe cases of aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder
  • Symptomatic support (control blood pressure, arrhythmias)
  • Treating hyperthermia with ice bath, cooling blanket
Amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions excoriation Excoriation Mastitis
  • Pupillary dilation
  • Restlessness, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, arrhythmia, hyperthermia
  • Hyperreflexia and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Psychosis (delusions, paranoia)
  • Dry mouth (leading to tooth decay)
  • Stabilize (rehydrate, correct electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes).
  • Treat hyperthermia.
  • Treat sympathetic overactivity.
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines: 1st-line option to decrease agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
Synthetic canthinones (“bath salts”): a stimulant found naturally in the khat plant
  • Severe agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, combativeness
  • Psychosis, delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
  • Myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Sympathetic overactivity (significantly increased blood pressure, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children)
  • Long-duration symptoms (days to weeks)

Summary of intoxication findings and their management: depressants

Table: Summary of intoxication findings and their management: depressants
Substance Intoxication findings Management
Alcohol
  • Mood elevation
  • Sedation
  • Behavioral disinhibition, emotional lability
  • Slurred speech Slurred Speech Cerebellar Disorders
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia (positive field sobriety test)
  • Self-resolving, requires supportive treatment only
  • Ensure safety of individual: airway Airway ABCDE Assessment, breathing, circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (ABCs)
  • Administer thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies.
  • Correct glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes, acid–base disorders.
Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Constricted pupils (not in all cases)
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy
  • Slurred speech Slurred Speech Cerebellar Disorders
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Respiratory depression
  • Maintain ABCs.
  • Administer naloxone Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. Opioid Analgesics.
  • Ventilatory support if naloxone Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. Opioid Analgesics fails to improve respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal)
Sedatives and hypnotics ( benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines, barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics)
  • Drowsiness, confusion, slurred speech Slurred Speech Cerebellar Disorders, impaired memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment
  • Incoordination, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, mood lability
  • Respiratory depression
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Impaired judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment, nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
  • Ensure safety of individual (ABCs)
  • Barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes for urine alkalinization
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines flumazenil Flumazenil A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. Benzodiazepines (use with caution, as may induce seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures)

Summary of intoxication findings and their management: hallucinogens

Table: Summary of intoxication findings and their management: hallucinogens
Substance Intoxication findings Management
Cannabis
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy or feeling relaxed
  • Conjunctival injection
  • Psychomotor slowing
  • Increased appetite
  • Dry mouth
  • Supportive treatment
Hallucinogens (e.g., phencyclidine ( PCP PCP Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP)))
  • Violent behavior, impulsivity Impulsivity Attention Deficit Hyperactivity Disorder
  • Severe hyperthermia
  • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Put the individual in a quiet room.
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines (1st-line)
  • Antipsychotics if needed
Hallucinogens (e.g., LSD)
  • Depersonalization Depersonalization State in which an individual perceives or experiences a sensation of unreality concerning the self or the environment; it is seen in disorders such as schizophrenia, affection disorders, organic mental disorders, and personality disorders. Depersonalization/Derealization Disorder
  • Hemodynamic changes ( tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension)
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Quiet room
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines (1st-line)
  • Clonidine Clonidine An imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension. Sympathomimetic Drugs if needed
Ecstasy Ecstasy An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants ( methylenedioxymethamphetamine Methylenedioxymethamphetamine An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants ( MDMA MDMA An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants))
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Psychosis
  • Sociability
  • Hyperthermia
  • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
  • Hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome
  • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome/acute tubular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage (ATN)
  • Stabilize individual (rehydrate, correct electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes).
  • Treat hyperthermia.
  • Treat sympathetic overactivity.
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines (1st-line) to decrease agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Consider dantrolene Dantrolene Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. Spasmolytics (postsynaptic muscle relaxant).
Inhalants
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy
  • Impaired judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment and memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment
  • Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, stupor, or coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Nasal crusting, rash Rash Rocky Mountain Spotted Fever ( dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema))
  • Intoxicated appearance, tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies, muscle weakness, hyporeflexia Hyporeflexia Duchenne Muscular Dystrophy, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Supportive care
  • Chelation if possible
  • Preventing and treating complications
  • Hyperbaric chamber
  • Psychological counseling
  • Antipsychotics

Summary of withdrawal findings and their management: stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants

Table: Summary of withdrawal findings and their management: stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants
Substance Withdrawal findings Management
Nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants/tobacco
  • Intense craving
  • Dysphoria
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
  • Poor concentration
  • Increased appetite, weight gain
  • Irritability, restlessness, and insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Malaise Malaise Tick-borne Encephalitis Virus, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, hypersomnolence Hypersomnolence Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., idiopathic hypersomnolence; narcolepsy; and kleine-levin syndrome) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, mental disorders, and sleep apnea syndrome). Whipple’s Disease
  • Depression, anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia, hunger, constricted pupils
  • Vivid dreams, psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or retardation
  • Increased suicidal ideation Suicidal ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. Suicide
  • Supportive treatment only
Amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants, synthetic canthinones (“bath salts”)
  • Increased appetite
  • Severe depression
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance and vivid dreams
  • Difficulty concentrating
  • Mostly supportive treatment
  • Antidepressants if suicidal
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines or antipsychotics to decrease irritability and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder

Summary of withdrawal findings and their management: depressants

Table: Summary of withdrawal findings and their management: depressants
Substance Withdrawal findings Management
Alcohol
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, tremors, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, palpitations Palpitations Ebstein’s Anomaly
  • Generalized tonic-clonic seizures Generalized tonic-clonic seizures A generalized seizure disorder characterized by recurrent major motor seizures. The initial brief tonic phase is marked by trunk flexion followed by diffuse extension of the trunk and extremities. The clonic phase features rhythmic flexor contractions of the trunk and limbs, pupillary dilation, elevations of blood pressure and pulse, urinary incontinence, and tongue biting. This is followed by a profound state of depressed consciousness (post-ictal state) which gradually improves over minutes to hours. The disorder may be cryptogenic, familial, or symptomatic (caused by an identified disease process). Epilepsy
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia (mainly visual)
  • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium tremens (confusion, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia, tremors)
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines ( lorazepam Lorazepam A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. Benzodiazepines is preferred with hepatic failure Hepatic failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis)
  • Vitamins ( thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies, folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12)
  • Correct electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Dysphoria (depression), insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
  • Lacrimation, rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus, yawning, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Sweating, piloerection, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, dilated pupils, abdominal cramps Cramps Ion Channel Myopathy
  • Arthralgias, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Moderate symptoms: clonidine Clonidine An imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension. Sympathomimetic Drugs, NSAIDs NSAIDS Primary vs Secondary Headaches
  • Severe symptoms: detoxification with buprenorphine Buprenorphine A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. Opioid Analgesics or methadone Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. Opioid Analgesics (usually resolve within 2–3 days)
Sedatives and hypnotics ( benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines, barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics)
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
  • Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies
  • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, psychosis
  • Perceptual disturbances
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, palpitations Palpitations Ebstein’s Anomaly
  • Taper using a long duration medication ( diazepam Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. Benzodiazepines, phenobarbital Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates gamma-aminobutyric acid action on gaba-a receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. First-Generation Anticonvulsant Drugs)

Summary of withdrawal findings and their management: hallucinogens

Table: Summary of withdrawal findings and their management: hallucinogens
Substance Withdrawal findings Management
Cannabis
  • Craving
  • Sleeping disturbances, vivid dreams
  • Restlessness
  • Hyperalgesia Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing nociceptors or injury to a peripheral nerve. Pain: Types and Pathways
  • Depression
  • Headaches, sweating, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
  • Decreased appetite
  • Supportive treatment
Inhalants
  • Craving and irritability
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance
  • Increase sweating
  • Muscle aches
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
  • Depression
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Supportive care
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines and antipsychotics may be helpful.
Ecstasy Ecstasy An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants
  • Depression, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, change in appetite
  • Decreases concentration, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
  • Supportive treatment
  • Antidepressants if suicidal

Diagnosis

The DSM-5 uses 11 criteria (including dependence criteria, abuse criteria, and craving) to classify substance use disorders. There are separate criteria for substance intoxication and withdrawal.

Criteria for substance use disorders (including gambling disorder Gambling disorder Gambling disorder is chronic, recurrent, maladaptive gambling behavior that results in impairment in social or personal life. The disorder fits under the umbrella of addictive disorders due to a strong compulsion to gamble as well as tolerance and withdrawal effects that are similar to substance use disorder. Gambling Disorder)

Diagnosis is made by a problematic pattern of use leading to significant impairment or distress manifested by ≥ 2 of the following in a 12-month period:

Impaired control:

  • Overconsumption of the substance
  • Inability to cut down or control use
  • Excessive time spent obtaining, using, or recovering from effects of a substance/gambling
  • Craving 

Social impairment:

  • Failure to fulfill major role obligations due to substance use/gambling
  • Continued use despite social or interpersonal problems caused by the substance
  • Reduction/stopping social, occupational, or recreational activities due to substance use/gambling

Risky use:

  • Recurrent substance use in physically hazardous situations
  • Continued use despite physical or psychological problems caused by the substance/gambling

Pharmacologic criteria inherent to the substance:

  • Tolerance Tolerance Pharmacokinetics and Pharmacodynamics, defined as either:
    • A need for an ↑ amount of the substance to achieve the desired effect, or 
    • A diminished effect with continued use of the substance
  • Withdrawal, manifested by either:
    • Withdrawal signs, or
    • Relief or avoidance of withdrawal symptoms by ingestion of the substance or similar substance

Other factors relevant to diagnosis:

  • Severity score = total of substance disorder criteria met MET Preoperative Care:
    • Mild: 2–3 criteria
    • Moderate: 4–5 criteria
    • Severe: > 6 criteria
  • There is no longer a diagnosis of “polysubstance use disorder” or “multiple substance use disorder”; each substance must be listed. 
  • There are no agreed-upon definitions for unhealthy use of substances other than alcohol:
    • Men:
      • > 5 drinks/day (1 drink = 12 g of ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism (43 mL (1.5 oz) of 80 proof liquor, 142 mL (5 oz) of wine, or 341 mL (12 oz) of beer))
      • > 14 drinks per week on average
    • Women (any age) or men > age 65:
      • > 4 drinks/day
      • > 7 drinks/week on average
    • For some other substances, any use may be considered unhealthy.

Criteria for substance intoxication and withdrawal

  • Intoxication:
    • Recent usage history
    • Intoxication signs/physiologic correlation Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability (varies by substance):
    • Clinically significant functional impairment
    • Exclusion of other medical conditions or mental disorders
  • Withdrawal: development of a substance-specific syndrome due to the cessation (or reduction) of substance after heavy and prolonged use:
    • Physical symptoms:
      • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
      • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
      • Chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever 
      • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
    • Psychological symptoms: compulsion or perceived need to use the substance
    • Clinically significant functional impairment
    • Exclusion of other medical conditions or mental disorders
  • Tolerance Tolerance Pharmacokinetics and Pharmacodynamics: need to increase the dose of the substance or intensity of the behavior to achieve the same desired effect 
  • Substance-induced psychiatric disorders: each substance may cause a range of psychiatric syndromes during intoxication or withdrawal phase.

Assessment

  • History:
    • Starts with a nonjudgmental interview; individuals are often unwilling to disclose substance use habits to a healthcare provider.
    • Include social issues related to substance use (e.g., lack of housing)
    • Inquire: use the SBIRT (Screening, Brief Intervention, and Referral to Treatment) tool
      • Screen individuals for substance use and addictive disorders.
      • Assess the severity of substance use.
      • Identify the appropriate level of treatment. 
      • Brief intervention (discussion about risks of unhealthy habits)
      • Assess motivation toward behavioral change.
      • Refer to specialty care if needed.
      • Follow up regularly.
  • Physical exam:
    • Identify medical diagnoses.
    • Concomitant psychiatric conditions
  • Lab studies to evaluate possible comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:
    • Chemistry panel: electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes, renal, hepatic function 
    • HIV HIV Anti-HIV Drugs and hepatitis serologies if IV substance use
  • Urine drug toxicology screen:
    • Useful in offering treatment during the intoxication or withdrawal phase 
    • Basic urine drug screens include:
      • Amphetamine
      • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines 
      • Cannabis
      • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
      • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
      • PCP PCP Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP) 
    • Many substances can cause false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests results.

Management and Complications

Substance use disorders often coexist with other medical and psychiatric conditions.

Management

  • Information gathered in the history, exam, and substance use assessment help identify:
    • Severity of the disorder; may warrant multiple treatment methods
    • Readiness for treatment
    • Level of treatment needed (outpatient versus inpatient)
  • Behavioral interventions:
    • Motivational interviewing Motivational interviewing It is a client-centered, directive method for eliciting intrinsic motivation to change using open-ended questions, reflective listening, and decisional balancing. This nonjudgmental, nonconfrontational interviewing style is designed to minimize a patient’s resistance to change by creating an interaction that supports open discussion of risky or problem behavior. Psychotherapy: an approach for behavioral modifications 
    • CBT:
      • Helps identify triggers for use 
      • Creates healthier coping skills
    • Group therapy Group therapy A form of therapy in which two or more patients participate under the guidance of one or more psychotherapists for the purpose of treating emotional disturbances, social maladjustments, and psychotic states. Psychotherapy or other peer support groups:
      • Alcoholics Anonymous Alcoholics Anonymous An organization of self-proclaimed alcoholics who meet frequently to reinforce their practice of abstinence. Alcoholic Liver Disease ( AA AA Amyloidosis)
      • Narcotics Anonymous (NA)
      • Gamblers Anonymous (GA)
      • Other community-based support groups
  • Pharmacotherapy: medications to decrease cravings or abuse:
    • Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder:
      • Naltrexone Naltrexone Derivative of noroxymorphone that is the n-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. Opioid Analgesics
      • Disulfiram
      • Acamprosate
      • Gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs
    • Opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation use disorder:
      • Methadone Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. Opioid Analgesics
      • Buprenorphine Buprenorphine A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. Opioid Analgesics
      • Naltrexone Naltrexone Derivative of noroxymorphone that is the n-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. Opioid Analgesics
      • Lofexidine
    • Hallucinogen Hallucinogen Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. Hallucinogen Use Disorder use disorder:
      • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines 
      • Antipsychotics 
    • Tobacco use disorder ( nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants):

Relapse Relapse Relapsing Fever and complications

  • Substance use and addiction:
    • Complex and chronic disease
    • Associated with compromised functioning in almost every organ system 
  • Relapse Relapse Relapsing Fever:
    • Rate of relapse Relapse Relapsing Fever: 40%–60% despite treatment
    • Does not indicate treatment failure; considered a normal part of recovery
    • Need to modify or change the treatment plan
    • Nonadherence Nonadherence Clinician–Patient Relationship: similar levels to other chronic illnesses (e.g., hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)
  • Dropout rate of in-person psychosocial substance use disorder treatment studies: variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables, but approximately 30%
  • Neonatal complications of mothers with substance use disorder:
  • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding: not contraindicated unless active use or untreated substance use disorder

References

  1. National Institute on Drug Abuse. (n.d.). Principles of effective treatment. https://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/principles-effective-treatment
  2. Sadock, B. J., Sadock, V. A., Ruiz, P. (2014). Substance use and addictive disorders. In Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 11th ed. Philadelphia: Lippincott Williams and Wilkins, pp. 616–693.
  3. Thompson, A. (2021). Clinical management of drug use disorders. DeckerMed Medicine. Retrieved February 16, 2021, https://doi.org/10.2310/im.13042
  4. Hoffman, R. (2021). Testing for drugs of abuse (DOAs). UpToDate. Retrieved March 7, 2021, from https://www.uptodate.com/contents/testing-for-drugs-of-abuse-doa 
  5. Chang, G. (2020). Substance use during pregnancy: screening and prenatal care. UpToDate. Retrieved March 7, 2021, from https://www.uptodate.com/contents/substance-use-during-pregnancy-screening-and-prenatal-care
  6. Hasin, D.S., et al. (2013). DSM-5 criteria for substance use disorders: recommendations and rationale. American Journal of Psychiatry 170:834–851. https://doi.org/10.1176/appi.ajp.2013.12060782
  7. Dugosh, K.L., Cacciola, J.S. (2019). Clinical assessment of substance use disorders. UpToDate. Retrieved August 26, 2021, from https://www.uptodate.com/contents/clinical-assessment-of-substance-use-disorders
  8. Lappan, S.N., Brown, A.W., Hendricks, P.S. (2019). Dropout rates of in-person psychosocial substance use disorder treatments: a systematic review and meta-analysis. Addiction 115:201–217. https://doi.org/10.1111/add.14793

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