Psychiatry · Substance-Related Disorders
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
Alcohol is the most commonly abused and tested substance; screen with the CAGE questionnaire, where >=2 positive answers suggest alcohol use disorder.
Alcohol withdrawal is treated with benzodiazepines (chlordiazepoxide, or lorazepam/oxazepam in liver disease) plus thiamine, folate, and multivitamins.
Give thiamine before glucose to prevent precipitating Wernicke encephalopathy.
Delirium tremens (autonomic instability, confusion, hallucinations) appears days after cessation and carries high mortality if untreated.
Opioid overdose causes pinpoint pupils and respiratory depression and is reversed with naloxone; opioid withdrawal is managed with clonidine, methadone, or buprenorphine.
Long-term alcohol pharmacotherapy includes naltrexone, acamprosate, and disulfiram, with Alcoholics Anonymous the most effective psychosocial intervention.
Flumazenil can precipitate seizures in benzodiazepine-dependent patients.
Vignette unlocked
A 56-year-old man admitted 2 days ago for pancreatitis becomes acutely confused, tremulous, and diaphoretic. He is tachycardic and hypertensive and reports seeing bugs crawling on the walls. His last alcoholic drink was the night before admission. He has a long history of heavy daily alcohol use.
Which of the following is the most appropriate next step in management?
Administer a benzodiazepine (with thiamine before glucose).
Confusion, tremor, autonomic instability, and visual hallucinations days after alcohol cessation in a hospitalized patient indicate delirium tremens. Benzodiazepines are the treatment of choice, and thiamine must be given before glucose to prevent Wernicke encephalopathy.
Full handout
High yield triage
Etiology / Epidemiology
Maladaptive substance use with continued use despite harm; alcohol is the most commonly abused/tested substance; screen with the CAGE questionnaire.
Clinical Manifestations
Distinct intoxication and withdrawal syndromes per substance; alcohol withdrawal to tremor, seizures, delirium tremens; opioid overdose to pinpoint pupils and respiratory depression.
Diagnosis
Clinical (DSM-5 use pattern) plus urine drug screen; >=2 positive CAGE answers suggest alcohol use disorder.
Treatment
Alcohol withdrawal: benzodiazepines + thiamine; opioid overdose: naloxone; maintenance: naltrexone, acamprosate, disulfiram (alcohol); methadone/buprenorphine (opioids).
Prognosis
Chronic relapsing; untreated delirium tremens carries high mortality.
Full handout
Epidemiology & Etiology
A substance use disorder is a maladaptive pattern of use leading to hazardous behavior, legal and interpersonal problems, failure to meet obligations, cravings, and continued use despite adverse consequences. Alcohol is the most commonly abused and most commonly tested substance. Before assigning any psychiatric diagnosis, always rule out substance use as a cause. Intoxication is a reversible substance-induced change; withdrawal is the syndrome following cessation or reduction after dependence.
Pertinent Anatomy
Addiction centers on the mesolimbic dopamine reward pathway, the ventral tegmental area projecting to the nucleus accumbens, which most drugs of abuse activate to release dopamine. Alcohol and benzodiazepines potentiate inhibitory GABA and inhibit NMDA glutamate receptors, so abrupt cessation causes glutamatergic hyperexcitability (withdrawal seizures, delirium tremens). Opioids act on mu receptors causing analgesia, euphoria, and respiratory depression (reversed by naloxone); stimulants block dopamine/norepinephrine reuptake.
Pathophysiology
Repeated drug exposure produces neuroadaptation in the dopaminergic reward circuit, driving tolerance, craving, and compulsive use. With alcohol/benzodiazepines, chronic GABA potentiation and NMDA suppression lead to compensatory receptor changes, so withdrawal unmasks a hyperexcitable, hyperadrenergic state (tremor, seizures, autonomic instability, delirium tremens). Opioid tolerance reflects mu-receptor adaptation; overdose kills via mu-mediated respiratory depression. Stimulant intoxication produces sympathetic and dopaminergic excess.
Clinical Manifestations
Each substance has characteristic intoxication and withdrawal syndromes. Alcohol withdrawal progresses from tremors and anxiety to hallucinations and seizures to delirium tremens (autonomic instability, confusion); a classic vignette is a hospitalized patient who becomes confused with tremors and visual hallucinations ("bugs on the walls") the day after admission. Opioid intoxication causes pupillary constriction, drowsiness, slurred speech, and respiratory depression/coma, while opioid withdrawal causes lacrimation, cramps, diarrhea, and piloerection. Stimulant (cocaine/amphetamine) intoxication causes euphoria, hypervigilance, dilated pupils, and autonomic hyperactivity.
Diagnosis
Diagnosis is clinical, based on the DSM-5 maladaptive-use pattern, supported by collateral history and a urine drug screen. For alcohol, the CAGE questionnaire (Cut down, Annoyed, Guilty, Eye-opener) is a quick screen, with >=2 positive answers warranting further assessment. Always consider substance use as the cause of new psychiatric or confusional presentations, particularly withdrawal in recently hospitalized patients.
Treatment
Alcohol withdrawal is treated with benzodiazepines (chlordiazepoxide, or lorazepam/oxazepam in liver disease) plus thiamine, folate, and multivitamins; give thiamine before glucose to prevent Wernicke encephalopathy. Opioid overdose is reversed with naloxone; opioid withdrawal is managed with clonidine, methadone, or buprenorphine. Long-term alcohol pharmacotherapy includes naltrexone, acamprosate, and disulfiram, with Alcoholics Anonymous the most effective psychosocial intervention. Stimulant intoxication is treated supportively with benzodiazepines/antipsychotics. Flumazenil can precipitate seizures in benzodiazepine-dependent patients.
Prognosis
Substance use disorders are chronic, relapsing conditions, but structured detoxification, rehabilitation, mutual-support groups, and pharmacotherapy substantially improve outcomes. Untreated delirium tremens carries significant mortality and is a medical emergency. Opioid overdose is rapidly fatal without naloxone. Comorbid psychiatric illness worsens prognosis, and integrated treatment of both conditions is essential.
Differential Diagnosis
Primary Psychiatric Disorder: psychosis or mood symptoms that persist despite abstinence and a negative drug screen suggest a primary disorder rather than substance-induced.
Delirium from medical cause: infection, metabolic derangement, or hypoxia can mimic withdrawal; review timing, vitals, and labs, withdrawal typically follows cessation.
Wernicke Encephalopathy: triad of confusion, ophthalmoplegia, and ataxia in alcohol use; reversible with prompt thiamine, distinct from delirium tremens.
Sedative-hypnotic (benzodiazepine) withdrawal: tremor and seizures resembling alcohol withdrawal; identify by medication history.
Sympathomimetic toxicity vs anticholinergic toxidrome: both cause agitation and dilated pupils, but anticholinergic patients are dry/flushed with urinary retention whereas stimulant users are diaphoretic.