Behavioral Health

Stimulant use disorder: management

Clinical Overview and When to Suspect Stimulant Use Disorder

— Cocaine and methamphetamine overdose deaths have surged, often co-involving fentanyl ("speedball" or contaminated supply).

— High comorbidity with opioid use disorder, ADHD, depression, bipolar disorder, PTSD, and HIV/HCV from injection or sexualized use ("chemsex").

— Young or middle-aged adult with new chest pain, hypertensive urgency, stroke, seizure, or psychosis without clear cardiac risk factors.

— Unexplained weight loss, dental decay ("meth mouth"), skin excoriations ("crank bugs"), nasal septal perforation, or recurrent epistaxis.

— Erratic prescription refill behavior in a patient on prescribed amphetamines/methylphenidate for ADHD.

— Recurrent ED visits for agitation, paranoia, or unintentional injury.

— USPSTF recommends asking adults about illicit drug use (Grade B, 2020) using validated tools: NIDA Quick Screen, TAPS, DAST-10, ASSIST.

— Annual screen in primary care; integrate with SBIRT (Screening, Brief Intervention, Referral to Treatment).

Definition: Stimulant use disorder (StUD) per DSM-5-TR involves problematic use of amphetamine-type substances (methamphetamine, prescription amphetamines), cocaine, or other stimulants causing ≥2 of 11 criteria over 12 months (mild 2–3, moderate 4–5, severe ≥6).

Epidemiology relevant to Step 3:

When to suspect in the ambulatory/ED setting:

Screening tools (Step 3 ambulatory care):

Step 3 management: A positive screen mandates a structured brief intervention in the same visit—do not defer. Use motivational interviewing, assess readiness, address co-occurring conditions, and arrange warm handoff to treatment within days, not weeks.

Board pearl: Unlike opioid or alcohol use disorder, no FDA-approved pharmacotherapy exists for StUD—contingency management (CM) is the most evidence-based intervention and a recurring vignette answer.

Presentation Patterns and Key History

— Euphoria, hyperalertness, grandiosity, pressured speech, decreased appetite/sleep, hypervigilance and paranoia.

— Dose-dependent progression to agitation, stereotyped behaviors (punding), psychosis with tactile/visual hallucinations, hyperthermia, rhabdomyolysis.

— Cocaine: shorter half-life (~1 hr), repeated bingeing; methamphetamine: 8–12 hr effect, prolonged psychosis.

— Dysphoria, hypersomnia, hyperphagia, anhedonia, vivid unpleasant dreams, psychomotor retardation, intense craving, suicidal ideation.

— Peaks 2–4 days, resolves over 1–2 weeks; protracted craving persists months.

— Not typically life-threatening but suicide risk is high—always screen.

— Substance, route (smoked, IN, IV, oral), quantity, frequency, last use, time-of-day pattern.

— Triggers and contexts: sexualized use (MSM, "PnP"), occupational (long-haul drivers, students), weight loss intent.

— Co-use: opioids, alcohol, benzodiazepines, cannabis, nicotine; assume fentanyl contamination.

— Prior treatment, longest abstinence, overdose history, naloxone access.

— Pregnancy status, custody/legal issues, housing, employment.

Acute intoxication syndrome:

Withdrawal ("crash"):

Key history questions (Step 3 outpatient framework):

Psychiatric screen: PHQ-9, GAD-7, C-SSRS, PCL-5, mood-disorder questionnaire; ADHD by Adult Self-Report Scale (ASRS) after ≥4 weeks abstinence before attributing symptoms to ADHD.

Key distinction: Primary psychotic disorder vs stimulant-induced psychosis—stimulant-induced typically resolves within days to a month of abstinence; persistence >1 month after sustained abstinence shifts diagnosis toward schizophrenia spectrum.

Board pearl: A patient with "ADHD" requesting escalating amphetamine doses, early refills, or multiple prescribers should trigger PDMP review and reassessment—diversion and StUD are exam triggers.

Physical Exam Findings (and Hemodynamic Assessment)

— Sympathomimetic toxidrome: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperreflexia.

— Hyperthermia >40°C is a medical emergency—predicts rhabdomyolysis, DIC, death.

— Differentiate from anticholinergic toxidrome: stimulants have diaphoresis and bowel sounds present; anticholinergic is dry and quiet.

— Cachexia, poor dentition with caries and bruxism ("meth mouth"), gingivitis.

— Excoriations, picking lesions, abscesses, track marks; necrotizing skin lesions suggest levamisole-contaminated cocaine.

— Nasal septum: erythema, perforation, saddle nose (intranasal cocaine).

— Listen for new murmurs (endocarditis in IV users—tricuspid most common), gallops (cocaine cardiomyopathy), bibasilar crackles ("crack lung").

— Asymmetric pulses or interscapular pain → suspect aortic dissection.

— Focal deficits → stroke (ischemic or hemorrhagic, including SAH from ruptured aneurysm).

— Choreoathetoid movements ("crack dancing"), tremor, clonus.

— Altered mentation: rule out hypoglycemia, hyponatremia (MDMA), intracranial hemorrhage.

— Pressured speech, hyperverbal, paranoid ideation, formication; assess insight, judgment, suicidality, homicidality.

Vital signs in acute intoxication:

General/skin:

Cardiopulmonary:

Neurologic:

Psychiatric exam:

CCS pearl: In a stimulant-intoxicated patient with chest pain, order ECG, troponin, CXR, CBC, BMP, CK, UDS, and acetaminophen/salicylate levels simultaneously; obtain CT head if altered mentation or focal deficit, and CT angiography if dissection or SAH suspected.

Board pearl: Beta-blocker monotherapy is contraindicated in acute cocaine/methamphetamine intoxication due to unopposed alpha vasoconstriction—use benzodiazepines first, then nitrates or phentolamine for refractory hypertension.

Diagnostic Workup — Initial Labs, Imaging, ECG, Biomarkers

— ECG: sinus tachycardia, QRS widening (sodium-channel block from cocaine—treat with sodium bicarbonate), QTc prolongation, ischemic ST changes.

— Troponin and serial ECGs for any chest pain; cocaine-associated MI peaks within 60 min but can occur up to 24 hr post-use.

— CBC, CMP, magnesium, calcium, phosphate—electrolyte derangements predispose to arrhythmia.

— CK and UA for rhabdomyolysis; lactate for shock; coags and fibrinogen if DIC suspected.

— Urine drug screen (immunoassay): detects cocaine metabolite (benzoylecgonine) ~2–4 days; amphetamines 1–3 days; methamphetamine cross-reacts. False positives: bupropion, pseudoephedrine, selegiline, trazodone, labetalol can trigger amphetamine screens—confirm with GC-MS or LC-MS/MS when clinically critical.

— Pregnancy test in all reproductive-age women.

— CXR for crack lung, pneumothorax (Valsalva from smoking), aspiration.

— CT head without contrast if seizure, altered mentation, focal deficit, or worst-ever headache.

— Baseline HIV, HCV, HBV, syphilis (RPR), gonorrhea/chlamydia (urine + extragenital per behavior).

— TB screen (IGRA) in high-risk settings.

— Hepatic and renal panels, lipids, A1c—stimulants disrupt metabolic health.

— ECG before initiating any QT-prolonging psychotropic (eg, antipsychotic for comorbid psychosis).

Acute presentations (intoxication/overdose):

Ambulatory/longitudinal workup:

Step 3 management: Always co-test for fentanyl with point-of-care strips; even patients denying opioid use may be exposed via contaminated supply—prescribe take-home naloxone universally.

Board pearl: A widened QRS in a cocaine-intoxicated patient is treated like TCA toxicity—IV sodium bicarbonate boluses to narrow the QRS, not lidocaine.

Diagnostic Workup — Advanced or Confirmatory Studies

— GC-MS or LC-MS/MS confirms immunoassay results; required for medicolegal cases, custody disputes, transplant evaluation, return-to-work, and pilot/physician monitoring programs.

— Hair testing captures use over ~90 days; useful in forensic and pediatric protection cases.

— Oral fluid/sweat patches in monitoring programs.

— Echocardiogram if heart failure symptoms, new murmur, prior MI, or pulmonary hypertension suspected—methamphetamine-associated cardiomyopathy is increasingly recognized and partially reversible with abstinence.

— Stress testing or coronary CTA for atypical chest pain after acute MI ruled out; cocaine accelerates atherosclerosis.

— Right-heart catheterization if pulmonary arterial hypertension confirmed on echo (methamphetamine is WHO Group 1 PAH cause).

— MRI brain in patients with persistent cognitive deficits, focal findings, or stroke—look for prior infarcts, white matter disease, vasculitis.

— CT/MR angiography for SAH workup or suspected RCVS (reversible cerebral vasoconstriction syndrome).

— Blood cultures × 2, TTE then TEE if endocarditis suspected; HIV viral load and CD4 if positive; HCV RNA if antibody positive.

— Routine STI screening every 3 months in high-risk patients.

— After 4+ weeks of verified abstinence, reassess for primary mood, anxiety, ADHD, or psychotic disorders. Premature diagnosis leads to inappropriate stimulant prescribing.

Confirmatory drug testing:

Cardiac evaluation in chronic users:

Neuroimaging:

Infectious workup in IV/sexualized use:

Psychiatric reassessment:

Key distinction: Stimulant-induced psychotic disorder vs schizophrenia—the former resolves with abstinence; persistent psychosis >1 month or strong family history shifts toward primary psychotic disorder. Treatment overlaps (antipsychotics) but longitudinal course determines diagnosis.

Board pearl: Methamphetamine is a recognized cause of pulmonary arterial hypertension—order echo in chronic users with dyspnea on exertion.

Risk Stratification and First-Line Management Logic

— Acute intoxication with hyperthermia >39°C, seizure, chest pain, AMS, rhabdomyolysis, or hemodynamic instability → ED resuscitation, ICU consideration.

— Acute agitation without instability → ED observation with benzodiazepine titration.

— Withdrawal without complications → outpatient management; admission only for severe depression with suicidality or inability to maintain safety.

— Stable patient seeking treatment → outpatient SUD program with psychosocial intervention.

— Level 1: outpatient (<9 hr/week).

— Level 2: intensive outpatient (IOP, 9–19 hr/week) or partial hospitalization.

— Level 3: residential.

— Level 4: medically managed inpatient.

— Contingency management (CM) = most effective single intervention; provides escalating tangible rewards (vouchers, prizes) for verified abstinence (negative UDS). NNT ~3–5 for sustained abstinence.

— Cognitive behavioral therapy (CBT) and Community Reinforcement Approach add benefit, especially combined with CM.

— Matrix Model: structured 16-week outpatient program combining CBT, family education, 12-step, and CM—first-line for methamphetamine.

— Mutual-help groups: Cocaine Anonymous, Crystal Meth Anonymous, SMART Recovery.

Triage decision tree:

Severity-based treatment matching (ASAM criteria):

Evidence hierarchy for StUD (cocaine and methamphetamine):

Step 3 management: Always offer all evidence-based modalities simultaneously: CM + CBT/Matrix + treat comorbid psychiatric/medical conditions + harm reduction (naloxone, fentanyl test strips, sterile equipment, PrEP).

CCS pearl: Order "social work consult" and "substance use counseling" early on the CCS case; schedule follow-up within 1 week of any new diagnosis or relapse.

Board pearl: When a vignette asks "most effective treatment for cocaine or methamphetamine use disorder," the answer is contingency management—not a medication.

Pharmacotherapy — First-Line and Off-Label Regimens

— Naltrexone (50 mg PO daily) + bupropion XL (450 mg PO daily) — the ADAPT-2 trial showed modest but significant reduction in use; reasonable first medication trial in moderate–severe disease. Avoid bupropion if seizure history or active eating disorder.

— Mirtazapine 30 mg qHS — reduces use in MSM populations; helpful when insomnia/depression coexist.

— Topiramate — reduces craving; titrate slowly to limit cognitive side effects.

— Topiramate (titrate to 200–300 mg/day) — best evidence; reduces use.

— Bupropion, modafinil, disulfiram — mixed evidence; disulfiram blocks dopamine β-hydroxylase, useful in patients with comorbid alcohol use disorder.

— Long-acting amphetamine agonist therapy (mixed amphetamine salts ER) — emerging evidence for cocaine; controversial.

— Depression: SSRIs (sertraline, escitalopram) after 2–4 weeks abstinence if symptoms persist.

— ADHD: treat only after sustained abstinence; prefer non-stimulants (atomoxetine, viloxazine, bupropion) or long-acting/extended-release stimulants under close monitoring with PDMP and UDS.

— Psychosis: second-generation antipsychotics (risperidone, olanzapine, aripiprazole); avoid first-gen with strong anticholinergic load.

— Insomnia: trazodone, mirtazapine, melatonin—avoid benzodiazepines and z-drugs long-term.

There is no FDA-approved medication for StUD. All pharmacotherapy is off-label and adjunctive to psychosocial treatment. Step 3 expects knowledge of best-evidence off-label options.

Methamphetamine use disorder:

Cocaine use disorder:

Treating comorbidities (often the highest-yield intervention):

Step 3 management: Co-prescribe naloxone to every patient with StUD and screen for OUD; if co-occurring OUD, start buprenorphine or methadone—treating OUD reduces overdose mortality more than any StUD-specific intervention.

Board pearl: Naltrexone + bupropion is the most exam-tested off-label combination for methamphetamine use disorder; topiramate is the best-evidence agent for cocaine use disorder.

Acute Management Procedures and Expanded Pharmacology

— First-line: IV/IM benzodiazepines (lorazepam 2 mg IV q5–10 min, or midazolam 5 mg IM) titrated to calm but arousable—addresses agitation, tachycardia, hypertension, hyperthermia, and seizure risk simultaneously.

— Refractory agitation: add antipsychotic (haloperidol 5 mg IM or olanzapine 10 mg IM)—avoid droperidol if QT prolonged.

— Hyperthermia >39°C: aggressive external cooling (cooled IV fluids, evaporative cooling, ice packs to groin/axillae); intubation and paralysis with non-depolarizing agent for refractory cases.

— Benzodiazepines first for anxiety/tachycardia.

— Aspirin, nitroglycerin, heparin as per ACS pathway.

— Phentolamine for refractory hypertension; CCBs (diltiazem) acceptable.

— Avoid beta-blockers acutely (unopposed alpha); labetalol is debated—most experts still avoid in first 24 hr.

— PCI for STEMI; medical management often sufficient for NSTEMI due to vasospasm component.

— Asymptomatic packer with intact packets → whole-bowel irrigation with polyethylene glycol; surgical removal if obstruction, rupture, or toxicity.

— Never endoscopically retrieve intact packets (risk of rupture).

— Largely supportive; treat sleep with trazodone/mirtazapine; monitor for suicidality.

— Consider short inpatient stay for severe depression or suicidal ideation.

Acute agitation/intoxication management (CCS sequence):

Cocaine-associated chest pain protocol:

Rhabdomyolysis: aggressive isotonic crystalloid to UOP 200–300 mL/hr; monitor K, Ca, phosphate; dialysis if AKI with refractory hyperkalemia.

Wide-complex tachycardia/QRS >100 ms from cocaine: sodium bicarbonate 1–2 mEq/kg IV bolus.

Body packer/stuffer:

Withdrawal management:

CCS pearl: In a cocaine chest-pain CCS case, lorazepam IV should appear on your order list before nitroglycerin—it's the highest-yield intervention.

Board pearl: Sodium bicarbonate reverses cocaine's sodium-channel blockade just as it does TCA toxicity.

Special Populations — Elderly and Renal/Hepatic Impairment

— Stimulant use is rising in older adults, often via prescribed amphetamines for ADHD or cognitive complaints, and via cocaine in long-standing users.

— Higher risk of MI, stroke, arrhythmia, and aortic dissection at any given dose due to baseline atherosclerosis.

— Screen with brief instruments; avoid prescribing stimulants in patients with uncontrolled hypertension, CAD, arrhythmia, or recent stroke (per AHA scientific statement).

— Watch for drug–drug interactions: stimulants ↑ effects of warfarin via competition, ↑ BP with SNRIs and MAOIs (avoid combination), serotonin syndrome risk with MDMA + serotonergic agents.

— Amphetamine clearance decreases with eGFR <30; lower starting doses if prescribing for ADHD comorbidity.

— Topiramate: reduce dose by 50% if CrCl <70 mL/min; avoid in nephrolithiasis history.

— Naltrexone: use caution if CrCl <50; avoid in severe impairment.

— Bupropion: reduce frequency and dose; avoid if CrCl <30.

— Rhabdomyolysis-induced AKI is common; aggressive hydration; monitor for compartment syndrome.

— Naltrexone is contraindicated in acute hepatitis or hepatic failure (LFTs >5× ULN); monitor LFTs at baseline, 1, 3, 6 months.

— Bupropion: reduce dose in severe hepatic impairment.

— Disulfiram: contraindicated in significant hepatic disease.

— Cocaine itself is hepatotoxic; methamphetamine can cause ischemic hepatitis during hyperthermia.

— Deprescribe agents that raise BP/HR (decongestants, atomoxetine).

— Reconcile QT-prolonging medications before adding antipsychotics.

Older adults (≥65):

Renal impairment:

Hepatic impairment:

Polypharmacy review:

Step 3 management: In older adults presenting with new "psychiatric" or "cardiac" symptoms, always obtain a UDS—stimulant use is frequently missed in this demographic and reshapes the differential.

Board pearl: Naltrexone requires LFT monitoring; baseline transaminases >5× ULN is a contraindication.

Special Populations — Pregnancy and Pediatrics

— Stimulant use in pregnancy is associated with placental abruption, preterm birth, IUGR, low birth weight, preeclampsia (cocaine), and stillbirth.

— Methamphetamine crosses the placenta freely; neonatal effects include jitteriness, poor feeding, hypertonia—generally no defined neonatal abstinence syndrome requiring pharmacotherapy (unlike opioids).

— Cocaine: increased risk of placental abruption and preterm labor; screen with a structured tool, not visual cues.

— Universal verbal screening at first prenatal visit (4 P's, NIDA Quick Screen) per ACOG—avoid biased testing.

— Treatment principles: psychosocial therapy is first-line; CM is safe and effective in pregnancy. Pharmacotherapy is generally avoided; bupropion category C, naltrexone category C with limited data.

— Coordinate with OB, MFM, addiction medicine, social work, and pediatrics; develop a Plan of Safe Care per CAPTA—substance use alone is not child abuse in most states but triggers POSC.

— Encourage breastfeeding only with sustained abstinence; methamphetamine and cocaine concentrate in breast milk.

— Screen with CRAFFT 2.1; use confidential interview separate from parent.

— Most stimulant exposure is prescription amphetamine misuse (for studying, weight loss, "smart drugs")—assess diversion, peer sharing.

— Treatment: family-based therapy, adolescent CM, school integration; avoid stimulant prescribing without strict controls.

— Confidentiality vs disclosure: state-specific; generally protect adolescent confidentiality but break for imminent harm.

Pregnancy:

Adolescents:

Step 3 management: In a pregnant patient with positive UDS, engage rather than report punitively; provide prenatal care, addiction treatment, naloxone, and Plan of Safe Care coordination.

Board pearl: Placental abruption in a pregnant patient with abdominal pain and vaginal bleeding → think cocaine until proven otherwise.

Complications and Adverse Outcomes

— MI (vasospasm + thrombosis + accelerated atherosclerosis), arrhythmias (AF, VT, sudden cardiac death), aortic dissection, hypertensive emergency, dilated cardiomyopathy (methamphetamine-associated; partially reversible), endocarditis (IV), pulmonary arterial hypertension (methamphetamine).

— Ischemic and hemorrhagic stroke, SAH, RCVS, seizures, movement disorders, cognitive impairment, chronic memory and executive dysfunction.

— "Crack lung" (diffuse alveolar damage), pulmonary hemorrhage, barotrauma (pneumothorax, pneumomediastinum), bronchospasm, infections.

— Stimulant-induced psychosis (may persist), severe depression with suicide, anxiety, anhedonia, sleep disorders, cognitive deficits, persistent psychosis in genetically susceptible individuals.

— Rhabdomyolysis with AKI, hyperthermia-related multi-organ failure, electrolyte derangements, DIC.

— Ischemic colitis (cocaine), hepatic injury, mesenteric ischemia.

— HIV, HCV, HBV from injection and sexualized use; STIs; skin/soft tissue infections; endocarditis; osteomyelitis; epidural abscess.

— Levamisole-induced agranulocytosis and cutaneous vasculitis (retiform purpura on ears/cheeks)—check CBC, ANCA, discontinue exposure.

Cardiovascular:

Neurologic:

Pulmonary:

Psychiatric:

Renal/metabolic:

GI/hepatic:

Infectious:

Dermatologic:

Dental: rampant caries, periodontitis, bruxism, tooth loss.

Social/legal: incarceration, custody loss, unemployment, housing instability, intimate partner violence.

CCS pearl: A cocaine user with retiform purpura on the ears and neutropenia points to levamisole contamination—order ANCA (often pANCA+), CBC with differential, and counsel cessation; bone marrow recovery follows abstinence.

Board pearl: Methamphetamine cardiomyopathy is partially reversible with sustained abstinence—LV function can recover with optimal GDMT + cessation.

When to Escalate Care — ICU, Consult, Inpatient

— Hyperthermia ≥40°C or refractory hyperthermia.

— Hemodynamic instability, shock, malignant arrhythmia.

— Status epilepticus or refractory seizures.

— Severe rhabdomyolysis with AKI requiring dialysis.

— Intracranial hemorrhage, large stroke, or refractory hypertensive emergency.

— Intubation for airway protection in severe agitation requiring paralysis.

— Multi-organ failure, DIC.

— Cocaine-associated chest pain ruled in for ACS or with positive troponin.

— Significant rhabdomyolysis without dialysis need.

— Severe withdrawal depression with suicidal ideation requiring monitoring.

— Endocarditis, osteomyelitis, severe SSTI requiring IV antibiotics.

— Acute suicidal ideation with plan or intent during withdrawal.

— Stimulant-induced psychosis with danger to self/others.

— Inability to maintain safety at home.

— Coordinate involuntary hold per state statute when criteria met (danger to self/others, grave disability).

— Addiction medicine/psychiatry for medication and disposition planning.

— Cardiology for ACS, cardiomyopathy, arrhythmia.

— Infectious disease for endocarditis, HIV management.

— Social work for housing, insurance, custody, Plan of Safe Care.

— Toxicology for body packers, levamisole toxicity, complex co-ingestions.

— Warm handoff beats referral slip—every relapse risk-point is highest at care transitions.

— Schedule outpatient follow-up within 7 days of discharge.

ICU admission criteria:

General medical/telemetry admission:

Psychiatric admission:

Consultations to consider early (CCS):

Disposition pearls:

Step 3 management: Before discharging any patient with StUD, ensure (1) naloxone in hand, (2) outpatient SUD appointment scheduled <7 days, (3) buprenorphine/methadone if co-occurring OUD, (4) PrEP discussion, (5) overdose education.

CCS pearl: Order "bridge clinic appointment" and "peer recovery specialist" on the discharge orders—both improve linkage-to-care metrics.

Key Differentials — Same-Category Causes

— Cocaine: shorter half-life, intense brief euphoria, repeated bingeing, local anesthetic + sodium-channel blockade (wide QRS), strong vasospasm → MI; UDS detects benzoylecgonine 2–4 days.

— Methamphetamine: 8–12 hr duration, prolonged psychosis, more cardiomyopathy and PAH, dental destruction; detected 1–3 days.

— Serotonergic and dopaminergic; hyponatremia from SIADH + free water intake, hyperthermia, serotonin syndrome with other serotonergics.

— Key distinction: suspect MDMA in young patient at rave/festival with seizure and Na <125—correct slowly, avoid overcorrection.

— Severe agitation and psychosis, may not show on standard UDS; treat as sympathomimetic with benzodiazepines.

— Misuse/diversion among students and professionals; assess via PDMP, pill counts, UDS.

— Tachycardia, anxiety, tremor; rarely seizures at extreme doses; supportive care.

— Lower abuse potential; misuse exists in shift workers and students.

— Can cause sympathomimetic symptoms and false-positive amphetamine UDS—confirm by GC-MS.

Differentiating stimulant types and mimics within the substance use category:

Cocaine vs amphetamines/methamphetamine:

MDMA ("ecstasy"/"Molly"):

Synthetic cathinones ("bath salts," mephedrone, MDPV):

Prescription stimulants (methylphenidate, amphetamine salts, lisdexamfetamine):

Caffeine intoxication:

Nicotine: comorbid in 60–80% of StUD; treat concurrently with varenicline, bupropion, NRT.

Synthetic amphetamine-like agents (modafinil, armodafinil):

Decongestants (pseudoephedrine, phenylephrine):

Key distinction: Stimulant intoxication vs serotonin syndrome—both have hyperthermia, agitation, autonomic instability, but serotonin syndrome adds clonus, hyperreflexia, ocular clonus and history of serotonergic agent exposure.

Board pearl: A young patient at a music festival with hyperthermia, seizure, and Na 122 = MDMA + water intoxication—restrict free water, use hypertonic saline cautiously.

Key Differentials — Other-Category Causes

— Tachycardia, tremor, hyperthermia, agitation, weight loss; check TSH, free T4, T3; look for goiter, ophthalmopathy.

— Paroxysmal hypertension, headache, palpitations, diaphoresis; plasma free metanephrines.

— Acute mania (bipolar I): grandiosity, decreased sleep, pressured speech—indistinguishable acutely from stimulant intoxication; UDS and collateral history differentiate.

— Schizophrenia/schizoaffective: persistent psychosis without recent stimulant use; abstinence ≥1 month clarifies diagnosis.

— Panic disorder, GAD: episodic autonomic surges without sustained tachycardia/HTN.

— ADHD: chronic inattention/hyperactivity from childhood; not paroxysmal.

Non-substance mimics of stimulant intoxication and StUD presentations:

Thyrotoxicosis/thyroid storm:

Pheochromocytoma:

Primary psychiatric disorders:

Anticholinergic toxidrome: dry skin, absent bowel sounds, urinary retention, mydriasis—distinguished by dry vs diaphoretic skin.

Sympathomimetic from prescription/OTC: decongestants, MAOI–tyramine reactions, theophylline toxicity.

Serotonin syndrome: clonus, hyperreflexia, recent serotonergic medication change.

Neuroleptic malignant syndrome: lead-pipe rigidity, hyperthermia, mental status changes, recent antipsychotic exposure, ↑CK, ↑WBC—develops over days, not minutes.

Sepsis with delirium: fever, tachycardia, hypotension, leukocytosis—UDS and infectious workup distinguish.

Hypoglycemia: always check fingerstick in any agitated/altered patient.

CNS pathology: stroke, encephalitis, meningitis, intracranial hemorrhage—low threshold for CT/LP if focal deficits or fever.

Withdrawal from sedatives: alcohol/benzodiazepine withdrawal can mimic stimulant intoxication—history of cessation timeline clarifies.

Key distinction: NMS vs serotonin syndrome vs sympathomimetic toxidrome—NMS has rigidity and bradyreflexia, serotonin syndrome has hyperreflexia and clonus, sympathomimetic has mydriasis and diaphoresis without rigidity.

Board pearl: Always check TSH and pregnancy test in a young woman with "new anxiety, weight loss, palpitations" before attributing to stimulants.

Secondary Prevention, Discharge Medications, Long-Term Plan

— Naloxone (2 doses intranasal) + education for patient and household.

— Fentanyl test strips and harm-reduction counseling.

— Buprenorphine or methadone if co-occurring OUD (start in ED when indicated).

— Pharmacotherapy for StUD: start naltrexone+bupropion (meth) or topiramate (cocaine) when severity warrants and contraindications cleared.

— PrEP (TDF/FTC or descovy or long-acting cabotegravir) for HIV-negative patients with sexualized stimulant use or IDU; DoxyPEP for MSM/transgender women with bacterial STIs.

— Vaccinations: HAV, HBV, HPV through 45, MPV, COVID, influenza, pneumococcal per risk.

— STI panel and treatment of any positives.

— HCV treatment referral—DAAs cure regardless of ongoing use.

— Smoking cessation: varenicline first-line.

— Contraception counseling for reproductive-age patients; LARC offered.

— Aspirin, high-intensity statin, ACEi/ARB if LV dysfunction or HTN, CCB or nitrate for vasospasm management.

— Beta-blockers controversial; if ongoing use, generally avoid; if sustained abstinence, carvedilol (mixed alpha/beta) is preferred.

— Strict BP control <130/80; LDL <70 if ASCVD.

— Outpatient psychiatry appointment within 1–2 weeks.

— Treat depression/anxiety/ADHD/psychosis per diagnosis after abstinence assessment.

— Enroll in CM program + CBT/Matrix Model.

— Mutual-help group introduction (CA, CMA, SMART Recovery).

— Peer recovery support specialist linkage.

— Address SDOH: housing (Housing First models), employment, legal aid.

Discharge checklist after any acute presentation:

Cardiovascular secondary prevention after cocaine-associated MI:

Mental health linkage:

Behavioral plan:

Step 3 management: Use the "5 A's" at every visit—Ask (use), Advise (cessation), Assess (readiness), Assist (CM/meds/referral), Arrange (follow-up <7 days). Document at every encounter.

Board pearl: Take-home naloxone is standard of care for any patient with any SUD, even without overt opioid use, given fentanyl contamination.

Follow-Up, Monitoring Parameters, and Counseling

— Weekly for first 4–8 weeks of treatment (especially during CM phase); transition to biweekly then monthly with sustained abstinence.

— Annual comprehensive review with metabolic panel, infectious screening, mental health, dental, and dermatologic exam.

— UDS at every visit during early treatment; quantitative testing as needed to verify gradual tapering vs new use.

— PDMP review at every prescribing decision.

— LFTs baseline, 1, 3, 6, 12 months on naltrexone.

— ECG at baseline and with dose changes of QT-prolonging agents.

— Echo repeat in 6–12 months if methamphetamine cardiomyopathy diagnosed and patient achieves abstinence (may show recovery).

— HIV viral load every 3 months if positive; STI rescreen every 3 months in high-risk patients; HCV reinfection screen annually after cure.

— CBC if on naltrexone-bupropion (monitor for agranulocytosis with levamisole exposure).

— Relapse prevention: identify triggers (people, places, paraphernalia, emotions); develop coping plan; rehearse refusal skills.

— Harm reduction: never use alone; carry naloxone; use test strips; sterile equipment; avoid mixing with opioids and alcohol.

— Sleep hygiene, nutrition, exercise—stimulants disrupt all three; structured routines aid recovery.

— Sexual health: PrEP adherence, STI prevention, healthy relationships.

— Dental care: referral; fluoride; behavioral interventions for bruxism.

— Employment, housing stability, relationship repair, quality-of-life scales—recovery is multidimensional.

Follow-up cadence:

Objective monitoring:

Counseling content:

Recovery metrics beyond abstinence:

CCS pearl: Document "motivational interviewing performed" and "relapse prevention plan reviewed" at each visit—both appear as preferred CCS actions for SUD cases.

Board pearl: A "negative UDS for 12 weeks" is the typical CM milestone; reward escalation maintains engagement. Premature discontinuation of CM is a common relapse trigger.

Ethical, Legal, and Patient Safety Considerations

— 42 CFR Part 2 governs substance use treatment records: more stringent than HIPAA; specific written consent required for disclosure even to other treating clinicians.

— Practical implication: SUD program records cannot be sent to PCP without explicit patient authorization; document carefully.

— Most states require reporting of suspected child abuse/neglect, not substance use alone in pregnancy; know your state law.

— CAPTA Plan of Safe Care: required for newborns affected by prenatal substance exposure—coordinated, not punitive.

— Impaired driving: reporting laws vary; counsel patient not to drive while intoxicated; document.

— Impaired professionals (physicians, pilots, commercial drivers): mandatory reporting to licensing boards in many states; offer Physician Health Programs (PHP) as alternative to discipline.

— Acute intoxication impairs capacity; defer non-emergent consent until sober when possible.

— Emergent treatment (eg, intubation for hyperthermia) proceeds under implied consent.

— Document capacity assessment when patient refuses care while intoxicated.

— Use person-first language ("person with stimulant use disorder," not "addict").

— Avoid biased drug testing in pregnancy—universal verbal screening is the standard.

— Highest overdose risk windows: post-incarceration, post-detox, post-hospitalization, post-residential treatment—tolerance drops, supply contamination risk persists.

— Ensure naloxone, warm handoff, and <7-day follow-up at every transition.

— Provision of sterile equipment, fentanyl test strips, and supervised consumption (where legal) is evidence-based and ethically supported by major medical societies.

— DOT requires reporting positive UDS for safety-sensitive positions; counsel patient on implications.

Confidentiality:

Mandatory reporting:

Informed consent edge cases:

Stigma and bias:

Transitions of care risk:

Harm reduction ethics:

Driving and DOT:

Step 3 management: When a hospitalized patient with StUD refuses recommended care while clearly intoxicated and agitated, perform documented capacity assessment, treat the intoxication, then revisit consent when sober—respect autonomy while protecting safety.

Board pearl: 42 CFR Part 2 consent is the high-yield ethics distinction—standard HIPAA authorizations are not sufficient for releasing SUD treatment records.

High-Yield Associations and Rapid-Fire Clinical Facts

Cocaine + ST elevation + young patient → benzodiazepines, ASA, nitrates, avoid beta-blockers; PCI for STEMI.

Wide QRS in cocaine toxicity → IV sodium bicarbonate.

Methamphetamine + dyspnea → think pulmonary arterial hypertension (WHO Group 1).

Methamphetamine + reduced EF → cardiomyopathy, partially reversible with abstinence + GDMT.

Retiform purpura on ears + neutropenia in cocaine user → levamisole contamination, pANCA+.

Pregnant patient with abruption → cocaine.

MDMA + seizure + Na 122 → SIADH + free water; restrict water, slow hypertonic saline.

Persistent psychosis >1 month after abstinence → reconsider primary psychotic disorder.

First-line treatment for cocaine or meth use disorder → contingency management (no FDA-approved medication).

Best off-label combo for methamphetamine → naltrexone + bupropion (ADAPT-2).

Best off-label medication for cocaine → topiramate.

Bupropion false-positive on UDS → amphetamine immunoassay; confirm with GC-MS.

Body packer with intact packets → whole-bowel irrigation; surgery if leaking/obstructed.

Sympathomimetic vs anticholinergic toxidrome → diaphoretic vs dry; present vs absent bowel sounds.

NMS vs serotonin syndrome → rigidity/bradyreflexia vs clonus/hyperreflexia.

Highest mortality reduction in co-occurring OUD+StUD → treat OUD with buprenorphine/methadone + universal naloxone.

Universal screening tool in pregnancy → verbal (4 P's), not biased urine testing.

42 CFR Part 2 → SUD records require specific consent, beyond HIPAA.

Post-incarceration period → highest overdose risk; arrange naloxone and warm handoff.

CRAFFT 2.1 → adolescent SUD screen; TAPS / DAST-10 / ASSIST → adult screens.

Step 3 management: Memorize the "discharge bundle": naloxone, fentanyl strips, MOUD if OUD, PrEP if at-risk, vaccinations, CM enrollment, follow-up <7 days.

Board pearl: When stuck, the answer for "next best step in stimulant use disorder" is almost always contingency management + treat comorbidities + harm reduction, not a specific medication.

Board Question Stem Patterns

Stem 1: 28-year-old man with chest pain 2 hr after cocaine use; BP 178/104, HR 122, ECG with diffuse ST elevation. → Next best step: IV lorazepam, then ASA, nitroglycerin, heparin; avoid metoprolol.

Stem 2: 35-year-old woman with methamphetamine use disorder requests treatment; has tried CBT and Matrix without sustained abstinence. → Most effective addition: contingency management.

Stem 3: 22-year-old at music festival with seizure, T 40.1°C, Na 121, recent "ecstasy." → Diagnosis: MDMA-associated hyponatremic encephalopathy; treat with hypertonic saline, cooling, benzodiazepines.

Stem 4: Pregnant patient at 32 weeks with sudden severe abdominal pain, vaginal bleeding, recent cocaine use. → Placental abruption; emergent OB management.

Stem 5: Cocaine user with retiform purpura on ears, WBC 1.8, ANC 600. → Levamisole contamination; stop exposure, supportive care, ANCA+.

Stem 6: Methamphetamine user with progressive DOE, JVD, EF 25%. → Methamphetamine cardiomyopathy; GDMT + abstinence may improve EF.

Stem 7: 19-year-old college student requests stimulant refill after losing prescription; PDMP shows 3 prescribers in 4 months. → Best next step: do not refill, assess for StUD, PDMP-based discussion, refer.

Stem 8: Hospitalized patient with cocaine use refuses anticoagulation for DVT while intoxicated. → Assess capacity; defer non-emergent decision until sober.

Stem 9: PCP wants SUD program records; patient signed HIPAA release. → Insufficient: 42 CFR Part 2 requires specific written consent.

Stem 10: Patient discharged after meth-induced psychosis. → Discharge bundle: naloxone, fentanyl strips, CM referral, follow-up <7 days, PrEP discussion.

Stem 11: UDS positive for amphetamines in patient taking bupropion only. → False positive; confirm with GC-MS.

Stem 12: Body packer asymptomatic with intact packets on CT. → Whole-bowel irrigation with polyethylene glycol.

Stem 13: Methamphetamine user with depressed mood and dyspnea, echo shows RVSP 65, normal LV. → Pulmonary arterial hypertension; refer for right-heart cath.

Stem 14: Patient with cocaine use and STEMI s/p PCI now stable, asking about discharge meds. → ASA, statin, ACEi; avoid beta-blocker if ongoing use; consider carvedilol if abstinent.

CCS pearl: On CCS cases, lorazepam IV should appear within the first 5 orders for any agitated stimulant-intoxicated patient.

Board pearl: When the stem asks "most effective long-term treatment," contingency management is almost always the answer for StUD.

One-Line Recap

— Contingency management is the single most effective intervention for both cocaine and methamphetamine use disorder; Matrix Model is the first-line structured program for methamphetamine.

— Best off-label pharmacotherapy: naltrexone + bupropion for methamphetamine (ADAPT-2 trial), topiramate for cocaine; treat comorbid OUD with buprenorphine or methadone to reduce overdose mortality.

— Acute intoxication: benzodiazepines first for agitation, hypertension, tachycardia, hyperthermia, and seizure prevention; sodium bicarbonate for cocaine-induced wide QRS; avoid beta-blockers acutely in cocaine; aggressive cooling for hyperthermia >40°C.

— Discharge bundle for every StUD encounter: naloxone + fentanyl test strips + warm handoff to outpatient SUD care within 7 days + PrEP/STI/HCV/vaccination screening + treat comorbid psychiatric illness after 4 weeks of abstinence; remember 42 CFR Part 2 for confidentiality and Plan of Safe Care for perinatal exposure.

One-liner: Stimulant use disorder has no FDA-approved pharmacotherapy, so management hinges on contingency management plus CBT/Matrix, aggressive treatment of comorbidities (OUD with MOUD, depression, ADHD only after abstinence), harm reduction (universal naloxone, fentanyl test strips, PrEP), and acute-care safety with benzodiazepines-first for intoxication—never beta-blocker monotherapy in cocaine toxicity.

High-yield recap bullets:

Board pearl: If a Step 3 vignette features stimulant use, the highest-yield levers are contingency management, treat-the-comorbidity, and harm reduction—not a magic-bullet medication.