Emergency & Toxicology

Tricyclic antidepressant overdose

Clinical Overview and When to Suspect TCA Overdose

— Fast Na⁺ channel blockade in myocardium → QRS widening, ventricular dysrhythmia, negative inotropy

— K⁺ channel blockade → QT prolongation, torsades risk

— Anticholinergic (antimuscarinic) → tachycardia, mydriasis, dry skin, urinary retention, ileus, delirium

— α1-adrenergic blockade → vasodilation, hypotension

— H1 blockade → sedation

— CNS GABA-A inhibition / monoamine reuptake → seizures, agitation

— Known prescription for chronic pain, migraine prophylaxis, neuropathy, enuresis, depression, or insomnia (low-dose doxepin)

— Adolescent or adult with intentional ingestion + anticholinergic toxidrome + QRS ≥ 100 ms

— Unexplained wide-complex tachycardia with hypotension and altered mental status after possible ingestion

— Pediatric "one pill can kill" exposure — as little as 10–20 mg/kg can be lethal in toddlers

Board pearl: A patient who looks "stable but sleepy" after a TCA ingestion is never reassuring; the window to intubate, alkalinize, and resuscitate closes abruptly when QRS widens past 100 ms. Treat suspected TCA overdose as a time-critical cardiotoxic emergency, not a routine "tox screen and observe" case — disposition is ICU until proven otherwise.

Tricyclic antidepressants (TCAs) — amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine — remain a leading cause of lethal pharmaceutical overdose despite declining prescriptions, because of their narrow therapeutic index and multi-receptor toxicity.

Mechanisms driving toxicity:

When to suspect:

Timeline: rapid deterioration is the rule. Patients can appear well at triage and crash within 1–2 hours as absorption peaks (slowed by anticholinergic gastric stasis).

Co-ingestants are common — alcohol, benzodiazepines, acetaminophen, SSRIs — and worsen prognosis.

Presentation Patterns and Key History

— Drowsiness, mild tachycardia, mydriasis, dry mucous membranes

— Patient may converse and minimize ingestion → easy to underestimate

— Coma, seizures (often brief, generalized, single — but prolonged seizure worsens acidosis and toxicity)

— Hypotension refractory to fluids

— Wide-complex tachycardia, rightward terminal QRS axis (R wave in aVR)

— Ventricular tachycardia, ventricular fibrillation, asystole

— Hyperthermia, rhabdomyolysis, aspiration, ARDS

— Drug name, formulation (immediate vs extended release), maximum possible dose

— Time of ingestion (anchor for decontamination decisions)

— Co-ingestants — especially acetaminophen (always screen) and alcohol

— Suicidality, prior attempts, psychiatric diagnoses

— Access to other household medications and firearms (safety planning later)

— Diphenhydramine overdose — pure anticholinergic + Na-channel toxicity, very similar

— Carbamazepine — structurally similar tricyclic, can mimic

— Cocaine, propranolol, type Ia/Ic antiarrhythmics — also widen QRS

Step 3 management: When EMS calls with "possible TCA overdose," the receiving order set should pre-stage IV access ×2, continuous cardiac monitoring, 12-lead ECG on arrival, sodium bicarbonate ampules at bedside, intubation equipment, and benzodiazepines. Do not wait for confirmatory levels — TCA serum levels do not guide acute management and are not rapidly available; clinical findings and ECG drive every decision.

Classic toxidrome trio: altered mental status + seizure + cardiotoxicity, layered on anticholinergic features.

Early phase (0–2 hours):

Mid phase (2–6 hours):

Late/severe:

Key history points to obtain rapidly (often from EMS, family, pill bottles, pharmacy callback):

Mimicking presentations to clarify on history:

Physical Exam Findings and Hemodynamic Assessment

— Tachycardia (sinus, anticholinergic) almost universal early

— Hypotension from α1 blockade and myocardial depression

— Hyperthermia from anticholinergic anhidrosis + agitation

— Tachypnea early; hypoventilation as coma deepens

— Mental status ranges from agitated delirium → obtundation → coma

— Myoclonus, hyperreflexia, extensor plantar responses common

— Seizures often brief and self-limited, but recurrent seizures suggest massive ingestion

— Pupils: mydriatic, sluggish (anticholinergic)

— "Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter, full as a flask"

— Dry axillae, flushed skin, absent bowel sounds, distended bladder (consider Foley)

— Wide-complex tachycardia on monitor

— Hypotension may be fluid-responsive early, then catecholamine-dependent

— Crackles → consider aspiration or ARDS

— Continuous telemetry + serial 12-lead ECGs every 1–2 hours until stable for 6 hours

— Arterial line if vasopressors started or repeated ABGs needed

— Bedside echo if shock — TCAs cause global myocardial depression, not just rhythm disturbance

Key distinction: Anticholinergic toxidrome with normal QRS and normal BP is most often antihistamine or pure anticholinergic; layering on QRS widening, hypotension, and seizures points to TCA. The presence of dry skin distinguishes anticholinergic poisoning from sympathomimetic (cocaine/amphetamine) toxidromes, which are diaphoretic — an important fork on the boards.

Vital signs — the bedside tell-all:

Neuro:

Anticholinergic toxidrome:

Cardiopulmonary:

Hemodynamic assessment priorities:

Diagnostic Workup — Initial Labs, ECG, and Biomarkers

— QRS > 100 ms → predicts seizures (≈30% risk)

— QRS > 160 ms → predicts ventricular dysrhythmia (≈50% risk)

— R wave in aVR > 3 mm OR R/S ratio in aVR > 0.7 → highly specific for TCA toxicity and predicts seizures/dysrhythmia

— Rightward terminal 40-ms QRS axis (terminal R in aVR, terminal S in I and aVL) — pathognomonic pattern

— Prolonged QTc, sinus tachycardia, AV blocks, Brugada-like pattern possible

— Acetaminophen and salicylate levels — mandatory in any intentional ingestion

— Basic metabolic panel — anion gap, K⁺ (alkalinization will lower K⁺)

— Venous or arterial blood gas — guide bicarbonate therapy, target pH 7.50–7.55

— Lactate — marker of shock severity

— CK if prolonged immobility, seizure, or hyperthermia

— Pregnancy test in reproductive-age females

— Ethanol level

— Qualitative urine TCA immunoassays exist but have poor sensitivity and false positives (carbamazepine, cyproheptadine, diphenhydramine)

— Serum TCA levels do not correlate well with toxicity and are not used acutely

— CXR if intubated, aspiration suspected, or hypoxic

— CT head only if focal deficits, prolonged coma not explained by ingestion, or trauma

Board pearl: The R wave in aVR ≥ 3 mm finding outperforms QRS duration alone for predicting TCA cardiotoxicity and is a favorite Step 3 ECG-interpretation question. If you see a wide-complex tachycardia with prominent terminal R in aVR in an overdose patient, start bicarbonate before the drug screen returns.

ECG is the single most important test — obtain immediately and repeat serially.

Core labs:

TCA-specific testing:

Imaging:

Diagnostic Workup — Advanced and Confirmatory Studies

— Every 1–2 hours while symptomatic

— After every bicarbonate bolus to assess QRS narrowing (target QRS < 100 ms)

— Before disposition decisions

— A patient who is asymptomatic with normal serial ECGs and normal mental status at 6 hours post-ingestion of an immediate-release TCA can generally be medically cleared (psychiatric clearance separate)

— Extended-release formulations or massive ingestions warrant longer observation

— Indicated in refractory shock — TCAs depress contractility globally

— Helps differentiate cardiogenic vs distributive shock for vasopressor selection

— Repeat ABG every 30–60 min during bicarbonate titration

— Consider lipid emulsion therapy levels are not measured but response is clinical

— VA-ECMO candidacy assessment in refractory cardiogenic shock — early consult to cardiothoracic surgery

— Dose-risk estimation

— Decontamination decisions

— Antidote dosing (bicarbonate, lipid emulsion)

— Disposition guidance

— Quantitative TCA level is not actionable acutely

— Urine drug screens with TCA panel — false negatives and false positives are common

CCS pearl: On a CCS case, after initial stabilization, order "continuous cardiac monitoring," "serial ECG every 2 hours," "ABG every 1 hour," and "Poison Control consultation." The clock advances; reassess QRS and pH at each interval and titrate bicarbonate accordingly. Skipping serial reassessment is a common point-loser.

Repeat ECG cadence:

Asymptomatic patient observation rule:

Echocardiography:

Continuous capnography if intubated — guides minute ventilation to maintain target pH

Advanced/refractory case workup:

Toxicology consult (regional Poison Control, 1-800-222-1222 in US) should be called early — they help with:

Avoid these tests:

Risk Stratification and First-Line Management Logic

— Airway: low threshold to intubate for coma, seizures, hypoventilation, or expected deterioration before procedures

— Breathing: hyperventilate to pH 7.50–7.55 if intubated

— Circulation: IV crystalloid bolus 10–20 mL/kg; if hypotensive after fluids → bicarbonate + norepinephrine

— Decontamination: activated charcoal 1 g/kg PO/NG if presentation within 1–2 hours AND airway protected (intubated or fully awake) — TCAs slow GI transit so window may be longer; discuss with toxicology

— No gastric lavage, no ipecac, no whole-bowel irrigation routinely

— Low risk: asymptomatic, normal ECG, normal mental status, > 6 h post-ingestion → observation, psychiatric eval

— Moderate risk: any symptom OR QRS 100–120 ms OR sinus tachycardia → monitored bed, bicarbonate, observation

— High risk: QRS > 120 ms, hypotension, seizures, dysrhythmia, altered mental status → ICU, intubation, aggressive bicarbonate, vasopressors

— QRS > 100 ms

— Hypotension not responsive to fluids

— Ventricular dysrhythmia

— Wide-complex tachycardia from suspected TCA

— First-line: benzodiazepines (lorazepam 2–4 mg IV, midazolam 5–10 mg IM/IV)

— Second-line: barbiturates, propofol

— Avoid phenytoin — also a Na-channel blocker, may worsen cardiotoxicity

Step 3 management: The single highest-yield decision is "is the QRS ≥ 100 ms?" If yes, push 1–2 mEq/kg IV sodium bicarbonate bolus, then start infusion. Re-image ECG. Repeat boluses until QRS narrows or pH reaches 7.55. This algorithm appears on Step 3 in management-vignette form repeatedly.

Immediate priorities (ABC-tox):

Risk-stratify by ECG and clinical:

First-line management triggers for sodium bicarbonate:

Seizures:

Pharmacotherapy — First-Line Drug Regimen

— Mechanism: serum alkalinization increases unbound drug ionization and Na⁺ load overcomes Na-channel blockade

— Bolus dose: 1–2 mEq/kg IV push, repeat every 3–5 min until QRS narrows (< 100 ms), BP improves, or pH = 7.55

— Infusion: mix 3 ampules (150 mEq) in 1 L D5W, run at 250 mL/hr; titrate to pH 7.50–7.55

— Monitor: ABG, K⁺ (alkalosis drives K⁺ intracellularly → supplement), Na⁺ (hypernatremia risk), pH

— Continue until QRS normalizes and patient is hemodynamically stable for several hours

— Norepinephrine is preferred — direct α1 agonist counters TCA α1 blockade

— Epinephrine acceptable

— Avoid dopamine — relies on endogenous norepinephrine release, which is depleted; often ineffective

— Lorazepam, midazolam, diazepam — escalate dose

— Propofol or phenobarbital for refractory seizures

— Avoid phenytoin and fosphenytoin

— Indication: cardiac arrest or refractory cardiotoxic shock unresponsive to bicarbonate and vasopressors

— Dose: 1.5 mL/kg bolus over 1 min, then 0.25 mL/kg/min infusion

— Mechanism: "lipid sink" sequesters lipophilic TCA

Board pearl: Three commonly tested "do-not-give" drugs in TCA overdose: phenytoin, procainamide, and physostigmine. Physostigmine, though it reverses anticholinergic delirium, can precipitate asystole and seizures in TCA poisoning.

Sodium bicarbonate — the cornerstone antidote:

Hypertonic saline — alternative when bicarbonate fails or pH already > 7.55; provides Na⁺ load without further alkalinization

Vasopressors for refractory hypotension:

Seizure control:

Lipid emulsion therapy (Intralipid 20%):

Magnesium for torsades; avoid class Ia, Ic, and III antiarrhythmics (procainamide, amiodarone may worsen QRS/QT) — use lidocaine if antiarrhythmic needed.

Flumazenil contraindicated — may precipitate seizures in TCA co-ingestion.

Procedures and Advanced/Refractory Management

— Indications: GCS decline, seizures, refractory shock, anticipated transport, severe acidosis requiring controlled hyperventilation

— Use ketamine or etomidate for induction; avoid hypotensive agents

— Post-intubation ventilation: target pH 7.50–7.55, respiratory rate often 16–20, tidal volume 6–8 mL/kg — verify by ABG; do not rely on EtCO2 alone for pH

— Activated charcoal 1 g/kg (max 50 g) PO or via NG; single dose typically; multi-dose charcoal not routinely beneficial for TCA

— Only if airway secure — aspiration of charcoal is a disaster

— Beyond 1–2 h, benefit diminishes but anticholinergic gastric stasis may extend window per toxicology

— VA-ECMO has growing literature support and case-series benefit

— Early activation of ECMO team if QRS > 160 ms with shock unresponsive to bicarbonate + norepinephrine + lipid emulsion

— Mechanical CPR devices to maintain perfusion during cannulation

CCS pearl: On a CCS case where the patient codes from refractory VT after TCA overdose, the sequence is CPR → bicarbonate push → epinephrine → lipid emulsion → consider ECMO consult. Defibrillation for shockable rhythms still applies, but standard antiarrhythmics (amiodarone, procainamide) should be avoided or used cautiously — lidocaine is the preferred antiarrhythmic.

Endotracheal intubation:

Decontamination details:

Hemodialysis is NOT effective — TCAs are highly protein-bound and have large volumes of distribution.

Lipid emulsion therapy: as in chunk 7; use in extremis.

Refractory cardiogenic shock or arrest:

Glucagon: not first-line, but considered if concomitant β-blocker or calcium channel blocker ingestion.

Temporary pacing: rarely needed; bradydysrhythmias usually preterminal and respond poorly.

Foley catheter — anticholinergic urinary retention is common and bladder distension can cause autonomic instability.

NG decompression for ileus when intubated.

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline anticholinergic burden, often on multiple QT-prolonging medications

— More sensitive to orthostatic hypotension and delirium even at therapeutic doses

— Coronary disease and conduction system disease lower the threshold for malignant arrhythmia

— Polypharmacy increases co-ingestion risk; obtain full med rec from pharmacy

— Lower seizure threshold from age-related CNS changes and concurrent medications (tramadol, bupropion)

— TCAs undergo extensive hepatic CYP2D6 metabolism; cirrhotics have prolonged half-life and accumulated active metabolites (nortriptyline from amitriptyline, desipramine from imipramine)

— Toxicity may be delayed and prolonged; extend observation

— Coagulopathy may complicate procedures

— Renal clearance is minor for parent drug, but active metabolites accumulate

— Watch electrolytes carefully during bicarbonate therapy — risk of hypernatremia, hypokalemia, fluid overload

— Dialysis does not remove TCA but may be needed for volume management

— SSRIs (fluoxetine, paroxetine) inhibit CYP2D6 → ↑ TCA levels

— Cimetidine, bupropion, quinidine — similar interactions

— Anticholinergics, antihistamines compound toxidrome

Step 3 management: In an elderly patient on amitriptyline for neuropathic pain who presents with confusion and a wide QRS after starting fluoxetine, recognize this as iatrogenic TCA toxicity from CYP2D6 inhibition, not a primary cardiac event. Stop both drugs, give bicarbonate if QRS > 100 ms, and reconsider chronic TCA use — gabapentin or duloxetine are safer long-term options.

Elderly patients:

Hepatic impairment:

Renal impairment:

CYP2D6 poor metabolizers (≈7% of Caucasians) — accumulate parent drug at standard doses; iatrogenic overdose possible

Drug interactions amplifying toxicity:

Special Populations — Pregnancy and Pediatrics

— TCAs cross the placenta; maternal overdose threatens both

— Maternal resuscitation = fetal resuscitation — do not delay bicarbonate, intubation, or pressors for fetal concerns

— Left lateral tilt (or manual uterine displacement) after 20 weeks gestation

— Continuous fetal monitoring after 23–24 weeks if viable; obstetric consult

— Norepinephrine acceptable despite uteroplacental vasoconstriction concerns when life-threatening hypotension

— Perimortem cesarean within 4 minutes of maternal arrest if ≥ 23 weeks

— Postpartum: screen for postpartum depression and means restriction

— Amitriptyline, imipramine, desipramine: a single adult tablet (75–150 mg) can be lethal in a toddler (10–20 mg/kg threshold)

— Any pediatric TCA exposure → ED evaluation with 6-hour observation minimum, ECG, mental status checks

— Decontamination with activated charcoal if early and airway protected

— Bicarbonate dosing: 1–2 mEq/kg per bolus, same indications

— Seizures: benzodiazepines (lorazepam 0.05–0.1 mg/kg)

— Lipid emulsion: same regimen, weight-based

— Intentional ingestion is the dominant pattern; assess suicidality, school stressors, bullying, substance use

— Mandatory child protective considerations for access and storage

— Means restriction counseling to caregivers before discharge — remove or lock all medications, firearms

Board pearl: A toddler who ingested "one or two of grandma's nerve pills" requires immediate ECG and 6-hour minimum observation even if asymptomatic. Counsel families on pediatric medication safety, Mr. Yuk stickers, child-resistant caps, and locked cabinets — these prevention items appear on Step 3 health-systems questions.

Pregnancy:

Pediatrics — "one pill can kill":

Adolescents:

Complications and Adverse Outcomes

— Ventricular tachycardia, ventricular fibrillation, asystole — leading cause of death

— Cardiogenic shock from myocardial depression

— Bradydysrhythmias and AV blocks in late/preterminal stages

— Brugada-like ECG patterns (may persist post-recovery, consider follow-up)

— Status epilepticus (rare but devastating)

— Anoxic brain injury after arrest

— Prolonged delirium during recovery, especially elderly

— Aspiration pneumonitis/pneumonia — common given altered mental status + anticholinergic ileus

— ARDS

— Iatrogenic complications of intubation

— Lactic acidosis from seizures and shock

— Hypokalemia from bicarbonate therapy → may worsen QT prolongation; replete K⁺ to keep 4.0–4.5 mEq/L

— Hypernatremia from bicarbonate Na⁺ load

— Hypoglycemia (rare)

— Rhabdomyolysis from seizures, immobility, hyperthermia → AKI

— Compartment syndrome with prolonged down-time

— Ileus, gastric retention, charcoal aspiration

— Bowel ischemia in severe shock

— Charcoal aspiration in unprotected airway — devastating chemical pneumonitis

— Inadvertent use of contraindicated drugs (phenytoin, procainamide, flumazenil, physostigmine)

— Over-alkalinization (pH > 7.55) → seizure threshold lowered, ionized hypocalcemia, tetany

Key distinction: Death in TCA overdose is cardiovascular, not neurologic. Recognizing and aggressively treating QRS widening before it progresses to ventricular dysrhythmia is the highest-impact intervention. Patients who survive the first 24 hours with appropriate management generally have excellent neurologic recovery unless they suffered anoxic injury.

Cardiovascular:

Neurologic:

Pulmonary:

Metabolic:

Renal/musculoskeletal:

Gastrointestinal:

Iatrogenic:

When to Escalate Care — ICU, Consults, and Triage

— QRS ≥ 100 ms at any point

— Altered mental status beyond mild drowsiness

— Seizure

— Hypotension or need for vasopressors

— Need for sodium bicarbonate infusion

— Dysrhythmia

— Intubation

— Significant co-ingestion (e.g., acetaminophen requiring NAC)

— Mild symptoms resolved, normal ECG, but within 6 h observation window

— Used uncommonly; most symptomatic TCA overdoses go straight to ICU

— Asymptomatic, normal serial ECGs, GCS 15, normal vitals, ≥ 6 hours post-immediate-release ingestion

— Psychiatric evaluation completed and disposition arranged

— Means restriction counseling documented

— Poison Control / Medical Toxicology — early, for all intentional or symptomatic exposures

— Psychiatry — for all intentional ingestions before medical-clearance discharge

— Cardiology — for refractory dysrhythmia, possible Brugada pattern follow-up

— Cardiothoracic surgery / ECMO team — refractory shock or arrest

— Social work, case management — outpatient mental health linkage, safety planning, child protective services if applicable

— If receiving facility lacks ICU, toxicology, or ECMO and patient is high-risk, initiate stabilization (intubation, bicarbonate, pressors) and transfer to tertiary center

CCS pearl: On CCS, after the patient stabilizes in the ED, the correct location move is "transfer to ICU" — not floor. Order psychiatry consult, toxicology consult, continuous monitoring, and acetaminophen/salicylate level as standing items. Failing to consult psychiatry before discharge planning is a frequently penalized omission.

ICU admission criteria (any one):

Step-down or telemetry:

Floor admission: rarely appropriate for acute TCA overdose; psychiatric inpatient transfer only after medical clearance

Discharge from ED:

Consultations:

Transfer considerations:

Key Differentials — Same-Category (Other Drug Overdoses)

— Carbamazepine: structurally a tricyclic; cardiotoxic, anticholinergic, sedating. Treat similarly with bicarbonate. Multi-dose activated charcoal is more useful here than in TCA.

— Diphenhydramine and other H1 antihistamines: anticholinergic toxidrome + Na-channel blockade; bicarbonate works.

— Cocaine: Na-channel blockade + sympathomimetic; bicarbonate for wide QRS; benzodiazepines first-line.

— Class Ia (quinidine, procainamide, disopyramide) and Class Ic (flecainide, propafenone) antiarrhythmic toxicity: wide QRS, dysrhythmia; bicarbonate indicated.

— Propranolol: lipophilic β-blocker with Na-channel activity at high doses; widens QRS plus bradycardia.

— Bupropion: seizures and QRS widening at high doses; bicarbonate for QRS.

— Hydroxychloroquine and chloroquine: profound Na-channel blockade + K-channel blockade; high mortality.

— Jimsonweed (Datura), atropine, scopolamine, benztropine — pure anticholinergic, less cardiotoxic

— Serotonin syndrome → hyperreflexia + clonus (especially lower extremity), diaphoresis, hyperthermia. TCAs cause hyperreflexia too, but diaphoresis is absent (anticholinergic dry skin).

Key distinction: All sodium channel blocker overdoses share a common cardiotoxic algorithm — bicarbonate for QRS > 100 ms, avoid class Ia/Ic antiarrhythmics, lidocaine if antiarrhythmic needed, lipid emulsion in extremis. Mastering this single pathway covers a large slice of toxicology questions on Step 3.

Other Na-channel blocker toxicities producing wide QRS:

Other anticholinergic overdoses:

Serotonin syndrome vs TCA toxicity:

Neuroleptic malignant syndrome — slower onset, lead-pipe rigidity, antipsychotic exposure history.

Key Differentials — Other-Category Causes

— VT from ischemia, cardiomyopathy, electrolyte derangement

— Hyperkalemia — wide QRS with peaked T waves; treat with calcium, insulin/dextrose, bicarbonate (overlaps in management)

— Pre-existing bundle branch block masquerading as wide complex

— Hepatic encephalopathy, uremia, hypoglycemia, severe hyponatremia/hypernatremia

— These cause altered mental status but rarely wide QRS

— Stroke, intracranial hemorrhage, meningitis, encephalitis — usually localizing findings or fever

— Status epilepticus from epilepsy — anticonvulsant history, no ingestion

— Isoniazid — refractory seizures, treat with pyridoxine

— Bupropion, tramadol — seizures with less cardiotoxicity (tramadol can prolong QT)

— Lithium — tremor, hyperreflexia, no QRS widening; treat with hemodialysis (unlike TCA)

— Salicylates — mixed acid-base, tinnitus, hyperventilation, hyperthermia

Board pearl: A patient with seizure + altered mental status + wide QRS + dry skin + mydriasis nearly always points to TCA or related sodium-channel blocker overdose on a Step 3 vignette. If the same picture has diaphoresis instead of dry skin, pivot toward sympathomimetic or serotonin syndrome. Skin moisture is the silent disambiguator examiners love to embed in the stem.

Primary cardiac causes of wide-complex tachycardia:

Metabolic encephalopathy:

Sepsis — distributive shock with altered mental status; lactate elevation, fever, source identifiable

CNS causes of seizure + coma:

Other ingestions presenting with seizure + altered mental status:

Thyroid storm, sympathomimetic intoxication — tachycardia + agitation, but diaphoretic skin

Anticholinergic plant ingestion — Datura, Atropa belladonna — usually less cardiotoxic

Trauma — always rule out occult head injury in altered-mental-status patient, especially if found down

Secondary Prevention, Discharge Planning, and Long-Term Care

— Asymptomatic ≥ 6 hours (or longer for extended-release / massive ingestions)

— Two consecutive normal ECGs

— Tolerating PO, normal mental status, normal vitals

— Co-ingestion workup complete (acetaminophen, salicylate, ethanol)

— Psychiatric clearance and disposition plan

— Most intentional TCA overdoses require inpatient psychiatric admission given lethality of the agent

— Voluntary vs involuntary hold per state law; document capacity assessment

— Safety plan, lethal-means restriction, family involvement

— Reconsider chronic TCA use — alternatives:

— Depression: SSRI, SNRI

— Neuropathic pain: gabapentin, pregabalin, duloxetine

— Migraine prophylaxis: topiramate, propranolol, CGRP antagonists

— Insomnia: CBT-I, trazodone (lower-risk in overdose), melatonin

— If TCA continued, prescribe limited quantities (e.g., 1-week supply, no refills without follow-up); engage pharmacy

— Document conversation with patient and family about removing or securing all medications, firearms, sharps

— Provide National Suicide & Crisis Lifeline: 988

— Psychiatry follow-up within 7 days post-discharge from inpatient psych

— Primary care follow-up within 1–2 weeks

— Therapy referral (CBT, DBT)

— Substance use counseling if co-occurring

— Warning signs requiring return: chest pain, palpitations, syncope, seizure, recurrent suicidal ideation

Step 3 management: When restarting any psychotropic at discharge, prescribe non-lethal-in-overdose alternatives preferentially, dispense small quantities, and document means restriction counseling — these are concrete, testable elements of suicide prevention on the boards.

Medical discharge criteria:

Psychiatric disposition:

Medication review and substitution:

Means restriction:

Outpatient linkage:

Patient education:

Follow-Up, Monitoring, and Counseling

— Follow-up ECG within 1–2 weeks if any cardiotoxicity occurred — persistent Brugada-like patterns warrant cardiology referral

— Electrolyte recheck (K⁺, Mg²⁺, Na⁺) if bicarbonate therapy used

— LFTs if hepatotoxicity from co-ingestion (acetaminophen) or shock

— Renal function follow-up if rhabdomyolysis or AKI occurred

— Within 7 days of inpatient psychiatric discharge — highest-risk window for repeat attempt

— Weekly to biweekly visits for first 1–3 months

— Continuity of care: assign a single prescriber, avoid fragmented refills

— Suicide safety plan: warning signs, internal coping strategies, social contacts, professional contacts, 988 lifeline, means restriction

— Family education on supervision and recognizing warning signs

— Substance use treatment if applicable

— Sleep hygiene, exercise, sunlight exposure as adjunctive non-pharmacologic measures

— Cognitive rehab if anoxic injury or prolonged delirium

— Physical therapy if rhabdomyolysis, prolonged immobilization

— Return-to-work / return-to-school planning, possibly modified

— Baseline and periodic ECG (especially in elderly)

— Drug interaction surveillance — beware CYP2D6 inhibitors

— Dispense in 30-day supplies with consistent pharmacy

— Regular suicidality screening (PHQ-9)

— Documentation of 7-day post-discharge follow-up is a HEDIS quality metric for behavioral health admissions

— Track repeat ED visits as a safety signal

Board pearl: The 7-day post-psychiatric-discharge follow-up window is a recurring Step 3 health-systems and patient-safety item. Patients are at greatest risk for repeat suicide attempt in the first 30 days post-discharge — early follow-up reduces this risk and is now a national quality measure.

Post-discharge monitoring:

Psychiatric follow-up cadence:

Counseling content:

Functional rehabilitation:

Long-term medication monitoring (if TCA must be continued, e.g., refractory neuropathic pain):

Quality measures:

Ethical, Legal, and Patient Safety Considerations

— A patient who just attempted suicide via TCA overdose typically lacks capacity to refuse psychiatric evaluation in the acute setting

— Use state-specific involuntary hold mechanisms (e.g., 5150 in CA, "psychiatric hold," "M1 hold")

— Document capacity assessment: understanding, appreciation, reasoning, communication of choice

— Allow least-restrictive intervention compatible with safety

— Emergency exception applies for life-saving interventions (intubation, bicarbonate, pressors) when patient is altered

— Document inability to consent and emergency doctrine in chart

— HIPAA permits disclosure to family for emergency care coordination and means restriction

— Mandatory reporting:

— Child protective services if pediatric exposure suggests neglect or unsafe storage

— Adult protective services if elderly patient with cognitive impairment had unsecured access

— Duty-to-warn obligations if specific threats to identifiable third parties

— Medication reconciliation at every handoff — TCA prescription should be reviewed and potentially discontinued

— Communicate to outpatient prescriber that patient overdosed on prescribed TCA

— Ensure pharmacy is notified; some systems flag controlled-fill alerts

— Avoid prescribing TCAs to patients with prior overdose history when alternatives exist

— Suicide risk assessment using validated tool (Columbia Protocol or similar)

— Means restriction counseling and confirmation by family

— Safety plan provided in writing

— Follow-up appointments scheduled before discharge ("warm handoff")

— If iatrogenic harm (e.g., contraindicated drug administered), submit institutional safety report

— Root-cause analysis for sentinel events

Step 3 management: A patient who tries to leave AMA after TCA overdose with persisting suicidal ideation does not have capacity to refuse. Place a psychiatric hold, document capacity assessment, and continue treatment — this is the most-tested ethical scenario in overdose vignettes.

Capacity and involuntary holds:

Informed consent edge cases:

Confidentiality and disclosure:

Transition-of-care safety:

Documentation essentials:

Patient safety event reporting:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: If you remember only one number for Step 3 TCA questions: QRS ≥ 100 ms → push sodium bicarbonate 1–2 mEq/kg IV. This single decision drives most management vignettes and dominates the cardiotoxicity treatment algorithm.

QRS > 100 ms → bicarbonate; > 160 ms → high arrhythmia risk

R wave in aVR > 3 mm or R/S ratio > 0.7 in aVR → TCA cardiotoxicity

Target serum pH 7.50–7.55 with bicarbonate therapy

Norepinephrine is the preferred vasopressor (direct α1 agonist); avoid dopamine

Lidocaine is the antiarrhythmic of choice; avoid procainamide, amiodarone (cautious), Ia/Ic agents

Phenytoin contraindicated for TCA seizures — use benzodiazepines first-line

Physostigmine contraindicated — risk of asystole and seizures

Flumazenil contraindicated in mixed overdose — may unmask seizures

Hemodialysis does NOT remove TCAs (high Vd, high protein binding)

Activated charcoal 1 g/kg within 1–2 h, airway protected only

Lipid emulsion for refractory cardiotoxic shock or arrest

ECMO considered for refractory cases

Six-hour observation for asymptomatic immediate-release ingestion; longer for extended-release

Pediatric "one pill can kill" — 10–20 mg/kg can be lethal

Suicide lifeline: 988; psychiatry follow-up within 7 days post-discharge

Mechanism summary: Na⁺ block → QRS widening; K⁺ block → QT prolongation; α1 block → hypotension; muscarinic block → anticholinergic toxidrome; CNS block → seizures, coma

Drug interactions to recognize: fluoxetine, paroxetine, bupropion, cimetidine inhibit CYP2D6 → ↑ TCA levels

Common TCAs by indication: amitriptyline, nortriptyline (pain, depression); clomipramine (OCD); imipramine (enuresis); doxepin (insomnia, low dose)

Brugada-like ECG pattern can persist post-recovery — consider cardiology follow-up

Means restriction counseling is the single most evidence-based suicide prevention intervention

Board Question Stem Patterns

Step 3 management: When in doubt on a TCA vignette, default answers cluster around sodium bicarbonate, benzodiazepines, norepinephrine, lidocaine, lipid emulsion, charcoal (if early), ICU admission, psychiatric consult, and 7-day follow-up. Wrong answers cluster around phenytoin, physostigmine, dopamine, procainamide, flumazenil, and hemodialysis.

Classic stem 1 — Intentional overdose: 22-year-old woman brought by EMS after found with empty bottle of amitriptyline. Drowsy, HR 130, BP 88/50, dry skin, dilated pupils. ECG: wide-complex tachycardia, QRS 140 ms, prominent R in aVR. → Answer: IV sodium bicarbonate. Distractors: amiodarone, phenytoin, physostigmine, hemodialysis.

Classic stem 2 — Pediatric exposure: 2-year-old swallowed "two of grandma's pills" for migraines. Currently alert, vitals normal, ECG normal. → Answer: ED observation ≥ 6 hours with serial ECGs, even though asymptomatic.

Classic stem 3 — Seizure management: TCA overdose patient develops generalized tonic-clonic seizure. → Answer: IV lorazepam. Distractor: phenytoin (wrong — contraindicated).

Classic stem 4 — Refractory hypotension: Wide QRS, BP 70/40 despite fluids and bicarbonate. → Answer: norepinephrine. Distractor: dopamine (less effective due to depleted endogenous catecholamines).

Classic stem 5 — ECG recognition: ECG shows sinus tachycardia, QRS 130 ms, R wave 5 mm in aVR. → Diagnosis: TCA toxicity.

Classic stem 6 — Drug interaction: Elderly patient on amitriptyline started on fluoxetine for depression, develops confusion and wide QRS. → Mechanism: CYP2D6 inhibition raising TCA levels.

Classic stem 7 — Discharge/ethics: Patient recovered from overdose now asks to leave; still endorses suicidal ideation. → Answer: psychiatric hold, capacity lacking; continue treatment.

Classic stem 8 — Avoid these drugs: Patient with TCA overdose develops VT. Best antiarrhythmic? → Answer: lidocaine (avoid procainamide, amiodarone preferred over Ia/Ic but still cautious).

Classic stem 9 — Decontamination: Patient arrives 30 min after ingestion, intubated. → Answer: activated charcoal via NG.

Classic stem 10 — Lipid emulsion: Cardiac arrest from TCA refractory to ACLS and bicarbonate → Intralipid 20%.

One-Line Recap

TCA overdose is a sodium-channel-blocking, anticholinergic, cardiotoxic emergency in which a QRS ≥ 100 ms or any hemodynamic instability mandates immediate IV sodium bicarbonate, supportive care with benzodiazepines for seizures and norepinephrine for hypotension, ICU admission, and post-stabilization psychiatric evaluation with means restriction and 7-day follow-up.

Board pearl: The Step 3 examinee who masters one algorithm — "QRS ≥ 100 ms → bicarbonate; seizure → benzodiazepine; shock → norepinephrine; refractory → lipid emulsion and ECMO; intentional → psych hold and 7-day follow-up" — will answer virtually every TCA overdose vignette correctly, including the ethical, pharmacologic, ECG-interpretation, and disposition variations the boards rotate through year after year.

Recognize: wide-complex tachycardia + anticholinergic toxidrome + altered mental status + seizure history; check for prominent R wave in aVR.

Treat: sodium bicarbonate boluses (1–2 mEq/kg) until QRS narrows or pH 7.50–7.55; benzodiazepines for seizures; norepinephrine for shock; lipid emulsion and ECMO for refractory cases.

Avoid: phenytoin, physostigmine, flumazenil, procainamide, dopamine, hemodialysis — these are the recurring "wrong answer" choices.

Disposition: ICU for any symptomatic patient; 6-hour observation for asymptomatic; psychiatric hold and inpatient admission for intentional ingestions; 7-day post-discharge follow-up; switch chronic TCA users to safer alternatives (SNRI, gabapentin, topiramate) with limited dispensing and means restriction counseling.