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Toxicity, Antidepressant: Treatment & Medication
Updated: Nov 13, 2008
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Treatment
Prehospital Care
Closely monitor vital signs and cardiovascular, neurological, and respiratory status in addition to ECG monitoring. Rapidly transport all patients with possible TCA ingestion to the hospital because clinical deterioration often occurs rapidly after overdose. Although the effectiveness of out-of hospital activated charcoal has not been studied in the prehospital setting, because of the aspiration risk involved, it is not routinely recommended. Aggressive airway support is vital. Flumazenil administration is contraindicated following TCA overdose.
Emergency Department Care
Immediate evaluation is imperative for any patient presenting with a suspected tricyclic overdose. Intravenous access should be obtained, and the patient should be connected to a cardiac monitor. If the patient presents with CNS depression, intubation should be considered. An ECG should be obtained, and basic laboratory studies, including electrolytes and glucose levels, should be sent. If the patient is presenting with altered mental status, an arterial blood gas measurement should be obtained.
- Dysrhythmias
- Sodium bicarbonate is the first-line therapy if TCA ingestion is known or strongly suspected. Sodium bicarbonate should be considered in life-threatening circumstances in the prehospital setting if there is a protocol for its use.
- Procainamide, quinidine, beta-blockers, and calcium channel blockers are contraindicated.
- Hypotension
- Hypotension is treated with sodium bicarbonate and intravenous fluids.
- Animal studies show a benefit to using hypertonic saline to reverse cardiotoxicity, but the doses for TCA poisoning have never been evaluated in humans. One case report describes the successful use of 7.5% NaCl to treat refractory hypotension and QRS widening. This modality could be considered in refractory cases but should not supersede treatment with NaHCO3.
- Vasopressors are recommended for refractory hypotension.
- Convulsions
- Benzodiazepines
Consultations
- Consider consulting a regional poison control center or medical toxicologist.
- Patients with abnormal vital signs or mental status changes will need intensive care unit (ICU) care, which may require the consultation of an intensivist.
Medication
The mainstay of specific treatment of significant TCA-related toxicity is NaHCO3 administered in conjunction with supportive care, including aggressive airway support, antiseizure, vasopressor, and dysrhythmic medications. Indications for NaHCO3 administration include QRS widening, hypotension, dysrhythmias, and seizures that are associated with QRS widening. NaHCO3 replaces lidocaine as the drug of choice for ventricular tachycardia following TCA overdose in a variation of the usual ACLS guidelines. Hypotension with evidence of shock not responsive to judicious fluid therapy and sodium bicarbonate are indications for pressors. Norepinephrine has been reported to reverse refractory hypotension. A few recent reports also support a trial of vasopressin for refractory hypotension. Narcan or thiamine and immediate measurement of serum glucose concentration are indicated for any patients with altered mental status, such as that which occurs with TCA toxicity.
Contraindicated medications include flumazenil, beta-blockers, calcium channel blockers, and class IA (procainamide, quinidine, disopyramide, moricizine), class IC (flecainide, propafenone), and possibly class III (bretylium, amiodarone, sotalol) antidysrhythmics.
GI decontaminant
Activated charcoal is indicated for all TCA ingestions unless bowel obstruction, ileus, or perforation is suspected, even when a patient presents late following ingestion. Since the anticholinergic effects of TCAs delay gastric emptying and slow GI motility, this may allow efficacy for charcoal when administered relatively late postingestion. In cases of altered mental status, the benefits of charcoal need to be weighed against the risk of aspiration. Therefore, prior to charcoal administration, the airway needs to be secured in patients with an altered mental status.
Activated charcoal (Liqui-Char)
Binds TCAs, limiting absorption and speeding elimination. Clinical benefit of multiple doses has not been demonstrated clearly and is not recommended.
Adult
1 g/kg PO/NGT initial (may be administered with sorbitol or comparable cathartic or in aqueous solution)
Pediatric
1 g/kg PO (typical 12.5-25 g)
<2 years: Use aqueous charcoal without cathartic
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway and absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not very effective in poisonings of ethanol, methanol, and iron salts; can be effectively administered in early stages of gastric lavage; gastric lavage returns are black; intubate before administration in altered mental status
Cardiovascular agents
Serum alkalinization with NaHCO3 is the first-line and most effective therapy for arrhythmias. Vasopressors can be useful in correcting hypotension. Lidocaine is the second-line agent behind alkalinization for arrhythmias. Class IA and IC antiarrhythmic agents (eg, procainamide, disopyramide, quinidine, flecainide, encainide) are contraindicated, as are beta-blockers and calcium channel blockers. Animal studies show that TCA Fab effectively reduces hypotension, shortens QRS duration, and improves survival in TCA-poisoned animals, and one study by Heard et al in humans involving 7 patients showed that the use of TCA Fab was associated with a fall in serum free TCA levels with none of the patients in the study developing worsening signs of TCA toxicity.2 Further studies are still needed to evaluate the routine use of TCA Fab in humans.
Sodium bicarbonate (Neut)
First-line drug for cardiovascular morbidity in TCA poisoning. Provides exogenous sodium to overcome the competitive fast sodium channel blockade produced by TCA, and produces an alkalemia (or reverses acidemia) that mitigates the fast sodium channel blockade by TCA.
Indicated for QRS widening, dysrhythmias, hypotension, and seizures that are associated with QRS widening. Patient can be monitored and given boluses of bicarbonate prn if QRS widening and block resolves with initial treatment. Following bolus administration, an IV drip may be prepared with 3 ampules of bicarbonate in 1 L of D5W, run at 150-250 mL/h (monitor pH = 7.45-7.55). Maintain serum potassium levels (see Precautions below). Resolution of QRS widening is a reasonable endpoint for NaHCO3 administration. However, since it may recur, patients who have had QRS widening need to be on a cardiac monitor that is being continuously monitored.
Adult
1-2 mEq/kg IV bolus, followed by an IV drip of 1000 mL of D5W to which 100-150 mEq of sodium bicarbonate has been added; initiate drip rate at 3 times maintenance IVF rate and titrate drip rate to urinary pH (target >8)
Pediatric
Administer as in adults
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine; may inactivate sympathomimetic agents (eg, epinephrine, norepinephrine)
Documented hypersensitivity; alkalosis (pH >7.5); volume overload; severe hypernatremia; hypocalcemia; severe pulmonary edema; unknown abdominal pain
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause alkalosis, therefore monitor serum pH; may also cause decreased plasma potassium, hypocalcemia, and hypernatremia, though these are rare; serum potassium level must be >4 mEq/L because urinary alkalinization cannot occur in the presence of hypokalemia; caution in electrolyte imbalances such as in patients with CHF, cirrhosis, edema, corticosteroid use, or renal failure; when administering, avoid extravasation, which can cause tissue necrosis
Norepinephrine (Levophed)
Norepinephrine is the drug of choice. Other vasopressors may also be used, but norepinephrine has been reported to reverse hypotension that was refractory to other agents. This is thought to be because severe TCA toxicity causes depletion of synaptic norepinephrine that can then only be reversed with exogenous norepinephrine administration. Norepinephrine's vasopressive effect is from its alpha alpha-adrenergic agonist properties. Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.
Adult
0.05-0.15 mcg/kg/min IV infusion; titrate to effect
Pediatric
0.1-1 mcg/kg/min IV infusion; titrate to effect
Chlorpromazine enhances the pressor response of norepinephrine by blocking the reflex bradycardia caused by norepinephrine
Documented hypersensitivity; peripheral, mesenteric, or other vascular thrombosis; ischemia may be increased and the area of the infarct extended; uncorrected hypovolemia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Correct blood volume depletion, if possible, before administering; extravasation may cause severe tissue necrosis and, thus, should be administered into a large vein; caution in occlusive vascular disease; consider risk vs benefit if hypercapnia is present
Epinephrine (Adrenaline)
Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypertension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Adult
1-10 mcg/min IV; titrate dose to desired effect; severe cardiac dysfunction may require doses >10 mcg/min (up to 0.1 mcg/kg/min)
Pediatric
0.1-1 mcg/kg/min IV; titrate dose to desired effect
Increases toxicity of beta-blocking and alpha-blocking agents and halogenated inhalational anesthetics
Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias. Correct blood volume depletion, if possible, before administering
Phenylephrine (Neo-Synephrine)
Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return. Generally not used as a first-line agent. Correct volume deficits before administration.
Adult
100-180 mcg/min IV; decrease to 40-60 mcg/min when pressure stabilizes
Pediatric
0.1 mg/min IV infusion or 3 mg/m2 body surface area IM/SC q1-2h prn; decrease to 0.04-0.06 mg/min when pressure stabilizes
Bretylium may potentiate action of vasopressors on adrenergic receptors, possibly resulting in arrhythmias; MAOIs may significantly enhance adrenergic effects, and pressor response may be increased 2- to 3-fold
Guanethidine may increase pressor response of direct-acting vasopressors, possibly resulting in severe hypertension
Documented hypersensitivity; severe hypertension; ventricular tachycardia; uncorrected hypovolemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly patients, hyperthyroidism, myocardial disease, bradycardia, partial heart block, or severe arteriosclerosis; with hypovolemia, phenylephrine use is not a substitute for replacement of blood, fluids with electrolytes, and plasma (these should be restored promptly when loss has occurred)
Lidocaine (Xylocaine)
Secondary to NaHCO3 for dysrhythmias due to TCA toxicity. Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue. Second-line agent for treatment of ventricular dysrhythmias.
Adult
1.5 mg/kg slow IV push over 2-3 min, loading dose; may repeat q5min up to 300 mg/h; if successful, begin infusion at 1-4 mg/min
Pediatric
1 mg/kg slow IV push, drip at 10-50 mcg/kg/min
Coadministration with cimetidine or beta-blockers, increases toxicity; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine
Documented hypersensitivity to amide-type local anesthetics; avoid in Adams-Stokes syndrome and Wolff-Parkinson-White syndrome; avoid in severe sinoatrial, AV, or intraventricular block, if artificial pacemaker not in place
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia, shock, respiratory-depression, and bradycardia; may increase risk of CNS and cardiac adverse effects in elderly patients; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities
Anticonvulsants
Most seizures are short, self-limited, and may resolve before treatment can be administered; however, if prolonged greater than several minutes or repetitive, treatment is indicated. Controversy exists about the indications for sodium bicarbonate with seizures. A trial of NaHCO3 is recommended for seizures that are associated with QRS widening, after benzodiazepine treatment. If seizures are refractory to all treatment, paralysis is indicated to stop motor activity and resultant metabolic acidosis. Benzodiazepines may calm a patient presenting with agitation secondary to the anticholinergic effects. However, their use may exacerbate CNS depression from TCA overdose, so their use for this indication must be accompanied by aggressive monitoring and management of the airway. Flumazenil is contraindicated in treatment of TCA toxicity.
Lorazepam (Ativan)
Increasing the action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation. DOC because of more prolonged anticonvulsant effects than diazepam or midazolam (4-6 h vs 1-3 h). Has an excellent safety profile.
Adult
0.05-0.1 mg/kg (2-7 mg) IV/IM initial over 1-2 min
Pediatric
Children: 0.05 mg/kg IV (range, 0.02-0.1 mg/kg)
Adolescents: Administer as in adults
Status epilepticus:
Adolescents: 0.07 mg/kg; not to exceed 4 mg, slowly over 2-5 min, with second dose in 10-15 min if needed
Infants and children: 0.1 mg/kg over 2-5 min, second dose of 0.05 mg/kg IV at 10-15 min if needed; not to exceed 4 mg/dose
Neonates: 0.05 mg/kg over 2-5 min; may repeat in 10-15 min if needed
Toxicity in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs
Documented hypersensitivity; preexisting CNS depression with an unsecured airway; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression and secure the airway if compromised; contains benzyl alcohol, which may be toxic to infants in high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Adult
2-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg
Pediatric
30 days to 5 years: 0.05-0.3 mg/kg/dose IV over 2-3 min (slowly) q15-30 min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg/dose IV over 2-3 min (slowly) q2-5min until symptoms resolve; not to exceed 10 mg
Increases toxicity in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses; as with other CNS depressants, the airway needs to be secured if compromised
Phenobarbital (Barbita, Luminal)
Not used often because of the preferable safety profile of benzodiazepines but an effective antiseizure medication.
Adult
120 mg IV over 10 min, then 5 mg/min up to 500-600 mg/d total
Pediatric
15-20 mg/kg IV load; 1-6 mg/kg/dose q15-30min prn maintenance
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects, hypotension, and fatality; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities also may occur)
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritic patients
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression and secure the airway if compromised; monitor for hypotension; with prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
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| Differential Diagnoses & Workup: Toxicity, Antidepressant |
 Treatment & Medication: Toxicity, Antidepressant |
| Follow-up: Toxicity, Antidepressant |
| Multimedia: Toxicity, Antidepressant |
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References
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Further Reading
Keywords
antidepressant toxicity, antidepressant overdose, tricyclic antidepressants, TCAs, cyclic antidepressants, antidepressant poisoning, TCA toxicity, TCA overdose, TCA exposure, treatment of depression
