Basics
Description
- Antidepressants are the most commonly prescribed psychiatric medications in US.
- Patients who overdose on antidepressants may be on various antidepressants, divided into SSRIs, SNRIs, and atypical. Concomitant usage of atypical antipsychotics and mood stabilizing medications, some of which are FDA approved for the treatment of depressive disorders, is common.
- Antidepressants may be prescribed for multiple other indications, including chronic pain syndromes, anxiety, eating disorders, substance abuse, and sleep disorders.
- Tricyclic antidepressants (TCAs) are covered in a separate chapter
Etiology
Mechanism
- SSRIs:
- Increase serotonin at the synapse by preventing the reuptake of serotonin by the presynaptic neuron.
- SSRIs include paroxetine, fluoxetine, sertraline, citalopram, and escitalopram
- SNRIs
- Similar to SSRIs, but also inhibit reuptake of norepinephrine.
- Developed because said to have fewer side effects than SSRIs at therapeutic dose, although not true for toxicity.
- SNRIs include venlafaxine, desvenlafaxine, and duloxetine.
- Atypical antidepressants:
- Have variable effects on serotonin, norepinephrine, and dopamine.
- Include mirtazapine, trazodone, and bupropion
- Atypical antipsychotics:
- Most antipsychotics have activity at dopamine receptors, although variable agonism/antagonism depending on medication and dopamine receptor.
- Additional activity at serotonin, α-adrenergic, histamine, and muscarinic receptors.
- Psychiatric medications also have variable potassium and sodium channel blockade, leading to cardiotoxicity (QT and QRS prolongation, respectively).
Diagnosis
Signs and Symptoms
- SSRIs:
- Traditional SSRIs (fluoxetine, paroxetine, sertraline):
- Sedation
- Serotonin syndrome
- In single substance overdose, rarely will cause severe medical effects
- Citalopram/Escitalopram:
- Somnolence, vomiting, tachycardia
- QTc prolongation
- Seizures (more common in citalopram)
- Exhibit delayed toxicity (up to 12 hr after ingestion)
- SNRIs:
- Duloxetine:
- Somnolence, vomiting, tachycardia
- Seizures rare
- Venlafaxine/Desvenlafaxine:
- Atypical antidepressants:
- Bupropion
- Sedation
- Seizures
- QRS & QTc prolongation
- Trazodone:
- Sedation
- QTc prolongation
- Hypotension
- Priapism
- Mirtazapine:
- Sedation
- QTc prolongation
- Possible neutropenia in chronic dosing
- Atypical antipsychotics:
- Variable dopamine receptor activity
- Developed for fewer extrapyramidal symptoms (EPS), particularly tardive dyskinesia, than typical antipsychotics
- Most common symptoms in overdose include sedation, tachycardia, and miosis
- Clozapine:
- Agranulocytosis (in up to 1% taking chronically)
- Sialorrhea
- Cardiomyopathy
- Anticholinergic delirium
- Olanzapine:
- Anticholinergic delirium
- QTc prolongation
- Quetiapine:
- Hypotension from significant α1-antagonism
- QTc prolongation
- Anticholinergic delirium
- Ziprasidone:
- Sedation
- QTc prolongation → increased risk of torsade
- Aripiprazole:
- No QTc prolongation
- Hypotension
- Prolonged CNS dysfunction
Essential Workup
- Determine agents ingested, dose, and time of ingestion:
- Investigate for coingested drugs.
- Rapid bedside glucose if altered mental status
Diagnosis Tests & Interpretation
Lab
- Specific drug levels rarely available and do not guide emergent management
- ECG:
- For evaluation of QTc and QRS width
- Urine pregnancy:
- In females of childbearing age
- Electrolytes, BUN, creatinine, glucose
- Urine drug of abuse screening:
- Rarely changes clinical management
- Salicylate and acetaminophen concentrations
- Very common coingestants in suicidal patients
- Serum ethanol:
- To evaluate ethanol intoxication as contributing to altered mental status
Imaging
- CT of brain to evaluate for other causes of depressed mental status
- CXR if intubated or hypoxic
Differential Diagnosis
- TCA overdose
- Ethanol overdose
- Isoniazid overdose
- Hypoglycemia
- Hypoxemia
- Hyponatremia
- Hypocalcemia
- Withdrawal syndromes
- Serotonin syndrome
- Head trauma
- Opioid intoxication
- Sedative-hypnotic overdose
- Mood stabilizer/antiepileptic overdose
- DKA
Treatment
Pre-Hospital
- In cases of suspected overdose, bring all medication bottles to hospital with patient.
- ABCs
- 0.9% NS IV fluids as needed for hypotension
- Benzodiazepines as needed for seizures
Initial Stabilization/Therapy
- ABCs:
- Administer oxygen.
- Place on cardiac monitor and measure pulse oximetry.
- Establish IV access
- Intubate as needed for airway protection or respiratory status.
- Rapid bedside glucose measurement
- Naloxone or D50W as indicated for altered mental status and rapid clinical evaluation
- Flumazenil is not recommended for mixed-overdose patients, patients with underlying seizure disorder, or patients chronically on benzodiazepines.
- May give diphenhydramine 25-50 mg IM/IV or Cogentin 1 mg IV for EPS
Ed Treatment/Procedures
- GI decontamination:
- Do not attempt decontamination in a patient who cannot protect their airway.
- Intubation solely for decontamination purposes, however, is not recommended.
- Activated charcoal may be beneficial in early presenting overdoses.
- For QRS widening, administer sodium bicarbonate IV bolus.
- Sodium bicarbonate infusion (i.e., "bicarb drip"�) is NOT appropriate for use with QRS widening, as it is ineffective and potentially limits ability to provide sodium bicarbonate boluses.
- Treat hypotension unresponsive to IV fluids with norepinephrine rather than dopamine owing to α1 receptor antagonism.
- Treat seizures with:
- Initial therapy: Benzodiazepines
- For refractory seizures: Barbiturates
- Treat symptoms of serotonin syndrome (fever, AMS, tachycardia, rigidity, hyperreflexia) with benzodiazepines and active cooling
Medication
- Activated charcoal: 50-75 g PO initial dose; better to give 10g charcoal per 1g ingested xenobiotic as tolerated up to 100g PO
- Benztropine 1 mg PO/IV
- Diazepam: 5-10 mg IV bolus (peds: 0.1 mg/kg IV bolus or 0.5 mg/kg rectal)
- Diphenhydramine 25-50 mg IM/IV (peds 1 mg/kg)
- Lorazepam: 2-4 mg (peds: 0.1 mg/kg) IV bolus
- Naloxone: 0.4-2 mg (peds: 0.1 mg/kg) initial bolus; may repeat up to a total of 10 mg
- Norepinephrine: 0.5-2 μg/kg IV infusion
- Phenobarbital: 15-20 mg/kg IV max. dose is 2 g; caution: Likely to develop respiratory depression with IV loading doses
- Sodium bicarbonate: 1 mEq/kg IV bolus (adult 8.4%; peds: <50 kg, 4.2%)
Follow-Up
Disposition
Admission Criteria
- 24 h telemetry admission for ingestions of the following: Citalopram, escitalopram, venlafaxine, desvenlafaxine, bupropion
- Asymptomatic patients 6 hr after ingestion of other antidepressant medications do not require medical admission
- Coma
- Altered mental status
- Symptoms of NMS
- Hemodynamic compromise
- ECG changes
- Suicidal patients should be on a 1:1 observation
Discharge Criteria
- Asymptomatic patients of less toxic antidepressants >6 hr after ingestion may be medically cleared for psychiatric admission.
- Discharge only asymptomatic patients who are not suicidal.
Followup Recommendations
Psychiatry referral for patients with intentional overdose �
Pearls and Pitfalls
- For QRS widening, administer sodium bicarbonate IV bolus.
- Overdose with citalopram, venlafaxine, and bupropion have the possibility of being more severe than overdoses with other SSRIs and SNRIs and should prompt medical observation prior to clearance for psychiatric hospitalization.
- For any overdose, call your regional poison center at 1-800-222-1222
Additional Reading
- Boyer �EW, Shannon �M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.
- Cooke �MJ, Waring �WS. Citalopram and cardiac toxicity. Eur J Clin Pharmacol. 2013;69(4):755-760.
- Levine �M, Ruha �AM. Overdose of Atypical Antipsychotics: Clinical presentation, mechanisms of toxicity, and management. CNS Drugs. 2012;26(7):601-611.
- Stork �CM. Serotonin reuptake inhibitors and atypical antidepressants. In: Nelson �LS, Lewin �NA, Howland �MA, et al., eds. Goldfranks Toxicologic Emergencies. 9th ed. Chicago, IL: McGraw-Hill Medical; 2011:1037-1048.
See Also (Topic, Algorithm, Electronic Media Element)
Tricyclic Antidepressant Poisoning �
Codes
ICD9
- 969.00 Poisoning by antidepressant, unspecified
- 969.02 Poisoning by selective serotonin and norepinephrine reuptake inhibitors
- 969.05 Poisoning by tricyclic antidepressants
- 969.03 Poisoning by selective serotonin reuptake inhibitors
- 969.01 Poisoning by monoamine oxidase inhibitors
- 969.04 Poisoning by tetracyclic antidepressants
- 969.09 Poisoning by other antidepressants
- 969.0 Poisoning by antidepressants
ICD10
- T43.201A Poisoning by unsp antidepressants, accidental, init
- T43.211A Poisn by slctv seroton/norepineph reup inhibtr, acc, init
- T43.221A Poisn by selective serotonin reuptake inhibtr, acc, init
- T43.011A Poisoning by tricyclic antidepressants, accidental, init
- T43.021A Poisoning by tetracyclic antidepressants, accidental, init
- T43.291A Poisoning by oth antidepressants, accidental, init
SNOMED
- 82276009 Poisoning by antidepressant (disorder)
- 216545008 Accidental poisoning by antidepressants (disorder)
- 69434005 Tricyclic antidepressant poisoning (disorder)
- 290888005 Selective serotonin re-uptake inhibitor poisoning
- 9291000 Poisoning by monoamine oxidase inhibitor (disorder)