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Emergency And Acute Medicine – Antidepressant Poisoning
Core Overview: Antidepressants are among the most commonly prescribed psychiatric medications in the United States. Overdose presentations often involve selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), or atypical antidepressants, frequently in combination with atypical antipsychotics or mood stabilizers. These agents are also prescribed for chronic pain, anxiety disorders, eating disorders, substance use disorders, and sleep disturbances. Tricyclic antidepressants are discussed separately.
Mechanisms And Causes:
SSRIs increase synaptic serotonin by inhibiting presynaptic reuptake (e.g., fluoxetine, paroxetine, sertraline, citalopram, escitalopram).
SNRIs inhibit reuptake of both serotonin and norepinephrine (e.g., venlafaxine, desvenlafaxine, duloxetine) and may be more toxic in overdose than initially assumed.
Atypical antidepressants have variable effects on serotonin, norepinephrine, and dopamine and include bupropion, trazodone, and mirtazapine.
Atypical antipsychotics act primarily on dopamine receptors with additional serotonergic, α-adrenergic, histaminic, and muscarinic effects. Many psychiatric medications can block potassium and sodium channels, resulting in QT or QRS prolongation and cardiotoxicity.
Clinical Features:
SSRIs commonly cause sedation and serotonin syndrome; most are benign in single-agent overdose, except citalopram and escitalopram, which may cause QTc prolongation, seizures, and delayed toxicity up to 12 hours.
SNRIs may cause somnolence, vomiting, tachycardia, seizures, and QTc prolongation, especially with venlafaxine and desvenlafaxine.
Atypical antidepressants: bupropion is associated with seizures and QRS/QTc prolongation; trazodone causes sedation, hypotension, QTc prolongation, and priapism; mirtazapine causes sedation and QTc prolongation, with rare neutropenia in chronic use.
Atypical antipsychotics typically cause sedation, tachycardia, and miosis, with drug-specific risks such as agranulocytosis and cardiomyopathy (clozapine), anticholinergic delirium (olanzapine, quetiapine), hypotension (quetiapine), QTc prolongation (ziprasidone), or prolonged CNS effects (aripiprazole).
Initial Assessment: Determine the specific agents, dose, timing, and possible coingestants. Check bedside glucose in patients with altered mental status.
Diagnostic Evaluation:
Laboratory drug levels are rarely helpful acutely. Obtain ECG to assess QRS and QTc intervals. Order electrolytes, renal function, glucose, urine pregnancy test when appropriate, urine drug screen (limited impact on management), acetaminophen and salicylate levels, and serum ethanol. CT brain imaging is reserved for unexplained depressed mental status; chest radiograph is indicated if intubated or hypoxic.
Key Differentials: TCA toxicity, ethanol or sedative–hypnotic overdose, isoniazid toxicity, hypoglycemia, hypoxemia, electrolyte disturbances, withdrawal syndromes, serotonin syndrome, head trauma, opioid intoxication, mood stabilizer or antiepileptic overdose, and diabetic ketoacidosis.
Prehospital Priorities: Transport all medication containers with the patient. Support airway, breathing, and circulation. Administer IV fluids for hypotension and benzodiazepines for seizures.
Early Stabilization: Provide oxygen, continuous cardiac monitoring, IV access, and pulse oximetry. Intubate if airway protection is needed. Check rapid glucose; administer naloxone or dextrose as clinically indicated. Flumazenil is not recommended in mixed or unknown overdoses or in patients with seizure risk. Treat extrapyramidal symptoms with diphenhydramine or benztropine.
Emergency Department Management: Avoid GI decontamination if the airway is unprotected; do not intubate solely for charcoal. Activated charcoal may be considered early after ingestion. Treat QRS widening with IV sodium bicarbonate boluses (continuous infusions are ineffective). Manage hypotension refractory to fluids with norepinephrine rather than dopamine. Treat seizures with benzodiazepines, escalating to barbiturates if refractory. Address serotonin syndrome with benzodiazepines and active cooling.
Medication Options: Activated charcoal 50–75 g PO (up to 100 g); benzodiazepines (diazepam or lorazepam) for seizures/agitation; diphenhydramine or benztropine for EPS; naloxone as indicated; norepinephrine infusion for hypotension; phenobarbital for refractory seizures; sodium bicarbonate 1 mEq/kg IV bolus for QRS widening.
Disposition Planning:
Admit for 24-hour telemetry after ingestion of citalopram, escitalopram, venlafaxine, desvenlafaxine, or bupropion, even if initially asymptomatic. Admit patients with coma, persistent altered mental status, ECG abnormalities, hemodynamic instability, or neuroleptic malignant syndrome. Suicidal patients require 1:1 observation.
Asymptomatic patients more than 6 hours after ingestion of less toxic antidepressants may be medically cleared for psychiatric admission if not suicidal.
Follow-Up Care: Psychiatry referral is required for intentional overdoses.
Clinical Pearls And Pitfalls: Administer IV sodium bicarbonate promptly for QRS widening. Overdoses involving citalopram, venlafaxine, and bupropion are more likely to cause severe toxicity and delayed complications, warranting medical observation before psychiatric clearance.
Core Overview: Antidepressants are among the most commonly prescribed psychiatric medications in the United States. Overdose presentations often involve selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), or atypical antidepressants, frequently in combination with atypical antipsychotics or mood stabilizers. These agents are also prescribed for chronic pain, anxiety disorders, eating disorders, substance use disorders, and sleep disturbances. Tricyclic antidepressants are discussed separately.
Mechanisms And Causes:
SSRIs increase synaptic serotonin by inhibiting presynaptic reuptake (e.g., fluoxetine, paroxetine, sertraline, citalopram, escitalopram).
SNRIs inhibit reuptake of both serotonin and norepinephrine (e.g., venlafaxine, desvenlafaxine, duloxetine) and may be more toxic in overdose than initially assumed.
Atypical antidepressants have variable effects on serotonin, norepinephrine, and dopamine and include bupropion, trazodone, and mirtazapine.
Atypical antipsychotics act primarily on dopamine receptors with additional serotonergic, α-adrenergic, histaminic, and muscarinic effects. Many psychiatric medications can block potassium and sodium channels, resulting in QT or QRS prolongation and cardiotoxicity.
Clinical Features:
SSRIs commonly cause sedation and serotonin syndrome; most are benign in single-agent overdose, except citalopram and escitalopram, which may cause QTc prolongation, seizures, and delayed toxicity up to 12 hours.
SNRIs may cause somnolence, vomiting, tachycardia, seizures, and QTc prolongation, especially with venlafaxine and desvenlafaxine.
Atypical antidepressants: bupropion is associated with seizures and QRS/QTc prolongation; trazodone causes sedation, hypotension, QTc prolongation, and priapism; mirtazapine causes sedation and QTc prolongation, with rare neutropenia in chronic use.
Atypical antipsychotics typically cause sedation, tachycardia, and miosis, with drug-specific risks such as agranulocytosis and cardiomyopathy (clozapine), anticholinergic delirium (olanzapine, quetiapine), hypotension (quetiapine), QTc prolongation (ziprasidone), or prolonged CNS effects (aripiprazole).
Initial Assessment: Determine the specific agents, dose, timing, and possible coingestants. Check bedside glucose in patients with altered mental status.
Diagnostic Evaluation:
Laboratory drug levels are rarely helpful acutely. Obtain ECG to assess QRS and QTc intervals. Order electrolytes, renal function, glucose, urine pregnancy test when appropriate, urine drug screen (limited impact on management), acetaminophen and salicylate levels, and serum ethanol. CT brain imaging is reserved for unexplained depressed mental status; chest radiograph is indicated if intubated or hypoxic.
Key Differentials: TCA toxicity, ethanol or sedative–hypnotic overdose, isoniazid toxicity, hypoglycemia, hypoxemia, electrolyte disturbances, withdrawal syndromes, serotonin syndrome, head trauma, opioid intoxication, mood stabilizer or antiepileptic overdose, and diabetic ketoacidosis.
Prehospital Priorities: Transport all medication containers with the patient. Support airway, breathing, and circulation. Administer IV fluids for hypotension and benzodiazepines for seizures.
Early Stabilization: Provide oxygen, continuous cardiac monitoring, IV access, and pulse oximetry. Intubate if airway protection is needed. Check rapid glucose; administer naloxone or dextrose as clinically indicated. Flumazenil is not recommended in mixed or unknown overdoses or in patients with seizure risk. Treat extrapyramidal symptoms with diphenhydramine or benztropine.
Emergency Department Management: Avoid GI decontamination if the airway is unprotected; do not intubate solely for charcoal. Activated charcoal may be considered early after ingestion. Treat QRS widening with IV sodium bicarbonate boluses (continuous infusions are ineffective). Manage hypotension refractory to fluids with norepinephrine rather than dopamine. Treat seizures with benzodiazepines, escalating to barbiturates if refractory. Address serotonin syndrome with benzodiazepines and active cooling.
Medication Options: Activated charcoal 50–75 g PO (up to 100 g); benzodiazepines (diazepam or lorazepam) for seizures/agitation; diphenhydramine or benztropine for EPS; naloxone as indicated; norepinephrine infusion for hypotension; phenobarbital for refractory seizures; sodium bicarbonate 1 mEq/kg IV bolus for QRS widening.
Disposition Planning:
Admit for 24-hour telemetry after ingestion of citalopram, escitalopram, venlafaxine, desvenlafaxine, or bupropion, even if initially asymptomatic. Admit patients with coma, persistent altered mental status, ECG abnormalities, hemodynamic instability, or neuroleptic malignant syndrome. Suicidal patients require 1:1 observation.
Asymptomatic patients more than 6 hours after ingestion of less toxic antidepressants may be medically cleared for psychiatric admission if not suicidal.
Follow-Up Care: Psychiatry referral is required for intentional overdoses.
Clinical Pearls And Pitfalls: Administer IV sodium bicarbonate promptly for QRS widening. Overdoses involving citalopram, venlafaxine, and bupropion are more likely to cause severe toxicity and delayed complications, warranting medical observation before psychiatric clearance.
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