Psychiatric drug poisoning

Poisoning from the ingestion of psychiatric drugs (e.g., antidepressants, antipsychotics, or mood stabilizers) may occur as a result of an accidental or intentional overdose, changes in metabolism or excretion, or interactions with other drugs or food. Clinical features vary depending on the medication, amount ingested, and duration of therapy. Diagnosis is primarily clinical, with supportive studies including toxicological studies (e.g., serum drug levels) for certain substances, ECG, and laboratory studies. Management is primarily supportive with early involvement of the local Poison Control Center. Symptomatic patients generally require admission for further monitoring and treatment.

See also “Sedative-hypnotic drug overdose” and for prescription stimulants, see “Stimulant intoxication and withdrawal.”

Overview ^[1]

• Antidepressants increase the availability of neurotransmitters (e.g., serotonin, norepinephrine).
• Features of antidepressant overdose depend on the mode of action, e.g.:
  • Tricyclic antidepressants (TCAs) can cause anticholinergic syndrome.
  • SSRIs and SNRIs can cause serotonin syndrome.
  • Bupropion and SNRIs can cause features of stimulant intoxication.
  • MAOIs can cause hyperadrenergic symptoms and serotonin syndrome.
• Overdoses of certain substances (particularly TCAs, venlafaxine, and citalopram) are associated with significant cardiotoxicity. ^[2]
• Morbidity from antidepressant overdose varies by drug class; it is greatest for TCAs and MAOIs. ^[3]

Approach to antidepressant overdose ^[1][4]

Diagnostics

• Antidepressant overdose is predominantly a clinical diagnosis based on toxicological history and physical examination.
• Perform a toxicological risk assessment and obtain routine diagnostic studies.
  • Common ECG findings include QTc and QRS prolongation.
  • Urine drug screens can help diagnose TCA poisoning and determine coingestants, but the results may be unreliable.
  • Serum drug levels are often unobtainable or not available in time to inform acute management.
• Serial ECGs and/or continuous cardiac monitoring are commonly indicated.

Initial management

• Perform an ABCDE approach in poisoning and initiate resuscitation.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Manage agitation and toxic seizures with benzodiazepines.
• Provide supportive care for poisoned patients, e.g., fluid resuscitation, treatment of hypoglycemia, and electrolyte repletion.

GI decontamination

• Activated charcoal is recommended for the majority of recent ingestions in patients who are alert and/or have a protected airway.
• Gastric lavage may be appropriate for recent TCA or MAOI poisoning because of the associated increased morbidity.

Substance-specific management

• Consider sodium bicarbonate for TCA, SNRI, and bupropion overdose with QRS prolongation or ventricular arrhythmias. ^[5]
• Initiate symptom-specific management, e.g., manage serotonin syndrome.
• For life-threatening symptoms, consider lipid emulsion therapy and/or ECMO under specialist guidance. ^[6]
• See sections on “TCA overdose,” “SSRI overdose,” “SNRI overdose,” “MAOI poisoning,” and “Bupropion overdose” for additional recommendations.

Consults and disposition ^[1][4]

Guidance for disposition is limited. Disposition should be determined based on individual risk in consultation with Poison Control.

• Consult psychiatry for all intentional overdoses.
• Admit symptomatic patients for continuous monitoring.
• Admit to the ICU if hemodynamic stabilization, mechanical ventilation, or dialysis is required.
• Consider discharge after ≥ 6 hours of observation for asymptomatic patients with a normal ECG.

Mechanism of action ^[7]

• Cardiac fast sodium channel inhibition
• Muscarinic ACh receptor inhibition
• A₁-adrenergic receptor inhibition
• H₁ receptor inhibition
• GABA_A inhibition

Clinical features ^[1][7][8]

• Anticholinergic syndrome; (e.g., hyperthermia; , delirium, ileus, urinary retention)
• Cardiotoxicity: hypotension, tachycardia, arrhythmias
• Neurotoxicity
  • Altered mental status (e.g., lethargy, coma)
  • Seizures
  • Respiratory depression
  • Myoclonus
  • Extrapyramidal syndrome

Diagnostics ^[1][4]

Tricyclic antidepressant (TCA) overdose is a clinical diagnosis, but studies may be performed to support the diagnosis and determine severity.

• ECG findings of TCA poisoning ; ^[7]
  • Sinus tachycardia
  • Prolonged QRS interval ^[1]
  • Prolonged QTc interval
  • Terminal R wave in aVR
  • Ventricular and supraventricular arrhythmias
• Toxicological studies
  • Serum TCA levels:
    • Correlate poorly with poisoning severity ^[1]
    • > 1 mcg/mL are generally associated with severe symptoms (e.g., seizures, dysrhythmias)
  • Urine drug screens:
    • Commonly test for the presence of TCAs
    • May be falsely positive in patients who take medications such as carbamazepine, cyclobenzaprine, antipsychotics, or antimuscarinics ^[1][4]
• Laboratory studies
  • BMP: to assess electrolyte levels
  • VBG: to assess for acidemia

Serial ECGs should be performed to detect dynamic changes. ^[1]

The three Cs of tricyclic poisoning: Convulsions, Coma, and Cardiac conduction abnormalities (prolonged QTc interval).

Management ^[1][4]

Initial management

• Follow the approach to antidepressant overdose.
• Provide supportive care.
  • Secure the airway in patients with altered mental status or hemodynamic instability.
  • Provide immediate hemodynamic support.
  • Initiate continuous cardiac monitoring.
• Consider GI decontamination.
  • Activated charcoal: for ingestions within the past 2 hours in alert or intubated patients
  • Gastric lavage: may be considered for ingestions within the past 2 hours in intubated patients

Symptom-specific management

• QRS interval > 100 ms and/or ventricular dysrhythmias
  • Administer hypertonic sodium bicarbonate (off-label). ^[1][5][6]
  • Repeat every 3–5 minutes until cardiac abnormality resolves (i.e., QRS < 100 ms, resolution of ventricular dysrhythmias) or pH is 7.50–7.55.
  • Consider a subsequent sodium bicarbonate infusion to maintain pH between 7.50 and 7.55.
  • Obtain serial ECGs to monitor response to treatment.
• Toxic seizures
  • First-line treatment: benzodiazepines
  • Second-line treatment: barbiturates
  • Refractory seizures: general anesthesia
  • Phenytoin is contraindicated because it worsens cardiovascular toxicity and is not effective.
  • See “Phase-based acute seizure management” for dosages.
• Life-threatening cardiotoxicity: Consider lipid emulsion therapy and/or ECMO. ^[6]

In patients with TCA overdose, sodium bicarbonate can help overcome sodium channel blockade and prevent ventricular dysrhythmias, reduce conduction delays, and increase blood pressure. ^[1]

Class IA antiarrhythmics, class IC antiarrhythmics, and class III antiarrhythmics are contraindicated in TCA overdose. ^[1]

Physostigmine is contraindicated in patients with suspected TCA overdose because it can precipitate cardiac arrest. ^[4]

Disposition ^[1][4]

• Admit patients requiring mechanical ventilatory support and/or with hemodynamic instability to the ICU.
• Admit patients with clinical features of cardiotoxicity or neurotoxicity for continuous cardiac monitoring.
• Consider discharging asymptomatic, nontachycardic patients with a normal ECG after ≥ 6 hours of observation.

Clinical features ^[1][4]

Selective serotonin reuptake inhibitors (SSRIs) have a high therapeutic index and thus overdoses are well-tolerated and rarely fatal. ^[4]

• Common: drowsiness, tremor, nausea, vomiting
• Rare: seizures, symptoms of serotonin syndrome

Diagnostics ^[1][4]

SSRI overdose is a clinical diagnosis.

• ECG findings
  • Sinus tachycardia
  • Prolonged QTc interval ^[9]
  • Wide QRS complex ^[10]
• Toxicological studies
  • Serum SSRI levels are not available at most hospitals.
  • Urine drug screens usually do not assess for SSRIs.

Management ^[1][4]

• Initial management: Follow the approach to antidepressant overdose.
• Symptom-specific management
  • QTc interval > 500 ms: Consider magnesium sulfate (off-label). ^[4]
  • Manage agitation and toxic seizures with benzodiazepines.
  • Manage serotonin syndrome if present.
• Citalopram or escitalopram overdose
  • Initiate cardiac monitoring to assess for delayed prolonged QTc interval.
  • Repeat the ECG at the end of the 6-hour observation period.

Clinical features ^[4]

• Hyperadrenergic symptoms (e.g., tachycardia, hypertension) ^[11]
• Seizures
• Symptoms of rhabdomyolysis (e.g., myalgia, generalized weakness)
• Symptoms of serotonin syndrome
• Hypotension due to AHF (in massive overdose) ^[12]

Diagnostics ^[4]

Selective serotonin norepinephrine reuptake inhibitor (SNRI) overdose is a clinical diagnosis.

• ECG findings ^[11]
  • Prolonged QTc interval
  • Prolonged QRS interval
  • Ventricular dysrhythmias
• Toxicological studies
  • Serum SNRI levels are not available at most hospitals.
  • Urine drug screens usually do not assess for SNRIs.
• Laboratory studies: CPK level to evaluate for rhabdomyolysis

Management ^[4]

• Initial management: Follow the approach to antidepressant overdose.
• QRS prolongation: Consider sodium bicarbonate (off-label). ^[1][5][6]
• Hypotension or hypertension
  • Manage hyperadrenergic symptoms, e.g., with IV antihypertensives.
  • Treat acute heart failure.
• Other symptom-specific management
  • Manage agitation and toxic seizures with benzodiazepines.
  • Manage serotonin syndrome.
  • Manage rhabdomyolysis.

Clinical features ^[1]

MAOI poisoning can be due to overdose, food-drug interactions, or drug-drug interactions. The symptoms of MAOI overdose are distinct from those of MAOI poisoning caused by food-drug or drug-drug interactions.

MAOI overdose

• Onset: within 24 hours of ingestion
• Duration: days
• Clinical features
  • Hyperadrenergic symptoms (early)
  • Hypotension (late) ^[4]
  • Hyperthermia
  • Seizures
  • Symptoms of rhabdomyolysis (e.g., myalgia, generalized weakness)

Hyperadrenergic crisis

• Etiology
  • Consumption of tyramine-containing foods
  • Exposure to other sympathomimetics (e.g., cocaine)
• Onset: minutes to hours after ingestion
• Duration: hours
• Symptoms: hyperadrenergic symptoms (e.g., tachycardia, hypertension, flushing, diaphoresis)

Tyramine is found in red wine, aged cheese, liver, smoked meat, and yeast extract. ^[1]

Hyperadrenergic crisis due to eating tyramine-containing foods can occur up to 3 weeks after discontinuation of MAOIs. ^[4]

Serotonin syndrome

• Etiology: exposure to other serotonergic drugs (e.g., SSRIs, amphetamines)
• Onset: minutes to hours after ingestion
• Duration: hours
• Symptoms: clinical features of serotonin syndrome (e.g., hyperreflexia, hyperthermia, autonomic instability)

Diagnostics ^[4]

MAOI poisoning is a clinical diagnosis.

• ECG findings
  • Prolonged QTc interval
  • Prolonged QRS interval
  • ECG findings of ischemia (e.g., ST elevations)
• Laboratory studies
  • CPK level: to evaluate for rhabdomyolysis
  • Troponin level: to evaluate for cardiac ischemia
• CT head: to evaluate for ICH in patients with seizures or focal neurological deficits

Patients taking selegiline will test positive for methamphetamine on drug screening, as methamphetamine is a metabolite of selegiline. ^[4]

Management ^[1][4]

• Initial management: Follow the approach to antidepressant overdose.
• Management of autonomic instability
  • Severe hypertension
    • Short-acting agents, e.g., phentolamine, nitroprusside
    • For dosages, see “Intravenous antihypertensives.”
  • Hypotension
    • IV fluid resuscitation
    • Titratable vasopressors, e.g., norepinephrine
    • For dosages, see “Inoconstrictor drugs.”
• Management of hyperthermia
  • Initiate cooling measures: e.g., apply cooling blankets or ice packs, administer cold IV fluids, ice baths.
  • Refractory hyperthermia: Sedate, paralyze, and intubate patients.
• Other symptom-specific management
  • Manage agitation and toxic seizures with benzodiazepines.
  • Manage serotonin syndrome.

Avoid indirectly acting vasopressors (e.g., dopamine) in patients with hypotension, as their effectiveness is likely to be reduced as a result of catecholamine depletion. ^[4]

Disposition ^[1][4]

• Asymptomatic patients with a suspected food-drug interaction may be discharged after ≥ 6 hours of observation.
• Admit patients with MAOI overdose for further monitoring, preferably to the ICU.
• Admit patients with autonomic instability or refractory hyperthermia to the ICU.

Clinical features ^[13]

• Seizures
• Agitation
• Tachycardia
• Hypertension
• Hallucinations

Extended-release bupropion overdose is associated with delayed-onset seizures. ^[4]

Diagnostics ^[4]

• Bupropion overdose is mainly a clinical diagnosis.
• ECG findings include:
  • Sinus tachycardia
  • Prolonged QTc interval
  • Prolonged QRS interval

Management ^[1][4]

• Follow the approach to antidepressant overdose.
• Manage toxic seizures with benzodiazepines.
• Consider sodium bicarbonate, although it may be ineffective. ^[5]
• Monitor patients who have ingested > 450 mg of extended-release bupropion for delayed seizures.
• See also “Management of stimulant intoxication” and “Cathinones.”

Clinical features ^[1][9]

Symptoms of antipsychotic overdose develop within hours of ingestion and vary based on the drug's affinity for dopamine, muscarinic, and/or adrenergic receptors.

• CNS depression (dose-dependent, e.g., sedation, coma)
• Variable pupil size
• Seizures
• Hypotension, tachycardia
• Anticholinergic syndrome (e.g., delirium, agitation) ^[4]
• Extrapyramidal syndrome (e.g., dystonia, akathisia)
• Symptoms of neuroleptic malignant syndrome (e.g., hyperthermia, muscle rigidity)

Diagnostics ^[1][4][14]

Antipsychotic overdose is mainly a clinical diagnosis based on a toxicological history and physical examination. Perform a toxicological risk assessment and obtain routine diagnostic studies.

• ECG findings: variable, nonspecific
  • Sinus tachycardia
  • Prolonged QRS interval
  • Prolonged QTc interval
• Toxicological studies
  • Serum antipsychotic levels are not available at most hospitals.
  • Urine drug screens usually do not assess for antipsychotics.

Management ^[1][4][15]

Initial management

• Perform an ABCDE approach in poisoning and initiate resuscitation.
• Secure the airway in patients with severe CNS depression.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Consider GI decontamination with activated charcoal for recent ingestions.
• Consider and manage possible coingestions, e.g., with naloxone for opioid overdose.
• Provide supportive care for poisoned patients, e.g., fluid resuscitation, treatment of hypoglycemia, and electrolyte repletion.

Symptom-specific management

• Manage agitation and toxic seizures with benzodiazepines.
• Consider sodium bicarbonate (off-label) for prolonged QRS duration or ventricular dysrhythmias. ^[1][5][6]
• Treat anticholinergic syndrome under specialist guidance. ^[16]
• For life-threatening cardiotoxicity, consider lipid emulsion therapy and/or ECMO under specialist guidance.
• For additional symptom-specific management, see also:
  • Treatment of extrapyramidal symptoms
  • Treatment of neuroleptic malignant syndrome

Disposition ^[4]

• Patients with a normal ECG and minimal to no symptoms may be discharged after ≥ 6 hours of observation.
• Patients with a prolonged QTc interval should be observed for at least 12 hours to assess response to treatment.
• Admit patients with hemodynamic instability, ventricular dysrhythmias, or airway compromise to the ICU.

Definitions ^[1][4]

• Acute lithium poisoning: toxic effects caused by acute lithium ingestion in patients not therapeutically taking lithium
• Acute-on-chronic lithium poisoning: toxic effects caused by acute lithium ingestion in patients therapeutically taking lithium who have achieved steady-state concentration
• Chronic lithium poisoning: toxic effects caused by a gradual increase in serum lithium levels in patients therapeutically taking lithium

Etiology ^[1][4]

• Excessive intake
  • Increase in prescribed dose (lithium has a narrow therapeutic window)
  • Accidental or intentional overdose
• Decreased excretion
  • Renal insufficiency
  • Hypovolemia (e.g., due to vomiting, diarrhea, or water restriction)
  • Medications that increase the renal absorption of lithium
    • Thiazide diuretics
    • NSAIDs (except aspirin)
    • ACE inhibitors
    • Angiotensin receptor blockers
  • Other medications: tetracyclines, cyclosporines, metronidazole

Clinical features ^[1][4][17]

• Symptoms by type of poisoning
  • Acute lithium poisoning
    • Early: gastrointestinal symptoms
    • Hours after ingestion: neurological symptoms
  • Acute-on-chronic lithium poisoning: Gastrointestinal and neurological symptoms may occur simultaneously.
  • Chronic lithium poisoning: Neurological symptoms predominate.
• Gastrointestinal: nausea, vomiting, and diarrhea
• Neurological
  • Altered mental status, confusion
  • Somnolence, coma
  • Delirium, encephalopathy, psychomotor impairment
  • Coarse tremors, seizures, fasciculations, myoclonus
  • Ataxia, slurred speech, nystagmus
  • Hyperreflexia
  • Extrapyramidal syndrome

Lithium slowly redistributes from the serum into the CNS. Therefore, in acute poisoning, GI symptoms predominate early, while in chronic poisoning, neurological symptoms predominate. ^[4]

Diagnostics ^[1][4]

Lithium poisoning is diagnosed based on history, clinical features, and serum lithium levels.

• Serum lithium level
  • Toxic effects occur when serum lithium levels are > 1.5 mEq/L. ^[18]
  • Collect samples in lithium-free tubes.
• BMP: to evaluate for electrolyte abnormalities (e.g., hypernatremia, hypercalcemia) and markers of renal dysfunction (e.g., elevated creatinine)
• ECG findings
  • T-wave flattening or inversion
  • Prolonged QTc interval

Management ^[1][4]

Initial management

• Perform an ABCDE approach in poisoning and initiate resuscitation.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Provide supportive care for poisoned patients, e.g., ventilatory support, fluid resuscitation, and electrolyte repletion.
• Discontinue lithium therapy.

GI decontamination

• Whole bowel irrigation may be used in patients with severe symptoms due to sustained-release preparations. ^[19]
• Activated charcoal does not bind to lithium.
• Ion exchange resins (e.g., sodium polystyrene sulfonate) are not routinely recommended.

Indications for hemodialysis ^[20]

• Hemodialysis is recommended in patients with either of the following:
  • Serum lithium concentration > 4 mEq/L and kidney dysfunction
  • Altered mental status, seizures, or life-threatening dysrhythmias
• Hemodialysis may be considered in patients with any of the following:
  • Serum lithium concentration > 5 mEq/L
  • Confusion
  • Serum lithium concentration not expected to decrease to < 1 mEq/L within 36 hours

Monitoring and disposition

• Obtain serial serum lithium levels every 2–4 hours until two consecutive declining levels are observed. ^[4]
• Symptomatic patients should be admitted for further monitoring and treatment.
• Admit patients with indications for hemodialysis to the ICU.
• Consider discharging asymptomatic patients with lithium levels within the therapeutic range after 6 hours (immediate-release) or 12 hours (sustained-release).

Clinical features rather than absolute serum lithium levels should guide treatment. ^[1]

Diuretics, osmotic agents, and carbonic anhydrase inhibitors are contraindicated in lithium poisoning, as they can worsen hypovolemia and increase lithium retention. ^[1]

Clinical features ^[1][21]

• Neurological
  • CNS depression (e.g., drowsiness, lethargy, coma)
  • Ataxia
  • Seizures
  • Encephalopathy
• Cardiopulmonary: respiratory depression, hypotension
• Gastrointestinal: clinical features of acute pancreatitis
• Multisystem: clinical features of acute liver failure

Diagnostics ^[1][22][23]

Valproate poisoning is diagnosed based on history, clinical features, and serum valproate levels.

• Serum total valproate level
  • 50–100 mcg/mL: therapeutic range
  • > 450 mcg/mL: symptoms likely
  • > 850 mcg/mL: associated with severe symptoms (e.g., coma, metabolic acidosis, respiratory depression)
• BMP: to evaluate for hypernatremia, hypocalcemia, and markers of metabolic acidosis
• CBC: to evaluate for thrombocytopenia and leukopenia
• VBG: to assess blood pH
• Serum ammonia level: to assess for hyperammonemia

Management ^[1][21]

Initial management

• Perform an ABCDE approach in poisoning and initiate resuscitation.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Administer activated charcoal for GI decontamination.
• Provide supportive care for poisoned patients, e.g., fluid resuscitation, treatment of hypoglycemia, and electrolyte repletion.
• Consider L-carnitine supplementation (off-label) for patients with hyperammonemia or signs of liver damage. ^[1][21]

Indications for hemodialysis ^[24]

• Hemodialysis is recommended in patients with either of the following:
  • Serum total valproate level > 1300 mcg/mL
  • Cerebral edema or shock
• Hemodialysis is suggested in patients with any of the following:
  • Serum total valproate level > 900 mcg/mL
  • Respiratory depression or coma requiring mechanical ventilation
  • Hyperammonemia
  • pH ≤ 7.1