Rosen & Barkin's 5-Minute Emergency Medicine Consult (61 page)

• 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
  

• 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

• 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:
    
    • Seizures
      
    • QTc prolongation
      
• 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 α
      ₁
      -antagonism
      
    • QTc prolongation
      
    • Anticholinergic delirium
      
  • Ziprasidone:
    
    • Sedation
      
    • QTc prolongation → increased risk of torsade
      
  • Aripiprazole:
    
    • No QTc prolongation
      
    • Hypotension
      
    • Prolonged CNS dysfunction
      

• Determine agents ingested, dose, and time of ingestion:
  
  • Investigate for coingested drugs.
    
• Rapid bedside glucose if altered mental status
  

• 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
    

• CT of brain to evaluate for other causes of depressed mental status
  
• CXR if intubated or hypoxic
  

• 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

• 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
  

• 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 D
  ₅₀
  W 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
  

• 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 α
  ₁
  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
  

• 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

• 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
  

• 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.
  

Psychiatry referral for patients with intentional overdose

• 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