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Updated: Dec 29 2021

Tricyclic Antidepressants (TCAs)

  • Snapshot
    • A 79-year-old male is brought in by ambulance to the emergency department after he was found by his son to be convulsing and unresponsive on the floor of his home. His son does not know how long the episode has lasted. The patient's past medical history is significant for major depressive disorder and the patient has been taking amitriptyline for the last 30 years. Medical history is otherwise unremarkable. Based on clinical suspicion of overdose an EKG is performed showing prolonged QRS complexes. Sodium bicarbonate is therefore given urgently as this is recognized to be a life threatening overdose situation.
  • introduction
    • Drugs
      • 3° TCAs
        • imipramine
        • amitriptyline
        • doxepin (most antihistaminic)
        • clomipramine
      • 2° TCAs
        • nortriptyline (best tolerated, used in geriatric populations)
        • desipramine (less anticholingeric, least antihistaminic) 
        • proptyline
      • others
        • amoxapine and maprotiline are tetracyclics 
      • Mechanism
        • block reuptake of NE and serotonin
      • Clinical use
        • major depression
        • enuresis (imipramine)  
        • imipramine is a second-line agent, used generally after desmopressin for the treatment of enuresis    
        • OCD (clomipramine)
        • fibromyalgia
      • Side effects
        • anticholinergic
          • tachycardia and urinary retention 
          • 3° TCAs worse than 2° TCAs
        • anti-α-adrenergic
          • sedation
            • desipramine is the least sedating
        • ↓ seizure threshold
      • Toxicity
        • do NOT mix with SSRIs and MAOIs → can be fatal
        • 3 C's of overdose 
          • Convulsions
          • Coma
          • Cardiotoxicity (arrhythmias)
            • QRS prolongation is the best indicator of overdose
        • respiratory depression and hyperpyrexia
        • confusion/hallucinations in the elderly
          • due to anticholinergic side effects
          • should use nortriptyline which has lesser side effects
        • treatment for overdose = NaHCO3 for cardiovascular toxicity
          • increases extracellular pH and sodium concentration
            • stabilizes cardiac membrane potentials
            • leads to increased binding of TCA to serum proteins
          • improved renal excretion of TCA 
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