Tricyclic Antidepressants

Tricyclic Antidepressants - Mood Menders

• Three-ring structure drugs.
• MoA: Inhibit reuptake of Norepinephrine (NE) & Serotonin (5-HT).
• Also block muscarinic (M1), histamine (H1), & α1-adrenergic receptors, leading to side effects.
• Examples: Imipramine, Amitriptyline, Nortriptyline, Clomipramine.
• Uses: Major depression, neuropathic pain, nocturnal enuresis (Imipramine).
• Side Effects: Anticholinergic (dry mouth, blurred vision), sedation, weight gain (H1), postural hypotension (α1).
• ⚠️ Toxicity: 📌 "Tri-C's": Coma, Convulsions, Cardiotoxicity.

  ⭐ Clomipramine is highly serotonin-selective; a key drug for Obsessive-Compulsive Disorder (OCD).

Tricyclic Antidepressants - Antidepressant Army

• Mechanism: Block reuptake of Norepinephrine (NE) & Serotonin (5-HT).
• Side effects: Anticholinergic (dry mouth, constipation), antihistaminic (sedation, weight gain), α1-block (orthostatic hypotension), cardiac toxicity (arrhythmias, QRS prolongation).
• Classified by amine structure:

Tricyclic Antidepressants - Beyond Blues

• Psychiatric Indications:
  • MDD (severe/SSRI-resistant).
  • Obsessive-Compulsive Disorder (OCD) - Clomipramine highly effective.
  • Panic Disorder, Generalized Anxiety Disorder (GAD).
  • Post-Traumatic Stress Disorder (PTSD).
  • ADHD (Desipramine, Nortriptyline).
• Non-Psychiatric Applications:
  • Neuropathic pain: Diabetic neuropathy, postherpetic neuralgia (Amitriptyline).
  • Migraine prophylaxis (Amitriptyline).
  • Nocturnal enuresis in children >6 years (Imipramine).
  • Insomnia (low-dose Doxepin, Amitriptyline).
  • IBS (pain predominant).
  • Peptic Ulcer Disease (Doxepin - H2 blockade).

⭐ Imipramine is a TCA approved for childhood enuresis (bedwetting).

Tricyclic Antidepressants - Caution Crew

• Adverse Effects (AEs): 📌 Mnemonic: "Tri-C's & A's"
  • Cardiotoxicity: Arrhythmias (QT prolongation), orthostatic hypotension. ECG: QRS >100ms in toxicity.
  • Convulsions: Lower seizure threshold (esp. Maprotiline).
  • Coma: In overdose.
  • Anticholinergic: Dry mouth, blurred vision, urinary retention, constipation. (Amitriptyline > Desipramine).
  • Antihistaminic (H1): Sedation, weight gain.
  • Anti-α1-adrenergic: Postural hypotension.
• Contraindications (CIs):
  • Acute recovery post-MI, arrhythmias.
  • Narrow-angle glaucoma.
  • MAOI use (within 14 days).
• Drug Interactions:
  • MAOIs, SSRIs: Serotonin syndrome.
  • CNS depressants: Additive sedation.
  • Warfarin: ↑ Anticoagulant effect.

⭐ TCA overdose is highly lethal; QRS duration >100ms is a critical sign. Mainstay of treatment: Sodium Bicarbonate.

Tricyclic Antidepressants - Overdose Alert

• 📌 3 C's of Toxicity: Coma, Convulsions, Cardiotoxicity.
• Cardiotoxicity: Sinus tachycardia, ↑PR/QRS/QT intervals. QRS >100ms indicates severe toxicity; QRS >160ms predicts ventricular arrhythmias.
• Anticholinergic effects: Mydriasis, dry mouth, urinary retention, ileus.
• Hypotension: Due to α1-adrenergic blockade.

⭐ Sodium bicarbonate is the mainstay of treatment for TCA cardiotoxicity, aiming to narrow QRS and reverse hypotension by increasing extracellular sodium and pH.

High‑Yield Points - ⚡ Biggest Takeaways

• TCAs inhibit norepinephrine (NE) and serotonin (5-HT) reuptake.
• Adverse effects: anticholinergic symptoms, sedation (H1 blockade), orthostatic hypotension (α1 blockade).
• Cardiotoxicity (arrhythmias, QT prolongation) is life-threatening, from Na+ channel blockade.
• Sodium bicarbonate is key for managing TCA-induced cardiotoxicity.
• Uses: Depression (second-line), neuropathic pain, migraine prophylaxis, enuresis (imipramine).
• Risk of serotonin syndrome or hypertensive crisis with MAOIs.
• Examples: Amitriptyline, Imipramine, Nortriptyline.