TCAs

• Examples:

  • Amitriptyline
  • Nortriptyline
  • Lotepramine
  • Trazodone
  • Clomipramine (OCD)
• MOA:

  • Block the reuptake of serotonin and noradrenaline by the presynaptic membrane
  • Additional actions - block acetylcholine and histamine receptors which give them anticholinergic and sedative side effects
• Indications:

  • Depression/anxiety disorders - now rarely used due to toxicity in overdose and risk of cardiac events
  • Amitriptyline - neuropathic pain and migraine prophylaxis
• Contraindications and cautions:

  • Suicidal ideation - cardiotoxic in overdose
  • History of psychosis/bipolar
  • QT interval prolongation - can worsen
  • Avoid in patient post MI or other cardiac issues - use sertraline
  • Caution - prostatic hypertrophy, urinary retention, chronic constipation, severe liver disease, increased intraocular pressure/high risk of developing acute angle-closure glaucoma
• Interactions:

  • Monoamine oxidase inhibitors - severe hypertensive crisis can occur - maintain 2 week gap
  • Anti-epileptic medications - TCAs lower the seizure threshold
  • Anti-arrhythmic medications - ventricular tachycardia can occur
  • Alcohol - increased sedation
• Elderly patients are more susceptible to all TCA side-effects, especially hyponatraemia
• Common side effects:

  • Anticholinergic effects - dry mouth, blurred vision, constipation
  • Antihistamine effects - drowsiness
  • Anti-adrenergic effects- postural hypotension
  • Metabolic effects - weight gain, altered blood glucose in diabetics
• Less common side effects:

  • Cardiotoxic in overdose
  • Neuroleptic malignant syndrome
  • Hyponatraemia
  • Thrombocytopenia
• Counselling:

  • Impairment of normal activities - driving and operating heavy machinery - increased sedation with alcohol
  • Important not to exceed maximum dose - screen for any suicidal ideation
  • Increased risk of seizures in epilepsy - lowers seizure threshold
  • Treatment cessation - withdrawal symptoms may occur within 4 days of stopping drug. symptoms tend to me mild but drug should be gradually withdrawn over 4 weeks
• Tricyclic antidepressants are particularly known to cause arrhythmias, including tachycardia, prolonged QT interval and bundle branch block. The effects are dose-dependent. Their effect on the heart makes them very dangerous in overdose, with a high risk of death.