Tricyclic Antidepressants

Question 1

What are the drugs classed as TCA’s?

Answer 1

imipramine, amitriptyline, dosulepine and lofepramine

Question 2

What are the mechanisms of action of TCA’s?

Answer 2

1. Inhibition of neurotransmitter reuptake: inhibit
   reuptake of serotonin and norepinephrine into presynaptic terminal
   2.Blocking receptors: Blockade of serotonergic, alpha adrenergic, histaminic and muscarinic receptors

Question 3

What do TCA’s do?

Answer 3

• Elevate mood
• Improve mental alertness
• Reduce morbid preoccupation

Question 4

How long does it take for TCA’s to work?

Answer 4

The onset of mood elevation is slow taking at least 2 weeks or longer

Question 5

How is dosage for TCA’s adjusted?

Answer 5

After a therapeutic response, the dosage can be gradually reduced to improve tolerability unless relapse occurs (before recovery is achieved but after remission has occured)

Question 6

What are the therapeutic uses of TCA’s?

Answer 6

• Effective in treating moderate to severe depression (150mg)
• In some pts with panic disorder
• Amitriptyline-Migraine and chronic pain syndrome eg neuropathic pain (10mg)

Question 7

How are TCA’s excreted?

Answer 7

Excreted as inactive metabolites via the kidney

Question 8

What are the adverse effects of TCA’s?

Answer 8

• Anticholinergic side effects (blurring of vision, dry mouth, constipation, urinary retention)
• Sedation (amitriptyline)
• Weight gain
• cardiotoxic in overdose
• CVS:postural hypotension, arrhythmia
• Discontinuation effects

Question 9

In which patients should TCA’s be avoided/used with precaution

Answer 9

• Bipolar patients (switch to manic state could occur when they are depressed)
• Suicidal patients (Narrow therapeutic index)
• Epileptic patients
• Patients with preexisting arrhythmias

Question 10

How should TCA’s be stopped?

Answer 10

Stopped gradually to avoid discontinuation syndrome and cholinergic rebound effects (nausea, vomiting, diarrhea)