Tricyclic antidepressants (TCAs) like imipramine, amitriptyline, and clomipramine work by blocking the reuptake of serotonin and norepinephrine. They also block receptors like muscarinic, alpha, and histamine receptors. Common adverse effects include dry mouth, constipation, blurred vision, sedation, orthostatic hypotension, and cardiac issues like arrhythmia. TCAs can have dangerous interactions with other drugs and should be used cautiously in certain patient populations such as the elderly, those with heart conditions, epilepsy, or suicidal thoughts. While primarily used to treat depression and anxiety, TCAs are also used for other conditions like migraine,

1. Tricyclic Antidepressants
(TCAs)
Prof. Sawsan Aboul-Fotouh
Department of pharmacology, faculty of Medicine, Ain-Shams University
TCAs
(Stahl ҆s essential psychopharmacology, 2013)

2. Tricyclic Antidepressants
(TCAs)
▪ Imipramine
▪ Clomipramine
▪ Amitriptyline
▪ Nortriptyline (NE >5HT)
▪ Desipramine (NE >5HT)
5HT>NE
5HT>NE

3. 1. Block reuptake of both 5-HT and NE.
2. Block Receptors : M, α , H (Autonomic)
Mechanism of action of TCAs
TCAs
(Stahl ҆s essential psychopharmacology, 2013)

4. SRI
NRI
M
H1
TCA
Urine retention
Dry mouth
Constipation
Postural
hypotension Drowsiness
&
Sedation
Arrythmia
Major adverse effects of
antidepressants classes
- Weight gain
- Cardiotoxic
- Sexual dysfunction
- May aggrevate: epilepsy, angina,
arrhythmia &BPH
- Narrow Therapeutic index

5. Adverse effects of TCAs
H1
Sedation
M
Dry mouth, Urinary retention
Constipation, Blurred vision,
↑Glaucoma, Confusion …..
Be Cautious in Elderly
Hypotension
Autonomic Blockade


6. Cardiotoxic
Convulsions
- Arrhythmia (↑QT)
- AV Block
Be Cautious in Cardiac
& Epileptics

7. US Pharm. 2015;40(11):HS34-HS40.
(>450 ms in males, >470 ms in females)

8. Sexual dysfunction
↓ Compliance
Obesity
↓ Safety Margin

9. (Used Cautiously in suicidal or
bipolar patients)
↑ Suicide Risk
Switch to mania

10. FDA, 2010 for
insomnia

11. Drug interactions with TCA:
1. Alcohol- anesthetics  Sedation.
2. Hypotensive drugs (potentiate postural hypotensive effects of TCAs).
3. TCAs potentiate sympathomimetics (↓uptake of biogenic amines).
4. Not to be given with MAOIs→ to avoid 5HT- syndrome.
5. SSRIs (Fluoxetine & paroxetine) inhibit TCA metabolism by CYP2D6 
↑TCAs level & may ↑risk of Toxicity

12. Uses of TCAs
1. Depression, Anxiety D, OCD, Eating D ……
2. Nocturnal enuresis: Control of bed-wetting in
children > 6 years “imipramine”
3. Migraine & Chronic pain (Neuropathic)
“Amitriptyline”
SNRIs & TCAs used in chronic Pain

13. Uses of TCAs (cont.)
5. Pruritus: Topical Doxepin for in atopic
dermatitis, lichen simplex chronicus (H1)
4. Insomnia: Doxepin (FDA, 2010), and
Amitriptyline (tryptizol) are off-labely used
Doxepin

14. TCAs Toxicity:
• Atropine toxicity- Convulsions
• Conduction block & arrhythmia- hypotension.
Management:
NaHCO3 for hypotension & arrhythmia.
Alkalinization of blood to a pH of 7.45-7.55 → uncouple TCA from myocardial Na channels