Major
Amitriptyline × clonidine
Tricyclic antidepressants (TCA)×Central α2-adrenergic agonist
Mechanism
Amitriptyline (TCA) blocks α2-receptors and antagonises clonidine. Clonidine's antihypertensive effect is fully lost; blood pressure returns to baseline or higher.
Symptoms
Return of hypertension: headache, dizziness, elevated readings on monitoring. In severe hypertension: risk of hypertensive crisis.
Management
The combination is not prescribed. Alternative antidepressants without α2-antagonism: SSRI (sertraline, escitalopram) or agomelatine. Alternative antihypertensives: an ARB or ACE-I with amlodipine (no clonidine).