Amitriptyline × Clonidine

Tricyclic antidepressants, amitriptyline included, can counteract centrally acting antihypertensives such as clonidine (amitriptyline SmPC). The clonidine SmPC adds that the blood pressure lowering effect of clonidine may be reduced or lost entirely. The combination can also cause or worsen orthostatic dysregulation, a drop in blood pressure on standing (clonidine SmPC).

Blood pressure drifts above target: home and clinic readings are higher than before, and some patients get headache or dizziness. On standing, orthostatic hypotension can cause dizziness and weakness (clonidine labels).

The combination is not recommended: the Spanish amitriptyline SmPC lists clonidine under combinations that are not recommended and advises reviewing all antihypertensive treatment while a tricyclic antidepressant is used. When reviewing it, keep in mind that clonidine may stop lowering blood pressure and that orthostatic dysregulation may get worse (clonidine SmPC). The FDA clonidine label notes that a higher clonidine dose may be needed with tricyclic antidepressants. If clonidine is to be stopped, do not stop it abruptly: taper the dose over 2–4 days, otherwise blood pressure can rise quickly. In a patient also taking a beta-blocker, withdraw the beta-blocker gradually first and clonidine after it (clonidine SmPC).