Tetracyclic antidepressants Clonidine

The authors recognized that mirtazapine alone could have caused the hypertensive event. In postmarketing surveillance of mirtazapine, hypertension occurred in at least 1% of patients. However, it is likely that the patient lost antihypertensive control because mirtazapine antagonized the antihypertensive effect of clonidine. Mirtazapine, a tetracyclic antidepressant, stimulates the noradrenergic system through antagonism at central alpha2 inhibitory receptors, which is precisely opposite to the effect of clonidine. 

The tricyclic antidepressants, clomipramine, desipramine and imipramine, reduce or abolish the antihypertensive effects of clonidine. Other tricyclics are expected to behave similarly. A hypertensive crisis developed in a woman taking clonidine who was also given imipramine, and severe pain ocenrred in a man taking amitriptyline and diamorphine when he was given intrathecal clonidine. Conversely, the tetracyclics, maprotiline and mianserin do not appear to alter the antihypertensive effects of clonidine. An isolated case report describes a hypertensive crisis in a patient taking mirtazapine and clonidine. Hypotension ocenrred in a boy taking clonidine and trazodone. 

The interaction between clonidine and the trieyelics is established and clinically important. The incidence is uncertain but it is not seen in all patients. Avoid concurrent use unless the effects can be monitored. Increasing the dosage of clonidine may possibly be effective. The clonidine dosage was apparently successfully titrated in 10 out of 11 hypertensive patients already on amitriptyline or imipramine. Only clomipramine, desipramine and imipramine have been implieated so far, but other tricyclics would be expected to behave similarly (amitriptyline, nortriptyline and protriptyline have been shown to interact in animals ). The tetracyclic antidepressants maprotiline and mianserin do not generally appear to interact with clonidine. The isolated case of hypotension with trazodone is of unknown general importance. 

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