Combining Mirtazapine with Phenelzine in Treatment-Resistant Depression

There is limited information on the use of monoamine oxidase inhibitors (MAOIs) with other psychotropic medications due to concern for drug-drug interactions in precipitating serotonin syndrome (toxicity). Given this perceived limitation, along with dietary restrictions, clinicians will rarely attempt MAOI therapy. This case report highlights successful concomitant use of phenelzine, a MAOI, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, for treatment resistant atypical depression. The patient was seen in the intensive outpatient setting and phenelzine was added onto mirtazapine after a 7-day washout of escitalopram. No serious adverse events occurred during initiation, titration, and on discharge date. The patient reported improvement in their symptoms of depression and anxiety. Co-prescription of phenelzine and mirtazapine is not very well documented or studied in literature. Use of tranylcypromine, another MAOI, with mirtazapine has been reported by one case series and by several expert clinicians. Drug reference databases such as Lexicomp and Micromedex report that use of these two medications together is contraindicated. In sum, the use of these two drug classes together may be effective when used under close supervision and under the care of an experienced clinician in psychiatry. It is important to note that recent systematic reviews of mirtazapine suggest that mirtazapine does not significantly elevate serotonin. Though more clinical data would be beneficial and the discussion cannot provide generalizable results, the goals of this case report are to re-examine concerns of potentially fatal interaction and to open discussion on mirtazapine’s role as a significantly serotonergic antidepressant.