NOT ALL MONOAMINE OXIDASE INHIBITORS ARE CREATED EQUAL

Abstract

To the Editor: Refractory depression is commonly encountered in psychiatric practice; it has been estimated that up to 15% of patients will fail to respond to aggressive treatment with multiple agents.1 Refractory depression is especially problematic for older patients, who are unable to withstand the ravages of a severe and prolonged depression as well as younger individuals;2, 3 it is common for such patients to be left with permanent disabilities even after finally treating the depression. Monoamine oxidase inhibitors (MAOIs) have been available since the late 1950s and have proved to be effective in up to 50% of patients with refractory depression.4, 5 The older MAOIs are infrequently used now, mainly because of their potentially fatal interactions with a variety of medications and foods; although Food and Drug Administration approval of transdermal selegiline has engendered some renewed interest, many psychiatrists are inexperienced with these valuable drugs. Because MAOIs are usually reserved for refractory depression, the question of whether a patient that fails one agent might respond to another is an important one but one that has never been addressed in the literature. Two elderly patients who failed to respond to phenelzine but had a rapid and dramatic improvement when switched to tranylcypromine are reported here. An 80-year-old man presented with an 8-month history of severe major depression with prominent somatic and nihilistic delusions. Over the subsequent 4 months of treatment, he failed to respond to multiple trials of antidepressants, augmenting strategies, and a course of nine bilateral electroconvulsive treatments. Ultimately, a trial of phenelzine was initiated and titrated to a maximal dosage of 75 mg per day; this was ineffective. Lithium was added, also with no effect. After 5 weeks, phenelzine was discontinued and tranylcypromine substituted, titrating to a maximal dosage of 60 mg per day. This resulted in a dramatic improvement in his depressive symptoms within approximately 10 days; he developed some subtle confusion, which resolved on discontinuation of lithium. His depression remained in full remission on tranylcypromine monotherapy until his death from congestive heart failure 5 years later. A 76-year-old man with a 13-year history of recurrent major depression with prominent somatic delusions had initially responded to electroconvulsive therapy and phenelzine but had eventually become refractory to both. His depression remained in remission for the following 5 years on lithium monotherapy but then recurred and again proved to be refractory to phenelzine in doses as high as 90 mg per day with continued lithium augmentation. Phenelzine was washed out and tranylcypromine substituted at a final dosage of 40 mg per day. His response to tranylcypromine was dramatic, with complete resolution of all depressive symptoms within 12 days; he developed moderate delirium that completely resolved with reduction of his lithium dosage. Both of these patients suffered from highly morbid, refractory depression, and their response to a second MAOI was gratifying. Because of their interactions with many antidepressants, switching to a non-MAOI strategy would have been much more cumbersome (although a wash-out period between MAOIs may be necessary as well6) and perhaps less effective. Although the past 5 decades have witnessed extraordinary progress in psychopharmacology, older medications should not be forgotten. Financial Disclosure: The Editor in Chief has determined that the author has no conflict of interest related to this letter. Author Contributions: Jonathan T. Stewart was responsible for the entire content of the letter. Sponsor's Role: None.