A Case Study in Treatment-Refractory Depression
Monoamine oxidase inhibitors (MAOIs) have a long and storied history as some of the earliest antidepressants created. The efficacy of these medications led to the development of the monoamine hypothesis of depression and the development of subsequent antidepressant medications. Despite their known efficacy, MAOIs have fallen out of favor in clinical practice, giving way to newer agents with more favorable adverse-effect profiles and improved tolerability. However, the contemporary psychiatrist would be remiss to disregard these medications as archaic or dangerous.
Depression is both common and challenging to treat. Most patients with MDD require more than one medication trial to obtain remission. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study highlighted the difficulty in treating depression to remission.1 Findings from this study indicate that only 67% of patients achieved remission after aggressive treatment through up to 4 levels of switching or adding medications and psychotherapy. Savvy clinicians would be well served to incorporate MAOIs into their arsenals for managing treatment-refractory depression.
To highlight the difficulty in treating refractory depression, consider the following Case Vignette.
A 66-year-old married, retired architect was treated at a large academic hospital and outpatient clinic for recurrent, severe, major depressive episodes. The depression was characterized by anxious distress, hypersomnolence, mood reactivity and, when severe, delusions of poverty. He was treated with several SSRIs and SNRIs without improvement, even when in combination with atypical antipsychotics.
He had some improvement with a course of ECT following a severe suicide attempt. Tranylcypromine was started after the course of ECT, which produced significant improvement in symptoms after titration to 70 mg daily in divided doses. Recurrence of depression was successfully treated with the addition of 100 mg of nortriptyline, and he remained in remission for many years. He resisted maintenance treatment with ECT because of lasting cognitive deficits.
The concept of atypical depression, characterized by mood reactivity, hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity, is an important consideration in this case. MAOIs were shown superior to tricyclic antidepressants (TCAs) in treating these patients.2,3 One double-blind crossover study of nonmelancholic, treatment-resistant depression revealed 67% of patients who failed treatment with imipramine had symptom remission with phenelzine.4 Moreover, phenelzine and tranylcypromine were found to be superior to TCAs in the treatment of outpatients with atypical depression.5
The consistency of these findings is remarkable because it is uncommon for studies of antidepressant efficacy to demonstrate comparative superiority of one medication over another. The utility of MAOIs extends beyond treatment of MDD. Primary anxiety disorders, particularly social anxiety disorder, have consistently responded to MAOIs—a finding that is supported by a meta-analysis.6
Dr. Morcos is Fourth-Year Resident, Department of Psychiatry, University of Michigan; Dr. Bostwick is Associate Chair and Clinical Associate Professor, Department of Clinical Pharmacy, University of Michigan College of Pharmacy, and Clinical Pharmacist in Psychiatry, Michigan Medicine, Ann Arbor.
1. Gaynes BN, Warden D, Trivedi MH, et al. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009;60:1439-1445.
2. Quitkin FM, Stewart JW, McGrath PJ, et al. Columbia atypical depression: a subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry. 1993;21(suppl):30-34.
3. Stewart JW, McGrath PJ, Quitkin FM, et al. Chronic depression: response to placebo, imipramine, and phenelzine. J Clin Psychopharmacol. 1993;13:391-396.
4. McGrath PJ, Stewart JW, Nunes EV, et al. A double-blind crossover trial of imipramine and phenelzine for outpatients with treatment-refractory depression. Am J Psychiatry. 1993;150:118-123.
5. Thase ME, Trivedi MH, Rush AJ. MAOIs in the contemporary treatment of depression. Neuropsychopharmacol. 1995;12:185-219.
6. Mayo-Wilson E, Dias S, Mavranezouli I, et al. Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2014;1:368-376.
7. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 3rd ed. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed August 4, 2017.
8. Kennedy SH, Lam RW, McIntyre RS, et al. CANMAT 2016 clinical guidelines for the management of adults with major depressive disorder: section 3: pharmacological treatments. Can J Psychiatry. 2016;61:540-560.
9. White K, Simpson G. The combined use of MAOIs and tricyclics. J Clin Psychiatry. 1984;45(7 pt 2):67-69.
10. Young JP, Lader MH, Hughes WC. Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients. Br Med J. 1979;2:1315-1317.
11. Davidson J, McLeod M, Law-Yone B, Linnoila M. A comparison of electroconvulsive therapy and combined phenelzine-amitriptyline in refractory depression. Arch Gen Psychiatry. 1978;35:639-642.
12. Pierre JM, Gitlin MJ. Bupropion-tranylcypromine combination for treatment-refractory depression. J Clin Psychiatry. 2000;61:450-451.
13. Quante A, Zeugmann S. Tranylcypromine and bupropion combination therapy in treatment-resistant major depression: a report of 2 cases. J Clin Psychopharmacol. 2012;32:572-574.
14. Feinberg SS. Combining stimulants and monoamine oxidase inhibitors: a review of uses and one possible additional indication. J Clin Psychiatry. 2004;65:1520-1524.
15. Fawcett J, Kravitz HM, Zajecka JM, Schaff MR. CNS stimulant potentiation of monoamine oxidase inhibitors in treatment-refractory depression. J Clin Psychopharmacol. 1991;11:127-132.
16. Clary C, Schweizer E. Treatment of MAOI hypertensive crisis with sublingual nifedipine. J Clin Psychiatry. 1987;48:249-250.
17. Golwyn DH, Sevlie CP. Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension. J Clin Psychopharmacol. 1993;13:77-78.
18. Thomas SJ, Shin M, McInnis MG, Bostwick JR. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression. Pharmacother. 2015;35:433-449.
19. Feighner JP, Boyer WF, Tyler KL, Neborsky RJ. Adverse consequences of fluoxetine-MAOI combination therapy. J Clin Psychiatry. 1990;51:222-225.