Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication

J Clin Psychiatry. 2004 Nov;65(11):1520-4. doi: 10.4088/jcp.v65n1113.


Background: Among antidepressant augmentation strategies, the addition of a stimulant to a monoamine oxidase inhibitor (MAOI) has received little attention in the literature in recent years because of the diminished clinical use of the latter and concerns of precipitating a hypertensive crisis or other serious complication. Despite that fact, experienced clinicians continue to use this combination for a variety of indications after other options have failed. This article reviews these reported uses and presents a case suggesting another possible indication.

Method: A MEDLINE search was conducted for articles published from 1962 to December 2003 using relevant search terms (psychostimulant, stimulant, amphetamine, dextroamphetamine, pemoline or methylphenidate, atomoxetine, bupropion, monoamine oxidase inhibitor, and selegiline). A manual search was conducted of cross-references and other relevant recent psychiatric sources (2000-2003).

Results: The described uses of the MAOI-stimulant combination have included treatment of refractory depression and the MAOI-related side effects of orthostatic hypotension and daytime sedation. No documented reports were found in the recent literature of hypertensive crises or fatalities occurring when the stimulant was cautiously added to the MAOI. Also presented here is another possible indication for this therapeutic regimen: treatment of attention-deficit/hyperactivity disorder in an adult patient whose major depression had uniquely responded to the MAOI tranylcypromine.

Conclusion: As in other fields of medicine, potentially hazardous medication combinations are utilized in psychiatry after cautiously weighing the danger of the treatment against the morbidity and risk of not adequately addressing the illness. Particularly, as the potential arrival of the apparently safer transdermal selegiline may increase the use of MAOIs, we feel this combination deserves additional controlled study.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Drug Therapy, Combination
  • Humans
  • Hypertension / chemically induced
  • Hypotension, Orthostatic / drug therapy*
  • Hypotension, Orthostatic / psychology
  • Male
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / therapeutic use*
  • Risk Assessment
  • Serotonin Syndrome / chemically induced
  • Sleep Disorders, Circadian Rhythm / drug therapy*
  • Sleep Disorders, Circadian Rhythm / psychology
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Monoamine Oxidase Inhibitors