CNS Spectrums


Opportunities for reversible inhibitors of monoamine oxidase-A (RIMAs) in the treatment of depression

Christopher T. Luma1 c1 and Stephen M. Stahla2

a1 Arbor Scientia, Carlsbad, California, USA

a2 Department of Psychiatry, University of California–San Diego, San Diego, California, USA


Treatment-resistant depression (TRD) may be implicated in 33–57% of depression cases. The currently available effective treatments include electroconvulsive therapy (ECT) or augmentation of serotonin selective reuptake inhibitors (SSRIs) with antipsychotics. ECT and antipsychotics are both associated with safety and tolerability concerns. Depression is hypothesized to result from a dysregulation of monoamine neurotransmitters, although the source of the dysregulation has been unclear. However, recent studies have revealed that an enzyme that degrades the neurotransmitters, known as monamine oxidase-A (MAO-A), may be overactive in patients with depression. Thus, treatments for depression that modulate MAO-A could act upstream relative to current antidepressant treatments. Monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders. Some evidence suggests that MAOIs may act by reversing excessive neurotransmitter depletion within the neuron and the synapse. MAOIs tend to be underutilized in clinical practice, due in part to misinformation and mythology about their dietary and drug interactions. The new class of reversible monoamine oxidase inhibitors (RIMAs) has shown efficacy in depression, with safety and tolerability comparable to SSRIs. This article discusses recent progress in RIMAs toward the treatment of TRD. Dietary and drug interactions of MAOIs will be covered, as well as guidelines for integrating these agents into clinical practice.

(Received April 26 2012)

(Accepted May 17 2012)

Key words

  • Treatment resistant depression;
  • reversible monoamine oxidase inhibitor;
  • serotonin syndrome;
  • hypertension;
  • dietary interaction;
  • drug interaction


c1 Address for correspondence: Christopher T. Lum, Arbor Scientia, 1930 Palomar Point Way, Ste. 100, Carlsbad, CA 92108, USA. (Email