SAFETY AND EFFICACY OF MONOAMINE OXIDASE INHIBITORS IN THE TREATMENT OF ANXIETY DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Freire *Rafael , Fidry Marcos , Faria Clara , Cabo Mariana , Matos Ursula , Steffen Ricardo , Nardi Antonio 
Published: February 2025

Background

Monoamine oxidase inhibitors (MAOI) are well known for its effectiveness on major depressive disorder. MAOI’ s prescription has been declining since the arrival of new antidepressant drugs, and there are few studies on their efficacy and safety in the treatment of anxiety disorders. MAOI are controversial drugs because, in one hand, their efficacy is potentially superior to other antidepressants, due to their distinct mechanism of action. On the other hand, there are concerns about safety of these medications.

Aims and Objectives

The authors performed a systematic review and meta- analysis to investigate the efficacy and safety of MAOI. We also looked for evidence of superiority over other stablished drugs.

Methods

MEDLINE, PsycINFO, Web of Science, EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for clinical trials using MAOI on anxiety disorders treatment, from January 1980 to May 2023. Review Manager 5 was used to analyze the effect size data, used as primary outcome.

Results

Over 2,972 records, 24 studies were included in the review. 19 studies were on social anxiety disorder treatment, 7 on panic disorder treatment. The studied MAOI were moclobemide, phenelzine, brofaromine and tranylcypromine. MAOI were superior to placebo in all 13 randomized controlled trials (RCT), except 2. MAOI were not superior to other antidepressants in comparative trials. They were effective on all 7 comparative trials and 4 open trials. 1,535 patients were pooled, only 6 (0.4%) showed severe adverse effects during trials. The risk of bias was high among the studies.

Discussion and Conclusion

MAOIs are effective treatments for social anxiety and panic disorders, although literature is scarce and there is high risk of bias. These medications demonstrated to be safe and effective. More clinical trials, with more stringent methodology are needed.

References

Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, Parikh S V, Patten SB, Ravindran A V. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. Netherlands; 2009 Oct;117 Suppl:S26-43. PMID: 19674794

Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, Antony MM, Bouchard S, Brunet A, Flament M, Rabheru K, Grigoriadis S, Richter PMA, Mendlowitz S, O’ Connor K, Robichaud M, Walker JR, Asmundson G, Klassen LJ, Lam RW, McIntyre RS, Szpindel I. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014. PMID: 25081580

Salzer HM, Lurie ML. Anxiety and depressive states treated with isonicotinyl hydrazide (isoniazid). Arch Neurol Psychiatry. 1953;

Youdim MBH, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nature Reviews Neuroscience. 2006. PMID: 16552415

Wimbiscus M, Kostenko O, Malone D. MAO inhibitors: Risks, benefits, and lore. Cleve Clin J Med. 2010; PMID: 21147941

ARNOT R. Calming effect of the monoamine oxidase inhibitors. Dis Nerv Syst. United States; 1960 Aug;21:448. PMID: 13794397Zisook S. A clinical overview of monoamine oxidase inhibitors. Psychosomatics. England; 1985 Mar;26(3):240-246,251. PMID: 3887453

Flockhart DA. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: An update. Journal of Clinical Psychiatry. 2012. PMID: 22951238

Balon R, Mufti R, Arfken CL. A survey of prescribing practices for monoamine oxidase inhibitors. Psychiatr Serv. United States; 1999 Jul;50(7):945–947. PMID: 10402617

Fiedorowicz JG, Swartz KL. The role of monoamine oxidase inhibitors in current psychiatric practice. Journal of Psychiatric Practice. 2004.