Monoamine Oxidase Inhibitors and Clinically Relevant Drug Interactions: A Guide for Preventing Serotonin Toxicity and Hypertensive Reactions

This article describes and clarifies the two significant interactions encountered with monoamine oxidase inhibitors (MAOIs): serotonin toxicity and the tyramine pressor response. This is important because of the amount of inaccurate and misleading information (including in United States Food and Drug Administration-approved product information sheets and online resource and database systems) promulgated over the last few decades, which continues to cause confusion and undue concern. There are few if any clinically relevant CYP450 interactions with psychotropic drugs and no significant pharmacokinetic interactions. Serotonin toxicity is now well understood and only occurs in a problematic form when MAOIs are given in conjunction with serotonin reuptake inhibitors. Major prolonged elevations of blood pressure from tyramine are now less of a concern because of greatly reduced tyramine levels in foods. Therefore, MAOIs are safer and simpler to use in clinical practice than has usually been stated and should be considered earlier in the treatment algorithm for both atypical and melancholic depression.