Despite long-standing concerns over hypertensive reactions, monoamine oxidase inhibitors (MAOIs) have grown in popularity and are now used in a variety of psychiatric disorders. The risk of hypertensive episodes is less than 1%. This is most likely the result of careful dietary instructions and prudent prescribing of concomitant medications. The possibility exists of spontaneous or unprovoked hypertensive crises in patients receiving MAOIs. In this report, we review the literature on spontaneous hypertensive episodes and present a case report. There has been a total of 11 cases described in six separate reports. We discuss the possible mechanism, risk factors, treatment, and safety of rechallenging the patients with the MAOI. Further research is needed to clarify this reaction. For now, it remains a rare but worrisome phenomenon. It should stand as an additional source of concern for clinicians who are already well aware of the risk of hypertensive episodes in patients receiving MAOIs.
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