Rapid Monoamine Oxidase Inhibitor Switches in Treatment-Resistant Depression: Safety Evaluation in 3 Cases

Current guidelines recommend a washout period of 1 to 2 weeks when switching between monoamine oxidase inhibitors (MAOIs) to reduce the risk of serotonin toxicity or hypertensive urgency/emergency. However, the evidence for these concerns is extremely limited, and reports of successful MAOI direct switches exist. This paper adds 3 new cases of rapidly executed MAOI direct switches without evidence of serotonin toxicity or hypertensive urgency/emergency. Case 1: A 25-year-old female on selegiline for 2 months was switched to phenelzine with only 1 medication-free day, then switched to tranylcypromine 2 weeks later with 1 medication-free day. Patient denied any concerning side effects during both transitions. Case 2: A 44-year-old male on selegiline was switched to phenelzine over 2 days. After 4 months of treatment inefficacy, he was switched to tranylcypromine over 2 days with no concerning side effects. Case 3: A 41-year-old female on isocarboxazid was switched to phenelzine with a 1-day washout period. The switch was well tolerated without any adverse events. These findings suggest MAOIs can be safely switched with a washout period of 2 days or less, although this should be reserved for specific clinical situations where the expected benefits outweigh the potential risks associated with any direct antidepressant switch.