Antidepressant Combinations with MAOIs: Safety Guidelines

Introduction to MAOI Safety

The American College of Psychiatry recommends that no antidepressants should be routinely combined with MAOIs due to the risk of life-threatening serotonin syndrome, with absolute contraindications including SSRIs, SNRIs, and clomipramine 1

The American Psychiatric Association states that SSRIs, SNRIs, and tricyclic antidepressants (TCAs) are strictly contraindicated with MAOIs due to serotonin syndrome risk 1
Combining two MAOIs is absolutely contraindicated, as recommended by the National Institute of Mental Health 1

The American College of Psychiatry recommends waiting at least 2 weeks after stopping an MAOI before starting any SSRI, SNRI, or TCA, and 5 weeks after stopping fluoxetine before starting an MAOI due to its long half-life 1

The National Institute of Mental Health advises watching for signs of serotonin syndrome, including mental status changes, autonomic instability, neuromuscular abnormalities, and "thunderclap" headache indicating hypertensive crisis 1
Failure to maintain adequate washout periods is the most common cause of preventable serotonin syndrome, as noted by the American Psychiatric Association 1
The American Medical Association emphasizes the importance of educating patients on MAOI use before receiving any new medications 1

Mirtazapine has been used in combination therapy with MAOIs, but carries risk and requires close monitoring, according to the European College of Neuropsychopharmacology 2