Drug Class:

Monoamine Oxidase Inhibitors (MAOI)

Medication names: 

Phenelzine, Tranylcypromine, Isocarboxazid

How they work:

Monoamine Oxidase has two types, A and B. The “A” form metabolizes Serotonin, Norepinephrine, and Dopamine, while the “B” form metabolizes trace amines and Dopamine. The medications work by stopping the enzymes from metabolizing those neurotransmitters.

What makes them unique:

These were the first antidepressant medications discovered. One was originally developed as an antituberculosis medication but then was found to have antidepressant effects.

Side effects:

One of the main reasons that these medications fell out of favor was the dietary restrictions. Extremely high blood pressure can result if the trace amine, Tyramine, is consumed in the diet. Some foods that must be avoided include smoked meat and fish, aged cheese, tap beers, and soy products. Tyramine consumption can cause sedation, constipation,  and sexual dysfunction. Additional side effects include hepatotoxicity, weight gain, and hypotension.

Rare side effects include seizures, induction of mania, and activation of suicidal ideation in people age 24 and younger.

How effective are they:

(1) A study looked at MAOI efficacy and safety in advanced, treatment-resistant depression. This was a retrospective review of 400 patient charts. 56% of patients on MAOIs resulted in a global assessment score of “very much better” or “much better”. 25% of patients were no better or worse after treatment.

(2) A study reviewed treatment-resistant patients that had failed 3 antidepressants. The patients were then placed on either Tranylcypromine (an MAOI) or Venlafaxine in combination with Mirtazapine (California Rocket Fuel). Remission rates were 6.9% in the Tranylcypromine group and 13.7% for the Venlafaxine with Mirtazapine group. Tranylcypromine had higher intolerance rates as well. Tranylcypromine faired worse in treatment-resistant depression as compared to Venlafaxine and Mirtazapine.

Clinical experience:

I have only seen one patient on one of the original MAOIs in clinical practice. This patient was admitted to an inpatient psychiatric unit and had tried and failed basically every other antidepressant. These medications are not very common at all mainly due to the dietary restrictions and risk of hypertensive crisis if certain foods are ingested. Pharmaceuticals should never be used as the sole treatment for mental illnesses. Therapy, exercise, meditation or other treatments should always accompany prescriptions.

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1. Amsterdam JD, Shults J. MAOI efficacy and safety in advanced stage treatment-resistant depression–a retrospective study. J Affect Disord. 2005 Dec;89(1-3):183-8. Epub 2005 Oct 6.

2. McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1531-41; quiz 1666.

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