MAOIs (aka Monoamine Oxidase Inhibitors) were the first antidepressant medications that date back to the 1950s. If you have heard the term MAOI, it is probably in conjunction with a TV ad about medications such as Prozac (fluoxetine) and the warning “not to take if you are on a MAO Inhibitor.” The truth is not many people nowadays take MAOIs because of dietary restrictions, drug interactions and the popularity of selective serotonin reuptake inhibitors (or SSRIs) but they are still available. You will probably never see a TV commercial about them and most psychiatrists won’t even mention them—especially my younger colleagues who have probably never prescribed them. However, even in this day and age of ketamine and TMS (Transcranial Magnetic Stimulation), I believe there is an important role for MAOIs especially when nothing else seems to work for depression, social phobia, or panic disorder. In this next article, I will highlight 3 patients over the past year who I have treated successfully with MAOIs.
During my training in the 1990s, there was a strong emphasis on knowing how to prescribe MAOIs especially in cases of atypical depression, melancholia, refractory depression, and even bipolar depression. At the time, if a patient did not respond to any other medication or ECT (Electroconvulsive Therapy), the MAOI would be the next step. Nowadays, we have many “next steps” that are more benign and so the idea of an MAOI doesn’t usually come up until all the other possibilities have been exhausted. When I mention the idea of an MAOI, I would say about half of the patients won’t even consider it at least right away but then may eventually warm up to it with some further research on their own.
A recent example was a 61 year old man who has had depression and anxiety for many years but nothing really seemed to work and he would develop severe side effects even at very tiny doses. Ketamine treatment made him feel worse. Genetic testing confirmed that he would probably not do well on any traditional antidepressant but the MAOI remained a good possibility. He eventually agreed to go on a low dose MAOI transdermal patch (called selegiline or EMSAM) that does not require any special diet since it bypasses the gut and within a couple weeks was feeling much better with minimal side effects.
I work with a younger man in his mid 20s who also struggled with depression and anxiety throughout college and during the pandemic. He was also sensitive to side effects and we went through all the traditional medications as well as Transcranial Magnetic Stimulation but he had no significant relief. Last year, within days of starting the MAOI medication, tranylcypromine, he reported benefit from a medication for the first time and is willing to stick with the special diet outlined below.
A more challenging situation involved a 35 year woman with Bipolar II Disorder who also struggled with severe depressive episodes that resulted in several hospitalizations. Ketamine and Transcranial Magnetic Stimulation were not effective and none of the traditional medications for bipolar depression seemed to be effective on their own. However, upon adding tranylcypromine, she also had a beneficial response. Adding an antidepressant to anyone with bipolar depression is risky because there is always a chance of inducing mania but it turns out MAOIs have a lower risk of inducing mania (at least compared to SSRIs) but the patient also needs to be on a mood stabilizer at the same time and be closely monitored.
So, in a nutshell what is the special diet all about? The diet restrictions are based on minimizing a patient’s exposure to tyramine, a breakdown product of the amino acid tyrosine found in several fermented foods but especially aged proteins like cheese or meat. Significant tyramine ingestion may cause an increase in blood pressure in people taking an MAOI but it turns out very few foods now contain problematically high tyramine levels; that is a result of great changes in international food production methods and hygiene regulation which wasn’t the situation in the 1960s. At one time, cheese did result in fatalities from high blood pressure but today most cheeses are quite safe in healthy-size portions. MAOIs do not themselves raise blood pressure but usually quite the opposite—they slightly lower the blood pressure. All patients who are prescribed an MAOI should also purchase a portable blood pressure cuff for those rare instances when a dietary indiscretion may have occurred and the person experiences a headache one or two hours after the ingestion. Most reactions are self-limited and resolve over 2 to 4 hours. However, patients who ingest more then 100 mg of tyramine should be evaluated by a physician. I’ve had only one person on an MAOI over a 30 year period who had to seek medical attention because she ingested food from a buffet table that may have been sitting out too long.
Ironically, despite MAOIs being the first antidepressants 70 years ago—they remain just as effective for treating depression and anxiety as anything else available today. I believe the primary reason MAOIs are underutilized is due to inadequate understanding of risk mechanisms and resultant fear of catastrophic outcomes. Clinicians and patients often feel that the MAOI diet is highly restrictive and onerous, making it hard to follow and not foolproof. However, in recent years, the tyramine diet has been simplified and streamlined, becoming more user friendly for patients with a lot less restrictions than was previously thought necessary. The MAOI transdermal patch I mentioned above came out in 2006 and it seemed very promising—no special diet at the lowest dose and no significant side effects such as weight gain or sexual dysfunction but it’s hardly used—the most significant issue is the cost as there is no generic alternative yet; however, a compounding pharmacy can make a transdermal gel for a fraction of the cost. The hesitancy to prescribe such drugs by clinicians is understandable, particularly when the marketplace has many other safer and less-restrictive antidepressant choices. The underutilization of this class of medication probably isn’t going to change in the future but when someone has tried every other alternative, the MAOI is still a great option that will continue to make a big difference in people’s lives.