Nardil: A Pharmaceutical Secret Weapon?

Nardil is a little used but highly effective antidepressant when others don’t work.

Steven Stahl, MD, Ph.D., author of Stahl’s Essential Psychopharmacology calls it “a pharmaceutical secret weapon for patients who fail to respond to the better-known agents.” An MAOI inhibitor first prescribed in the 1950s, Nardil’s reputation for side effects soon suppressed its use.

Past research backs up Dr. Stahl’s claim. A study in Journal of Clinical Psychiatry in 2001 reported that in a group of 182 patients, those on Nardil improved more than those on newer antidepressants.

The drug is particularly effective for treatment-resistant depression. Jonathan Cole, MD, a psychiatry professor at Harvard noted, “In our experience, MAOIs succeed in at least one-half the depressed patients who have failed on other antidepressants.”

By some, Nardil is considered the “gold standard” for social anxiety that includes acute self-consciousness, public speaking anxiety, severe shyness and fear in socially interactive situations. Boston University researchers in 2014 completed a meta-analysis of 49 well-constructed studies on social anxiety and found phenelzine “significantly outperforming the other drug classes.”

And from the Nordic Journal of Psychiatry (2003), we hear of Nardil’s success with treatment of social phobia: “No patient should be considered treatment resistant without being offered a trial of Nardil,” according to that source.

Mixed Reviews

Though potent, Nardil comprises less than one percent of all prescribed antidepressants. Doctors regard it as a troublesome drug, but Internet forum users certainly do not. Participants in anxiety forums often laud Nardil.

Since the late 1980’s on the Compuserve Mental Health Forum, and later on Psychobabble, The Anxiety Forum, Psych Central and the Social Anxiety Forum, users have lavished praise on Nardil. “Nardil is the real deal. It WORKS!” said one user.

Another contributor described deep depression, but, “then came a miracle named Nardil.”

Another waxed poetic: “Nardil will always be my one true love. She calms me down when the waters are rough. She keeps me low when the tide is high!”

Informal Internet polls reflect the enthusiasm. A tally of 8,000 respondents to a poll on “Askapatient.com” shows Nardil the best antidepressant, tied with another MAOI.

Oddly, a drug endorsed by the researchers who study it and the patients who take it still seems ignored by the physicians who have the power to prescribe it.

What is the reluctance?

Critics blame drug companies that will not promote an older, unprofitable drug and say that prescribing habits are markedly influenced by these firms.

Additionally, older studies from the 1960s reported that Nardil might have dangerous side effects with users risking hypertensive crisis if they ingested certain foods or certain other medications. Such crisis involved spiking blood pressure. Doctors were obliged to prescribe, along with Nardil, a restrictive diet that eliminated many convenient and tasty foods such as chocolate, sausage, bananas, fava beans, picked products and alcohol. By the 1970s, Nardils use plummeted.

Recent research, though, suggests MAOIs are safer than previously thought.

“Sadly, much of what has been written about MAOIs is simply second or third rate scholarship, much of which is factually incorrect,” says Ken Gillman, MD, an Australian psychiatrist and advocate for MAOI inhibitors.

Patients do not have to adhere to a restricted diet. That belief is “wildly exaggerated” according to James Cole, MD, of Harvard University. There was also a fear that some drugs are risky and interact with Nardil such as amphetamine and SSRI antidepressants like Zoloft, Paxil, Prozac and Lexapro. But his experience suggests otherwise.

Yet frightening information about Nardil persists in books and in medical education and is rampant on the Internet. “The idea that taking MAOIs is difficult and dangerous is a complete myth,” said Gillman. “Doctors who say that are revealing their own limited knowledge of pharmacology.”

University of Torontos Kenneth Schulman, MD, agreed. “Unfamiliarity and ignorance lead to apprehensions concerning MAOIs, removing an excellent therapeutic option.”

John England, M.D., of Panama City, Florida concurred. “They still hammer away at the MAOI toxicity at conferences,” he said. Dr. England, an emergency room doctor who founded Seawind Clinic, has been safely using MAOI inhibitors for decades and noted that the food studies had been disproved by careful research.

In 2014, a literature review found “no reported cases of hypertensive crisis associated with concomitant administration of L-tyrosine and phenelzine” in more than 50 years of use. But in prescribing information, there is still a warning against ingesting L-tyrosine.

In his years as an ER physician, Dr. England said that he has never seen a hypertensive crisis from a MAO. Asked whether he saw changes in prescription patterns, Dr. England was guardedly optimistic. “Yes, I do, at least in the psychiatry realm. But you know, primary care doctors do most of the prescribing of the milder antidepressants. Ive not seen any push to get primary care into MAO inhibitors.”

What Does the Future Hold?

New data may cause modest ripples in prescribing habits. Nardil may garner a higher profile because it was recently found to have neuroprotective properties. In other words, it may reduce wear and tear on neurons and protect the brain from neuro-generative disorder.

Nardil most likely will remain difficult to obtain. Amongst non-psychiatrists, prescription of Nardil is extremely rare. Drug companies have no monetary incentive to promote an old drug and physicians often regard it as too troublesome.

For now, people with refractory or severe depression who wish to avail themselves of this potent drug will have to search locally or in other environs for physicians who can meaningfully discuss this option.