You'd never know it to meet me—my name is Sunny, after all—but I've been on antidepressants most of my adult life. They worked well for a long time, but in the past few years, my occasional down days became down weeks and started occurring more often. Then, last August, an unshakable sense of hopelessness came over me. For the first time ever, I yearned to go to bed and not wake up.

Concerned, I talked to my psychiatric nurse practitioner, who tweaked my meds and prescribed more downtime, sleep and regular exercise. The changes helped, but the side effects of the boosted medication were awful—blurry vision, swollen fingers, painfully inflamed wrist tendons. After three months, I still felt emotionally fragile. That's when I remembered a study a therapist friend had mentioned: Scientists had linked a certain gene mutation to depression—and discovered that a type of B vitamin might help depressed people who have the mutation feel better.

I dove into the research, and what I learned blew my mind. The brain needs folate—a B vitamin in spinach, kidney beans and avocado—to produce mood-regulating chemicals like serotonin and dopamine. But a mutation in the MTHFR gene (yes, that's really the name) may make it hard for some people to break down folate into methylfolate, a metabolized form capable of crossing from the bloodstream into the brain, says John Zajecka, MD, director of the Woman's Board Depression Treatment and Research Center at Rush University Medical Center in Chicago. Not having enough methylfolate can increase a person's risk for depression.

The uplifting news: Scientists have created supplement forms of the vitamin that can cross the blood-brain barrier. In a 2012 trial, Zajecka and fellow researchers gave people with treatment-resistant depression a daily dose of 15 milligrams of methylfolate to take along with their antidepressants. After 30 days, nearly a third reported fewer—and less severe—symptoms, like hopelessness, insomnia and difficulty concentrating. In a 2016 follow-up study, Zajecka and his colleagues put 57 people who hadn't achieved remission during the earlier trial back on the vitamin; a year later, 61 percent no longer felt depressed.

In these studies, methylfolate appeared to cause virtually no side effects. A 2016 review in the American Journal of Psychiatry concluded that although evidence is far from definitive, there are enough compelling data to support trying methylfolate in conjunction with antidepressants if the meds alone don't seem to be working anymore.

So why aren't more psychiatrists talking about it? Well, many are—with caution. "While the results we have on methylfolate are encouraging, we need more rigorous clinical trials," says Drew Ramsey, MD, an integrative psychiatrist and assistant clinical professor of psychiatry at Columbia University who's been using methylfolate in his practice for more than five years. "I do feel like the more traditional mental health services are neglecting some of the innovation that's happening, but it's in part because doctors want to protect patients from treatments that have too much hype and not enough science."

There are two main prescription brands of methylfolate for depression: Deplin and EnLyte. A study funded by the manufacturer of the latter found that after eight weeks of taking EnLyte and no other antidepressants, 67 of the 159 participants—all of whom had major depression and had tested positive for an MTHFR mutation—achieved remission. (Prescription methylfolate isn't widely covered by insurance; smaller doses are available at health food stores, but aren't as potent.)

I wanted to know whether I carried the mutation, both to satisfy my own curiosity and for the sake of my two kids. So I dug into some results from an at-home genetic test, and there it was: the C677T MTHFR mutation.

My practitioner confirmed its presence with a lab test and wrote a prescription for methylfolate. After three months, we were able to lower the dosages on both of my antidepressants, and I felt better than I had in a few years—more emotionally resilient, energetic and clearheaded.

Six months later, I'm still healthier and still taking methylfolate with my meds. My only regret is not looking into this earlier. So now I'm spreading the word.

Methylfolate Math
Studies have found that around 12 to 25% of people who initially find success with antidepressants relapse. Methylfolate could potentially help many of them achieve remission: While it's been estimated that about 33% of the population has the C677T MTHFR mutation, several studies have found that approximately 80% of people with treatment-resistant depression do. Not all docs believe that genetic testing is necessary—talk to yours about methylfolate's pros and cons.

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