I have begun taking L-methylfolate as an adjunct to my anti-depressant - which is Viibryd (at a dose of 40 mg per day). I have been on a number of different anti-depressants and so far Viibryd has been the most effective - although for me it seems to have more of an anti-anxietant effect than an anti-depressant effect. Based on years of experience I largely consider myself to be I be some what resistant to the effects of anti-depressants - though Viibryd seems to have lifted my mood by a couple of notches. I also began taking Sam-e a few months ago and currently dose in an amount of 800 mg (400 mg twice) each day. I take the Sam-E largely for its supposed anti-arthritic properties. I have been cautioned about taking too much Sam-e while on an anti-depressant, however I have noticed no meaningful improvement in my mood at the current 800 mg dosing.
My question pertains to the action of L-methyfolate as an anti-depressant. My understanding is that L-methylfolate's anti-depressant effect comes from allowing the body to naturally produce Sam-e. But is that the only anti-depressant mechanism of L-methylfolate? If it is, why don't people just take Sam-e? Is taking Sam-e and L-methylfolate for depression redundant? As I gradually increase my intake of L-methylfolate (currently just started at 1,000 mcg per day) should I reduce my intake of Sam-e?
Any observations or advice would be greatly appreciated. Thank you in advance.
I take methylfolate, Deplin 15 because if MTHFR gene. Does nothing for my depression, doesn’t matter if I take it with or without antidepressants. Have tried many antidepressants. And even had genetic testing for the best antidepressant... Also cannot tolerate birth control pills, makes depression 50x worse. I wish there was an easy answer!
25 Oct 2017
I am a psychiatric physician and utilize nutrient supplements in addition to conventional psychopharmacology -- where evidence exists to support safety and effectiveness. Contrary to what is generally believed, failure to have FDA approval (and thus become a prescribable medication in the USA) is not always because no evidence exists, but sometimes because it isn't economically feasible for a drug company to spend the vast sums needed to support studies, FDA submission, etc. Also, it won't happen for substances that cannot be exclusively patented (like lithium carbonate, only approved in the US in the early 1970's after decades of successful use elsewhere in the world).
Though there are other augmentation strategies that can work (including adding novel antipsychotic drugs like Abilify and supplementation with some thyroid hormones or lithium even for people who aren't hypothyroid or bipolar ) I've long used l-methylfolate to augment the effects of prescription antidepressants which are for many people marginally effective if effective at all. Trying a sequence of antidepressants is often done without much greater success (though it should usually be tried) but after several drug failures the odds of another being effective declines steeply. In such cases augmentation of antidepressants (i.e. using a substance or medication that may not itself be an antidepressant in addition) is often a better strategy. L-methylfolate is often effective and it is established that 15mg daily is what's needed for that purpose (7.5 mg and the even lower doses found in supplements including prenatal vitamins are not enough). Before l-methylfolate was available I often used high doses of "regular" folic acid, but it is far less effective. Many but not all patients benefit from l-methylfolate augmentation. Though often effective in people with an MTHFR mutation, I have NOT found that they are the only patients who may benefit nor have I found that all with an MTHFR do.
"Medical foods" are a class of substances that by definition require a prescription. The makers of Deplin have marketed it that way and done much to inform practitioners. But as the cost gradually increased along with the continued hassle of needing a prescription for what is, in fact, a nutritional supplement, other companies entered the market, selling it as a nutritional supplement (which in the US is therefore not FDA approved but can be sold as long as no explicit claims are made that it prevents or treats any disease or condition). "Methylpro" is one, sometimes I believe called "extrafolate." Initially reluctant to advise patients to try it instead of Deplin, over time many have switched. It is less pricey and more convenient to order. None of my patients who did well on Deplin have had any loss of benefit when changing.
I also often use s-adenosylmethionine (SAME) for augmentation or alone for depression.
CAUTION: just because something is sold as a supplement over the counter does not necessarily mean it is safe. SAMe, for instance, may trigger mania in someone with a bipolar disorder. And as depression itself can be disabling and dangerous, anyone with moderate to severe depression should not rely on self-treatment alone but work with a skilled professional. Sometimes psychotherapy such as cognitive-behavioral therapy helps greatly, with or without medication. When the "brain piece" seems to be holding back recovery a psychiatrist or other physician experienced in treating depression should be consulted. It can be hard to find someone well-trained and knowledgeable in both standard pharmacology and nonstandard supplements like these; if/when choosing a doctor it may be useful to ask what he/she knows about l-methylfolate and SAMe and also omega-3 essential fatty acid supplementation to help decide. There should, at minimum, be a willingness to learn more. Knowing nothing or debunking the options because they're not FDA approved should, in my opinion, be disqualifying.
5 April 2015
First of all, methylfolate is not an anti-depressant. It is not connected to the body's ability to produce SAMe. It is used in the brain. If you are only taking 1mg of methylfolate, you are nowhere near taking an effective dose. You are just taking an arbitrary FDA-approved amount. There are two dosages of methylfolate: 7 1/2 milligrams and 15 milligrams. It's not necessary to slowly increase a dosage of methylfolate. I started at 15mg with no problems.
We take folic acid in our food and vitamins, but it's not active in the body. It has to be converted into an active form that the body can use. An enzyme in the body called methylenetetrahydrofolate reductase, or MTHFR for short, converts folic acid into l-methylfolate (the "L" means that it's natural.) Why is that important? Because only this active form, methylfolate, can cross the blood-brain barrier and enter the brain. When it gets there, another enzyme already in the brain uses the methylfolate to produce our neurotransmitters, e.g., serotonin, norepinephrine, dopamine. It is THESE NEUROTRANSMITTERS that are largely responsible for helping to lift our depression and g-d alone knows how many other functions. Why do we need l-methylfolate? Because many of us have MTHFR that is unable to do its job properly in converting the folic acid to methylfolate. We need the already converted form.