Folate and Depression

Folate, which is involved in making neurotransmitters such as serotonin and dopamine, has been found to be low in some individuals with depression. And low levels appear to be associated with a decreased response to antidepressants.

In an article from the December, 2012 issue of the American Journal of Psychiatry, Papakostas and colleagues found that L-methylfolate (folate is converted into L-methylfolate prior to it’s role in making neurotransmitters) increased the number of responders when it was added to an SSRI-type antidepressant. These patients had been taking an SSRI (a category which includes fluoxetine, sertraline, citalopram, paroxetine and others) for 8 weeks without responding to the SSRI alone. 32% responded to L-methylfolate plus SSRI, versus 14% taking placebo and SSRI.

The number needed to treat (NNT, one of the better measures of the practical usefulness of a treatment) was 6, which means it is a clinically useful strategy.

l-Methylfolate was well tolerated when added to an SSRI, with rates of side effects no different from those reported with placebo plu an SSRI.

An important unanswered question is whether it is necessary to use L-methylfolate (marketed as Deplin at about $90-$95 dollars a month), or if over the counter, very inexpensive, folic acid would be just as effective. Another question is what dose of folic acid should be used if added as an augmentation agent in the treatment of depression.

l-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials

George I. Papakostas, M.D., et. al.

The Evolving Story of Folate in Depression and the Therapeutic Potential of l-Methylfolate

J. Craig Nelson, M.D.

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