Guide to Folic Acid for Depression

Learn whether folic acid can help to treat depression and whether it's safe to take during pregnancy.

Every pregnant woman is encouraged to take folic acid as a supplement during pregnancy. Folate is important for the formation of the neural tube – the precursor to the spine and brain. But did you know it has also been studied as a treatment for depression?

What is folate and how does it relate to depression?

Folate is one of the B Vitamins, and can be found naturally in foods like leafy vegetables and fruits. Folic acid is a synthetic form of folate that can be purchased as a supplement. It is necessary in the biochemical pathway for the creation of the molecule serotonin, a neurochemical that is deficient in depression and which is a primary target of antidepressant medication

Research has found both that up to a third of those with depression have decreased folate levels and those with low levels do not respond as well to antidepressants. For these reasons, folate has been studied as a means of improving antidepressant treatment.

Does treatment with folate improve depression?

There has been some mixed research on whether taking supplemental folate helps improve depressive symptoms – both by itself and in conjunction with other antidepressants. Some studies where patients were prescribed folic acid did not find a difference, while others did find that folate led to improvement in symptoms. In several of the instances where a difference was noted, the researchers prescribed patients the active form of folate (called L-methylfolate).

Are folate and folic acid safe to take in pregnancy?

Folic acid is important to take in pregnancy. Most likely, your obstetrician recommended you take folic acid as soon as you start planning for conception and through the pregnancy. This is especially important for women whose babies are vulnerable to the development of neural tube defects (problems with the brain/spine). In fact, for these higher risk pregnancies, physicians sometimes recommend much higher doses of folic acid (4mg, rather than the dose most common in supplements of 800-1000mcg).

The active form of folate, L-methyfolate (brand names include Deplin) has been studied less in pregnancy in part because this is a much newer form of the vitamin. In essence, it is what folic acid is metabolized into by the body. Therefore we can also view it as safe in pregnancy. It would be particularly helpful for women whose bodies are unable to completely convert folic acid into its active form. However, there are no current studies (nor a recommendation by the FDA) for the appropriate dose of L-methylfolate in pregnancy.

Does taking additional folate or folic acid in pregnancy improve perinatal depression?

There have been only a handful of small studies looking specifically at the relationship of folate and depression in pregnancy and postpartum. So far, there has not been one that demonstrated a clear link between the risk of depression with the intake of B vitamins or with folate concentration in the blood. There are some helpful preliminary data, however. For example, in one study, there was a trend that women with postpartum depression reported taking less folate supplements in pregnancy. Similarly, it was noted that the likelihood of perinatal and postpartum depression decreased with each dose increase of folate. It is important to keep in mind that these are associations, rather than causations.

Take home points

Overall, the research suggests that folic acid, already known to be essential in pregnancy, is helpful in the management of depression, and is an intervention with few side effects. Make sure that you are getting this important vitamin before, during, and after your pregnancy. It will be important to work with your physician to determine which formulation and what dose is most appropriate for you, given your particular risks or metabolic needs.

If you are struggling with depression, first line treatments including psychotherapy and medications about which we have more information (both in terms of safety and efficacy) are a good place to start (See: Medication Safety Review Series on SSRIs). As more research comes out about folate for depression in pregnancy, we may see this as a more mainstream treatment option.

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References:
Bedson, E. et. al. Folate augmentation of treatment – Evaluation for depression (FolATED): Randomized trial and economic evaluation. Health Technology Assessment 18(48): July 2014.

Nelson, J.C. The evolving story of folate in depression and the therapeutic potential of L-Methylfolate.  2012) American Journal of Psychiatry 169(12): 1223-25.
Morris, D.W., Trivedi, M.H., and Rush, A.J. Folate and unipolar depression. (2008) The Journal of Alternative and Complimentary Medicine 14(3): 277-285.
Chong, M.F.F. et. al. Relationships of maternal folate and vitamin B12 status during pregnancy with perinatal depression: The GUSTO study. (2014) Journal of Psychiatric Research 55: 110-116.
Greenberg, J.A. and Bell, S.J. Multivitamin supplementation during pregnancy: Emphasis on folic acid and L-methylfolate. (2011) Reviews in Obstetrics & Gynecology 4(3-4): 126-127.