L-Methylfolate For Depression

In an ongoing search to find increasingly effective treatments for depression, nutritional supplements often come up as a relatively benign, and possibly effective option. One supplement that has received significant attention is folic acid – readily available over the counter, and Deplin (L-methylfolate). Folic acid is converted to L-methylfolate, which is believed to play a key role in the synthesis of the neurotransmitters serotonin, dopamine and norepinephrine – targets of most anti-depressant treatments. Unlike folic acid, L-methylfolate is able to cross the blood brain barrier and play its role in neurotransmitter synthesis. Some people are believed to be poor converters of folic acid to L-methylfolate, for which reason PamLab markets the metabolite, L-methylfolate (Deplin) – a much more expensive alternative to the folic acid supplements available in most pharmacies.

Most studies thus far have found a small but significant relationship between low folic acid levels and depression ( (Gilbody S et al., J Epidemiol Community Health 2007;61:631-637)) The data supporting the efficacy of L-methylfolate has been more impressive. 0.5mg per day of folic acid (not Deplin) in combination with fluoxetine, beat placebo by 38% vs 18%, but only 10 weeks after treatment. (Coppen A and Bailey J, J Affect Disord 2000; 60:121-130). Other studies have yielded mixed results – in 2012 – an analysis of 15mg Deplin added to an SSRI for treatment resistant depression, yielded no improvement in the first trial, and a marked improvement in the second ( American Journal of Psychiatry. 169(12), 1267-74.)

Bottom Line: Folic acid supplementation is a relatively benign augmenting strategy for treatment resistant depression, and certainly worth a try, ideally with the inexpensive, readily available supplements first. Up to 10 weeks may be required to notice its effect. Recommended doses of Deplin are 7.5 to 15mg daily, while the recommended dose of folic acid is 0.4mg, or 400 micrograms per day – the latter is far less expensive, and certainly worth a try before Deplin.

Menlo Park Psychiatry has been working with patients for Depression over the years and the insight and experience collected has made us known as one of the best sources in the area for treatment. For more information on how we can help with Depression, contact us at: www.siliconpsych.com