L-methylfolate is an active form of folic acid which enters the brain. Folic acid supplementation has been considered for decades in treating depression, with varying results (generally mildly positive). The mechanism in the brain is generally as an indirect enhancer of the production of neurotransmitters, through its involvement in the metabolic pathway.
Here are some recent studies looking at l-methylfolate as an augmentation:
http://www.ncbi.nlm.nih.gov/pubmed/21311704
Here, a dose of 15 mg/day of l-methylfolate (but not 7.5 mg) added to an SSRI led to a doubling of the response rate for depressed patients, after 30 days (about 30% vs. 15%). These patients had previously been on the same SSRI alone without response. There were no side effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/23212058
Another positive study from 2011. Again showing a significant improvement in response rate with l-methylfolate augmentation, with no side effect problems (probably fewer side effects in the folate group). But this is a much weaker study due to it being retrospective.
As I look further at this I see some controversy about whether there may be bias here, as the methylfolate is quite an expensive product. I would want to see a comparison study between methylfolate and the much more inexpensive ordinary folic acid. In discussions I've looked at pertaining to this issue, the argument is made that the dose of ordinary folic acid would be very high to match 15 mg of l-methylfolate. Maybe so--but it would be very simple to do a comparison study, since if there is no clinical superiority of one over the other, then the more affordable product should be recommended.
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