For almost 40 years, it has been suspected that folate plays a role in depression. We have a general sense that low folate can cause depressive symptoms, and that treatment with folate (of low folate patients) can help, but it is still debatable whether or not folate supplementation helps people who are not otherwise deficient.
Folate vs. Deplin (R)
Additionally, it is known that some medications, especially seizure meds such as valproate, carbamazepine and to some degree lamotrigine, reduce the amount of available folate. (And so it is always a good idea to be taking a folate supplement if you are on these meds.)
Recently, a new drug l-methylfolate (trade name Deplin), a shortening of the proper name l-methyltetrahydrofolate (MTHF), has been investigated for the treatment of depression. Why? Because folate itself is converted to MTHF, the active chemical that actually produces the results in depression.
Suffice it to say some studies have found it to work. Is there a difference between supplementing with MTHF and regular folate? (Folic acid is the synthetic version of folate, which is what is added to foods or contained in multivitamins.) Folic is converted (after four steps) into MTHF. If all enzymes in those steps are working well, or various intermediary steps are not being diverted to create other chemicals, then increasing folic acid would be as good as increasing MTHF. However, supplementing with MTHF is a more direct and reliable way of increasing MTHF.
In ordinary circumstances, of course, folate alone is good enough. The key question is whether or not people with (at least a specific kind of) depression are not susceptible to the diversion or reduced enzyme activity described above. This is still unclear.
Another issue is B12 deficiency. In people with malnourishment, or B12/folate deficiencies specifically such as alcoholics, patients with certain dementias, etc, supplementing with folate can actually mask a B12 deficiency. MTHF would not have this effect since it is the end product of folate metabolism.
How does folate and MTHF actually work? I don't know is a common refrain in psychiatry, but we do know that MTHF controls a co-factor for the synthesis of serotonin, dopamine, and norepinephrine. In creating this cofactor BH4, MTHF drives the introductory steps that will ultimately result in serotonin or dopamine. Dopamine is later converted to norepinephrine. Thus, MTHF controls the synthesis of certain neurotransmitters - the same neurotransmitters that are associated with the way we treat depression. It's for this reason that MTHF is considered an addition to regular antidepressants, not a replacement. IT works best by helping regulate the neurotransmitters the drugs are affecting.
MTHF (Deplin) can only be prescribed by a physician, but it isn't considered a medication. IT is classified as a "medical food" which means that it is a food or food supplement used specifically for the treatment of a medical illness, under the direction of a doctor.