When searching for the right therapy to help a patient reach remission treating depression, it can (at times) become very frustrating from patients. Approximately 2/3 of individuals do not achieve remission for depression with serotonin-norepinephrine reuptake inhibitor (SNRI) and selective serotonin reuptake inhibitor (SSRI) monotherapy. Basically, this means that a psychiatrist who has 20 clients and is treating them for depression could have 14 who have no (or very little) improvement with their symptoms. Treatment-resistant depression (TRD) is a term that is used to describe these type of patients. It is used to describe people with Major Depressive Disorder that do not reach remission after multiple antidepressant trials.

Individuals who suffer from uncontrolled depression are more likely to have high medical bills, employment problems, and suicidal thoughts. One reason psychiatrist may think patients suffer from TRD is because patients may have an L-methylfolate deficiency. This deficiency may be the reason why treatment with traditional antidepressant medication is not effective in managing symptoms of depression.

In order to understand what it is, you first need to understand Folate. Folate is found in green leafy vegetables, orange juice, nuts, and even some fruits. It is normally part of a healthy diet. Folate is something that the body requires for cell growth and reproduction. Folate is a necessity for overall health.

Folic acid is the synthetic form of folate and must be digested and process before the body can even use it. There are even several steps the body has to go through to break it down. These need to be done for a person to reap the full benefit of folic acid. As a result of these detailed steps to break it down, the body then makes a more specific version of the folate called L-Methylfolate.

L-methylfolate is very important because unlike folic acid, it crosses the blood brain barrier. It has been shown that many people have a genetic error called the MTHFR polymorphism. This limits their body’s ability to break down the folic acid into L-methylfolate. It is the ‘limit’in this polymorphism that causes patients to not metabolize antidepressants, which creates the TRD.

Additional risk factors that may cause L-methylfolate deficiency:

  • Certain medications

  • Diseases

  • Lifestyle habits

  • Age

  • Not enough folate in your diet

This deficiency can lead to decreased red blood cells (anemia) or even cause high levels of some amino acids in blood (hyperhomocysteinemia).

Presently, the US-FDA has approved only one form of folate—l-methylfolate (Deplin). Deplin has not been approved as a primary treatment, but rather as an adjunctive treatment. It should be taken in addition to a client's regular psychiatric medications. The specifics of this treatment option need to be discussed with a patient’s family and physicians.


For additional information, please give us a call. If you think that current medication are not working for your body like they were or never feel that they did work effectively, feel free to reach us and schedule an appointment with our specialized health care professionals.

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