Is Deplin Effective For Depression?

In our latest question and answer, the pharmacist discusses whether or not Deplin is effective for the treatment of depression.

Mar 07, 2018

TheLobster asked

Is Deplin effective for the treatment of depression in people with normal folic acid levels?


Deplin (L-methylfolate) has been studied for the treatment of depression, either alone, or in combination with antidepressant medication such as SSRIs (Selective Serotonin Reuptake Inhibitors).

While there haven't been many large scale studies evaluating the effectiveness of Deplin for the treatment of depression, small studies have shown some potential positive effects for reducing depressive symptoms.

Deplin For Depression

Deplin is a medical food, a classification in-between over the counter medication and prescription medication. Per the FDA, medical foods are defined as: 

"a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."

Like prescription drugs, medical foods must be prescribed by a doctor (or authorized prescriber) and dispensed by a pharmacy.

Data indicates a fairly strong link between depression and folate deficiency. There are multiple theories as to why this is but one theory is that folates are needed to make a variety of neurotransmitters in the brain, such as:

  • Serotonin
  • Norepinephrine
  • Dopamine

Deplin contains l-methylfolate. Unlike folic acid, which must be transformed in the body to l-methylfolate, l-methylfolate is the primary form of folate in circulation and can cross the blood brain barrier, while folic acid cannot. As such, l-methylfolate is considered the "active form" of folate.

L-methylfolate is also known as:

  • 5-MTHF
  • L-5-MTHF
  • Levomefolic acid

Deplin For Depression: What Do The Studies Say?

It has been theorized that supplementation with L-methylfolate, which is the active ingredient in Deplin, can help treat depression. While most studies are small, there is some evidence that suggests that supplementing with folate products alone, or in combination with an antidepressant, can help treat depression. 

Folic acid is necessary for the production of many neurotransmitters in the brain, especially serotonin. Therefore, folic acid supplementation may increase neurotransmitter levels. In addition, some studies show that lower folate levels are linked to poor response rates for many individuals that take antidepressant. Again, folic acid supplementation may help this.

  • One small study in the year 2000 showed that a higher percentage of individuals who took folic acid in addition to Prozac (fluoxetine) had significant reductions in depressive symptoms when compared to those who took Prozac alone (94% for those taking folic acid and Prozac compared to ~60% for those taking Prozac alone). The study did note that women seemed to respond better than men and therefore higher doses may be needed in men.
  • A 2009 study showed that in individuals who were diagnosed with low folate levels, supplementation of 7.5 mg of L-methylfolate daily can significantly increase response rates to antidepressant therapy.
  • A 2011 retrospective analysis showed that L-methylfolate supplementation with antidepressants was more effective in improving depressive symptoms and function than with antidepressants alone. In addition, the antidepressants were better tolerated in terms of side effects.
  •  Studies have also shown the potential benefits of using L-methylfolate alone, not in combination with other antidepressants. In addition, supplementing with folate products may even help those who don't have low blood levels of folate. The prescribing information for Deplin references several studies in which depressive symptoms are reduced in those taking L-methylfolate when compared to placebo.


While most studies regarding the efficacy of Deplin (or L-methylfolate supplementation) are small, data indicates that supplementing may be beneficial to try for many individuals for the treatment of depression. Multiple studies have published results that show folate supplementation can:

  • Improve response rates to antidepressant medications
  • Reduce depressive symptoms when used alone
  • Reduce depressive symptoms in those with low folate blood levels
  • Reduce depressive symptoms in those with normal folate blood levels

More large scale, well designed studies are needed to get a better idea of just how well l-methylfolate works for depression and the dosages needed for good response rates.

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