L-methylfolate, Depression, and What You Need to Know

L-methylfolate, Depression, and What You Need to Know

L-methylfolate is commonly prescribed as a supplementary medicine to patients with treatment-resistant depression who are already prescribed SSRIs or SNRIs. But what is L-methylfolate, and what are the outcomes of its use in depression treatment? Mid City TMS can help you understand L-methylfolate, depression, and your various depression treatment options, such as transcranial magnetic stimulation (TMS):

What Is L-methylfolate?

Folate, a B vitamin, is one of the 13 essential vitamins that the human body needs in order to properly function and grow. L-methylfolate is the bioactive form of this vitamin. L-methylfolate is the only folate form that is capable of passing the blood-brain barrier, a border created by endothelial cells that allows nutrients into the brain. Once it crosses this barrier, l-methylfolate participates in the production of the neurotransmitters serotonin, dopamine, and norepinephrine.

Folate Levels and Depression

The deficiency of red blood cell folate and serum folate levels are considered independent risk factors for Major Depressive Disorder (MDD). Folate deficiency is also associated with poor responses to medicinal depression treatment, as well as more severe episodes of depression. L-methylfolate increases folate levels for patients with a deficiency of this vitamin, which is meant to positively impact the body’s response to medicinal depression treatment.

L-methylfolate, SSRIs and SNRIs

L-methylfolate is occasionally prescribed alongside either selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). L-methylfolate serves as a medicinal supplement to these antidepressants for patients who have shown partial or no response to SSRIs alone.

Research on L-methylfolate and Depression Treatment

It is important to understand the benefits and potential risks of L-methylfolate in the treatment of MDD.

Positive Outcomes of L-methylfolate in Depression Treatment

Ongoing psychiatric research shows that L-methylfolate has an overall positive impact on the body’s response to SSRIs and SNRIs in treatment-resistant depression. A 2012 study conducted by researchers at Massachusetts General Hospital involved two parallel comparison design trials meant to record the impact of L-methylfolate on the treatment of patients with SSRI-resistant MDD.

Over the course of two 30-day trial periods, 148 patients with SSRI-resistant MDD were randomly divided into three groups in a 2:3:3 ratio. The first group received 7.5 mg per day of L-methylfolate for the first trial, with an increased dosage of 15 mg per day for the second trial. The second group received a placebo for the first trial, followed by 7.5 mg per day of L-methylfolate for the second trial. The third group received a placebo during both trials.

  • During the first trial, there were no significant differences between the groups in their reception to medicinal depression treatments.
  • During the second trial, 15 mg per day doses of L-methylfolate were shown to greatly improve the first group’s overall response rate and degree of change in depression symptom scores, as compared to the results of the second and third group. There were also no adverse effects directly related to this dosage of L-methylfolate.

Overall, this study found that a 15 mg per day supplement of L-methylfolate could lead to a more effective and safe treatment strategy for patients with SSRI-resistant MDD.

L-methylfolate for Patients with MTHFR Mutations

L-methylfolate can have a positive impact on MDD treatment for patients with certain mutations in their gene code. The gene code mutations C677T and A1298C in the enzyme methylenetetrahydrofolate reductase (MTHFR) prevent some individuals from converting folate from foods or from folic acid into an active form. A 2019 study found that L-methylfolate was related to an significant improvement in the severity of depressive symptoms in 182 patients with MTHFR mutations. The significant association of the 677T genotype with improvement in depressive symptoms following L-methylfolate treatment is consistent with the literature indicating the 677TT genotype contributes to L-methylfolate deficiency and depressive symptoms.

Can L-methylfolate Help Me Treat MDD?

L-methylfolate’s effectiveness in treating your MDD will depend on a variety of factors, including whether or not you experience folate deficiency or have MTHFR mutations (which can be tested by pharmacogenetic testing). Ultimately, your mental healthcare provider can provide your best guidance on L-methylfolate, depression treatment, and your best treatment options.

Find Depression Relief through Mid City TMS

Many patients experiencing treatment-resistant depression wonder what options they have for depression relief. Over three decades of clinical research, transcranial magnetic stimulation (TMS) therapy has shown positive results amongst patients with treatment resistant depression. Contact Mid City TMS today to talk with one of our healthcare experts about the benefits of TMS treatment for depression.

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