What to Know About Deplin (L-methylfolate)

A Medical Food Prescribed for Major Depressive Disorder and Schizophrenia

Woman taking a pill.

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Deplin (L-methylfolate) is a prescription medical food, also called a nutraceutical, made up of folic acid—a form of vitamin B. Folic acid is the synthetic form of folate, which occurs naturally in our bodies and various foods, but is sometimes deficient in people with major depressive disorder and schizophrenia.

Learn more about Deplin, including how it's used, what you should know before taking this drug, and how to take and store it. It's also important to understand Deplin's side effects, warnings, and potential interactions with other drugs, so we will cover these topics as well.

The Most Important Information to Know About Deplin

  • Common side effects of Deplin can include agitation, anxiety, and gastrointestinal issues. Talk with your healthcare provider to discuss your options if you experience these effects and they are problematic.
  • If you have an allergic reaction to Deplin, call 911 or seek immediate medical attention.

How Deplin Works

Dietary folic acid must be "activated" or converted to L-methylfolate for it to cross the blood-brain barrier. Deplin is made up of L-methylfolate—an already-active form of folic acid that doesn't require conversion, making it ready to use for individuals who have trouble with the activation of this nutrient.

Once in the brain, L-methylfolate undergoes a series of chemical reactions to convert it to its final form, which is used in the synthesis of the neurotransmitters serotonin, dopamine, and norepinephrine. Having adequate levels of these neurotransmitters is important as it can affect mood. If they are out of balance, this can also play a role in mental illness development.

Uses for Deplin

Folate deficiency, which Deplin is designed to help correct, has been linked with certain mental health disorders, namely major depressive disorder and schizophrenia.

Major Depressive Disorder

Research has found a two-way connection between folate levels and depression. When a person has low folate levels, it can increase their risk of depression. And if someone with depression becomes deficient in folate due to a poor diet, this can aggravate the depression, making it worse.

A 2013 study assessed the effects of taking L-methylfolate on depression. Researchers found that when L-methylfolate was used alongside antidepressants, participants with major depressive disorder reported improvement in depression symptoms and greater satisfaction with their medication treatment.

A 2021 review of six studies found similar results. It noted that when L-methylfolate or folic acid was combined with primary depression treatments, patients had improved depression scores, response rates, and remission rates.

Other pieces of research indicate that some individuals with treatment-resistant depression have variations of the methylenetetrahydrofolate reductase (MTHFR) gene, which is involved in folate conversion. This variation leads to reduced conversion of folic acid to L-methylfolate. So, these individuals are likely to benefit from L-methylfolate in addition to taking antidepressants.

Deplin is not an antidepressant but can be used alongside antidepressants to help treat depression, enhancing the effects of those medications.


Low folate levels are also associated with an increased risk of schizophrenia. Folate helps break down the amino acid homocysteine. If folate levels are low, this breakdown cannot effectively occur, leading to high homocysteine levels. High homocysteine can cause neurodegeneration, which is a characteristic of schizophrenia.

A 2018 study involved 55 subjects with schizophrenia. Some received L-methylfolate for 12 weeks and the rest received a placebo or sham treatment. Those receiving L-methylfolate had improvement in their schizophrenia symptoms while there was no difference in the group receiving a placebo.

Before Taking Deplin

Before prescribing Deplin, your healthcare provider will conduct a thorough review of your medical history. If you have any allergies to folate or the other ingredients contained in Deplin, let your healthcare provider know.

You can ask your provider for a comprehensive list of active and inactive ingredients to be sure.

It's also important to tell your provider if you have low vitamin B12 levels or red blood cell counts, or if you've had a reaction to any type of food, dye, or preservative.

Precautions and Contraindications 

Methylfolate supplements are generally considered safe in pregnancy. However, if you are pregnant, plan to become pregnant, or just had a baby and intend to breastfeed, let your healthcare provider know this before taking Deplin. Your dose may need to be adjusted during these times.

Dosage of Deplin

Deplin is available in two dosages: 7.5 milligrams (mg) and 15 milligrams (mg). It is typically prescribed to be taken once a day. To avoid missing any doses, it can be helpful to set an alarm for the same time as a reminder.

As a prescription medical food, Deplin's dosage is decided by your healthcare provider based on your specific nutritional needs. It's important to not increase or reduce the dosage prescribed to you without first consulting your physician.

Deplin is also available in a generic formulation as L-methylfolate calcium (Metafolin) and Algae-S powder (Schizochytrium).

How to Take and Store Deplin

You can take Deplin with or without food. However, it should be swallowed whole and not chewed or split into two. If you miss a dose, take it as soon as you remember. But if it’s close to the time for your next dose, skip the missed dose to avoid the risk of overdosing. 

Store your medication in a dry place, at room temperature, and away from direct sunlight. Avoid storing it in your bathroom as bathrooms can be humid and moist.

Deplin should be taken regularly for the most optimal benefits. Don't discontinue Deplin without first consulting your doctor, and don't share it with any family or friends who might have similar symptoms as you.


If you have taken too much Deplin and suspect that you may be experiencing an overdose, or if someone you know has overdosed on Deplin, call your local poison control center or emergency room immediately, or call 911.

Potential Side Effects of Deplin 

In studies, people taking L-methylfolate generally reported no more side effects than those taking a placebo or sugar pill. However, some have experienced adverse effects when taking an L-methylfolate supplement.

The most well-known side effects of L-methylfolate supplementation include:

  • Agitation
  • Anxiety
  • Gastrointestinal issues 

If you experience any of these effects or notice any other unusual effects that are not life-threatening but could be bothersome, speak to your provider. They may adjust your dosage to lessen these effects, discontinue the use of Deplin, or switch you to a different medication. 

Warnings and Interactions for Deplin

Some people might experience an allergic reaction while using this drug. Even though this is rare, the following are signs that you may be allergic to Deplin: 

  • Difficulty breathing 
  • Dizziness 
  • Skin rash 
  • Swelling of the face, tongue, or throat

If you notice any of the above symptoms, stop using Deplin immediately and seek medical attention or call 911.

The question of whether Deplin may interact with other medications has not been adequately studied. To be safe, before taking Deplin, give your healthcare provider a list of all other drugs, vitamins, or supplements you are currently taking.

If you are already on Deplin and need to start taking another drug, update your provider then as well to help reduce the risk that adverse reactions will occur.

14 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Toketemu Ohwovoriole
Toketemu has been multimedia storyteller for the last four years. Her expertise focuses primarily on mental wellness and women’s health topics.