What to Know About Deplin (L-methylfolate)

Table of ContentsView AllTable of ContentsHow It WorksUsesBefore TakingDosageHow to Take and StoreSide EffectsWarnings and Interactions

Table of ContentsView All

View All

Table of Contents

How It Works

Uses

Before Taking

Dosage

How to Take and Store

Side Effects

Warnings and Interactions

Close

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 withmajor depressive disorderand 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 DeplinCommon 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, call911or seek immediate medical attention.

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, call911or 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 inmental illnessdevelopment.

How Neurotransmitters Work and What They Do

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 indepression symptomsand 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 withprimary 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 isnotan antidepressant but can be used alongside antidepressants to help treat depression, enhancing the effects of those medications.

An Overview of Treatment-Resistant Depression

Schizophrenia

Low folate levels are also associated with an increasedrisk 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 theirschizophrenia symptomswhile 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

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.

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.

EmergencyIf you have taken too much Deplin and suspect that you may beexperiencing an overdose, or if someone you know has overdosed on Deplin, call your local poison control center or emergency room immediately, or call 911.911

Emergency

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

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:

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:

If you notice any of the above symptoms, stop using Deplin immediately and seek medical attention or call911.

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 supplementsyou 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 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Altaf R, Gonzalez I, Rubino K, Nemec II EC.Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.Complement Ther Med. 2021;61:102770. doi:10.1016/j.ctim.2021.102770Roffman JL, Petruzzi LJ, Tanner AS, et al.Biochemical, physiolotic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial.Mol Psychiatry. 2018;23(2):316-322. doi:10.1038/mp.2017.41Alfasigma USA, Inc.The active folate in DEPLIN is different from folic acid.Choudhury A, Sahu T, Ramanujam PL, et al.Neurochemicals, behaviours and psychiatric perspectives of neurological diseases.Neuropsychiatry. 2018;8(1):395-424. doi:10.4172/Neuropsychiatry.1000361Reynolds EH.Chapter 61 - The neurology of folic acid deficiency.Handbook of Clin Neurol. 2014;120:927-943. doi:10.1016/B978-0-7020-4087-0.00061-9Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV.Assessing effects of L-methylfolate in depression management: Results of a real-world patient experience trial.Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520Dartois LL, Stutzman DL, Morrow MA.L-methylfolate augmentation to antidepressants for adolescents with treatment-resistant depression: A case series.J Child Adol Psychopharmacol. 2019;29(5):386-391. doi:10.1089/cap.2019.0006University of Michigan Medicine.L-methylfolate.Wang D, Zhai JX, Liu DW.Serum folate levels in schizophrenia: A meta-analysis.Psychiatry Res. 2016;235:83-89. doi:10.1016/j.psychres.2015.11.045Cleveland Clinic.Levomefolate tablets and capsules.Freeman MP, Savella GM, Church TR, et al.A prenatal supplement with methylfolate for the treatment and prevention of depression in women trying to conceive and during pregnancy.Ann Clin Psychiatry. 2019;31(1):4-16.Deplin.com.Deplin capsules.American Psychiatric Publishing, Inc.Medication information for parents and teachers: L-methylfolate—Deplin.Hardin A, Baldwin-Sayre C.L-methylfolate as a monotherapy for treatment-resistant depression: A case study.Integr Med (Encinitas). 2020;19(4):14-18.

14 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Altaf R, Gonzalez I, Rubino K, Nemec II EC.Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.Complement Ther Med. 2021;61:102770. doi:10.1016/j.ctim.2021.102770Roffman JL, Petruzzi LJ, Tanner AS, et al.Biochemical, physiolotic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial.Mol Psychiatry. 2018;23(2):316-322. doi:10.1038/mp.2017.41Alfasigma USA, Inc.The active folate in DEPLIN is different from folic acid.Choudhury A, Sahu T, Ramanujam PL, et al.Neurochemicals, behaviours and psychiatric perspectives of neurological diseases.Neuropsychiatry. 2018;8(1):395-424. doi:10.4172/Neuropsychiatry.1000361Reynolds EH.Chapter 61 - The neurology of folic acid deficiency.Handbook of Clin Neurol. 2014;120:927-943. doi:10.1016/B978-0-7020-4087-0.00061-9Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV.Assessing effects of L-methylfolate in depression management: Results of a real-world patient experience trial.Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520Dartois LL, Stutzman DL, Morrow MA.L-methylfolate augmentation to antidepressants for adolescents with treatment-resistant depression: A case series.J Child Adol Psychopharmacol. 2019;29(5):386-391. doi:10.1089/cap.2019.0006University of Michigan Medicine.L-methylfolate.Wang D, Zhai JX, Liu DW.Serum folate levels in schizophrenia: A meta-analysis.Psychiatry Res. 2016;235:83-89. doi:10.1016/j.psychres.2015.11.045Cleveland Clinic.Levomefolate tablets and capsules.Freeman MP, Savella GM, Church TR, et al.A prenatal supplement with methylfolate for the treatment and prevention of depression in women trying to conceive and during pregnancy.Ann Clin Psychiatry. 2019;31(1):4-16.Deplin.com.Deplin capsules.American Psychiatric Publishing, Inc.Medication information for parents and teachers: L-methylfolate—Deplin.Hardin A, Baldwin-Sayre C.L-methylfolate as a monotherapy for treatment-resistant depression: A case study.Integr Med (Encinitas). 2020;19(4):14-18.

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Altaf R, Gonzalez I, Rubino K, Nemec II EC.Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.Complement Ther Med. 2021;61:102770. doi:10.1016/j.ctim.2021.102770Roffman JL, Petruzzi LJ, Tanner AS, et al.Biochemical, physiolotic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial.Mol Psychiatry. 2018;23(2):316-322. doi:10.1038/mp.2017.41Alfasigma USA, Inc.The active folate in DEPLIN is different from folic acid.Choudhury A, Sahu T, Ramanujam PL, et al.Neurochemicals, behaviours and psychiatric perspectives of neurological diseases.Neuropsychiatry. 2018;8(1):395-424. doi:10.4172/Neuropsychiatry.1000361Reynolds EH.Chapter 61 - The neurology of folic acid deficiency.Handbook of Clin Neurol. 2014;120:927-943. doi:10.1016/B978-0-7020-4087-0.00061-9Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV.Assessing effects of L-methylfolate in depression management: Results of a real-world patient experience trial.Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520Dartois LL, Stutzman DL, Morrow MA.L-methylfolate augmentation to antidepressants for adolescents with treatment-resistant depression: A case series.J Child Adol Psychopharmacol. 2019;29(5):386-391. doi:10.1089/cap.2019.0006University of Michigan Medicine.L-methylfolate.Wang D, Zhai JX, Liu DW.Serum folate levels in schizophrenia: A meta-analysis.Psychiatry Res. 2016;235:83-89. doi:10.1016/j.psychres.2015.11.045Cleveland Clinic.Levomefolate tablets and capsules.Freeman MP, Savella GM, Church TR, et al.A prenatal supplement with methylfolate for the treatment and prevention of depression in women trying to conceive and during pregnancy.Ann Clin Psychiatry. 2019;31(1):4-16.Deplin.com.Deplin capsules.American Psychiatric Publishing, Inc.Medication information for parents and teachers: L-methylfolate—Deplin.Hardin A, Baldwin-Sayre C.L-methylfolate as a monotherapy for treatment-resistant depression: A case study.Integr Med (Encinitas). 2020;19(4):14-18.

Altaf R, Gonzalez I, Rubino K, Nemec II EC.Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.Complement Ther Med. 2021;61:102770. doi:10.1016/j.ctim.2021.102770

Roffman JL, Petruzzi LJ, Tanner AS, et al.Biochemical, physiolotic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial.Mol Psychiatry. 2018;23(2):316-322. doi:10.1038/mp.2017.41

Alfasigma USA, Inc.The active folate in DEPLIN is different from folic acid.

Choudhury A, Sahu T, Ramanujam PL, et al.Neurochemicals, behaviours and psychiatric perspectives of neurological diseases.Neuropsychiatry. 2018;8(1):395-424. doi:10.4172/Neuropsychiatry.1000361

Reynolds EH.Chapter 61 - The neurology of folic acid deficiency.Handbook of Clin Neurol. 2014;120:927-943. doi:10.1016/B978-0-7020-4087-0.00061-9

Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV.Assessing effects of L-methylfolate in depression management: Results of a real-world patient experience trial.Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520

Dartois LL, Stutzman DL, Morrow MA.L-methylfolate augmentation to antidepressants for adolescents with treatment-resistant depression: A case series.J Child Adol Psychopharmacol. 2019;29(5):386-391. doi:10.1089/cap.2019.0006

University of Michigan Medicine.L-methylfolate.

Wang D, Zhai JX, Liu DW.Serum folate levels in schizophrenia: A meta-analysis.Psychiatry Res. 2016;235:83-89. doi:10.1016/j.psychres.2015.11.045

Cleveland Clinic.Levomefolate tablets and capsules.

Freeman MP, Savella GM, Church TR, et al.A prenatal supplement with methylfolate for the treatment and prevention of depression in women trying to conceive and during pregnancy.Ann Clin Psychiatry. 2019;31(1):4-16.

Deplin.com.Deplin capsules.

American Psychiatric Publishing, Inc.Medication information for parents and teachers: L-methylfolate—Deplin.

Hardin A, Baldwin-Sayre C.L-methylfolate as a monotherapy for treatment-resistant depression: A case study.Integr Med (Encinitas). 2020;19(4):14-18.

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