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L-methylfolate and Depression

Depression: What Is It?

Depression may include different symptoms and usually lasts longer than 2 weeks. Depression is believed to be caused by an imbalance of chemicals in the brain that are linked to mood. The scientific name for these chemicals is neurotransmitters. Their job is to send messages to brain cells. Depressive symptoms may occur if the neurotransmitters do not work properly. Serotonin, norepinephrine and dopamine are different types of neurotransmitters.

Your doctor may choose a therapy that targets one or more of these neurotransmitters. It is important to share all of your symptoms so your doctor can choose the best therapy. Some depressive symptoms you may experience and should tell your doctor about include:

  • Sadness, hopelessness or the inability to feel pleasure
  • Feeling tired, tearful or discouraged
  • Irritability, anxiousness or low energy levels
  • Lack of concentration or motivation
2 out of 3 depressed individuals may not adequately respond to their antidepressants.¹

The Role of L-methylfolate in Depression

One theory of depression is that the brain is not developing enough neurotransmitters. This may be due to insufficient amounts of L-methylfolate in the brain.2 L-methylfolate is needed to regulate serotonin, norepinephrine and dopamine production. Without enough L-methylfolate, it may be difficult to produce enough neurotransmitters for antidepressants to work fully.3

Up to seventy percent of depressed patients may have a specific genetic factor that limits their ability to convert folic acid or folate from food to L-methylfolate.4 Other factors limiting absorption include:5-11

  • Taking certain medications such as lamotrigine, valproate, methotrexate, sulphasalazine, oral contraceptives, metformin, fluoxetine, niacin, fenofibrates and warfarin
  • Other health conditions such as diabetes, atrophic gastritis, Crohn’s, colitis, renal failure and hypothyroidism
  • Lifestyle factors such as excess alcohol consumption, smoking and poor nutrition
  • Aging – L-methylfolate in the brain decreases with age

Deplin® and Depression

Deplin® contains 7.5 mg or 15 mg of L-methylfolate, the only active form of folate that helps the brain balance neurotransmitters affecting mood.2

Deplin® works by providing higher amounts of L-methylfolate in the brain, which is needed by some depressed individuals in order to regulate serotonin, norepinephrine and dopamine.2

Short-term and long-term research studies show that Deplin® is “well-tolerated.” This means that, for most people, Deplin® was no different than placebo in terms of side effects (such as weight gain, insomnia or sexual dysfunction).12,13 Your doctor may prescribe Deplin® once each day. You can take it with or without food.

You may start feeling better as soon as 1 or 2 weeks after taking Deplin®. By 4 to 6 weeks, you and others are likely to notice a big improvement in your mood,14 such as feeling:

  • More motivated, with increased energy and initiative
  • More alert, with better concentration
  • Happier and more social

Talk with your doctor about how long to take Deplin®. Some people benefit from “long-term therapy” (taking Deplin® for up to 12 months). Together, you and your doctor can make a management plan that is best for you.

Deplin® is a medical food, dispensed by prescription, for the clinical dietary management of the metabolic imbalances associated with depression. Use under medical supervision


  1. Trivedi M et al. Am J Psych. 2006;163(1):28-40.
  2. Stahl SM. CNS Spectrums. 2007;12(10):739-744.
  3. Farah A and Shelton R. Primary Psychiatry. 2009;166:1(Suppl 1):1-8.
  4. Kelly CB et al. J Psychopharmacol. 2004;18(4):567-71.
  5. Bottiglieri T. 2005;29:1103-1112.
  6. Stahl, SM. J Clin Psychiatry. 2008. 69;9:1352-1353.
  7. Sobczynska-Malefora A, et al. Blood Coagulation and Fibrinolysis. 2009:20:279-302.
  8. Amilburu A et al.J physiol. Biochem. 2201; 57(2):71-80
  9. PDR® For Nutritional Supplements, 2001;ISBN: 1-56363-364-7:157-67.
  10. Garg R., et al. Am Heart J. 1999; 138:1082-7.
  11. Bolander-Gouaille C, Bottiglieri T., Homocystiene Related Vitamins and Neuropsychiatric Disorders. France: Springer-Verlag; 2003.
  12. Ginsberg LD, Oubre A, Daoud Y. Innov Clin Neurosci. 2011;8(1):19-28.
  13. Fava M, Shelton R, Zajecka J, et al. Poster presented at the 49th Annual Meeting of the American College of Neuropsychopharmacology, Miami Beach, FL.
  14. Papakostas G, et al. Am J Psychiatry 2012;169(12):1267-1274.
  15. deplin

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To see how Deplin® has impacted the lives of individuals like you, view The Deplin® Experience.