EC Nutrition

Aim: Current treatment options for depression have remained unsatisfactory because some patients experience symptoms even after completing multiple antidepressants and more aggressive treatments, besides experiencing side effects and uncertain adherence. Several studies have shown an association between magnesium and depression but have not consistently shown significant results.

Methods: Ninety subjects with moderate or severe major depressive disorder were randomized into a double-blind placebo-controlled trial to receive a treatment of 200 mg of magnesium glycinate or placebo tablets twice daily orally with selective serotonin reuptake inhibitors for the 8 weeks intervention period. Subjects were assessed with the Depression Anxiety Stress Scale 21 items Bangla Version for depression symptoms at baseline, at the end of the 4 weeks, and at the end of the 8 weeks intervention, and to evaluate the appearance of adverse effects.

Results: Supplementation of oral magnesium glycinate for 8 weeks resulted in a significant reduction in Depression Anxiety Stress Scale 21 items score from baseline (P < 0.05) and this reduction was observed from the end of 4 weeks treatment. Also, at the end of 8 weeks, the Depression Anxiety Stress Scale 21 items score was significantly lower than that of the control arm (P = 0.02). No changes were noted in the reporting of adverse effects while on the treatment.

Conclusion: Magnesium glycinate significantly reduces symptoms in moderate to severe depression, works quickly, and is well tolerated; this result is consistent with the literature. The link between changes in the Depression Anxiety Stress Scale 21 items and the severity of depression symptoms supports the idea that magnesium glycinate could be utilized to treat major depressive disorder, a persistent medical problem.

Trial was registered in the ClinicalTrials.gov with the trial ID number NCT04880460.

Keywords: Control; DASS-21; Depression; Intervention; Magnesium; SSRIs

1. World Health Organization. Depression and other common mental disorders: global health estimates. Geneva: World Health Organization (2017).
2. World Health Organization. Bangladesh WHO Special Initiative for Mental Health Situational Assessment. WHO (2020).
3. Roth GA., et al. “Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study”. Lancet10159 (2017): 1736-1788.
4. World Health Organization. The World Health Report 2004: Changing History, Annex Table 3: Burden of Disease in DALYs by Cause, Sex, and Mortality Stratum in WHO Regions, Estimates for 2002. World Health Organization, Geneva (2004).
5. Alvarez-Mon MA., et al. “Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects”. Pharmaceuticals8 (2021): e14080821.
6. Papakostas GI., et al. “Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a pilot and replication study”. Molecular Psychiatry3 (2013): 332-339.
7. Lv X., et al. “The establishment of the objective diagnostic markers and personalized medical intervention in patients with major depressive disorder: rationale and protocol”. BMC Psychiatry1 (2016): 1-10.
8. Moret C and Briley M. “The importance of norepinephrine in depression”. Neuropsychiatric Disease and Treatment1 (2011): 9-13.
9. Anderson HD., et al. “Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: a retrospective US claims study”. Clinical Therapeutics1 (2012): 113-123.
10. Bondolfi G., et al. “A stepwise drug treatment algorithm to obtain complete remission in depression: a Geneva study”. Swiss Medical Weekly5-6 (2006): 78-85.
11. Keller MB., et al. “Time to recovery, chronicity, and levels of psychopathology in major depression: a 5-year prospective follow-up of 431 subjects”. Archives of General Psychiatry10 (1992): 809-816.
12. Keller MB., et al. “Relapse in major depressive disorder: analysis with the life table”. Archives of General Psychiatry8 (1982): 911-915.
13. Malhi GS., et al. “Treatment-resistant depression: resistant to definition?” Acta Psychiatrica Scandinavica4 (2005): 302-309.
14. Rush AJ., et al. “Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report”. The American Journal of Psychiatry11 (2006): 1905-1917.
15. Li Z., et al. “Major depressive disorder: advances in neuroscience research and translational applications”. Neuroscience Bulletin6 (2021): 863-880.
16. Botturi A., et al. “The role and the effect of magnesium in mental disorders: a systematic review”. Nutrients6 (2020): 1-19.
17. Khan F., et al. “Vitamin B6 and magnesium on neurobehavioral status of autism spectrum disorder: a randomized, double-blind, placebo controlled study”. The Korean Journal of Internal Medicine1 (2021): 12-18.
18. Kirkland AE., et al. “The role of magnesium in neurological disorders”. Nutrients6 (2018): e10060730.
19. Ranade VV and Somberg JC. “Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans”. American Journal of Therapeutics5 (2001): 345-357.
20. Serefko A., et al. “Magnesium in depression”. Pharmacological Reports3 (2013): 547-554.
21. Eby GA and Eby KL. “Rapid recovery from major depression using magnesium treatment”. Medical Hypotheses 67.2 (2006): 362-370.
22. Camardese G., et al. “Plasma magnesium levels and treatment outcome in depressed patients”. Nutritional Neuroscience2 (2012): 78-84.
23. Tarleton EK and Littenberg B. “Magnesium intake and depression in adults. The Journal of the American Board of Family Medicine”. Journal of the American Board of Family Medicine2 (2015): 249-256.
24. Yary T., et al. “Dietary magnesium intake and the incidence of depression: A 20-year follow-up study”. Journal of Affective Disorders 193 (2016): 94-98.
25. Ryszewska-Pokras´niewicz B., et al. “Effects of magnesium supplementation on unipolar depression: a placebo-controlled study and review of the importance of dosing and magnesium status in the therapeutic response”. Nutrients8 (2018): e10081014.
26. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5); American Psychiatric Pub: Washington, DC, USA (2020): 213.
27. Lovibond PF and Lovibond SH. “The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories”. Behaviour Research and Therapy3 (1995): 335-343.
28. Lovibond SH and Lovibond PF. Overview of the DASS and its uses (2009): 15.
29. Antony MM., et al. “Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales in clinical groups and a community sample”. Psychological Assessment2 (1998): 176-181.
30. Alim SA., et al. “Translation of DASS 21 into Bangla and validation among medical students”. Bangladesh Journal of Psychiatry2 (2014): 67-70.
31. Guerrera MP., et al. “Therapeutic uses of magnesium”. American Family Physician2 (2009): 157-162.
32. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for calcium, phosphorous, magnesium, vitmain D, and flouride. Washington, DC: National Academy Press (1997): 190-249.
33. Tarleton EK., et al. “The association between serum magnesium levels and depression in an adult primary care population”. Nutrients7 (2019): e11071475.
34. Tarleton EK., et al. “Role of magnesium supplementation in the treatment of depression: A randomized clinical trial”. PLoS One6 (2017): e0180067.
35. Bagis S., et al. “Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?” Rheumatology International1 (2013): 167-172.
36. Barragan-Rodriguez L., et al. “Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial”. Magnesium Research4 (2008): 218-223.
37. Rajizadeh A., et al. “Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial”. Nutrition 35 (2017): 56-60.
38. Mehdi SM., et al. “Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression”. Psychiatry and Clinical Neurosciences3 (2017): 204-211.
39. Nutting PA., et al. “Barriers to initiating depression treatment in primary care practice”. Journal of General Internal Medicine2 (2002): 103-111.