Role of magnesium supplementation in the treatment of depression: A randomized clinical trial

Abstract

Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression. An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.

Pharmacological signatures of the reduced incidence and the progression of cognitive decline in ageing populations suggest the protective role of beneficial polypharmacy

“…These conclusions were produced based on the analysis of > 50000 patients, > 1900 dosage forms and > 300 clinical trials linked in a single alignment presented earlier (Tables 1 and 2). The mechanisms at the highest tier of database signals in Table 1 and Files A-C in S1 Data (Mg+2, Zn+2, Se, biotin, chromium picolinate, vitamin A-lutein) are traditionally prescribed as life-extending or preventing retinal degeneration and substantial evidence of mechanistic involvement or clinical efficiency are available for each, including successful controlled clinical trials or successful treatment of organic neurological conditions in humans, based on incremental definition of "success" ( [63][64][65][66][67][68][69][70][71][72], Tables 1 and 2).…”

“…But our data in > 50000 patients indicate strong negative correlation between complex combinations of factors analogous to those in [72][73][74][75] and dementia prevalence. This argues against insufficient trial sizes in [69][70][71][72][73][74][75] as the reason for the observations, plus the results can be pooled as produced by similar multi-component methodologies. Specifically, MEND involves multiple subgroups recruited in the study over multiple years.…”

“…On the other side, analgesics (0.45, 46 df), corticosteroids (0.34, 42 df), anti-acid (0.45, 16 df), anti-arrythmic (0.55, 13 df), antibiotics (0.5, 5 df), anti-cancer therapies (0.25, 29 df), statins (0.6, 13 df), antidepressants (0.45, 17 df), antifungals (0.4, 19 df), overall antihypertensives (0.9, 28 df), bronchodilators (0.6, 17 df) display the opposite trend of distributing in favour of the lower Z-score octiles. Thus, PDE5 inhibitors [42], antiplatelet [43,44], vasodilators [43,45], antimigraine [38,39], antivirals [46], probiotics [47], magnesium [48,49], transdermal oestrogen ( Table 2) and possibly metformin [40,41,50,51] are the agents of interest to perhaps combine with the multivitamin-multimineral formulas of Table 2. Conversely, the signals by corticosteroids [52,53], anti-cancer therapies [54,55], anti-acid drugs [56,57], infections underlying use of antibiotics and antifungals [58], the link between dementia and respiratory deficiency [59], between dementia and cardiac arrythmia [44] mostly align with outside evidence of involvement in neurodegeneration.…”

The Role of Iron, Zinc, Copper and Magnesium in the Prevention and Treatment of Depression

“…Ancak, takviye yapılmayan süreçte bir değişiklik görülmemiştir. 65 Öte yandan, 2016 senesinde yapılan bir kohort çalışmasında, depresyonu olan 837 katılımcının magnezyum alımları incelendiğinde, depresyon oluşumu ile magnezyum alımı arasında herhangi bir bağlantı bulunamamıştır. 66 Ancak, 1984 senesinde Finlandiya'da başlamış ve 20 sene devam etmiş olan, 2.320 erkeğin magnezyum alımları ve depresif semptomları arasında bir ilişki olup olmadığının incelendiği bir kohort çalışmasının gösterdiği üzere, diyetle magnezyum alımı ve depresyon tanısı arasında bir ters ilişki olabilir.…”

Total and Ionized Calcium and Magnesium Are Significantly Lowered in Drug-Na&iuml;ve Depressed Patients: Effects of Antidepressants and Associations with Immune Activation

“…Zieba et al, 2000;Cheungpasitporn et al, 2015) and that the incidence of hypomagnesemia is elevated in depressed patients as compared with controls(Levine et al, 1999). Chronic stress, alcohol abuse and diets rich in carbohydrates and fats may cause prolonged Mg deficiency leading to development of depressive symptoms(Tarleton et al, 2017), suggesting that reducedMg levels participate in the pathophysiology of MDD (Rajizadeh et al, 2016; Islam et al, 2018). Possible causes of the lowered Mg levels in MDD are decreased appetite and Mg-impoverished diets (Jacka et al, 2009), whereas Mg rich diets may reduce depressive symptoms (Derom et al, 2013).…”