Role of magnesium in major depressive disorder
DOI:
https://doi.org/10.3329/bjp.v20i2.81249Keywords:
Magnesium, Major depressive disorder, Mini-reviewAbstract
Major depressive disorder, a common and complex disorder, has its onset associated with many factors. Common management includes antidepressant agents, together with psychotherapy in severe cases, but a significant percentage of patients do not improve. The urgency of newer approaches is a need, and clinical trials are studying the role of magnesium in depression. However, findings are inconclusive. To evaluate the evidence about the effects of magnesium on adults with depression, a systematic review was conducted. The search was conducted using scientific records from online databases between 2000 to 2023 concerning magnesium in depression. Eight studies showed mainly positive results; three studies after magnesium add-on with traditional antidepressants, and two studies showed no improvement. The review's evidence suggested that magnesium supplementation might be effective. Therefore, further clinical trials must be designed to evaluate the efficacy of magnesium alone or in addition to other therapies following biochemical assessments.
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References
Abiri B, Sarbakhsh P, Vafa M. Randomized study of the effects of vitamin D and/or magnesium supplementation on mood, serum levels of BDNF, inflammation, and SIRT1 in obese women with mild to moderate depressive symptoms. Nutr Neurosci. 2022; 25: 2123-35.
Afsharfar M, Shahraki M, Shakiba M, Asbaghi O, Dashipour A. The effects of magnesium supplementation on serum level of brain derived neurotrophic factor (BDNF) and depression status in patients with depression. Clin Nutr ESPEN. 2021; 42: 381-86.
Alvarez-Mon MA, Ortega MA, García-Montero C, Fraile-Martinez O, Monserrat J, Lahera G, Mora F, Rodriguez-Quiroga A, Fernandez-Rojo S, Quintero J, Alvarez-Mon M. Exploring the role of nutraceuticals in major depressive disorder (MDD): Rationale, state of the art and future prospects. Pharmaceuticals 2021; 14: 821.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). Texas, American Psychiatric Association, 2013.
Anderson HD, Pace WD, Libby AM, West DR, Valuck RJ. Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: A retrospective US claims study. Clin Ther. 2012; 34: 113-23.
Ang AW, Ko SM, Tan CH. Calcium, magnesium, and psycho-tic symptoms in a girl with idiopathic hypoparathyroidism. Psychosom Med. 1995; 57: 299-302.
Bagis S, Karabiber M, As I, Tamer L, Erdogan C, Atalay A. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia? Rheumatol Int. 2013; 33: 167-72.
Bajpai A, Verma AK, Srivastava M, Srivastava R. Oxidative stress and major depression. J Clin Diagn Res. 2014; 8: CC04-07.
Barragan-Rodríguez L, Rodriguez-Morán M, Guerrero-Romero F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: A randomized, equivalent trial. Magnes Res. 2008; 21: 218-23.
Bondolfi G, Aubry JM, Golaz J, Gex-Fabry M, Gervasoni N, Bertschy G. A stepwise drug treatment algorithm to obtain complete remission in depression: A Geneva study. Swiss Med Wkly. 2006; 136: 78-85.
Booij SH, Bos EH, de Jonge P, Oldehinkel AJ. Markers of stress and inflammation as potential mediators of the relationship between exercise and depressive symptoms: Findings from the TRAILS study. Psychophysiology 2015; 52: 352-58.
Botturi A, Ciappolino V, Delvecchio G, Boscutti A, Viscardi B, Brambilla P. The role and the effect of magnesium in mental disorders: A systematic review. Nutrients 2020; 12: 1661.
Camardese G, De Risio L, Pizi G, Mattioli B, Buccelletti F, Serrani R, Leone B, Sgambato A, Bria P, Janiri L. Plasma magnesium levels and treatment outcome in depressed patients. Nutr Neurosci. 2012; 15: 78-84.
Castilho RF, Ward MW, Nicholls DG. Oxidative stress, mitochondrial function, and acute glutamate excitotoxicity in cultured cerebellar granule cells. J Neurochem. 1999; 72: 1394-01.
Chandley MJ, Szebeni A, Szebeni K, Crawford JD, Stockmeier CA, Turecki G, Kostrzewa RM, Ordway GA. Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression. Int J Neuropsychopharmacol. 2014; 17: 1569-78.
De Souza MC, Walker AF, Robinson PA, Bolland K. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: A randomized, double-blind, crossover study. J Women Health Gend Based Med. 2000; 9: 131-39.
Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006; 67: 362-70.
Elhai JD, Contractor AA, Tamburrino M, Fine TH, Prescott MR, Shirley E, Chan PK, Slembarski R, Liberzon I, Galea S, Calabrese JR. The factor structure of major depression symptoms: A test of four competing models using the Patient Health Questionnaire-9. Psychiatry Res. 2012; 199: 169-73.
Elia M, Normand C, Laviano A, Norman K. A systematic review of the cost and cost effectiveness of using standard oral nutritional supplements in community and care home settings. Clin Nutr. 2016; 35: 125-37.
Fard FE, Mirghafourvand M, Mohammad-Alizadeh Charan-dabi S, Farshbaf-Khalili A, Javadzadeh Y, Asgharian H. Effects of zinc and magnesium supplements on postpartum depression and anxiety: A randomized controlled clinical trial. Women Health. 2016; 57: 1115-28.
Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF. The efficacy and safety of nutrient supplements in the treatment of mental disorders: A meta‐review of meta‐analyses of randomized controlled trials. World Psychiatry. 2019; 18: 308-24.
Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for calcium, phosphorous, magnesium, vitmain D, and flouride. Washington DC, National Academy Press, 1997, pp 190-49.
Gartlehner G, Hansen RA, Carey TS, Lohr KN, Gaynes BN, Randolph LC. Discontinuation rates for selective serotonin reuptake inhibitors and other second-generation antidepressants in outpatients with major depressive disorder: A systematic review and meta-analysis. Int Clin Psychopharmacol. 2005; 20: 59-69.
Gray AL, Hyde TM, Deep-Soboslay A, Kleinman JE, Sodhi MS. Sex differences in glutamate receptor gene expression in major depression and suicide. Mol Psychiatry. 2015; 20: 1057-68.
Guerrera MP, Volpe SL, Mao JJ. Therapeutic uses of magne-sium. Am Fam Physician. 2009; 80: 157-62.
Guidi J, Fava GA. Sequential combination of pharmacotherapy and psychotherapy in major depressive disorder: A systematic review and meta-analysis. JAMA Psychiatry. 2021; 78: 261-69.
Gullander M, Hogh A, Hansen ÅM, Persson R, Rugulies R, Kolstad HA, Thomsen JF, Willert MV, Grynderup M, Mors O, Bonde JP. Exposure to workplace bullying and risk of depression. J Occup Environ Med. 2014; 56: 1258-65.
Hale A, Corral RM, Mencacci C, Ruiz JS, Severo CA, Gentil V. Superior antidepressant efficacy results of agomelatine versus fluoxetine in severe MDD patients: A randomized, double-blind study. Int Clin Psychopharmacol. 2010; 25: 305-14.
Hirschfeld RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry. 2000; 61: 4-6.
Horwitz, A.V., Wakefield, J.C. and Lorenzo-Luaces, L. History of depression. The Oxford handbook of mood disorders. 2016, pp 11-23.
Hosain GM, Chatterjee N, Ara N, Islam T. Prevalence, pattern and determinants of mental disorders in rural Bangladesh. Public Health. 2007; 121: 18-24.
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012; 5: i3-14.
Keller MB, Lavori PW, Mueller TI, Endicott J, Coryell W, Hirschfeld RM, Shea T. Time to recovery, chronicity, and levels of psychopathology in major depression: A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry. 1992; 49: 809-16.
Keller MB, Shapiro RW, Lavori PW, Wolfe N. Relapse in major depressive disorder: Analysis with the life table. Arch Gen Psychiatry. 1982; 39: 911-15.
Kirkland AE, Sarlo GL, Holton KF. The role of magnesium in neurological disorders. Nutrients 2018; 10: 730.
Krause JS, Reed KS, McArdle JJ. Factor structure and predictive validity of somatic and nonsomatic symptoms from the patient health questionnaire-9: A longitudinal study after spinal cord injury. Arch Phys Med Rehabil. 2010; 91: 1218-24.
Kronbauer M, Metz VG, Roversi K, Dias VT, de David Antoniazzi CT, da Silva Barcelos RC, Burger ME. Influence of magnesium supplementation on movement side effects related to typical antipsychotic treatment in rats. Behav Brain Res. 2017; 320: 400-11.
Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: A systematic review and meta-ana-lysis of observational studies. Mol Psychiatry. 2019; 24: 965-86.
Li Z, Ruan M, Chen J, Fang Y. Major depressive disorder: Advances in neuroscience research and translational applications. Neurosci Bull. 2021; 37: 863-80.
Li Z, Zhang Y, Wang Z, Chen J, Fan J, Guan Y, Zhang C, Yuan C, Hong W, Wang Y, Wu Z. The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: Data from multicenter, prospective, longitudinal clinic practice. J Psychiatr Res. 2013; 47: 8-14.
Lv X, Si T, Wang G, Wang H, Liu Q, Hu C, Wang J, Su Y, Huang Y, Jiang H, Yu X. The establishment of the objective diagnostic markers and personalized medical intervention in patients with major depressive disorder: Rationale and protocol. BMC Psychiatry. 2016; 16: 1-10.
Malhi GS, Parker GB, Crawford J, Wilhelm K, Mitchell PB. Treatment‐resistant depression: Resistant to definition? Acta Psychiatr Scand. 2005; 112: 302-09.
Marcus, M., Yasamy, M.T., van Ommeren, M.V., Chisholm, D. and Saxena, S. Depression: A global public health concern. 2012 [Available at: http://www.who.int/mental_health/management/depression/who_paper_depression_fmh_ 2012.pdf, accessed on December 19, 2021].
Mehdi SM, Atlas SE, Qadir S, Musselman D, Goldberg S, Woolger JM, Corredor R, Abbas MH, Arosemena L, Caccamo S, Campbell CS. Double‐blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment‐resistant depression. Psychiatry Clin Neurosci. 2017; 71: 204-11.
Moabedi M, Aliakbari M, Erfanian S, Milajerdi A. Magnesium supplementation beneficially affects depression in adults with depressive disorder: A systematic review and meta-analysis of randomized clinical trials. Front Psychiatry. 2023; 14: 1-7.
Moher D, Liberati A, Tetzla J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009; 6: 1-6.
Moret C, Briley M. The importance of norepinephrine in depre-ssion. Neuropsychiatr Dis Treat. 2011; 7: 9-13.
Nazarinasab M, Behrouzian F, Abdi L, Moghaddam AA, Sade-ghi S. Investigating the effect of magnesium supplement in patients with major depressive disorder under selective serotonin reuptake inhibitor treatment. J Family Med Prim Care. 2022; 11: 7800-05.
Noah L, Dye L, Bois De Fer B, Mazur A, Pickering G, Pouteau E. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post‐hoc analysis of a randomised controlled trial. Stress Health. 2021; 37: 1000-09.
Ordak M, Muszynska E, Nasierowski T, Maj-Zurawska M, Bujalska-Zadrozny M. Level of magnesium in psychiatry- What is the cause of ambiguous results? Gen Hosp Psychia-try. 2017; 51: 136.
Phelan D, Molero P, Martínez-González MA, Molendijk M. Magnesium and mood disorders: Systematic review and meta-analysis. BJPsych Open. 2018; 4: 167-79.
Philipson TJ, Snider JT, Lakdawalla DN, Stryckman B, Goldman DP. Impact of oral nutritional supplementation on hospital outcomes. Am J Manag Care. 2013; 19: 121-28.
Pochwat B, Szewczyk B, Sowa-Kucma M, Siwek A, Dobos-zewska U, Piekoszewski W, Gruca P, Papp M, Nowak G. Antidepressant-like activity of magnesium in the chronic mild stress model in rats: Alterations in the NMDA receptor subunits. Int J Neuropsychopharmacol. 2014; 17: 393-05.
Qaseem A, Barry MJ, Kansagara D, Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016; 164: 350-59.
Racagni G, Popoli M. Cellular and molecular mechanisms in the long-term action of antidepressants. Dialogues Clin Neurosci. 2008; 10: 385-400.
Rajizadeh A, Mozaffari-Khosravi H, Yassini-Ardakani M, Deh-ghani A. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition 2017; 35: 56-60.
Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, Abdela J, Abdelalim A, Abdollahpour I. 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 2017. Lancet 2018; 392: 1736-88.
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR* D report. Am J Psychiatry. 2006; 163: 1905-17.
Ryan MF. The role of magnesium in clinical biochemistry: An overview. Ann Clin Biochem. 1991; 28: 19-26.
Ryszewska-Pokrasniewicz B, Mach A, Skalski M, Januszko P, Wawrzyniak ZM, Poleszak E, Nowak G, Pilc A, Radziwoń-Zaleska M. 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. Nutrients 2018; 10: 1014.
Serefko A, Szopa A, Wlaź P, Nowak G, Radziwoń-Zaleska M, Skalski M, Poleszak E. Magnesium in depression. Pharmacol Rep. 2013; 65: 547-54.
Seyama T, Kamei Y, Iriyama T, Imada S, Ichinose M, Toshi-mitsu M, Fujii T, Asou H. Pretreatment with magnesium sulfate attenuates white matter damage by preventing cell death of developing oligodendrocytes. J Obstet Gynaecol Res. 2018, 44: 601-07.
Spasov AA, Iezhitsa IN, Kravchenko MS, Kharitonova MV. Features of central neurotransmission in animals in conditions of dietary magnesium deficiency and after its correction. Neurosci Behav Physiol. 2009; 39: 645-53.
Stangherlin A, O’Neill JS. Signal transduction: Magnesium manifests as a second messenger. Curr Biol. 2018; 28: R1403-05.
Sultana S, Rahman MS. Effect of magnesium supplementation in selective serotonin reuptake inhibitors treated major depressive disorder patients: A randomized, double-blind, placebo-controlled trial. EC Nutr. 2023; 18: 25-34.
Sun Q, Weinger JG, Mao F, Liu G. Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration. Neuropharmacology 2016; 108: 426-39.
Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PloS One. 2017; 12: e0180067.
Tarleton EK, Littenberg B. Magnesium intake and depression in adults. J Am Board Fam Med. 2015; 28: 249-56.
Veronese N, Demurtas J, Pesolillo G, Celotto S, Barnini T, Calusi G, Caruso MG, Notarnicola M, Reddavide R, Stubbs B, Solmi M. Magnesium and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr. 2020; 59: 263-72.
Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ, Coggeshall M. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388: 1545-02.
World Health Organization (WHO). Bangladesh WHO Special Initiative for Mental Health Situational Assessment. 2020. [Available at: https://www.who.int, accessed on July 28, 2022].
World Health Organization (WHO). Depression and other common mental disorders: Global health estimates (No. WHO/MSD/MER/2017.2). 2017. [Available at: https://apps.who.int, accessed on June 30, 2022].
Yary T, Lehto SM, Tolmunen T, Tuomainen TP, Kauhanen J, Voutilainen S, Ruusunen A. Dietary magnesium intake and the incidence of depression: A 20-year follow-up study. J Affect Disord. 2016; 193: 94-98.
Zhang JJ, Gao TT, Wang Y, Wang JL, Guan W, Wang YJ, Wang CN, Liu JF, Jiang B. Andrographolide exerts significant antidepressant-like effects involving the hippocampal BDNF system in mice. Int J Neuropsychopharmacol. 2019; 22: 585-600.
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