{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:57:57Z","timestamp":1760234277165,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Gda\u0144ski Uniwersytet Medyczny","doi-asserted-by":"publisher","award":["ST-02-0039\/07\/221"],"award-info":[{"award-number":["ST-02-0039\/07\/221"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Relationship between depression and magnesium levels is reported. This observational study examined whether serum magnesium concentration change over time of ketamine treatment course, also whether association between magnesium concentrations and treatment response measured with Montgomery-\u00c5sberg Depression Rating Scale (MADRS) score occurs. Moreover, interlink between changes in Young Mania Rating Scale (YMRS) score, somatic comorbidities, and magnesium concentration was studied. Inpatients with major depressive disorder or bipolar disorder were rated weekly by clinician using MADRS and YMRS. Magnesium levels assessments were carried out weekly, before start of ketamine treatment and then every second infusion and one week after last ketamine infusion. The concentration of Mg2+ ions differs depending on the measurement. The Mg2+ concentration in pre-measurement was significantly higher than in measurement after five infusions (p = 0.031) and after seven infusions (p = 0.003). No significant correlation was observed between changes in magnesium serum levels and MADRS or YMRS. The concentration of Mg2+ ion in course of the treatment was not associated with somatic comorbidities. The study supports data for role of magnesium in treatment-resistant depression, particularly related to ketamine treatment, but provides no clear evidence of straightforward association between magnesium serum concentration and treatment response or comorbidity.<\/jats:p>","DOI":"10.3390\/ph14050430","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T22:51:42Z","timestamp":1620255102000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Magnesium in Ketamine Administration in Treatment-Resistant Depression"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5771-5654","authenticated-orcid":false,"given":"Natalia","family":"G\u00f3rska","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-8454","authenticated-orcid":false,"given":"Wies\u0142aw Jerzy","family":"Cuba\u0142a","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-0208","authenticated-orcid":false,"given":"Jakub","family":"S\u0142upski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariusz Stanis\u0142aw","family":"Wiglusz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Ga\u0142uszko-W\u0119gielnik","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateusz","family":"Kawka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Grzegorzewska","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-952 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gelenberg, A.J. (2010). The prevalence and impact of depression. J. Clin. Psychiatry.","DOI":"10.4088\/JCP.8001tx17c"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"McIntyre, R.S., Filteau, M.J., Martin, L., Patry, S., Carvalho, A., Cha, D.S., Barakat, M., and Miguelez, M. (2014). Treatment-resistant depression: Definitions, review of the evidence, and algorithmic approach. J. Affect. Disord.","DOI":"10.1016\/j.jad.2013.10.043"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ionescu, D.F., Rosenbaum, J.F., and Alpert, J.E. (2015). Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues Clin. Neurosci.","DOI":"10.31887\/DCNS.2015.17.2\/dionescu"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gaynes, B., Warden, D., Trivedi, M., Wisniewski, S., Fava, M., and Rush, A.J. (2009). What Did STAR*D Teach Us? Results From a Large-Scale, Practical, Clinical Trial for Patients With Depression. Psychiatr. Serv.","DOI":"10.1176\/appi.ps.60.11.1439"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Berman, R.M., Cappiello, A., Anand, A., Oren, D.A., Heninger, G.R., Charney, D.S., and Krystal, J.H. (2000). Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry.","DOI":"10.1016\/S0006-3223(99)00230-9"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zarate, C.A., Singh, J.B., Carlson, P.J., Brutsche, N.E., Ameli, R., Luckenbaugh, D.A., Charney, D.S., and Manji, H.K. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry.","DOI":"10.1001\/archpsyc.63.8.856"},{"key":"ref_7","unstructured":"Razmjou, S., Litteljohn, D., Rudyk, C., Syed, S., Clarke, M., Pentz, R., Dwyer, Z., and Hayley, S. (2016). The interactive effects of ketamine and magnesium upon depressive-like pathology. Neuropsychiatr. Dis. Treat."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Serafini, G., Howland, R., Rovedi, F., Girardi, P., and Amore, M. (2014). The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review. Curr. Neuropharmacol.","DOI":"10.2174\/1570159X12666140619204251"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Murck, H. (2013). Ketamine, magnesium and major depression\u2014From pharmacology to pathophysiology and back. J. Psychiatr. Res.","DOI":"10.1016\/j.jpsychires.2013.02.015"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Coyle, C.M., and Laws, K.R. (2015). The use of ketamine as an antidepressant: A systematic review and meta-analysis. Hum. Psychopharmacol.","DOI":"10.1002\/hup.2475"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kishimoto, T., Chawla, J.M., Hagi, K., Zarate, C.A., Kane, J.M., Bauer, M., and Correll, C.U. (2016). Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: A meta-analysis of efficacy, safety and time trajectories. Psychol. Med.","DOI":"10.1017\/S0033291716000064"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cuba\u0142a, W.J., Landowski, J., Szyszko, M., and Czarnowski, W. (2014). Magnesium in drug-na\u00efve patients with a short-duration, first episode of major depressive disorder: Impact on psychopathological features. Magnes. Res.","DOI":"10.1016\/j.jad.2013.12.043"},{"key":"ref_13","unstructured":"Serefko, A., Szopa, A., and Poleszak, E. (2016). Magnesium and depression. Magnes. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tarleton, E.K., Littenberg, B., MacLean, C.D., Kennedy, A.G., and Daley, C. (2017). Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180067"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tarleton, E.K., and Littenberg, B. (2015). Magnesium intake and depression in adults. J. Am. Board Fam. Med.","DOI":"10.3122\/jabfm.2015.02.140176"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cheungpasitporn, W., Thongprayoon, C., Mao, M.A., Srivali, N., Ungprasert, P., Varothai, N., Sanguankeo, A., Kittanamongkolchai, W., and Erickson, S.B. (2015). Hypomagnesaemia linked to depression: A systematic review and meta-analysis. Intern. Med. J.","DOI":"10.1111\/imj.12682"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Poleszak, E., Wla\u017a, P., Kedzierska, E., Nieoczym, D., Wr\u00f3bel, A., Fidecka, S., Pilc, A., and Nowak, G. (2007). NMDA\/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacol. Biochem. Behav.","DOI":"10.1016\/j.pbb.2007.07.018"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"G\u00f3rska, N., Cuba\u0142a, W.J., S\u0142upski, J., and Ga\u0142uszko-W\u0119gielnik, M. (2018). Ketamine and magnesium common pathway of antidepressant action. Magnes. Res.","DOI":"10.1684\/mrh.2018.0440"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Singewald, N., Sinner, C., Hetzenauer, A., Sartori, S.B., and Murck, H. (2004). Magnesium-deficient diet alters depression- and anxiety-related behavior in mice\u2014Influence of desipramine and Hypericum perforatum extract. Neuropharmacology.","DOI":"10.1016\/j.neuropharm.2004.08.010"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Szewczyk, B., Szopa, A., Serefko, A., Poleszak, E., and Nowak, G. (2018). The role of magnesium and zinc in depression: Similarities and differences. Magnes. Res.","DOI":"10.1684\/mrh.2018.0442"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Poleszak, E., Wla\u017a, P., Szewczyk, B., K\u0229dzierska, E., Wyska, E., Librowski, T., Szymura-Oleksiak, J., Fidecka, S., Pilc, A., and Nowak, G. (2005). Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice. Pharmacol. Biochem. Behav.","DOI":"10.1016\/j.pbb.2005.03.017"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Begon, S., Pickering, G., Eschalier, A., Mazur, A., Rayssiguier, Y., and Dubray, C. (2001). Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats. Br. J. Pharmacol.","DOI":"10.1038\/sj.bjp.0704354"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Orser, B., Smith, D., Henderson, S., and Gelb, A. (1997). Magnesium deficiency increases ketamine sensitivity in rats. Can. J. Anaesth.","DOI":"10.1007\/BF03013166"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Islam, M.R., Islam, M.R., ShalahuddinQusar, M.M.A., Islam, M.S., Kabir, M.H., Mustafizur Rahman, G.K.M., Islam, M.S., and Hasnat, A. (2018). Alterations of serum macro-minerals and trace elements are associated with major depressive disorder: A case-control study. BMC Psychiatry.","DOI":"10.1186\/s12888-018-1685-z"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Stycze\u0144, K., Siwek, M., Sowa-Ku\u0107ma, M., Dudek, D., Reczy\u0144ski, W., Szewczyk, B., Misztak, P., Top\u00f3r-M\u0105dry, R., Opoka, W., and Nowak, G. (2015). The serum magnesium concentration as a potential state marker in patients with unipolar affective disorder. Psychiatr. Pol.","DOI":"10.12740\/PP\/OnlineFirst\/44137"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cardoso, C.C., Lobato, K.R., Binfar\u00e9, R.W., Ferreira, P.K., Rosa, A.O., Santos, A.R.S., and Rodrigues, A.L.S. (2009). Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog. Neuro-Psychopharmacol. Biol. Psychiatry.","DOI":"10.1016\/j.pnpbp.2008.11.007"},{"key":"ref_27","unstructured":"Barrag\u00e1n-Rodr\u00edguez, L., Rodr\u00edguez-Mor\u00e1n, M., and Guerrero-Romero, F. (2008). 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."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Eby, G.A., and Eby, K.L. (2006). Rapid recovery from major depression using magnesium treatment. Med. Hypotheses.","DOI":"10.1016\/j.mehy.2006.01.047"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nechifor, M. (2009). Magnesium in major depression. Magnes. Res.","DOI":"10.1684\/mrh.2009.0177"},{"key":"ref_30","first-page":"1209","article-title":"Effects of ketamine on sensory perception: Evidence for a role of N- methyl-D-aspartate receptors","volume":"260","author":"Oye","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rabiner, E.A. (2007). Imaging of striatal dopamine release elicited with NMDA antagonists: Is there anything there to be seen?. J. Psychopharmacol.","DOI":"10.1177\/0269881107077767"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Morgan, C.J.A., and Curran, H.V. (2012). Ketamine use: A review. Addiction.","DOI":"10.1111\/j.1360-0443.2011.03576.x"},{"key":"ref_33","first-page":"554","article-title":"Efficacy of ketamine in bipolar depression: Focus on anhedonia","volume":"31","author":"Wiglusz","year":"2019","journal-title":"Psychiatr. Danub."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lally, N., Nugent, A.C., Luckenbaugh, D.A., Ameli, R., Roiser, J.P., and Zarate, C.A. (2014). Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl. Psychiatry.","DOI":"10.1038\/tp.2014.105"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cao, B., Zhu, J., Zuckerman, H., Rosenblat, J.D., Brietzke, E., Pan, Z., Subramanieapillai, M., Park, C., Lee, Y., and McIntyre, R.S. (2019). Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic review. Prog. Neuro-Psychopharmacol. Biol. Psychiatry.","DOI":"10.1016\/j.pnpbp.2019.01.002"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"W\u0142odarczyk, A., and Cuba\u0142a, W.J. (2020). Safety and tolerability of ketamine use in treatment-resistant bipolar depression patients with regard to central nervous system symptomatology: Literature review and analysis. Medicina, 56.","DOI":"10.3390\/medicina56020067"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Trivedi, M.H., Corey-Lisle, P.K., Guo, Z., Lennox, R.D., Pikalov, A., and Kim, E. (2009). Remission, response without remission, and nonresponse in major depressive disorder: Impact on functioning. Int. Clin. Psychopharmacol.","DOI":"10.1097\/YIC.0b013e3283277614"},{"key":"ref_38","unstructured":"Romeo, V., Cazzaniga, A., and Maier, J.A.M. (2019). Magnesium and the blood-brain barrier in vitro: Effects on permeability and magnesium transport. Magnes. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ryan, M.F., and Barbour, H. (1998). Magnesium measurement in routine clinical practice. Ann. Clin. Biochem.","DOI":"10.1177\/000456329803500401"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/5\/430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:56:50Z","timestamp":1760162210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/5\/430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,3]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ph14050430"],"URL":"https:\/\/doi.org\/10.3390\/ph14050430","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2021,5,3]]}}}