Magnesium Bisglycinate in Major Depressive Disorder

Официальное название

Efficacy and Safety of Add-on Magnesium Bisglycinate in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Обзор

Depression is a common illness that can affect a person's mood, sleep, energy, ability to work, and overall quality of life. While medicines are available to treat depression, many people do not get complete relief from their symptoms. This study will evaluate whether adding a magnesium supplement in the form of magnesium bisglycinate to regular antidepressant treatment can help improve symptoms of depression. Adults with depression who are already receiving treatment will be randomly assigned to receive either magnesium bisglycinate or a placebo (an inactive substance) along with their usual medication. The study will compare the two groups to see whether the supplement leads to greater improvement in symptoms, sleep, and day-to-day functioning. Information on any side effects will also be collected. The findings may help determine whether magnesium bisglycinate can be used as a safe and affordable additional treatment for people with depression.

Подробное описание

The DREAM-BiG (Depression REsponse to Adjunctive Magnesium-BisGlycinate) study is a single-centre, randomized, double-blind, placebo-controlled, parallel-arm academic clinical trial designed to evaluate the efficacy and safety of adjunctive magnesium bisglycinate in adults with Major Depressive Disorder (MDD) receiving stable standard-of-care antidepressant therapy. The study will be conducted in the Departments of Pharmacology and Psychiatry at AIIMS Bhubaneswar. Eligible participants will be men and women aged 18-65 years with a DSM-5 diagnosis of MDD and mild-to-severe depressive symptoms, defined by a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥7, who are receiving a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Following written informed consent, participants will undergo detailed clinical evaluation, anthropometric assessment, and baseline measurement of clinical and biochemical parameters. A total of 84 participants will be randomization using computer-generated block randomization with a block size of six and a 2:1 allocation ratio favoring the intervention arm. Allocation concealment will be ensured through sequentially numbered, identical-appearing capsule containers, and participants, treating psychiatrists, outcome assessors, and investigators will remain blinded to treatment allocation throughout the study. Participants in the intervention group will receive magnesium bisglycinate capsules providing 220 mg elemental magnesium daily, while those in the control group will receive matching placebo capsules containing microcrystalline cellulose; both interventions will be administered as add-on therapy for 8 weeks alongside ongoing antidepressant treatment. Clinical assessments will be conducted at baseline and Week 8 using validated rating scales, including MADRS for depressive symptoms, Hamilton Anxiety Rating Scale (HAM-A) for anxiety, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) for sleep-related outcomes, and Clinical Global Impression scales (CGI-S and CGI-I) for overall clinical status. Blood samples will be collected at baseline and follow-up for estimation of serum magnesium, glycine, and brain-derived neurotrophic factor (BDNF). Treatment-emergent adverse events will be actively monitored throughout the study, with severity and causality assessed using standardized pharmacovigilance tools. Statistical analyses will compare changes from baseline to Week 8 between study groups, with change in MADRS score serving as the primary efficacy endpoint.

Вмешательства

• Пищевая добавка Magnesium Bisglycinate
  Magnesium Bisglycinate (220 mg elemental mangnesium and 1350 mg glycine) per day for 8 weeks
• Другое Microcrystalline cellulose
  The placebo capsules will contain Microcrystalline cellulose (inactive excipient) and will be of similar colour, shape and size as of magnesium bisglycinate capsules and will be given once daily for 8 weeks.

Первичные конечные точки

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score [Срок оценки: Baseline (week 0) and follow-up (week 8)]

Вторичные конечные точки (9)

• Change in Hamilton Anxiety Rating Scale (HAM-A) score [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Change in Pittsburgh Sleep Quality Index (PSQI) score [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Change in Epworth Sleepiness Scale (ESS) score [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Change in Clinical Global Impression Severity (CGI-S) score [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Clinical Global Impression Improvement (CGI-I) [Срок оценки: Week 8]
• Change in serum brain-derived neurotrophic factor (BDNF) [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Change in serum magnesium [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Change in serum glycine [Срок оценки: Baseline (week 0) and follow-up (week 8)]
• Incidence of Treatment-emergent adverse events (TEAEs) [Срок оценки: week 4 and week 8]

Критерии участия

Критерии включения

• Patients with a diagnosis of Major Depressive Disorder (MDD) as per DSM-5 criteria.
• Patients of either sex within the age group of 18-65 years.
• Mild to severe depression, defined as a baseline MADRS score ≥7.
• Currently receiving a stable dose of antidepressant monotherapy (SSRI or SNRI) in equivalent doses.
• Willing and able to provide written informed consent.

Критерии исключения

• Known hypersensitivity or allergy to magnesium supplements or glycine.
• History of renal impairment (previous history of AKI, CKD, currently on dialysis).
• Diagnosis of bipolar affective disorder, schizoaffective disorder, schizophrenia, or any other psychotic disorder.
• Active suicidal ideation with intent or a recent suicide attempt (within the past 6 months), as assessed by the treating psychiatrist.
• Current substance use disorder (except nicotine, alcohol and caffeine), as per DSM-5 criteria.
• Pregnancy, lactation, or women of childbearing potential not using adequate contraception.
• Concurrent use of magnesium-containing supplements, antacids, or laxatives.
• History of significant severe medical comorbidity, including uncontrolled hypothyroidism, Cushing's syndrome, active malignancy, myasthenia gravis, or severe hepatic impairment.
• Use of medications with significant pharmacokinetic interactions with magnesium (e.g., tetracyclines, fluoroquinolones, bisphosphonates, diuretics) that cannot be temporally separated by ≥2 hours.
• Electroconvulsive therapy (ECT) received within the past 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Индия · 1 центр

• All India Institute of Medical Sciences (AIIMS) — Bhubaneswar

Публикации

• Riemann D, Krone LB, Wulff K, Nissen C. Sleep, insomnia, and depression. Neuropsychopharmacology. 2020 Jan;45(1):74-89. doi: 10.1038/s41386-019-0411-y. Epub 2019 May 9. PMID 31071719
• Tripathi A, Shukla R, Kar SK, Gupta S, Saran P, Pattojoshi A, Rao T. Clinical practice guideline for assessment and management of depression in India. Indian J Psychiatry. 2026 Jan;68(1):68-93. doi: 10.4103/indianjpsychiatry_1321_25. Epub 2026 Jan 27. PMID 41694045
• Wichniak A, Wierzbicka A, Walecka M, Jernajczyk W. Effects of Antidepressants on Sleep. Curr Psychiatry Rep. 2017 Aug 9;19(9):63. doi: 10.1007/s11920-017-0816-4. PMID 28791566
• Meng Y, Liu S, Yu M, Liang H, Tong Y, Song J, Shi J, Cai W, Wu Q, Wen Z, Wang J, Guo F. The Changes of Blood and CSF Ion Levels in Depressed Patients: a Systematic Review and Meta-analysis. Mol Neurobiol. 2024 Aug;61(8):5369-5403. doi: 10.1007/s12035-023-03891-x. Epub 2024 Jan 8. PMID 38191692
• Pochwat B, Szewczyk B, Sowa-Kucma M, Siwek A, Doboszewska 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 Mar;17(3):393-405. doi: 10.1017/S1461145713001089. Epub 2013 Sep 26. PMID 24067405
• Pochwat B, Sowa-Kucma M, Kotarska K, Misztak P, Nowak G, Szewczyk B. Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway. Psychopharmacology (Berl). 2015 Jan;232(2):355-67. doi: 10.1007/s00213-014-3671-6. Epub 2014 Jul 16. PMID 25027582
• 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 Dec 22;14:1333261. doi: 10.3389/fpsyt.2023.1333261. eCollection 2023. PMID 38213402
• Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeda T, Bannai M, Nishino S. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015 May;40(6):1405-16. doi: 10.1038/npp.2014.326. Epub 2014 Dec 23. PMID 25533534

Идентификаторы

NCT: NCT07633080 · IEC/AIIMSBBSR/PGTh/2026-27/01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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