Combination Therapy of Different Antidepressants With Dietary Supplements

NCT05931965 | Completed DMC

• 1 other identifier: Riphah/IIMC/IRC/22/2069
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical trial is to compare the effect of antidepressants in combination with different dietary supplements in patients with depression. Our main objective is to compare the efficacy of antidepressants in combination with either L-methyl folate, Vit B12, or magnesium) in patients with depressive disorders. The levels of depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9) at base level and during follow-up.

Conditions

Depression

Keywords

Depression; magnesium; Vit B12; L-methylfolate

Outcome Measures

Primary Outcomes (1)

• Patient Health Questionnaire (PHQ-9)

  The change in the total PHQ-9 score between baseline and 4-weeks follow-up is the primary outcome measure. This measure is a patient-rated inventory of depressive symptoms. All items are scored on scales ranging from 0-3 and the sum of the scores provides the total score for the measure. On this scale, higher scores indicate poorer outcomes. Scores 9-19 and 20-27 are considered moderate and severe depression respectively.

  Baseline and 4 weeks

Secondary Outcomes (3)

• Patient Health Questionnaire (PHQ-9)

  Baseline, 2-weeks and 4-weeks

• Side-effects

  Baseline, 2-weeks, and 4-weeks follow up

• Depressive symptoms remission

  Baseline, 2 weeks, 4 weeks

Study Arms (4)

Antidepressant

NO INTERVENTION

Participants receive either escitalopram 10-20mg, sertraline 50-100mg, fluoxetine 20-40mg, duloxetine 30-60mg, mirtazapine 15-30mg, venlafaxine 75-150mg, trazodone 50-100mg, amitriptyline 25-75mg, or clomipramine 25-75mg orally daily for 4 weeks.

Antidepressant and L-methylfolate

EXPERIMENTAL

Participants receive a combination of antidepressant and L-methylfolate 400µg twice daily orally for 4 weeks

Dietary Supplement: L-methylfolate

Antidepressant and injectable mecobalamin

EXPERIMENTAL

Participants receive a combination of antidepressant and mecobalamin 500µg intramuscularly stat on alternate days (6 total injections)

Dietary Supplement: Vitamin B12

Antidepressant and Magnesium

EXPERIMENTAL

Participants receive a combination of antidepressant and magnesium glycinate 400mg (Elemental: ≈120mg) twice daily orally for 4 weeks

Dietary Supplement: magnesium

Interventions

L-methylfolate DIETARY_SUPPLEMENT

Participants receive L-methylfolate 400µg orally twice daily for 4 weeks

Also known as: 5-methyl-terahydrofolate

Antidepressant and L-methylfolate

Vitamin B12 DIETARY_SUPPLEMENT

Participants receive mecobalamin 500µg intramuscularly stat on alternate days (6 total injections)

Also known as: mecobalamin

Antidepressant and injectable mecobalamin

magnesium DIETARY_SUPPLEMENT

Participants receive magnesium glycinate 400mg twice daily orally for 4 weeks (elemental 120mg approx.)

Also known as: Mg

Antidepressant and Magnesium

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Depressive Disorder having PHQ-9 Score 9 and above
• Age 12 and above
• Patients having low/marginal and low normal levels for arms 2 and 3 of respective supplements
• Patients having low/normal serum magnesium for arm 4

You may not qualify if:

• Patients having psychiatric diagnosis other than Depressive Disorder according to the International Classification of Diseases 11th Revision (ICD-11)
• History of kidney disease, myasthenia gravis
• Mentally handicapped or terminally ill patients
• Age less than 12 years
• Patients already taking multiple nutritional supplements
• Patients on polypharmacy with potential interactions with antidepressants and supplements in this study.

Sponsors & Collaborators

• Riphah International University: lead

Study Sites (1)

Pakistan Railway Hospital, IIMC-T, Riphah International University

Rawalpindi, Punjab Province, Pakistan

Location

Related Publications (11)

• Serefko A, Szopa A, Poleszak E. Magnesium and depression. Magnes Res. 2016 Mar 1;29(3):112-119. doi: 10.1684/mrh.2016.0407.

  PMID: 27910808 BACKGROUND

• 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 Jun 27;12(6):e0180067. doi: 10.1371/journal.pone.0180067. eCollection 2017.

  PMID: 28654669 BACKGROUND

• Sun C, Wang R, Li Z, Zhang D. Dietary magnesium intake and risk of depression. J Affect Disord. 2019 Mar 1;246:627-632. doi: 10.1016/j.jad.2018.12.114. Epub 2018 Dec 27.

  PMID: 30611059 BACKGROUND

• 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 Dec;37(5):1000-1009. doi: 10.1002/smi.3051. Epub 2021 May 6.

  PMID: 33864354 BACKGROUND

• Chaban capital O, CyrillicS, Khaustova OO, Assonov DO, Sak LV. SAFETY AND EFFICACY OF THE COMPLEX DEPRILIUM(R) IN REDUCING SUBCLINICAL SYMPTOMS OF DEPRESSION IN PATIENTS WITH CHRONIC NON-COMMUNICABLE DISEASES: DOUBLE-BLIND RANDOMIZED CONTROLLED STUDY. Wiad Lek. 2023;76(1):136-144. doi: 10.36740/WLek202301119.

  PMID: 36883502 BACKGROUND

• Maruf AA, Poweleit EA, Brown LC, Strawn JR, Bousman CA. Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders. Pharmacopsychiatry. 2022 May;55(3):139-147. doi: 10.1055/a-1681-2047. Epub 2021 Nov 18.

  PMID: 34794190 BACKGROUND

• Hardin A, Baldwin-Sayre C. L-Methylfolate as a Monotherapy for Treatment-Resistant Depression: A Case Study. Integr Med (Encinitas). 2020 Aug;19(4):14-18.

  PMID: 33132780 BACKGROUND

• Dartois LL, Stutzman DL, Morrow M. L-methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series. J Child Adolesc Psychopharmacol. 2019 Jun;29(5):386-391. doi: 10.1089/cap.2019.0006. Epub 2019 May 6.

  PMID: 31058543 BACKGROUND

• Markun S, Gravestock I, Jager L, Rosemann T, Pichierri G, Burgstaller JM. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients. 2021 Mar 12;13(3):923. doi: 10.3390/nu13030923.

  PMID: 33809274 BACKGROUND

• Carter B, Zenasni Z, Moat SJ, Hudson PR, Russell IT, McCaddon A; FolATED group consists of the following authors. Plasma Methylmalonic Acid Concentration in Folic Acid-Supplemented Depressed Patients with Low or Marginal Vitamin B-12: A Randomized Trial. J Nutr. 2021 Dec 3;151(12):3738-3745. doi: 10.1093/jn/nxab280.

  PMID: 34510193 BACKGROUND

• Siddique A, Khokhar MM, Waheed A, Naeem U, Aziz SA. Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder. BMC Pharmacol Toxicol. 2025 Jan 22;26(1):14. doi: 10.1186/s40360-025-00846-x.

  PMID: 39844190 DERIVED

MeSH Terms

Conditions

Depression

Interventions

5-methyltetrahydrofolate; Vitamin B 12; mecobalamin; Magnesium

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Afifa Siddique, MBBS

  IIMC-T, Riphah International University, Rawalpindi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2023
• First Posted: July 6, 2023
• Study Start: October 5, 2022
• Primary Completion: July 30, 2023
• Study Completion: August 31, 2023
• Last Updated: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)