Combination Therapy of Different Antidepressants With Dietary Supplements

Depression Clinical Trial

Official title:

Comparative Efficacy of Antidepressants With L-methylfolate, B12, and Magnesium in Depressive Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05931965
• Other study ID #: Riphah/IIMC/IRC/22/2069
• Status: Completed
• Phase: N/A
• Start date: October 5, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2023
• Source: Riphah International University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is an open-label study assessing the comparative efficacy of antidepressants in combination therapy of either L-methylfolate, mecobalamin, or magnesium in patients with Depressive Disorder. The plan is to enroll 84 patients with depression based on Patient Health Questionnaire (PHQ-9) score of 9 and above, which is a valid and reliable Structured Clinical Interview. The investigators will collect data from the enrolled patient populations. The participants will be able to receive their results, on request, upon completion of the study. The investigators hypothesize that depressive symptoms can be improved by the addition of above mentioned nutritional supplementations with antidepressant medication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: August 31, 2023
• Est. primary completion date: July 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Depression

Intervention

Dietary Supplement:
• L-methylfolate
Participants receive L-methylfolate 400µg orally twice daily for 4 weeks
• Vitamin B12
Participants receive mecobalamin 500µg intramuscularly stat on alternate days (6 total injections)
• magnesium
Participants receive magnesium glycinate 400mg twice daily orally for 4 weeks (elemental 120mg approx.)

Locations

Country	Name	City	State
Pakistan	Pakistan Railway Hospital, IIMC-T, Riphah International University	Rawalpindi	Punjab

Sponsors (1)

Lead Sponsor	Collaborator
Riphah International University

Country where clinical trial is conducted

Pakistan, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Patient Health Questionnaire (PHQ-9)	The change in the total PHQ-9 score between baseline, and the intermediate 2-weeks, and 4-weeks follow-up is the secondary outcome measures. 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, 2-weeks and 4-weeks
Secondary	Side-effects	A self-assessment questionnaire for undesirable effects in psychopharmacological treatment, developed by the Department of Psychiatry, Riphah International University, Pakistan. This is to investigate the presence or absence of 4 symptoms (diarrhea, drowsiness, insomnia, and rash), and their relationship with the treatment.	Baseline, 2-weeks, and 4-weeks follow up
Secondary	Depressive symptoms remission	Remission rate of Major Depression in the two groups over the course of treatment, defining remission as a score = 4 on the PHQ-9 scale.	Baseline, 2 weeks, 4 weeks