AzTrials
AzTrials

DepressionNCT05931965

Combination Therapy of Different Antidepressants With Dietary Supplements

A study testing L-methylfolate, Vitamin B12 and magnesium in people with Depression, run by Riphah International University at 1 site in Pakistan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Depression
What is being tested?
L-methylfolate, Vitamin B12 and magnesium
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
1 sitePakistan
Study dates
5 Oct 2022to 31 Aug 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Pakistan1 site

  • Pakistan Railway Hospital, IIMC-T, Riphah International University

    Rawalpindi, Punjab Province

Other trials in Pakistan

About this study

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

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.

Read the detailed 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.

Conditions
Depression
Being tested
L-methylfolate, Vitamin B12, magnesium
Keywords
Depression, magnesium, Vit B12, L-methylfolate
Medical subject headings
Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L-methylfolateDietary supplement

    Also called 5-methyl-terahydrofolate

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

  • Vitamin B12Dietary supplement

    Also called mecobalamin

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

  • magnesiumDietary supplement

    Also called Mg

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

Study groups in NCT05931965
Study groupRoleWhat they receive
AntidepressantNo interventionParticipants 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-methylfolateExperimentalParticipants receive a combination of antidepressant and L-methylfolate 400µg twice daily orally for 4 weeks
Receives: Dietary Supplement: L-methylfolate
Antidepressant and injectable mecobalaminExperimentalParticipants receive a combination of antidepressant and mecobalamin 500µg intramuscularly stat on alternate days (6 total injections)
Receives: Dietary Supplement: Vitamin B12
Antidepressant and MagnesiumExperimentalParticipants receive a combination of antidepressant and magnesium glycinate 400mg (Elemental: ≈120mg) twice daily orally for 4 weeks
Receives: Dietary Supplement: magnesium

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and 4 weeks

Secondary outcomes (3)

  1. 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.

    Measured: Baseline, 2-weeks and 4-weeks

  2. 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.

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

  3. 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.

    Measured: Baseline, 2 weeks, 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2023
  2. Study start5 Oct 2022
  3. Primary completion30 Jul 2023
  4. Study completion31 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05931965
Sponsor's protocol ID
Riphah/IIMC/IRC/22/2069
Status last verified
Sep 2023
First submitted
14 Jun 2023
Last updated
11 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

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

    PubMed 27910808

  • 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.

    PubMed 28654669

  • 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.

    PubMed 30611059

  • 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.

    PubMed 33864354

  • 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.

    PubMed 36883502

  • 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.

    PubMed 34794190

  • 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.

    PubMed 33132780

  • 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.

    PubMed 31058543

  • 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.

    PubMed 33809274

  • 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.

    PubMed 34510193

  • Siddique A, Naeem U, Khokhar MM, Irshad M, Farooq T, Kanwal S. Clinical evaluation of adjunctive magnesium therapy in patients receiving antidepressants for depression-open label, nonrandomized clinical trial. Naunyn Schmiedebergs Arch Pharmacol. 2026 Jun 12. doi: 10.1007/s00210-026-05540-1. Online ahead of print.

    PubMed 42283837

  • 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.

    PubMed 39844190

Questions about this trial

What is this clinical trial studying?

A study testing L-methylfolate, Vitamin B12 and magnesium in people with Depression, run by Riphah International University at 1 site in Pakistan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patient Health Questionnaire (PHQ-9) (time frame: Baseline and 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05931965, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in