Combination Therapy of Different Antidepressants With Dietary Supplements

NCT ID: NCT05931965

Last Updated: 2023-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-05

Study Completion Date

2023-08-31

Brief Summary

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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.

Detailed Description

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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

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Depression

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Antidepressant

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Antidepressant and L-methylfolate

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

Group Type EXPERIMENTAL

L-methylfolate

Intervention Type DIETARY_SUPPLEMENT

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

Antidepressant and injectable mecobalamin

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

Group Type EXPERIMENTAL

Vitamin B12

Intervention Type DIETARY_SUPPLEMENT

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

Antidepressant and Magnesium

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

Group Type EXPERIMENTAL

magnesium

Intervention Type DIETARY_SUPPLEMENT

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

Interventions

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L-methylfolate

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

Intervention Type DIETARY_SUPPLEMENT

Vitamin B12

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

Intervention Type DIETARY_SUPPLEMENT

magnesium

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

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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5-methyl-terahydrofolate mecobalamin Mg

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Riphah International University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Afifa Siddique, MBBS

Role: PRINCIPAL_INVESTIGATOR

IIMC-T, Riphah International University, Rawalpindi

Locations

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Pakistan Railway Hospital, IIMC-T, Riphah International University

Rawalpindi, Punjab Province, Pakistan

Site Status

Countries

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Pakistan

References

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

Reference Type BACKGROUND
PMID: 27910808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28654669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30611059 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33864354 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36883502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34794190 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33132780 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31058543 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33809274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34510193 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39844190 (View on PubMed)

Other Identifiers

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Riphah/IIMC/IRC/22/2069

Identifier Type: -

Identifier Source: org_study_id

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