Combination Therapy of Different Antidepressants With Dietary Supplements

Sponsor

Riphah International University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05931965

Collaborator

(none)

Enrollment

Location

Arms

10.8

Anticipated Duration (Months)

8.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression	Dietary Supplement: L-methylfolate Dietary Supplement: Vitamin B12 Dietary Supplement: magnesium	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 5, 2022

Anticipated Primary Completion Date :

Jul 30, 2023

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: 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.
Experimental: Antidepressant and L-methylfolate Participants receive a combination of antidepressant and L-methylfolate 400µg twice daily orally for 4 weeks	Dietary Supplement: L-methylfolate Participants receive L-methylfolate 400µg orally twice daily for 4 weeks Other Names: 5-methyl-terahydrofolate
Experimental: Antidepressant and injectable mecobalamin Participants receive a combination of antidepressant and mecobalamin 500µg intramuscularly stat on alternate days (6 total injections)	Dietary Supplement: Vitamin B12 Participants receive mecobalamin 500µg intramuscularly stat on alternate days (6 total injections) Other Names: mecobalamin
Experimental: Antidepressant and Magnesium Participants receive a combination of antidepressant and magnesium glycinate 400mg (Elemental: ≈120mg) twice daily orally for 4 weeks	Dietary Supplement: magnesium Participants receive magnesium glycinate 400mg twice daily orally for 4 weeks (elemental 120mg approx.) Other Names: Mg

Outcome Measures

Primary Outcome Measures

Patient Health Questionnaire (PHQ-9) [Baseline and 4 weeks]
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.

Secondary Outcome Measures

Patient Health Questionnaire (PHQ-9) [Baseline, 2-weeks and 4-weeks]
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.
Side-effects [Baseline, 2-weeks, and 4-weeks follow up]
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.
Depressive symptoms remission [Baseline, 2 weeks, 4 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.