Combination Therapy of Different Antidepressants With Dietary Supplements

Study Overview
=================
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.

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.

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

Conditions
-----------------
Depression

Intervention / Treatment
-----------------
* Dietary Supplement: L-methylfolate
* Dietary Supplement: Vitamin B12
* Dietary Supplement: magnesium


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, magnesium, Vit B12, L-methylfolate