Efficacy of Metformin as an Adjunct to Standard Antidepressant Therapy in Treating Depression Among Obese Patients

NCT06707012 | Recruiting Phase 4 DMC

• 2 other identifiers: frpmc.edu.pk@sadiakhan12345678FMC, University
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

To evaluate the efficacy of metformin as an adjunct therapy in improving depressive symptoms and metabolic markers in newly diagnosed obese depressed patients on standard antidepressant therapy. investigator will compare between Two groups 1\. metformin group 2 placebo group Primary outcome measure will be the improvement in depressive symptoms, indicating by a reduction in Hamilton Depression Rating Scale (HAM-D) scores. Secondary outcome measures will include the assessment of oxidative stress markers, specifically by measuring the increase in enzymatic activity of superoxide dismutase, catalase, and glutathione peroxidase Investigators hypothesize that the addition of metformin to standard antidepressant treatment will result in a significant reduction in symptoms of depression among newly diagnosed obese individuals.

Conditions

Depression

Keywords

Depression; oxidative stress; antidepressants; obesity

Outcome Measures

Primary Outcomes (1)

• Decrease scoring of Hamilton depression rating scale

  Primary outcome measure will be the improvement in depressive symptoms, indicating by a change in Hamilton Depression Rating Scale (HAM-D) scores. Decrease in the score will be considered as indicator of improvement in depression. 0-7: Normal (no depression) 8-13: Mild depression 14-18: Moderate depression 19-22: Severe depression 23 and above: Very severe depression Investigators will compare the change in both groups.

  18 months

Secondary Outcomes (1)

• elevation in oxidative enzymes level (superoxide dismutase,catalase,glutathione peroxidase

  18 months

Other Outcomes (1)

• change in Basal Metabolic Rate

  18 months

Study Arms (2)

Experimental

EXPERIMENTAL

We will prescribe metformin with starting dose of 500 mg metformin once daily, titrated up to 2000 mg/day based on tolerance along with standard treatment of depression according to Maudsley guidelines.

Drug: Metformin Hydrochloride

placebo group

PLACEBO COMPARATOR

Identical placebo tablets, following the same titration schedule as the metformin group along with standard treatment of depression

Drug: Metformin Hydrochloride

Interventions

Metformin Hydrochloride DRUG

Participants will be divided in 2 groups 1 group will receive metformin and 2nd group will receive placebo

Also known as: GLUCOPHAGE

Experimental; placebo group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age \>18 to \<45 years
• Gender: Both genders (Male and Female)
• BMI \>25
• Diagnosis: Newly diagnose cases of depression (mild to severe)
• HBA1C: Less than 5.7% (non-diabetic range)

You may not qualify if:

• Existing diabetes
• Acute illnesses like acute kidney injury, recent history of myocardial infarction, acute liver injury
• Intellectual disabilities or inability to understand due to any reason
• Presence of Psychiatric disorders other than depression
• Chronic kidney disease (eGFR \< 45 mL/min/1.73 m²).
• Use of any psychotropic medication within the past 6 months.

Sponsors & Collaborators

• Fazaia Ruth Pfau Medical College: lead

Study Sites (2)

Fazaia Rurh Pfau Medical College

Karachi, Sindh, 75120, Pakistan

RECRUITING

Fazaia Ruth Pfau Medical College

Karachi, Sindh, 75120, Pakistan

RECRUITING

Related Publications (10)

• Guo M, Mi J, Jiang QM, Xu JM, Tang YY, Tian G, Wang B. Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. Clin Exp Pharmacol Physiol. 2014 Sep;41(9):650-6. doi: 10.1111/1440-1681.12265.

  PMID: 24862430 BACKGROUND

• Farooq S, Khan T, Zaheer S, Shafique K. Prevalence of anxiety and depressive symptoms and their association with multimorbidity and demographic factors: a community-based, cross-sectional survey in Karachi, Pakistan. BMJ Open. 2019 Nov 19;9(11):e029315. doi: 10.1136/bmjopen-2019-029315.

  PMID: 31748286 BACKGROUND

• Heiskanen TH, Niskanen LK, Hintikka JJ, Koivumaa-Honkanen HT, Honkalampi KM, Haatainen KM, Viinamaki HT. Metabolic syndrome and depression: a cross-sectional analysis. J Clin Psychiatry. 2006 Sep;67(9):1422-7. doi: 10.4088/jcp.v67n0913.

  PMID: 17017829 BACKGROUND

• Lang UE, Beglinger C, Schweinfurth N, Walter M, Borgwardt S. Nutritional aspects of depression. Cell Physiol Biochem. 2015;37(3):1029-43. doi: 10.1159/000430229. Epub 2015 Sep 25.

  PMID: 26402520 BACKGROUND

• Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010 Mar;67(3):220-9. doi: 10.1001/archgenpsychiatry.2010.2.

  PMID: 20194822 BACKGROUND

• Lee A, Morley JE. Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res. 1998 Jan;6(1):47-53. doi: 10.1002/j.1550-8528.1998.tb00314.x.

  PMID: 9526970 BACKGROUND

• Seifarth C, Schehler B, Schneider HJ. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):27-31. doi: 10.1055/s-0032-1327734. Epub 2012 Nov 12.

  PMID: 23147210 BACKGROUND

• AlHussain F, AlRuthia Y, Al-Mandeel H, Bellahwal A, Alharbi F, Almogbel Y, Awwad O, Dala'een R, Alharbi FA. Metformin Improves the Depression Symptoms of Women with Polycystic Ovary Syndrome in a Lifestyle Modification Program. Patient Prefer Adherence. 2020 Apr 15;14:737-746. doi: 10.2147/PPA.S244273. eCollection 2020.

  PMID: 32346286 BACKGROUND

• Calkin CV, Chengappa KNR, Cairns K, Cookey J, Gannon J, Alda M, O'Donovan C, Reardon C, Sanches M, Ruzickova M. Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study): A Randomized, Quadruple-Masked, Placebo-Controlled Clinical Trial. J Clin Psychiatry. 2022 Feb 1;83(2):21m14022. doi: 10.4088/JCP.21m14022.

  PMID: 35120288 BACKGROUND

• Jitca G, Gall Z, Jitca CM, But MG, Majai E. Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study. Pharmaceutics. 2024 Mar 15;16(3):403. doi: 10.3390/pharmaceutics16030403.

  PMID: 38543297 BACKGROUND

MeSH Terms

Conditions

Depression; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• sadia khan, MBBS

  Fazaia Ruth Pfau Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sadia khan, MBBS

CONTACT

0331359046; sadiakhansk30@gmail.com

Asghar Mehdi, MBBS,PHD

CONTACT

03008228284; drasgharmehdi@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be double blind study in which participant and investigator who prescribe the drug will be blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Sadia Khan MBBS resident FCPS Pharmacology

Model Details: Study Design This is a comparative clinical study with randomized groups. Participants will be allocated to either the metformin group or the placebo group in conjunction with standard antidepressant therapy. Randomization will be achieved using computer generated numbers in 1:1 ratio. Metformin Group: Starting dose of 500 mg metformin once daily, titrated up to 2000 mg/day based on tolerance along with standard treatment of depression according to Maudsley guidelines. Placebo Group: Identical placebo tablets, following the same titration schedule as the metformin group along with standard treatment of depression Setting: At psychiatric Out Patient Department of Fazaia Ruth Pfau Medical College and Hospital Karachi Pakistan Study Duration: 18 months

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: November 27, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (2)