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Completed

NCT Number: NCT04088448

The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients

The aim of our study was to test whether the combined administration of the SSRI fluoxetine and metformin, a drug improving metabolic profile and therefore potentially able to mimic the influence of supportive living conditions on treatment outcome, results in an improved antidepressant efficacy compared with fluoxetine alone.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Faculty of Medicine

Tanta, Egypt

About this study

Selective Serotonin Reuptake Inhibitors (SSRIs) represent the standard treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete. In order to explain, at least in part, such variable efficacy, we have shown that SSRI administration does not affect mood per se but, by enhancing neural plasticity, amplifies the influence of the living conditions on mood. Consequently, in a favorable environment, SSRI treatment leads to a reduction of symptoms while, in stressful conditions, it could lead to a worse prognosis. Here, we test the hypothesis that, given the clear association between living conditions and metabolic profile, the modulation of the latter may mimic the effect of the environment on SSRI outcome, determining treatment efficacy.

Metformin is widely used as a first line treatment for patients with type 2 diabetes mellitus for more than 60 years for the reduction of hepatic glucose output and increase of the insulin mediated utilization of glucose. Previous studies demonstrated that metformin can rapidly cross the blood brain barrier and has several beneficial effects in the brain such as anti-inflammatory and neuroprotective effects. Furthermore, metformin, along with its anti-glycemic effects, has been documented to possess anti-depression effects in patients with type 2 diabetes. In Guo's study, 58 participants diagnosed with depression and type 2 diabetes were divided into two groups: one treated with metformin and the other with a placebo for 24 weeks. Analysis of MADRS and HRSD-17 scores showed that metformin significantly reduced MADRS scores and HRSD-17 scores. Metformin administration improves depressive symptoms in type 2 diabetes mellitus.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without psychotic features and a total 17 item HAM-D score of at least 18 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).
  • Patients were requested to be free of all the psychotropic and anti-inflammatory medications for at least 4 weeks before participating in the study.

Exclusion criteria

  • Patients with bipolar I or bipolar II disorder
  • Patients with personality disorders
  • Patients with eating disorders
  • Patients with substance dependence or abuse
  • Patients with concurrent active medical condition
  • Patients with history of seizures
  • Patients with history of receiving Electroconvulsive therapy (ECT)
  • Patients with diabetes and other inflammatory disorders
  • Patients with allergy or contraindications to the used medications
  • Patients with finally pregnant or lactating females

Treatment and study plan

Placebo oral tablet

Drug

Fluoxetine 20 mg capsule plus Placebo tablet administered once daily after food

metformin

Drug

Fluoxetine 20 mg capsule plus Metformin 1000 mg extended release tablet administered once daily after food

Primary outcomes

  1. Effect on Hamilton Depression rating scale score (HAM-D score)

    Time frame: Baseline to week 12

    The principal measure of the outcome was the 17-items HAM-D. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-13 suggest mild depression, 14-17 moderate depression and scores over 17 are indicative of severe depression. Remission is defined as HAM-D total score ≤ 7 (primary outcome). Treatment response is defined as ≥ 50% drop in the HAM-D total score.

Secondary outcomes

  1. TNF-α

    Time frame: Baseline to week 12

    Serum level of tumor necrosis factor alpha (TNF-α)

  2. BDNF

    Time frame: Baseline to week 12

    Serum level of brain derived neurotrophic factor (BDNF),

  3. CRP

    Time frame: Baseline to week 12

    Serum level of C-Reactive Protein

  4. IGF-1

    Time frame: Baseline to week 12

    Serum level of Insulin-Like Growth Factor

Sponsors and collaborators

Lead sponsor

Sadat City University

Other

Registry information

Official study title

The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Sep 12, 2019
Registry last updated
Jun 16, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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