NCT04088448

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

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: Sadat City University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	Placebo oral tablet	Fluoxetine 20 mg capsule plus Placebo tablet administered once daily after food
DRUG	Metformin	Fluoxetine 20 mg capsule plus Metformin 1000 mg extended release tablet administered once daily after food

Timeline

• Start date: 2017-01-01
• Primary completion: 2020-06-01
• Completion: 2020-06-01
• First posted: 2019-09-12
• Last updated: 2020-06-16

Locations

1 site across 1 country: Egypt