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

NCT ID: NCT04088448

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2020-06-01

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control group

Fluoxetine 20 mg capsule once daily for 12 week plus placebo tablet once daily for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

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

Metformin group

Fluoxetine 20 mg capsule once daily for 12 week plus Metformin 1000 mg XR tablet once daily for 12 weeks

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

Interventions

Placebo oral tablet

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

Intervention Type: DRUG

Metformin

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sadat City University

OTHER

Sponsor Role: lead

Responsible Party

Mahmoud Samy Abdallah

Lecturer of Clinical Pharmacy, PhD.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Faculty of Medicine

Tanta, , Egypt

Countries

Egypt

References

Abdallah MS, Mosalam EM, Zidan AA, Elattar KS, Zaki SA, Ramadan AN, Ebeid AM. The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. Neurotherapeutics. 2020 Oct;17(4):1897-1906. doi: 10.1007/s13311-020-00878-7.

Reference Type: DERIVED

PMID: 32500486 (View on PubMed)

Related Links

https://link.springer.com/article/10.1007/s13311-020-00878-7

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

Other Identifiers

0056/2018

Identifier Type: -

Identifier Source: org_study_id