Clinical trial NCT04088448: The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: Sadat City University
Sponsor class: OTHER
First posted: 2019-09-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Effect on Hamilton Depression rating scale score (HAM-D score)
timeFrame: Baseline to week 12
Secondary outcomes:
measure: TNF-α
timeFrame: Baseline to week 12
measure: BDNF
timeFrame: Baseline to week 12
measure: CRP
timeFrame: Baseline to week 12
measure: IGF-1
timeFrame: Baseline to week 12
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Faculty of Medicine
Study officials:
References:
citation: 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.