The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial.
Mahmoud S AbdallahEsraa M MosalamAbdel-Aziz A ZidanKhaled S ElattarShimaa A ZakiAhmed N RamadanAbla M EbeidPublished in: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2021)
Metformin (MET) has been reported to have antidepressant effects in animal models and in diabetic patients with depression, owing to its anti-inflammatory, antioxidant, and neuroprotective activity. Accordingly, we proposed that MET would show antidepressant effects in patients with major depressive disorder (MDD) without other comorbidities. In this double-blind placebo-controlled study, 80 adult outpatients with MDD (DSM-IV criteria) and a Hamilton Depression Rating Scale (HAM-D) score >18 were randomized to receive fluoxetine 20 mg once daily plus placebo (n = 40) or fluoxetine 20 mg once daily plus MET 1000 mg once daily for 12 weeks. Patients were assessed by HAM-D score (weeks 0, 4, 8, and 12). The serum levels of TNF-α, IL-1β, IL-6, IGF-1, MDA, CRP, BDNF, and serotonin were measured before and after therapy. Mixed-effects model repeated-measures analysis of covariance was used to compare the HAM-D scores and the biological markers between the two groups. After 4, 8 and 12 weeks, patients in the MET group showed a statistically significant decline in HAM-D score relative to the placebo group (least squares mean difference [LSMD] -2.347, p = 0.000, LSMD -3.369, p = 0.000, and LSMD -3.454, p = 0.000, respectively). Response and remission rates were significantly higher in the MET group (89% and 81%, respectively) than in the placebo group (59% and 46%, respectively). Moreover, the MET group was superior in conserving the measured biological markers compared with the placebo group. Our findings suggest MET as a promising, effective, and safe short-term adjunctive approach in nondiabetic MDD patients. Trial registration ID: NCT04088448.
Keyphrases
- major depressive disorder
- double blind
- placebo controlled
- phase iii
- bipolar disorder
- end stage renal disease
- clinical trial
- tyrosine kinase
- phase ii
- chronic kidney disease
- newly diagnosed
- ejection fraction
- open label
- peritoneal dialysis
- type diabetes
- depressive symptoms
- lymph node
- rheumatoid arthritis
- squamous cell carcinoma
- stem cells
- systemic lupus erythematosus
- physical activity
- cell death
- cell proliferation
- blood brain barrier
- gestational age
- rectal cancer
- disease activity