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.

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Background &Aims: With the introduction of sofosbuvir based regimens, there have been achieved high cure rates and decreased duration. Several studies showed variances in SVR rates between different genotypes, with lower rates of SVR among cirrhotic patients . The aim of our study was to assess the safety and effectiveness of sofosbuvir-based antiviral regimens for the treatment of HCV-infected Egyptian cirrhotic patients. Methods: This was a retrospective observational comparative study. Nine hundred forty six cirrhotic patients with chronic HCV genotype 4 infection who were eligible for direct acting drugs (DAAs) therapy were enrolled. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by SVR at 12 Weeks After discontinuation of therapy (SVR12) and the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. Results: Among the 946 patients enrolled in the study; 527 patients (55.7%) were males and 419 patients (44.3 %) were females with mean age 54.00±8.88 years. 20.2 % were diabetics and 19.1% were hypertensive. Patients were classified according to Child -Pugh classifications; 818 patients (86.46%) were Child-Pugh class A cirrhosis, 28 patients (13.53 %) were Child-Pugh class B cirrhosis. SVR12 rate was 96.93% (917 /946). Treatment response in the Child-Pugh class A cirrhosis was 794 (97%) after 12 weeks while treatment response in the Child-Pugh class B cirrhosis was 123 (96%). Mild side effects were observed in 76 patients. Conclusions: Sofosbuvir based regimens were effective and safe in the treatment of cirrhotic patients with chronic hepatitis C genotype 4.

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