Efficacy of empagliflozin as adjunctive therapy to citalopram in major depressive disorder: a randomized double-blind, placebo-controlled clinical trial

Abstract

Background Major depressive disorder is one of the most common psychiatric disorders, which is associated with a high disease burden. Current treatments using antidepressants have limitations, so using medication with neuromodulating and anti-inflammatory properties alongside them could be helpful. In a clinical trial, we studied the effectiveness of empagliflozin, a blood sugar-lowering drug, as an adjunctive therapy to reduce the severity of depression symptoms. Methods A number of outpatients with moderate to severe depression (Hamilton Depression Rating Scale (HDRS) > = 17) who were not under related medication or had not taken medication for at least the last two months, had an age range of 18–60 years and had written informed consent to enter the study (N = 90) were randomly divided into two groups receiving placebo or empagliflozin (10 mg daily) combined with citalopram (40 mg daily) based on permuted block randomization method in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the HDRS in weeks 0, 4, and 8. Results HDRS scores were equal to 28.42(± 3.83), 20.20(± 3.82), and 13.42(± 3.42) in the placebo group during weeks 0,4, and 8, respectively. These scores were 27.36(± 3.77), 13.76(± 1.40), and 7.00(± 1.13), respectively, for the group treated with empagliflozin. Compared to the control group, patients treated with empagliflozin using repeated-measures ANOVA showed greater improvement in reducing the severity of depression symptoms over time (p value = 0.0001). Conclusions Considering the promising findings in this clinical trial, further study of empagliflozin as adjunctive therapy in MDD with larger sample sizes and longer follow-ups is recommended.

Sodium‐glucose cotransporter 1/2 inhibition and risk of neurodegenerative disorders: A Mendelian randomization study

“…Population‐based studies suggest that SGLT2 inhibitors are associated with a decreased risk of dementia and depression (Liebers et al., 2023 ; Wu et al., 2023 ). Preclinical experiments have shown that these medications can improve brain energetics (Pawlos et al., 2021 ), and a recent randomized controlled trial demonstrated improved mood outcomes with the selective SGLT2 inhibitor empagliflozin in combination with citalopram (Zandifar et al., 2024 ). These findings suggest that SGLT2 inhibitors may have a broader therapeutic potential beyond their glycemic control effects.…”