1. Combination therapy of empagliflozin and citalopram reduced symptom severity in patients with major depressive disorder.

2. This average reduction in symptom severity was statistically significant over time in comparison to the reduction of symptoms seen in the placebo-citalopram group.

Evidence Rating Level: 1 (Excellent)

Antidepressants like selective serotonin reuptake inhibitors (SSRIs) are presently first-line in the treatment of major depressive disorder (MDD). Unfortunately, only about 60% of patients with MDD see an improvement in their condition on SSRIs. Treatment for MDD is often supplemented with forms of psychotherapy like cognitive behavioural therapy. Recent studies have demonstrated a link between inflammatory processes and MDD. Empagliflozin, a sodium-glucose cotransporter inhibitor (SGLT2i) often used in the treatment of diabetes, and heart failure has been shown to reduce inflammatory processes and may be suitable as an adjunct to MDD treatment. The effectiveness of empagliflozin as an adjunct to MDD treatment however has not been investigated.

This 8-week double-blinded, placebo-controlled clinical trial compared the effectiveness of empagliflozin as an adjunct to citalopram (an SSRI) in the treatment of MDD to placebo-citalopram treatment. Ninety patients were randomly divided into a treatment and placebo group. Patients aged 18-60, who received a formal diagnosis by two psychiatrists based on DSM-V criteria, and who had moderate to severe MDD based on the Hamilton Depression Rating Scale (HDRS) were included. An HDRS score > 22 was regarded as moderate to severe. Patients who had another major psychiatric, or medical disorder, or who had received an antidepressant in the past 2 months, or SGLT2i in the past 3 months were excluded. The severity of symptoms was assessed using the HDRS at the beginning of the trial, at 4 weeks, and at the end. The primary outcome measured the severity of MDD symptoms using the HDRS.

HDRS scores of the group receiving empagliflozin + citalopram significantly improved versus the control group. At 4 weeks, the HDRS scores were 20.02 vs 13.76 in the control vs treatment groups, respectively. These scores improved to 13.42 and 7.00 at the completion of the study. While both groups experienced a reduction in symptom severity, further statistical analysis also showed that the average downtrend of the HDRS scores in the treatment group was greater and significant over time. One limitation of this study is that patients were initiated on citalopram at the onset of the study. Citalopram typically takes effect between 2-6 weeks. Therefore, the measure of symptom severity may be inaccurate in the study, and could also be attributed to external factors. Nevertheless, this study provides valuable results on the effectiveness of SGLT2is as an adjunct to the treatment of MDD. Further research should focus on further understanding the mechanism by which SGLT2is accomplishes this, as well as investigating the effectiveness through a larger study.

Click here to read this study in BMC Psychiatry.

Image: PD

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