Does BMI matter when treating depression with esketamine? A retrospective analysis of real-world data

Intranasal (IN) esketamine was approved as a therapy for treatment-resistant depression in March 2019. There continues to be interest in the field to better understand factors associated with response to treatment. The aim of the current study is to assess the association between BMI and response to esketamine.

A retrospective analysis was conducted on all patients treated with intranasal esketamine at the Yale Interventional Psychiatry Service between January 2015 and May 2023. The primary outcome was the association between BMI (ctegorized as obese vs. non-obese) and response to treatment (≥50 % improvement) by Montgomery-Åsberg Depression Rating Scale (MADRS). Statistical models, including generalized linear mixed-effects models were employed.

A total of 190 patients met criteria for inclusion in the study, out of which 34.2 % were categorized as obese. Patients with obesity were significantly more likely to respond to esketamine treatment (RR = 1.63; p = 0.033) compared to non-obese patients. No linear association between BMI and treatment response was observed when BMI was treated as a continuous variable (RR = 1.02, p = 0.163).

Obesity appears to be associated with a higher response rate to intranasal esketamine treatment for depression. Although the underlying mechanisms of this association are still unknown, increased body fat may prolong the presence of lipid-soluble compounds such as ketamine/esketamine or their active metabolites.