SUMMARY

• No significant differences in the pharmacokinetics of esketamine nasal spray were observed for total body weight (>39 to 170 kg) based on a population pharmacokinetic (PK) analysis. Alternative dosing regimen is not required based on body weight.¹
• A population PK model in Japanese patients found that a higher body weight may decrease exposure to esketamine; however, the changes were within the 0.8-1.25 range and, therefore, were not considered to be clinically meaningful.²
  • Geometric mean ratio (90% confidence interval [CI]) of esketamine exposure in patients with body weight <60 kg and >90 kg relative to that of patients with body weight 60-90 kg was 1.07 (1.02-1.13) and 0.86 (0.82-0.91) for maximum plasma concentration (C_max), and 1.09 (1.04-1.15) and 0.83 (0.79-0.86) for area under the plasma concentration-time curve from 0 to 24 hours (AUC_0-24h), respectively.
  • Geometric mean ratio (90% CI) of noresketamine exposure in patients with body weight <60 kg and >90 kg relative to that of patients with body weight 60-90 kg was 1.10 (1.01-1.19) and 0.91 (0.85-0.99) for C_max, and 1.15 (1.08-1.22) and 0.86 (0.81-0.91) for AUC_0-24h, respectively.
• A post hoc subgroup analysis of the ESCAPE-TRD³ study (a 32-week, randomized, phase 3b study that investigated SPRAVATO vs quetiapine extended-release [QUE-XR] in patients with treatment-resistant depression) examined weight and metabolic changes associated with SPRAVATO and QUE-XR, including the impact of body mass index (BMI) on depression symptoms.⁴
  • Patients were categorized based on BMI as underweight (BMI <18.5; SPRAVATO, n=5; QUE-XR, n=5), normal (BMI 18.5 to <25; SPRAVATO, n=103; QUE-XR, n=82), overweight (BMI 25 to <30; SPRAVATO, n=86; QUE-XR, n=88), obese (BMI 30-35; SPRAVATO, n=40; QUE-XR, n=71), and morbidly obese (BMI >35; SPRAVATO, n=21; QUE-XR, n=16).
  • Patients treated with SPRAVATO showed greater improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores across all BMI categories compared to QUE-XR by the end of the study. There was an approximately 15- to 20-point improvement based on the least squares mean change from baseline in the MADRS total score for each BMI category in the SPRAVATO arm.
  • The small sample size in the underweight and morbidly obese categories may limit the generalizability of results for these patient populations.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 21 October 2024.