Association Between Body Mass Index and Treatment Response to Intranasal Esketamine in an Outpatient Clinical Setting

Abstract

Research Questions: This study aims to determine if body mass index influences response rates of patients treated with intranasal esketamine after 8 treatments in the non-trial outpatient clinical setting.

Background, Significance, and rationale: Major depressive disorder (MDD) is the most common psychiatric illness in the United States and presents with a significant economic, emotional, and healthcare burden. Treatment-resistant depression (TRD), a subset of MDD, is especially challenging to manage, with most current interventions proving largely unsuccessful at reaching long-term remission. Given that up to one-third of patients with MDD meet the criteria for TRD, there is a need for innovative approaches to helping this suffering patient population. Recently, intranasal esketamine was approved as the first mechanistically distinct medication for depression in over 50 years. Multiple proposed mechanisms of esketamine’s anti-depressive functions exist, as do functional imaging studies that demonstrate the neurobehavioral changes of ketamine. The data and anecdotal evidence thus far are promising that esketamine can provide a real solution for patients with treatment-resistant depression. Work with intravenous ketamine has demonstrated a potential weight-based dosing effect with treatment. To the knowledge of the author, no similar work has been performed for intranasal esketamine to determine if BMI impacts treatment response. Further investigation will allow for the optimization of treatment regimens in the outpatient setting.

Materials and Methods: This study is conducted as a retrospective chart review of more than 40 patients who received treatment with intranasal esketamine at the BL6 clinic at UT Southwestern medical center in Dallas, Texas. Inclusion criteria consist of patients aged 18 and older, with a primary diagnosis of major depressive disorder with failure of two or more oral antidepressants in the current depressive episode, and who have received intranasal esketamine for at least 8 treatments. All patients were treated with a 56mg starting dose of intranasal esketamine, unless otherwise specified, and received treatment at an escalated 86mg dose on a standardized 8-week schedule. The efficacy of treatment was determined by collecting survey data of indexes of depression and suicidality that are integrated into each patient's EPIC Flowsheet. These include the Patient Health Questionnaire (PHQ-9), Quik Inventory of Depression Symptomology Clinical Rating/Self Reporting (QIDS-SR/C), the Clinical Global Impressions Scale (CGI), and the Generalized Anxiety Disorder 7-Item (GAD-7).

Results: After 8 treatments of intranasal esketamine, patients experienced a statistically significant reduction in the PHQ-9, QIDS-SR, and CGI depression questionnaires. The GAD-7 questionnaire likewise revealed a statistically significant reduction in anxiety symptoms after 8 treatments.

Conclusion: Prior to the stratification of BMI, analysis of efficacy on the full cohort of 40 patients deemed esketamine effective at reducing the severity of depression and anxiety. After stratification, observational results demonstrate some moderate changes in efficacy by BMI. No statistical analysis can support these observations due to the limited cohort size. Overall, the data provide no clear link that weight or BMI are linked to esketamine efficacy, echoing the results of the intravenous ketamine study.