Role of BMI in predicting treatment response to standard dose intranasal esketamine

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2022

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Shah, Dilan
Czysz, Andy

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Purpose: The current work aims to determine the effects of BMI on the response and remission rates of patients treated with standard dosed intranasal esketamine after 8 treatments. Introduction: 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 for which nearly 30% of patients meet criteria, is especially challenging to manage, with most current interventions proving largely unsuccessful at reaching long-term remission. While definitions can vary, failure of two oral antidepressants of adequate dose and duration is the most common definition of TRD. Recently intranasal esketamine was approved as the first mechanistically distinct medication for depression in over 50 years. Proposed mechanisms of esketamine's anti-depressive function include NMDA receptor antagonism and modulation of the mTOR signaling cascade to affect synaptogenesis. Functional imaging also demonstrates esketamine's effect on multiple brain regions, including the medial prefrontal, motor, cingulate, and somatosensory cortex regions as well as subcortical regions. Though there is limited research beyond the recently concluded phase 3 clinical trials, the data and anecdotal evidence thus far have been promising that esketamine can provide a real solution for patients with treatment-resistant depression. Previous studies have been conducted to determine the treatment response in patients with MDD who received weight-based intravenous ketamine. No work exists, to the author's knowledge, investigating how BMI affects the response to standard-dosed intranasal esketamine. 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 consisted of patients ages 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 received intranasal esketamine treatment. All patients were treated with a 56mg starting dose of intranasal esketamine and received treatment at an escalated 86mg dose on a standardized 8-week schedule. 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), Quick Inventory of Depression Symptomology Clinical Rating/Self Reporting (QIDS-SR/C), and the Clinical Global Impressions Scale (CGI). Patients were then stratified by body mass index and differences in response to esketamine treatment were delineated. Statistical analyses are underway. Impact: The need to bring real effective treatment to patients suffering from treatment-resistant depression is needed now more than ever, as societal unrest and hardship continue to exacerbate the mental health pandemic. Innovation in care is needed to meet demand and bring more patients to long-term remission. As new treatment options like intranasal esketamine surface, further investigation into the confounding factors of treatment is needed.

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