Evaluation of Depression Severity Items on the Patient Health Questionnaire (PHQ-9) and Sheehan Disability Scale (SDS) in Patients With Treatment-Resistant Depression Treated With Esketamine Nasal Spray

Introduction: Major depressive disorder is a leading cause of disability and about 30% of patients are diagnosed with treatment-resistant depression (TRD) after failing two pharmacological treatments. This study objective was to evaluate individual items of the PHQ-9 and SDS to show differences by treatment arm over the course of treatment.

Methods: TRANSFORM-2 (NCT02418585) was a Phase 3 trial that evaluated efficacy and safety of flexible esketamine nasal spray (56 mg or 84 mg) in combination with newly initiated oral antidepressant (ESK+AD) vs oral antidepressant + placebo nasal spray (AD+PBO) in TRD patients. Patient-reported outcome instruments were used to assess self-reported depression symptoms (PHQ-9) and functional disability (SDS). Instrument total scores reflect a single construct of depression severity or functional disability and each instrument item assesses a depression symptom, or aspect of function. Change from baseline were analyzed using a mixed-effects model using repeated measures (MMRM). Generalized estimation equations (GEE) of logistic regression models were used to estimate the likelihood of improvement for individual items of these instruments.

Results: The magnitude of total score change from baseline for the SDS and PHQ-9 was larger for ESK+AD compared to AD+PBO. Odds of improvement for single items favored ESK+AD for both measures (Odds ratio 1.367-2.767 for the PHQ-9 and 1.994 – 3.378 for the SDS).

Conclusions: This study shows that while the magnitude of improvement varied on individual items, treatment with ESK+AD leads to symptom improvement in TRD patients. This assists interpretation of the total scores generated by these PRO measures.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.