Discussion
TRD, anxiety, depressive symptoms, depressed, depression/anxiety, depression, AD, disability, AD +
DISEASE, SECONDARY, BLIND
The results of this secondary analysis of data from TRANSFORM-2 evaluating HRQoL and health status in patients with TRD demonstrated clinically meaningful responses with ESK + AD vs. AD + PBO using the EQ-5D-5L, PHQ-9, and the SDS scores. The proportion of patients who reported impairment in each of the 5 EQ-5D-5L health state dimensions decreased from baseline to the end of the 4-week double-blind treatment phase in both treatment groups. Results in each of the 5 dimensions of EQ-5D-5L, the weighted HSI score (based on responses in all 5 dimensions), and the EQ-VAS score numerically favored the ESK + AD group over the AD + PBO group, and the 95% CI for the mean difference between groups at Day 28 did not overlap 0 in 4 of the 5 dimensions. Notably the category that showed the greatest number of patients reporting problems at Day 28 was for the depression/anxiety dimension. This may be explained by the double-barreled question combining anxiety and depression where patients may have responded based on either symptom. Additionally, while patients in both treatment groups showed clinically meaningful improvement in depression symptoms according to Montgomery Asberg Depression Rating Scale (MADRS) scores and PHQ-9 scores, not all patients achieved complete resolution of depression and still reported symptoms of mild depression. Responses for level 2 symptoms (I am slightly anxious or depressed) were 41.3% for ESK + AD and 29% for ESK + PBO and support this assessment. These factors may explain the high level of patients reporting problems in the depression/anxiety EQ-5D-5L dimension.At the end of the double-blind treatment phase, patients treated with ESK + AD self-reported greater improvements from baseline in functioning and associated disability as assessed by the SDS scores than those treated with AD + PBO. Importantly, consistent advantages in patient reported HRQoL and functioning improvement were observed in this secondary analysis, supporting the clinical meaningfulness of the improvement observed in the primary endpointData collected on HRQoL and health status using the EQ-5D-5L provide additional context for the improvement in depressive symptoms noted in the results from the primary efficacy analysis [While EQ-5D-5L is a generic measure of quality of life across 5 dimensions, the SDS assesses functional impairment and associated disability across 3 domains (work/school, social life/leisure activities, and family life/home responsibilities). As improvement in function is often distal to the improvement in depressive symptoms for patients with TRD, it is notable that patients treated for 4 weeks with ESK + AD reported greater improvement in function than those treated with AD + PBO. Furthermore, a combination of EQ-5D-5L and SDS supports the overall impact of the disease and treatment on HRQoL.The improvement in HRQoL with ESK + AD may translate into enhancement of the patients’ overall ability to perform daily activities, concentrate on work, and engage more with family/friends, as demonstrated in an analysis of responses to semi-structured interviews conducted in patients who received long-term esketamine treatment [The results of this study must be viewed with caution given some notable limitations. Esketamine treatment has known transient dissociative effects that are difficult to blind and could have biased patient responses [