ABSTRACT
Background: Digital technologies have the potential to provide objective and precise tools to detect depression-related symptoms. Deployment of digital technologies in clinical research can enable collection of large volumes of clinically relevant data that may not be captured using conventional psychometric questionnaires and patient-reported outcomes. Rigorous methodology studies to develop novel digital endpoints in depression are warranted. Objective: We conducted an exploratory, cross-sectional study to evaluate several digital technologies in subjects with major depressive disorder (MDD) and persistent depressive disorder (PDD), and healthy controls. The study aimed at assessing utility and accuracy of the digital technologies as potential diagnostic tools for unipolar depression, as well as correlating digital biomarkers to clinically validated psychometric questionnaires in depression. Methods: A cross-sectional, non-interventional study of 20 participants with unipolar depression (MDD and PDD/dysthymia) and 20 healthy controls was conducted at the Centre for Human Drug Research (CHDR), the Netherlands. Eligible participants attended three in-clinic visits (days 1, 7, and 14), at which they underwent a series of assessments, including conventional clinical psychometric questionnaires and digital technologies. Between the visits, there was at-home collection of data through mobile applications. In all, seven digital technologies were evaluated in this study. Three technologies were administered via mobile applications: an interactive tool for the self-assessment of mood, and a cognitive test; a passive behavioral monitor to assess social interactions and global mobility; and a platform to perform voice recordings and obtain vocal biomarkers. Four technologies were evaluated in the clinic: a neuropsychological test battery; an eye motor tracking system; a standard high-density electroencephalogram (EEG)-based technology to analyze the brain network activity during cognitive testing; and a task quantifying bias in emotion perception. Results: Our data analysis was organized by technology - to better understand individual features of various technologies. In many cases, we obtained simple, parsimonious models that have reasonably high diagnostic accuracy and potential to predict standard clinical outcome in depression. Conclusion: This study generated many useful insights for future methodology studies of digital technologies and proof-of-concept clinical trials in depression and possibly other indications.
ABSTRACT
INTRODUCTION: This study investigated if optimized dose regimens of escitalopram and bupropion combination from treatment initiation can be superior to either drug alone in speed of onset, remission rate, and maintenance of therapeutic efficacy. METHODS: Patients from a single site (N=85) within a larger double-blind 12-week trial (N=245) showed a lower dropout rate (14% vs 40%) and used higher doses; therefore, this cohort was analyzed separately. Uniquely at this single site, after 12 weeks, non-remitters on a single drug received the other one in addition and combination non-remitters underwent a switch of escitalopram for duloxetine for a 6-week period. Escitalopram could be given up to 40 mg/day and bupropion up to 450 mg/day. A 6-month prolongation was then implemented in remitters, maintaining the double-blind design throughout. Remission was defined as ≤7 on the 17-item Hamilton Rating Scale for Depression, as in the initial publication. RESULTS: At week 2, combination treatment was superior in remission rate (5/28) compared with both bupropion (0/26) and escitalopram monotherapies (0/31; P=0.03 and P=0.02, respectively). The week 12 remission rate of combination treatment showed a higher rate (15/28) relative to bupropion monotherapy (7/26; P=0.04), but not statistically different from escitalopram monotherapy (11/31; P=0.13). The 6-week augmentation produced remission in 7/21 monotherapy non-remitters and 0/6 in the switch group (P=0.13). Remission was sustained in 28/31 patients enrolled in the 6-month maintenance. CONCLUSION: These results suggest that combination of escitalopram and bupropion from treatment initiation is superior to either monotherapy in speed of onset. The addition of a second drug in non-remitters can lead to additional remissions, as shown with other combinations of medications. Treatment prolongation using optimized regimens leads to low relapse rates.
