Optimized regimens of combined medications for the treatment of major depressive disorder: a double-blind, randomized-controlled trial
Bibliographic record
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. Keywords: antidepressant, escitalopram, bupropion, action onset, augmentation, prolongation
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".