Optimized regimens of combined medications for the treatment of major depressive disorder: a double-blind, randomized-controlled trial

Zoë Zuilhof, Sandhaya Norris, Claude Blondeau, Pierre Tessier, Pierre Blier Department of Psychiatry, University of Ottawa, The Royal Ottawa Institute of Mental Health Research, Ottawa, ON, Canada 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 remissio