Early switch strategy in patients with major depressive disorder: a double-blind, randomized study.
OBJECTIVE
Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder.


METHODS
Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥ 50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤ 7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses.


RESULTS
Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048).


CONCLUSIONS
Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.
Clinical Research Physician Neuroscience, Medical Department, Eli Lilly and Company, Madrid, Spain. romera_irene@lilly.com
Irene
I
Romera
Victor
V
Pérez
Jose Manuel
JM
Menchón
Alexander
A
Schacht
Rita
R
Papen
Doris
D
Neuhauser
Mocrane
M
Abbar
Pär
P
Svanborg
Inmaculada
I
Gilaberte
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015283:Citalopram / Q000008:administration & dosage*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000187:drug effects*; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D013876:Thiophenes / Q000627:therapeutic use*
D000928:Antidepressive Agents; D013876:Thiophenes; D015283:Citalopram; D000068736:Duloxetine Hydrochloride