A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode.
Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors (SSRIs) in severe major depressive disorder (MDD). This prospective pragmatic trial tests this hypothesis. Patients with severe MDD were randomly assigned to either duloxetine (a serotonin and norepinephrine-reuptake inhibitor) or physicians' choice of four generic SSRIs. Nonblinded, flexibly dosed treatment was used to mimic clinical practice. To address potential investigator bias, the patient-reported Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) was used as the primary efficacy outcome measure. A total of 750 outpatients (19.2%, African descent; 14.8%, Hispanic) were randomized. The primary outcome, remission at week 12 by QIDS-SR, was numerically greater for duloxetine compared with SSRIs (36 vs. 32%), but this difference was not statistically significant. Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item, the Brief Pain Inventory, and the Sheehan Disability Scale. Remission superiority on the QIDS-SR was not achieved. Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning. Study demographics suggest a more generalizable racial and ethnic population than is typical in randomized clinical trials.
Lilly USA, LLC, Lilly Corporate Center, Indianapolis, IN 46285, USA. martinezjames@lilly.com
James Michael
JM
Martinez
Wayne
W
Katon
John H
JH
Greist
Kurt
K
Kroenke
Michael E
ME
Thase
Adam L
AL
Meyers
Sara Elizabeth
SE
Edwards
Lauren B
LB
Marangell
Scarlett
S
Shoemaker
Ralph
R
Swindle
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004185:Disability Evaluation; D016568:Drugs, Generic / Q000009:adverse effects / Q000627:therapeutic use*; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D016568:Drugs, Generic; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes