Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported.


METHODS
Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks.


RESULTS
Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups.


CONCLUSIONS
In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo.
Michelson
David
D
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind., USA. david_michelson@merck.com
Adler
Lenard A
LA
Amsterdam
Jay D
JD
Dunner
David L
DL
Nierenberg
Andrew A
AA
Reimherr
Frederick W
FW
Schatzberg
Alan F
AF
Kelsey
Douglas K
DK
Williams
David W
DW
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011437:Propylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index
D018759:Adrenergic Uptake Inhibitors; D000069445:Atomoxetine Hydrochloride; D011437:Propylamines; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline