title: Apathy in currently nondepressed patients treated with a SSRI for a major depressive episode: outcomes following randomized switch to either duloxetine or escitalopram.
abstract: Apathy in the context of treated major depressive disorder (MDD) is a common but understudied symptom. This multicenter, double-blind, randomized study investigated whether switching from a selective serotonin reuptake inhibitor (SSRI) to a serotonin-norepinephrine reuptake inhibitor (SNRI), compared with switching to another SSRI, improved apathy symptoms in patients who had been treated with a SSRI for MDD for ≥ 3 months, were no longer depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤ 15), and continued to have apathy (Apathy Evaluation Scale--Clinician rated version [AES-C] total score >30). Following 8 weeks of treatment, both the duloxetine (SNRI, 244 patients) and escitalopram (SSRI, 239 patients) groups significantly improved from baseline on the AES-C total score (least squares mean change [standard error]: duloxetine -13.9 [0.54]; escitalopram -13.5 [0.54], both P < 0.001), and on the secondary apathy, depression, and functional outcomes. There were no significant differences between the two groups on any measure, including AES-C total score (least squares mean difference [95% confidence interval]: -0.4 [-1.87 to 1.10], P = 0.612; primary objective). There was a significant within-group improvement in apathy in the subgroup who received escitalopram before and during the study. There were few differences in safety between the two groups. This study did not support the hypothesis that switching from a SSRI to a SNRI has a beneficial effect on apathy symptoms. However, given the study limitations, it is possible that more specific targeting of the noradrenergic pathway would be of benefit.
authors.affiliation: Lilly Research Laboratories, Eli Lilly Canada, 3650 Danforth Ave, Toronto, ON, Canada M1N 2E8. Raskin_Joel@lilly.com
authors.forename: Joel
authors.initials: J
authors.lastname: Raskin
authors.forename: Thomas
authors.initials: T
authors.lastname: George
authors.forename: Renee E
authors.initials: RE
authors.lastname: Granger
authors.forename: Nadia
authors.initials: N
authors.lastname: Hussain
authors.forename: George Weizhong
authors.initials: GW
authors.lastname: Zhao
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D057565:Apathy / Q000187:drug effects*; D015283:Citalopram / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015283:Citalopram; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes