title: Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression: An Analysis of the IRL-GRey Randomized Clinical Trial.
abstract: OBJECTIVE
  Safe, efficacious, second-line pharmacological treatment options exist for the large portion of older adults with major depressive disorder who do not respond to first-line pharmacotherapy. However, limited evidence exists to aid clinical decision making regarding which patients will benefit from which second-line treatments.
  
  
  OBJECTIVE
  To test the moderating role of pretreatment executive function, severity of anxiety, and severity of medical comorbidity in remission of treatment-resistant late-life depression after aripiprazole augmentation.
  
  
  METHODS
  As follow-up to a 12-week randomized clinical trial of aripiprazole augmentation for first-line treatment-resistant late-life depression (Incomplete Response in Late-Life Depression: Getting to Remission [IRL-GRey]), we evaluated the effects of the following potential moderators and their interactions with treatment: baseline assessments of executive function (set shifting measured by the Trail Making Test) and response inhibition control (measured by a Color-Word Interference task), anxiety symptoms, and medical comorbidity. Analyses were conducted in May and June 2015.
  
  
  METHODS
  Aripiprazole or placebo tablets were started at 2 mg daily and titrated as tolerated, to a maximal dose of 15 mg daily.
  
  
  METHODS
  Remission of treatment-resistant late-life depression (defined as a Montgomery-Åsberg Depression Rating Scale score of ≤10 at both of the last 2 consecutive visits).
  
  
  RESULTS
  Of 181 trial participants (103 female [56.9%]) who were 60 years of age or older and whose major depression had failed to remit with venlafaxine hydrochloride monotherapy, 91 received aripiprazole and 90 received placebo. Remission occurred in 40 (43%) who received aripiprazole and 26 (29%) who received placebo. Baseline set shifting moderated the efficacy of aripiprazole augmentation (odds ratio [OR], 1.66 [95% CI, 1.05-2.62]; P = .03 for interaction with treatment). Among participants with a Trail Making Test scaled score of 7 or higher, the odds of remission were significantly higher with aripiprazole than with placebo (53% vs 28%; number needed to treat, 4; OR, 4.11 [95% CI, 1.83-9.20]). Among participants with a Trail Making Test scaled score of less than 7, aripiprazole and placebo were equally efficacious (OR, 0.64 [95% CI, 0.15-2.80]). Greater severity of anxiety at baseline predicted a lower remission rate but did not moderate aripiprazole efficacy; each standard deviation greater anxiety severity was associated with 50% reduced odds of remission in both aripiprazole and placebo arms. Medical comorbidity and Color-Word Interference test performance were neither general predictors nor treatment-moderating factors.
  
  
  CONCLUSIONS
  Set-shifting performance indicates which older adults with treatment-resistant depression may respond favorably to augmentation with aripiprazole and thus may help to personalize treatment.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00892047.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Shriya H
authors.initials: SH
authors.lastname: Kaneriya
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Robbins-Welty
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Smagula
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.affiliation: Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.affiliation: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Blumberger
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Anderson
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania6Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania7Department of Epidemiology, University of.
authors.forename: Mary Amanda
authors.initials: MA
authors.lastname: Dew
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Francis
authors.initials: F
authors.lastname: Lotrich
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Department of Mental Health, Federal University of Minas Gerais School of Medicine, Belo Horizonte, Minas Gerais, Brazil11Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston.
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania12Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pi.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000517:prevention & control; D000068180:Aripiprazole / Q000627:therapeutic use*; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000523:psychology*; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012718:Set, Psychology; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000627:therapeutic use
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D000069470:Venlafaxine Hydrochloride; D000068180:Aripiprazole