title: Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder.
abstract: Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size = 0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size = 0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address: sfs26@pitt.edu.
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, PA, USA.
authors.forename: Meredith L
authors.initials: ML
authors.lastname: Wallace
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
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, PA, USA; VA Pittsburgh Healthcare System, Geriatric Research, Education, and Clinical Center, USA.
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.affiliation: Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.affiliation: Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.affiliation: Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
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, PA, USA.
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Departments of Psychology, Epidemiology, Biostatistics, and Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA, USA.
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, PA, USA; Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
mesh_terms: D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D000068180:Aripiprazole / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014145:Trail Making Test; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000069470:Venlafaxine Hydrochloride; D000068180:Aripiprazole
keywords: Aripiprazole; Combined moderators; Late-life depression; Moderators; Personalized medicine