Dynamic Prediction of Treatment Response in Late-Life Depression

Abstract

Objective 1) identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and 2) use signal detection theory to develop decision trees to guide clinical decision making Method We treated 277 participants with current major depression using open-label venlafaxine XR (up to 300 mg/day) for 12 weeks, in an NIMH-sponsored randomized, placebo-controlled augmentation trial of adjunctive aripiprazole. Multiple logistic regression and signal detection approaches identified predictors of remission in both completer and intent-to-treat samples. Results Higher baseline depressive symptom severity (OR, 0.86, 95% CI, 0.80-0.93; p <0.001), smaller symptom improvement during the first two weeks of treatment (OR, 0.96, 95% CI, 0.94-0.97; p <0.001), male sex (OR, 0.41 95% CI, 0.18-0.93, p=0.03), duration of current episode ≥ 2 years (OR, 0.26 95% CI, 0.12-0.57, p<0.001) and adequate past depression treatment (ATHF >=3) (OR, 0.34 95% CI, 0.16-0.74, p=0.006) predicted lower probability of remission in the completer sample. Subjects with Montgomery Asberg (MADRS) decreasing by >27% in the first two weeks and with baseline MADRS scores of <27 (percentile rank = 51) had the best chance of remission (89%). Subjects with small symptom decrease in the first 2 weeks with adequate prior treatment and younger than 75 yrs old had the lowest chance of remission (16%). Conclusion Our results suggest the clinical utility of measuring pre-treatment illness severity and change during the first two weeks of treatment in predicting remission of late-life major depression.

Response to Antidepressant Medications in Late-Life Depression Across the Spectrum of Cognitive Functioning

“…In contrast, non-completers did not differ significantly in a pre-treatment measure of cognition. This pattern replicates findings that we recently reported in an independent sample of older patients with MDD—namely, that depression severity at start of treatment and longer index MDE correlate more strongly with response variability than cognitive function 17 . The current analyses were limited by incomplete data on non-completers, however, and we cannot discount that outcomes may have been influenced by selection bias, such that individuals who would not respond to treatment may have had greater propensity to drop out of the study prior to completion.…”

“…We also observed a fair amount of variability in response times, with some participants responding within a typical 12 week treatment course, and others requiring several months of treatment prior to reaching criteria for stable response. Of note, findings from an ongoing study 17 by our group suggest that it may be possible to shorten time to response by examining early indicators of response probability.…”

Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults

“…We obtained data from a prospective treatment study of late-life depression conducted at three academic sites (University of Pittsburgh, University of Toronto/Centre for Addiction and Mental Health, Washington University) (Joel et al in press) in 2009–2011. The institutional review boards at the three participating institutions approved the study protocol and all participants provided written informed consent.…”

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

“…First-line pharmacological treatments fail for over 50% of older adults with major depressive disorder (Joel et al, 2014, Mulsant et al, 2014, Smagula et al, 2015). Safe and efficacious adjunctive treatments for late-life major depressive disorder (LLD) are in high demand for the rapidly aging global population (Cauley, 2013).…”

“…We examined the roles of pain, physical function difficulties, and suicidality, which may mark etiopathological differences relevant to aripiprazole response. We also considered clinical characteristics previously related to first-line treatment outcomes (e.g., duration of the current depressive episode (Joel, Begley, 2014, Nelson et al, 2012, Smagula, Butters, 2015)). Variability in individual depressive symptom expression (i.e.…”