Regular Research Article
Dynamic Prediction of Treatment Response in Late-Life Depression

https://doi.org/10.1016/j.jagp.2012.07.002Get rights and content

Objective

To identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and to 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 (odds ratio [OR]: 0.86, 95% confidence interval [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 greater than 27% in the first 2 weeks and with baseline MADRS scores of less than 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 years 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 2 weeks of treatment in predicting remission of late-life major depression.

Section snippets

Participants

Between July 20, 2009, and April 13, 2012, we screened 759 depressed patients aged 60 years and older, with 351 excluded because of failure to satisfy inclusion/exclusion criteria of the study. We excluded patients with a lifetime diagnosis of bipolar disorder, schizophrenia, schizoaffective, or other psychotic disorders; current psychotic symptoms; dementia; scores of 20 or less on the Folstein Mini-Mental Status Examination; a history of alcohol or substance abuse within the past 3 months;

Results

As presented in Table 1 (univariate analyses of the completer sample), 105 participants (48.0%) were classified as remitters and 114 (52.0%) as non-remitters, with no significant differences in referral sources or use of benzodiazepines between them. Non-remitters received higher end-phase doses (mg/day) of venlafaxine than did remitters (279 versus 201). Twelve variables were associated with remission at p less than 0.05 and were included in the multivariate models: age, sex, education,

Discussion

In depressed older adults, easily measured patient characteristics (sex, baseline level of depressive symptoms, and evidence of symptomatic improvement at Week 2) predicted the likelihood of remission after 12 weeks of treatment with venlafaxine XR. If a profile suggests treatment resistance, the clinician and patient can consider other treatment strategies, such as switching medication or augmentation of the initial antidepressant early in the course of treatment. Conversely, for older

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