Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms

Abstract

Background: Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.

Method: We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D).

Results: The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates.

Conclusions: Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.

Trial registration: ClinicalTrials.gov NCT00021528.

Figures

Fig. 1

Depression symptom structure. The figure reviews the results of categorical-factor analysis of items from three depression rating scales: the Montgomery–Åsberg Depression Rating Scale (MADRS), the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the Beck Depression Inventory (BDI). Categorical item factor analysis identified three major factors: observed mood, cognitive symptoms and neurovegetative symptoms. These three factors further split into six dimensions: mood, anxiety, pessimism, interest-activity, sleep and appetite. * The items measuring activity and energy loaded on the observed mood factor in the three-factor solution, but in the six-factor solution, these items cross-loaded evenly between the mood and the interest-activity dimensions.

Fig. 2

Association between the interest-activity symptom dimension at baseline and percentage improvement over 12 weeks of treatment on the primary outcome measures in (a) Genome-based Therapeutic Drugs for Depression (GENDEP) and (b) Sequenced Treatment Alternatives to Relieve Depression (STAR*D). For the purpose of plotting, subjects in each study were separated into quintiles (1 to 5 on the x axis) according to increasing interest-activity scores at baseline. The primary outcome measure in GENDEP is the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS). The primary outcome measure in STAR*D is the 17-item Hamilton Rating Scale for Depression (HAMD-17) rated by an independent outcome assessor. The percentage reduction on the primary outcome scale over 12 weeks of treatment was adjusted for age, sex and centre differences. Missing week-12 data were imputed by the best unbiased linear estimate from a mixed linear regression model.

Fig. 3

Association between the interest-activity symptom dimension at baseline and remission [Hamilton Rating Scale for Depression (HAMD)-17 score ≤7] in (a) Genome-based Therapeutic Drugs for Depression (GENDEP) and (b) Sequenced Treatment Alternatives to Relieve Depression (STAR*D). Subjects in each study are separated into quintiles of interest-activity scores at baseline (1–5 on the x axis). The proportion reaching remission at last visit is plotted on the y axis.