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.

Clinical Characteristics and Psychotropic Prescribing Patterns Associated with impaired Concentration in Asians with Depressive Disorders: The REAP-AD Study

“…Indecisiveness and the other interest-activity depressive symptoms (including low interest, reduced activity, and lack of enjoyment) were proposed as predictors of poor treatment outcomes to escitalopram and nortriptyline in 811 adults with moderate to severe depression in the study Genome-based Therapeutic Drugs for Depression (GENDEP) (Ulher et al 2009). Similar findings have been reported in 3,637 MDD adults treated with citalopram in Sequenced Treatment Alternatives to Relieve Depression (STAR*D) (Ulher et al 2012). In addition, indecisiveness, guilt, ideas of reference, depressed mood, insomnia and other symptom dimension were proposed as predictors of depression that is resistant to escitalopram and nortriptyline in 793 adults with MDD (Iniesta et al 2016).…”

“…It has been reported that cognitive dysfunction is already present at an early stage of depressive disorders and is maintained even in remission (Woo et al 2016). Impaired concentration or indecisiveness has been proposed as a predictor of poor antidepressant treatment outcome (Ulher et al 2012). Regarding psychiatric taxonomy, impaired concentration has been a symptom of depression, although it is also a criterion for other disorders (Zimmerman et al 2006).…”

Pharmacogenomic Testing and Personalized Treatment of Depression

“…The enthusiasm for biomarker identification has overshadowed a long history of efforts to direct prescribing on the basis of clinical observations, i.e., by identifying patient subgroups on the basis of clinical symptomatology or comorbidity (34 ). For example, anxiety, psychotic-like symptoms, and other sets of depressive symptoms have been associated with poorer treatment response (35)(36)(37). Two relatively recent developments might make this strategy more practical: the emergence of larger clinical data sets, including those drawn from large effectiveness studies, electronic health records (38 ), and patient self-report in direct-to-consumer genomics testing (39 ), as well as the application of newer machine learning tools.…”

137. Association between Habenula Dysfunction and Motivational Symptoms in Unmedicated Major Depressive Disorder

“…Anhedonia, defined as a loss of interest or pleasure in previously enjoyable activities, is linked with disrupted transmission in the mesocorticolimbic dopamine system and is clinically important because it predicts poor response to standard antidepressant treatment (McMakin et al, 2012;Uher et al, 2012). Although there is currently no effective treatment specifically for anhedonia, suppression of habenula neuron firing has been shown to resolve depressive-like behaviour in rats (Li et al, 2011) and was reported to treat symptoms in a treatment-refractory patient through deep-brain stimulation (DBS) (Sartorius et al, 2010), suggesting a potential avenue for the development of novel therapeutic strategies.…”