Trajectories of depression symptom change during and following treatment in adolescents with unipolar major depression

Abstract

Objective: To classify a cohort of depressed adolescents recruited to the UK IMPACT trial, according to trajectories of symptom change. We examined for predictors and compared the data-driven categories of patients with a priori operational definitions of treatment response. Method: Secondary data analysis using growth mixture modelling (GMM). Missing data were imputed. Trajectories of self-reported depressive symptoms were plotted using scores taken at six nominal time points over 86 weeks from randomisation in all 465 patients. Results: A piecewise GMM categorised patients into two classes with initially similar and subsequently distinct trajectories. Both groups had a significant decline in depressive symptoms over the first 18 weeks. Eighty-four per cent (84.1%, n = 391) of patients were classed as 'continued-improvers' with symptoms reducing over the duration of the study. A further class of 15.9% (n = 74) of patients were termed 'halted-improvers' with higher baseline depression scores, faster early recovery but no further improvement after 18 weeks. Presence of baseline comorbidity somewhat increased membership to the halted-improvers class (OR = 1.40, CI: 1.00-1.96). By end of study, compared with classes, a clinical remission cut-off score (≤27) and a symptom reduction score (≥50%) indexing treatment response misclassified 15% and 31% of cases, respectively. Conclusions: A fast reduction in depressive symptoms in the first few weeks of treatment may not indicate a good prognosis. Halted improvement is only seen after 18 weeks of treatment. Longitudinal modelling may improve the precision of revealing differential responses to treatment. Improvement in depressive symptoms may be somewhat better in the year after treatment than previously considered. and ig104@cam.ac.uk (I.M.D.) Key pointsAt least 20% of moderate to severely depressed adolescents show no response to current treatments. Modelling of depressive symptom trajectories of change suggested that 84.1% of depressed adolescents could be considered as 'continued responders', whilst 15.9% could be classed as 'halted responders', that is showing significant decrease in depression severity over the first 18 weeks, which then halted over the subsequent year.By the end of study, 'continued responders' showed on average a 60.5% improvement in depressive symptoms, compared with 11.0% amongst the halted-improvers.A fast reduction in depressive symptoms may not indicate a good prognosis. Clinical progress continues in the year after treatment and overall may be better than previously considered.

Trajectories of change in depression symptoms and suicidal ideation over the course of evidence-based treatment for depression: Secondary analysis of a randomised controlled trial of cognitive behavioural therapy plus fluoxetine in young people

“…These young people had severe depression at baseline and experienced early significant improvement in their symptoms such that, by week 4 of the trial, their scores on the MADRS were below the cut point used for entry into the trial, indicative of treatment response (Hawley et al, 2002). This early improvement is consistent with what has been observed in previous similar studies in adults (Batterham et al, 2017) and adolescents (Davies et al, 2019; Scott et al, 2019). However, in this study, almost one-half of those who began the trial with severe depression experienced only slight improvement in depression symptomatology over the course of the trial, continuing to experience clinically significant levels of depression, despite treatment.…”

“…This study was a secondary analysis of data from a randomised controlled trial of CBT plus fluoxetine (CBT + FLX) versus CBT plus placebo (CBT + PLO) for the treatment of 15- to 25-year-old young people diagnosed with major depression (Davey et al, 2019). Two distinct trajectories for clinician-rated depression symptoms were identified over the course of the 12-week trial, in line with trajectory analysis of data from clinical trials undertaken with community-based adults (Batterham et al, 2019) and adolescents treated in a tertiary clinic setting (Davies et al, 2019). Half were assigned to the Improving group.…”

Predictors, Moderators, and Mediators Associated With Treatment Outcome in Randomized Clinical Trials Among Adolescents With Depression

“…Across these 81 publications, a wide range of variables were tested as predictors, moderators, and mediators associated with depression outcome. Fifty-one publications (63%) 29,31,[33][34][35]39,41,43,[45][46][47]49,50,53,54,65,66,68,71,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88]95,96,98,[100][101][102][103]105,[107][108][109][110][111][113][114][115] tested baseline predictors, 45 (56%) 28,30,…”

Conflicted Anger as a Central Dynamic in Depression in Adolescents—A Double Case Study

“…The process of developing unique case formulations for individual patients may be necessary for therapeutic change, and to develop new patterns in their life [ 14 , 24 , 25 ]. Davies and colleagues (2020) [ 26 ] conducted a study about the trajectories of depression symptom change during and following treatment in adolescents with unipolar major depression. A fast reduction in depressive symptoms in the first few weeks of treatment may not indicate a good prognosis.…”

“…Longitudinal modelling may improve the precision of revealing differential responses to treatment. Improvement in depressive symptoms may be somewhat better in the year after treatment than previously considered [ 26 ].…”