Trajectories of change in depression severity during treatment with antidepressants

Abstract

Background. Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change.Method. Growth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses.Results. The final two-piece growth mixture model categorized participants into a majority (75 %) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results.Conclusions. Latent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

Folate Augmentation of Treatment – Evaluation for Depression (FolATED): randomised trial and economic evaluation

“…48 25 weeks, is entirely consistent with the model reported in the large GENDEP sample of 807 patients with major depressive disorder treated with escitalopram or nortriptyline. 154 Also in line with the published literature, baseline severity of depressive symptoms predicted greater response to ADM. 155 Treatment with SSRIs also led to better outcomes over 25 weeks than treatment with other antidepressants. This supports previous reviews suggesting better practical outcomes for SSRIs are due to much better completion of therapeutic courses for SSRIs compared with other antidepressants like TCAs.…”

Trajectories of prosocial behaviors conducive to civic outcomes during the transition to adulthood: The predictive role of family dynamics☆

“…Because quadratic growth terms were not significant for any class models, the best final solution was represented by the linear model (see Table 3). Following Uher et al (2010), and because the four trajectory solution presented one class with a very low proportion of subjects (27 subjects ¼ 4% of the sample), we found that the three trajectory solution provided the most interpretable description of prosocial development. This solution presented an adequate classification quality, as Table 2 Descriptive statistics and correlations among prosocial behavior, family dynamics and civic outcomes.…”

Data-Driven Course Trajectories in Primary Care Patients With Major Depressive Disorder

“…[20] Despite the use of similar techniques, the number of identified course groups varied (2)(3)(4)(5). This could be explained by differences in numbers of follow-ups (7 [14] to 24 [20]), interval lengths (1 week [18] to 3 months [14]), and instruments. Interestingly, a short-term week-to-week perspective led to two to three classes, [17,18] whereas more widely spaced time frames resulted in four to six classes.…”

“…This could be explained by differences in numbers of follow-ups (7 [14] to 24 [20]), interval lengths (1 week [18] to 3 months [14]), and instruments. Interestingly, a short-term week-to-week perspective led to two to three classes, [17,18] whereas more widely spaced time frames resulted in four to six classes. [14,20] Although insightful, the inconsistent results so far make it hard to form a coherent view of typical course trajectories in clinical practice.…”