Predicting Treatment Response in Major Depressive Disorder: The Impact of Early Symptomatic Improvement

Abstract

Objective: Antidepressants (ADs) are the mainstay of treatment for major depressive disorder (MDD). Despite their widespread usage, a consensus does not exist as to the timing of clinically significant symptomatic improvement during an AD trial. The objective of this review is to provide practitioners with empirically based recommendations pertaining to the optimal duration of index (initial) AD therapy before a clinical intervention is warranted. Methods:We conducted a nonsystematic review, using a combination of a MeSH key word search, Google Scholar, and the Scopus database. Our search strategy focused on research papers reporting on the early symptomatic response to AD therapy.Results: Available evidence suggests that there are several subpopulations that exist within whole-group data assigned to an AD treatment. Among the responder subgroups, an early responder group (that is, less than 3 weeks) and later responder group (that is, 3 weeks or more) are identified. People who exhibit early partial symptomatic improvement are more likely to respond to therapy thereafter. However, the interpretability of extant evidence is complicated by the use of disparate statistical approaches with differing computational complexity and sample heterogeneity. Conclusions:Response outcomes in MDD are heterogeneous. Available data suggest that people may respond early, late, and (or) continuously over time, and may represent distinct subpopulations that provide a proximate indication for treatment response outcomes. Notwithstanding, a pragmatic recommendation would be to consider a treatment intervention (for example, dosage optimization and [or] augmentation) if, after 3 to 4 weeks, symptomatic improvement is insufficient. W W WObjectif : Les antidépresseurs (AD) sont le soutien principal du traitement du trouble dépressif majeur (TDM). Malgré leur usage répandu, il n'y a pas de consensus sur la chronologie de l'amélioration symptomatique cliniquement significative durant un essai d'AD. L'objectif de cette étude est de fournir aux médecins des recommandations éclairées par les preuves empiriques concernant la durée optimale d'un premier traitement (initial) par AD avant qu'une intervention clinique soit justifiée.Méthodes : Nous avons mené une revue non systématique, à l'aide d'une combinaison de recherche par mot clé dans MeSH, Google Scholar, et Scopus Database. Notre stratégie de recherche portait sur les articles de recherche traitant de la réponse symptomatique précoce au traitement par AD.Résultats : Les données probantes disponibles suggèrent qu'il existe plusieurs souspopulations au sein des données de groupes entiers associées à un traitement par AD. Parmi les sous-groupes de répondants, un groupe de répondants précoces (c'est-à-dire, moins de 3 semaines) et un groupe de répondants tardifs (c'est-à-dire, 3 semaines ou plus) sont identifiés. Les personnes qui affichent une amélioration symptomatique partielle précoce sont plus susceptibles de répondre au traitement par la suite. Cependant, l'interprétabilité des donné...

Treatment-Resistant Depression in Primary Care across Canada

“…However, the duration of time before treatment adjustment was longer than recommended: 6 weeks for the TRD group and 8 weeks for the non-TRD group. Current evidence suggests making a change if there is no improvement after 4 to 6 weeks 58. This is due to findings that lack of early improvement is predictive of nonresponse 59,60…”

Early Switching Strategies in Antidepressant Non-Responders: Current Evidence and Future Research Directions

“…insomnia) are prone to improve or worsen early in treatment as a consequence of side effects of the antidepressant, and hence will confound the assessment of early improvement. There is also some evidence that certain depressive symptoms may improve earlier and to a greater extent than other core symptoms [11,15,29]. Further research into new clinical metrics, possessing greater item sensitivity and specificity for detection of these early effects of antidepressant therapy, is required.…”

“…Evidence derived from older antidepressant studies suggested a delayed onset of therapeutic response [6][7][8][9], leading to the conventional belief that patients need to wait at least 8 weeks before concluding whether or not they are responding to an antidepressant [10]. However, recent reviews [10,11] have summarized the many subsequent studies that showed an early onset (within 1-2 weeks) of antidepressant effects in ultimate responders, thereby contradicting the delayed-onset hypothesis and suggesting that responders can be identified earlier in the course of treatment.…”

“…An early study of fluoxetine response found that early improvement at 2 weeks could predict 75 % of eventual responders [14]. Furthermore, other studies have suggested that lack of early improvement at 2 weeks may serve to reliably identify a subpopulation of non-responders [11]. Having this non-responder subpopulation wait 8-12 weeks before switching to another antidepressant may not be justified.…”

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“…A double blind, placebo controlled study of elderly outpatients found that those who showed early response, based on a 20% or greater decrease in the 21-item Hamilton Rating Scale for Depression (HAM-D21), in weeks 1, 2 or 3, were more likely to respond well by week 6 [21]. A 2012 nonsystematic review of antidepressant studies in depressed subjects concluded that, whereas outcomes in major depression are heterogeneous, people who respond partially in the first three weeks are more likely to respond more fully later on [22].…”