In patients with major depressive disorder (MDD), early improvement in symptom clusters was associated with desvenlafaxine treatment compared with placebo, which significantly predicts symptomatic or functional remission at week 8, according to data published in the Journal of Psychopharmacology.

The investigators sought to evaluate the effect of 50 mg or 100 mg of desvenlafaxine vs placebo on symptom cluster scores in patients with MDD, as well as the association between early improvement in symptom clusters and symptomatic or functional remission at 8 weeks. Data from a total of 4317 patients from 9 multicenter randomized double-blind placebo-controlled studies of desvenlafaxine were included in the analysis.

The symptom cluster scores were based on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Logistic regression was used to analyze the association between early improvement in symptom clusters (ie, ≥20% improvement from baseline at week 2), as well as symptomatic and functional remission (ie, HAMD total score ≤7; Sheehan Disability Scale score <7) at week 8. Symptom clusters according to the Montgomery-Åsberg Depression Rating Scale (MADRS) were also analyzed.

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For all symptom clusters, treatment with 50 mg or 100 mg desvenlafaxine was associated with significant improvements from baseline compared with placebo for all symptom clusters (P <.001) other than a sleep symptom cluster for desvenlafaxine 100 mg. Furthermore, early improvement was significantly associated with the achievement of symptomatic and functional remission in all treatment arms at week 8 with all symptom clusters (P ≤.0254).

Major study limitations include the reliance on a post hoc analysis of data from studies that were not designed specifically to evaluate the effects of early improvements on later outcomes. Moreover, even though the total HAMD-17 and MADRS scales were included as efficacy outcomes in the pooled analyses, none of the studies was designed to evaluate factors or subscales.

The investigators concluded that the results of the present analysis contribute to the understanding of how the symptom profiles of patients with MDD may inform treatment decisions and assist in monitoring progress aimed at the goal of full functional recovery in this population. They noted, “If clinicians can understand what differentiates early responders from nonresponders, they can increase their chances of prescribing effective medications early in treatment, with the prospect of meaningfully improving patient outcomes.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Katzman MA, Wang X, Wajsbrot DB, Boucher M. Effects of desvenlafaxine versus placebo on MDD symptom clusters: a pooled analysis [published online January 8, 2020]. J Psychopharmacol. doi:10.1177/0269881119896066