Specific symptomatology profile associated with treatment resistant depression: A multicentric study from the Group for the Study of Resistant Depression with a focus on sex

Background: Clinical predictors of treatment-resistant depression could improve treatment strategies. Depressive symptom profiles at baseline are potential outcome predictors, but little evidence is available, and sex-specific profiles have been scarcely investigated. Methods: Baseline symptom scores of 1294 patients with major depressive disorder were assessed by the Montgomery-Åsberg depression rating scale (MADRS) as part of a multicenter study by the “Group for the Studies of Resistant Depression”. Treatment outcomes were assessed according to the MADRS after ≥4 weeks of naturalistic treatment. We tested if individual MADRS item scores at baseline were associated with treatment outcome in the whole sample and in sex-stratified subgroups. Results: A specific baseline symptom profile was associated with non-response in the whole sample. In particular, apparent and reported sadness, reduced sleep, lassitude, inability to feel, and pessimistic thoughts were the only MADRS items that scored higher at baseline in patients with subsequent lack of response. In the sex-stratified analysis, females showed a similar profile overall, however they showed higher baseline levels of inner tension, inability to feel, and pessimistic thoughts compared to males, and these symptoms were associated with lack of response in females but not in males. Neurovegetative symptoms were poorly predictive. Overall baseline severity related to poor response. Limitations: This is a post-hoc analysis. The naturalistic design of the study with a retrospective assessment is potential limitations. Conclusion: A specific baseline symptom profile characterized by higher sadness, reduced sleep and anhedonic features may be indicative of poor treatment outcome. Females showed a distinctive baseline profile associated with poor response.