Clinical Factors Associated With Treatment Resistance in Major Depressive Disorder

TLDR

Few studies have examined clinical features linked to treatment‑resistant depression defined by failure of at least two consecutive antidepressant trials. This multicenter study aimed to identify clinical and demographic factors associated with treatment‑resistant depression in patients who did not respond to at least two adequate antidepressant treatments. The analysis included 702 major depressive disorder patients, classifying 356 as treatment‑resistant (HAMD ≥ 17 after two trials) and 346 as nonresistant, and applied Cox regression to evaluate associations between clinical variables and TRD. Eleven variables were associated with TRD, with comorbid anxiety disorder being the strongest predictor (OR = 2.6), followed by panic disorder, early onset, recurrent episodes, and nonresponse to the first antidepressant.

Abstract

Article Abstract Objectives: Very few studies have investigated clinical features associated with treatment-resistant depression (TRD) defined as failure of at least 2 consecutive antidepressant trials. The primary objective of this multicenter study was to identify specific clinical and demographic factors associated with TRD in a large sample of patients with major depressive episodes that failed to reach response or remission after at least 2 consecutive adequate antidepressant treatments. Method: A total of 702 patients with DSM-IV major depressive disorder, recruited from January 2000 to February 2004, were included in the analysis. Among them, 346 patients were considered as nonresistant. The remaining 356 patients were considered as resistant, with a 17-item Hamilton Rating Scale for Depression score remaining greater than or equal to 17 after 2 consecutive adequate antidepressant trials. Cox regression models were used to examine the association between individual clinical variables and TRD. Results: Among the clinical features investigated, 11 variables were found to be associated with TRD. We found anxiety comorbidity (p < .001, odds ratio = 2.6), comorbid panic disorder (p 1 (p = .003, OR = 1.6), recurrent episodes (p = .009, OR = 1.5), early age at onset (p = .009, OR = 2.0), and nonresponse to the first antidepressant received lifetime (p = .019, OR = 1.6) to be the factors associated with TRD. Conclusions: Our findings provide a set of 11 relevant clinical variables associated with treatment resistance in major depressive disorder that can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated with TRD.