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W31

ANXIOUS DEPRESSION AS PREDICTOR OF CLINICAL OUTCOMES IN TREATMENT-RESISTANT DEPRESSION (ASCERTAIN-TRD)

Stefania Chaikali — Clotilde Guidetti1, Silvia Ioannou1, Madhukar H. Trivedi4, Richard Shelton5, Dan V. Iosifescu6, Michael E. Thase7, Manish Jha4, Sanjay J. Mathew8, Charles Debattista9, Mehmet E. Dokucu10, Olga Brawman-Mintzer11, Glenn W. Currier12, William Vaughn McCall13, Mandana Modirrousta14 1Harvard Medical School/Massachusetts General Hospital, 4University of Texas Southwestern Medical Center, 5University of Alabama At Birmingham, 6Icahn School of Medicine at Mount Sinai, 7Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. Crescenz VAMC, 8Baylor College of Medicine, 9Stanford University School of Medicine, 10Dartmouth Geisel School of Medicine, 11Ralph H. Johnson VA Medical Center, Medical University of South Carolina Charleston, 12Morsani College of Medicine, University of South Florida, 13Medical College of Georgia, Augusta University, 14DMax Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

2026 ASCP Annual Meeting

Background

Major depressive disorder (MDD) is a severe and debilitating illness. Despite the available pharmacological and non-pharmacological treatment options, clinical outcomes remain suboptimal in some subsets of patients. Anxious depression, a subtype characterized by the co-occurrence of anxiety symptoms, accounts for approximately 46–53% of patients with MDD and is associated with insufficient symptom improvement, regardless of the type of antidepressant used. The present study investigated the relationship between the presence of anxious depression features and clinical outcomes in patients with MDD enrolled in ASCERTAIN-TRD trial (NCT02977299).

Methods

This is a secondary data analysis investigating the relationship between anxiety subtype and response to treatment in the multi-site, randomized (1:1:1), open-label, effectiveness ASCERTAIN-TRD trial (NCT02977299) comparing three treatment arms (aripiprazole augmentation, repetitive transcranial magnetic stimulation (rTMS) augmentation, switching to venlafaxine XR or duloxetine) in MDD patients with TRD who are currently on ongoing, stable and adequate antidepressant therapy (ADT) as per the MGH Antidepressant Treatment Response Questionnaire (ATRQ). Baseline anxious depression was defined using the Hamilton Depression Rating Scale Anxiety and Somatization Subscale (HAMD‑AS). Subjects with HAMD-AS score ≥7 classified as the anxious depressive subtype. Response to treatment was evaluated based on the change in MADRS scores (MGH CTNI-administered by blinded raters) from baseline to week 8. For the MADRS analyses, mixed-effects models with repeated measures (MMRM) were used.

Results

In total, 278 subjects were randomly assigned to one of three treatment groups: aripiprazole (n=92), rTMS (n=70), or venlafaxine/duloxetine (n=98). Of these 253 (91%) had at least one post-baseline MADRS score and 136 (48.9%) were identified with anxious subtype (65 in the aripiprazole augmentation group, 46 in the rTMS augmentation group, and 71 in the venlafaxine/duloxetine switch group). The presence of anxious depression was not significantly associated with changes in MADRS scores (p=0.89, aripiprazole augmentation group; p=0.53, rTMS group; p=0.88, venlafaxine/duloxetine switch group). Moreover, no significant difference in treatment response between the aripiprazole augmentation and venlafaxine/duloxetine switching groups was found based on anxious depression status (p=0.57). Similarly, the comparison between rTMS augmentation and the venlafaxine/duloxetine switching strategy revealed no statistically significant difference in treatment response with respect to anxious depression status (p=0.70).

Conclusion

Although anxious depression has been associated with increased symptom severity and greater functional impairment, our findings indicate that it does not function as a reliable moderator or predictor of treatment response within the context of TRD. These findings may be a useful guidance for clinicians, suggesting that standard TRD treatments remain applicable in the anxious MDD subtype.