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COGNITIVE IMPAIRMENT IN MAJOR DEPRESSIVE DISORDER: A PATIENT-PRIORITIZED TARGET FOR FUNCTIONAL RECOVERY

Manish K. Jha — Philip D. Harvey2, Dana DiBenedetti3, Katherine Kosa3, Leah Aluisio4, Steven T. Szabo4, Cecilia Brain4, Jaskaran B. Singh4, Neel Shah4, Chris Wallick4 1UT Southwestern Medical School, 2University of Miami Miller School of Medicine, 3RTI Health Solutions, 4Neurocrine Biosciences, Inc.

2026 ASCP Annual Meeting

Background

Cognitive symptoms are less recognized as a core feature of major depressive disorder (MDD) and associated functional impairment. Clinical care and MDD trials often prioritize change in mood symptoms and fail to monitor for improvement in cognitive symptoms. Understanding the patient-perceived burden of cognitive symptoms may inform treatment development and optimization strategies.

Methods

Semi-structured qualitative interviews were conducted with 15 US adults who had clinician-diagnosed MDD (≥3 months current or prior antidepressant use) and 5 clinicians treating MDD (2 primary care, 3 psychiatry). Interviews explored symptom experience, functional impact, and treatment priorities. Transcripts were analyzed using established qualitative methods.

Results

Of the 15 adult patients who were interviewed, 13 (86.7%) reported experiencing cognitive symptoms, such as trouble concentrating and thinking. Of the 5 clinicians who were interviewed, 4 (80.0%) reported that patients with MDD typically present with cognitive symptoms. When patients were asked which symptoms were most bothersome, the most common responses were cognitive symptoms and lack of motivation (26.7% [4/15] for each symptom). When asked which symptoms that they most wanted to see improved with new treatment, one-third of patients (33.3% [5/15]) responded with cognitive symptoms. Patients described cognitive symptoms as being persistent and functionally disruptive, contributing to decreased work productivity, difficulty learning new material, impaired task completion, and strained interpersonal communication. While clinicians identified fatigue and depressed mood as primary treatment targets, patients consistently highlighted the need for improvements in cognitive symptoms, such as improved mental clarity and focus.

Conclusions

Cognitive symptoms represent a prevalent and highly prioritized dimension for treatment among patients with MDD. Targeting cognitive improvement is often not prioritized by clinicians; however, addressing these symptoms is an unmet need that is critical to functional recovery.