Global cognitive functioning in TRD and non-TRD patients: longitudinal real-world evidence from the PROMPT study
V. T. H. Wahner, S. Jörgens, B. T. Baune,Introduction
The exact role of cognitive functioning (CF) and impairment in treatment-resistant depression (TRD) is not well understood. In particular, the lack of longitudinal and comparative data with non-TRD patients represents a major gap in the current literature.
Objectives
This study sought to compare 12-week trajectories of global CF between TRD and non-TRD patients in a real-world setting.
Methods
This prospective observational study included 146 inpatients with major depressive disorder (MDD) who were assessed with a standardized cognitive test battery (BAC-A) and structured clinical interviews at baseline, week 8, and week 12. Fifty-four patients (mean age = 48.5±15.5; 48% female) met the criteria for TRD, defined as nonresponse to at least two antidepressant regimens during the current episode, and were compared with ninety-two non-TRD patients (mean age = 33.9±12.8; 50% female). Composite cognitive z -scores (age- and sex-adjusted) were analysed using linear mixed-effects models to examine the effects of group, time and their interaction. In a second step, the model was adjusted for symptom severity (MADRS scores), recurrence, years of education, current medication (benzodiazepines, antipsychotics) and psychiatric comorbidities (anxiety disorders, personality disorders).
Results
Global CF improved significantly over 12 weeks (β = 0.29,
p
< .001). The TRD group showed lower baseline CF (β = -0.45,
p
= .032). This group effect was no longer significant after adjustment for clinical covariates. Higher education predicted better CF (β = 0.12,
p
< .001), whereas antipsychotic use was associated with poorer CF (β = -0.74,
p
< .001). The non-significant group × time interaction indicated similar trajectories between groups. Random-effects variances (intercept = 1.05; slope = 0.00) suggested substantial between-subject variability at baseline and parallel improvement trajectories. Figure 1 depicts group mean trajectories of global CF over 12 weeks.
Image 1: Long description.