Patient-reported depression severity and cognitive symptoms as determinants of functioning in patients with major depressive disorder: a secondary analysis of the 2-year prospective PERFORM study

Abstract

Purpose: To investigate the temporal interrelationship between depression severity, cognitive symptoms, and functioning in patients with major depressive disorder (MDD) in the PERFORM study (NCT01427439).

Patients and methods: PERFORM was a 2-year, multicenter, prospective, noninterventional cohort study in outpatients with MDD who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Patients were enrolled by a general practitioner or psychiatrist. Structural equation model (SEM) analysis was used to explore temporal associations between patient-reported depression severity (9-item Patient Health Questionnaire score), cognitive symptoms (5-item Perceived Deficits Questionnaire score), and functional impairment (Sheehan Disability Scale total score). Standardized regression coefficients (SRCs) were used to evaluate the relationship between each outcome and scores from the most recent prior visit over the 2 years of follow-up.

Results: Between February 25, 2011, and February 19, 2015, 1,159 eligible patients with MDD completed the baseline and ≥1 follow-up visit at 194 sites in five European countries (France, Germany, Spain, Sweden, and the UK). Overall, 1,090 patients had assessments for ≥1 outcome measure at two consecutive visits. Severity of cognitive symptoms at baseline and Months 2 and 18 predicted functional impairment at Months 2, 6, and 24, respectively (SRC: 0.18, 0.15, and 0.22; P<0.001). Depression severity at Months 2, 6, and 12 predicted functional impairment at Months 6, 12, and 18, respectively (SRC: 0.17, 0.25, and 0.22; P<0.001). Severity of cognitive symptoms at baseline and Month 18 predicted depression severity at Months 2 and 24, respectively (SRC: 0.19 and 0.22; P<0.001). Functional impairment did not significantly predict the severity of depression or cognitive symptoms, and depression severity did not significantly predict the severity of cognitive symptoms at any time point.

Conclusion: Patient-reported severity of cognitive symptoms appears to be an independent and significant determinant of subsequent functional impairment and depression severity in patients with MDD.

Keywords: cognitive symptoms; functional impairment; major depressive disorder; structural equation model.

Figure 1

Illustration of the (A) saturated structural equation model (SEM) and (B) G-computation model. Notes: (A) The SEM estimates all regression coefficients between 5-item Perceived Deficit Questionnaire (PDQ-5) score, Sheehan Disability Scale (SDS) total score, and 9-item Patient Health Questionnaire (PHQ-9) score at subsequent visits (solid one-headed arrows), as well as variances and covariances between PDQ-5 score, SDS total score, and PHQ-9 score at the same visits (dotted double-headed arrows), in a single analysis. (B) In the G-computation of the causal effect of PDQ-5 score at Month 2 on SDS total score at Month 6 (example highlighted in gray box), SDS total score and PHQ-9 score at Month 2 are potential confounders and are therefore accounted for, whereas PDQ-5 and PHQ-9 scores at Month 6 are mediating variables and are therefore not accounted for.

Figure 2

Distribution of depression severity (9-item Patient Health Questionnaire [PHQ-9] score, range 0–27), functional impairment (Sheehan Disability Scale [SDS] total score, range 0–30) and cognitive symptoms (5-item Perceived Deficit Questionnaire [PDQ-5] score, range 0–20) by visit. Note: Higher scores indicate worse outcomes.

Figure 3

Significant regression coefficients based on the structural equation model standardized by time point. Note: Only effects that were significant at the P<0.001 level are shown; the thickness of the arrows is proportional to the effect estimates. Abbreviations: PDQ-5, 5-item Perceived Deficit Questionnaire; PHQ-9, 9-item Patient Health Questionnaire; SDS, Sheehan Disability Scale.

Figure 4

Causal effect sizes from G-computation standardized by time point. Note: Effects that were significant at the P<0.001 level are shown in black, and effects that were significant at the P<0.05 level (but not at the 0.001 level) are shown in gray; the thickness of the arrows is proportional to the effect estimates. Abbreviations: PDQ-5, 5-item Perceived Deficit Questionnaire; PHQ-9, 9-item Patient Health Questionnaire; SDS, Sheehan Disability Scale.