OBJECTIVES: Little information is available to assist with interpretation of meaningful change of the Sheehan Disability Scale (SDS) and Patient Health Questionnaire (PHQ-9), which evaluate symptoms, functioning, and disability of major depressive disorder (MDD). This analysis explores the relationship between the Clinical Global Impression–Severity (CGI-S) scale and the SDS and PHQ-9 in patients with treatment-resistant depression (TRD), which can provide insight into interpretation of treatment effect.

METHODS: This post hoc analysis used an international clinical trial database (N=223) composed of a 4-week, randomized, active-controlled study of esketamine plus new antidepressant therapy versus new antidepressant therapy alone in symptomatic subjects with MDD who failed ≥2 prior pharmacologic treatments for TRD within the current episode. All subjects, who were rated by a clinician using the CGI-S scale, completed the SDS, and PHQ-9 instruments. Parametric and nonparametric simple and multiple regression models explored relationships between ratings among these scales from baseline to week-4 endpoint. Clinically meaningful improvement was defined as a 1-point change in the CGI-S scale.

RESULTS: Mean (SD) baseline CGI-S, SDS, and PHQ-9 scores were 5.1 (0.67), 24.1 (4.22), and 5.1 (0.67), respectively. A multiple regression model suggested that a 1-point change in the CGI-S corresponded to a 3.8-point (SE=0.3) change in the SDS and to a 3.1-point (SE=0.2) change in the PHQ-9. A multiple logistic regression model determined changes in CGI-S categories suggested an average 28% probability of a shift of 1 category at endpoint when SDS score changed by 1 point and 41% probability of a shift when PHQ-9 score changed by 1 point.

CONCLUSIONS: Interpretation of patient-level change in depressive symptoms identified by the CGI-S scale corresponds to approximately a 3.8- and 3.1-point improvement from baseline on the SDS and PHQ-9 scales, respectively, in subjects with TRD. Supported by Janssen Scientific Affairs, LLC.