OBJECTIVES: Montgomery-Åsberg Depression Rating Scale (MADRS), a 10-item questionnaire (each scored on a 7-point scale [0-6]) is a validated tool for physicians to determine response to antidepressant treatment and is used widely in clinical trial settings. The Clinical Global Impressions-Severity (CGI-S) scale with one question scored on a 7-point response scale is a more practical tool for clinicians in real-world practice. The appropriateness of using CGI-S-based assessment for identifying responders to short-term antidepressant treatment among patients with treatment-resistant depression (TRD) was determined by evaluating agreement with the established MADRS-based assessment of response.

METHODS: Data from a phase-3 randomized, double-blind study (NCT02418585; TRANSFORM-2) of flexible-dosing esketamine (or placebo) nasal spray + a newly-initiated oral antidepressant for acute treatment in adults with moderate-to-severe TRD were analyzed. Patients with ≥50% reduction in MADRS from baseline at the end of the 4-week acute treatment phase were pre-specified as responders. For the alternative CGI‑S-based assessment of response, patients with ≥2 points decrease from baseline or a CGI-S score of ≤3 (mildly depressed to normal) were considered responders. Cohen's kappa coefficient was calculated to assess the level of agreement between MADRS- and CGI-S-based assessment. Sensitivity and specificity of the CGI-S-determined response was estimated, using MADRS-based classification as reference.

RESULTS: At the end of 4-week treatment, the proportion of responders among all study patients (n=201) was similar based on MADRS (61%) and CGI-S (62%). Substantial agreement between the two methods was observed (Cohen’s kappa= 0.76; sensitivity= 92%; specificity= 84%). Similar results were observed in esketamine-treated patients (n=101); proportion of responders: 69% (MADRS-based) and 68% (CGI-S-based), with substantial agreement (Cohen’s kappa=0.75; sensitivity= 91%; specificity= 84%).

CONCLUSIONS: The CGI-S could be a practical and reliable tool for clinicians to assess the response to short-term antidepressant treatment in patients with moderate-to-severe TRD, when MADRS is not feasible in real-world practice.