An examination of symptoms, function and quality of life as conjoint clinical outcome domains for treatment-resistant depression.

OBJECTIVE: The treatment of depression aims to improve depressive symptoms, daily function and quality of life (QoL). These exploratory analyses of a database of convenience from the RECOVER trial evaluated how a "tripartite" metric based on these 3 outcome domains might perform in treatment-resistant depression (TRD). METHODS: Outcome domains included depressive symptoms (MADRS, QIDS-C, QIDS-SR), function (WPAI item-6) and QoL (Mini-Q-LES-Q) obtained at months 3, 6, 9 and 12 in outpatients with markedly TRD in the double-blind RECOVER trial that compared sham to active adjunctive vagus nerve stimulation (VNS). For each domain, clinically meaningful differences were defined a priori. Analyses addressed 3 questions: 1) Does each domain detect meaningful benefits undetected by the other domains? 2) Is the tripartite metric validated by an independent clinician-rated global index of improvement (CGI-I)? 3) How well does the tripartite metric detect treatment group differences in the RECOVER trial? RESULTS: Clinically meaningful reductions in depressive symptoms alone missed 25-51 % of all participants who evidenced clinically meaningful benefits in depressive symptoms, function or QoL. The tripartite metric strongly correlated with CGI-I ratings (tetrachoric r = 0.73-0.85), with stronger relationships than each component individually. The tripartite metric successfully separated active from sham adjunctive VNS in a 1-year trial of patients with markedly TRD. CONCLUSION: Symptoms, function and QoL capture distinct, clinically significant and valid outcomes that identify persons with markedly TRD with a range of clinically meaningful benefits. Whether these results pertain to other major depressive disorder patient groups and treatments deserves study.