Nonresponder does not mean not better: Improvement in nonsymptom domains in complex depressed patients who are not symptomatic responders to intensive treatment

What is meant when saying that a depressed patient has not responded to treatment?

In studies of the treatment of depression, response is typically defined as a 50% or greater reduction in scores on a measure of depression symptom severity (Frank et al., 1991; Nierenberg and Dececco, 2001). Reviews and meta-analyses estimating and comparing rates of response for various interventions base such estimates on this definition of response (e.g., (Chen and Shan, 2019; Cipriani et al., 2018; Gartlehner et al., 2008; Li et al., 2021; Omori et al., 2009; Undurraga and Baldessarini, 2017; Watanabe et al., 2008). Improvement in nonsymptom domains such as functioning, quality of life, or ability to cope with the daily stresses of life are not considered in the definition of response. Consistent with this approach towards evaluating treatment response, regulatory agencies only require that treatment for depression reduce symptom severity (US Food and Drug Administration, 2018).

However, this approach towards defining treatment response is not consistent with patients’ opinions of the primary goals of treatment. Multiple surveys and focus groups of depressed patients have found that patients prioritize improved functioning and quality of life objectives over symptom resolution as the most important goal of treatment (Baune and Christensen, 2019; Grosse Holtforth et al., 2009; Morton et al., 2022). Consistent with this patient-centered approach towards treatment, some third-wave cognitive-behavioral therapies give precedence to nonsymptom goals. For example, Acceptance and Commitment Therapy (ACT) puts emphasis on increasing psychological flexibility and improving quality of life (e.g., work performance, physical health) (Hayes et al., 2006). Likewise, the primary goal of Dialectical Behavior Therapy (DBT) is to help patients create a life worth living, thereby focusing on overall well-being and functioning even in the presence of symptoms (Linehan, 2014). Despite de-emphasizing symptom reduction, both ACT and DBT are effective psychotherapy techniques in reducing symptoms for a range of psychiatric disorder (e.g., (Arch et al., 2012; Bai et al., 2020; Cristea et al., 2017; Falabella et al., 2022).

The goal of the present study from the Rhode Island Methods to Improve Diagnostic and Services (MIDAS) project is to widen the lens of assessing the outcome of depression treatment by examining response in nonsymptom domains in patients who are, by convention, considered nonresponders to treatment when response is based solely on a measure of depression symptom severity. We hypothesized that many patients who are nonresponders based on insufficient improvement in depressive symptoms would nonetheless manifest clinically significant improvement in nonsymptom domains. Moreover, we hypothesized that response on nonsymptom domains would be associated with patients’ global rating of improvement made upon treatment completion, and that patients’ global rating of improvement would be associated with the number of nonsymptom domains on which the patients had achieved responder status.

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