Optimizing personalized management of depression: the importance of real-world contexts and the need for a new convergence paradigm in mental health

Abstract

In this issue of the journal, Maj et al1 have revisited a fundamental tenet of psychiatric medicine, namely, that more precise clinical characterization of patients with depression will enhance the provision of personalized management – and the likelihood of optimal outcomes. The authors have conducted a comprehensive and balanced review of relevant domains, including clinical symptoms, severity of illness, depression subtypes, functional status, staging of illness, neurocognition, medical and psychiatric comorbidities, early life adversity, personality dysfunction, and environmental stressors. They have highlighted the importance of measurement-based assessment and care via the use of instruments both psychometrically sound and amenable to implementation in practice. Although not aiming to deal specifically with biomarkers, the authors suggest that progress in the identification and clinical use of biomarkers will be facilitated through multidimensional clinical assessment. It is indeed plausible that biomarkers will be found to correlate more closely with dimensions of psychopathology than with categorical diagnostic measures, which often hide important treatment-relevant aspects of illness. As such, biomarkers may become more useful as predictors, modifiers and mediators of response variability. An analogy with diabetes mellitus seems appropriate: finding an abnormal blood glucose (like a positive screen for depression) mandates a clinical workup across a number of dimensions to inform appropriate clinical management, aided by the use of laboratory tests that facilitate monitoring of progress in response to treatment and in prevention of adverse sequelae. Viewed from the perspective of someone living with depression, an optimal outcome entails both restoration of a sense of well-being and re-engagement in major social, vocational and family roles. As Maj et al note, these are among the outcomes that matter most to patients. Although reduction in symptom burden is clearly important (because residual symptoms indicate increased risk for a relapsing and chronic course), patients and their family carers hope for the return of pleasure and meaning in life, resumption of major roles, and mitigation of carer burden and its attendant demoralization. Answering the question "How well is well?" depends, therefore, upon taking both a patient-focused and family-centered approach. Depression does not occur monadically, but more often within a family context. Nor does it occur apart from myriad social, cultural and medical issues. Optimal care involves aiming at more than relief of anguish in the pursuit of personalized management. To say that depression does not occur "in pure culture" is thus to highlight several real-world contexts in which the more precise clinical characterization of depressed patients needs to occur. Relevant contexts for optimizing depression assessment and management include, among others, sociocultural, medical, and systems-based care-delivery issues. These contexts may be understood as a way of further grounding multidimensional clinical characterization in vivo. With respect to sociocultural context, for example, persons from different racial and ethnic groups vary in their understanding of what depression is, what constitutes acceptable treatment, and even whether treatment is needed at all. For some, "depression" is both stigmatized and stigmatizing. Furthermore, engaging persons living in low-resource settings, very different from high-income countries, may be quite challenging, particularly if family members do not "buy in" to the need for treatment. Using like-ethnic community health workers, as members of a treatment team, can be useful for gaining trust and for promoting engagement in treatment, treatment adherence, and access to community resources needed by impoverished or disadvantaged depressed adults in their journey to full recovery. Optimizing treatment outcomes, the goal of precise clinical characterization, begs the question of how best to close the world's treatment gap for depression2. The treatment gap arises especially from the dearth of mental-health specialty expertise in low- and middle-income countries (as well as in rural areas of high-income countries), where social determinants of ill-health, including depression, may be particularly powerful. Work-force issues further underscore the importance of early interventions to pre-empt or prevent depression in vulnerable people, as Maj et al emphasize in their discussion of staging. The implied analogy to cancer is especially compelling since, as with cancer, early preventive intervention may be curative or at least mitigate down-stream complications. In the case of depression, it may mitigate emergence of treatment resistance, chronicity, and adverse outcomes such as suicide and dementia. How to leverage mental health expertise broadly in the service of personalized prevention and treatment, therefore, becomes the centra