Elsevier

Journal of Affective Disorders

Volume 203, October 2016, Pages 190-198
Journal of Affective Disorders

Research paper
Association of treatment response with obesity and other metabolic risk factors in adults with depressive disorders: Results from a National Depression Cohort study in Korea (the CRESCEND study)

https://doi.org/10.1016/j.jad.2016.06.018Get rights and content

Highlights

  • ā€¢

    Male sex and obesity predicted poor treatment outcomes in patients treated with antidepressants.

  • ā€¢

    Male with concurrent metabolic problems had significantly higher risk for poor antidepressant treatment outcomes.

  • ā€¢

    Obesity predicted insufficient response in post-menopausal female patients with depressive disorders.

Abstract

Background

Available studies indicate that obesity may exert a moderational effect on antidepressant treatment response. The aim of this study was to investigate the relationship between treatment response and metabolic abnormalities amongst patients with depressive disorders in a large naturalistic clinical setting.

Methods

A nationwide prospective study was conducted in 18 hospitals in South Korea; 541 depressive patients meeting DSM-IV criteria were recruited. After baseline evaluation, subjects received naturalistic clinician-determined antidepressant interventions. Assessment was performed at baseline and weeks 1, 2, 4, 8, 12, 24 and 52. Treatment response was defined as a ā‰„50% reduction from baseline on at least one evaluation point.

Results

In univariate comparison, the patients who showed insufficient response to antidepressant therapy were more likely to be male, unmarried, unemployed, and obese. After adjusting for baseline variables, male sex (OR=1.82) and obesity (OR=1.55) remained as were significant variables. Stratification of the subjects into one of three groups, i.e. male, pre-menopausal female and post-menopausal female, revealed that males with concurrent metabolic problems, (i.e. the presence of one or more of hypertension, hyperglycemia, or hypercholesterolemia) had significantly higher risk for insufficient response (OR=2.32) and, after adjusting for baseline variables, obesity predicted insufficient response in post-menopausal female (OR=2.41).

Conclusions

The presence of metabolic abnormalities in patients with depressive disorders was associated with decreased treatment response to antidepressants. These results underscore the neurobiological relationship between obesity and the central nervous system, and provide empiric evidence supporting stratification of treatment response in depression.

Introduction

Despite the availability of over a dozen first-line antidepressant agents, treatment outcomes remain very disappointing. This deficiency provides a rationale for identifying pre-treatment variables that moderate treatment outcome. Identifying predictors of outcome is essential as the field attempts to replace trial-and-error approaches with precision/personalized medicine. However, no known reliable and robust pre-treatment predictors of outcome in depressive disorders have proven relevant to naturalistic practice (Bennabi et al., 2015).

Previous research has suggested a bidirectional relationship between components of metabolic syndrome (MetS) and depressive disorders. For example, results from epidemiologic studies showed that the incidence of depressive disorders was higher in individuals with components of MetS and vice versa (Kinder et al., 2004, Vanhala et al., 2009). The relationship of MetS and its components with depressive disorders is hypothesized to be mediated by many factors including, but not limited to, neurohormonal, inflammatory, and behavioral factors (McIntyre et al., 2009). Moreover, results from clinical studies also indicate that bipolar disorders and MetS commonly co-occur and that the presence of MetS significantly affects clinical outcomes in bipolar disorders (Kemp et al., 2010). However, relatively fewer studies have evaluated the impact of MetS on treatment response outcomes in depressive disorders.

Sagud et al. (2013) investigated whether MetS, its components, or other cardiovascular risk factors were related to insufficient treatment response in patients with major depressive disorder (MDD). They reported that the prevalence of MetS was similar in those with an insufficient response to antidepressants and those who responded to therapy. They also observed that the distribution of patients exhibiting particular components of MetS (i.e., elevated glucose, elevated triglycerides (TG), low high-density lipoprotein (HDL), elevated blood pressure, and increased waist circumference), or alteration in other cardiovascular risk factors did not significantly differ between patients with and without treatment resistant depression. In a separate study, Vogelzangs et al. (2014) followed patients with depressive disorders (MDD and dysthymia) who were in antidepressant treatment for 2 years and measured baseline values of metabolic and inflammatory factors. The study found that the co-occurrence of four or more metabolic/inflammatory dysregulations in an individual with depressive disorders negatively affected the clinical course and treatment outcome. Several neurobiological processes may even act as mediators in this association. Although several studies have considered the association between metabolic abnormalities and outcomes in the treatment of bipolar disorders (Calkin et al., 2009, Calkin et al., 2015, Ruzickova et al., 2003), relatively few studies have evaluated antidepressant outcomes in depressive disorders wherein MetS is a pre-treatment condition.

This study examined whether Korean adults with MDD who had one or more metabolic conditions exhibited differential therapeutic outcomes with antidepressant therapy.

Section snippets

Study overview

The present study used data gathered by the Clinical Research Center for Depression (CRESCEND), whose design has been detailed elsewhere (Kim et al., 2011). A summary of the study design is presented below.

Between January 2006 and August 2008, CRESCEND enrolled 1183 patients with depressive disorders (major depressive disorder, dysthymic disorder, and depressive disorders not otherwise specified) from 18 South Korean hospitals (16 university hospitals and 2 general hospitals). Enrollment

Characteristics of the sample

Of a total of 1183 patients screened for the CRESCEND study, 541 (45.7%) met the inclusion and exclusion criteria for the analysis described here. Further information from the SCID was available in 492 (90.9%) of these. Of 541 patients, 144 (26.6%) were male, 181 (33.5%) were pre-menopausal females, and 216 (39.9%) were post-menopausal females. Baseline socio-demographic and clinical characteristics of the full sample are summarized in the first column of Table 1. A total of 178 (32.9%)

Discussion

The design and settings of the CRESCEND study were specifically chosen as the data set because the set represents ā€œreal world patientsā€ receiving treatment under naturalistic conditions. We found that approximately a third of individuals had an insufficient response to treatment, which aligns with treatment results reported elsewhere (Carney and Freedland, 2009, Sagud et al., 2013).

Conclusions

This 1-year naturalistic study found the presence of metabolic abnormalities in patients with depressive disorders to be associated with decreased treatment response to antidepressants. Despite the limitations noted above, this study has important implications for clinicians and for further research. Comorbid obesity or other metabolic conditions might be considered predictors of insufficient treatment response in depressive disorders in clinical practice. Future research that includes

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