Both body weight and BMI predicts improvement in symptom and functioning for patients with major depressive disorder

Abstract

Background

Obesity has shown a positive association with depression. We aimed to investigate the relationships among body weight, body mass index (BMI=kg/m²), change in a depression rating scale, and change in a functional scale with fluoxetine treatment for hospitalized patients with major depressive disorder (MDD).

Methods

A total of 131 acutely ill inpatients with MDD were enrolled to receive 20 mg of fluoxetine daily for 6 weeks. The 17-item Hamilton Depression Rating Scale (HAMD-17) for symptom and the Work and Social Adjustment Scale (WSAS) for functioning were assessed at weeks 0, 1, 2, 3, 4, and 6. Remission was defined as a score of≤7 on the HAMD-17 at endpoint. Body weight, body length, and BMI were measured at baseline. Pearson correlation coefficients (r) were calculated among body weight, BMI, HAMD-17 score change, and WSAS score change.

Results

Of the 131 participants, 126 (96.2%) had at least one post-baseline assessment and were included in the analysis. Significant differences in body weight and BMI existed between remitters and nonremitters. There were statistically significant relationships among baseline body weight, baseline BMI, HAMD-17 score change, and WSAS score change at end point.

Limitations

This is a short-term trial with relatively small sample size.

Conclusions

Nonremitters had greater body weight and BMI before treatment. Increased body weight and BMI is correlated with the decreased improvement in symptom and functioning at end point. Depression and obesity should be treated concurrently to optimize clinical outcomes for the treatment of depression.

Introduction

The high prevalence of major depressive disorder and obesity are important global public health issues in the world (Baskin et al., 2005, Chu, 2005, Luppino et al., 2010, Simon et al., 2006, Stover et al., 2003).

Obesity is positively correlated with depression in the population (Luppino et al., 2010, Mather et al., 2009, McIntyre et al., 2006, Simon et al., 2006, Yu et al., 2011). This suggests that depression and obesity may have overlapping pathophysiology. Disturbances of the hypothalamus-pituitary-adrenocortical axis, gluocorticoid receptors (Holsboer, 2000, Kloiber et al., 2007, Ljung et al., 2002, Salehi et al., 2005), or specific neurotransmitters in brain (Bjorntorp and Rosmond, 2000) may increase risk for depression and obesity. Therefore, body weight may influence antidepressant response through pharmacokinetic and pharmacodynamic mechanisms (Davis, 2002). Rosmond (2004) proposes that obesity and depression may represent different manifestations of the same disease process.

Five studies (Khan et al., 2007, Kloiber et al., 2007, Oskooilar et al., 2009, Papakostas et al., 2005, Uher et al., 2009) have examined whether body weight or body mass index (BMI) modifies the therapeutic effect of antidepressants in western countries. BMI, a continuous measure of body weight relative to body length, is calculated as body weight in kilograms divided by the square of body length in meters (kg m⁻²). Categorical definitions of underweight (BMI<19), normal (19≦BMI<25), overweight (25≦BMI<30), and obesity (BMI≥30) are based on the parameters set out by the World Health Organization (WHO, 1998) and the US National Institute of Health (NIH, 1998). Hamilton Depression Rating Scale (HAMD) (Hamilton, 1960) or the Montgomery–Asberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979) were used to measure the severity of depression. Response is defined as having a 50% or greater reduction in HAMD or MADRS scores. Outcomes include dichotomized outcomes (response/nonresponse) or reduction in HAMD scores or MADRS scores at end point. The results of these studies are mixed with no consistent finding. One study indicates that overweight or obesity does not predict response to fluoxetine, but body weight can (Papakostas et al., 2005). Another study (Uher et al., 2009) reports that higher BMI and obesity is predictive for a poor response to nortriptyline, but not escitalopram. Khan et al. (2007) concludes that obesity is linked to a smaller reduction in HAMD symptoms, but does not impact post-treatment MADRS scores. Two studies (Kloiber et al., 2007, Oskooilar et al., 2009) exclude underweight subjects. Their findings show that patients with normal BMI have greater clinical improvement with the antidepressants when compared with overweight and obese.

One of possible explanations for this inconsistency is that these five mentioned studies classify the alternative procedures to categorical variables. Based on statistical theory, any downscaling procedures (e.g., a continuous variable to categorical variables) results in a loss of statistical power (Ragland, 1992, Streiner, 2002, Taylor et al., 2006). Defining obesity as BMI≥30 may not reveal the adverse impact of excessive body weight on the treatment of depression appropriately (Papakostas et al., 2005). Statistical approach of using body weight or BMI as a continuous variable may be more appropriate (Uher et al., 2009).

From both the clinical and research perspective, more attention is paid to depressive symptoms than to functional impairments. The American Psychiatric Association (APA) guideline for the treatment of patients with major depressive disorder (APA, 2010) also emphasizes the importance of adding functional measures to adequately capture the full impact of depression and its treatment. On the other hand, obesity has been reported to be related to the risk of psychosocial impairment (Bellanger and Bray, 2005, Karlsson et al., 2003).

We hypothesized that higher body weight or BMI would predict poor improvement in depressive symptoms and functional impairment for antidepressant treatment. We aimed to investigate the relationships among body weight, BMI, change in a depression rating scale, and change in a functional scale for hospitalized patients with major depressive disorder (MDD) on the treatment of fluoxetine.