Validating pre-treatment body mass index as moderator of antidepressant treatment outcomes: Findings from CO-MED trial

Background: Currently, there are no valid clinical or biological markers to personalize the treatment of depression. Recent evidence suggests that body mass index (BMI) may guide the selection of antidepressant medications with different mechanisms of action. Methods: Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants with BMI measurement (n = 662) were categorized as normal-or underweight (< 25), overweight (25 - <30), obese I (30- < 35), and obese II+ (>= 35). Logistic regression analysis with remission as the dependent variable and treatment arm-by-BMI category interaction as the primary independent variable was used to evaluate if BMI differentially predicted response to escitalopram (SSRI) monotherapy, bupropion-escitalopram combination, or venlafaxine-mirtazapine combination, after controlling for gender and baseline depression severity. Results: Remission rates among the three treatment arms differed on the basis of pre-treatment BMI (chi-square=12.80, degrees of freedom=6, p =. 046). Normal-or under-weight participants were less likely to remit with the bupropion-SSRI combination (26.8%) than SSRI monotherapy (37.3%, number needed to treat or NNT = 9.5) or venlafaxine-mirtazapine combination (44.4%, NNT = 5.7). Conversely, obese II + participants were more likely to remit with bupropion-SSRI (47.4%) than SSRI monotherapy (28.6%, NNT = 5.3) or venlafaxine-mirtazapine combination (37.7%, NNT = 10.3). Remission rates did not differ among overweight and obese I participants. Limitations: Secondary analysis, higher rates of obesity than the general population. Conclusions: Antidepressant selection in clinical practice can be personalized with BMI measurements. Bupropion-SSRI combination should be avoided in normal-or under-weight depressed outpatients as compared to SSRI monotherapy and venlafaxine-mirtazapine combination and preferred in those with BMI >= 35.