Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology — Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.)

Completed a maximal fitness treadmill test and self-report measures of habitual physical activity, depressive symptoms (Center for Epidemiological Studies Scale for Depression; CES-D) and emotional well-being (General Well-Being Schedule; GWB). To evaluate the dose–response gradient of the association, we classified the sample, separately for men and women, into three levels of relative cardiorespiratory (CR) fitness (low, moderate, high) on the maximal treadmill test, and four levels on a physical activity index of weekly walking, jogging, and running. Results: In both men and women, there was a significant inverse graded dose–response relationship between maximal CR fitness and the CES-D score (P < 0.0001), and a significant positive graded dose–response relationship between CR fitness and the GWB score (P < 0.0001). We also observed dose–response associations between the level of physical activity and both CES-D and GWB scores (P < 0.0001) that peaked at 11–19 miles per week. Conclusion: Among men and women in the ACLS, relative increases in maximal CR fitness and habitual physical activity are cross-sectionally associated with lower depressive symptomatology and greater emotional well-being. Prospective epidemiological studies and controlled clinical trials are needed to identify the minimal and optimal levels of physical activity and CR fitness associated with various mental health benefits in different segments of the general population....