Obesity continues to present ongoing challenges to the adequate management of patients with schizophrenia. Non-pharmacological interventions for weight reduction present a viable option but their effectiveness has not been investigated thus far. In this second revised resubmission, we propose to test a behavioral program for weight reduction in the short term, and weight maintenance in the long term in overweight / obese patients with schizophrenia. The sample for the proposed study has been increased, and a two-year follow up period has been added to examine the durability of our program. In the interim period since the last submission, we have examined the effectiveness of our weight loss program in an additional 65 overweight / obese patients with schizophrenia recruited from 12 sites across the US. Among those who completed the program, 50% of patients who were randomly assigned to behavioral treatment were able to lose 4% or more body weight from baseline. In contrast, only 14.3% of patients in the control group (treatment as usual) lost 4% or more weight. In addition, it was observed that significant improvements in anthropometric measures of cardiovascular health (i.e., BMI, waist and hip circumference) were associated with 4% or greater weight loss among patients who received the behavioral treatment. We now propose a randomized, parallel group, clinical trial in 300 overweight / obese schizophrenia patients to rigorously assess the effectiveness of our treatment. The experimental treatment will be compared to social skills training, of similar duration and intensity, as well as treatment as usual. Overweight but clinically stable schizophrenia patients will be randomly assigned to behavioral treatment for weight reduction (BT), social skills (SS), or usual care (UC), in the ratio 4:1:1. The BT and SST groups will receive behavioral interventions for weight reduction and social skills training respectively over a 14-week period (Phase I) Immediately following these interventions, patients in the BT group who achieve 4% of higher weight loss will enrolled in a 24 month study examining the effectiveness of a maintenance treatment aimed at preventing weight re-gain (Phase II). In this phase, patients will be randomly assigned (2:1) to either receive booster treatments, one every 2 weeks, or treatment as usual over a 2 year duration. The study will also examine the effects of antipsychotic medications and their possible interaction with the behavioral treatment, demographic and clinical factors predictive of weight loss, effects of weight loss on quality of life and self esteem and the relationship between weight loss and cardiovascular risk factors such as glucose regulation, serum lipids, blood pressure, physical fitness and physical exercise. This is the first attempt ever to conduct a large randomized trial of an intervention for weight reduction, and maintenance of weight loss, in schizophrenia, and of the effects of weight reduction on cardiovascular risk factors in this population.
