Context: The serotonin and norepinephrine transporter inhibitor sibutramine is a widely used anti-obesity drug. In acute studies, sibutramine's peripheral sympathomimetic effect was counteracted by a central sympatholytic action.

Objective: To test the hypothesis that blood pressure responses to long-term sibutramine therapy may be related to sympathetic nerve traffic before treatment.

Design: prospective, open-label

Setting: Academic clinical research center

Patients: Twenty obese subjects (BMI 30-40 kg/m², age 30-57 yrs.)

Intervention: five days placebo treatment followed by open label 15 mg/day sibutramine and hypocaloric diet over 12 weeks

Main outcome measures: We measured body weight, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA, microneurography), plasma catecholamines, and adipose tissue gene expression.

Results: Open label sibutramine treatment decreased body weight 4.1 kg (p<0.01) and MSNA 17 bursts/minute (p=0.001)} and increased diastolic blood pressure 3 mmHg (p<0.05) and heart rate 8 bpm (p<0.01). The change in blood pressure with sibutramine treatment was inversely correlated with initial MSNA (r²=0.34, p<0.01). Chronic sibutramine treatment increased adrenoreceptor gene expression and plasma catecholamines.

Conclusions: The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment.