Sibutramine: A Serotonin–Norepinephrine Reuptake-Inhibitor for the Treatment of Obesity

Abstract

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, adverse effects, and drug interactions of sibutramine as a treatment for obesity. DATA SOURCES: English-language clinical studies, abstracts, and review articles were identified using MEDLINE, EMBASE, and a manual search from January 1980 through December 1998. References were also obtained from the reference section of published articles. STUDY SELECTION AND DATA EXTRACTION: All articles identified were evaluated for possible inclusion in this review. Evaluative and comparative data from prospective, open-label, double-blind, and controlled studies were reviewed. DATA SYNTHESIS: Sibutramine is a serotonin–norepinephrine reuptake-inhibitor effective in the treatment of obesity. It does not act as a releasing agent of these neurotransmitters. Sibutramine undergoes extensive metabolism in the liver via CYP3A4, forming two pharmacologically active metabolites. This agent has demonstrated efficacy superior to placebo in reducing weight when used as part of an integrated regimen involving behavior modification, physical activity, and a reduced-calorie intake. The most frequently reported adverse effects include dry mouth, anorexia, headache, insomnia, and constipation. Sibutramine has also been shown to substantially increase blood pressure and heart rate in some patients. CONCLUSIONS: Based on anorectic efficacy data, sibutramine, a serotonin–norepinephrine reuptake-inhibitor, is a viable therapeutic option for the treatment of obesity. Recommended candidates for this medication are patients with a body mass index (BMI) ≥30 kg/m² without concomitant risk factors or patients with a BMI ≥27 kg/m² with concomitant risk factors. Sibutramine should be used with caution in patients with a history of hypertension and should not be used in those with uncontrolled hypertension and concomitant cardiovascular disease. Further studies need to be conducted in order to identify long-term outcomes beyond one year.