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

Abstract

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) > or = 30 kg/m2 without concomitant risk factors or patients with a BMI > or = 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.

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

“…Increases of 1 to 3 mm Hg and increases in pulse rate (PR) of 4 to 5 beats per minute (bpm) at doses up to 20 mg have been reported. 8 In a dose-ranging study, at a sibutramine treatment dose of 15 mg, the current maximum recommended dose, changes in BP (+2.7 mm Hg, SBP; +3.4 mm Hg, DBP) were not statistically significantly different from BP changes observed with placebo treatment. 5 In recent, large, placebo-controlled trials with sibutramine, however, the numbers of patients in whom an increase in BP became clinically significant, or in whom mild hypertension appeared, leading to withdrawal from treatment, were generally not significantly different between sibutramine-and placebo-treated patients.…”

“…The data presented in Figure 3 possibly suggest an upward trend for heart rate over time among patients treated with sibutramine. Statistically significant differences in mean supine PR for sibutramine-treated patients compared to placebo-treated patients were found at weeks 4,8,12, and at the follow-up visit (P р 0.022). Mean PR at week 12 were sibutramine treatment, 67.1 bpm and placebo treatment, 61.5 bpm (difference, 5.6 bpm; P Ͻ 0.01 sibutramine compared with placebo).…”

“…8,9 Its mechanism as a serotonin-noradrenaline reuptake inhibitor is distinct from the mechanisms of fenfluramine, dexfenfluramine, and the amphetamines. Sibutramine and its metabolites do not stimulate neuronal monoamine release, lack the abuse potential associated with amphetamines, 8,10,11 and have not been associated with the cardiovascular pathologies which have been seen with fenfluramine. 12,13 Both preclinical and clinical studies strongly suggest that dopamine is not a target for sibutramine at pharmacologically relevant concentrations.…”

“…12,13 Both preclinical and clinical studies strongly suggest that dopamine is not a target for sibutramine at pharmacologically relevant concentrations. 8,10,11,14 Consistent with its enhancement of noradrenergic activity relative to placebo, normotensive obese patients on sibutramine treatment have experienced small mean increases in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Increases of 1 to 3 mm Hg and increases in pulse rate (PR) of 4 to 5 beats per minute (bpm) at doses up to 20 mg have been reported.…”

Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors

“…[9][10][11] Based on its activity in weight reduction, sibutramine used with a general weight reduction programme should help patients with hypertension to lose weight and maintain the loss over time. However, because of its mechanism as a noradrenaline reuptake inhibitor, sibutramine has the potential to raise blood pressure (BP) 12 and its use in obese patients with hypertension has been questioned, even if hypertension is already well controlled. The primary objective of this study was to investigate the effects of sibutramine 20 mg once daily (higher than the currently approved doses of 10 mg and 15 mg once daily) on weight loss in obese patients whose hypertension was well controlled with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy.…”