BACKGROUND:Sibutramine, a serotonin and norepinephrine transporter blocker, is a common adjunctive obesity treatment. Acute studies in healthy subjects suggested that an inhibitory central nervous mechanism might attenuate the peripheral stimulatory effect on the sympathetic nervous system. This notion has not been tested in overweight and obese patients. METHODS: We conducted a randomized, controlled clinical study in hypertensive patients with BMI > or = 27 to < 40 kg/m(2). After 4 week placebo run-in period patients were randomized to four different antihypertensive treatments or placebo. After 4 weeks of antihypertensive therapy, patients were additionally treated with sibutramine 15 mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing and a graded head-up tilt test at the end of each phase. RESULTS:Mean body weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run-in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2, 145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after antihypertensive titration (ns) and end of sibutramine treatment (ns), respectively. Blood pressure was affected similarly during head up tilt testing. The systolic blood pressure response to cold pressor testing was diminished with sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure oscillations in the supine position (p<0.01). CONCLUSIONS:Resting blood pressure tends to increase with sibutramine, whereas blood pressure during sympathetic stimulation and low frequency blood pressure oscillations are decreased. These paradoxical changes are consistent with previous studies in healthy subjects and suggest a combination of peripheral and central nervous system mechanisms.
RCT Entities:
BACKGROUND:Sibutramine, a serotonin and norepinephrine transporter blocker, is a common adjunctive obesity treatment. Acute studies in healthy subjects suggested that an inhibitory central nervous mechanism might attenuate the peripheral stimulatory effect on the sympathetic nervous system. This notion has not been tested in overweight and obesepatients. METHODS: We conducted a randomized, controlled clinical study in hypertensivepatients with BMI > or = 27 to < 40 kg/m(2). After 4 week placebo run-in period patients were randomized to four different antihypertensive treatments or placebo. After 4 weeks of antihypertensive therapy, patients were additionally treated with sibutramine 15 mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing and a graded head-up tilt test at the end of each phase. RESULTS: Mean body weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run-in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2, 145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after antihypertensive titration (ns) and end of sibutramine treatment (ns), respectively. Blood pressure was affected similarly during head up tilt testing. The systolic blood pressure response to cold pressor testing was diminished with sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure oscillations in the supine position (p<0.01). CONCLUSIONS: Resting blood pressure tends to increase with sibutramine, whereas blood pressure during sympathetic stimulation and low frequency blood pressure oscillations are decreased. These paradoxical changes are consistent with previous studies in healthy subjects and suggest a combination of peripheral and central nervous system mechanisms.
Authors: J J Sramek; M T Leibowitz; S P Weinstein; E D Rowe; C M Mendel; B Levy; F G McMahon; W S Mullican; P D Toth; N R Cutler Journal: J Hum Hypertens Date: 2002-01 Impact factor: 3.012
Authors: J R Shannon; N L Flattem; J Jordan; G Jacob; B K Black; I Biaggioni; R D Blakely; D Robertson Journal: N Engl J Med Date: 2000-02-24 Impact factor: 91.245
Authors: W P James; A Astrup; N Finer; J Hilsted; P Kopelman; S Rössner; W H Saris; L F Van Gaal Journal: Lancet Date: 2000 Dec 23-30 Impact factor: 79.321
Authors: G A Bray; G L Blackburn; J M Ferguson; F L Greenway; A K Jain; C M Mendel; J Mendels; D H Ryan; S L Schwartz; M L Scheinbaum; T B Seaton Journal: Obes Res Date: 1999-03
Authors: R V Seimon; D Espinoza; L Ivers; V Gebski; N Finer; U F Legler; A M Sharma; W P T James; W Coutinho; I D Caterson Journal: Int J Obes (Lond) Date: 2014-01-10 Impact factor: 5.095