Sibutramine in obesity

Sibutramine is a specific inhibitor of noradrenaline and serotonin reuptake into nerve terminals, and is believed to inhibit food intake by promoting satiety [113] it may also increase thermogenesis [114-116], Short- and long-term clinical trials of sibutramine in obese subjects documents weight loss of approximately 10 % of initial weight with... 

In a study of the efficacy and safety of sibutramine in obese white and African Americans with hypertension, the most common adverse event resulting in withdrawal... 

Kaukua, J. K., T. A. Pekkarinen and A. M. Rissanen (2004). Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes. Int J Obes Relat Metab Disord 28(4) 600-5. 

Susceptibility factors Genetic Patient selection based on candidate genes may enhance the response to sibutramine in obesity [106 ]. 

The newest appetite suppressant, sibutramine (Meridia), works by blocking the reuptake of both serotonin and norepinephrine. It does not stimulate nerve cells to release serotonin, as do fenfluramine and dexfenfluramine. Administered at 20 mg/ day, sibutramine effectively reduces weight in obese patients, but its use has not been assessed in eating disorder patients. The most common side effects of this medication are insomnia, dry mouth, and constipation. It has not been associated with the more serious heart and lung complications observed with fenfluramine and dexfenfluramine. Because sibutramine acts in part through modulation of norepinephrine, there is no rational basis for coadministering phentermine, which acts via this same mechanism. 

Heusser, K. et al., Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects, Clin. Pharmacol. Ther., 79(5), 500-508, 2006. 

As previously discussed, two weight loss medications are currently available by prescription. Sibutramine (Meridia), which suppresses appetite, is approved for use in obese patients age 16 or older. Orlistat (Xenical), a fat blocker, is approved for children 12 and older and adults. Candidates for these medications are not simply people who want to lose a few pounds, even if their doctors tell them they should lose weight. A patient must be severely overweight and meet certain other criteria before a doctor will consider prescribing medication. 

In a multicenter, double-blind, randomized, parallel-group, placebo-controlled trial in 22 European centers for specialist diabetes care over 6 months, sibutramine, in conjunction with moderate caloric restriction, enabled obese patients with type 2 diabetes taking sulfonylureas to achieve clinically significant weight loss (7). This was... 

Smith IG, Goulder MA. On Behalf of the Members of the Sibutramine Chnical Study 1047 Team. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. J Fam Pract 2001 50(6) 505-12. 

Serrano-Rios M, Melchionda N, Moreno-Carretero E. Spanish Investigators. Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Diabet Med 2002 19(2) 119-24. 

Sramek JJ, Leibowitz MT, Weinstein SP, Rowe ED, Mendel CM, Levy B, McMahon FG, Mullican WS, Toth PD, Cutler NR. Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents a placebo-controlled, double-blind, randomised trial J Hum Hypertens 2002 16(1) 13-19. 

McMahon FG, Weinstein SP, Rowe E, Ernst KR, Johnson F, Fujioka K. Sibutramine in Hypertensives Clinical Study Group. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002 16(1) 5-11. 

Aydin, N., P. Topsever, A. Kaya, M. Karasakal, C. Duman and A. Da-gar (2004). Orlistat, sibutramine, or combination therapy which performs better on waist circumference in relation with body mass index in obese patients TohokuJ Exp Med 202(3) 173-80. 

McNulty, S. J., E. Ur and G. Williams (2003). A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. Diabetes Care 26(1) 125-31. 

Sibutramine is eontraindicated in obese patients with preexisting eardiovascular diseases because it eauses a small but significant increase in both systolie blood pressure and supine heart rate (62). Sibutramine elevates synaptic levels of NE, resulting in activation of sympathomimetic pathways involved in blood pressure regulation. Sibutramine does not appear to cause valvular heart disease, unlike other agents that potently stimulate 5-HT release like dexfenfluramine. 

Topecatan inhibits topoisomerase I in cancer cases 1,000 Sibutramine for obesity combined with treatment plan 22,500... 

Sibutramine (meridia), an inhibitor of the reuptake of 5-HT, ME, and DA, is used as an appetite suppressant in the management of obesity two active metabolites probably account for sibu-tramine s therapeutic effects. Whether effects on a single neurotransmitter system are primarily responsible for sibutramine s effects in obese patients is unclear. 

McLaughlin T, Abbasi F, Lamendola C, et al. Metabolic changes following sibutramine-assisted weight loss in obese individuals role of plasma free fatty acids in the insulin resistance of obesity. Metabolism 2001 50 819-882. 

Long-term data on the effect of sibutramine on obesity-related morbidity and mortahty are still lacking. However, the current Sibutramine Cardiovascular Outcomes (SCOUT) trial is evaluating the efficacy of sibutramine on major cardiovascular evmts (myocardial infarction, stroke, and mortality). It is planned that this study should be finished in 2008. 

Sibutramine may be useful in patients where the obese state is characterised by overeating and snacking because of its appetite reducing effects. Sibutramine should not be used in patients with uncontrolled hypertension or with tachy-arrhythmia. Rimonabant may be preferred in obese patients with the metabolic syndrome particularly in those with low HDL and high triglyceride. Because of few data rimonabant should be avoided in patients with psychiatric illness, particularly in patients with major depressions and in patients in antidepressive treatment. These suggestions are not evidence based but the recommendations that can be used until more direct head-to-head investigations have been performed. 

Gmdell ABM, Sweetser S, Camilleri M, Eckert DJ, Vazquez-Rocque MI, Carlson PJ, Burton DD, Braddock AE, Qark MM, Graszer KM, Kalsy SA, Zinsmeister AR. A controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese and overweight adults. Gastroenterology 2008 135 1142-54. 

Siuciak, JA, Clark, MS, Rind, HB, Whittemore, SR and Russo, AF (1998) BDNF induction of tryptophan hydroxylase mRNA levels in the rat brain. J. Neurosci. Res. 52 149-158. Sprague, JE, Everman, SL and Nichols, DE (1998) An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine. Neuro toxicology 19 427-A42. Stock, MJ (1997) Sibutramine a review of the pharmacology of a novel anti-obesity agent. Int. J. Obesity 21 (Suppl 1) S25-S29. 

A number of azetidine-based compounds have been disclosed in patent applications from Aventis Pharma for CBi-modulated treatment of diseases such as obesity, Parkinson s disease, schizophrenia, respiratory and neurological diseases [330-334]. Compound (556) was specifically claimed for use in two formulation patent applications [330, 331] for a stable semi-solid composition and oral emulsion composition, respectively. The optional coadministration of an agent that activates norepinephrinergic and se-rotoninergic neurotransmission (for example, sibutramine) or dopaminergic neurotransmission was also claimed for the treatment of obesity. The optional use of a dopamine agonist (for example, levodopa) was claimed... 

The starting dose of sibutramine is usually 10 to 15 mg once a day. The drawback of this drug is that, as with all medications used to treat obesity, the lost weight eventually reappears unless the patient continues to engage in healthy eating habits and an exercise program. 

Although it is often classified as a SNRI, sibutramine (26) is metabolized in vivo to produce metabolites that have varying degrees of inhibition of NE, 5-HT and DA reuptake [83,84]. It has been approved for the control of obesity in the U.S. and many other countries. 

Sibutramine is a centrally acting appetite suppressant used as an adjunct in the management of obesity. It inhibits the re-uptake of noradrenaline and serotonin. 

Fenfluramine (Pondimin) and phentermine (Adipex-P, Fastin) are anorexigenic drugs that produce depression of the CNS and at one time were used (Fen-phen) in the treatment of obesity. Sibutramine (Meridia) is also available for the treatment of obesity. 

Additional dual 5HT-NE reuptake inhibitors include sibutramine, which is approved for the treatment of obesity but not depression. Tramadol is a kappa opiate agonist approved for the treatment of pain, but it also has serotonin and norepinephrine reuptake inhibitor properties. Dual reuptake inhibitors in clinical testing as antidepressants include milnacipran and duloxetine. 

In 1997, the FDA approved sibutramine, a medication sold under the brand name Meridia. Sibutramine is an appetite suppressant prescribed for long-term treatment of severely obese patients. However, safety and effectiveness had not been determined when the sibutramine was taken for more than one year. 

Most prescription diet pills are prescribed for shortterm use of not more than several months. Sibutramine and orlistat have been prescribed for longer use in the treatment of significantly obese people. For both medications, this treatment ranged from six months to one year. The safety and effectiveness of use for longer than one year have not been determined. 

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