Adipositas - Ursachen, Folgeerkrankungen, Therapie 2018; 12(02): 60-67
DOI: 10.1055/s-0038-1654051
Übersichtsarbeit
Schattauer GmbH

Naltrexon/Bupropion in der Adipositastherapie

Naltrexone/Bupropion for chronic weight management
M. Blüher
1   Universität Leipzig
› Author Affiliations
Further Information

Publication History

Publication Date:
04 May 2018 (online)

Zusammenfassung

In der Therapie der Adipositas reichen häufig konservative Basistherapiemaßnahmen wie eine energiereduzierte Mischkost, eine Erhöhung der körperlichen Aktivität sowie eine Verhaltensmodifikation nicht aus, um die individuellen Gesundheitsziele langfristig zu erreichen. Eine medikamentöse Therapie kann bei nicht ausreichendem Erfolg in Kombination mit dem Basisprogramm erwogen werden. Seit Januar 2018 ist mit Naltrexon 32mg/Bupropion 360mg eine neue Pharmakotherapie der Adipositas in Deutschland eingeführt. Naltrexon ist ein _-Opioidrezeptor- Antagonist und Bupropion ein schwacher Inhibitor der neuronalen Dopamin- und Noradrenalin- Wiederaufnahme die zusammen über die Wirkung auf den Nucleus arcuatus des Hypothalamus und das mesolimbische dopaminerge Belohnungssystem zu einer Verringerung der Nahrungsaufnahme beitragen. Die Wirksamkeit und Sicherheit von Naltrexon/Bupropion wurde zusätzlich zur Basistherapie in vier doppelblinden Placebo-kontrollierten Phase III-Studien bei 4 536 Personen mit Adipositas oder Übergewicht über einen Zeitraum von 56 Wochen untersucht (COR-I, COR-II, CORBMOD, COR-Diabetes). Unter Naltrexon/Bupropion wurde in der COR-I Studie eine durchschnittliche prozentuale Gewichtsabnahme von 5,4% im Vergleich zu 1,3% in der Placebogruppe erzielt. Zu den häufigsten Nebenwirkungen von Naltrexon/Bupropion zählen Übelkeit, Erbrechen, Obstipation, Durchfall, Schlaflosigkeit, Kopfschmerzen, Schwindel und Mundtrockenheit.

Summary

Obesity treatment with caloric restriction, increased physical activity and behavior modification are frequently not effective to achieve individual weight loss or health goals in the long term. Pharmacotherapy may be considered if these basic conservative therapies are not sufficient. Since January 2018, a proprietary formulation of extended release Naltrexone 32mg/Bupropion 360mg is available for the pharmacotherapy of obesity in Germany. Naltrexone is a _-opioid receptor antagonist and Bupropion a noradrenergic/dopaminergic antidepressant, which together have effects on the Nucleus arcuatus in the hypothalamus and the mesolimbic dopaminergic reward system to reduce food intake. Efficacy and safety of Naltrexone/Bupropion (NB) has been investigated in combination with behavior modification in four double blind, placebo-controlled phase III clinical trials in 4,536 individuals with obesity or overweight for 56 weeks outcomes (COR-I, COR-II, COR-BMOD, COR-Diabetes). In the COR-I trial, Naltrexone/ Bupropion led to a mean weight loss of 5.4% compared to 1.3% in the placebo group. Common adverse effects of Naltrexone/Bupropion include nausea, vomiting, constipation, diarrhea, headache, dizziness, insomnia and dry mouth.

 
  • Literatur

  • 1 World Health Organization (WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organiz- ation Technical Report Series 2000; 894: 1-253.
  • 2 Hauner H, Moss A, Berg S. et al. Interdisziplinäre Leitlinie der Qualität S3 zur “Prävention und Therapie der Adipositas”. Adipositas 2014; 08: 179-221.
  • 3 JP Wilding. Combination therapy for obesity. J Psychopharmacol 2017; 31: 1503-1508.
  • 4 GA Bray, Frühbeck G, DH Ryan, JP Wilding. Management of obesity. Lancet 20167; 387: 1947-1956.
  • 5 https://ec.europa.eu/health/documents/community- register/2015/20150326130850/anx_130850_de.pdf.
  • 6 KF Ali, AP Shukla, LJ Aronne. Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moder- ate obesity. Expert Rev Clin Pharmacol 2016; 09: 27-34.
  • 7 Tek C. Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selec- tion and perspectives. Patient Prefer Adherence 2016; 10: 751-759.
  • 8 SZ Yanovski, JA Yanovski. Naltrexone extended-re- lease plus bupropion extended-release for treat- ment of obesity. JAMA 2015; 313: 1213-1214.
  • 9 KH Saunders, LI Igel, LJ Aronne. An Update on Naltrexone/Bupropion Extended-Release in the Treatment of Obesity. Expert Opin Pharmacother. 2016; 17: 2235-2242.
  • 10 BA Gosnell, AS Levine. Reward systems and food intake: role of opioids. Int J Obes (Lond) 2009; 33: S54-S58.
  • 11 ML Kirby, SG Holtzmann. Effects of chronic opi- ate administration of spontaneous activity of fetal rats. Pharmacol Biochem Behav 1982; 16: 263-269.
  • 12 DB Kurbanov, PJ Currie, DC Simonson, Borsook D, Elman I. Effects of naltrexone on food intake and body weight gain in olanzapine-treated rats. J Psychopharmacol 2012; 26: 1244-1251.
  • 13 RL Atkinson, LK Berke, CR Drake, ML Bibbs, Wil-liams FL, DL Kaiser. Effects of long-term therapy with naltrexone on body weight in obesity. Clin Pharmacol Ther 1985; 38: 419-422.
  • 14 SK Billes, MA Cowley. Catecholamine reuptake inhibition causes weight loss by increasing loco- motor activity and thermogenesis. Neuropsy- chopharmacology 2008; 33: 1287-1297.
  • 15 SA Thomas, RD Palmiter. Disruption of the dopa- mine beta-hydroxylase gene in mice suggests roles for norepinephrine in motor function, learning, and memory. Behav Neurosci 1997; 111: 579-589.
  • 16 JL Verpeut, NT Bello. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opin Drug Saf 2014; 13: 831-841.
  • 17 EC Settle, SM Stahl, SR Batey, JA Johnston, JA Ascher. Safety profile of sustained-release bupropion in depression: results of three clinical trials. Clin Ther 1999; 21: 454-463.
  • 18 JW Anderson, FL Greenway, Fujioka K, KM Gadde, McKenney J, O’Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, place- bo- controlled trial. Obes Res 2002; 10: 633-641.
  • 19 FL Greenway, Dunayevich E, Tollefson G, Erick-son J, Guttadauria M, Fujioka K, Cowley MA. NB-201 Group Study Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab 2009; 94: 4898-4906.
  • 20 SK Billes, Sinnayah P, MA Cowley. Naltrexone/bu- propion for obesity: an investigational combi- nation pharmacotherapy for weight loss. Pharma- col Res 2014; 84: 1-11.
  • 21 FL Greenway, Fujioka K, RA Plodkowski, Mudaliar S, Guttadauria M, Erickson J, DD Kim, Dunayevich E COR-I Group Study. Effect of naltre- xone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, rando- mised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376: 595-605.
  • 22 CM Apovian, Aronne L, Rubino D, Still C, Wyatt H, Burns C, Kim D, Dunayevich E COR-II Group Study. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 2013; 21: 935-943.
  • 23 TA Wadden, JP Foreyt, GD Foster, JO Hill, Klein S, O’Neil PM, MG Perri, FX Pi-Sunyer, CL Rock, Er-ickson JS, HN Maier, DD Kim, Dunayevich E. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011; 19: 110-120.
  • 24 Hollander P, AK Gupta, Plodkowski R, Greenway F, Bays H, Burns C, Klassen P, Fujioka K COR- Diabetes Group Study. Effects of naltrexone sus- tained-release/bupropion sustained-release com- bination therapy on body weight and glycemic pa- rameters in overweight and obese patients with type 2 diabetes. Diabetes Care 2013; 36: 4022-4029.
  • 25 SE Nissen, KE Wolski, Prcela L, Wadden T, JB Buse, Bakris G, Perez A, SR Smith. Effect of Naltre- xone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clini- cal Trial. JAMA 2016; 315: 990-1004.
  • 26 www.cheplapharm.com/ppc-mysimba.de.