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An open-label trial on the efficacy and tolerability of naltrexone/bupropion SR for treating altered eating behaviours and weight loss in binge eating disorder

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Abstract

Purpose

Binge eating disorder (BED) has a considerable clinical relevance by virtue of its high numerous psychiatric and medical comorbidities; among the latter, the most frequent is obesity. Available treatments for BED have shown frequent relapse of binges or weight regain in the long term. The new combination of naltrexone and bupropion sustained release (NB) has proved to be effective for weight loss among obese patients. As NB acts on hypothalamic and reward circuits, that seem involved in the pathogenesis and maintenance of BED symptoms, this study aims to evaluate the efficacy of NB in improving pathological eating behavior and losing weight in BED patients.

Methods

In this preliminary study, 23 obese-BED patients and a control group of 20 obese non-BED patients (respectively, Groups 1 and 2) who had previously undergone at least 5 unsuccessful weight-loss programs were treated with NB in addition to modified life style. Evaluation at t0 and after 16 weeks of treatment (t1) included anthropometric measurement, eating behavior assessment and psychopathological questionnaires (EDE-Q, BES, YFAS, BDI and STAI).

Results

A significant and similar weight loss (ΔBMI% ≈ 8%) was evident for both groups. Pathological eating behavior (i.e., binge, grazing, emotional eating, craving for carbohydrates, and post-dinner eating), BES score and YFAS severity significantly improved, especially among BED. NB was well tolerated and drop-out rate was low.

Conclusion

Treatment with NB, in addition to a reduced-calorie diet and increased physical activity, seems an effective and well-tolerated option for improving pathological eating behavior and losing weight in obese-BED patients.

Level of evidence

Level III case–control study.

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References

  1. Guerdjikova AI, Mori N, Casuto LS, McElroy SL (2019) Update on binge eating disorder. Med Clin N Am 103:669–680. https://doi.org/10.1016/j.mcna.2019.02.003

    Article  PubMed  Google Scholar 

  2. Hay P (2020) Current approach to eating disorders: a clinical update. Intern Med J 50:24–29. https://doi.org/10.1111/imj.14691

    Article  PubMed  PubMed Central  Google Scholar 

  3. Segura-Garcia C, Caroleo M, Rania M et al (2017) Binge eating disorder and bipolar spectrum disorders in obesity: psychopathological and eating behaviors differences according to comorbidities. J Affect Disord 208:424–430. https://doi.org/10.1016/j.jad.2016.11.005

    Article  PubMed  Google Scholar 

  4. Succurro E, Segura-Garcia C, Ruffo M et al (2015) Obese patients with a binge eating disorder have an unfavorable metabolic and inflammatory profile. Medicine (United States) 94:1–7. https://doi.org/10.1097/MD.0000000000002098

    Article  CAS  Google Scholar 

  5. Brownley KA, Berkman ND, Peat CM et al (2016) Binge-eating disorder in adults a systematic review and meta-analysis. Ann Intern Med 165:409–420

    Article  PubMed  PubMed Central  Google Scholar 

  6. Amodeo G, Cuomo A, Bolognesi S et al (2019) Pharmacotherapeutic strategies for treating binge eating disorder. Evidence from clinical trials and implications for clinical practice. Expert Opin Pharmacother 20:679–690

    Article  CAS  PubMed  Google Scholar 

  7. Valbrun LP, Zvonarev V (2020) The opioid system and food intake: use of opiate antagonists in treatment of binge eating disorder and abnormal eating behavior. J Clin Med Res 12:41–63. https://doi.org/10.14740/jocmr4066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fornaro M, Solmi M, Perna G et al (2016) Lisdexamfetamine in the treatment of moderate-to-severe binge eating disorder in adults: systematic review and exploratory meta-analysis of publicly available placebo-controlled, randomized clinical trials. Neuropsychiatr Dis Treat 12:1827–1836. https://doi.org/10.2147/NDT.S109637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stancil SL, Adelman W, Dietz A, Abdel-Rahman S (2019) Naltrexone reduces binge eating and purging in adolescents in an eating disorder program. J Child Adolesc Psychopharmacol 29:721–724. https://doi.org/10.1089/cap.2019.0056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Contrave Prescribing Information (2014) https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf. Accessed 20 Mar 2020

  11. Mysimba | European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/mysimba. Accessed 20 Mar 2020

  12. Hollander P, Gupta AK, Plodkowski R et al (2013) Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 36:4022–4029. https://doi.org/10.2337/dc13-0234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wadden TA, Foreyt JP, Foster GD et al (2011) Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 19:110–120. https://doi.org/10.1038/oby.2010.147

    Article  CAS  Google Scholar 

  14. Morton GJ, Meek TH, Schwartz MW (2014) Neurobiology of food intake in health and disease. Nat Rev Neurosci 15:367–378. https://doi.org/10.1038/nrn3745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Morton GJ, Blevins JE, Williams DL et al (2005) Leptin action in the forebrain regulates the hindbrain response to satiety signals. J Clin Invest 115:703–710. https://doi.org/10.1172/JCI22081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Volkow ND, Wang G-J, Baler RD (2011) Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci 15:37–46. https://doi.org/10.1016/j.tics.2010.11.001

    Article  CAS  PubMed  Google Scholar 

  17. Caroleo M, Primerano A, Rania M et al (2018) A real world study on the genetic, cognitive and psychopathological differences of obese patients clustered according to eating behaviours. Eur Psychiatry 48:58–64. https://doi.org/10.1016/j.eurpsy.2017.11.009

    Article  PubMed  Google Scholar 

  18. Gormally J, Black S, Daston S, Rardin D (1982) The assessment of binge eating severity among obese persons. Addict Behav 7:47–55

    Article  CAS  PubMed  Google Scholar 

  19. Fairburn CG, Beglin SJ (1994) Assessment of eating disorders: interview or self-report questionnaire? Int J Eat Disord 16:363–370

    CAS  PubMed  Google Scholar 

  20. Aloi M, Rania M, Rodríguez Muñoz RC et al (2017) Validation of the Italian version of the Yale Food Addiction Scale 2.0 (I-YFAS 2.0) in a sample of undergraduate students. Eat Weight Disord 22:527–533. https://doi.org/10.1007/s40519-017-0421-x

    Article  Google Scholar 

  21. Manzoni GM, Rossi A, Pietrabissa G et al (2018) Validation of the Italian Yale Food Addiction Scale in postgraduate university students. Eat Weight Disord 23:167–176. https://doi.org/10.1007/s40519-018-0495-0

    Article  PubMed  Google Scholar 

  22. Imperatori C, Fabbricatore M, Lester D et al (2019) Psychometric properties of the modified Yale Food Addiction Scale Version 2.0 in an Italian non-clinical sample. Eat Weight Disord 24:37–45. https://doi.org/10.1007/s40519-018-0607-x

    Article  PubMed  Google Scholar 

  23. Manzoni GM, Rossi A, Pietrabissa G et al (2020) Structural validity, measurement invariance, reliability and diagnostic accuracy of the Italian version of the Yale Food Addiction Scale 2.0 in patients with severe obesity and the general population. Eat Weight Disord. https://doi.org/10.1007/s40519-020-00858-y

    Article  PubMed  Google Scholar 

  24. Hardoy M, Cadeddu M, Murru A et al (2005) Validation of the Italian version of the Mood Disorder Questionnaire for the screening of bipolar disorders. Clin Pract Epidemiol Mental Health 1:8. https://doi.org/10.1186/1745-0179-1-8

    Article  Google Scholar 

  25. Beck AT, Ward CH, Mendelson M et al (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Article  CAS  PubMed  Google Scholar 

  26. Spielberger C, Gorsuch R, Lushene R (1970) STAI Manual for the State-Trait Anxiety Inventory. Palo Alto

  27. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Associates Inc., Hillsdale

    Google Scholar 

  28. Greenway FL, Dunayevich E, Tollefson G et al (2009) Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab 94:4898–4906. https://doi.org/10.1210/jc.2009-1350

    Article  CAS  PubMed  Google Scholar 

  29. Smith SR, Fujioka K, Gupta AK et al (2013) Combination therapy with naltrexone and bupropion for obesity reduces total and visceral adiposity. Diabetes Obes Metab 15:863–866. https://doi.org/10.1111/dom.12095

    Article  CAS  PubMed  Google Scholar 

  30. Sherman MM, Ungureanu S, Rey JA (2016) Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults. P T 41:164–172

    PubMed  PubMed Central  Google Scholar 

  31. Apovian CM, Aronne L, Rubino D et al (2013) A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 21:935–943. https://doi.org/10.1002/oby.20309

    Article  CAS  Google Scholar 

  32. Greenway FL, Fujioka K, Plodkowski RA et al (2010) Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 376:595–605. https://doi.org/10.1016/S0140-6736(10)60888-4

    Article  CAS  PubMed  Google Scholar 

  33. Billes SK, Sinnayah P, Cowley MA (2014) Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss. Pharmacol Res 84:1–11. https://doi.org/10.1016/j.phrs.2014.04.004

    Article  CAS  PubMed  Google Scholar 

  34. Davis C (2017) A commentary on the associations among ‘food addiction’, binge eating disorder, and obesity: overlapping conditions with idiosyncratic clinical features. Appetite 115:3–8. https://doi.org/10.1016/j.appet.2016.11.001

    Article  PubMed  Google Scholar 

  35. Gadde KM, Allison DB, Ryan DH et al (2011) Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet (London, England) 377:1341–1352. https://doi.org/10.1016/S0140-6736(11)60205-5

    Article  CAS  Google Scholar 

  36. Appolinario JC, Godoy-Matos A, Fontenelle LF et al (2002) An open-label trial of sibutramine in obese patients with binge-eating disorder. J Clin Psychiatry 63:28–30. https://doi.org/10.4088/JCP.v63n0106

    Article  CAS  PubMed  Google Scholar 

  37. Pataky Z, Gasteyger C, Ziegler O et al (2013) Efficacy of rimonabant in obese patients with binge eating disorder. Exp Clin Endocrinol Diabetes 121:20–26. https://doi.org/10.1055/s-0032-1329957

    Article  CAS  PubMed  Google Scholar 

  38. Smith SR, Blundell JE, Burns C et al (2007) Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study. Am J Physiol Endocrinol Metab 293:E620–E627. https://doi.org/10.1152/ajpendo.00217.2007

    Article  CAS  PubMed  Google Scholar 

  39. McElroy SL, Guerdjikova AI, Kim DD et al (2013) Naltrexone/bupropion combination therapy in overweight or obese patients with major depressive disorder: results of a pilot study. Prim Care Companion J Clin Psychiatry. https://doi.org/10.4088/PCC.12m01494

    Article  Google Scholar 

  40. Halseth A, Shan K, Gilder K et al (2018) Quality of life, binge eating and sexual function in participants treated for obesity with sustained release naltrexone/bupropion. Obes Sci Pract 4:141–152. https://doi.org/10.1002/osp4.156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Reas DL, Grilo CM (2015) Pharmacological treatment of binge eating disorder: update review and synthesis. Expert Opin Pharmacother 16:1463–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Stefano SC, Bacaltchuk J, Blay SL, Appolinário JC (2008) Antidepressants in short-term treatment of binge eating disorder: systematic review and meta-analysis. Eat Behav 9:129–136

    Article  PubMed  Google Scholar 

  43. Leombruni P, Lavagnino L, Fassino S (2009) Treatment of obese patients with binge eating disorder using topiramate: a review. Neuropsychiatr Dis Treat 5:385–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kelley AE, Berridge KC (2002) The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci 22:3306–3311. https://doi.org/10.1523/JNEUROSCI.22-09-03306.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Peciña S, Berridge KC (2005) Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 25:11777–11786. https://doi.org/10.1523/JNEUROSCI.2329-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sinnayah P, Wallingford N, Evans A, Cowley M (2007) Bupropion and naltrexone interact synergistically to decrease food intake in mice. In: North American association for the study of obesity annual scientific meeting, New Orleans

  47. Kessler RM, Hutson PH, Herman BK, Potenza MN (2016) The neurobiological basis of binge-eating disorder. Neurosci Biobehav Rev 63:223–238. https://doi.org/10.1016/j.neubiorev.2016.01.013

    Article  PubMed  Google Scholar 

  48. Jiménez-Murcia S, Agüera Z, Paslakis G et al (2019) Food addiction in eating disorders and obesity: analysis of clusters and implications for treatment. Nutrients 11:2633. https://doi.org/10.3390/nu11112633

    Article  CAS  PubMed Central  Google Scholar 

  49. Gearhardt AN, White MA, Potenza MN (2011) Binge eating disorder and food addiction. Curr Drug Abuse Rev 4:201–207

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gearhardt AN, White MA, Masheb RM et al (2012) An examination of the food addiction construct in obese patients with binge eating disorder. Int J Eat Disord 45:657–663. https://doi.org/10.1002/eat.20957

    Article  PubMed  Google Scholar 

  51. Gearhardt AN (2011) Neural correlates of food addiction. Arch Gen Psychiatry 68:808. https://doi.org/10.1001/archgenpsychiatry.2011.32

    Article  PubMed  PubMed Central  Google Scholar 

  52. Colantuoni C, Schwenker J, McCarthy J et al (2001) Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. NeuroReport 12:3549–3552

    Article  CAS  PubMed  Google Scholar 

  53. Davis C, Levitan RD, Kaplan AS et al (2014) Food cravings, appetite, and snack-food consumption in response to a psychomotor stimulant drug: the moderating effect of “food-addiction”. Front Psychol 5:403. https://doi.org/10.3389/fpsyg.2014.00403

    Article  PubMed  PubMed Central  Google Scholar 

  54. Gordon EL, Ariel-Donges AH, Bauman V, Merlo LJ (2018) What is the evidence for “food addiction?” A systematic review. Nutrients. https://doi.org/10.3390/NU10040477

    Article  PubMed  PubMed Central  Google Scholar 

  55. Yanovski SZ, Yanovski JA (2015) Naltrexone extended-release plus bupropion extended-release for treatment of obesity. JAMA 313:1213. https://doi.org/10.1001/jama.2015.1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ali KF, Shukla AP, Aronne LJ (2016) Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moderate obesity. Expert Rev Clin Pharmacol 9:27–34. https://doi.org/10.1586/17512433.2016.1100072

    Article  CAS  PubMed  Google Scholar 

  57. Saunders KH, Umashanker D, Igel LI et al (2018) Obesity Pharmacotherapy. Med Clin N Am 102:135–148

    Article  PubMed  Google Scholar 

  58. White MA, Grilo CM (2013) Bupropion for overweight women with binge-eating disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 74:400–406. https://doi.org/10.4088/JCP.12m08071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Anderson JW, Greenway FL, Fujioka K et al (2002) Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Obes Res 10:633–641. https://doi.org/10.1038/oby.2002.86

    Article  CAS  PubMed  Google Scholar 

  60. Witkamp RF (2011) Current and future drug targets in weight management. Pharm Res 28:1792–1818. https://doi.org/10.1007/s11095-010-0341-1

    Article  CAS  PubMed  Google Scholar 

  61. Morton GJ, Cummings DE, Baskin DG et al (2006) Central nervous system control of food intake and body weight. Nature 443:289–295. https://doi.org/10.1038/nature05026

    Article  CAS  PubMed  Google Scholar 

  62. Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight. N Engl J Med 332:621–628. https://doi.org/10.1056/NEJM199503093321001

    Article  CAS  PubMed  Google Scholar 

  63. Patel DK, Stanford FC (2018) Safety and tolerability of new-generation anti-obesity medications: a narrative review. Postgrad Med. https://doi.org/10.1080/00325481.2018.1435129

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bello NT (2019) Update on drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opin Drug Saf. https://doi.org/10.1080/14740338.2019.1618268

    Article  PubMed  Google Scholar 

  65. Halpern B, Mancini MC (2017) Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release. Expert Opin Drug Saf 16:27–39. https://doi.org/10.1080/14740338.2017.1247807

    Article  CAS  PubMed  Google Scholar 

  66. Violante R, Santoro S, González C (2011) Prevalence of depression and anxiety in a cohort of 761 obese patients: impact in adherence to therapy and its outcome. Vertex 22:85–93

    PubMed  Google Scholar 

  67. Blom TJ, Mingione CJ, Guerdjikova AI et al (2014) Placebo response in binge eating disorder: a pooled analysis of 10 clinical trials from one research group. Eur Eat Disord Rev 22:140–146. https://doi.org/10.1002/erv.2277

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank all the patients who accepted to participate in this research and the pharmaceutical company Bruno Farmaceutici for providing the drug free of charge to every patient in the study.

Funding

No incentive was offered either to the patients or researchers who participated in the study.

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Authors and Affiliations

  1. Psychiatric Unit, Department of Health Sciences, University “Magna Graecia”, Viale Europa, 88100, Catanzaro, Italy

    Elvira Anna Carbone, Mariarita Caroleo, Marianna Rania, Giuseppina Calabrò, Filippo Antonio Staltari, Renato de Filippis, Matteo Aloi & Francesca Condoleo

  2. Outpatient Service for Research and Treatment of Eating Disorders, University Hospital Mater Domini, 88100, Catanzaro, Italy

    Elvira Anna Carbone, Mariarita Caroleo, Marianna Rania, Giuseppina Calabrò, Filippo Antonio Staltari, Renato de Filippis, Matteo Aloi, Francesca Condoleo & Cristina Segura-Garcia

  3. Internal Medical Unit, Department of Medical and Surgical Sciences, University “Magna Graecia”, Viale Europa, 88100, Catanzaro, Italy

    Franco Arturi

  4. Psychiatric Unit, Department of Medical and Surgical Sciences, University “Magna Graecia”, Viale Europa, 88100, Catanzaro, Italy

    Cristina Segura-Garcia

Authors
  1. Elvira Anna Carbone
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  2. Mariarita Caroleo
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  10. Cristina Segura-Garcia
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Contributions

CSG designed the study. EAC, MC, MR, GC, FAS and RF collected the data. CSG and MA performed the statistical analysis. EAC, MC, MR wrote the first draft of the manuscript. CSG, GC, FAS, RF and FA made the first critical review; EAC wrote the final manuscript. All authors commented on, read and approved the final manuscript.

Corresponding author

Correspondence to Cristina Segura-Garcia.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval was obtained from the ethics committee of “Comitato Etico Regione Calabria, Area Centro” (no. 65/2018). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the studies before any procedure took place.

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Carbone, E.A., Caroleo, M., Rania, M. et al. An open-label trial on the efficacy and tolerability of naltrexone/bupropion SR for treating altered eating behaviours and weight loss in binge eating disorder. Eat Weight Disord 26, 779–788 (2021). https://doi.org/10.1007/s40519-020-00910-x

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