Progress in Developing Pharmacologic Agents to Treat Bulimia Nervosa

Abstract

This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others. The only available drugs with established efficacy in BN at this time include antidepressants (especially selective serotonin reuptake inhibitors [SSRIs]) and the antiepileptic topiramate, though the efficacy of these compounds is modest at best. The only medications we found currently receiving empirical study in people with BN were fluoxetine, other serotonergic antidepressants, intranasal naloxone, lisdexamfetamine dimesylate, phentermine–topiramate combination, the antiandrogenic oral contraceptive ethinyl estradiol plus drospirenone, and prazosin. Preclinical models suggest that nociceptin receptor antagonists, the selective serotonin 5-HT2C receptor agonist lorcaserin, monoamine stabilizers, and selective orexin-1 receptor antagonists might be helpful. We found no evidence of a drug developed specifically for the treatment of individuals with BN. Future areas for research in the pharmacotherapy of BN are suggested. Importantly, until drugs are developed specifically for eating disorders, drugs developed for other conditions that are centrally acting and associated with beneficial psychotropic effects and/or reduced appetite or weight loss might be considered for repurposing in BN.

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References

  1. 1.

    Kessler RC, Berglund PA, Chiu WT, Deitz AC, Hudson JI, Shahly V, et al. The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys. Biol Psychiatry. 2013;73(9):904–14. https://doi.org/10.1016/j.biopsych.2012.11.020.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Swanson SA, Crow SJ, Le Grange D, Swendsen J, Merikangas KR. Prevalence and correlates of eating disorders in adolescents: results from the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry. 2011;68:714–23. https://doi.org/10.1001/archgenpsychiatry.2011.22.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007;61(3):348–58. https://doi.org/10.1016/j.biopsych.2006.03.040.

    PubMed  Article  Google Scholar 

  4. 4.

    Fichter MM, Quadflieg N, Hedlund S. Long-term course of binge eating disorder and bulimia nervosa: relevance for nosology and diagnostic criteria. Int J Eat Disord. 2008;41(7):577–86. https://doi.org/10.1002/eat.20539.

    PubMed  Article  Google Scholar 

  5. 5.

    Zeeck A, Weber S, Sandholz A, Joos A, Hartmann A. Stability of long-term outcome in bulimia nervosa: a 3-year follow-up. J Clin Psychol. 2011;67(3):318–27. https://doi.org/10.1002/jclp.20766.

    PubMed  Article  Google Scholar 

  6. 6.

    Eddy KT, Tabri N, Thomas JJ, Murray HB, Keshaviah A, Hastings E, et al. Recovery from anorexia nervosa and bulimia nervosa at 22-year follow-up. J Clin Psychiatry. 2017;78(2):184–9. https://doi.org/10.4088/JCP.15m10393.

    PubMed  Article  Google Scholar 

  7. 7.

    Crow SJ, Peterson CB, Swanson SA, Raymond NC, Specker S, Eckert ED, et al. Increased mortality in bulimia nervosa and other eating disorders. Am J Psychiatry. 2009;166(12):1342–6. https://doi.org/10.1176/appi.ajp.2009.09020247.

    PubMed  Article  Google Scholar 

  8. 8.

    Agh T, Kovacs G, Supina D, Pawaskar M, Herman BK, Voko Z, et al. A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder. Eat Weight Disord. 2016;21(3):353–64. https://doi.org/10.1007/s40519-016-0264-x.

    PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Hay P, Chinn D, Forbes D, Madden S, Newton R, Sugenor L, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of eating disorders. Aust N Z J Psychiatry. 2014;48(11):977–1008. https://doi.org/10.1177/0004867414555814.

    PubMed  Article  Google Scholar 

  10. 10.

    National Institute for Clinical Excellence (NICE). Eating disorders: recognition and treatment. Clinical guideline no. 9. London: UKMay; 2017.

    Google Scholar 

  11. 11.

    Yager J. Management of patients with chronic, intractable eating disorders. In: Yager J, Powers PS, editors. Clinical manual of eating disorders. Washington, DC: American Psychiatric Publishin; 2007. p. 407–39.

    Google Scholar 

  12. 12.

    Himmerich H, Treasure J. Psychopharmacological advances in eating disorders. Expert Rev Clin Pharmacol. 2018;11(1):95–108. https://doi.org/10.1080/17512433.2018.1383895.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Monteleone AM, Castellini G, Volpe U, Ricca V, Lelli L, Monteleone P, et al. Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(Pt B):132–42. https://doi.org/10.1016/j.pnpbp.2017.02.020.

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Mueller SV, Morishima Y, Schwab S, Wiest R, Federspiel A, Hasler G. Neural correlates of impaired reward-effort integration in remitted bulimia nervosa. Neuropsychopharmacology. 2018;43(4):868–76. https://doi.org/10.1038/npp.2017.277.

    PubMed  Article  Google Scholar 

  15. 15.

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.

    Google Scholar 

  16. 16.

    ICD-11. The international classification diseases, Eleventh Revision. 2018.

  17. 17.

    van Gestel MA, Kostrzewa E, Adan RA, Janhunen SK. Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans. Br J Pharmacol. 2014;171(20):4767–84. https://doi.org/10.1111/bph.12789.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  18. 18.

    Fluoxetine Bulimia Nervosa Collaborative Study Group. Fluoxetine in the treatment of bulimia nervosa: A multicenter, placebo-controlled, double-blind trial. Arch Gen Psychiatry. 1992;49(2):139–47.

    Article  Google Scholar 

  19. 19.

    Shapiro JR, Berkman ND, Brownley KA, Sedway JA, Lohr KN, Bulik CM. Bulimia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40(4):321–36. https://doi.org/10.1002/eat.20372.

    PubMed  Article  Google Scholar 

  20. 20.

    Yager J, Powers PS. Clinical manual of eating disorders. Washington, DC: American Psychiatric Publishing; 2007.

    Google Scholar 

  21. 21.

    Aigner M, Treasure J, Kaye W, Kasper S. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry. 2011;12(6):400–43. https://doi.org/10.3109/15622975.2011.602720.

    PubMed  Article  Google Scholar 

  22. 22.

    Bacaltchuk J, Hay P. Antidepressants versus placebo for people with bulimia nervosa. Cochrane Database Syst Rev. 2003;4:CD003391. https://doi.org/10.1002/14651858.CD003391.

    Article  Google Scholar 

  23. 23.

    Horne RL, Ferguson JM, Pope HG Jr, Hudson JI, Lineberry CG, Ascher J, et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988;49(7):262–6.

    PubMed  CAS  Google Scholar 

  24. 24.

    Walsh BT, Hadigan CM, Devlin MJ, Gladis M, Roose SP. Long-term outcome of antidepressant treatment for bulimia nervosa. Am J Psychiatry. 1991;148(9):1206–12. https://doi.org/10.1176/ajp.148.9.1206.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Fichter MM, Kruger R, Rief W, Holland R, Dohne J. Fluvoxamine in prevention of relapse in bulimia nervosa: effects on eating-specific psychopathology. J Clin Psychopharmacol. 1996;16(1):9–18.

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    Romano SJ, Halmi KA, Sarkar NP, Koke SC, Lee JS. A placebo-controlled study of fluoxetine in continued treatment of bulimia nervosa after successful acute fluoxetine treatment. Am J Psychiatry. 2002;159(1):96–102.

    PubMed  Article  Google Scholar 

  27. 27.

    El-Giamal N, de Zwaan M, Bailer U, Lennkh C, Schussler P, Strnad A, et al. Reboxetine in the treatment of bulimia nervosa: a report of seven cases. Int Clin Psychopharmacol. 2000;15(6):351–6.

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    El-Giamal N, de Zwaan M, Bailer U, Strnad A, Schussler P, Kasper S. Milnacipran in the treatment of bulimia nervosa: a report of 16 cases. Eur Neuropsychopharmacol. 2003;13(2):73–9.

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Fassino S, Daga GA, Boggio S, Garzaro L, Piero A. Use of reboxetine in bulimia nervosa: a pilot study. J Psychopharmacol. 2004;18(3):423–8. https://doi.org/10.1177/026988110401800314.

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Hazen E, Fava M. Successful treatment with duloxetine in a case of treatment refractory bulimia nervosa: a case report. J Psychopharmacol. 2006;20(5):723–4. https://doi.org/10.1177/0269881106060502.

    PubMed  Article  Google Scholar 

  31. 31.

    Noma S, Uwatoko T, Yamamoto H, Hayashi T. Effects of milnacipran on binge eating - a pilot study. Neuropsychiatr Dis Treat. 2008;4(1):295–300.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  32. 32.

    Guerdjikova AI, McElroy SL, Winstanley EL, Nelson EB, Mori N, McCoy J, et al. Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial. Int J Eat Disord. 2012;45:281–9. https://doi.org/10.1002/eat.20946.

    PubMed  Article  Google Scholar 

  33. 33.

    Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390(10093):480–9. https://doi.org/10.1016/S0140-6736(17)31264-3.

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Ionescu DF, Papakostas GI. Experimental medication treatment approaches for depression. Transl Psychiatry. 2017;7(3):e1068. https://doi.org/10.1038/tp.2017.33.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  35. 35.

    Bacaltchuk J, Hay P, Trefiglio R. Antidepressants versus psychological treatments and their combination for bulimia nervosa. Cochrane Database Syst Rev. 2001;4:CD003385. https://doi.org/10.1002/14651858.CD003385.

    Article  Google Scholar 

  36. 36.

    Walsh BT, Agras WS, Devlin MJ, Fairburn CG, Wilson GT, Kahn C, et al. Fluoxetine for bulimia nervosa following poor response to psychotherapy. Am J Psychiatry. 2000;157(8):1332–4.

    PubMed  CAS  Article  Google Scholar 

  37. 37.

    Safer DL, Telch CF, Agras WS. Dialectical behavior therapy for bulimia nervosa. Am J Psychiatry. 2001;158(4):632–4. https://doi.org/10.1176/appi.ajp.158.4.632.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  38. 38.

    Kaplan AS, Garfinkel PE, Darby PL, Garner DM. Carbamazepine in the treatment of bulimia. Am J Psychiatry. 1983;140(9):1225–6.

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Kaplan AS. Anticonvulsant treatment of eating disorders. In: Garfinkel PE, Garner DM, editors. The role of drug treatments for eating disorders. New York: Brunner/Mazel; 1987. p. 96–123.

    Google Scholar 

  40. 40.

    Hudson JI, Pope HG Jr. The role of anticonvulsants in the treatment of bulimia. In: McElroy SL, Pope Jr HG, editors. Use of anticonvulsants in psychiatry. Clifton, NJ: Oxford Health Care; 1988. p. 141–53.

    Google Scholar 

  41. 41.

    Hedges DW, Reimherr FW, Hoopes SP, Rosenthal NR, Kamin M, Karim R, et al. Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 2: improvement in psychiatric measures. J Clin Psychiatry. 2003;64(12):1449–54.

    PubMed  CAS  Article  Google Scholar 

  42. 42.

    Hoopes SP, Reimherr FW, Hedges DW, Rosenthal NR, Kamin M, Karim R, et al. Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures. J Clin Psychiatry. 2003;64(11):1335–41.

    PubMed  CAS  Article  Google Scholar 

  43. 43.

    Nickel C, Tritt K, Muehlbacher M, Pedrosa Gil F, Mitterlehner FO, Kaplan P, et al. Topiramate treatment in bulimia nervosa patients: a randomized, double-blind, placebo-controlled trial. Int J Eat Disord. 2005;38(4):295–300. https://doi.org/10.1002/eat.20202.

    PubMed  Article  Google Scholar 

  44. 44.

    McElroy SL, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim MR, et al. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160(2):255–61.

    PubMed  Article  Google Scholar 

  45. 45.

    McElroy SL, Hudson JI, Capece JA, Beyers K, Fisher AC, Rosenthal NR, et al. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study. Biol Psychiatry. 2007;61(9):1039–48. https://doi.org/10.1016/j.biopsych.2006.08.008.

    PubMed  CAS  Article  Google Scholar 

  46. 46.

    Claudino AM, de Oliveira IR, Appolinario JC, Cordas TA, Duchesne M, Sichieri R, et al. Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive-behavior therapy in binge-eating disorder. J Clin Psychiatry. 2007;68(9):1324–32.

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    McElroy SL, Mori N, Guerdjikova AI, Keck PE Jr. Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature. Med Hypotheses. 2018;111:90–3. https://doi.org/10.1016/j.mehy.2017.12.029.

    PubMed  CAS  Article  Google Scholar 

  48. 48.

    Cifani C, Polidori C, Melotto S, Ciccocioppo R, Massi M. A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: Effect of sibutramine, fluoxetine, topiramate, and midazolam. Psychopharmacology. 2009;204(1):113–25. https://doi.org/10.1007/s00213-008-1442-y.

    PubMed  CAS  Article  Google Scholar 

  49. 49.

    Czyzyk TA, Sahr AE, Statnick MA. A model of binge-like eating behavior in mice that does not require food deprivation or stress. Obesity (Silver Spring). 2010;18(9):1710–7. https://doi.org/10.1038/oby.2010.46.

    Article  Google Scholar 

  50. 50.

    Barbee JG. Topiramate in the treatment of severe bulimia nervosa with comorbid mood disorders: a case series. Int J Eat Disord. 2003;33(4):468–72. https://doi.org/10.1002/eat.10154.

    PubMed  Article  Google Scholar 

  51. 51.

    Bruno A, Riganello D, Marino A. Treatment with aripiprazole and topiramate in an obese subject with borderline personality disorder, obsessive-compulsive symptoms and bulimia nervosa: a case report. Cases J. 2009;2:7288. https://doi.org/10.4076/1757-1626-2-7288.

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Felstrom A, Blackshaw S. Topiramate for bulimia nervosa with bipolar II disorder. Am J Psychiatry. 2002;159(7):1246–7.

    PubMed  Article  Google Scholar 

  53. 53.

    Knable M. Topiramate for bulimia nervosa in epilepsy. Am J Psychiatry. 2001;158(2):322–3.

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Colom F, Vieta E, Benabarre A, Martinez-Aran A, Reinares M, Corbella B, et al. Topiramate abuse in a bipolar patient with an eating disorder. J Clin Psychiatry. 2001;62(6):475–6.

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    Chung AM, Reed MD. Intentional topiramate ingestion in an adolescent female. Ann Pharmacother. 2004;38(9):1439–42. https://doi.org/10.1345/aph.1D572aph.1D572.

    PubMed  Article  Google Scholar 

  56. 56.

    Lebow J, Chuy JA, Cedermark K, Cook K, Sim LA. The development or exacerbation of eating disorder symptoms after topiramate initiation. Pediatrics. 2015;135(5):e1312–6. https://doi.org/10.1542/peds.2014-3413.

    PubMed  Article  Google Scholar 

  57. 57.

    Guerdjikova AI, Blom TJ, Martens BE, Keck PE Jr, McElroy SL. Zonisamide in the treatment of bulimia nervosa: an open-label, pilot, prospective study. Int J Eat Disord. 2013;46(7):747–50. https://doi.org/10.1002/eat.22159.

    PubMed  Article  Google Scholar 

  58. 58.

    McElroy SL, Kotwal R, Guerdjikova AI, Welge JA, Nelson EB, Lake KA, et al. Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry. 2006;67(12):1897–906.

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Herridge PL, Pope HG Jr. Treatment of bulimia and rapid-cycling bipolar disorder with sodium valproate: a case report. J Clin Psychopharmacol. 1985;5(4):229–30.

    PubMed  CAS  Article  Google Scholar 

  60. 60.

    McElroy SL, Keck PE Jr, Pope HG Jr. Sodium valproate: its use in primary psychiatric disorders. J Clin Psychopharmacol. 1987;7(1):16–24.

    PubMed  CAS  Google Scholar 

  61. 61.

    Shapira NA, Goldsmith TD, McElroy SL. Treatment of binge-eating disorder with topiramate: a clinical case series. J Clin Psychiatry. 2000;61(5):368–72.

    PubMed  CAS  Article  Google Scholar 

  62. 62.

    Trunko ME, Schwartz TA, Marzola E, Klein AS, Kaye WH. Lamotrigine use in patients with binge eating and purging, significant affect dysregulation, and poor impulse control. Int J Eat Disord. 2014;47(3):329–34. https://doi.org/10.1002/eat.22234.

    PubMed  Article  Google Scholar 

  63. 63.

    Guerdjikova AI, McElroy SL, Welge JA, Nelson E, Keck PE, Hudson JI. Lamotrigine in the treatment of binge-eating disorder with obesity: a randomized, placebo-controlled monotherapy trial. Int Clin Psychopharmacol. 2009;24(3):150–8. https://doi.org/10.1097/YIC.0b013e328329c7b5.

    PubMed  Article  Google Scholar 

  64. 64.

    Younus I, Reddy DS. A resurging boom in new drugs for epilepsy and brain disorders. Expert Rev Clin Pharmacol. 2018;11(1):27–45. https://doi.org/10.1080/17512433.2018.1386553.

    PubMed  CAS  Article  Google Scholar 

  65. 65.

    Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204–11. https://doi.org/10.1212/WNL.0000000000005254.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  66. 66.

    Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of cannabidiol on drop seizures in the lennox-gastaut syndrome. N Engl J Med. 2018;378(20):1888–97. https://doi.org/10.1056/NEJMoa1714631.

    PubMed  CAS  Article  Google Scholar 

  67. 67.

    Mitchell JE, Christenson G, Jennings J, Huber M, Thomas B, Pomeroy C, et al. A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia. J Clin Psychopharmacol. 1989;9(2):94–7.

    PubMed  CAS  Article  Google Scholar 

  68. 68.

    Alger SA, Schwalberg MD, Bigaouette JM, Michalek AV, Howard LJ. Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. Am J Clin Nutr. 1991;53(4):865–71.

    PubMed  CAS  Article  Google Scholar 

  69. 69.

    Marrazzi MA, Bacon JP, Kinzie J, Luby ED. Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. Int Clin Psychopharmacol. 1995;10(3):163–72.

    PubMed  CAS  Article  Google Scholar 

  70. 70.

    Drewnowski A, Krahn DD, Demitrack MA, Nairn K, Gosnell BA. Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am J Clin Nutr. 1995;61(6):1206–12.

    PubMed  CAS  Article  Google Scholar 

  71. 71.

    Raingeard I, Courtet P, Renard E, Bringer J. Naltrexone improves blood glucose control in type 1 diabetic women with severe and chronic eating disorders. Diabetes Care. 2004;27(3):847–8.

    PubMed  CAS  Article  Google Scholar 

  72. 72.

    Jonas JM, Gold MS. The use of opiate antagonists in treating bulimia: a study of low-dose versus high-dose naltrexone. Psychiatry Res. 1988;24(2):195–9.

    PubMed  CAS  Article  Google Scholar 

  73. 73.

    Marrazzi MA, Markham KM, Kinzie J, Luby ED. Binge eating disorder: response to naltrexone. Int J Obes Relat Metab Disord. 1995;19(2):143–5.

    PubMed  CAS  Google Scholar 

  74. 74.

    Neumeister A, Winkler A, Wober-Bingol C. Addition of naltrexone to fluoxetine in the treatment of binge eating disorder. Am J Psychiatry. 1999;156(5):797.

    PubMed  CAS  Google Scholar 

  75. 75.

    McElroy SL, Guerdjikova AI, Blom TJ, Crow SJ, Memisoglu A, Silverman BL, et al. A placebo-controlled pilot study of the novel opioid receptor antagonist ALKS-33 in binge eating disorder. Int J Eat Disord. 2013;46(3):239–45. https://doi.org/10.1002/eat.22114.

    PubMed  Article  Google Scholar 

  76. 76.

    Ziauddeen H, Chamberlain SR, Nathan PJ, Koch A, Maltby K, Bush M, et al. Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects. Mol Psychiatry. 2013;18(12):1287–93. https://doi.org/10.1038/mp.2012.154.

    PubMed  CAS  Article  Google Scholar 

  77. 77.

    Alho H, Lahti T, Appelberg B, Ketunen J, Sinclair D. Opioid antagonist naloxone nasal spray treatment for patients with binge eating disorder: a randomized controlled trial (Poster # NR4-29). Presented at American Psychiatric Association 166th Annual Meeting; May 18–22; San Francisco, CA 2013.

  78. 78.

    Mundin G, McDonald R, Smith K, Harris S, Strang J. Pharmacokinetics of concentrated naloxone nasal spray over first 30 minutes post-dosing: Analysis of suitability for opioid overdose reversal. Addiction. 2017;112(9):1647–52. https://doi.org/10.1111/add.13849.

    PubMed  Article  Google Scholar 

  79. 79.

    McElroy SL, Guerdjikova AI, Winstanley EL, O’Melia AM, Mori N, McCoy J, et al. Acamprosate in the treatment of binge eating disorder: a placebo-controlled trial. Int J Eat Disord. 2011;44(1):81–90. https://doi.org/10.1002/eat.20876.

    PubMed  Article  Google Scholar 

  80. 80.

    McElroy SL, Hudson JI, Mitchell JE, Wilfley D, Ferreira-Cornwell MC, Gao J, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72(3):235–46.

    PubMed  Article  Google Scholar 

  81. 81.

    McElroy SL, Hudson J, Ferreira-Cornwell MC, Radewonuk J, Whitaker T, Gasior M. Lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder: results of two pivotal phase 3 randomized controlled trials. Neuropsychopharmacology. 2016;41(5):1251–60. https://doi.org/10.1038/npp.2015.275.

    PubMed  CAS  Article  Google Scholar 

  82. 82.

    Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J, Gasior M. Efficacy of lisdexamfetamine in adults with moderate to severe binge-eating disorder: a randomized controlled clinical trial. JAMA Psychiatry. 2017;74(9):903–10. https://doi.org/10.1001/jamapsychiatry.2017.1889.

    PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Ong YL, Checkley SA, Russell GF. Suppression of bulimic symptoms with methylamphetamine. Br J Psychiatry. 1983;143:288–93.

    PubMed  CAS  Article  Google Scholar 

  84. 84.

    Drimmer EJ. Stimulant treatment of bulimia nervosa with and without attention-deficit disorder: three case reports. Nutrition. 2003;19(1):76–7.

    PubMed  Article  Google Scholar 

  85. 85.

    Dukarm CP. Bulimia nervosa and attention deficit hyperactivity disorder: a possible role for stimulant medication. J Womens Health (Larchmt). 2005;14(4):345–50. https://doi.org/10.1089/jwh.2005.14.345.

    Article  Google Scholar 

  86. 86.

    Guerdjikova AI, McElroy SL. Adjunctive methylphenidate in the treatment of bulimia nervosa co-occurring with bipolar disorder and substance dependence. Innov Clin Neurosci. 2013;10(2):30–3.

    PubMed  PubMed Central  Google Scholar 

  87. 87.

    Keshen A, Ivanova I. Reduction of bulimia nervosa symptoms after psychostimulant initiation in patients with comorbid ADHD: five case reports. Eat Disord. 2013;21(4):360–9. https://doi.org/10.1080/10640266.2013.797828.

    PubMed  Article  Google Scholar 

  88. 88.

    Schweickert LA, Strober M, Moskowitz A. Efficacy of methylphenidate in bulimia nervosa comorbid with attention-deficit hyperactivity disorder: a case report. Int J Eat Disord. 1997;21(3):299–301. https://doi.org/10.1002/(SICI)1098-108X(199704)21:3%3c299:AID-EAT11%3e3.0.CO;2-W.

    PubMed  CAS  Article  Google Scholar 

  89. 89.

    Sokol MS, Gray NS, Goldstein A, Kaye WH. Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder. Int J Eat Disord. 1999;25(2):233–7. https://doi.org/10.1002/(SICI)1098-108X(199903)25:2%3c233:AID-EAT14%3e3.0.CO;2-2.

    PubMed  CAS  Article  Google Scholar 

  90. 90.

    McElroy SL, Guerdjikova A, Kotwal R, Welge JA, Nelson EB, Lake KA, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiatry. 2007;68(3):390–8.

    PubMed  CAS  Article  Google Scholar 

  91. 91.

    Koblan KS, Hopkins SC, Sarma K, Jin F, Goldman R, Kollins SH, et al. Dasotraline for the treatment of attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled, proof-of-concept trial in adults. Neuropsychopharmacology. 2015;40(12):2745–52. https://doi.org/10.1038/npp.2015.124.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  92. 92.

    Navia B, Hudson J, McElroy S, Guerdjikova A, Deng L, Sarma K et al., editors. Dasotraline for the treatment of moderate-to-severe binge eating disorder in adults: results from a randomized, double-blind, placebo-controlled study. APA Meeting; 2017; May 20–24, San Diego.

  93. 93.

    Goldman R, Hudson JI, McElroy SL, Grilo CM, Tsai J, Deng L et al. Efficacy and safety of dastroline in adults with binge-eating disorder: a randomized, double-blind, fixed dose trial. To be presented at ACNP 12/2018.2018.

  94. 94.

    Bello NT, Walters AL, Verpeut JL, Caverly J. Dietary-induced binge eating increases prefrontal cortex neural activation to restraint stress and increases binge food consumption following chronic guanfacine. Pharmacol Biochem Behav. 2014;125:21–8. https://doi.org/10.1016/j.pbb.2014.08.003.

    PubMed  CAS  Article  Google Scholar 

  95. 95.

    Childress A, Tran C. Current investigational drugs for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Investig Drugs. 2016;25(4):463–74. https://doi.org/10.1517/13543784.2016.1147558.

    PubMed  CAS  Article  Google Scholar 

  96. 96.

    Wigal TL, Newcorn JH, Handal N, Wigal SB, Mulligan I, Schmith V, et al. A double-blind, placebo-controlled, phase II study to determine the efficacy, safety, tolerability and pharmacokinetics of a controlled release (CR) formulation of mazindol in adults with DSM-5 attention-deficit/hyperactivity disorder (ADHD). CNS Drugs. 2018;32(3):289–301. https://doi.org/10.1007/s40263-018-0503-y.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  97. 97.

    Manor I, Ben-Hayun R, Aharon-Peretz J, Salomy D, Weizman A, Daniely Y, et al. A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012;73(12):1517–23. https://doi.org/10.4088/JCP.12m07767.

    PubMed  CAS  Article  Google Scholar 

  98. 98.

    Wigal SB, Duong S. Pharmacokinetic evaluation of eltoprazine. Expert Opin Drug Metab Toxicol. 2011;7(6):775–81. https://doi.org/10.1517/17425255.2011.580275.

    PubMed  CAS  Article  Google Scholar 

  99. 99.

    Gravius A, Dekundy A, Vanaga A, Franke L, Danysz W. Further pharmacological characterization of eltoprazine: focus on its anxiolytic, anorexic, and adverse effect potential. Acta Neurobiol Exp (Wars). 2017;77(1):77–85.

    PubMed  Google Scholar 

  100. 100.

    Elia J, Ungal G, Kao C, Ambrosini A, De Jesus-Rosario N, Larsen L, et al. Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling. Nat Commun. 2018;9(1):4. https://doi.org/10.1038/s41467-017-02244-2.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  101. 101.

    Faris PL, Kim SW, Meller WH, Goodale RL, Oakman SA, Hofbauer RD, et al. Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial. Lancet. 2000;355(9206):792–7. https://doi.org/10.1016/S0140-6736(99)09062-5.

    PubMed  CAS  Article  Google Scholar 

  102. 102.

    Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med. 2005;143(5):380–5.

    PubMed  Article  Google Scholar 

  103. 103.

    Blouin AG, Blouin JH, Perez EL, Bushnik T, Zuro C, Mulder E. Treatment of bulimia with fenfluramine and desipramine. J Clin Psychopharmacol. 1988;8(4):261–9.

    PubMed  CAS  Article  Google Scholar 

  104. 104.

    Russell GF, Checkley SA, Feldman J, Eisler I. A controlled trial of d-fenfluramine in bulimia nervosa. Clin Neuropharmacol. 1988;11(Suppl 1):S146–59.

    PubMed  Google Scholar 

  105. 105.

    Fahy TA, Eisler I, Russell GF. A placebo-controlled trial of d-fenfluramine in bulimia nervosa. Br J Psychiatry. 1993;162:597–603.

    PubMed  CAS  Article  Google Scholar 

  106. 106.

    Stunkard A, Berkowitz R, Tanrikut C, Reiss E, Young L. d-fenfluramine treatment of binge eating disorder. Am J Psychiatry. 1996;153(11):1455–9.

    PubMed  CAS  Article  Google Scholar 

  107. 107.

    Appolinario JC, Bacaltchuk J, Sichieri R, Claudino AM, Godoy-Matos A, Morgan C, et al. A randomized, double-blind, placebo-controlled study of sibutramine in the treatment of binge-eating disorder. Arch Gen Psychiatry. 2003;60(11):1109–16. https://doi.org/10.1001/archpsyc.60.11.110960/11/1109.

    PubMed  CAS  Article  Google Scholar 

  108. 108.

    Milano W, Petrella C, Casella A, Capasso A, Carrino S, Milano L. Use of sibutramine, an inhibitor of the reuptake of serotonin and noradrenaline, in the treatment of binge eating disorder: a placebo-controlled study. Adv Ther. 2005;22(1):25–31.

    PubMed  CAS  Article  Google Scholar 

  109. 109.

    Wilfley DE, Crow SJ, Hudson JI, Mitchell JE, Berkowitz RI, Blakesley V, et al. Efficacy of sibutramine for the treatment of binge eating disorder: a randomized multicenter placebo-controlled double-blind study. Am J Psychiatry. 2008;165(1):51–8. https://doi.org/10.1176/appi.ajp.2007.06121970.

    PubMed  Article  Google Scholar 

  110. 110.

    Pataky Z, Gasteyger C, Ziegler O, Rissanen A, Hanotin C, Golay A. Efficacy of rimonabant in obese patients with binge eating disorder. Exp Clin Endocrinol Diabetes. 2013;121(1):20–6. https://doi.org/10.1055/s-0032-1329957.

    PubMed  CAS  Article  Google Scholar 

  111. 111.

    Xu P, He Y, Cao X, Valencia-Torres L, Yan X, Saito K, et al. Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice. Biol Psychiatry. 2017;81(9):737–47. https://doi.org/10.1016/j.biopsych.2016.06.005.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  112. 112.

    Scherma M, Fattore L, Satta V, Businco F, Pigliacampo B, Goldberg SR, et al. Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats. Br J Pharmacol. 2013;169(4):820–33. https://doi.org/10.1111/bph.12014.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  113. 113.

    Dalai SS, Adler S, Najarian T, Safer DL. Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. Contemp Clin Trials. 2018;64:173–8. https://doi.org/10.1016/j.cct.2017.10.007.

    PubMed  Article  Google Scholar 

  114. 114.

    Guerdjikova AI, Fitch A, McElroy SL. Successful treatment of binge eating disorder with combination phentermine/topiramate extended release. Prim Care Companion CNS Disord. 2015. https://doi.org/10.4088/PCC.14l01708.

    PubMed  PubMed Central  Article  Google Scholar 

  115. 115.

    McElroy SL, Guerdjikova AI, Kim DD, Burns C, Harris-Collazo R, Landbloom R, et al. Naltrexone/bupropion combination therapy in overweight or obese patients with major depressive disorder: results of a pilot study. Prim Care Companion CNS Disord. 2013. https://doi.org/10.4088/PCC.12m01494.

    PubMed  PubMed Central  Article  Google Scholar 

  116. 116.

    Guerdjikova AI, Walsh B, Shan K, Halseth AE, Dunayevich E, McElroy SL. Concurrent improvement in both binge eating and depressive symptoms with naltrexone/bupropion therapy in overweight or obese subjects with major depressive disorder in an open-label, Uncontrolled Study. Adv Ther. 2017;34(10):2307–15. https://doi.org/10.1007/s12325-017-0613-9.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  117. 117.

    Robert SA, Rohana AG, Shah SA, Chinna K, Wan Mohamud WN, Kamaruddin NA. Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with liraglutide - A pilot study. Obes Res Clin Pract. 2015;9(3):301–4. https://doi.org/10.1016/j.orcp.2015.03.005.

    PubMed  Article  Google Scholar 

  118. 118.

    Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387:1947–56. https://doi.org/10.1016/S0140-6736(16)00271-3.

    PubMed  PubMed Central  Article  Google Scholar 

  119. 119.

    Srivastava G, Apovian C. Future pharmacotherapy for obesity: new anti-obesity drugs on the horizon. Curr Obes Rep. 2018;7(2):147–61. https://doi.org/10.1007/s13679-018-0300-4.

    PubMed  Article  Google Scholar 

  120. 120.

    Burkey BF, Hoglen NC, Inskeep P, Wyman M, Hughes TE, Vath JE. Preclinical efficacy and safety of the novel antidiabetic, antiobesity MetAP2 inhibitor ZGN-1061. J Pharmacol Exp Ther. 2018;365(2):301–13. https://doi.org/10.1124/jpet.117.246272.

    PubMed  CAS  Article  Google Scholar 

  121. 121.

    Golay A, Laurent-Jaccard A, Habicht F, Gachoud JP, Chabloz M, Kammer A, et al. Effect of orlistat in obese patients with binge eating disorder. Obes Res. 2005;13(10):1701–8. https://doi.org/10.1038/oby.2005.208.

    PubMed  CAS  Article  Google Scholar 

  122. 122.

    Grilo CM, Masheb RM, Salant SL. Cognitive behavioral therapy guided self-help and orlistat for the treatment of binge eating disorder: a randomized, double-blind, placebo-controlled trial. Biol Psychiatry. 2005;57(10):1193–201. https://doi.org/10.1016/j.biopsych.2005.03.001.

    PubMed  CAS  Article  Google Scholar 

  123. 123.

    Fernandez-Aranda F, Amor A, Jimenez-Murcia S, Gimenez-Martinez L, Turon-Gil V, Vallejo-Ruiloba J. Bulimia nervosa and misuse of orlistat: two case reports. Int J Eat Disord. 2001;30(4):458–61. https://doi.org/10.1002/eat.1108.

    PubMed  CAS  Article  Google Scholar 

  124. 124.

    Malhotra S, McElroy SL. Orlistat misuse in bulimia nervosa. Am J Psychiatry. 2002;159(3):492–3.

    PubMed  Article  Google Scholar 

  125. 125.

    Cochrane C, Malcolm R. Case report of abuse of Orlistat. Eat Behav. 2002;3(2):167–9.

    PubMed  Article  Google Scholar 

  126. 126.

    Deb KS, Gupta R, Varshney M. Orlistat abuse in a case of bulimia nervosa: the changing Indian society. Gen Hosp Psychiatry. 2014;36(5):549 e3–4. https://doi.org/10.1016/j.genhosppsych.2014.05.006.

    Article  Google Scholar 

  127. 127.

    Kim YR, Eom JS, Yang JW, Kang J, Treasure J. The impact of oxytocin on food intake and emotion recognition in patients with eating disorders: a double blind single dose within-subject cross-over design. PLoS One. 2015;10(9):e0137514. https://doi.org/10.1371/journal.pone.0137514.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  128. 128.

    Sundblad C, Landen M, Eriksson T, Bergman L, Eriksson E. Effects of the androgen antagonist flutamide and the serotonin reuptake inhibitor citalopram in bulimia nervosa: a placebo-controlled pilot study. J Clin Psychopharmacol. 2005;25(1):85–8.

    PubMed  CAS  Article  Google Scholar 

  129. 129.

    Naessen S, Carlstrom K, Bystrom B, Pierre Y, Hirschberg AL. Effects of an antiandrogenic oral contraceptive on appetite and eating behavior in bulimic women. Psychoneuroendocrinology. 2007;32(5):548–54. https://doi.org/10.1016/j.psyneuen.2007.03.008.

    PubMed  CAS  Article  Google Scholar 

  130. 130.

    von Wietersheim J, Muler-Bock V, Rauh S, Danner B, Chrenko K, Buhler G. No effect of spironolactone on bulimia nervosa symptoms. J Clin Psychopharmacol. 2008;28(2):258–60. https://doi.org/10.1097/JCP.0b013e3181678a1700004714-200804000-00031.

    Article  Google Scholar 

  131. 131.

    Devlin MJ, Kissileff HR, Zimmerli EJ, Samuels F, Chen BE, Brown AJ, et al. Gastric emptying and symptoms of bulimia nervosa: effect of a prokinetic agent. Physiol Behav. 2012;106(2):238–42. https://doi.org/10.1016/j.physbeh.2012.02.009.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  132. 132.

    Hsu LK, Clement L, Santhouse R, Ju ES. Treatment of bulimia nervosa with lithium carbonate. A controlled study. J Nerv Ment Dis. 1991;179(6):351–5.

    PubMed  CAS  Article  Google Scholar 

  133. 133.

    McElroy SL, Kotwal R, Keck PE Jr, Akiskal HS. Comorbidity of bipolar and eating disorders: Distinct or related disorders with shared dysregulations? J Affect Disord. 2005;86(2–3):107–27.

    PubMed  Article  Google Scholar 

  134. 134.

    Takaki M, Okabe N. Aripiprazole may be effective as an add-on treatment in bulimic symptoms of eating disorders. J Clin Psychopharmacol. 2015;35(1):93–5. https://doi.org/10.1097/JCP.0000000000000233.

    PubMed  Article  Google Scholar 

  135. 135.

    Trunko ME, Schwartz TA, Duvvuri V, Kaye WH. Aripiprazole in anorexia nervosa and low-weight bulimia nervosa: case reports. Int J Eat Disord. 2011;44(3):269–75. https://doi.org/10.1002/eat.20807.

    PubMed  Article  Google Scholar 

  136. 136.

    Brewerton TD, Shannon M. Possible clozapine exacerbation of bulimia nervosa. Am J Psychiatry. 1992;149(10):1408–9.

    PubMed  CAS  Article  Google Scholar 

  137. 137.

    Crockford DN, Fisher G, Barker P. Risperidone, weight gain, and bulimia nervosa. Can J Psychiatry. 1997;42(3):326–7.

    PubMed  CAS  Article  Google Scholar 

  138. 138.

    Theisen FM, Linden A, Konig IR, Martin M, Remschmidt H, Hebebrand J. Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine. J Neural Transm. 2003;110(1):111–21. https://doi.org/10.1007/s00702-002-0792-6.

    PubMed  CAS  Article  Google Scholar 

  139. 139.

    Gebhardt S, Haberhausen M, Krieg JC, Remschmidt H, Heinzel-Gutenbrunner M, Hebebrand J, et al. Clozapine/olanzapine-induced recurrence or deterioration of binge eating-related eating disorders. J Neural Transm. 2007;114(8):1091–5. https://doi.org/10.1007/s00702-007-0663-2.

    PubMed  CAS  Article  Google Scholar 

  140. 140.

    Berner LA, Bocarsly ME, Hoebel BG, Avena NM. Baclofen suppresses binge eating of pure fat but not a sugar-rich or sweet-fat diet. Behav Pharmacol. 2009;20(7):631–4. https://doi.org/10.1097/FBP.0b013e328331ba47.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  141. 141.

    Broft AI, Spanos A, Corwin RL, Mayer L, Steinglass J, Devlin MJ, et al. Baclofen for binge eating: an open-label trial. Int J Eat Disord. 2007;40(8):687–91. https://doi.org/10.1002/eat.20434.

    PubMed  Article  Google Scholar 

  142. 142.

    Weibel S, Lalanne L, Riegert M, Bertschy G. Efficacy of high-dose baclofen for alcohol use disorder and comorbid bulimia: a case report. J Dual Diagn. 2015;11(3–4):203–4. https://doi.org/10.1080/15504263.2015.1104483.

    PubMed  Article  Google Scholar 

  143. 143.

    Corwin RL, Boan J, Peters KF, Ulbrecht JS. Baclofen reduces binge eating in a double-blind, placebo-controlled, crossover study. Behav Pharmacol. 2012;23(5–6):616–25. https://doi.org/10.1097/FBP.0b013e328357bd6200008877-201209000-00018.

    PubMed  CAS  Article  Google Scholar 

  144. 144.

    de Beaurepaire R, Joussaume B, Rapp A, Jaury P. Treatment of binge eating disorder with high-dose baclofen: a case series. J Clin Psychopharmacol. 2015;35(3):357–9. https://doi.org/10.1097/JCP.0000000000000332.

    PubMed  Article  Google Scholar 

  145. 145.

    Kiel LB, Hoegberg LC, Jansen T, Petersen JA, Dalhoff KP. A nationwide register-based survey of baclofen toxicity. Basic Clin Pharmacol Toxicol. 2015;116(5):452–6. https://doi.org/10.1111/bcpt.12344.

    PubMed  CAS  Article  Google Scholar 

  146. 146.

    Guerdjikova AI, Blom TJ, Mori N, McElroy SL. N-acetylcysteine in bulimia nervosa—open-label trial. Eat Behav. 2013;14(1):87–9. https://doi.org/10.1016/j.eatbeh.2012.11.001.

    PubMed  Article  Google Scholar 

  147. 147.

    Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009;66(7):756–63. https://doi.org/10.1001/archgenpsychiatry.2009.60.

    PubMed  CAS  Article  Google Scholar 

  148. 148.

    Dansky BS, Brewerton TD, Kilpatrick DG, O’Neil PM. The National Women’s Study: relationship of victimization and posttraumatic stress disorder to bulimia nervosa. Int J Eat Disord. 1997;21(3):213–28.

    PubMed  CAS  Article  Google Scholar 

  149. 149.

    Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63(6):629–32. https://doi.org/10.1016/j.biopsych.2007.07.001.

    PubMed  CAS  Article  Google Scholar 

  150. 150.

    Raskind MA, Peskind ER. Prazosin for post-traumatic stress disorder. N Engl J Med. 2018;378(17):1649–50. https://doi.org/10.1056/NEJMc1803171.

    PubMed  Article  Google Scholar 

  151. 151.

    Hermanussen M, Tresguerres JA. A new anti-obesity drug treatment: first clinical evidence that, antagonising glutamate-gated Ca2+ ion channels with memantine normalises binge-eating disorders. Econ Hum Biol. 2005;3(2):329–37. https://doi.org/10.1016/j.ehb.2005.04.001.

    PubMed  CAS  Article  Google Scholar 

  152. 152.

    Brennan BP, Roberts JL, Fogarty KV, Reynolds KA, Jonas JM, Hudson JI. Memantine in the treatment of binge eating disorder: an open-label, prospective trial. Int J Eat Disord. 2008;41(6):520–6. https://doi.org/10.1002/eat.20541.

    PubMed  Article  Google Scholar 

  153. 153.

    McElroy SL, Guerdjikova AI, Winstanley EL, O’Melia AM, Mori N, Keck PE Jr, et al. Sodium oxybate in the treatment of binge eating disorder: an open-label, prospective study. Int J Eat Disord. 2011;44(3):262–8. https://doi.org/10.1002/eat.20798.

    PubMed  Article  Google Scholar 

  154. 154.

    Statnick MA, Chen Y, Ansonoff M, Witkin JM, Rorick-Kehn L, Suter TM, et al. A novel nociceptin receptor antagonist LY2940094 inhibits excessive feeding behavior in rodents: a possible mechanism for the treatment of binge eating disorder. J Pharmacol Exp Ther. 2016;356(2):493–502. https://doi.org/10.1124/jpet.115.228221.

    PubMed  Article  Google Scholar 

  155. 155.

    Feltmann K, Giuliano C, Everitt BJ, Steensland P, Alsio J. The effects of the monoamine stabilizer (−)-OSU6162 on binge-like eating and cue-controlled food-seeking behavior in rats. Neuropsychopharmacology. 2018;43(3):617–26. https://doi.org/10.1038/npp.2017.215.

    PubMed  CAS  Article  Google Scholar 

  156. 156.

    Xu P, Cao X, Xu Y. Targeting brain estrogen receptor for binge eating. Oncotarget. 2015;6(27):23044–5. https://doi.org/10.18632/oncotarget.5239.

    PubMed  PubMed Central  Article  Google Scholar 

  157. 157.

    Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M, Montanari D, et al. Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacology. 2012;37(9):1999–2011. https://doi.org/10.1038/npp.2012.48.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  158. 158.

    Alcaraz-Iborra M, Carvajal F, Lerma-Cabrera JM, Valor LM, Cubero I. Binge-like consumption of caloric and non-caloric palatable substances in ad libitum-fed C57BL/6J mice: pharmacological and molecular evidence of orexin involvement. Behav Brain Res. 2014;272:93–9. https://doi.org/10.1016/j.bbr.2014.06.049.

    PubMed  CAS  Article  Google Scholar 

  159. 159.

    Walsh BT, Fairburn CG, Mickley D, Sysko R, Parides MK. Treatment of bulimia nervosa in a primary care setting. Am J Psychiatry. 2004;161(3):556–61.

    PubMed  Article  Google Scholar 

  160. 160.

    Brambilla F, Samek L, Company M, Lovo F, Cioni L, Mellado C. Multivariate therapeutic approach to binge-eating disorder: Combined nutritional, psychological and pharmacological treatment. Int Clin Psychopharmacol. 2009;24(6):312–7. https://doi.org/10.1097/YIC.0b013e32832ac828.

    PubMed  Article  Google Scholar 

  161. 161.

    Woodside BD, Staab R. Management of psychiatric comorbidity in anorexia nervosa and bulimia nervosa. CNS Drugs. 2006;20(8):655–63.

    PubMed  Article  Google Scholar 

  162. 162.

    Mazzeo SE, Slof-Op’t Landt MC, Jones I, Mitchell K, Kendler KS, Neale MC, et al. Associations among postpartum depression, eating disorders, and perfectionism in a population-based sample of adult women. Int J Eat Disord. 2006;39(3):202–11. https://doi.org/10.1002/eat.20243.

    PubMed  Article  Google Scholar 

  163. 163.

    Monteleone P, Luisi M, Colurcio B, Casarosa E, Monteleone P, Ioime R, et al. Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa. Psychosom Med. 2001;63(1):62–8.

    PubMed  CAS  Article  Google Scholar 

  164. 164.

    Heymsfield SB, Avena NM, Baier L, Brantley P, Bray GA, Burnett LC, et al. Hyperphagia: current concepts and future directions proceedings of the 2nd international conference on hyperphagia. Obesity (Silver Spring). 2014;22(Suppl 1):S1–17. https://doi.org/10.1002/oby.20646.

    PubMed Central  Article  Google Scholar 

  165. 165.

    Brady LS, Winsky L, Goodman W, Oliveri ME, Stover E. NIMH initiatives to facilitate collaborations among industry, academia, and government for the discovery and clinical testing of novel models and drugs for psychiatric disorders. Neuropsychopharmacology. 2009;34(1):229–43. https://doi.org/10.1038/npp.2008.125.

    PubMed  Article  Google Scholar 

  166. 166.

    Bowden CL, Perlis RH, Thase ME, Ketter TA, Ostacher MM, Calabrese JR, et al. Aims and results of the NIMH systematic treatment enhancement program for bipolar disorder (STEP-BD). CNS Neurosci Ther. 2012;18(3):243–9. https://doi.org/10.1111/j.1755-5949.2011.00257.x.

    PubMed  CAS  Article  Google Scholar 

  167. 167.

    Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–23. https://doi.org/10.1056/NEJMoa051688.

    PubMed  CAS  Article  Google Scholar 

  168. 168.

    Rush AJ. Star-D: lessons learned and future implications. Depress Anxiety. 2011;28(7):521–4. https://doi.org/10.1002/da.20841.

    PubMed  Article  Google Scholar 

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Correspondence to Susan L. McElroy.

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No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of Interest

SLM is a consultant to or member of the scientific advisory boards of Allergan, Avanir, Bracket, F. Hoffmann-La Roche Ltd., Mitsubishi Tanabe Pharma America, Myriad, Opiant, Shire, and Sunovion. She is a principal or co-investigator on studies sponsored by the Allergan, Avanir, Brainsway, the  Marriott Foundation, Myriad, Neurocrine, Novo Nordisk, Shire, and Sunovion. She is also an inventor on US patent no. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and—along with the patent’s assignee—University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson in the past, which has exclusive rights under the patent. AIG, NM, and FR-N have no conflicts of interest that are directly relevant to the content of this article.

Ethical Approval

All procedures performed in studies involving human participants, to the best of our knowledge, were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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McElroy, S.L., Guerdjikova, A.I., Mori, N. et al. Progress in Developing Pharmacologic Agents to Treat Bulimia Nervosa. CNS Drugs 33, 31–46 (2019). https://doi.org/10.1007/s40263-018-0594-5

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