Eating Disorders Are Notoriously Difficult to Treat

Classified as serious psychiatric conditions, eating disorders not only have medical and psychological consequences but economic and societal repercussions as well.^1-3

Notoriously difficult to manage, they usually require both behavioral and nutritional intervention.^1,4 Nonresponse and relapse are common.⁵ And although clinicians use medications with varying degrees of success, few drugs are effective. Table 1^1,6-11 summarizes the 3 primary eating disorders: anorexia nervosa (AN), binge-eating disorder (BED), and bulimia nervosa (BN).

Pharmacologic Treatment

The following drug classes offer hopes for ameliorating or curing eating disorders.

Anticonvulsants

Prescribed off label for BN, topiramate (median dosage 100 mg/day; range 25 to 400 mg/day) was superior to the placebo at reducing symptoms but also body weight.¹² Although usually well tolerated at low doses, topiramate has been reported by some patients to cause cognitive haziness and paresthesia in fingers and toes.¹² Results of zonisamide (Zonegran) trials indicated it can reduce binge eating and body weight in the short term and at 1-year follow-up but may be poorly tolerated.^13-16

Antidepressants

Unfortunately, randomized controlled trials (RCTs) have not identified any antidepressants that help manage AN.^17,18 Neither first- nor second-generation antidepressants improve eating and weight outcomes. In addition, bupropion is contraindicated in eating disorders because of elevated seizure risk.^17,18

Antidepressants are sometimes used successfully for BN. Experts prefer selective serotonin reuptake inhibitors (SSRIs) to first-generation antidepressants because of their better safety profile. Research supports the use of various SSRIs but suggests that high-dose fluoxetine is most effective. Two 8-week trials found that participants taking 60 mg per day of fluoxetine experienced significantly less binge eating and vomiting than those taking 20 mg per day and those taking placebo.^19,20 Other trials have found that participants who continued on fluoxetine were significantly less likely to relapse and that the drug is also effective in adolescents.^21-23 Fluoxetine was approved by the FDA in 1994 for maintenance of BN.²⁴

The use of citalopram, escitalopram, fluvoxamine, and fluoxetine for BED is similar to the use of fluoxetine for BN.¹³ In general, SSRIs reduce binge eating when compared with placebo. A recent meta-analysis of 7 placebo-controlled RCTs found that treatment with antidepressants also reduces remission rates.²⁵ However, antidepressants have no effect on the weight of individuals with BED.

Antipsychotics

Research results showed that olanzapine, an atypical antipsychotic, has a modest effect on weight restoration.^26-28 In a recent RCT, 152 adult outpatients with AN received olanzapine (median dosage 7.77 mg/day; range 2.5 to 10 mg/day) or placebo for 16 weeks. Olanzapine was associated with an average gain of approximately 1 lb per month more than placebo. However, the cognitive rigidity and obsessionality associated with AN—and the self- reported anxiety—did not improve significantly.²⁹

Stimulants

Investigators have also turned to stimulants for BED because of their tendency to suppress appetite. The FDA approved lisdexamfetamine for use in BED in 2015. A short, double-blind RCT compared the chemical (30 mg/ day, 50 mg/day, and 70 mg/day) with placebo. Binge eating decreased significantly more in participants taking 50- and 70-mg doses than in those taking placebo.³⁰ Two additional 12-week studies replicated these results and found that body weight, general well-being, and obsessive-compulsive symptoms had also improved.³⁰ Subsequent studies suggest lisdexamfetamine may prevent relapse better than placebo.³¹ Although considered effective and safe, lisdexamfetamine has adverse effects and a potential for abuse that should prompt careful pretreatment evaluation and monitoring during treatment.²⁴ Limited research is available to support the use of other stimulants in BED. Table 2^12-30 summarizes the use of medication in eating disorders.

Conclusion

Although many drugs have been studied as a treatment for eating disorders, few have demonstrated success. AN continues to be the most difficult to manage. Better outcomes have been obtained in BN and BED, and as a result the FDA has approved 2 agents: fluoxetine 60 mg per day for BN and lisdexamfetamine for BED.

About The Author

Jeannette Y. Wick, MBA, RPh, FASCP, is the director of pharmacy professional development at the University of Connecticut in Storrs.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.

2. van Hoeken D, Hoek HW. Review of the burden of eating disorders: mortality, disability, costs, quality of life, and family burden. Curr Opin Psychiatry. 2020;33(6):521-527. doi:10.1097/YCO.0000000000000641

3. Streatfeild J, Hickson J, Austin SB, et al. Social and economic cost of eating disorders in the United States: evidence to inform policy action. Int J Eat Disord. 2021;54(5):851-868. doi:10.1002/eat.23486

4. American Psychiatric Association. Treatment of patients with eating disorders, third edition. Am J Psychiatr. 2006;163(suppl 7):4-54.

5. Khalsa SS, Portnoff LC, McCurdy-McKinnon D, Feusner JD. What happens after treatment? A systematic review of relapse, remission, and recovery in anorexia nervosa. J Eat Disord. 2017;5:20. doi:10.1186/s40337-017-0145-3

6. Fichter MM, Quadflieg N. Mortality in eating disorders - results of a large prospective clinical longitudinal study. Int J Eat Disord. 2016;49(4):391-401. doi:10.1002/eat.22501

7. Muratore AF, Attia E. Current therapeutic approaches to anorexia nervosa: state of the art. Clin Ther. 2021;43(1):85-94. doi:10.1016/j.clinthera.2020.11.006

8. Westmoreland P, Krantz MJ, Mehler PS. Medical complications of anorexia nervosa and bulimia. Am J Med. 2016;129(1):30-37. doi:10.1016/j.amjmed.2015.06.031

9. Gibson D, Workman C, Mehler PS. Medical complications of anorexia nervosa and bulimia nervosa. Psychiatr Clin North Am. 2019;42(2):263-274. doi:10.1016/j.psc.2019.01.009

10. Mitchell JE. Medical comorbidity and medical complications associated with binge-eating disorder. Int J Eat Disord. 2016;49(3):319-323. doi:10.1002/eat.22452

11. Wassenaar E, Friedman J, Mehler PS. Medical complications of binge eating disorder. Psychiatr Clin North Am. 2019;42(2):275-286. doi:10.1016/j.psc.2019.01.010

12. Nickel C, Tritt K, Muehlbacher M, et al. Topiramate treatment in bulimia nervosa patients: a randomized, double-blind, placebo-controlled trial. Int J Eat Disord. 2005;38(4):295-300. doi:10.1002/eat.20202

13. McElroy SL. Pharmacologic treatments for binge-eating disorder. J Clin Psychiatry. 2017;78(suppl 1):14-19. doi:10.4088/JCP.sh16003su1c.03

14. McElroy SL, Kotwal R, Guerdjikova AI, et al. Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry. 2006;67(12):1897-1906. doi:10.4088/jcp.v67n1209

15. McElroy SL, Kotwal R, Hudson JI, Nelson EB, Keck PE. Zonisamide in the treatment of binge-eating disorder: an open-label, prospective trial. J Clin Psychiatry. 2004;65(1):50-56. doi:10.4088/jcp.v65n0108

16. Ricca V, Castellini G, Lo Sauro C, Rotella CM, Faravelli C. Zonisamide combined with cognitive behavioral therapy in binge eating disorder: a one-year follow-up study. Psychiatry (Edgmont). 2009;6(11):23-28.

17. Marvanova M, Gramith K. Role of antidepressants in the treatment of adults with anorexia nervosa. Ment Health Clin. 2018;8(3):127-137. doi:10.9740/mhc.2018.05.127

18. Himmerich H, Kan C, Au K, Treasure J. Pharmacological treatment of eating disorders, comorbid mental health problems, malnutrition and physical health consequences. Pharmacol Ther. 2021;217:107667. doi:10.1016/j.pharmthera.2020.107667

19. 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):139-147.

20. Goldstein DJ, Wilson MG, Thompson VL, Potvin JH, Rampey AH Jr; Fluoxetine Bulimia Nervosa Research Group. Long-term fluoxetine treatment of bulimia nervosa. Br J Psychiatry. 1995;166(5):660-666. doi:10.1192/bjp.166.5.660

21. 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. doi:10.1176/appi.ajp.159.1.96

22. Pope HG Jr, Hudson JI. Antidepressant drug therapy for bulimia: current status. J Clin Psychiatry. 1986;47(7):339-345.

23. Kotler LA, Devlin MJ, Davies M, Walsh BT. An open trial of fluoxetine for adolescents with bulimia nervosa. J Child Adolesc Psychopharmacol. 2003;13(3):329-335. doi:10.1089/104454603322572660

24. Bello NT, Yeomans BL. Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder. Expert Opin Drug Saf. 2018;17(1):17-23. doi:10.1080/14740338.2018.1395854

25. Stefano SC, Bacaltchuk J, Blay SL, Appolinário JC. Antidepressants in short-term treatment of binge eating disorder: systematic review and meta-analysis. Eat Behav. 2008;9(2):129-136. doi:10.1016/j.eatbeh.2007.03.006

26. Bissada H, Tasca GA, Barber AM, Bradwejn J. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008;165(10):1281-1288. doi:10.1176/appi.ajp.2008.07121900

27. Dold M, Aigner M, Klabunde M, Treasure J, Kasper S. Second-generation antipsychotic drugs in anorexia nervosa: a meta-analysis of randomized controlled trials. Psychother Psychosom. 2015;84(2):110-116. doi:10.1159/000369978

28. Attia E, Kaplan AS, Walsh BT, Gershkovich M, Yilmaz Z, Musante D, et al. Olanzapine versus placebo for out-patients with anorexia nervosa. Psychol Med. 2011;41(10):2177-2182. doi:10.1017/S0033291711000390

29. Attia E, Steinglass JE, Walsh BT, Wang Y, Wu P, Schreyer C, et al. Olanzapine versus placebo in adult outpatients with anorexia nervosa: a randomized clinical trial. Am J Psychiatry. 2019;176(6):449-456. doi:10.1176/appi.ajp.2018.18101125

30. McElroy SL, Mitchell JE, Wilfley D, Gasior M, Ferreira-Cornwell MC, McKay M, et al. Lisdexamfetamine dimesylate effects on binge eating behaviour and obsessive-compulsive and impulsive features in adults with binge eating disorder. Eur Eat Disord Rev. 2016;24(3):223-231. doi:10.1002/erv.2418

31. 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 clinical trial. JAMA Psychiat. 2017;74(9):903-910. doi:10.1001/jamapsychiatry.2017.1889