Integrating Treatment in Eating Disorders

While anorexia nervosa was the first eating disorder to be recognized through the 19th century reports of Gull (1874) and Las?que (1873), bulimia nervosa and the less well-defined eating disorder not otherwise specified (EDNOS) syndromes are more common. Bulimia nervosa was first described by Russell in 1979 and was introduced into the American Psychiatric Association classification scheme in the 1980 DSM-III, where it was termed bulimia. In clinical samples, however, people with EDNOS may comprise one-third to one-half of patients seen (Hall and Hay, 1991; Herzog et al., 1993). The EDNOS syndromes include people who fall below the diagnostic criteria for bulimia nervosa or anorexia nervosa. Binge-eating disorder is a third classification of eating disorder and is listed as the sixth example of an EDNOS syndrome in the DSM-IV as "recurrent episodes of binge eating in the absence of the regular use of inappropriate compensatory behaviors characteristic of Bulimia Nervosa" (APA, 1994). It is also in Appendix B with suggested criteria as a diagnostic group for further study.

With an estimated point prevalence of 0.5% in young women, anorexia nervosa is not a common condition (Aalto-Setala et al., 2001). A systematic review of 12 cumulative incidence studies reported an estimated mean annual incidence in the general population of 18.46 per 100,000 (SD=21.01) in women and 2.25 per 100,000 (SD=2.63) a year in men (Pawluck and Gorey, 1998). There is limited evidence for changes in the overall incidence of anorexia nervosa over time, although the authors reported a significant increase in its incidence in young women from 1950 to 1992.

In contrast, bulimia nervosa is more common, with estimated incidence of 28.8 (SD=29.7) in women and 0.8 (SD=0.0) in men per 100,000 per year (Pawluck and Gorey, 1998). The general population lifetime prevalence of bulimia nervosa is around 1%. Point prevalence in young women from combined estimates has also remained around 1% (e.g., Bushnell et al., 1990) since the 1980s, when there was an increase in clinical incidence following its recognition as a disorder (e.g., Hall and Hay, 1991). Finally, the prevalence of EDNOS syndromes is estimated between 2% and 5% in young women (e.g., Hay, 1998).

Overview of Treatments

Historically, the treatment of people with eating disorders has moved from a focus on medically supervised physical weight restoration, as described by Gull (1874), through the introduction of the first variants of psychodynamic psychotherapy in the 20th century and, later, the development of specific focus symptom-based treatments, such as cognitive-behavioral therapy (CBT).

Alongside these developments in psychotherapy has been the use of pharmacological therapies, as they became available to the wider psychiatric clinical services. A number of the older tricyclic antidepressants, typical neuroleptic medications and, more recently, selective serotonin reuptake inhibitors have been trialed in eating disorders. A range of other medications have been also used in eating disorders to specifically treat comorbidity, such as depression or severe anxiety, and medical complications, such as severe constipation, delayed gastric emptying and osteopenia found in anorexia nervosa. An authoritative and comprehensive overview of these developments is found in Garner and Garfinkel (1997).

Anorexia Nervosa

With regard to integrating treatments, pharmacotherapy is used most often in patients with anorexia nervosa as an adjunct to inpatient weight-restoration programs or to outpatient psychotherapy and weight-maintenance programs. A systematic review presented to the ninth Cochrane Colloquium identified 19 randomized, controlled trials (Hay et al., 2001). Trials were identified by the author from a search of six databases and a hand search of The International Journal of Eating Disorders. Most trials had fewer than 50 subjects and were negative. Space precludes a discussion of all these trials; this paper focuses on those that have evaluated antidepressants (Table 1).

The double-blind, randomized, controlled trial by Kaye et al. (2001) is notable for its long duration and placebo-controlled evaluation of fluoxetine (Prozac), previously found to be effective in bulimia nervosa (Bacaltchuk et al., 2000). Kaye et al. studied 35 subjects with restricting and restricting-purging types of anorexia nervosa recruited during an inpatient program and followed them for one year. Weight gain and psychological measures (core eating disorder symptoms, depression, anxiety, obsessions and compulsions) improved only in the 10 patients who remained on fluoxetine treatment. Dropouts were much higher in the placebo group (84% versus 37%). The high refusal rate and small numbers limited conclusions from the study. The authors postulated that there may be a relative serotonin "resistance" due to a compromised release of serotonin from presynaptic storage in underweight individuals with anorexia nervosa. The authors argued that this may reverse with weight gain and may explain the greater efficacy of SSRIs in normal-weight people with eating disorders.

Therefore, there is insufficient evidence at this stage to support antidepressant therapy in combination with psychotherapies and various nutritional rehabilitation programs alone. As patients with anorexia nervosa are in a compromised physical state due to the effects of starvation, low dosage and caution is recommended in the use of most psychotropics and other agents, including antidepressants, for which there is limited evidence of efficacy (Treasure and Schmidt, 2001).

Cyproheptadine, a serotonin and histamine antagonist, has also been the subject of randomized, controlled trials for anorexia nervosa treatment, with one relatively large study (n=72, Halmi et al., 1986) supportive and another (n=105, Goldberg et al., 1980) not so. As with antidepressants, there is insufficient evidence as yet of its efficacy.

Bulimia Nervosa

In contrast, for bulimia nervosa, the use of medication--most commonly antidepressants--in combination with psychotherapy is often useful, and there are now several published randomized, controlled trials. A recent meta-analysis (summarized in Table 2) found that where antidepressants are combined with focused psychotherapies and compared with either antidepressants alone or with psychotherapy alone, the combination is favored (Bacaltchuk et al., 2001).

How medications and psychotherapies--biological and psychological--act together to give a better outcome is unknown, but it is a phenomena not confined to eating disorders. For example, in obsessive-compulsive disorder, brain imaging changes have been reported to occur following psychological treatments (Schwartz et al., 1996). Whether similar effects occur in the treatment of patients with bulimia nervosa is speculative, but reports by Hirano and colleagues (1999) and Kaye and colleagues (2001) support further exploration of the biological mechanisms in treatment and the mode of synergy of combination therapies. In addition, the effect of antidepressants has been found across a number of trials in study subjects most often without comorbid severe depression (Bacaltchuk et al., 2000). This supports there being a specific effect in bulimia nervosa, not merely a general effect on depressive symptoms.

In these meta-analyses, however, non-completion rates are high in the groups where medications are included compared to those that have psychotherapy alone. This suggests that patients find antidepressants less acceptable than psychotherapy. Why this should be so has not been rigorously explored in treatment studies. One possibility is because of greater side effects, but it could also be because taking tablets lacks credibility for patients. It is known that a range of important personal and social-cultural factors are likely to contribute to the etiology of bulimia nervosa and similar disorders (e.g., Fairburn et al., 1998; Fairburn et al., 1997). Thus, treatments (such as CBT or interpersonal psychotherapy) that appear to address these issues are easy to explain to patients with respect to their theoretical underpinnings. Similarly, however, as already noted, there is evidence that biological mechanisms such as possible serotonin depletion (Kaye et al., 2001) are likely to also be important. Whether these changes are a cause or consequence of bulimia nervosa is unclear, but they do provide some rationale for the use of, for example, the SSRIs in the treatment of bulimia nervosa.

There are several instances where I have found it most useful to integrate an antidepressant and psychotherapy, which accords with other opinion (Garfinkel and Walsh, 1997). (I commonly use the staged and manualized form of CBT as described by Wilson et al., 1997). The first is in cases of very frequent and severe binge-eating and the antidepressant aids reduction in bingeing to a point where the patient has a greater capacity to engage in psychotherapy. This is similar to the second instance, in which the patient suffers moderate to severe depressive symptoms. The third most common situation in which I use antidepressants is when patients have made some improvement with CBT but moderate eating disorder symptoms remain. Finally, when specialized psychotherapeutic help is difficult for patients to access, primary care physicians often may commence antidepressants while awaiting a specialist opinion.

Conclusion

While the evidence for integrating treatments in eating disorders is not strong, there is sufficient evidence to support combining antidepressant and psychotherapies in the active treatment of bulimia nervosa. This may, however, be at the cost of people withdrawing from treatment, due possibly to side effects or the lack of treatment credibility.

References:

References

Aalto-Setala T, Marttunen M, Tuulio-Henriksson A et al. (2001), One-month prevalence of depression and other DSM-IV disorders among young adults. Psychol Med 31(5):791-801.

APA (1994), Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. Washington, D.C.: American Psychiatric Association, p550.

Bacaltchuk J, Hay P, Mari JJ (2000), Antidepressants versus placebo for the treatment of bulimia nervosa: a systematic review. Aust N Z J Psychiatry 34(2):310-317.

Bacaltchuk J, Hay P, Trefiglio R (2001), Antidepressants versus psychological treatments and their combination for bulimia nervosa (Cochrane Review). In: The Cochrane Library, Issue 4. Oxford, England: Update Software.

Bushnell JA, Wells JE, Hornblow AR et al. (1990), Prevalence of three bulimia syndromes in the general population. Psychol Med 20(3):671-680.

Fairburn CG, Doll HA, Welch SL et al. (1998), Risk factors for binge eating disorder: a community-based case-control study. Arch Gen Psychiatry 55(5):425-432.

Fairburn CG, Welch SL, Doll HA et al. (1997), Risk factors for bulimia nervosa. A community-based case-control study. Arch Gen Psychiatry 54(6):509-517.

Garfinkel PE, Walsh BT (1997), Drug therapies. In: Handbook of Treatment for Eating Disorders, 2nd Edition, Garner DM, Garfinkel PE, eds. New York: Guilford Press, pp372-380.

Garner DM, Garfinkel PE, eds. (1997), Handbook of Treatment for Eating Disorders, 2nd Edition. New York: Guilford Press.

Goldberg SC, Casper RC, Eckert ED et al. (1980), Effects of cyproheptadine in anorexia nervosa. Psychopharmacology Bulletin 16(2):29-30.

Gull WW (1874), Anorexia nervosa (apepsia hysterica, anorexia hysterica). Transactions of the Clinical Society of London 7:22-28.

Hall A, Hay PJ (1991), Eating disorder patient referrals from a population region 1977-1986. Psychol Med 21(3):697-701.

Halmi KA, Eckert E, LaDu TJ, Cohen J (1986), Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline. Arch Gen Psychiatry 43(2):177-181.

Hay P (1998), The epidemiology of eating disorder behaviors: an Australian community-based survey. Int J Eat Disord 23(4):371-382.

Hay P, Ben-Tovim D, Walker K (2001), The quantity and quality of the evidence base for treatments used in anorexia nervosa: a matter for concern. P-157. Presented at the Ninth International Cochrane Colloquium. Lyon, France; Oct. 12-13.

Herzog DB, Hopkins JD, Burns CD (1993), A follow-up study of 33 subdiagnostic eating disordered women. Int J Eat Disord 14(3):261-267.

Hirano H, Tomura N, Okane K et al. (1999), Changes in cerebral blood flow in bulimia nervosa. J Comput Assist Tomogr 23(2):280-282.

Kaye WH, Nagata T, Weltzin TE et al. (2001), Double-blind placebo-controlled administration of fluoxetine in restricting- and restricting-purging-type anorexia nervosa. Biol Psychiatry 49(7):644-652.

LasŠque C (1873), De l'anorexia hyst‚rique. Archives G‚n‚rales de M‚decine 1:385-403.

Pawluck DE, Gorey KM (1998), Secular trends in the incidence of anorexia nervosa: integrative review of population-based studies. Int J Eat Disord 23(4):347-352.

Russell G (1979), Bulimia nervosa: an ominous variant of anorexia nervosa. Psychol Med 9(3):429-448.

Schwartz JM, Stoessel PW, Baxter LR et al. (1996), Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 53(2):109-113.

Treasure J, Schmidt U (2001), Anorexia nervosa. Clinical Evidence 5:0-12.

Wilson GT, Fairburn CG, Agras WS (1997), Cognitive-behavioral therapy for bulimia nervosa. In: Handbook of Treatment for Eating Disorders, 2nd Edition, Garner DM, Garfinkel PE, eds. New York: Guilford Press, pp67-93.