Bulimia nervosa and binge eating disorder are complex eating disorders. Psychotherapeutic interventions are the first-choice treatment. Combined psychotherapy and pharmacotherapy produces better outcomes.
Bulimia nervosa and binge eating disorder are complex eating disorders. Psychotherapeutic interventions are the first-choice treatment. Combined psychotherapy and pharmacotherapy produces better outcomes.
Bulimia nervosa and binge eating disorder are complex eating disorders. Psychotherapeutic interventions are the first-choice treatment. Combined psychotherapy and pharmacotherapy produces better outcomes.
PSYCHIATRY 7:4 161 2008 Elsevier Ltd. All rights reserved.
Treatment of bulimia nervosa and binge eating disorder Frederique Van den Eynde Ulrike Schmidt Abstract Bulimia nervosa and binge eating disorder are complex eating disorders with a major impact on the life of the patient and that of their family. Over the past two decades, increasing prevalence and incidence rates have confronted primary care and mental health services with high demands for treatment for these disorders that are difcult to meet. Psychotherapeutic interventions are the rst-choice treatment. Cognitivebehavioural therapy (CBT) is efcacious in both bulimia nervosa and binge eating disorder, but there is a need to improve outcomes further. Interpersonal psychotherapy (IPT) has also been shown to have benets, although in bulimia nervosa the response has been slower than with CBT. In general, delivering psycho- therapy is costly and is often hampered by limited availability. Self-help versions of CBT may help to overcome these difculties. Although prom- ising, further exploration is required as to whether self-help strategies are an alternative to or can reduce therapist involvement. Alternatively, pharmacotherapy is a potential treatment option for bulimia nervosa and binge eating disorder, with evidence predominantly on antidepressants. Fluoxetine in a higher dose has been recommended because it is relatively better tolerated than antidepressants of other classes. Overall, combined psychotherapy and pharmacotherapy in patients with bulimia nervosa produces somewhat better outcomes than pharmacotherapy alone, but is not clearly superior to psychotherapy alone. Data on combination treat- ment in binge eating disorder are less conclusive. Although the therapeu- tic arsenal for the treatment of bulimia nervosa and binge eating disorder is expanding, several domains required further investigation. Keywords antidepressant; binge eating disorder; bulimia nervosa; cognitivebehavioural therapy; interpersonal therapy; treatment
Introduction Bulimia nervosa (BN) was rst described by Gerald Russell in 1979, binge eating disorder (BED) was conceptualized a decade later, and purging disorder (PD) 1 has recently gained attention. Despite the very recent recognition of these disorders, and in stark contrast to anorexia nervosa, a major body of research into the treatment of these conditions has been produced and has been summarized in several high-quality systematic reviews. It is Frederique Van den Eynde MD is a Marie Curie Research Fellow at the Section of Eating Disorders, Institute of Psychiatry, London, UK. Conicts of interest: none declared. Ulrike Schmidt MRCPysch PhD is Head of the Section of Eating Disorders, Institute of Psychiatry, London, UK. Conicts of interest: none declared. likely that these research efforts were driven by the considerable public interest in these disorders, fuelled by celebrity cases, but also by the increasing incidence and prevalence rates of bulimia during the last two decades of the 20th century. 2 Psychological treatment of bulimia nervosa Cognitivebehavioural therapy and interpersonal therapy A specic form of cognitivebehavioural therapy (CBT) was developed by Fairburn et al. (1993) 3 and focuses on address- ing bulimic behaviours and cognitions, such as overvalued beliefs about weight, shape and appearance. A schematic form of the model underlying this treatment is presented in Figure 1. Currently, this form of CBT is considered the rst-choice treat- ment for adults with bulimia nervosa. 4,5 With 16 to 20 sessions of this treatment, about 3040% of people are symptom free at the end of treatment, and these gains are usually maintained in the longer term. CBT has been found to be superior to remaining on the waiting list and to a range of comparison treatments. 4 Several trials have compared CBT to interpersonal psychotherapy (IPT). 6,7
People with BN often present with interpersonal difculties, thus a treatment such as IPT, which focuses on these, appears highly relevant. CBT has been found to be superior to IPT in terms of reducing bulimic symptoms and achieving remission, 8,9 but this difference disappears over time and longer-term outcomes are similar. 7,9 A recent systematic review has conrmed that CBT yields a faster reduction of bulimic symptoms, whereas IPT is equally efcacious in the longer term. 4 Modications to cognitivebehavioural therapy, and what if it fails? Attempts to dismantle CBT and determine the active ingredients led to identication of the cognitive component as critical to Over-evaluation eating, shape and weight and their control Strict dieting and other weight-control behaviour Binge eating Compensatory vomiting/laxative misuse Cognitivebehavioural model of the maintenance of bulimia nervosa Adapted with permission from Fairburn CG, Cooper Z, Shafran R. Cognitive behaviour therapy for eating disorders: a transdiagnostic theory and treatment. Behav Res Ther 2003; 41: 50928. 16 Figure 1 MANAGEMENT ISSUES PSYCHIATRY 7:4 162 2008 Elsevier Ltd. All rights reserved. therapeutic outcome (for review see Shapiro et al., 2007). 10 Modi- cations to CBT such as the addition of exposure and response prevention did not enhance its efcacy. 11 In contrast, translating CBT into self-help modalities is promising (see below). Several recent efcacy studies (e.g. reference 12) have compared group with individual CBT, motivated by the notion that group treat- ment might be more cost effective. These studies suggest a slight advantage for individual over group treatment in terms of clinical outcomes. However, these ndings are not clear-cut, as these studies are likely to have been underpowered. In the management of CBT non-responders, several possible strategies can be applied, such as switching from CBT to admin- istration of antidepressants, or another form of psychotherapy. However, Mitchell et al. (2002) 13 found that an augmentation strategy with either IPT or antidepressants in CBT non-responders did not signicantly improve response rates. This led the authors to suggest that offering lengthy sequential treatments to people with BN may be of little value. 13 This needs further exploration, as others have reported a benecial effect for augmentation of CBT with antidepressants. 14 Another approach is to alter or add to CBT to make it more effective. 15 For example, Fairburn and colleagues (2003) 16 have described a new model of eating disorders, the so-called trans- diagnostic model. This model and the treatment based on it, in addition to addressing symptoms of the eating disorder, tackle other areas in which these patients commonly experience prob- lems. These include clinical perfectionism, core low self-esteem, affective instability, and interpersonal problems. Other research- ers, such as Cooper and co-workers (2004) 17 and Waller et al. (2007), 18 have also developed promising additions and adapta- tions to CBT-BN, although to date there have been no compari- sons of CBT-BN with these more sophisticated approaches. Interventions for adolescents The majority of treatment trials in BN have focused on adults, and the National Institute for Health and Clinical Excellence (NICE) guideline identied the need for trials on adolescents as a research priority. 4 Since then, two randomized controlled trials (RCTs) of the treatment of adolescents with BN have been published. Schmidt et al. (2007) 19 compared family therapy and CBT-based guided self-help in adolescents aged 1320 years with BN or eating disor- der not otherwise specied (EDNOS)-BN. Guided self-help had a slight advantage over family therapy in terms of producing a more rapid reduction of bingeing, lower cost, and higher acceptability. A second, US-based, trial 20 compared family therapy with supportive psychotherapy in adolescents aged 1219 years with BN. Family therapy was superior to supportive psychotherapy, although these effects appeared to wane by the 6-month follow-up. Other interventions Dialectical behavioural therapy (DBT) 21 and nutritional and stress management 22 in BN look promising as they reduce bingeing and purging. Higher abstinence rates than for waiting list were observed in the DBT group. 21 Preliminary ndings on guided imaginary 23 and light therapy 24,25 are encouraging as well. Response prediction Early response to treatment predicts the post-treatment outcome in BN. 6,8,26,27 High frequency of bingeing and longer duration of illness appear to predict a worse outcome from psychological treatments. There is no evidence for differential outcome by sociodemographic factors. 10 Psychological treatment of binge eating disorder In BED the goals of treatment are two-fold: rst, to help people reduce or stop distressing binges and, second, as BED is often associated with obesity, to reduce weight. CBT is the rst-choice treatment in BED as its efcacy in terms of binge reduction has been well documented. 28,29 However, CBT does not usually lead to a signicant weight loss in these patients. Modications such as additional spousal involvement 28 and body exposure/ cognitive restructuring of negative body cognitions 29 were not benecial. Apart from CBT, IPT has also been shown to improve binge- ing symptoms. 30 Other promising results that need further investigation have come from a RCT with DBT, 31 and virtual reality and psychonutritional control. 32 It remains unclear whether behavioural weight loss treatments are efcacious for weight loss in obese patients with BED. 33 Compared with guided self-help CBT, behavioural weight loss treatment was less efcacious in improving BED symptomatology, but resulted in similar weight reduction. 34 Overall, a systematic review 35
considered the evidence for the efcacy of behavioural inter- ventions in BED to be moderate, but weak for self-help and other interventions. Again, no consistency on predictive factors was reached. Self-help and guided self-help As specialist psychological treatment is not always easily access- ible, or only with considerable delays, self-help treatments might help to bridge the gap between demands and available resources. Self-help treatments use audiovisual materials for the purpose of gaining understanding or solving problems relevant to a persons therapeutic needs. 36 In guided self-help, guidance by a health- care professional or a layperson is offered, to monitor progress, clarify procedures, to answer general questions, or to provide general support or encouragement. 37 Is it efcacious? Two systematic reviews have summarized the available litera- ture on self-help treatments in BN, BED, and EDNOS in adults. These reviews underline their utility as a rst treatment step and regard them as potential alternatives to formal therapist- delivered psychological therapy. 38,39 In comparison with wait- ing list, self-help, in particular with guidance, leads to a greater improvement in eating disorder symptoms (but not bingeing or purging), other psychiatric symptomatology, and interpersonal functioning. There is also some evidence suggesting that guided self-care may be as effective as other formal psychological treat- ments, 38 although others 40 have cautioned that this area needs further study. The relative efcacy of self-help interventions compared with pharmacological interventions remains unclear. Much is still to be learnt about who benets from what kind of self- help, in what setting, and with how much and what type of guidance. MANAGEMENT ISSUES PSYCHIATRY 7:4 163 2008 Elsevier Ltd. All rights reserved. Pharmacological treatment of bulimia nervosa Antidepressants Efcacy: pharmacological intervention in BN has focused prim- arily on antidepressants. The rationale for this was high co- morbidity between BN and affective disorders, and ndings of serotonin system dysfunctions in BN. 41 According to some authors antidepressants have antibulimic properties regardless of the presence of mood symptoms, 42 but according to others it remains unclear whether this effect is direct or indirect by lower- ing depressive symptoms. 43 A systematic review of RCTs comparing different tricyclic antidepressants (TCAs), a selective serotonin reuptake inhibitor (SSRI), and monoamine oxidase inhibitors (MAOIs) concluded that the use of a single antidepressant in patients with BN was clinically effective and associated with an overall greater remis- sion rate, but also higher drop-out rates than placebo. 43 Differ- ent classes of antidepressant did not differ in efcacy, although patients taking TCAs were more likely to interrupt treatment prematurely and uoxetine was more acceptable. To date, only uoxetine has been approved by the US Food and Drug Admin- istration in the treatment of BN. It is of note that promising nd- ings for other antidepressants (mianserin, reboxetine, sertraline, milnacipran, and trazodone) have been published, as well as negative ndings for others (e.g. lack of efcacy for uvoxamine in a large multicentre randomized placebo-controlled trial). 44 Dosage, side effects, and duration of treatment: TCA and MAOI doses applied in BN are comparable to those in depression. 43 For uoxetine, a doseresponse study showed a high dose (60 mg) to be superior to a lower dose (20 mg) and placebo. 45 Data on adolescent subjects with BN are scarce, but a high dose of uox- etine has been argued to be safe and effective. 46 Side effects can negatively inuence compliance and increase discontinuation rates. Fluoxetine was repeatedly reported to be the best tolerated antidepressant with proven efcacy in BN. 43 Its use is not associ- ated with increased suicidality. 47 A recurrent clinical dilemma concerns the duration for which a treatment should be continued. The literature is inconclusive, but high relapse rates after treatment discontinuation 48 and improved relapse prevention with treatment continuation 49 sug- gest that the effect of antidepressant treatment is most likely not enduring. Based on these ndings, the NICE guidelines 4 recom- mend that antidepressants can be tried as a rst step in treat- ment, but should be discontinued if found not to be effective quickly. Who is going to respond? According to some authors, antidepressant responders can be reliably identied in the rst 2 weeks of treatment. 50 However, this does not enable clinicians to make accurate predictions on an individual level, as there is a subgroup of people who respond more slowly. 8 The literature on predictors of treatment outcome is inconsistent, but a high level of bulimic symptoms and a his- tory of substance abuse/dependence were shown negatively to inuence treatment outcome, whereas a good therapeutic alli- ance increased the likelihood of remission. 8 Greater concern for body shape and weight, higher weight, and longer duration of illness have been associated with a more favourable outcome. 48 Other psychotropics Numerous pharmacological compounds have been studied in BN, although these trials were not always clearly driven by hypoth- eses. Mood stabilizers (phenytoin, carbamazepine, and lithium), L-tryptophan, naltrexone, and fenuramine have not been found to be effective. In contrast, one small RCT found the 5-HT 3 ago- nist ondansetron to be superior to placebo in the short term, although the feasibility of this treatment is questionable as it is expensive and multiple daily dosing is required. 51 Several RCTs (e.g. reference 52) have suggested that topiramate reduces binge days; this warrants further exploration. Pharmacological treatment of binge eating disorder SSRIs (citalopram, sertraline, uoxetine, and uvoxamine) have mainly been used as the active compound in pharmacological tri- als of patient with BED. Overall, they generated a reduction of binge eating behaviour and were well tolerated. However, they were also associated with higher discontinuation rates. 35 A large case-series has also provided promising results for venlafaxine in BED. 53 Apart from antidepressants, topiramate 54,55 and subitra- mine 56 reduce binge eating symptoms, but only subitramine also improved mood symptoms and resulted in signicant weight loss. Is combination treatment the answer? Bulimia nervosa Findings on combined psychotherapy and antidepressant treatment in BN are rather inconsistent and do not show a clear additive, let alone multiplicative, effect. Furthermore, complex study designs do not contribute to a straightforward interpretation of the literature. Most authors have reported that addition of an antidepressant to CBT did not amplify the efcacy of CBT alone, 5759 whereas others found that it did. 14 A further question is whether combina- tion treatment is more efcacious than medication alone. Again, conicting results have been reported, with positive 14,58,59 and negative 57 ndings. Other forms of psychotherapy have been poorly studied in this respect. Neither the combination of an antidepressant and IPT in CBT non-responders, 13 nor the combination of an antide- pressant and psychodynamically oriented supportive therapy, 14
proved to be superior to medication alone. However, the anti- depressant and supportive therapy combination was signicantly better than psychotherapy alone, 14 whereas this was not the case for a structured group therapy. 60 Where combined self-help intervention and antidepressant treatment were delivered, the active component reducing bulimic symptoms appeared to be the antidepressant, whereas self-help interventions had no independent effect. 61,62 Kotler and Walsh (2000) 46 emphasized that the modest gains of adding medication to psychotherapy should be weighed against the risk of side effects and the costs of medication and its monitoring. Conversely, the gains of adding psychological treat- ment to medication must be examined in the context of costs and limited availability. Binge eating disorder The addition of antidepressants to CBT is a successful strategy in BED 63,64 and was shown to be better than medication alone. 34,65
MANAGEMENT ISSUES PSYCHIATRY 7:4 164 2008 Elsevier Ltd. All rights reserved. Data on its ability to reduce binge eating and weight vs CBT alone, are conicting. 34,65,66 In contrast, the addition of orlistat 67
or topiramate 55 to CBT increased the efcacy of the latter. Both dietary counselling 68 and behavioural therapy 69 com- bined with an antidepressant also resulted in weight reduction. This was not the case for nutritional management. 65 Conclusion On the whole, treatment of bulimic syndromes is characterized by low remission and high relapse rates. For both BN and BED, CBT is the rst-choice treatment, but associated costs and limited availability are disadvantages of this. In BN, CBT and IPT appear to be equally effective in the longer term, although CBT induces a faster response. In BED, CBT is the best-established therapeu- tic option, but does not reduce weight. Self-help interventions, guided or not, have the potential to allow clinicians to overcome the present gap between high demands for treatment and limited resources. Pharmacological interventions are part of the armamentarium for treating bulimic syndromes, especially when affective symp- toms are present. 46 A higher dose of uoxetine is considered effective and safe in adults and adolescents. However, there is a need for more replication studies. 41 It is an advantage of anti- depressant treatment that it can be easily and successfully imple- mented in primary care settings. 62 As to whether a combination of psychotherapy and pharmacology is the solution, this remains uncertain. In general, combination treatment is more effective than medication alone, but not than psychotherapy alone. Even if unsuccessful in the short term, engaging patients in an active treatment seems to improve social functioning after a decade, compared with giving no active treatment. 70 Many domains in the treatment of bulimic syndromes are yet to be explored. Generalizability of current ndings is largely lim- ited to young adult patients without severe co-morbidity. Uni- form adequate outcome measures need to be dened, including clear conceptualization of remission, recovery, and relapse in bulimic syndromes. 43
REFERENCES 1 Keel PK, Wolfe BE, Liddle RA, De Young KP, Jimerson DC. Clinical features and physiological response to a test meal in purging disorder and bulimia nervosa. Arch Gen Psychiatry 2007; 64: 105866. 2 Currin L, Schmidt U, Treasure J, Jick H. Time trends in eating disorder incidence. Br J Psychiatry 2005; 186: 1325. 3 Fairburn C, Marcus M, Wilson G. Cognitive-behavioral therapy for binge eating and bulimia nervosa: a comprehensive treatment manual. In: Fairburn CG, Wilson GT, eds. Binge eating: nature, assessment and treatment. New York: Guilford Press, 1993. 4 National Collaborating Centre for Mental Health. Eating disorders: core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. London: National Institute for Clinical Excellence, 2004. 5 Hay PJ, Baltchuk J, Stefano S. Psychotherapy for bulimia nervosa and binging. Cochrane Database Syst Rev 2004; (3): CD000562. doi:10.1002/14651858.CD000562.pub2. 6 Agras WS, Crow SJ, Halmi KA, Mitchell JE, Wilson GT, Kraemer HC. Outcome predictors for the cognitive behavior treatment of bulimia nervosa: data from a multisite study. Am J Psychiatry 2000; 157: 13028. 7 Fairburn CG, Jones R, Peveler RC, Hope RA, OConnor M. Psychotherapy and bulimia nervosa. Longer-term effects of interpersonal psychotherapy, behavior therapy, and cognitive behavior therapy. Arch Gen Psychiatry 1993; 50: 41928. 8 Wilson GT, Loeb KL, Walsh BT, et al. Psychological versus pharmacological treatments for bulimia nervosa: predictors and progress of change. J Consult Clin Psychol 1999; 67: 4519. 9 Wiley D, Agras W, Telch C, et al. Group cognitive-behavior therapy and group interpersonal psychotherapy for the nonpurging bulimic individual: a controlled comparison. J Consult Clin Psychol 1993; 61: 296305. 10 Shapiro JR, Berkman ND, Brownley KA, Sedway JA, Lohr KN, Bulik CM. Bulimia nervosa treatment: a systematic review of randomised controlled trials. Int J Eat Disord 2007; 40: 32136. 11 Bulik C, Sullivan P, Carter F, et al. The role of exposure with response prevention in the cognitive-behavioral therapy for bulimia nervosa. Psychol Med 1998; 28: 61123. 12 Nevonen L, Broberg AG. A comparison of sequenced individual and group psychotherapy for patients with bulimia nervosa. Int J Eat Disord 2006; 39: 11727. 13 Mitchell JE, Halmi K, Wilson T, Agras WS, Kraemer H, Crow S. A randomized secondary treatment study of women with bulimia nervosa who fail to respond to CBT. Int J Eat Disord 2002; 32: 27181. 14 Walsh BT, Wilson TW, Loeb KL, et al. Medication and psychotherapy in the treatment of bulimia nervosa. Am J Psychiatry 1997; 154: 52331. 15 Wilson GT, Grilo CM, Vitousek KM. Psychological treatment of eating disorders. Am Psychol 2007; 62: 199216. 16 Fairburn CG, Cooper Z, Shafran R. Cognitive behaviour therapy for eating disorders: a transdiagnostic theory and treatment. Behav Res Ther 2003; 41: 50928. 17 Cooper MJ, Wells A, Todd G. A cognitive model of bulimia nervosa. Br J Clin Psychol 2004; 43: 116. 18 Waller G, Cordery H, Corstorphine E, et al. eds. Cognitive behavioral therapy for eating disorders. A comprehensive treatment guide. Cambridge: Cambridge University Press, 2007. 19 Schmidt U, Lee S, Beechman J, et al. A randomized controlled trial of family therapy and cognitive behavior therapy guided self-care for adolescents with bulimia nervosa. Am J Psychiatry 2007; 164: 5918. 20 Le Grange D, Crosby RD, Rathouz PJ, Leventhal BL. A randomized controlled comparison of family-based treatment and supportive psychotherapy for adolescent bulimia nervosa. Arch Gen Psychiatry 2007; 64: 104956. 21 Safer DL, Telch CF, Agras WS. Dialectical behavioural therapy for bulimia nervosa. Am J Psychiatry 2001; 158: 6324. 22 Laessle RG, Beumont PJ, Butow P, et al. A comparison of nutritional management with stress management in the treatment of bulimia nervosa. Br J Psychiatry 1991; 159: 25061. 23 Esplen MJ, Garnkel PE, Olmsted M, Gallop SM, Kennedy R. A randomized controlled trial of guided imaginary in bulimia nervosa. Psychol Med 1998; 28: 134757. 24 Lam RW, Goldner EM, Solyom L, Remyck RA. A controlled study of light therapy for bulimia nervosa. Am J Psychiatry 1994; 151: 74450. MANAGEMENT ISSUES PSYCHIATRY 7:4 165 2008 Elsevier Ltd. All rights reserved. 25 Braun DL, Sunday SR, Fornari VM, Halmi KA. Bright light therapy decreases winter binge frequency in woman with bulimia nervosa. A double-blind, placebo-controlled study. Compr Psychiatry 1999; 40: 44248. 26 Wilson GT, Fairburn C, Agras WS, Walsh BT, Kraemer H. Cognitive- behavioral therapy for bulimia nervosa: time course and mechanisms of change. J Consult Clin Psychol 2002; 70: 26774. 27 Fairburn CG, Agras WS, Walsh BT, Wilson GT, Stice E. Prediction of outcome in bulimia nervosa by early change in treatment. Am J Psychiatry 2004; 161: 23224. 28 Gorin A, Le Grange D, Stone A. Effectiveness of spouse involvement in cognitive behavioural therapy for binge eating disorder. Int J Eat Disord 2003; 33: 42133. 29 Hilbert A, Tuschen-Cafer B. Body image interventions in cognitive- behavioural therapy of binge-eating disorder: a component analysis. Behav Res Ther 2003; 42: 132539. 30 Wiley DE, Welch RR, Stein RI, et al. A randomized comparison of group cognitive-behavioral therapy and group interpersonal psychotherapy for the treatment of overweight individuals with binge-eating disorder. Arch Gen Psychiatry 2002; 59: 71321. 31 Telch CF, Agras WS, Linehan MM. Dialectical behavior therapy for binge eating disorder. J Consult Clin Psychol 2001; 69: 10615. 32 Riva G, Bachatta M, Baruf M, Molinari E. Virtual-reality-based multidimensional therapy for the treatment of body image disturbances in binge eating disorders: a preliminary controlled study. IEEE Trans Inf Technol Biomed 2002; 6: 22434. 33 Gladis MM, Wadden TA, Vogt R, Foster G, Kuehnel RH, Bartlett SJ. Behavioral treatment of obese binge eaters: do they need different care? J Psychosom Res 1998; 44: 37584. 34 Grilo CM, Masheb RM, Wilson GT. Efcacy of cognitive behavioral therapy and uoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison. Biol Psychiatry 2005; 57: 3019. 35 Brownley KA, Berkman ND, Sedway JA, Lohr KN, Bulik CM. Binge eating disorder treatment: a systematic review of randomized controlled trials. Int J Eat Disord 2007; 40: 33748. 36 Williams C. New technologies in self-help: another effective way to get better? Eur Eat Disord Rev 2003; 11: 17082. 37 Gould RA, Clum GA. A meta-analysis of self-help treatment approaches. Clin Psychol Rev 1993; 13: 16986. 38 Perkins SJ, Murphy R, Schmidt U, Williams C. Self-help and guided self-help for eating disorders. Cochrane Database Syst Rev 2006; (3): CD004191. 39 Stefano SC, Bacaltchuk J, Blay SL, Hay P. Self-treatments for disorders of recurrent binge eating: a systematic review. Acta Psychiatr Scand 2006; 113: 4529. 40 Sysko R, Walsh BT. A critical evaluation of the efcacy of self-help interventions for the treatment of bulimia nervosa and binge-eating disorder. Int J Eat Disord 2007 [epub ahead of print]. 41 Kaye W, Gendall K, Strober M. Serotonin neural function and selective serotonin reuptake inhibitor treatment in anorexia and bulimia nervosa. Biol Psychiatry 1998; 44: 82538. 42 Goldstein DJ, Wilson MG, Ascroft RC, al-Banna M. Effectiveness of uoxetine therapy in bulimia nervosa regardless of comorbid depression. Int J Eat Disord 1999; 25: 1927. 43 Bacaltchuk J, Hay P. Antidepressant versus placebo for people with bulimia nervosa. Cochrane Database Syst Rev 2003; (4): CD003391. doi:10.1002/14651858.CD003391. 44 Schmidt U, Cooper PJ, Essers H, et al. Fluvoxamine and graded psychotherapy in the treatment of bulimia nervosa: a randomized, double-blind, placebo-controlled, multicenter study of short-term and long-term pharmacotherapy combined with a stepped care approach to psychotherapy. J Clin Psychopharmacol 2004; 24: 54952. 45 Fluoxetine Bulimia Nervosa Collaborative Study Group. Fluoxetine in the treatment of bulimia nervosa. A multicenter, placebo-controlled double-blind trial. Arch Gen Psychiatry 1993; 150: 7704. 46 Kotler LA, Walsh BT. Eating disorders in children and adolescents: pharmacological therapies. Eur Child Adolesc Psychiatry 2000; 9: 10816. 47 Wheadon DE, Rampey AH, Thompson VL, Potvin JH, Masica DN, Beasley Jr CM. Lack of association between uoxetine and suicidality in bulimia nervosa. J Clin Psychiatry 1992; 53: 23541. 48 Walsh BT, Hadigan CM, Devlin MJ, Gladis M, Roose SP. Long-term outcome of antidepressant treatment for bulimia nervosa. Am J Psychiatry 1991; 12: 16368. 49 Romano SJ, Halmi KA, Sarkar NP, Koke SC, Lee JS. A placebo- controlled study of uoxetine in continued treatment of bulimia nervosa after successful acute uoxetine treatment. Am J Psychiatry 2002; 159: 96102. 50 Walsh BT, Sysko R, Parides MK. Early response to desipramine among women with bulimia nervosa. Int J Eat Disord 2006; 39: 725. 51 Faris PL, Kim SW, Meller WH, et al. Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised double-blind trial. Lancet 2000; 355: 7927. 52 Nickel C, Tritt K, Muehlbacher M, et al. Topiramate treatment in bulimia nervosa patients. Int J Eat Disord 2005; 38: 295300. 53 Malhortra S, King KH, Wege JA, Brusman-Lovins L, McElroy SL. Venlafaxine treatment of binge-eating disorder associated with obesity: a series of 35 patients. J Clin Psychiatry 2002; 63: 8026. 54 McElroy SL, Hudson JI, Capece JA, et al. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo- controlled study. Biol Psychiatry 2007; 61: 103948. 55 Claudino AM, de Oliveira IR, Appolinario JC, et al. Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive- behavior therapy in binge-eating disorder. J Clin Psychiatry 2007; 68: 132432. 56 Appolinario JC, Bacaltchuk J, Sichieri R, et al. A randomized, double- blind placebo-controlled study of subitramine in the treatment of binge-eating disorder. Arch Gen Psychiatry 2003; 60: 110916. 57 Goldbloom DS, Olmsted M, Davis R, et al. A randomised controlled trial of uoxetine and cognitive-behavior therapy for bulimia nervosa: short-term outcome. Behav Res Ther 1997; 35: 80311. 58 Agras WS, Rossiter EM, Arnow B, et al. Pharmacologic and cognitive- behavioral treatment for bulimia nervosa: a controlled comparison. Am J Psychiatry 1992; 49: 827. 59 Agras W, Rossiter E, Arnow B, et al. One year follow-up of psychosocial and pharmacologic treatments for bulimia nervosa. J Clin Psychiatry 1994; 55: 17983. 60 Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Pomeroy C, Zimmerman R. A comparison study of antidepressants and structured group psychotherapy in the treatment of bulimia nervosa. Arch Gen Psychiatry 1990; 47: 14957. 61 Mitchell JE, Fletcher L, Hanson K, et al. The relative efcacy of uoxetine and manual-based self-help in the treatment of outpatients with bulimia nervosa. J Clin Psychopharmacol 2001; 21: 298304. MANAGEMENT ISSUES PSYCHIATRY 7:4 166 2008 Elsevier Ltd. All rights reserved. 62 Walsh BT, Fairburn CG, Mickley D, Sysko R, Parrides MK. Treatment of bulimia nervosa in a primary care setting. Am J Psychiatry 2004; 161: 55661. 63 Agras WS, Telch CF, Arnow B, et al. Weight loss, cognitive- behavioral, and desipramine treatments in binge eating disorder. An addictive design. Behav Ther 1994; 25: 22538. 64 Devlin MJ, Goldfein JA, Dobrow I. What is this thing called BED? Current status of binge eating disorder nosology. Int J Eat Disord 2003; 34(suppl): S2S7. 65 de Zwaan M, Nutzinger DO, Schoenbeck G. Binge eating in overweight women? Compr Psychiatry 1992; 33: 25661. 66 Ricca V, Manucci E, Mezzani B, et al. Fluoxetine and uvoxamine combined with individual cognitive-behaviour therapy in binge eating disorder: a one year follow-up study. Psychother Psychosom 2001; 70: 298306. 67 Grilo CM, Masheb RM, Salant SL. Cognitive behavioral therapy guided self-help and orlistat for the treatment of binge eating disorder. A randomised double blind placebo-controlled trial. Biol Psychiatry 2005; 57: 1193201. 68 Laederach-Hofmann K, Graf C, Horber F, et al. Imipramine and diet counseling with psychological support in the treatment of obese binge-eaters: a randomized placebo-controlled double-blind study. Int J Eat Disord 1999; 26: 23144. 69 Marcus MD, Wing RR, Ewing L, Kern E, McDermott M, Gooding W. A double-blind, placebo-controlled trial of uoxetine plus behavior modication in the treatment of obese binge-eaters and non-binge eaters. Am J Psychiatry 1990; 147: 87681. 70 Keel PK, Mitchell JE, Davis TL, Crow SJ. Long-term impact of treatment in women diagnosed with bulimia nervosa. Int J Eat Disord 2002; 31: 1518.