Practice Guideline for the Treatment of Patients With Eating (PDF)

1 C H A P T E R GUIDELINE WATCH (AUGUST 2012): PRACTICE GUIDELINE FOR THE TREATMENT OF PATIENTS WITH EATING DISORDERS, 3RD EDITION Joel Yager, M.D. Michael J. Devlin, M.D. Katherine A. Halmi, M.D. David B. Herzog, M.D. James E. Mitchell III, M.D. Pauline Powers, M.D. Kathryn J. Zerbe, M.D. This guideline watch reviews new evidence and highlights salient developments since the 2006 publication of APA’s Practice Guideline for the Treatment of Patients With Eating Disorders, 3rd Edition. The authors of this watch constituted the work group that developed the 2006 guideline. We find the guideline to remain substantially correct and current in its recommendations. The sole exception is a recommenda- tion (with moderate-level confidence) for sibutramine for binge-eating disorder. In 2010, the U.S. Food and Drug Ad- ministration (FDA) withdrew approval for sibutramine be- cause clinical trials showed increased risk of heart attack and stroke, and the manufacturer, Abbott Laboratories, subse- quently withdrew this medication from the U.S. market. Noteworthy recent publications about the treatment of eating disorders include systematic reviews by the Agency for Healthcare Research and Quality (Berkman et al. 2006; Bulik et al. 2007); practice guidelines from international groups, including the Catalan Agency for Health Informa- tion, Assessment and Quality (Working Group of the Clin- ical Practice Guideline for Eating Disorders 2009), the World Federation of Societies of Biological Psychiatry (Aigner et al. 2011), and the German Society of Psychoso- matic Medicine and Psychotherapy and the German Col- lege for Psychosomatic Medicine (Herpertz et al. 2011); and a 2011 guidance statement by the Academy for Eating Disorders, which was written by some of the authors of this From December 2011 to July 2012 (the time period during which this watch was developed), Drs. Yager, Devlin, Halmi, Herzog, Mitchell, Powers, and Zerbe report no competing interests. The American Psychiatric Association’s (APA’s) practice guidelines are developed by expert work groups using an explicit meth- odology that includes rigorous review of available evidence, broad peer review of iterative drafts, and formal approval by the APA Assembly and Board of Trustees. APA practice guidelines are intended to assist psychiatrists in clinical decision making. They are not intended to be a standard of care. The ultimate judgment regarding a particular clinical procedure or treatment plan must be made by the psychiatrist in light of the clinical data presented by the patient and the diagnostic and treatment options available. Guideline watches summarize significant developments in practice that have occurred since publication of an APA practice guideline. Watches may be authored and reviewed by experts associated with the original guideline development effort and are approved for publication by APA’s Executive Committee on Practice Guidelines. Thus, watches represent the opinion of the authors and approval of the Executive Committee but not APA policy.  2 APA PRACTICE GUIDELINES watch. In our opinion, the findings, conclusions, and rec- ommendations of these recent reviews and guidelines are consistent with the 2006 APA guideline. Recent textbooks provide useful practical information for clinicians who wish to learn how to deliver treatments recommended in the practice guideline. The authors of a textbook edited by Grilo and Mitchell (2010) describe ther- apeutic approaches and reviews supporting evidence on all aspects of eating disorders treatment, from assessment through nutritional rehabilitation to managing the chron- ically ill. The authors state that there is no single treat- ment for patients with eating disorders. Rather, a diversity of approaches is recommended. In another recent textbook, Cloak and Powers (2010) review and synthesize the small but growing evidence base for psychodynamic treatment approaches in eating disorders. As do Grilo and Mitchell, the authors recommend integration of treatment modali- ties. An edited manual by Yager and Powers (2007) and a textbook by Zerbe (2008) also provide practical strategies for providing integrated treatment. These texts highlight that given the long-term nature of eating disorders, it is important to address countertransference issues, medical and psychiatric comorbidities, and quality of life. These and other textbooks also provide practical infor- mation about psychodynamic psychotherapy. For example, Zerbe (2008) synthesizes research that demonstrates that clinicians of differing theoretical orientations have been shown to have similar countertransference reactions. Thompson-Brenner and colleagues (2010) review the grow- ing evidence base for psychodynamic psychotherapy in pa- tients with anorexia nervosa, bulimia nervosa, and binge- eating disorder. The studies included in their review suggest that attending to the transference, symptom symbolism, key conflicts, narcissistic vulnerabilities, and relational dynam- ics are important for reducing core personality and symp- tom difficulties. METHODS The literature review for the 2006 guideline ended in 2003. For this watch, we searched MEDLINE, using PubMed, for randomized, controlled trials and meta-analyses pub- lished from 2003 through December 13, 2011, using the following terms: “bulimia,” “bulimia nervosa,” “bulimic,” “anorexia nervosa,” “binge eating,” “binge eating disorder,” “binge eating episode,” “eating disorder,” “eating disor- dered,” and “eating disorders.” Terms for limiting the search (using Boolean “or” logic) included the following: “system- atic review,” “random allocation,” “randomly allocated,” “randomly assigned,” “randomization,” “randomize,” “ran- domized,” “randomized controlled trial,” “placebo,” “active comparator,” “double blind,” “double blinded,” “controlled clinical trial,” “meta analysis,” “meta-analytic,” and not “ed- itorial,” “letter,” “case report,” or “comment.” We limited the search to English-language articles. We also searched the Cochrane database, using the terms “anorexia nervosa,” “bulimia,” and “binge eating” as well as corresponding Medical Subject Headings (MeSH) for re- views published from 2003 through December 13, 2011. These search strategies yielded 1,346 articles. Of these articles, 693 were rejected as not relating to treatment of eating disorders. We retained and reviewed 91 articles pertaining to anorexia nervosa, 84 to bulimia nervosa, 95 to binge eating, 12 to osteoporosis treatment in eating dis- orders, and 60 to miscellaneous topics, most of which cov- ered more than one eating disorder. The following discussion focuses on randomized, con- trolled trials identified by our search but also includes some recent open trials of which we are aware. For some topics, instead of discussing all studies, in this watch we summarize the conclusions of an available systematic re- view. This watch is not intended to be a comprehensive review of all possible treatments for eating disorders. Rather, we review recent research that relates to key rec- ommendations of the 2006 APA practice guideline. CLINICAL ASSESSMENT DSM-5, to be published in 2013, is expected to contain some revisions of the diagnostic criteria for anorexia ner- vosa, bulimia nervosa, and eating disorder not otherwise specified (EDNOS). For example, amenorrhea may be dropped as a necessary criterion for anorexia nervosa, binge-eating disorder may become a distinct diagnosis apart from EDNOS, and the frequency criteria for both bulimia nervosa and binge-eating disorder may drop from  Guideline Watch for the Practice Guideline for the Treatment of Patients With Eating Disorders 3 twice per week to once per week. These changes are un- likely to affect utility of the 2006 practice guideline, which recommends that patients with subsyndromal anorexia nervosa or bulimia nervosa, such as patients with EDNOS who meet all criteria for anorexia nervosa except for being amenorrheic for 3 months, should receive treatment sim- ilar to that of patients who fulfill all criteria for these di- agnoses. Proposed revisions to the criteria are available on the DSM-5 development website, www.dsm5.org, under “Feeding and Eating Disorders.” ANOREXIA NERVOSA The quality of evidence for treatments for anorexia nervosa remains limited, according to recent systematic reviews and meta-analyses (e.g., Fitzpatrick and Lock 2011; Hartmann et al. 2011). There are few randomized, controlled trials, and available studies suffer from small sample sizes, short dura- tion, and methodological problems. A contributing factor is that study recruitment is generally poor and dropout rates are high. For example, in a study of two clinical trials for an- orexia nervosa, Halmi and colleagues (2005) reported that 46% of patients who had entered into the study dropped out. The only predictor of treatment acceptance Halmi et al. identified was high self-esteem, not a particularly common characteristic of patients with eating disorders. Further- more, available studies are primarily about symptom relief rather than recovery (Strober and Johnson 2012). Predictors of recovery from anorexia nervosa remain poorly defined. In a systematic review of studies published from 1990 to 2005 on anorexia nervosa treatments, Espin- dola and Blay (2009) identified 3,415 studies, of which 16 addressed recovery. The authors concluded that a complex- ity of factors, extending well beyond conventional treat- ment factors and including self-acceptance, determination, and spirituality, accounts for recovery. In another system- atic review of 12 randomized, controlled trials, Crane and colleagues (2007) found that obsessive-compulsive person- ality disorder traits were associated with poorer outcome in patients with anorexia nervosa and opined that treatment might moderate these traits. In a study by Schebendach and colleagues (2011), 41 weight-restored patients with an- orexia nervosa who had been hospitalized were followed for up to 1 year. Differences were observed in the total number of different foods selected by patients with “success” out- comes (n=29) versus patients with “failure” outcomes (n=12). The authors stated that the results suggest that a diet limited in variety may be associated with relapse. CHOICE OF SETTING The guideline states that it is important to consider a pa- tient’s overall physical condition, psychology, behaviors, and social circumstances when choosing a treatment set- ting. Although investigators have attempted to study the advantages of specific settings, conclusions from available research are limited because there are many local varia- tions in the essential features of settings. In a large multicenter, randomized, controlled trial conducted in the United Kingdom (the Trial of Outcomes for Child and Adolescent Anorexia Nervosa, or TOuCAN study), Gowers and colleagues (2007) randomly assigned 167 adolescent patients with anorexia nervosa to specialist inpatient, specialist outpatient, or routine general outpa- tient treatment. Improvement on outcome measures was good across all treatment groups, but full recovery rates were poor, at only 33% after 2 years (of the 96% of the sam- ple available for follow-up). Adherence was lowest in the inpatient treatment group, at 50%, as compared with 71% for the routine outpatient and 77% for the specialist out- patient groups. Inpatient treatment predicted poor out- come (either when patients were initially randomly as- signed or after they were transferred from outpatient care). Patients who did not respond to outpatient treatment did very poorly (Gowers et al. 2010). The authors concluded that first-line inpatient treatment does not provide advan- tages over outpatient management, and that patients who do not respond to outpatient treatment do poorly on transfer to inpatient facilities (however, it is possible that patients in these difficult cases would do poorly in any set- ting) (Gowers et al. 2007). This same study found no sta- tistical differences in outcomes after 2 years, but specialist outpatient treatment was shown to be most cost-effective (Byford et al. 2007). On the whole, these investigators concluded that under the British National Health Service there is little support for long-term inpatient care, either for clinical or for health economic reasons (Gowers et al. 2010). These investigators also interviewed 215 patients and their parents to compare satisfaction with specialist versus generalist care. Levels of satisfaction were high across all types of treatment, but higher for specialist care. Parents reported higher levels of satisfaction than did ad- olescents (Roots et al. 2009).  4 APA PRACTICE GUIDELINES In the meta-analysis by Hartmann and colleagues (2011), 57 studies, covering 84 treatment areas and involving 2,273 patients, were analyzed. With respect to choice of setting, the authors concluded that there is little high- quality evidence on which to base specific guidance, find- ing only that perhaps patients gain more rapidly on inpa- tient than on outpatient treatment settings. NUTRITIONAL REHABILITATION For underweight individuals with anorexia nervosa, the guideline recommends that hospital-based programs for nutritional rehabilitation should be considered. A study by Garber and colleagues (2012) lends additional support to the utility of inpatient care for underweight patients to reduce complications of nutritional rehabilitation, partic- ularly the refeeding syndrome. In that study, 35 adoles- cent patients were followed during a hospital-based refeeding protocol in which calorie intake was increased every other day, from an average of 1,205 to 2,668, over an average length of stay of 16 days. No patients had refeed- ing syndrome, but 20% had low serum phosphorus levels. Percent mean body mass index (BMI) increased from 80.1 (11.5) to 84.5 (9.6), and overall gain was 2.10 (1.98) kg. Most of the patients (83%) initially lost weight, an impor- tant finding for clinicians who must justify the value of hospital-based nutritional rehabilitation programs to in- surance companies. Mean percent BMI did not increase significantly until day 8. Higher calories prescribed at baseline were significantly associated with faster weight gain and a shorter hospital stay. For patients who refuse to eat and require life-preserv- ing nutrition, the guideline recommends nasogastric feeding. The utility of nasogastric feedings has been stud- ied in open trials by Rigaud and colleagues (2007, 2011). In the first trial (2007), malnourished patients with anorexia nervosa were randomly assigned to a tube-feeding group (n=41) or a control group (n=40) groups. After 2 months, weight gain was 39% higher in the tube-feeding group, binge-eating episodes were decreased, and most patients thought the intervention improved their eating disorder. After discharge, the tube-feeding group had a longer re- lapse-free period (34.3±8.2 weeks vs. 26.8±7.5 weeks). In the second trial (2011), adult outpatients with anorexia ner- vosa or bulimia nervosa were randomly assigned to 2 months of cognitive-behavioral therapy (CBT) alone (n=51) or CBT plus tube feeding (n=52). By the end of treatment those receiving CBT plus tube feeding were more rapidly and frequently abstinent from binge eating and purging, had more improvement on symptoms of depression and anxiety, and had a better quality of life. These superior re- sults were also seen 1 year later. It should be noted that the average BMI for patients entered into the tube feeding plus CBT arm in the 2011 study was 18.2±3.3, thin but not severely underweight, and the analysis did not sepa- rate normal-weight patients with bulimia nervosa from patients with anorexia nervosa, binge-eating purging type. As described in the practice guideline, there are po- tential harms to nasogastric feeding, and the guideline does not specifically recommend it for normal-weight pa- tients. PSYCHOSOCIAL INTERVENTIONS The practice guideline recommends psychotherapeutic management during acute refeeding and weight gain and states that psychotherapy can be helpful once malnutri- tion has been corrected and weight gain has begun. These recommendations were based on strong consensus but weak evidence. Research on psychotherapy for anorexia nervosa remains limited. It is difficult to carry out rigor- ously designed trials of psychotherapies, and as with trials of pharmacotherapy, long-term follow-up is uncommon. In addition, available studies have used a variety of psy- chosocial interventions, often in mixed populations (i.e., with patients with different kinds of eating disorders). As a result, the following studies do not significantly change the overall quality of evidence supporting psychosocial in- terventions for anorexia nervosa. In an open trial that used a “transdiagnostic” approach and broad inclusion criteria, Byrne and colleagues (2011) administered 20–40 individual sessions of “enhanced” CBT, which included aspects of interpersonal therapy (IPT), to 125 patients at a public outpatient clinic. The in- vestigators reported that two-thirds of those completing treatment (and 40% of the total) achieved partial remis- sion. However, only 53% of those who entered the trial completed treatment. Since motivation for treatment is a problem for many patients with anorexia nervosa or bulimia nervosa, several groups have examined ways to enhance motivation at the start of treatment. In general, results have not been dra- matic, but some are promising. Wade and colleagues (2009) randomly assigned 47 young adult inpatients with anorexia nervosa to four sessions of motivational inter- viewing with a “novice” therapist (n=22) or treatment as usual (n=25). Not surprisingly, those who had started out with higher motivation did better overall. Patients receiv- ing motivational interviewing were more likely to move from low to high readiness to change at 2- and 6-week fol- low-up. In a similar study by Dean and colleagues (2008), 42 inpatients were randomly assigned to receive four ini- tial motivational interviewing sessions or treatment as usual. In this study, although no significant differences  Guideline Watch for the Practice Guideline for the Treatment of Patients With Eating Disorders 5 were seen between the groups, motivational enhancement treatment appeared to foster longer-term motivation and engagement and thus promote treatment continuation. Carter and colleagues (2011) investigated long-term outcomes of specialized psychotherapies in women with broadly defined anorexia nervosa who had participated (an average of 6.7 years prior to Carter et al.’s analysis) in a randomized, controlled trial comparing conventional CBT and a modified form of IPT in which therapists were constrained from discussing nutrition, weight, and shape issues, as well as a control condition (specialist supportive clinical management). No differences were seen in out- comes among the three groups. Only 43 of the original sample of 56 patients participated in this follow-up study, leaving the study underpowered. Several studies have examined the impact of exercise or strength training on patients with eating disorders. In a nonrandomized study, Calogero and Pedrotty (2004) compared 127 women in a residential treatment center who participated in an exercise program plus treatment as usual with 127 nonparticipants who received treatment as usual only. Women in the exercise group who had an- orexia nervosa gained more than a third as much weight and demonstrated significantly reduced obligatory atti- tudes toward exercise compared with those in the com- parison group. The authors acknowledged that these dif- ferences may reflect initial selection biases. In a small study, Chantler and colleagues (2006) ran- domly assigned 14 hospitalized adolescent females to an 8-week program of light resistance training or treatment as usual, with all participants receiving the same caloric intake. The training group showed increased knee and el- bow strength. However, another small (n=22) study by del Valle and colleagues (2010) found few benefits for a low- to moderate-intensity strength training program (two ses- sions/week for 3 months) when combined with treatment as usual (conventional psychotherapy and refeeding) com- pared with treatment as usual alone, even though the in- tervention was well tolerated and did not cause significant weight loss and no deleterious effects were seen. Results of small randomized trials involving treatment approaches that include mindfulness training along with CBT and other therapeutic approaches have been re- ported. Courbasson and colleagues (2011) randomly as- signed 25 outpatients with comorbid mixed eating disor- ders and substance abuse disorders to a 1-year program of either dialectical behavior therapy (DBT) or treatment as usual. Those patients receiving DBT showed so much greater retention (80% vs. 20% at posttreatment) that the protocol was terminated early. The authors suggest that DBT may be effective at keeping such patients in treatment. A review of eight studies of variable quality that used mind- fulness training for the treatment of patients with eating disorders suggests that available evidence supports the value of such interventions (Wanden-Berghe et al. 2011). Other therapies for anorexia nervosa and related con- ditions that have been studied include spirituality focused group therapy, eye movement desensitization and repro- cessing (EMDR), yoga, and body awareness therapy. Available studies on these therapies, as described below, have design limitations. In one randomized, controlled study conducted at a treatment center that provides Christian therapy, 122 fe- male inpatients with mixed eating disorder diagnoses were randomly assigned to treatment as usual plus either spirituality focused group therapy or cognitive and emo- tional group therapy. The spirituality group was reported to have a faster therapeutic response (Richards et al. 2006). The authors noted several limitations to the study, including small sample size, small magnitude of effect, and uncertain generalizability beyond the unique study setting (a facility known for promoting spirituality in treatment). As for many psychotherapy research studies, another limitation is possible expectancy bias from both therapists and patients. In another study, 86 women in a residential treatment program were randomly assigned to treatment as usual plus EMDR or treatment as usual only. Those receiving the addition of EMDR reported less distress related to negative body image memories and less body dissatisfac- tion at 3, 6, and 12 months compared with the treatment- as-usual group, but no other differences in body image measures or other clinical outcomes were seen (Bloom- garden and Calogero 2008). Limitations acknowledged by the authors include contamination effects and lack of blinding. In addition, the control group did not receive an active psychotherapy. In a pilot study by Carei et al. (2010), 54 adolescent outpatients with mixed eating disorders were randomly assigned to treatment as usual with or without eight ses- sions of yoga. Although both groups maintained BMI lev- els and reported reduced anxiety and depression scores over time, those in the yoga group demonstrated greater sustained reduction in eating disorder symptoms and de- creased food preoccupation. Limitations of this pilot study include small sample size, anticipation effects from the use of repeated measures, and uncertain generalizabil- ity to inpatient or community samples. In a pilot study by Catalan-Matamoros and colleagues (2011), 28 outpatients with mixed eating disorders who had been symptomatic for less than 5 years were randomly assigned to treatment as usual with or without five ses- sions of basic body awareness therapy. Those patients in the body awareness therapy group showed modest but  6 APA PRACTICE GUIDELINES consistent improvements in measures of body dissatisfac- tion compared with those who received treatment as usual alone. The authors acknowledged that this small study had high dropout rates and was unblinded. In actual practice, clinicians who treat patients with eat- ing disorders, including anorexia nervosa, use a wide array of psychosocial interventions. Tobin and colleagues (2007) surveyed 265 clinicians, who were recruited online and at professional meetings, about the treatment modalities they use. Only 6% of respondents reported they adhered closely to treatment manuals, and 98% indicated they used both behavioral and dynamically informed interventions. Factor analysis suggested theoretically linked dimensions of treat- ment but also dimensions that are common across models. The authors concluded that overlapping of treatment mo- dalities is a common practice, and more studies are needed to assess what clinicians actually do. FAMILY THERAPY The practice guideline strongly recommends family treat- ment for children and adolescents with eating disorders and suggests that family assessment and involvement may be useful for older patients as well. Family therapy of var- ious types for anorexia nervosa continues to be a focus of considerable research. Results continue to provide sup- port for the value of family therapy, but the overall quality of the evidence remains poor. In a Cochrane review, Fisher and colleagues (2010) evaluated the efficacy of family therapy compared with standard and other treatments. Thirteen trials were in- cluded in the analysis. The authors concluded that there is some evidence to suggest that family therapy may be more effective than treatment as usual in the short run, but they cautioned that the few available studies are small and have potential biases. In a review of family therapy for adolescents with an- orexia nervosa, Gardner and Wilkinson (2011) identified six randomized, controlled trials, the large majority with small sample sizes, and concluded that these studies were on the whole weak. In one of the stronger studies (Lock et al. 2010), 121 patients with anorexia nervosa ages 12–18 years were randomly assigned to 24 outpatient hours of family-based therapy or to adolescent-focused individual therapy delivered over 12 months. At the end of treatment no group differences in full remission were seen, but there were more patients in partial remission in the family- based therapy group, and at 6- and 12-month follow-up there were greater rates of full remission in this group. In an earlier study of family-based therapy by Lock and colleagues (2005), 86 adolescents were randomly assigned to receive family-based therapy either short term (10 ses- sions over 6 months) or long term (20 sessions over 12 months). There were no differences in outcome. How- ever, patients with obsessive-compulsive personality dis- order and patients from non-intact families received greater benefit from the longer-term protocol. In this study, more dropouts occurred when patients had comor- bid psychiatric disorders, were older, were assigned to the longer term protocol, or had problematic family behav- iors (Lock et al. 2006). Ball and Mitchell (2004) randomly assigned 25 adoles- cents and young adults with anorexia nervosa who were liv- ing with their families either to a 12-month program in- volving 21–25 sessions of CBT or to behavioral family therapy. Sixty percent of the intent-to-treat group and 72% of completers were rated as having “good outcomes,” with no differences in outcomes seen between the groups. The majority of patients did not achieve symptomatic recovery. In a 5-year follow-up of 40 adolescent patients with an- orexia nervosa who had participated in a randomized study of two forms of family therapy (conjoint or sepa- rated), Eisler and colleagues (2007) found no differences in outcomes. Seventy-two percent of the patients had re- covered. However, patients from families with elevated levels of maternal criticism gained less weight and gener- ally did less well with conjoint family therapy. The inves- tigators suggested that for these families, conjoint therapy should be avoided, at least early on in treatment when raised levels of parental criticism are evident. Finally, Godart and colleagues (2012) randomly as- signed 60 female adolescent patients with anorexia ner- vosa at time of hospital discharge either to 18 months of ambulatory treatment as usual or to treatment as usual augmented with family therapy (1.5 hours every 3–4 weeks) focusing on family dynamic issues and the “here and now” but not on eating behaviors or weight. Fifty-one of the 60 families were intact. Treatment as usual con- sisted of individual consultations, regular interviews in- volving the parents, and individual psychotherapy with another therapist if required. As necessary, psychiatrists prescribed medication, offered parental guidance regard- ing conflicts with daughters, and secured nutritional/di- etetic advice for patients gaining insufficient weight. At 18 months, good outcomes were observed in 40% of the group receiving family therapy versus 17.2% of the group receiving treatment as usual. Parents and other close family members of patients with anorexia nervosa have been found to have high levels of psychological distress, burden, and expressed emotion (EE) (Zabala et al. 2009). Interventions to help these in- dividuals cope with their burdens have been studied. Gro- ver and colleagues (2011) randomly assigned 64 caregivers of individuals with eating disorders, primarily anorexia  Guideline Watch for the Practice Guideline for the Treatment of Patients With Eating Disorders 7 nervosa, to a Web-based CBT program designed to help caregivers plus limited clinician-supported guidance by e- mail or phone or to treatment as usual, consisting of usual support from caregiver organizations. At 4- and 6-month follow-up posttreatment, those patients who participated in the Web-based program reported reduced anxiety and depression, and a trend was observed in reduced EE. The same investigator group (Rhodes et al. 2009) also ran- domly assigned and compared 10 caregivers receiving treatment as usual with 10 who received “carer to carer” (i.e., parent-to-parent) consultations to supplement Maudsley model care. Qualitative analysis showed that those receiving parent-to-parent care felt less alone and more empowered. Further, educational workshops and skills training given to two families together was as effec- tive as individual family therapy (Whitney et al. 2012). PHARMACOTHERAPY The practice guideline describes limited evidence for the use of medications to restore weight, prevent relapse, or treat chronic anorexia nervosa. Evidence for antipsychotic medications, consisting of case series at the time the guideline was developed, now includes some randomized, controlled trials, but the stud- ies have shown mixed results and have methodological limitations, including small sample sizes. In addition, as described in the guideline, these medications have serious potential adverse effects. A task force on eating disorders of the World Federation of Societies of Biological Psychiatry (Aigner et al. 2011) systematically reviewed all studies for the pharmacological treatment of eating disorders published between 1977 and 2010. The task force concluded that Grade B evidence (i.e., limited positive evidence from controlled studies) supports the use of olanzapine for weight gain. Evidence for other second-generation (“atypical”) antipsychotics was deter- mined to be Grade C (positive evidence from uncontrolled studies or case reports/expert opinion). A review by McKnight and Park (2010) of four ran- domized, controlled trials and five open-label trials found limited evidence that olanzapine, quetiapine, and risperi- done may have positive effects on depression, anxiety, and core eating pathology, but insufficient evidence regarding weight gain. The olanzapine studies include a randomized, placebo- controlled trial of 34 patients with anorexia nervosa by Bissada and colleagues (2008), which demonstrated bene- fits for olanzapine in decreasing obsessive symptoms in addition to increasing weight. More recently, Attia and colleagues (2011) randomly assigned 23 outpatients with anorexia nervosa at two different sites either to 8 weeks of olanzapine (2.5 mg/day, up to 10 mg/day as tolerated) or to placebo. Patients receiving olanzapine showed a signif- icantly better gain in BMI. The medication was well tol- erated, and no adverse metabolic effects were observed. However, Kafantaris and colleagues (2011) found no dif- ferences in percentage change in median body weight, rates of weight gain, or improvement in psychological measures 5 or 10 weeks after a small single-site, random- ized, controlled trial of olanzapine versus placebo in 20 adolescent females, 5 of whom did not complete the study. Furthermore, these investigators saw a trend of increasing fasting glucose and insulin levels only in the olanzapine- treated group. Adverse effects were also observed in a study of the metabolic effects of olanzapine by Swenne and Rosling (2011). In this study, 47 adolescents with an- orexia nervosa had increased levels of thyroid-stimulating hormone and prolactin, which the investigators attributed to medication effects rather than to weight gain. Risperidone was studied in a double-blind randomized, controlled trial of 40 hospitalized adolescents with anor- exia nervosa (Hagman et al. 2011). The investigators found no advantage for risperidone (average dose 2.5 mg/day, pre- scribed up to 4 weeks) over placebo for weight restoration. The practice guideline states that although no specific hormone treatments or vitamin supplements have been shown to be helpful for weight restoration, zinc supple- mentation may be useful. The Task Force on Eating Dis- orders of the World Federation of Societies of Biological Psychiatry (Aigner et al. 2011) described the evidence for zinc supplementation as Grade B. In a meta-analysis of four randomized, controlled trials and two cohort studies, Sim and colleagues (2010) concluded that estrogen prep- arations have uncertain benefits for amenorrhea associ- ated with anorexia nervosa and should therefore be avoided. In contrast, results from a randomized, controlled trial by Misra and colleagues (2011) suggest that physiologic es- tradiol replacement is useful in teenage (13– to 18-year- old) girls with anorexia nervosa with low bone density. In this study, 96 mature girls with anorexia nervosa (in whom statural growth was almost complete) were randomly as- signed either to transdermal 17 estradiol (100-mcg patch applied twice weekly) and cyclic progesterone or to pla- cebo for 18 months, while 14 younger girls with anorexia nervosa were randomly assigned to receive very small in- cremental doses of oral ethinyl estradiol (3.75 mcg daily in the first 6 months, 7.5 mcg daily in the second 6 months, and 11.25 mcg daily in the final 6 months) or placebo. The rationale was that unlike oral estrogen, which suppresses insulin-like growth factor-1 (IGF-1) (an important bone trophic factor) when used in doses found in birth control pills, replacement doses of transdermal estradiol and very low incremental oral estrogen doses that mimic the early  8 APA PRACTICE GUIDELINES pubertal rise in estrogen do not suppress IGF-1. Girls with anorexia nervosa randomly assigned to receive this form of physiologic estrogen replacement had a 2.6% in- crease in spine bone density in this study, compared with only 0.3% in girls randomly assigned to receive placebo. This intervention also prevented the decrease in bone density at the hip observed in girls randomly assigned to receive to placebo. The practice guideline states that the limited available evidence on the use of antidepressants for weight gain suggests that they confer no benefit. This position is sup- ported by a Cochrane review by Claudino and colleagues (2006) that identified four randomized, controlled trials. The studies lacked quality information, and the authors concluded that there is no evidence to support the use of antidepressants for weight, eating disorder core pathol- ogy, or associated pathology. Following publication of this review, Walsh and colleagues (2006) reported that in a two-site study, the addition of fluoxetine to CBT follow- ing weight restoration for patients with anorexia nervosa showed no benefit for fluoxetine over placebo. In this study the best predictors of weight maintenance following discharge for anorexia nervosa were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment (Kaplan et al. 2009). OTHER SOMATIC TREATMENTS Janas-Kozik and colleagues (2011) randomly assigned 24 adolescent girls with anorexia nervosa with restrictor sub- type and depressive symptoms to receive additional bright light therapy for 6 weeks. The intervention group had greater improvement in depression, but no difference in BMI was found at 6 weeks. In a randomized, controlled trial of “warming therapy” involving 21 female patients with anorexia nervosa, wearing a heating vest for 3 hours per day for 21 days offered no advantage compared with wear- ing the vest but with the heating function turned off (Bir- mingham et al. 2004). OSTEOPENIA AND OSTEOPOROSIS To treat physiological complications of malnutrition from semistarvation, including osteopenia and osteoporosis, the guideline recommends weight gain through nutri- tional rehabilitation—namely, sufficient intake of dietary protein, carbohydrates, fats, calcium, and vitamin D. Ves- covi and colleagues (2008) recommended the same in a re- view of 26 randomized, controlled trials, cross-sectional studies, and case series of pharmacological and nonphar- macological interventions to treat bone mineral density or bone turnover in women with functional hypothalamic amenorrhea. In another systematic review of treatment for bone loss, Mehler and MacKenzie (2009) found that no good evidence exists to guide medical interventions once loss has occurred. The authors concluded that early detection and weight restoration are therefore of utmost importance. As described earlier in this watch, Misra and colleagues (2011) found beneficial effects of physiologic estrogen re- placement on bone density in adolescent girls with anorexia nervosa. This finding is in contrast to previous studies that reported no beneficial effects of estrogen when given orally as a birth control pill (Strokosch et al. 2006). The guideline does not recommend the use of bisphos- phonates such as alendronate. Golden and colleagues (2005) conducted a randomized, placebo-controlled trial of alendronate for osteopenia in 32 adolescent females with anorexia nervosa. At 1-year follow-up, patients treated with alendronate had increased bone mineral den- sity of the lumbar spine and femoral neck. However, body weight was the most important determinant of bone min- eral density. The authors concluded that further research is needed on the efficacy and long-term safety of alendro- nate. Risedronate, another bisphosphonate, was studied in a trial by Miller and colleagues (2011), in which 77 women with anorexia nervosa were randomly assigned to receive risedronate 35 mg weekly, low-dose testosterone, both, or placebo for 12 months. Compared with placebo, risedro- nate increased bone mineral density in the posteroante- rior spine 3%, the lateral spine 4%, and the hip 2%; tes- tosterone did not increase bone mineral density but increased lean body mass. Few side effects were seen with either therapy. Further studies are needed to weigh the benefits and harms of using risedronate clinically. BULIMIA NERVOSA As for studies about treatments for anorexia nervosa, re- cent studies about treatments for bulimia nervosa were primarily short term and focused on symptom relief rather than recovery. As described in a randomized, controlled trial of CBT by McIntosh and colleagues (2011) that is cited in the discussion below, “a substantial group remains  Guideline Watch for the Practice Guideline for the Treatment of Patients With Eating Disorders 9 unwell in the long term. Definition of recovery impacts markedly on recovery rates” (p. 32). CHOICE OF SETTING The practice guideline recommends outpatient treatment of bulimia nervosa, except when there are complicating fac- tors (e.g., serious general medical problems, suicidal behav- ior, psychosis) or severe disabling symptoms that do not respond to outpatient treatment. Zeeck and colleagues (2009) compared two options for such patients: inpatient and day clinic treatment. In this German study, 55 patients with severe bulimia nervosa were randomly assigned to one of these two settings. At 3 months posttreatment, both set- tings reduced general and specific pathology. The authors noted that more deterioration in bulimic symptoms oc- curred following inpatient than day clinic treatment but de- scribed the results overall as comparable. In a Korean study by Kong (2005), 43 adolescent pa- tients with a mixture of eating disorder symptoms were randomly assigned to day treatment based on a University of Toronto model (as described, for example, by Olmsted et al. 2003) or to a traditional outpatient program that in- cluded CBT, IPT, and/or medication. Patients assigned to the day treatment group showed greater improvement with regard to BMI and binge eating and purging, as well as improved scores on the Eating Disorder Inventory–2, the Beck Depression Inventory, and the Rosenberg Self- Esteem Scale. NUTRITIONAL REHABILITATION Similar to recommendations for patients with anorexia nervosa, the guideline recommends that normalization of nutrition and eating habits is a central goal in the treat- ment of patients with bulimia nervosa. A study by Burton and Stice (2006) suggests that healthy dieting and modest weight loss may not be incompatible with this goal. In this study, 85 women with full and subthreshold bulimia ner- vosa were randomly assigned to a 6-session healthy diet- ing intervention or a wait-list control condition. At 3- month follow-up, the intervention group showed modest weight loss and significant and persistent improvement in bulimic symptoms. While these findings are preliminary and require replication and extension, they suggest that contrary to popular belief controlled dieting behaviors do not necessarily maintain bulimia nervosa. PSYCHOSOCIAL INTERVENTIONS The guideline recommends CBT as the most effective and best-studied intervention for patients with bulimia nervosa. IPT is recommended for patients who do not re- spond to CBT. Studies have continued to demonstrate effectiveness for a variety of CBT- and IPT-oriented in- terventions in both individual and group settings. In ad- dition, studies continue to investigate “self-care” psycho- social programs delivered online or via CD-ROM. In an update of a previous Cochrane review, Hay and colleagues (2009) identified 48 studies of CBT for the treatment of bulimia nervosa. The studies included 3,054 participants. The review supported the efficacy of both CBT and a manual-based CBT designed specifically for patients with bulimia nervosa. Other psychotherapies, particularly IPT in the longer term, were also found to be efficacious. Self-help approaches that used highly struc- tured CBT treatment manuals were described as promis- ing. Exposure and response prevention did not enhance the efficacy of CBT, and the review found that psycho- therapy alone is unlikely to reduce or change body weight in people with bulimia nervosa or similar eating disorders. The authors concluded that there is a small body of evi- dence for the efficacy of CBT in bulimia nervosa and sim- ilar syndromes, but the quality of trials is highly variable and sample sizes are often small. Studies of psychotherapy for bulimia nervosa published since the 2006 practice guideline include those discussed below. Some of these studies were included in the 2009 Cochrane review by Hay and colleagues. As noted in that review, more and larger trials are still needed of all psy- chotherapies. In a study conducted at two sites by Agras and colleagues (2000, referenced in the guideline), 219 patients with bu- limia nervosa were randomly assigned to receive CBT or a version of IPT in which no attention was paid at any stage of treatment to eating habits or attitudes toward weight and shape. The IPT also did not contain any of the spe- cific behavioral or cognitive procedures that characterize CBT, and there was no self-monitoring. All patients did better with CBT than with IPT. Subsequent analyses of the study data have found that among patients who received IPT, blacks did better than whites (Chui et al. 2007), and early change in the frequency of purging was the best pre- dictor of response at 8 months (Fairburn et al. 2004). Several studies have examined the potential value of in- cluding motivational enhancement strategies in treat- ment. Results have been mixed. In a two-phase study, Katzman and colleagues (2010) randomly assigned 225 patients with bulimia nervosa or EDNOS to receive either CBT or motivational enhancement (phase 1), then ran- domly assigned patients to 12 weeks of group or individ- ual CBT (phase 2). At 1- and 2.5-year follow-up, patients across all interventions had improved significantly, with only minor differences among groups.  10 APA PRACTICE GUIDELINES Geller and colleagues (2011) assessed 181 outpatients with eating disorders for motivation pretreatment and then randomly assigned them to five sessions of prepara- tory readiness and motivation therapy or to a wait-list control. At 6-week and 3-month follow-up, both the in- tervention group and the control group showed improve- ments in readiness for change, depression, drive for thin- ness, and bulimia symptoms. Those patients receiving readiness and motivation therapy were found to have less ambivalence toward treatment. To examine the potential utility of a common behavioral intervention for bulimia nervosa, McIntosh and colleagues (2011) randomly assigned 135 patients with bulimia ner- vosa who had received eight sessions of CBT to either re- laxation training or one of two types of exposure with re- sponse prevention: one type focused on pre-binge cues, and the other focused on pre-purge cues. At 5 years, those pa- tients treated with either form of exposure with response prevention were more likely to be abstinent (43% who re- ceived the intervention focused on pre-binge cues, whereas 54% who received the intervention focused on pre-purge cues; the difference was not statistically significant) than those treated with relaxation training (27%). Several studies have examined other factors affecting course and outcome of treatment for bulimia nervosa. Mitchell and colleagues (2004) found that simply telling patients with bulimia nervosa who have achieved absti- nence after a course of CBT to return for additional ses- sions if they fear relapse was not effective for preventing relapse. In this multicenter trial, patients were randomly assigned to follow-up only or to a crisis intervention model. In the follow-up only group, none of the 30 indi- viduals who had relapsed during the study period returned for additional treatment visits. The investigators sug- gested that planned visits or phone calls should be consid- ered as alternative relapse prevention strategies. Rowe and colleagues (2008) compared course and out- come in 134 females with bulimia nervosa who received CBT. Patients included 59 with bulimia nervosa alone, 38 with bulimia nervosa plus borderline personality disorder, and 37 with bulimia nervosa plus other personality disor- ders. No differences in eating-disorder symptomatology or general psychopathology were seen among the groups at 3-year follow-up. Studies have examined the use of telemedicine and the Internet as routes for administration of psychotherapy for bulimia nervosa. In a randomized, controlled trial involving 128 females with bulimia nervosa, treatment with CBT de- livered face-to-face or via telemedicine for 20 weeks was similarly effective (Mitchell et al. 2008), and telemedicine was more cost-effective (Crow et al. 2009). In this study, pa- tients rated therapeutic factors more highly than did ther- apists and accepted telemedicine CBT more easily than face-to-face CBT (Ertelt et al. 2011). In a study of Internet-based CBT plus e-mail support, Sanchez-Ortiz and colleagues (2011) randomly assigned 76 female students with bulimia nervosa or EDNOS to an intervention group or to a wait-list group, who received the intervention after 3 months’ delay. At 3- and 6-month follow-up, those students getting immediate treatment had better outcomes than those assigned to the wait list followed by treatment, suggesting the importance of pro- viding services as soon as possible when problems are identified. SELF-HELP PROGRAMS As described in the guideline, a variety of self-help pro- grams have been studied and shown to be effective for bu- limia nervosa. Studies continue to support the usefulness of self-help programs as well as identify limitations. One such program is “guided self-help,” a CBT-based approach in which patients do much of the treatment on their own, using a workbook, while also receiving some counseling and support from a mental health professional. Several randomized, controlled trials have shown the value of guided self-help and its superiority to wait-list control conditions, including a study by Traviss and col- leagues (2011) of 81 patients with bulimia nervosa or binge-eating disorder. The authors found that guided self-help was significantly more effective than being on the waiting list...