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Drug Prescribing in Child and Adolescent Eating Disorder Services
Abstract
Background: Psychotropic drugs are not recommended for child and adolescent eating disorders, though they are used empirically for symptomatic treatment and co-morbid conditions. Little is known about rates of prescribing or the beneficial and adverse effects.
Objective: To ascertain rates and outcomes of psychotropic drug prescribing in child and adolescent eating disorder services.
Method: Retrospective case note study of eating disorder cases (n = 308), seen in one year in seven specialist UK services, covering indications, response to treatment, beneficial and adverse effects.
Results: Drugs were prescribed for 27%, (mainly anorexia nervosa), 12% before referral to specialist services. The most commonly prescribed drugs were fluoxetine and olanzapine, but 26 different drugs were used. The most common indications were depression, anxiety and ‘pseudo-psychotic’ concerns about weight. Drugs were generally well tolerated, but their effectiveness was uncertain.
Conclusions: Non-specialists commonly prescribe psychotropic medication to this vulnerable group without reference to specialist services. Specialists prescribe regularly on empirical grounds, without apparent undue consequences, though these may be under-reported. A prospective clinical trial would further clarify risks and benefits.
... 7 Despite a lack of guidelines for the use of antidepressant and antipsychotic medications in the treatment of eating disorders (EDs) like AN, 8 9 they are sometimes prescribed to treat the symptoms associated with AN or to treat comorbidities, particularly if there is a less than optimal treatment response with first-line psychological treatments. 10 A retrospective chart review study in the USA investigated the rates of psychopharmacological medication use in adolescents and young people in the USA who were referred to adolescent medicine-based ED programmes for the treatment of EDs. 11 They found that at 1-year follow-up, psychopharmacological medications continue to be prescribed at a high rate (58.7% compared with 20.4% at intake) in adolescents and young people with AN. ...
... 17 18 A previous UK study conducted on drug prescribing in CAED services using case notes found that 26 different drugs were used for AN treatment, with fluoxetine and olanzapine being the most widely used medications. 10 However, large randomised controlled trials, which are needed to support evidence-based olanzapine prescribing, 14 15 19 20 are lacking. The trials range in sample size from 15 to 152 patients in recent years and are not specific to the CAED population of interest. ...
... 16 18 Another study has reported the maximum olanzapine dose used as 7.5 mg/day in 43 adolescent girls aged 10-17 years old, of whom 31 were diagnosed with AN. 17 Similarly, Gowers et al found that the median dose of olanzapine prescribed was 7.5 mg/day, with doses ranging from 1.2 to 20 mg/day in some cases. 10 These differences in dosage could be due to a lack in guidelines on psychotropic treatment in AN and are based on empirical judgements and experiences of the CAED psychiatrists. ...
Objectives
To survey current prescribing practices of psychotropic drugs by child and adolescent eating disorder (CAED) psychiatrists in the treatment of anorexia nervosa (AN).
Design
Cross-sectional self-administered survey.
Setting
All children and young people eating disorder services (CYP EDS) in England during a national training programme.
Participants
44 CAED psychiatrists practising in CYP EDS in England.
Primary and secondary outcome measures
CAED psychiatrists completed a questionnaire regarding the pattern of psychopharmacological care in AN that they provide and the medication treatment pattern at their CYP EDS. Secondary outcome measures included the process of continuing pharmacotherapy from secondary care to primary care.
Results
Of the 77 CYP EDS representing every team in England, 44 teams represented by a CAED psychiatrist responded, despite 13 having no psychiatrists in post at the time of the study (response rate 69%). Most (40%) respondents estimated that <10% of patients with AN were prescribed psychotropic medications. Olanzapine was reported as the most commonly prescribed medication for AN by 38% of the respondents, followed by fluoxetine (29%) and sertraline (10%). The most common minimum olanzapine initiation dose in this study was at 2.5 mg/day for a duration of 2–4 weeks, reaching a maximum dose of 5 mg/day. Most (68%) reviewed medications every week (30%) or every 2 weeks (38%). Over 50% of the respondents reported continuation of olanzapine prescribing within the CYP EDS teams.
Conclusions
This nationally representative survey showed that despite a lack of evidence, psychotropic medications are commonly prescribed to a minority of patients, most frequently, olanzapine. Further evidence is needed on which patients may potentially benefit from pharmacotherapy as an adjunct to psychological interventions.
... While the evidence for the efficacy, safety and acceptability of psychotropic medications in adults with EDs is marginal at best, there is even less evidence to support using these medications with children and adolescents. In a retrospective review of 308 child and adolescent cases seen in eating disorder specialist services, Gowers et al. [13] found that 27 % of the sample was prescribed psychotropic medications either before assessment or while in treatment (12 % before assessment and 24 % in treatment). No drugs were prescribed in those below the age of 12. ...
... More than half (56.3 %) of the adults were receiving two or more medications and 32.7 % were receiving three or more psychotropic medications (versus 30.6 and 12.6 % of adolescents, respectively). Furthermore, the widespread use of psychotropic medication with adolescent patients reported here and by Gowers et al. [13] is troubling in light of the lack of evidence-based guidelines for their use in younger patients [7,10]. Whereas Gowers et al. [13] reported that no psychotropic medication was prescribed for patients under 12 years old, we found that two patients in our sample were on antidepressants. ...
... Furthermore, the widespread use of psychotropic medication with adolescent patients reported here and by Gowers et al. [13] is troubling in light of the lack of evidence-based guidelines for their use in younger patients [7,10]. Whereas Gowers et al. [13] reported that no psychotropic medication was prescribed for patients under 12 years old, we found that two patients in our sample were on antidepressants. ...
Aim
The current study examined the frequency of psychotropic prescriptions in a clinical sample of eating disorder (ED) patients confirming earlier research indicating their use is very common but inconsistent with evidence-based recommendations.
Methods
The sample consisted of 501 ED patients admitted to an adult partial hospitalization or adolescent residential program. Patients were divided into two diagnostic groups: anorexia nervosa (AN = 287) and bulimia nervosa (BN = 214), as well as two age groups: adults (age ≥18; N = 318) and adolescents (age <18; N = 183).
Results
Forty-one different psychotropic medications (891 prescriptions in all) were prescribed for 429 patients. Overall, 85.6 % of the total sample reported using one or more psychotropic medications. Of 429 patients using any medications, 46.9 % were on two or more, 25.3 % on three or more, and 11.0 % four or more. Antidepressants were most commonly prescribed (89.5 % of those on medication) with no significant differences in usage patterns based on diagnosis. However, there was greater medication use among adults (89.6 %) compared to adolescents (78.7 %). Results indicate psychotropic medication prescription is more widespread in a clinical sample than in an earlier report screening for osteoporosis in AN women.
Discussion
Treatment recommendations suggest medication should not be the primary treatment for EDs and empirical evidence demonstrates their ineffectiveness in AN. Nevertheless, there were no differences in frequency found between diagnostic groups, confirming little relationship between evidence-based recommendations and actual clinical use for those referred to a specialized ED treatment facility. This study adds new evidence regarding age-based comparisons of psychotropic prescription frequency in clinical EDs and comparison between AN and BN which has not been examined in earlier studies.
... The evidence for the use of pharmacotherapy in C&As is especially insufficient, with mostly case series and open label studies having been reported. In practice, psychotropic agents are frequently used in C&As with AN, with antidepressants the most frequently prescribed, followed by antipsychotics (Gowers et al. 2010). The most common indications for using medication are depression, anxiety and almost delusional concerns regarding weight, with a minority being prescribed medications specifically for the treatment of AN (Gowers et al. 2010). ...
... In practice, psychotropic agents are frequently used in C&As with AN, with antidepressants the most frequently prescribed, followed by antipsychotics (Gowers et al. 2010). The most common indications for using medication are depression, anxiety and almost delusional concerns regarding weight, with a minority being prescribed medications specifically for the treatment of AN (Gowers et al. 2010). Generally, the medications are well tolerated in C&As, but their effectiveness remains uncertain (Gowers et al. 2010). ...
... The most common indications for using medication are depression, anxiety and almost delusional concerns regarding weight, with a minority being prescribed medications specifically for the treatment of AN (Gowers et al. 2010). Generally, the medications are well tolerated in C&As, but their effectiveness remains uncertain (Gowers et al. 2010). ...
In this review we synthesised current literature on the psychopharmacological management of eating disorders (EDs) in children and adolescents (C&As). We focus specifically on anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). The treatment of EDs is determined by physical and psycho-social factors and needs. Pharmacological management should therefore be viewed and incorporated as one component of a multi-disciplinary comprehensive treatment plan for specific requirements of a patient depending on the stage of the disorder. As there is a dearth of studies evaluating the use of psychopharmacology for EDs in C&As we first review the findings from studies performed in adults and then discuss specific studies performed in C&As. We include information from reviews and treatment guidelines to assist the clinician with an approach to the use of psychopharmacological agents in the treatment of EDs in C&As.
... Adverse events were reported for 29% of prescriptions. In a retrospective case note study of 308 ED cases seen in seven specialist UK child and adolescent ED services during 2005 to 2006 [36], psychotropic drugs were prescribed for 27% of patients, mainly those with AN. Fluoxetine and olanzapine were the most common prescriptions, and the most common indications were depression, anxiety and "pseudo-psychotic" concerns about weight. ...
... The prevalence of psychotropic prescription in this study was higher than reported by Gowers et al. [36] or Rossi et al. [35]. It is difficult to compare services operating in different countries, which probably have different patient populations, service resources, and care philosophies. ...
... It is difficult to compare services operating in different countries, which probably have different patient populations, service resources, and care philosophies. In our sample 57% received inpatient treatment at some time compared with 41% in Gowers et al. [36]. These figures are not directly comparable, as different services have different criteria for admission, but may suggest a more severely unwell population in our study. ...
Background
To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service.
Methods
Retrospective case note study of all active eating disorder patients (N = 115) over the period of treatment from referral to time of study (M = 2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects.
Results
Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second generation antipsychotic prescription was associated with subsequent new onset binge eating, in this preliminary observational study. Self-harm by overdose of psychotropics occurred in 11% of patients prescribed medication.
Conclusions
Psychotropic medications were frequently prescribed to adolescent eating disorder patients to treat distressing symptoms. Prospective randomised controlled trials to clarify efficacy and safety are needed. Given the difficulties of conducting clinical trials in this population, services are encouraged to monitor and audit medication safety and efficacy in everyday practice, and to report their findings.
... The medication use rate in this sample was slightly lower than another report of a sample including children and young adults presenting for ED treatment in the United States (45.3%; Mizusaki et al., 2018), but double that of youth with any psychiatric disorder (14%) in a population-based sample (Merikangas et al., 2013) and triple that of treatment-seeking youth who presented to ED programmes in the United Kingdom (Gowers et al., 2010). The use of two or more medications was highly common (40%), comparable to other studies of youth (31%; Garner, Anderson, Keiper, Whynott, & Parker, 2016). ...
... The use of two or more medications was highly common (40%), comparable to other studies of youth (31%; Garner, Anderson, Keiper, Whynott, & Parker, 2016). Of note, prior work suggests that medication use may differ according to ED treatment setting, as lower rates were shown upon entry to adolescentmedicine based hospital and outpatient programmes in the United Kingdom (8%) (Gowers et al., 2010) and United States (12%) (Monge et al., 2015), whereas higher rates were found in an academic medical centre (45%; Mizusaki et al., 2018) and residential ED programmes in the United States (79%; Garner et al., 2016). ...
Objective:
Psychotropic medication use in youth with eating disorders (EDs) is poorly understood despite high co-occurrence of psychiatric disorders. This study examined characteristics associated with medication use in treatment-seeking youth with EDs.
Method:
Youth up to age 18 reported on medication use when presenting to an academic medical center outpatient ED service in the United States. Data presented were collected between 1998-2015.
Results:
The sample (N = 604) was predominantly female (90.6%) with a mean age of 15.3 years (SD = 2.3). Approximately one-third (30%, n = 173) were taking psychotropic medications (40%, n = 70, were taking multiple medications). Antidepressant use was most common (26%, n = 152), followed by atypical antipsychotics (8%, n = 43). Adjusting for co-occurring psychiatric disorders, non-Hispanic Whites who had received prior treatment (psychotherapy, hospitalization) were significantly more likely to be using medication. Longer illness duration and prior treatment were associated with greater antidepressant use. For atypical antipsychotics, prior hospitalization was associated with greater use.
Conclusions:
Findings confirm moderate psychotropic medication use among young patients with EDs despite a lack of clarity regarding optimally effective pharmacologic interventions in this population. Pharmacological trials examining the efficacy of medications for young patients with EDs are warranted to inform future prescribing practice.
... Given that anti-psychotic medications were prescribed to two-thirds of participants included in the current study and that a predominant reason espoused for prescribing anti-psychotic medications within this population is the expected reduction in anxiety and agitation (McKnight and Park, 2010), this null finding warrants further consideration. On the one hand, the administration of the medication to this population is in line with the limited evidence supporting the tolerability of olanzapine in underweight adolescents with AN (Gowers et al., 2010), patients tended not to be discharged from hospital on anti-psychotic medication. Thus, if the antipsychotic medications were not found to effectively reduce individuals' experience of anxiety and were not formulated as part of a long-term treatment, findings from the current study may challenge the increasingly routine administration of antipsychotic medications within this population. ...
The current study aimed to examine the temporal relationship between anxiety symptoms and weight gain for adolescents with anorexia nervosa over the course of an inpatient admission targeting weight restoration through rapid refeeding. Participants were 31 females presenting to a specialist inpatient unit. Psychometric assessments using standardized procedures were conducted to assess co-morbid anxiety diagnoses, and eating disorder symptom severity at admission and discharge. Study protocols were completed on a weekly basis over the course of their admission and were compared with weekly BMI change. Multiple mixed-effects linear models with random intercepts were used to assess change in weight status and psychological variables. Results indicated a reduction in anxiety over the course of hospitalization; however, there was no evidence to support a relationship between anxiety change and weight restoration. The clinical implications of these results are discussed and directions for future research recommended.
... Furthermore, while the majority of the studies accounted for the concurrent use of antidepressant medication, other psychotropic medications were either unaccounted for or participants were excluded on the basis of their use. Evidence around the efficacy of these psychopharmacological interventions is sparse and largely inconclusive [68,69]. Nevertheless, atypical antipsychotic medication is increasingly used in the routine treatment of AN patients [70] as a result of models purporting the utility of the desirable side effect of weight gain as well as their presumed effectiveness in targeting anxiety symptomology. ...
Weight restoration is considered a principal outcome for treatment of Anorexia Nervosa (AN) due to the significant physiological disturbances resultant from acute states of malnutrition. Treatment outcomes for populations with AN are relatively poor, with increasing evidence suggesting that weight restoration alone is insufficient for long-term recovery. Research aimed at understanding the psychological sequaele of AN, in particular during weight restoration, nevertheless remain scarce. This systematic review aimed to evaluate existing research regarding anxiety symptoms during treatment for AN, and the relationship of anxiety symptomology and weight restoration. Twelve articles were identified from a systematic search of three electronic databases (PsycINFO, MEDLINE, and Web of Science), and were eligible for inclusion. Study methodology, results and quality were reviewed. Results regarding change in anxiety symptomology were inconsistent, though evidence did not support a relationship between anxiety change and weight restoration. Reasons for these inconsistencies and limitations of included studies were reviewed. Further research is warranted to elucidate the role of anxiety in AN and its implications for treatment and longer-term outcome.
Eating disorders are common and have a high morbidity and mortality rates. They present with a range of comorbid features and require specialized treatment to achieve a positive outcome. The literature on eating disorders has expanded rapidly in the past 20 years and this article reviews diagnostic and defining features, assessment, etiology, comorbidities and treatment options. Recent advances in the understanding and treatment of eating disorders can be expected to produce positive outcomes in most cases.
Feeding and eating disorders occur across the age range from infancy to adulthood, varying in type and severity. In the case of children and adolescents there has been a relatively poor fit between available diagnostic categories and commonly described clinical presentations, which has contributed to a situation characterized by limited knowledge about epidemiology, prognosis, course and outcome. Some presentations, such as anorexia nervosa and bulimia nervosa, have received greater research attention than others, resulting in a patchy field in terms of evidence based guidance for assessment and intervention. This presents challenges for clinicians treating patients with feeding and eating disturbances, in particular for those who do not regard themselves as specialists in this field. This chapter aims to cover the full range of feeding and eating disorders likely to be seen in child and adolescent mental health care settings from presentations in infancy to those approaching adulthood. These include: anorexia nervosa, bulimia nervosa, binge eating disorder, avoidant/restrictive food intake disorder, pica and rumination disorder. The diagnostic category feeding disorder of infancy or early childhood no longer exists as a specific diagnosis in DSM-5, although feeding disorder of infancy and childhood remains in use in ICD-10, and is therefore also discussed. Our aim is to present the practicing clinician with a concise, scholarly update on the field of child and adolescent feeding and eating disorders and as well as to provide a useful source chapter to guide assessment and intervention.
Background:
During the last 10 years, the use of psychotropic medications in youth with psychiatric disorders, including eating disorders, has significantly increased, but their role in the treatment of adolescent anorexia nervosa is still controversial.
Objective:
This paper aims to review the literature on the use of antidepressants and antipsychotics in adolescents with anorexia nervosa, comparing the efficacy and tolerability in this population with those reported in trials with patients not selected by age.
Method:
A systematic review of the available literature published so far.
Results:
Only few studies met the selection criteria. No strong evidence of beneficial effects was found in using antidepressants and antipsychotics neither in adults nor in adolescents. Side effects were more frequently reported in studies including adolescent population. Among psychotropic drugs, the majority of studies focused on olanzapine, which seems to have, in some studies, only positive effects on body mass index, eating disorder symptoms and functional impairment in both age groups.
Objective:
To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments.
Design:
A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa.
Setting:
Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool.
Participants:
Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group.
Interventions:
Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months.
Main outcome measures:
Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and Adolescent Service Use Schedule (CA-SUS). Satisfaction was measured quantitatively using a questionnaire designed for the study and qualitative (free) responses on it. The questionnaire data were supplemented by qualitative analysis of user and carer focus groups.
Results:
Of the 167 patients randomised, 65% adhered to the allocated treatment. Adherence was lower for inpatient treatment (49%) than for general CAMHS (71%) or specialist outpatient treatment (77%) (p = 0.013). Every subject was traced at both 1 and 2 years, with the main outcome measure completed (through contact with the subject, family members or clinicians), by 94% at 1 year, 93% at 2 years, but only 47% at 5 years. A validated outcome category was assigned for 98% at 1 year, 96% at 2 years and 60% at 5 years. There was significant improvement in all groups at each time point, with the number achieving a good outcome being 19% at 1 year, 33% at 2 years and 64% (of those followed up) at 5 years. Analysis demonstrated no difference in treatment effectiveness of randomisation to inpatient compared with outpatient treatment, or, specialist over generalist treatment at any time point, when baseline characteristics were taken into account. Generalist CAMHS treatment was slightly more expensive over the first 2 years of the study, largely because greater numbers were subsequently admitted to hospital after the initial treatment phase. The specialist outpatient programme was the dominant treatment in terms of incremental cost-effectiveness. Specialist treatments had a higher probability of being more cost-effective than generalist treatments and outpatient treatment had a higher probability of being more cost-effective than inpatient care. Parental satisfaction with treatment was generally good, though better with specialist than generalist treatment. Young people's satisfaction was much more mixed, but again better with specialist treatment, including inpatient care.
Conclusion:
Poor adherence to randomisation (despite initial consent to it), limits the assessment of the treatment effect of inpatient care. However, this study provides little support for lengthy inpatient psychiatric treatment on clinical or health economic grounds. These findings are broadly consistent with existing guidelines on the treatment of anorexia nervosa, which suggest that outpatient treatments should be offered to the majority, with inpatient treatment offered in rare cases, though our findings lend little support to a stepped-care approach in which inpatient care is offered to outpatient non-responders. Outpatient care, supported by brief (medical) inpatient management for correction of acute complications may be a preferable approach. The health economic analysis and user views both support NICE guidelines, which suggest that anorexia nervosa should be managed in specialist services that have experience and expertise in its management. Comprehensive general CAMHS might, however, be well placed to manage milder cases. Further research should focus on the specific components of outpatient psychological therapies. Although family-based treatments are well established, trials have not established their effectiveness compared with good-quality individual psychological therapies and the combination of individual and family approaches is untested. Further research is needed to establish which patients (if any) might respond to inpatient psychiatric treatment when unresponsive to outpatient care, the positive and negative components of it and the optimum length of stay.
Trial registration:
NRR number (National Research Register) N0484056615; Current Controlled Trials ISRCTN39345394.
Context Antidepressant medication is frequently prescribed for patients with anorexia nervosa.
Objective To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.
Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial.
Interventions Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy.
Main Outcome Measures The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.
Results Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64).
Conclusions This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches.
Anorexia nervosa is an often chronic disorder with high morbidity and mortality. Many people relapse after weight restoration. This study was designed to determine whether a selective serotonin reuptake inhibitor would improve outcome and reduce relapse after weight restoration by contributing to maintenance of a healthy normal weight and a reduction of symptoms.
We administered a double-blind placebo-controlled trial of fluoxetine to 35 patients with restricting-type anorexia nervosa. Anorexics were randomly assigned to fluoxetine (n = 16) or a placebo (n = 19) after inpatient weight gain and then were observed as outpatients for 1 year.
Ten of 16 (63%) subjects remained on fluoxetine for a year, whereas only three of 19 (16%) remained on the placebo for a year (p =.006). Those subjects remaining on fluoxetine for a year had reduced relapse as determined by a significant increase in weight and reduction in symptoms.
This study offers preliminary evidence that fluoxetine may be useful in improving outcome and preventing relapse of patients with anorexia nervosa after weight restoration.
Antidepressant medication is frequently prescribed for patients with anorexia nervosa.
To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.
Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial.
Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy.
The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.
Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64).
This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches.
clinicaltrials.gov Identifier: NCT00288574.
This paper aims to review the research literature on the use of medication for eating disorders in children and adolescents.
The literature was reviewed on the pharmacotherapy of anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified (EDNOS). The PubMed database was searched for all articles on medication use in the child and adolescent population using the terms medication, antipsychotic, antidepressant, child, adolescent, eating disorders, anorexia nervosa and bulimia nervosa.
Very little literature exists on the use of medication for the treatment of eating disorders in children and adolescents. There is one retrospective study on the use of SSRIs and some case reports on atypical antipsychotics for children and adolescents with AN, and one small open trial on SSRIs for adolescent BN.
Evidence-based pharmacological treatment for children and adolescents with eating disorders is not yet possible due to the limited number of studies available. It appears that olanzapine and other atypical antipsychotics may prove to be promising for AN at low body weights. It remains uncertain whether SSRIs are helpful in preventing relapse in AN. For children and adolescents with BN, the first line pharmacological option is fluoxetine given the large evidence base of this drug with the adult population and a small open trial of adolescents with BN.
The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects.
Important advances in the treatment of eating disorders, particularly bulimia nervosa, have been made during the past decade. Controlled trials for bulimia nervosa have demonstrated significant benefit from short-term pharmacotherapy with antidepressant medications and from short-term individual and group psychotherapies. Despite these advances, treatment of a patient often involves complex clinical decisions around such issues as choice of initial treatment modality, incomplete resolution of symptoms, and the role of long-term maintenance treatment. To address these questions, this review focuses primarily on summarizing results of published controlled trials of pharmacotherapy in patients with bulimia nervosa. In addition, it outlines the more limited literature on controlled pharmacotherapy trials for anorexia nervosa and for the provisionally identified syndrome of binge eating disorder.
To evaluate fluoxetine efficacy in the treatment of bulimia nervosa patients with or without comorbid depression.
Two parallel, multicenter, double-blind, randomized, placebo-controlled fluoxetine clinical trials were retrospectively analyzed to determine the effect of comorbid depression on bulimia treatment response. Patients were stratified by their 21-item Hamilton Rating Scale for Depression (HAMD21) scores at baseline and by the presence or absence of historical or current depression. Change from baseline to endpoint in the number of binge eating and vomiting episodes was used to assess efficacy.
Fluoxetine 60 mg treatment statistically significantly reduced (p < .05) the median number of binge eating and vomiting episodes. These improvements were independent of baseline HAMD21 score and of historical or current comorbid depression diagnosis.
Fluoxetine 60 mg was effective in treating bulimia nervosa, regardless of the presence or absence of comorbid depression. Fluoxetine's efficacy in treating bulimia nervosa is not simply a secondary effect of its antidepressant properties.
A recent case report suggested that olanzapine resulted in improved weight gain and maintenance, as well as decreased anxiety and agitation, for two hospitalized inpatients with anorexia nervosa (AN). However, a subsequent larger case study did not show a relationship between the use of olanzapine and rate of weight gain among a primarily adult population. The aim of this case report was to clinically examine the therapeutic benefit and tolerability of olanzapine as an adjunctive treatment for four children with AN in a pediatric inpatient setting.
Olanzapine use was associated with considerable weight gain and maintenance, with an average rate of weight gain during hospitalization of 0.99 kg per week. In addition to weight gain, olanzapine was associated with a clinically notable decrease in levels of agitation and premeal anxiety and almost immediate improvement in sleep, general functioning, and overall compliance with treatment. Olanzapine was also well tolerated in these young patients.
These case report findings warrant more controlled research, including randomized controlled studies, to better determine the therapeutic benefits and safety of olanzapine use in children with AN.
Bulimia Nervosa (BN) represents an important public health problem and is related to serious morbidity and even mortality. This review attempted to systematically evaluate the use of antidepressant medications compared with placebo for the treatment of bulimia nervosa.
The primary objective of this review was to determine whether using antidepressant medications was clinically effective for the treatment of bulimia nervosa. The secondary objectives were:(i) to examine whether there was a differential effect for the various classes/types of antidepressants with regard to effectiveness and tolerability(ii) to test the hypothesis that the effect of antidepressants on bulimic symptoms was independent of its effect on depressive symptoms
(1) electronic searches of MEDLINE (1966 to December 2002), EMBASE (1980-December 2002), PsycINFO (to December 2002), LILACS & SCISEARCH (to 2002)(2) the Cochrane Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register - ongoing(3) inspection of the references of all identified trials(4) contact with the pharmaceutical companies and the principal investigator of included trials(5) inspection of the International Journal of Eating Disorders - ongoing
Inclusion criteria: every randomised, placebo-controlled trial in which antidepressant medications were compared to placebo to reduce the symptoms of bulimia nervosa in patients of any age or gender.Quality criteria: reports were considered adequate if they were classified as A or B according to the Cochrane Manual. The Jadad scale, with a cut off of 2 points, was applied to check the validity of the above referred criterion but was not used as an inclusion criterion.
Data were extracted independently by two reviewers for each included trial. Dichotomous data were evaluated by the relative risk with 95% confidence intervals (CI) around this measure, based on the random effects model; continuous data were evaluated by the standardised mean difference with the 95% CI. NNT was calculated using the inverse of the absolute risk reduction.
Currently the review includes 19 trials comparing antidepressants with placebo: 6 trials with TCAs (imipramine, desipramine and amitriptyline), 5 with SSRIs (fluoxetine), 5 with MAOIs (phenelzine, isocarboxazid, moclobemide and brofaromine) and 3 with other classes of drugs (mianserin, trazodone and bupropion). Similar results were obtained in terms of efficacy for these different groups of drugs. The pooled RR for remission of binge episodes was 0.87 (95% CI 0.81-0.93; p<0,001) favouring drugs. The NNT for a mean treatment duration of 8 weeks, taking the non-remission rate in the placebo controls of 92% as a measure of the baseline risk was 9 (95% CI 6 - 16). The RR for clinical improvement, defined as a reduction of 50% or more in binge episodes was 0.63 (95% CI 0.55-0.74) and the NNT for a mean treatment duration of 9 weeks was 4 (95% CI 3 - 6), with a non-improvement rate of 67% in the placebo group. Patients treated with antidepressants were more likely to interrupt prematurely the treatment due to adverse events. Patients treated with TCAs dropped out due to any cause more frequently that patients treated with placebo. The opposite was found for those treated with fluoxetine, suggesting it may be a more acceptable treatment. Independence between antidepressant and anti-bulimic effects could not be evaluated due to incomplete published data.
The use of a single antidepressant agent was clinically effective for the treatment of bulimia nervosa when compared to placebo, with an overall greater remission rate but a higher rate of dropouts. No differential effect regarding efficacy and tolerability among the various classes of antidepressants could be demonstrated.
This open clinical trial examined the feasibility, tolerability, and efficacy of treating adolescents who suffer from bulimia nervosa with fluoxetine.
Ten adolescents, ages 12-18 years received 8 weeks of fluoxetine 60 mg/day with supportive psychotherapy. Primary outcome measures included frequencies of binge eating and purging and ratings on the Clinical Global Impressions-Improvement scale (CGI-I). Secondary outcome measures included self-report measures of eating disorder, depression, and anxiety symptoms. Safety and tolerability of this dose of fluoxetine were also assessed.
Average weekly binges decreased significantly from 4.1 +/- 3.8 to 0 (p < 0.01). Average weekly purges decreased significantly from 6.4 +/- 5.2 to 0.4 +/- 0.9 (p < 0.005). All patients improved on the CGI-I scale, with 20% rated as much improved, 50% improved, and 30% slightly improved. All subjects tolerated the 60-mg dose of fluoxetine, and there were no dropouts due to adverse effects from the medication.
Fluoxetine is generally well tolerated and may be an effective treatment option for adolescents with bulimia nervosa.
Although selective-serotonin-reuptake-inhibitors (SSRI) have been of limited efficacy in the treatment of eating disorder psychopathology and comorbid symptoms of malnourished patients with anorexia nervosa (AN), there is recent data suggesting that SSRI may play a role in preventing relapse among weight-restored patients. Though some previous studies included patients in late adolescence, the vast majority of investigated subjects have been adults. The aim of our retrospective study was to assess the effects of SSRI treatment in partially weight-restored children and adolescents with AN. Thirty two females with AN (mean 14.5+/-1.4 years) were investigated three times during inpatient treatment and at 3- and 6-month follow-up for BMI, eating disorder psychopathology, depressive symptomology, and obsessive-compulsive symptomology. Medication history during inpatient and outpatient treatment was reconstructed at the 6-month follow-up. Nineteen patients received SSRI treatment, while 13 subjects were non-medicated. In comparison to the non-SSRI group, the SSRI group had similar BMI and obsessive-compulsive scores, but higher levels of core eating disorder psychopathology and depressive symptoms at the start of medication. Rates of re-admissions were similar in both groups (SSRI group: 36%, non-SSRI group: 31%, Phi: p=0.72). Repeated measures ANOVA revealed no significant group with time interactions for BMI-SDS (p=0.84), core eating disorder symptoms (ANIS, p=0.79), depression (DIKJ, p=0.75), and obsessive-compulsive (CY-BOCS, p=0.40) scores indicating minimal or no effects of SSRI medication on the course of these variables. In conclusion, our results challenge the efficacy of SSRI medication in the treatment of eating disorder psychopathology as well as depressive and obsessive-compulsive comorbidity in adolescent AN. Clinicians should be chary in prescribing SSRI in adolescent AN unless randomized controlled trials have proofed the benefit of these drugs.
To report the use of Mirtazapine in the treatment of anorexia nervosa with depression primarily regarding its propensity for weight gain.
We present an outpatient case report of anorexia nervosa with depression. The patient's subsequent progress was recorded.
The patient gained 2.5 kg within 3 months to eventually attain a body mass index of 15 after 5 months. Her depression achieved full remission at 6 weeks of treatment.
Mirtazapine is the choice medication in this case. However, treating depression requires caution, given these patients' physical vulnerability. Controlled trials of Mirtazapine for anorexia nervosa are needed.
Eating disorders: Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders
- L A Kotler
- M J Devlin
- M Davies
- B T Walsh
Kotler, L.A., Devlin, M.J., Davies, M., & Walsh, B.T. (2003). An
open trial of fluoxetine for adolescents with bulimia nervosa.
Journal of Child Adolescent Psychopharmacology, 13, 329-335.
National Collaborating Centre for Mental Health (NCCMH)
(2004). Eating disorders: Core interventions in the treatment
and management of anorexia nervosa, bulimia nervosa and
related eating disorders. London: National Institute for
Clinical Excellence.