Wendy Spettigue

Evidence-based pharmacotherapy of eating disorders

The objective was to review scientific evidence for efficacy and safety of pharmacotherapy in adults or children with an eating disorder (ED). We conducted a computer search for all randomized controlled trials (RCTs) published between 1960 and May 2010 for treatment of anorexia nervosa (AN), bulimia nervosa (BN) or binge-eating disorder (BED). For drugs for which no RCT was found, open trials or case reports were retrieved. Clinically relevant RCTs in the treatment of AN have used atypical antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and zinc supplementation. Olanzapine demonstrated an adjunctive effect for in-patient treatment of underweight AN patients, and fluoxetine helped prevent relapse in weight-restored AN patients in 1/2 studies. For treatment of BN, controlled studies have used SSRIs, other antidepressants, and mood stabilizers. In 9/11 studies, pharmacotherapy yielded a statistically significant although moderate reduction in binge/purge frequency, and some additional benefits. For BED, RCTs have been conducted using SSRIs and one serotonin norepinephrine reuptake inhibitor (SNRI), mood stabilizers, and anti-obesity medications. In 11/12 studies, there was a statistically significant albeit limited effect of medication. Meta-analyses on efficacy of pharmacotherapy for BN and BED support moderate effect sizes for medication, but generally low recovery rates. Treatment resistance is an inherent feature of AN, where treatment should focus on renourishment plus psychotherapy. For BN and BED, combined treatment with pharmacotherapy and cognitive behaviour therapy has been more effective than either alone. Data on the long-term efficacy of pharmacotherapy for EDs are scarce. Short- and long-term pharmacotherapy of EDs still remains a challenge for the clinician.

Exploring avoidant/restrictive food intake disorder in eating disordered patients: A descriptive study

OBJECTIVEnTo assess and compare clinical characteristics of patients with avoidant/restrictive food intake disorder (ARFID) to those with anorexia nervosa (AN).nnnMETHODnA retrospective review of adolescent eating disorder (ED) patients assessed between 2000 and 2011 that qualified for a diagnosis of ARFID was completed. A matched AN sample was used to compare characteristics between groups.nnnRESULTSnTwo hundred and five patients met inclusion criteria and were reviewed in detail. Of these, 34 (5%) patients met criteria for ARFID. A matched sample of 36 patients with AN was used to draw comparisons. Patients with ARFID were younger than those with AN, more likely to present before age 12, and more likely to be male. Patients in both groups presented at low weights. Common eating-specific behaviors and symptoms in the ARFID group included food avoidance, loss of appetite, abdominal pain, and fear of vomiting. Rates of comorbid psychiatric diagnoses and medical morbidity were high in both groups. Almost 80% of AN patients and one-third of ARFID patients required hospital admission as a result of medical instability. Symptom profiles in 4/34 ARFID patients resulted in eventual reclassification to AN.nnnDISCUSSIONnThis study supports the notion that a small percentage of adolescent patients presenting with restrictive eating disorders meet criteria for ARFID. Patients are younger than average, more likely to be male compared to adolescent AN samples, and have high rates of psychiatric and medical morbidity. The study also suggests that a proportion of patients evolve into AN as treatment progresses.

Factors Influencing Research Drug Trials in Adolescents With Anorexia Nervosa

This study examined factors that contributed to patients eligibility and participation in a randomized controlled trial involving olanzapine for the adjunctive treatment of anorexia nervosa (AN). Factors involving patient eligibility and willingness to participate were systematically recorded for all patients approached to participate. Of the 92 patients that were assessed and treated over the study timeframe, only 27 patients (29%) met full criteria for inclusion, of which just 7 enrolled (26%). The most common reasons for study refusal related to fears associated with medication effects and refusal to consider medication as a treatment option (70%). Factors affecting recruitment in psychopharmacological studies involving AN in youth are discussed.

A Family-Based Eating Disorder Day Treatment Program for Youth: Examining the Clinical and Statistical Significance of Short-Term Treatment Outcomes

This article describes an innovative family-based day treatment program (DTP) for youth with moderate to severe eating disorders. A sample of 65 youth completed a battery of psychological measures pre- and post-treatment and 6 months after program completion. Treatment outcomes were assessed in three main domains: (a) medical stabilization, (b) normalization of eating behavior, and (c) improved psychological functioning. Overall, patients demonstrated statistically significant and clinically meaningful improvements on all outcome measures. Findings indicate that a comprehensive DTP can successfully facilitate positive outcomes in youth with eating disorders and that these improvements can be maintained 6 months post-treatment.

A Psycho-Education Intervention for Parents of Adolescents With Eating Disorders: A Randomized Controlled Trial

This study evaluated the efficacy of a 2-hour psycho-education session combined with bi-weekly telephone support in increasing parent/caregiver knowledge about eating disorders, increasing self-efficacy by empowering parents to support their child’s recovery, and decreasing the impact of eating disorder symptoms on the family. The intervention was targeted at parents/caregivers whose child was waiting to be assessed for an eating disorder. Participants included 51 parents/caregivers and 36 youths. The brief intervention successfully increased parent/caregiver knowledge of the illness, feelings of self-efficacy, and help-seeking behaviors. These findings are clinically useful as waiting lists are common in Canada.

The safety of olanzapine in young children: a systematic review and meta-analysis.

BackgroundOlanzapine is frequently prescribed in young children for psychiatric conditions. It may be an option for chemotherapy-induced nausea and vomiting (CINV) control in children. The objective of this review was to describe the safety of olanzapine in children less than 13xa0years of age to determine if safety concerns would be a barrier to its use for CINV prevention.MethodsElectronic searches were performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus. All studies in English reporting adverse effects associated with olanzapine use in children younger than 13xa0years or with a mean/median age less than 13xa0years were included. Adverse outcomes were synthesized for prospective studies.ResultsA total of 47 studies (17 prospective) involving 387 children aged 0.6–18xa0years were included; nine described olanzapine poisonings. Weight gain or sedation were reported in 78xa0% [95xa0% confidence interval (CI) 63–95] and 48xa0% (95xa0% CI 35–67), respectively. Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9xa0% (95xa0% CI 4–21) and 14xa0% (95xa0% CI 7–26), respectively. Elevation in liver function tests or blood glucose abnormalities were reported in 7xa0% (95xa0% CI 2–20) and 4xa0% (95xa0% CI 1–17), respectively. No deaths were attributed to olanzapine.LimitationsNo studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous.ConclusionsMost adverse events associated with olanzapine use in children less than 13xa0years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials.

Building evidence for the use of descriptive subtypes in youth with avoidant restrictive food intake disorder

OBJECTIVEnTo examine characteristics of patients with Avoidant/Restrictive Food Intake Disorder (ARFID) in an effort to identify and describe subtypes of the disorder.nnnMETHODnA retrospective chart review was completed for patients aged 8-17xa0years assessed over a 17-year period.nnnRESULTSnSeventy-seven patients were included in the study, the majority of whom were female (nxa0=xa056, 73%). The average age of patients was 13.7xa0years (SDxa0=xa02.4xa0years). Three specific subtypes of ARFID (aligning with example presentations outlined in the DSM-5) were identified: (a) those with weight loss and/or medical compromise as a consequence of apparent lack of interest in eating (nxa0=xa030, 39%); (b) restriction arising as a result of sensory sensitivity (nxa0=xa014, 18%); and (c) restriction based upon food avoidance and/or fear of aversive consequences of eating (nxa0=xa033, 43%). Clinical characteristics of patients varied depending on the assigned subtype.nnnDISCUSSIONnOur findings highlight the need for further research into the relative merit of subtype-assignment in patients with ARFID and whether such practice would aid in the recommended treatment. Further research is required to understand whether these categories are generalizable and applicable to other samples such as young children or adults with ARFID, and how treatment options might differ according to subtype.

Eating Disorder Symptom Severity Scale: A New Clinician Rated Measure

This study describes the development and validation of the clinician-rated Eating Disorder Symptom Severity Scale (EDS3), created to address a gap in measurement options for youth with eating disorders. The EDS3 is modeled on the Childhood Severity and Acuity of Psychiatric Illness Scales (Lyons, J. S, 1998). Factor analysis revealed a 5-factor solution and accounted for 78% of the variance, and internal consistency within the subscales was good (Cronbach alphas: 0.69 to 0.93). The EDS3 is a valid and reliable measure designed for clinicians to help assess the severity of a youths eating disorder and to facilitate outcomes research.

Treatment of children and adolescents with avoidant/restrictive food intake disorder: a case series examining the feasibility of family therapy and adjunctive treatments

BackgroundTo date, little research has examined the effectiveness of either modified Family-Based Therapy or psychopharmacological treatments for patients diagnosed with avoidant/restrictive food intake disorder (ARFID), and there is little evidence to guide clinicians treating children and adolescents with ARFID.xa0This case series describes the clinical presentations, treatments and outcomes ofxa0six patient diagnosed with ARFID whoxa0werexa0treated sequentiallyxa0by a child psychiatrist and adolescent medicine physician in a hospital-based eating disorder program.xa0Case PresentationsFive out of six cases were female and median age of patients at assessment was 12.9 (SDu2009=u20091.13) years. On average, patients’ percentage of treatment goal weight was 80.5% at initial assessment (SDu2009=u20098.56) and 81.9% (SDu2009=u20097.08) when family therapy began. Cases 1, 2 and 3 were admitted to a specialized inpatient unit at assessment due to medical instability (2) or failed outpatient treatment (1), and all six cases presented with severe co-morbid anxiety. All patients were treated using a combination of medical monitoring, family therapy, medication (including olanzapine, fluoxetine and in two cases cyproheptadine), and cognitive behavioural therapy. At treatment termination, all six patients had achieved their goal weight.ConclusionThese cases illustrate the complex ways in which young patients with ARFID can present, the illness’ effect on development and mental health, and the positive outcomes associated with weight gain and concurrent treatment for co-morbid anxiety disorders.

Comment on: Olanzapine for chemotherapy-induced nausea: Lessons learned from child and adolescent psychiatry

To the Editor: We are responding to a recent commentary regarding olanzapine use for chemotherapy-induced nausea and vomiting (CINV).1 Olanzapine is currently recommended only for the management of breakthrough or refractory CINV in pediatric patients.2 These areweak recommendations based on low or very low quality evidence. Published evidence describing the use of olanzapine for CINV prophylaxis in pediatric oncology patients is not sufficient to recommend its routine use.3 Samsel et al. warn of metabolic effects, sedation, extrapyramidal symptoms, and QTc prolongation in pediatric patients receiving long-term olanzapine. We are apprehensive that the safety concerns voiced by Samsel et al. may create unnecessary barriers to the shortterm use of olanzapine for pediatric patients who experience CINV despite administration of clinical practice guideline (CPG)-consistent prophylaxis. Whenweighing the risks andbenefits of olanzapineas anantiemetic in pediatric patients, consideration of its safety in pediatric psychiatry and its efficacy in adult oncology is important. In a meta-analysis describing adverse effects associated with olanzapine use in pediatric patients with psychiatric conditions, the adverse effects most commonly reportedwereweight gain and sedation.4 Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9% (95%CI 4-21) and 14% (95% CI 7-26), respectively. QTc prolongation was not observed in any patient with electrocardiogram abnormalities. In descriptions of olanzapine use for CINV prophylaxis in pediatric oncology patients,4,5 olanzapine was well tolerated, with sedation being the most common adverse effect. Changes in body weight were not observed.We are concerned that regular measuring of waist circumference, as recommended by Samsel et al., may be detrimental in youth who have body image concerns. Since QTc prolongation has not been reported in adult patients receiving serotonin-receptor antagonist andolanzapine-containing regimens forCINVprophylaxis,6 we do not believe that a baseline electrocardiogram is required in patients without known risk factors for QTc prolongation. We agree with the suggestion that clinicians be mindful of hyperglycemia in patients receiving olanzapine. Further, an association with olanzapine should be considered in patients with hyperprolactinemia, hyperamylasemia, or elevated hepatic transaminase concentrations. The contribution of olanzapine toCINVprevention in adult patients iswell recognized.6 In adults, olanzapine 10mgPOonce daily is recommended startingwith the first dose of chemotherapy andending3days later.7 Initiation several days before chemotherapy administration is not required. The optimal pediatric olanzapine dose for CINV prophylaxis is unknown. Samsel et al. recommend an olanzapine dose of 1.25 mg or 2.5 mg BID. We have suggested an initial oral olanzapine dose of 0.1mg/kg/dose (maximum: 10mg/dose) once daily beginning just prior to the first chemotherapy dose.5 We do not advocate intramuscular olanzapine administration for CINV treatment or prophylaxis. Randomized controlled trials are required to determine an accurate picture of the benefits and risks of including olanzapine in the antiemetic regimen of pediatric oncology patients. If not being offered in the context of a trial, olanzapine may be offered judiciously to pediatric patients who have failed CPG-consistent CINV prophylaxis and for whom the benefits are likely to outweigh the risks.