*Review* **Medication in AN: A Multidisciplinary Overview of Meta-Analyses and Systematic Reviews**

**Corinne Blanchet 1,2,3, Sébastien Guillaume 3,4,5, Flora Bat-Pitault 3,6,7, Marie-Emilie Carles 1, Julia Clarke 3,8,9, Vincent Dodin 3,10,11, Philibert Duriez 3,9,12, Priscille Gerardin 3,13,14, Mouna Hanachi-Guidoum 3,15,16, Sylvain Iceta 3,17,18, Juliane Leger 19,20,21, Bérénice Segrestin 3,17,22, Chantal Stheneur 3,23,24 and Nathalie Godart 3,16,25,26,\***


Received: 15 January 2019; Accepted: 20 February 2019; Published: 25 February 2019

**Abstract:** Drugs are widely prescribed for anorexia nervosa in the nutritional, somatic, and psychiatric fields. There is no systematic overview in the literature, which simultaneously covers all these types of medication. The main aims of this paper are (1) to offer clinicians an overview of the evidence-based data in the literature concerning the medication (psychotropic drugs and medication for somatic and nutritional complications) in the field of anorexia nervosa since the 1960s, (2) to draw practical conclusions for everyday practise and future research. Searches were performed on three online databases, namely MEDLINE, Epistemonikos and Web of Science. Papers published between September 2011 and January 2019 were considered. Evidence-based data were identified from meta-analyses, if there were none, from systematic reviews, and otherwise from trials (randomized or if not open-label studies). Evidence-based results are scarce. No psychotropic medication has proved efficacious in terms of weight gain, and there is only weak data suggesting it can alleviate certain psychiatric symptoms. Concerning nutritional and somatic conditions, while there is no specific, approved medication, it seems essential not to neglect the interest of innovative therapeutic strategies to treat multi-organic comorbidities. In the final section we discuss how to use these medications in the overall approach to the treatment of anorexia nervosa.

**Keywords:** anorexia nervosa; drug-treatment; pharmacotherapy; medication; nutrition; comorbidity; complication

#### **1. Introduction**

Anorexia nervosa (AN) is a severe condition with high morbidity and mortality rates resulting from both somatic and psychiatric aspects of the disorder [1]. International guidelines recommend treatment based on a multidisciplinary approach, including nutritional, somatic, psychiatric, and social aspects [2–5]. This global treatment is mainly based on nutritional and psychotherapeutic approaches associated with the treatment of medical and socio-familial complications. In the National Institute for Health and Care Excellence (NICE) guidelines [4] it is clearly mentioned that medications cannot be seen as the sole treatment for anorexia nervosa (Number 1.3.24 see Table 1).

As stated by Aigner et al. [6] the treatment objectives in AN include weight gain, prevention of weight loss, a change in eating behaviours, reduction of associated psychopathologies (e.g., preoccupations with body image, depression, anxiety, obsessive compulsive symptoms) and the treatment of associated medical conditions (e.g., disturbances of the gonadal axis, infertility, osteoporosis). Medication for its part is used to treat AN symptoms including eating disorder symptoms (eating attitudes, refusal to gain weight, preoccupation about shape and weight, obsessions about food ... ) and psychiatric symptoms (depression, anxiety, obsessions, and compulsions.). In addition, AN patients frequently have severe malnutrition and medical complications that can be treated by medication. Indeed, while the return to a normal weight by re-feeding associated with multidisciplinary care is crucial and enables the correction of many somatic functional disorders, it seems essential not to neglect the usefulness of somatic medication in limiting the short and long-term physical complications, optimizing quality of life and promoting a favourable outcome in all fields affected by AN (somatic, psychiatric and social).

In 2011 the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders [6] concluded that the majority of the drugs to treat AN are used off-label [6]. These drugs are widely prescribed, but not in compliance with international guidelines [7,8], and can therefore be potentially unsafe for patients with AN.

For everyday practice, clinicians need improved recommendations about what medications can be used, for what purpose and in which conditions. Current guidelines give some indications for the use of different medications, but they lack precision and do not define who can be treated, when, and with which medication (as seen in Table 1, NICE recommendations for medication in AN). When

clinicians try to find information in the literature, it is not easy, as there are numerous publications on the subject. For example, since the WFSBP guidelines were established for the pharmacological treatment of eating disorders, there have been around 300 reports on the topic of medication and AN, and no review covering all drugs used in the nutritional, somatic, and psychiatric fields.

The main aim of this work is to offer clinicians a multidisciplinary overview of the evidence-based published literature concerning drug treatments in the field of AN. This overview is based on the conclusions of meta-analyses, failing that on systematic reviews, and otherwise on trials (randomized or if not open-label studies). Unlike other reviews, this one is not restricted to drugs used to treat AN symptoms or psychiatric symptoms, but also includes the treatment of the medical conditions and the nutritional aspects associated with AN.

**Table 1.** Extract from the National Institute for Health and Care Excellence (NICE) recommendations [4] for medication in anorexia nervosa (chapter 1.3) and eating disorders in general including anorexia nervosa (chapter 1.8).

#### **Recommendations**

#### **Medication for anorexia nervosa**

1.3.24 Do not offer medication as the sole treatment for anorexia nervosa.

Dietary advice for people with anorexia nervosa [ . . . ]

1.3.21 Encourage people with anorexia nervosa to take an age-appropriate oral multi-vitamin and multi-mineral supplement until their diet includes enough to meet their dietary reference values.

#### **Comorbid mental health problems**

1.8.12 When deciding in which order to treat an eating disorder and a comorbid mental health condition (in parallel, as part of the same treatment plan or one after the other), take the following into account:




1.8.13 Refer to the NICE guidelines on specific mental health problems for further guidance on treatment.

**Medication risk management**

1.8.14 When prescribing medication for people with an eating disorder, and comorbid mental or physical health conditions, take into account the impact that malnutrition and compensatory behaviours can have on medication effectiveness and the risk of side effects.

1.8.15 When prescribing for people with an eating disorder and comorbidity assess how the eating disorder will affect medication adherence (for example, for medication that can affect body weight).

1.8.16 When prescribing for people with an eating disorder, take into account the risks of medication that can compromise physical health due to pre-existing medical complications.

1.8.17 Offer electrocardiogram (ECG) monitoring for people with an eating disorder who are taking medication that could compromise cardiac functioning (including medication that could cause electrolyte imbalance, bradycardia below 40 beats per minute, hypokalaemia, or a prolonged QT interval).

#### **Substance or medication misuse**

1.8.18 For people with an eating disorder, who are misusing substances, or over-the-counter or prescribed medication, provide treatment for the eating disorder unless the substance misuse is interfering with this treatment.

1.8.19 If substance misuse or medication is interfering with treatment, consider a multidisciplinary approach with substance misuse services.

#### **Growth and development**

1.8.20 Seek specialist paediatric or endocrinology advice for delayed physical development or faltering growth in children and young people with an eating disorder.
