Étude personnelle : Etude des modalités d’utilisation et de surveillance des traitements psychotropes chez les patients âgés hospitalisés en psychiatrie en

France

La population âgée est une population ayant une consommation élevée de médicaments psychotropes et notamment de benzodiazépine. Les études précédentes, menées en population générale semblent montrer que les recommandations de bon usage des médicaments psychotropes ne sont pas complètement respectées dans la population âgée. En raison des spécificités de cette population : polypathologie, altération physiologique de l’état de santé lié à l’âge, majoration du risque de la survenue d’effets indésirables, elle apparaît comme particulièrement à risque en cas de non respect des bonnes pratiques d’utilisation de ce type de médicaments. L’usage des médicaments psychotropes concerne plus particulièrement les personnes traitées en psychiatrie pour des troubles aigus et il nous a paru important d’étudier leurs modalités de prescription dans une population particulière, les patients âgés hospitalisés en psychiatrie.

Il s’agit d’une étude transversale observationnelle, menée au Centre Hospitalier Charles Perrens dans les unités du Pôle G05-06 de Psychiatrie d’Adultes Universitaire et dans les unités du Pôle G01-02 de Psychiatrie d’Adultes. Elle concerne les patients de plus de 65 ans, hospitalisés à trois dates déterminées de manière aléatoire et espacées de deux mois, au cours de l’année 2014. Un même patient n’est inclus qu’une seule fois dans l’étude.

L’objectif principal de notre étude était d’étudier le respect des AMM et des recommandations de prescription et d’utilisation des médicaments psychotropes, publiées en

119 France entre 2006 et 2009, au sein d’une population clinique: les personnes âgées admises dans les services de psychiatrie. Nous nous sommes intéressés au respect des recommandations particulières aux sujets âgés et à leurs caractéristiques, en termes d’indication, de posologie, de co-prescription et de surveillance. Notre objectif secondaire était d’identifier les facteurs associés à la non conformité pour chaque classe de psychotrope dans cette population.

Au total 117 patients ont été inclus dans cette étude et les informations ont été recueillies à l’aide du dossier patient informatisé.

Cette étude est actuellement acceptée pour publication dans le journal Fundamental & Clinical Pharmacology.

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Compliance of psychotropic drug prescription with clinical practice guidelines in older in-patients

Running title: Compliance of psychotropic prescription guidelines in older patients

Fanny Etchepare1,2, MSc; Elodie Pambrun1, MSc; Bernard Bégaud1,2,3, MD PhD; Hélène Verdoux1,2,4_{, MD PhD; Marie Tournier}1,2,4_{, MD PhD}

1. INSERM U657. F-33000 Bordeaux. France

2. Univ. de Bordeaux. U657. F-33000 Bordeaux. France 3. Centre Hospitalier Universitaire. F-33000 Bordeaux, France 4. Centre Hospitalier Charles Perrens. F-33000 Bordeaux. France

Correspondence to: Marie Tournier

Centre Hospitalier Charles Perrens, 121 rue de la Béchade, 33076 Bordeaux cedex, France Tel: +33 5 56 56 17 71; Fax: +33 5 56 56 35 46; E-mail: mtournier@ch-perrens.fr

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Abstract

Several practice guidelines were published by French regulatory agencies between 2006 and 2009 to improve psychotropic drug use in older patients. The objectives of the study were to assess compliance with these guidelines in older patients hospitalized in psychiatric units

and to identify characteristics associated with compliance. A cross-sectional study was conducted in 117 patients aged 65 years and older hospitalized in two psychiatric

departments of a public hospital, at three dates randomly chosen between January and May 2014. Medical and sociodemographic characteristics were collected from electronic medical records. In all, 8% of psychotropic prescriptions were compliant with guidelines. 98% of antidepressant prescriptions complied with guidelines for product selection (no tricyclics) and 72% for initial dosage (half of that recommended for younger adults). Regarding benzodiazepines, short half-life drugs were chosen in 73% of treatments, low maintenance dosage was found in 64% of treatments, and a discontinuous administration rhythm was noted in 33% of treatments. Regarding antipsychotics, initial dosage was a quarter of the allowed initial dosage for younger adults in 39% of prescriptions and metabolic blood testing was performed in 17% of prescriptions. Neurological and cognitive tolerance was monitored in 41% and 61% of prescriptions, respectively. Few clinical factors were found to be associated with compliance or noncompliance with guidelines in older psychiatric inpatients. Practice guidelines on psychotropic drug prescription were partially respected in older inpatients. Practitioners should take into account the risks associated with non- recommended patterns of psychotropic drug use in this vulnerable population.

Key words

Psychotropic drugs, practice guidelines, older people, antidepressant, benzodiazepine, antipsychotic

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Abbreviations

ATC: Anatomical Therapeutic Chemical BMI: Body Mass Index

ESA: Etude Sur la santé des Ainés, i.e. Study on the health of seniors ESMEeD: Epidemiology of Mental Disorders

EVA: Epidemiology of Vascular Aging study ICD: International Classification of Disorders MAOIs: Monoamine Oxidase Inhibitors

Paquid: Personnes âgées quid, i.e. older people quid SSRIs: Selective Serotonin Re-uptake Inhibitors TCAs: Tricyclics

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1 Introduction

According to the European Study of the Epidemiology of Mental Disorders (ESMEeD), 23% of French people aged 65 years and over in 2001-2003 had consumed at least one psychotropic drug during the previous year, while the annual prevalence was 19% in six

European countries overall [1, 2]. The prevalence of psychotropic drug use increased between 2005 and 2010 to reach 33% of French women and 14% of French men aged 55 to

75 years [3]. Inadequate use of psychotropic drugs is also frequently observed in this population. For example, the prevalence of antidepressant use was found to be low in older depressed patients despite an increased risk of suicide and somatic morbidity [4]. Duration of antidepressant treatment is often too short and adherence to treatment often inadequate in older people [5]. On the contrary, benzodiazepine treatments are too often continued for long periods despite the risk of dependence, memory impairment and reduced effectiveness over time. Furthermore, they frequently concern non-recommended products such as long half-life drugs [6-8]. Psychotropic drug use is particularly worrying in the older population, as they are more exposed to adverse drug events and to complications of psychiatric conditions such as suicide, undernutrition, dehydration and institutionalization owing to pharmacodynamic changes, reduction in the functional reserve of vital organs with aging and the coexistence of multiple chronic diseases [9-12].

While health regulatory authorities worldwide have published guidelines and warnings regarding psychotropic drugs [13-15], they rarely target older patients. The French health regulatory authorities have published recommendations in recent years to improve the prescription of psychotropic drugs in older patients [16]. Good practice guidelines concerned the use of antidepressant treatment for depressive and anxiety disorders in adults in 2006

[17], the use of benzodiazepine and related drugs in older patients in 2007 and 2008 [4, 18], and the management of disruptive behaviour disorders in Alzheimer's disease and related disorders in 2009 [19]. The regulatory agencies have drawn attention to the deleterious overprescription and off-label use of antipsychotics especially in behavioural disturbances presented by older patients with dementia, and their recommendations have also concerned

5 the use of antipsychotic drugs in these patients [20]. Indeed, although antipsychotics may be effective, they are associated with an increased risk of death, stroke and extra-pyramidal syndrome and it is advisable to reserve these drugs for the most severe cases.

Some studies investigating compliance with these guidelines have been carried out in

older patients [21, 22, 5]-8, 18-23[23]. However, they focused on the duration, adherence and dosage of antidepressant treatments [21, 22, 5], on the duration and selection of drugs

for benzodiazepine treatments [24, 25, 8, 26, 7, 6], or on the metabolic monitoring of patients treated with antipsychotics [27-31]. Few studies have examined the dosage of benzodiazepine treatments and no study to date has explored the rhythm of benzodiazepine administration, the patterns of prescription or the monitoring of neurological and cognitive tolerance in patients treated with antipsychotics. Furthermore, no study has assessed compliance with guidelines in older patients with psychiatric disorders, especially those hospitalized in a psychiatric department who represent the most severe cases, and none has examined all psychotropic drug classes. Yet older patients with psychiatric disorders appear more vulnerable than those without a psychiatric disorder. For example, they are at greater risk of presenting cardiovascular disease [32] and of dying after hospitalization owing to myocardial infarction [33], mainly because they are insufficiently treated and monitored by physicians.

The main objective of the study was to assess the compliance of psychotropic drug prescription with practice guidelines in older patients (65 years and over) who were hospitalized in psychiatric units with regard to the guidelines for older patients published by the French regulatory agencies between 2006 and 2009. The secondary objectives were to identify the characteristics associated with compliance with practice guidelines for each class

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