Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset

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Abstract

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio = 2.04, p = .025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Introduction

Case reports of akathisia have appeared since 1960, when Kruse published three case reports on patients who developed “muscular restlessness” after treatment with phenothiazines (Kruse, 1960). Akathisia is probably the most common and one of the more distressing of the movement disorders associated with antipsychotic drugs (Barnes, 1989). This syndrome consists of a subjective feeling of inner restlessness and the urge to move, as well as objective components (rocking while standing or sitting, lifting feet as if marching on the spot and crossing and uncrossing the legs while sitting). Little is known about the prevalence of akathisia and its risk factors in real-world schizophrenia to date (Rummel-Kluge et al., 2012).

A recent meta-analysis based on 7 randomized controlled trials (N = 998) suggested that second-generation antipsychotics (SGA) outperformed first-generation (FGA) regarding akathisia onset (Zhang et al., 2013). However, another meta-analysis highlighted that studies using scale-derived data for akathisia assessment (Barnes, 1989) were scant (Rummel-Kluge et al., 2012). Moreover, patients included in clinical trials are not always representative of real world patients, especially regarding co-administered medications. Patients with schizophrenia are often administered antipsychotic polytherapy (Correll and Gallego, 2012, Rajan and Clarke, 2013, Young et al., 2015), antidepressants, anxiolytics (Paton et al., 2000), and anticholinergic drugs (Dixon et al., 2001). All these drugs may influence akathisia. Antipsychotic polytherapy has been associated with higher extra-pyramidal side effects including akathisia (Young et al., 2015). Antidepressive agents, especially Selective Serotonin Reuptake Inhibitors (SSRIs), were also described to be associated with increased akathisia (Lane, 1998). Conversely, benzodiazepines (Lima et al., 2002) and anticholinergic drugs (Miller and Fleischhacker, 2000) were suggested as a potent treatment for acute akathisia, though with weak evidence. Most of the evidence is based on akathisia following treatment onset, but studies on akathisia in community-dwelling patients with schizophrenia are scarce to date (see Nyhuis et al., 2010).

The main objective of this study was to determine the prevalence of akathisia and to determine the risk factors and the treatments associated with akathisia in a non-selected community-dwelling sample of patients with schizophrenia.

Section snippets

Study population

The FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia; Schürhoff et al., 2015) cohort is based on a French national network of 10 Schizophrenia Expert Centers (Bordeaux, Clermont-Ferrand, Colombes, Créteil, Grenoble, Lyon, Marseille, Montpellier, Strasbourg, Versailles), set up by a scientific cooperation foundation in France, the FondaMental Foundation (www.fondation-fondamental.org) and created by the French Ministry of Research in order to create a platform that links

Results

Data on akathisia was available for 372 patients with schizophrenia (N = 291) or schizoaffective disorder (N = 81) enrolled in the FACE-SZ cohort and all these patients were included in this study. Table 1 shows demographical and clinical characteristics of the sample. Twenty-one patients were examined in Bordeaux (5.7%), 42 in Clermont-Ferrand (11.3%), 33 in Colombes (8.9%), 92 in Créteil (24.7%), 25 in Grenoble (6.7%), 17 in Lyon (4.6%), 27 in Marseille (7.3%), 30 in Montpellier (8.1%), 39 in

Discussion

Our major findings may be summarized as follows: the global prevalence of akathisia was 18.5% in our community-dwelling sample of patients with schizophrenia. Antipsychotic polytherapy (which included 30.4% of our sample) was associated with a higher risk of akathisia, independently of factors considered to have an influence on akathisia such as the daily-administered dose of antipsychotics or the co-administration of SSRI. Patients taking SGA were at lower risk of akathisia than those taking

Conflicts of interest

None declared.

Contributors

F. Berna and G. Fond wrote the first complete draft of the manuscript, L. Boyer, F. Berna and G. Fond performed the statistical analyses, D. Misdrahi and P-M. Llorca provided substantial modification to the final manuscript. All authors were involved in the collection of the data and approved the final manuscript.

Role of Funding Source

This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), Fondation Fondamental (RTRS Santé Mentale), by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale).

Acknowledgments

We express all our thanks to the nurses, and to the patients who were included in the present study. We thank Hakim Laouamri, and his team (Stéphane Beaufort, Seif Ben Salem and Karmène Souyris) for the development of the FACE-SZ computer interface, data management and quality control. We also thank Sarah King for proofreading the manuscript.

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