Evaluating quality of life in epilepsy: The role of screening for adverse drug effects, depression, and anxiety
Introduction
It is increasingly recognized that optimal epilepsy care is based on managing “more than seizures”, by taking into account consequences and comorbidities of epilepsy at the individual level [1]. Health-related quality of life (QoL) in people with epilepsy (PWE) is known to be influenced by many variables including seizure freedom, comorbid psychiatric problems, and burden of antiepileptic drug (AED) adverse effects, as well as cognitive function, psychosocial factors, and perceived stigma [1], [2], [3]. A recent large study of pharmacoresistant epilepsy showed AED adverse effects and depression symptoms to account for most of the variance of the QOLIE-31 score, whereas epilepsy-related variables such as seizure frequency and epilepsy type had no effect [4]. These results accorded with Gilliam's landmark study that launched the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) [5], a reliable and accurate short self-reported questionnaire that has since been promoted as a multilingual screening tool for major depressive disorder (MDD) in PWE [6].
Given the high prevalence of AED adverse effects and their known impact on QoL, assessment of perceived AED side effects is important [7], but routine screening appears to be rare in practice [1]. Specific screening instruments allow more effective assessment of symptoms than an unstructured interview, and provide a means of quantifying these [8]. The Adverse Events Profile (AEP) is a reliable and accurate self-reported questionnaire that was developed over 20 years ago to evaluate the most common negative AED adverse effects reported by patients taking AED [9], whose routine use in the epilepsy clinical setting has been advocated [8], and which has now been validated in Spanish [10], Chinese [11], Portuguese [12], Korean [13], and Bulgarian [14] language versions.
Apart from AED effects, depression has emerged as the other main determinant of QoL in epilepsy [4], [5]. However, anxiety is increasingly recognized to be highly prevalent and disabling, with a significant, independent effect on QoL that appears to be at least as great as that of depression [15], [16], [17], [18]. Indeed, anxiety disorders have recently been highlighted as an important and relatively “neglected” comorbidity in epilepsy [19]. In order to promote screening for generalized anxiety disorder (GAD), the most frequent anxiety disorder in PWE, the Neuropsychiatry Commission of the International League Against Epilepsy (ILAE) has encouraged multilanguage validation of the GAD-7 questionnaire, a reliable and accurate short self-reported questionnaire to diagnose GAD in epilepsy [20]. While MDD and GAD are often related, and may have some overlapping symptoms as well as overlap with AED effects [19], the GAD-7 and NDDI-E questionnaires have been shown to provide different information and are thus, well-suited as complementary instruments for rapid screening in the clinical setting [20]. The coexistence of anxiety and depressive disorders in epilepsy appears particularly detrimental [16], being associated with higher rates of suicidal ideation [21] and poorer QoL [16], although information on prevalence of this group is still quite scarce [19]. Individually, anxiety and depressive disorders are each associated with increased reported adverse effects of AED [22]. The interactions between AED effects, anxiety, and depression and their effect on the QoL in PWE are recognized to be complex [22], [23] with, in addition, some evidence of sex differences in clinical expression [24]. However, very few previous studies have simultaneously examined all of these variables. In addition, existing studies show quite heterogeneous methodology, with most using screening instruments that evaluate depressive ± anxiety symptoms (using validated scales such as the Beck Depression Inventory (BDI) or the Hospital Anxiety and Depression Scale), and a smaller number identifying the presence or absence of a specific diagnostic condition (MDD or GAD as comorbid psychiatric disorder associated with epilepsy) using criterion-based structured interview such as the MINI (see Table 1). It should be borne in mind that screening instruments, while often providing valuable data, should not be used and interpreted as psychiatric diagnoses [32].
In order to evaluate interactions between QoL, depression, anxiety, and AED adverse effects in a population of people with epilepsy (PWE), we used validated standard screening tools (NDDI-E, GAD-7, AEP, and QOLIE-31). Dimensional (depressive and anxiety symptoms) and categorical (MDD and GAD) analyses were performed to investigate interactions between QoL and AEP. No French version of the AEP was available, so we also assessed the validity and reliability of a translated version.
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Participants
People with epilepsy (PWE) were recruited from the Clinical Neurophysiology Department of the Timone University Hospital, Marseille and the Hôpital Henri Gastaut, Marseille (these 2 centers forming part of an integrated specialist tertiary epilepsy service) over an 11-month period (November 2014–September 2015). Inclusion criteria were the following: native French-speaking adult patients (> 18 years) with any type of active epilepsy according to the ILAE criteria, treated or not by antiepileptic
Description of the population
A total of 132 native French speakers with epilepsy were included. None of the patients reported any difficulties in understanding the items of the AEP.
The mean age was 38.83 years (SD = 13.84, range: [18–70] years); 65.9% (87) were women; 58.3% (77) were employed, and 49.2 (65) were married.
Concerning epilepsy, 76.5% had focal epilepsy (101) of which 48.5% (64) were temporal lobe epilepsies. Only 3 subjects were untreated by antiepileptic drugs. The mean age of onset of epilepsy was 20.35 (SD =
Discussion
This study shows that the combination of three standard tools designed for rapid screening (NDDI-E, GAD-7, and AEP) has a strong power for evaluating the quality of life in PWE. This study, firstly, highlights the incremental power of the NDDI-E, the GAD-7, and the AEP to explain variance in overall QoL scores in PWE; secondly, it demonstrates the differential effects of these factors (depression symptoms, anxiety symptoms, and AED effects) on QOLIE-31 subscales; and thirdly, it confirms, from
Conclusion
Overall, our results highlight the usefulness of specific screening tools (NDDI-E for MDD, GAD-7 for GAD, and AEP for AED effects) designed for the population with epilepsy; and emphasize the importance of interictal symptoms and signs, especially those related to depressive and anxiety symptoms and/or AED adverse effects, as the most important determinants of QoL in epilepsy [39], [40]. Thus, screening tools that facilitate detection and management of interictal adverse drug effects,
Conflict of interest
None of the authors has any conflict of interest to disclose.
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Acknowledgments
This paper has been carried out within the Federation Hospitalo-Universitaire (FHU) EPINEXT thanks to the support of the A*MIDEX project (ANR-11-IDEX-0001-02) funded by the “Investissements d'Avenir” French Government program managed by the French National Research Agency (ANR).
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