Epilepsy & Behavior 144 (2023) 109253 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh Clinical relevance of interictal dysphoric disorder and its impact on quality of life in drug-resistant epilepsy E. Monteagudo-Gimeno a,b,⇑, R. Sánchez-González c,d, J. Raduà-Castaño e,f,g,h,i, L. Fortea-González e,g,j, T. Boget-Llucià e,j,k, M. Carreño-Martínez e,j,k, A. Donaire-Pedraza e,j,k, N. Bargalló-Alabart e,k, X. Setoain-Perego e,j,k,l, J. Rumià-Arboix j,k, A. Bulbena-Vilarrasa a,c, L. Pintor-Pérez e,j,m a Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Spain b Benito Menni Mental HealthCare Complex, Sant Boi de Llobregat, Barcelona, Spain c Department of Psychiatry, Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona, Spain d IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain e Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, Spain f FIDMAG Research Foundation, Sant Boi de Llobregat, Barcelona, Spain g Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain h Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden i Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK j Clinical Institute of Neurosciences, Hospital Clinic of Barcelona, Barcelona, Spain k Epilepsy Unit, Neurology Department, Hospital Clinic of Barcelona, Barcelona, Spain l Biomedical Imaging Group, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain m Consultation-Liaison Service, Department of Psychiatry, Institut de Neurociències. Universitat de Barcelona, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain a r t i c l e i n f o a b s t r a c t Article history: Objective: This study aims to assess the prevalence of Interictal Dysphoric Disorder (IDD) in drug- Received 3 March 2023 resistant epilepsy (DRE) and to describe its clinical and psychopathological profile, including personality, Revised 28 April 2023 as well as its impact on quality of life (QOL). Accepted 28 April 2023 Method: A retrospective cross-sectional study from an Epilepsy Unit from January 2007 to December Available online 14 May 2023 2017. All patients were diagnosed with DRE. Patients underwent a battery of tests (HADS, SCL-90R, PDQ-4+, QOLIE-31) and a psychiatrist assessed the presence of Axis-I disorders and IDD. Statistical pro- Keywords: cedures were carried out using R-4.0.1 software. Drug-Resistant Epilepsy Psychopathology Results: A total of 282 patients were included. A statistically significant association was found between Interictal Dysphoric Disorder IDD and mood and anxiety disorders (p < 0.001 and p < 0.05 respectively), and between IDD and higher scores in all HADS and SCL-90-R items compared to subjects without IDD (p < 0.001). A statistically sig- nificant association was also found between IDD and obsessive–compulsive, borderline and depressive personality disorder (p < 0.05). Scores in all QOLIE-31 items except for ‘medication effects’ were signifi- cantly lower in subjects with IDD compared with subjects without IDD (p < 0.001). Conclusions: In DRE, IDD subjects show differences in the psychopathological profile and QOL scores com- pared to subjects without a diagnosis of IDD. An early diagnosis of IDD could facilitate prompt interven- tions which might positively impact QOL. Ó 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Abbreviations: DRE, Drug-resistant epilepsy; HADS, Hospital Anxiety and Depression Scale; IDD, Interictal Dysphoric Disorder; ILAE, International League Against Epilepsy; PD, Psychiatric disorder; PDQ-4+, Personality Diagnostic Questionnaire-4+; QOL, Quality of life; QOLIE-31, Quality of Life in Epilepsy Inventory-31; QOLIET, QOLIE-31overall score; SCID-IV, Structured Clinical Interview for DSM-IV; SCL-90R, Symptom Checklist-90-R questionnaire. ⇑ Corresponding author at: Department of Psychiatry and Legal Medicine, School of Medicine, Universitat Autònoma de Barcelona, Edifici M 08193 Bellaterra, Cerdanyola del Vallès, Spain. E-mail addresses: emonteagudo.hbmenni@hospitalarias.es (E. Monteagudo-Gimeno), rsanchezgonzalez@psmar.cat (R. Sánchez-González), radua@recerca.clinic.cat (J. Raduà-Castaño), lfortea@recerca.clinic.cat (L. Fortea-González), tboget@clinic.cat (T. Boget-Llucià), mcarreno@clinic.cat (M. Carreño-Martínez), jdonaire@clinic.cat (A. Donaire-Pedraza), bargallo@clinic.cat (N. Bargalló-Alabart), setoain@clinic.cat (X. Setoain-Perego), jrumia@clinic.cat (J. Rumià-Arboix), antoni.bulbena@uab.cat (A. Bulbena- Vilarrasa), lpintor@clinic.cat (L. Pintor-Pérez). https://doi.org/10.1016/j.yebeh.2023.109253 1525-5050/Ó 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). E. Monteagudo-Gimeno, R. Sánchez-González, J. Raduà-Castaño et al. Epilepsy & Behavior 144 (2023) 109253 1. Introduction The study was approved by the Human Research Ethics Com- mittee of University Hospital Clínic de Barcelona. All patients were Epilepsy is a major health problem as studies point to an esti- recruited upon written consent. mated prevalence rate of 6.38 per 1,000 persons [1]. Drug- resistant epilepsy (DRE) accounts for around 30% of patients with 2.2. Assessment epilepsy [2,3] and implies most of the burden of epilepsy in the population as a result of psychological dysfunction, social stigma- During the subjects’ admission to the Epilepsy Unit, they were tization, cognitive deficits, reduced quality of life, increased risk evaluated by neurologists, psychiatrists, and neuropsychologists. of mortality and presence of comorbid illnesses [4,5]. They all underwent video-encephalography monitoring and com- Among comorbidities, special focus must be placed on Interictal prehensive neuropsychological testing. Sociodemographic infor- Dysphoric Disorder (IDD), the concept of which primarily derives mation (age, gender, education level, employment) and epilepsy from Kraepelin and Bleuler’s observations of patients with characteristics (frequency of seizures, age of onset, frequency, untreated epilepsy [6,7]. The term IDD was latterly coined by Blu- duration, focus, AEDs, neuroimaging) were extracted from clinical mer and described as a pleomorphic affective disorder that appears records. in epilepsy and is characterized by labile depressive symptoms (depressive mood, anergia, pain, insomnia), labile affective symp- toms (fear, anxiety), and the specific symptoms euphoria and 2.2.1. Psychiatric assessment paroxysmal irritability [8]. These symptoms occur intermittently, Axis-I disorders were assessed by a psychiatrist following the without external triggers, and have a duration that may last from Structured Clinical Interview for DSM-IV (SCID-IV) [16]. Disorders a few hours up to two days, with a rapid beginning and end. The were grouped into four clusters: mood disorders, anxiety disorders, pharmacological treatment for IDD includes antiepileptic drugs, psychotic disorders, and other disorders. antidepressants, and, sometimes, low doses of neuroleptics. Anxiety and depressive symptoms were assessed using the Despite the high variability in epidemiological data, the actual Spanish version of the Hospital Anxiety and Depression Scale prevalence of IDD is expected to be high and it is thought to be pre- (HADS) [17]. This scale was designed to measure anxiety and sent to a higher extent in DRE [9] – some authors even consider it depressive symptoms in non-psychiatric populations during the the key psychiatric syndrome associated with epilepsy [10]. week prior to the evaluation, to facilitate the detection and man- There is a small body of evidence that describes an existing rela- agement of mood and anxiety disorders [18] and has been estab- tionship between IDD, clinical aspects, and quality of life (QOL) in lished as an efficient screening instrument in people with patients with epilepsy [11–13], suggesting that IDD is associated epilepsy [19]. It consists of 14 multiple-choice items divided into with the presence of psychiatric disorders, depressive episodes, anxiety and depression subscales. The items are scored from 0 to and lower QOL. Moreover, no studies have attempted to define or 3 and the final score ranges from 0 to 21. quantify psychiatric symptoms in DRE, such as depression, anxiety, Psychological distress was ascertained by the Spanish version of or personality traits, amongst others, and there are no investiga- the Symptom Checklist-90-R questionnaire (SCL-90R) [20]. This tions on QOL in this specific group of patients with DRE and IDD. scale assesses symptoms over the previous week, and it is com- Also, psychiatric symptoms in epilepsy are often difficult to classify prised of 90 items, rated 0 to 4, divided into nine primary symptom into any of the standardized diagnostic systems, as they might not scales including somatization, obsessive-compulsiveness, interper- meet full diagnostic criteria. This can lead to underdiagnosis and sonal sensitivity, depression, anxiety, hostility, phobic anxiety, undertreatment, and thus lower quality of life, as psychiatric paranoid ideation, and psychoticism. It provides three indexes: symptoms have been proven to be the strongest predictors of the Global Severity Index, which measures overall mental distress, QOL in DRE [14]. the Positive Symptom Total Score, which considers the total num- The current study aimed to assess the occurrence of IDD in DRE ber of symptoms independent of their severity, and the Positive and to describe its clinical and psychopathological profile, includ- Symptom Distress Index, which indicates the measure of the inten- ing personality, as well as its impact on QOL in DRE. sity of symptoms perceived by patients. Higher scores indicate higher psychological distress. Personality was assessed using the Spanish version of the Per- 2. Material and methods sonality Diagnostic Questionnaire-4+ (PDQ-4+) [21,22]. It is a self-report questionnaire developed for the evaluation of personal- We carried out a retrospective cross-sectional study of patients ity disorders based on DSM-IV criteria. It is made up of a total of 99 with DRE from an Epilepsy Unit at University Hospital Clínic de Bar- items distributed throughout 12 subscales where items are celona from January 2007 to December 2017. answered using a yes/no format. It assesses ten specific personality disorders (Paranoid, Schizoid, Schizotypal, Antisocial, Borderline, 2.1. Patients Histrionic, Narcissistic, Avoidant, Dependent, and Obsessive- Compulsive) along with two personality disorders proposed in Adult subjects with DRE that had been admitted to an Epilepsy the DSM-IV Appendix B (Negativistic (Passive-Aggressive) and Unit between January 2007 and December 2017 were enrolled in Depressive). It has demonstrated satisfactory psychometric relia- the study. All patients were considered to have DRE according to bility [23–25]. the definition of the International League Against Epilepsy (ILAE), The presence of an Interictal Dysphoric Disorder was evaluated which defines DRE as ‘‘failure of adequate trials of two tolerated according to the diagnostic criteria established by Blumer [10] fol- and appropriately chosen and used AED schedules (whether as lowing the questions incorporated into the Seizure Questionnaire. monotherapies or in combination) to achieve sustained seizure These require at least three of eight main symptoms -depressive freedom” [15]. Patients were excluded according to the following mood, anergia, pain, insomnia, fear, anxiety, euphoria, or paroxys- criteria: diagnosis of mental retardation, primary sensory or motor mal irritability- of moderate or serious severity, leading to moder- impairment altering test performance, non-Spanish speakers, and ate or severe limitation. The symptoms must have been present in those who had undergone prior intracranial surgery. the previous 12 months. 2 E. Monteagudo-Gimeno, R. Sánchez-González, J. Raduà-Castaño et al. Epilepsy & Behavior 144 (2023) 109253 2.2.2. Quality of life assessment 3.2.4. PDQ Quality of life was evaluated using the Spanish version of the In the analysis of the association between different personality Quality of Life in Epilepsy Inventory-31 (QOLIE-31), which evalu- traits and the presence of IDD diagnosis, scores in the overall clus- ates patients’ subjective feelings towards their quality of life in ter C group, and the subgroups obsessive–compulsive, borderline various aspects related to epilepsy [26,27]. It consists of seven and depressive personality disorder were statistically significantly multi-item subscales that assess the Overall Quality of Life (QOL), higher in IDD patients compared with non-IDD patients. See results energy/fatigue (EF), emotional well-being (EWB), social function- in Table 3. ing (SF), cognition (COG), medication effects (ME) and seizure worry (SW). Each subscale has an item measuring the level of sub- 3.3. Quality of life jective distress of that particular subscale. The overall score ranges from 1 to 100. Higher scores indicate higher quality of life. An In the analysis of the association between QOL and IDD, scores overall score (QOLIET) results from a weighted average of the in all items of QOLIE-31 except for ‘‘medication effects” were sta- multi-item scale scores. tistically significantly lower in subjects with IDD compared with subjects without IDD. Results from the total sample of the evalua- 2.3. Data analysis tion of the quality of life using QOLIE-31 are shown in Table 4. We compared whether patients with IDD differed from patients without IDD in the following variables: the presence of a psychi- 4. Discussion atric disorder (PD) diagnosis according to SCID-IV, three HAD vari- ables, sixteen PDQ variables, thirteen SCL-90R variables, and eight The main finding of our study is that DRE subjects with IDD QOLIE-31 variables. To conduct these comparisons, we used show differences in the clinical and psychopathological profiles chi-squared tests for categorical variables (e.g., PD diagnosis) and compared to subjects without a diagnosis of IDD, and these differ- t-tests for numeric variables (e.g., HADA score). To correct for mul- ences have a relevant impact on QOL, showing lower QOL scores in tiple comparisons, we applied Bonferroni correction within each IDD in comparison with subjects without IDD. scale. Corrected P values < 0.05 were regarded as statistically sig- Firstly, from the scarce previous studies that have estimated the nificant. All statistical procedures were carried out using R-4.0.1 prevalence of IDD in epilepsy (without distinction between DRE software. and not DRE), most results have ranged from 17% to 21.3% [9,12,13,28]. The fact that we have observed a higher occurrence might be explained by the consideration that our sample was com- 3. Results posed only of subjects with DRE. De Araujo et al. [9] estimated a prevalence of 18.4% in a sample of DRE. However, it must be noted 3.1. Sociodemographic and clinical characteristics that they did not perform a diagnosis of IDD if participants met diagnostic criteria for an Axis I disorder according to DSM, which A total number of 282 patients met the inclusion criteria. From we believe may have contributed to the discrepancy among preva- the total sample, 98 patients had a diagnosis of IDD (34.8%), while lences. In our sample, one-third of patients with DRE had a diagno- 184 (65.2%) did not. Sociodemographic and clinical characteristics, sis of IDD, which we consider to be high. Given our results, the along with differences between groups are summarized in Table 1. presence of IDD should always be considered by physicians when The only statistically significant difference found among both attending patients with DRE, in an attempt to reduce its misdiag- groups is marital status. nose and possible undertreatment. Furthermore, it has been suggested that psychiatric symptoma- 3.2. Psychopathological profile tology in epilepsy does not find a place in the current standardized classificatory systems [29]. However, we aimed to evaluate the 3.2.1. SCID-IV association between IDD and PD, in order to characterize the disor- As previously stated, 98 patients had a diagnosis of IDD (34.8%), ders that are most frequently associated with IDD in DRE. Previous 70 (71.4%) of which were diagnosed with a psychiatric disorder studies in epilepsy have found high comorbidity of IDD with other (PD) according to SCID-IV, in contrast to 44 (23.9%) subjects in psychiatric disorders, especially mood and anxiety disorders the group without IDD being diagnosed with a PD (p-value < 0.0 [12,28,30], while some have even encouraged future research to 01), suggesting a higher prevalence of any psychiatric comorbidity validate whether IDD is nosologically independent of other psychi- in IDD patients with an odds ratio (OR) of 7.88. Patients with IDD atric conditions. Nonetheless, no investigations are assessing the were also more likely to have a diagnosis of mood or anxiety disor- presence of IDD and other PD in DRE. We report an association der. See results in Table 2. between IDD and resistant epilepsy and PD, as more than two- thirds of subjects with IDD from our sample (71.4%) had at least one psychiatric diagnosis, indicating that patients with DRE and 3.2.2. HADS IDD are at a higher risk of suffering from comorbid PDs, in partic- In the analysis of the association between depressive and anx- ular anxiety or mood disorders. Previous studies have stated that ious symptoms and IDD, statistically significant differences were psychiatric comorbidities are underrecognized and go untreated found in all HADS items. Scores in all HADS items were higher in in patients with epilepsy [31]. Given the high comorbidity found subjects with IDD compared with subjects without IDD. See results in our study, one of the key points when assessing these patients in Table 3. should be recognizing comorbid psychopathology. Whether existing psychiatric classificatory systems are ade- 3.2.3. SCL-90-R quate or not in epilepsy, a greater understanding of the psy- In the analysis of the association between different psychiatric chopathology in these subjects through psychometric scales symptoms and the presence of IDD diagnosis, scores in all the could also contribute to improving clinical practice in this specific items of SCL-90-R were statistically significantly higher in subjects subgroup of patients. We assessed anxiety and depressive symp- with IDD compared with subjects without IDD. See results in toms using HADS and found statistically significant differences Table 3. between patients with IDD and without IDD, where the group with 3 E. Monteagudo-Gimeno, R. Sánchez-González, J. Raduà-Castaño et al. Epilepsy & Behavior 144 (2023) 109253 Table 1 Sociodemographic and neurological characteristics. Whole sample group IDD group No IDD group Difference (p-value) (N = 282) (N = 98) (N = 184) % Mean sd % Mean sd % Mean sd Sociodemographic Age 38.15 11.93 39.17 12.26 37.6 11.75 0.3 Gender 0.5322 Women 55.7 59.2 53.8 Men 44.3 40.8 46.2 Education 1 1 0.753 Primary 42.2 43.9 41.3 Secondary 42.5 38.8 44 Tertiary 14.9 16.3 14.3 No data 0.7 0.5 1 Occupation 0.3838 Inactive 37.6 41.8 35.3 Housewife/student 16.7 18.4 15.8 Active 45.4 38.8 48.9 No data 0.3 1 0 Marital status Married 53.5 62.2 48.9 0.0239** Divorced/widowed 10.3 13.3 8.7 Single 35.1 23.5 41.3 No data 1 1 1 Neurological Etiology 0.4959 Idiopathic 63.8 66.3 59.2 Secondary 36.2 33.7 40.8 Type of seizures 0.587 Focal onset 69.5 73.5 67.4 Generalized onset 24.8 22.4 26.1 No data 5.7 4.1 6.5 Locus 0.3836 Temporal 48.2 50 47.3 Extratemporal 22 16.3 25 Unestablished 18.1 19.4 17.4 No data 11.7 14.3 10.3 Hemisphere 0.2285 Right 37.9 40.8 36.4 Left 37.3 29.6 41.3 Bilateral 7.4 6.1 8.1 Unknown 4.3 7.1 2.7 No data 13.1 16.3 11.4 Number of seizures per month 0.7543 <1 5 6.1 4.3 1–5 40.4 37.8 41.8 >5 53.5 55.1 52.7 **Statistically significant difference in marital status between patients with and without IDD. Table 2 Association of SCID-IV and IDD diagnoses. Whole sample IDD No IDD Difference Odds Ratio 95% Confidence Interval (N = 282) (N = 98) (N = 184) SCID diagnoses N (%) N (%) N (%) p-value Mood Disorder 64 (22.7) 46 (46.9) 18 (9.8) <0.001 8.40 4.34–16.88 Anxiety Disorder 54 (19.1) 28 (28.6) 26 (14.1) 0.017 2.48 1.30–4.76 Psychosis Disorder 10 (3.5) 6 (6.1) 4 (2.2) 0.285 2.97 0.68–14.58 Other disorders 4 (1.4) 3 (3.1) 1 (0.5) 0.411 5.83 0.46–309.31 Any Disorder 114 (40.4) 70 (71.4) 44 (23.9) <0.001 7.88 4.42–14.41 Estimates in boldface are statistically significant (p < 0.05). IDD showed higher scores in the anxiety and depression subscales, that subjects with IDD scored significantly higher in all subscales as well as in the total scale. Previous literature has shown that DRE compared to those without a diagnosis of IDD. As mentioned in is significantly associated with anxious and depressive symptoms, the introduction, IDD is characterized by eight main symptoms: which are in turn associated with impaired QOL [32], but no stud- depressive mood, anergia, pain, insomnia, fear, anxiety, euphoria, ies have addressed these symptoms in IDD with resistant epilepsy. and paroxysmal irritability [8]. However, our results show signifi- Continuing with this approach, psychological distress was eval- cant differences in symptoms addressed in SCL-90-R that are not uated with SCL-90-R, which has not been used in precedent litera- included in the main assessment established for IDD, such as ture in the assessment of patients with DRE and IDD. We found obsessive-compulsiveness, interpersonal sensitivity, paranoid 4 E. Monteagudo-Gimeno, R. Sánchez-González, J. Raduà-Castaño et al. Epilepsy & Behavior 144 (2023) 109253 Table 3 Psychopathological characteristics. Whole sample IDD No IDD Difference (N = 282) (N = 98) (N = 184) Mean Std Mean Std Mean Std p-value HADS Anxiety 7.5 4.27 10.04 4.18 6.15 3.66 <0.001 Depression 5.12 4.07 7.5 4.49 3.87 3.19 <0.001 Total score 12.62 7.42 17.57 7.58 10.01 5.86 <0.001 SCL-90-R Anxiety 1.16 0.79 1.59 0.82 0.93 0.67 <0.001 Depression 1.45 0.89 1.96 0.90 1.17 0.76 <0.001 Hostility 0.95 0.76 1.25 0.90 0.79 0.62 <0.001 Interpersonal sensitivity 1.20 0.77 1.52 0.82 1.03 0.68 <0.001 Obsessive-compulsiveness 1.76 0.89 2.18 0.91 1.53 0.79 <0.001 Paranoid ideation 1.12 0.83 1.45 0.97 0.94 0.69 <0.001 Phobic anxiety 0.90 0.91 1.29 1.02 0.69 0.77 <0.001 Psychoticism 0.77 0.63 1.04 0.68 0.63 0.55 <0.001 Somatization 1.23 0.84 1.62 0.94 1.02 0.70 <0.001 Additional items 1.24 0.80 1.60 0.84 1.04 0.71 <0.001 Global severity index 1.21 0.68 1.59 0.74 1.00 0.55 <0.001 Positive symptom distress index 2.02 0.54 2.26 0.56 1.89 0.49 <0.001 Total score 50.74 19.80 60.47 17.73 45.47 18.88 <0.001 PDQ Paranoid 38.39 25.93 42.68 28.62 36.07 24.14 1 Schizoid 30.42 21.33 30.62 21.70 30.32 21.21 1 Schizotypal 30.68 21.27 33.40 24.29 29.20 19.37 1 Antisocial 13.69 16.17 16.22 19.47 12.32 13.94 1 Borderline 32.30 21.94 39.46 23.03 28.42 20.38 <0.001 Histrionic 29.40 17.74 32.79 18.99 27.56 16.81 0.693 Narcissistic 23.92 18.63 22.62 18.03 24.63 18.98 1 Avoidant 39.62 25.76 43.42 25.77 37.56 25.61 1 Dependent 26.07 24.15 31.82 24.22 22.96 23.62 0.152 Obsessive-compulsive 44.42 21.70 50.42 22.32 41.17 20.72 0.047 Depressive 50.19 28.04 61.14 26.79 44.26 26.97 <0.001 Negativistic 34.45 21.58 36.58 22.11 33.30 21.27 1 Cluster A 33.73 18.37 36.38 20.75 32.3 16.85 1 Cluster B 25.12 14.02 27.96 15.54 23.58 12.92 0.565 Cluster C 36.42 18.12 41.71 18.01 33.56 17.58 0.023 Total 32.51 14.98 36.41 15.84 30.4 14.1 0.091 Std: standard deviation. Table 4 Quality of life characteristics. Whole sample IDD No IDD Difference (N = 282) (N = 98) (N = 184) Mean Std. Mean Std. Mean Std. p-value QOLIE-31 Cognition 45.91 10.75 41.20 10.01 48.35 10.33 <0.001 Energy/Fatigue 49.61 9.10 45.48 8.60 51.76 8.62 <0.001 Emotional well-being 44.80 10.29 39.99 9.13 47.30 9.99 <0.001 Medication effects 46.22 9.45 44.23 9.67 47.27 9.18 0.112 Overall quality of life 44.37 9.82 41.16 9.55 46.04 9.56 <0.001 Social functioning 43.11 9.33 39.85 8.62 44.81 9.26 <0.001 Seizure worry 43.63 10.08 39.90 8.97 45.57 10.10 <0.001 Total score 43.13 10.06 37.64 9.08 46.03 9.34 <0.001 Std: standard deviation. ideation, and psychoticism. To our knowledge, no previous Moreover, research on how epilepsy can affect neural circuits research has investigated these symptoms in IDD. These results mediating personality has shown that seizures may lead to the possibly support the pleomorphic nature of IDD, which along with development of maladaptive personality traits [33,34]. The pres- the intermittent duration of its symptoms might favor its frequent ence of abnormal personality profiles in patients with epilepsy is failure to meet criteria for standardized diagnostic systems. We high, being more severe in DRE [35]. An interictal personality has believe that this broad range of symptoms has an impact on QOL been described [36], formerly known as Gastaut-Geschwind Syn- and could be considered a predictor of lower QOL [14]. Therefore, drome and frequently found in temporal lobe epilepsy, but there the identification and management of not only anxious and is limited investigation on further personality traits on IDD. Suda depressive symptoms, but a wider range of psychiatric symptoms, et al [12] found no association between IDD and antisocial person- should become a crucial issue when attending to these patients. ality disorder assessed with the Mini-International Neuropsychi- 5 E. Monteagudo-Gimeno, R. Sánchez-González, J. Raduà-Castaño et al. Epilepsy & Behavior 144 (2023) 109253 atric Interview [37] but did not assess other personality disorders Declaration of Competing Interest and the sample was not DRE specific. We evaluated all personality disorders using PDQ-4+ and found an association between IDD and The authors declare that they have no known competing finan- Borderline Personality Disorder, Obsessive-Compulsive Personality cial interests or personal relationships that could have appeared Disorder, and Depressive Personality Disorder. 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[11] do Nascimento PPG, Oliva CH, Ribeiro Franco CM, Mazetto L, Yamashiro AS, de and lacks a control group. Results should not be generalized as it Araújo Filho GM, et al. Transtorno disfórico interictal: Uma comorbidade is a monocentric study. Moreover, the type and duration of AED psiquiátrica frequente entre pacientes com epilepsia acompanhados em dois treatment were not controlled. AEDs have psychotropic effects that serviços terciários. Arq Neuropsiquiatr 2013;71(11):852–5. [12] Suda T, Tatsuzawa Y, Mogi T, Yoshino A. Interictal dysphoric disorder in might result in psychopathological manifestations, being difficult patients with localization-related epilepsy: Diagnostic relationships with to differentiate from symptoms secondary to epilepsy itself. DSM-IV psychiatric disorders and the impact of psychosocial burden. Despite using the Seizure Questionnaire to assess IDD, the Interic- EpilepsyBehav 2016;54:142–7. [13] Tedrus G, de Lima Silva R. Cognitive and clinical variables associated with tal Dysphoric Disorder Inventory [42] could have brought greater interictal dysphoric disorder in patients with epilepsy. Epilepsy Behav consistency to the objective assessment of IDD. Finally, subjects 2018;82:175–8. diagnosed with different types of epilepsy were included in the [14] Johnstone B, Malpas CB, Velakoulis D, Kwan P, O’Brien TJ. Psychiatric symptoms are the strongest predictors of quality of life in patients with study which may lead to certain heterogeneity. However, we con- drug-resistant epilepsy or psychogenic nonepileptic seizures. Epilepsy Behav trolled for types of epilepsy (idiopathic/secondary), types of sei- 2021;117. zures, hemispheres, and locus. [15] Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2009;51 (6):1069–77. 5. 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