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DOI: 10.1016/j.sedeng.2020.03.001
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Available online 4 October 2020
Have mood disorders any influence over seizure control in patients with epilepsy?
¿Influyen los trastornos del ánimo en el control de crisis de pacientes con epilepsia?
Alejandra Fumanal Doménech, Laia Grau López
Corresponding author

Corresponding author.
, Joaquín Broto, Marta Jiménez, Eva Chies Pérez, Olga Fagundez Garzón, Rosa M. López Castilla, Juan Luis Becerra Cuñat
Departamento de Neurociencias, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
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Tables (5)
Table 1. Neurological disorder depression inventory in patients with epilepsy (NDDI). Adapted Spanish version.
Table 2. Generalized Anxiety Disorder [GAD-7]) scale. Adapted Spanish version.
Table 3. Socio-demographic and clinical characteristics of the subjects included in the study (n = 152).
Table 4. Univariate analysis. Seizure control-associated factors.
Table 5. Multivariate analysis. Factors associated independently with poorer seizure control.
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To study the prevalence of mood disorders in patients with epilepsy and their relationship with seizure control.


We conducted an observational and cross-sectional study of epileptic patients treated in our centre from January-2017 to June-2019. We classify patients into two groups according to crisis control: good control (≤1 crisis/month) and poor control (> 1 crisis/month) and we compare the demographic variables (age, sex, employment status and civil status), clinics (epilepsy type, crisis type, years of evolution of epilepsy), therapeutic (antiepileptic, antidepressant and anxiolytic drugs), presence of depression (NDDIE scale), anxiety (GAD7 scale) and quality of life (QOLIE10). The data was collected by doctors and nurses after informed consent was signed.


152 patients participated, 53% were men with a mean age of 44 ± 11 years. Sixty-eight percent (n = 103) had good crisis control and 32% (n = 49) poor control. Thirty-six point six percent had depression (NDDIE > 15) and 42% anxiety (GAD > 10). Sixty percent of patients with depression and 54% with anxiety did not receive antidepressant and/or anxiolytic treatment. The factors associated with poor crisis control were the presence of depression (OR 2.3, P = .02) and a worse quality of life (OR 1.8, P = .01).


The presence of altered mood in patients with epilepsy is frequent. In our series, depression and a worse quality of life were related to worse crisis control.

Mood disorders
Quality of life

Estudiar la prevalencia de trastornos del ánimo en pacientes con epilepsia y su relación con el control de crisis.


Se realizó un estudio observacional y transversal de pacientes epilépticos atendidos en nuestro centro desde enero-2017 a junio-2019. Se clasificó a los pacientes en dos grupos según el control de crisis: buen control (≤1 crisis/mes) y mal control (>1 crisis/mes) y se comparó entre ambos grupos las variables demográficas (edad, sexo, estado laboral y civil), clínicas (tipo epilepsia, tipo crisis, años evolución de epilepsia), terapéuticas (fármacos antiepilépticos, antidepresivos y ansiolíticos), presencia de depresión (escala NDDIE), ansiedad (escala GAD7) y calidad de vida (QOLIE10). Los datos fueron recogidos por médicos y enfermeras tras la firma del consentimiento informado.


Participaron 152 pacientes, el 53% fueron varones con edad media de 44 ± 11 años. El 68% (n = 103) tenía buen control de crisis y el 32% (n = 49) mal control. El 37,6% tuvo depresión (NDDIE > 15) y el 42% ansiedad (GAD > 10). El 60% de los pacientes con depresión y el 54% con ansiedad no recibían tratamiento antidepresivo y/o ansiolítico. Los factores asociados a un mal control de crisis fueron la presencia de depresión (OR 2,3, P = ,02) y una peor calidad de vida (OR 1,8, P = ,01).


La presencia de alteración del estado del ánimo en pacientes con epilepsia es frecuente. En nuestra serie, la depresión y una peor calidad de vida se relacionaron con peor control de crisis.

Palabras clave:
Alteración del estado de ánimo
Calidad de vida
Full Text

The most common psychiatric comorbidity in patients with epilepsy are mood disorders. Between 20%–50% of patients with poorly controlled epilepsy and between 3%–9% of patients with well controlled epilepsy may present with depression at some time in their lives.1 Different studies show that, compared with the general population, people with epilepsy are 5–10 times more likely to suffer from mood disorders.2,3 Furthermore, psychiatric comorbidity in these patients has a severe impact on their quality of life and even greater impact on seizure control.4

The relationship between depression and epilepsy has been described as bidirectional since the incidence and prevalence of depression is greater before and after the epilepsy diagnosis. It has also been suggested that epilepsy and mood disorders have a pathophysiological mechanism in common since there is an overlapping of neuro-anatomical regions that are affected in both diseases, including the temporal region, the orbitofrontal and prefrontal cortex regions and an alteration of specific neurotransmitters in both depression and epilepsy.5

Several authors have reasoned that mood disorders may influence the course of epilepsy. It has been reported that patients with epilepsy and depression have poorer epileptic seizure control,6 are more resistant to anti-epileptic drugs, have lower tolerance to them and do not respond to epilepsy surgery so well.7–9 However, other studies have not made an association between seizure control and depression or anxiety,10 with the result that the impact of mood disorders on seizure control remains unsolved.

Despite demonstrating that depression is a common comorbidity in epileptic patients, they often do not receive antidepressant treatment since some of these drugs reduce seizure threshold. It may now be confirmed that maprotiline, bupropion and tricyclic antidepressants present with higher seizure risk. In contrast, citalopram, fluoxetine and fluvoxamine appear to be lowest risk antidepressants. This effect appears to depend on dose. The frequency of appearance of epileptic seizures ranges between 0.1% and 1.5% at therapeutic doses and may rise to 30% in situations of overdosing.11

The hypothesis of our study is that mood disorders are prevalent in patients with epilepsy and are associated with seizure control. To analyse this hypothesis the presence of anxiety and depression was determined in patients with epilepsy and its association with seizure control was analysis after classifying patients into 2 groups, depending on good or poor seizure control.


A cross-sectional study was conducted with patients with epilepsy who were controlled in the Epilepsy Unit of the Hospital Germans Trias i Pujol (tertiary hospital in Barcelona) between January 2017 and June 2019. Patients over 18 years of age were included, with a diagnosis of focal or generalized epilepsy, and patients with cognitive disability which impeded completion of interviews were excluded.

Patients were recruited consecutively in chronological order to avoid selection bias.

The protocol was approved by the Ethics Committee of our hospital and all respondents voluntarily participated after signing their informed consent. Patient data was treated confidentially.

Clinical evaluation

During routine visits the patients were interviewed and information was collected on demographic variables (age, sex, civil status, employment status) monthly seizure frequency (mean number of seizures per month in the 6 months prior to study inclusion), type of seizure (focal onset aware; focal onset awareness impaired; primary generalised seizure; focal onset with secondary generalisation), the duration of epilepsy (defined as the time from initiation of the regular seizures), the number and type of anti-epilepsy drugs, antidepressants and anxiolytics.

To analyze quality of life, the Quality of Life in Epilepsy Inventory-10 (QOLIE-10) was used. This scale is used to determine the quality of life of patients with epilepsy.12 Standardised results were used between 0–100. The highest scores indicated better quality of life than the lowest ones. The scale used was validated into Spanish.13

To assess the presence of depression, the nursing staff of the Epilepsy Unit used the depression inventory in patients with neurological disorders for epilepsy (NDDI-E) (Table 1).This scale was designed in 2006 as a rapid and effective method of diagnosis of depressive symptoms to be used as routine tools in the assessment of patients with epilepsy.14 It is a Likert type scale which consists of 6 items with 4 possible alternatives of response in keeping with the frequency of the symptom. Depression was considered to be present with a cut-off score above 15; minimum and maximum scores were between 6 and 24 points. This scale was translated and validated by di Capua in a Spanish population in 2014.15

Table 1.

Neurological disorder depression inventory in patients with epilepsy (NDDI). Adapted Spanish version.

  Always or almost always  Sometimes  Rarely  Never 
Everything is a struggle 
Nothing I do is right 
Feel guilty 
I would be better off dead 
Feel frustrated 
Difficulty finding pleasure 

To assess the presence of anxiety the nursing staff from the Epilepsy Unit applied the generalised anxiety disorder scale (GAD7) (Table 2).16 The questionnaire was directly translated from its original source. It contains 7 questions to be scored between 0 and 3, with the possible minimum and maximum scores being 0 and 21, respectively. The following scores were taken as cut-off points: between 0 and 4 no anxiety is present, between 5 and 9 anxiety is mild, between 10 and 14 it is moderate, and between 15 and 21 anxiety is severe. The authors of the scale recommend consultation with a health professional when a score of 10 or higher is obtained.

Table 2.

Generalized Anxiety Disorder [GAD-7]) scale. Adapted Spanish version.

Mark how frequently you have suffered from the following problems in the last fortnight  Never  Less than half of the time  More than half of the time  Almost all the time 
Feeling nervous, anxious or on edge 
Not been able to stop or control worrying 
Worrying too much about different things 
Trouble relaxing 
Being so restless that it is hard to sit still 
Becoming easily irritated or angry 
Feeling afraid as if something awful might happen 

In keeping with the classification specified in previous studies,17 patients were classified into 2 groups depending on seizure control: good control (≤1 seizure/months)and poorer control (>1 seizure/month).

Statistical analysis

The variables were compared between patients with good and poor seizure control. A descriptive analysis was made of the main variables (mean ± standard deviation [SD] and tables of frequency). The chi-square test was used to compare categorical variables and the Student’s t-test and Mann-Whitney U test to compare the continuous variables. Logistic regression analysis with the Enter method was used to determine the independent effect of each variable in seizure control. The statistical package for social sciences SPSS version 18.0 was used and a statistical significance of P < .05.was accepted.


Demographic and clinical characteristics of patients are summarised in Table 3. Out of the 152 patients included, 53% (n = 80) were male. Mean age was 44.3 ± 13.7 years. 90% (n = 137) of patients lived with other people and at least half of them (48%) were actively employed. The mean duration of epilepsy was 16.4 ± 14.8 years. The most common type of epilepsy was extratemporal (43.2%) and most patients presented with focal onset impaired awareness seizures as the most prevalent (39.8%). 14% of patients had refractory epilepsy and the mean frequency of monthly seizure was 2.1 ± 5.4.

Table 3.

Socio-demographic and clinical characteristics of the subjects included in the study (n = 152).

Age (years) (mean ± SD)    44.3 ± 13.7 
Male sex, n (%)80 (53) 
Cohabiting (accompanied)Alone, n (%)  15 (10) 
Accompanied, n (%)  137 (90) 
Active employment status, n (%)Active  73 (48) 
Unemployed  29 (19) 
Disabled  22 (14,7) 
Retired  26 (17) 
Time of evolution, epilepsy (years) (mean ± SD)16.4 ± 14.8 
ype of seizure, n (%)Focal onset awareness  18 (11.6) 
Focal onset impaired awareness  60 (39.8) 
Generalised primary  25 (16.3) 
Generalised secondary  49 (32.3) 
Type of epilepsy, n (%)Generalised  26 (17) 
Temporal  39 (26.1) 
Extratemporal  66 (43.2) 
Multi-regional  10 (6.8) 
Refractory epilepsy, n (%)21 (14) 
Number of anti-epileptic drugs (mean ± SD)2.1 ± .8 
Depression57 (37.6) 
Anxiety64 (42) 
Quality of life (QOLIE-10)51.9 ± 8.6 

68% (n = 103) had good seizure control with a mean frequency of 1 seizure/month and 32% (n = 49) had poorer seizure control with a mean frequency of >1 seizure/month.

Patients received a mean of 2.1 ± .8 anti-epileptic drugs.

37.6% of patients had scores of ≥15 s on the NDDI-E scale, indicating the presence of depression; 42% had scores >10 on the GAD7 scale, indicating the presence of anxiety, and the standardized mean of quality of life (QOLIE-10) was 51.9 ± 8.6.

The percentage of patients with mood disorders who received specific treatment for them was low, since 60% of patients with depression and 54% with anxiety did not receive antidepressant or anxiolytic treatment.

Factors associated with seizure control

Table 4 contains the results of the univariate analysis which was performed to analyse the seizure control-associated variables. It was observed that in the group with the poorest seizure control there was a higher percentage of patients with secondarily generalised focal seizure (P = .001), the patients had greater duration of epilepsy (P = .02) and took more anti-epileptic drugs (P = .001).

Table 4.

Univariate analysis. Seizure control-associated factors.

    Good control (n = 103)  Poorer control (n = 49)  P 
Age (years) (mean ± SD)41.89 ± 15.7  42.83 ± 13.18  .5a 
Male sex, n (%)37 (63.7)  19 (63.3)  .5b 
Cohabiting (accompanied), n (%)25 (43.1)  14 (46.6)  .2b 
Active employment status, n (%)33 (52.4)  14 (46.6)  .2b 
Time of evolution, epilepsy (years) (mean ± SD)13.8 ± 13.6  22.03 ± 15.94  .019a 
Type of seizure, n (%)Focal onset aware  12 (11.6)  2 (6.7%)  [3,0].04a
Focal onset impaired awareness  36 (35)  8 (26.7) 
Generalised primary  31 (30)  3 (3.8) 
Generalised secondary  23 (22.3)  21 (40.3) 
Type of epilepsy, n (%)Generalised  21 (20.3)  5 (9.6)  [3,0].1a
Temporary  35 (34)  18 (34.6) 
Extratemporal  33 (32)  21 (40.3) 
Multi-regional  11 (10.6)  8 (15.3) 
Number of anti-epileptic drugs (mean ± SD)1.02 ± .71  2.7 ± .62  .001a 
Depression, n (%)18 (18)  21 (40,3)  .002b 
Anxiety, n (%)43 (43)  40 (77)  .002b 
Quality of life (QOLIE-10)67.4 ± 6.5  28.3 ± 9.1  .001a 

Statistic: Mann-Whitney U test.


Statistic: Chi-square.

Depression and anxiety were more common in patients with poorer seizure control (40.3% vs. 18%, P = .001 and 77% vs. 43%, P = .001, respectively) and had a worse quality of life (P < .001). There were no differences between the compared groups regarding age, sex, civil status and type of epilepsy.

In the multivariate analysis, the presence of depression (OR 2.3, P = .02) and poorer quality of life (OR 1.8, P = .01) were independently associated with poorer seizure control (Table 5).

Table 5.

Multivariate analysis. Factors associated independently with poorer seizure control.

  OR ( 95% CI)  P 
Years of epilepsy  1.03 (.48–2.25)  .23 
Type of seizure (secondarily generalised)  1.66 (.9–1.9)  .6 
Number of anti-epileptic drugs  1.54 (.67–6.78)  .08 
Depression  2.3 (1.5–7.1)  .02 
Anxiety  1.26 (.85–3.31)  .4 
Poorer quality of life (QOLIE-10)  1.8 (1.1–2.5)  .01 

This study assessed the prevalence of mood disorders in patients with epilepsy and its association with seizure control. The results of this study indicate that mood changes are a common comorbidity in epilepsy, since of the 152 patients analysed, 37.6% suffered from depression and 42% from anxiety. These data coincide with previous results where it was reasoned that mood changes were common in patients with epilepsy with prevalence ranging between 27% and 50%. However, according to population studies, the prevalence of mood disorders is lower, being 20% in women and 12% in men.18

Despite depression being a prevalent disorder in patients with epilepsy, a large proportion of these patients had not been diagnosed or had not received treatment. This under-diagnosis may have been due to the fact that depression in these patients usually presents with atypical traits that do not meet with the DSM-5 criteria. Also, it is uncommon for appropriate anamnesis or screening for these disorders to take place in medical consultations and these symptoms are often interpreted as reactive to the diagnosis of epilepsy.19 In our study, only 40% of the patients with depression and 46% of the patients with anxiety received antidepressant or anxiolytic treatment, and our data concur with other published studies, where less than a quarter of the patients with epilepsy and depression were being treated.20,21

The fact that the patients with epilepsy are undertreated is mostly based on the underdiagnosis of this disorder, due to the absence of appropriate scales or higher care demand. Due to non-identification no appropriate treatment can be initiated. This highlights the need for specialized health personnel (either clinicians or nurses with particular training in epilepsy) to create patient scales to be consulted in the Epilepsy units to detect mood disorders. Also, several studies have described cases of patients with epilepsy treated with tricyclic antidepressants which have reduced seizure threshold. However, the majority of clinical studies have shown that antidepressant drugs are safe22–24 and there are even several studies that show that they may have a positive effect on epilepsy itself, reducing the number of seizures.25

In this study, in the group of patients with the poorest seizure control there was a higher percentage of patients with secondarily generalised focal seizures, the patients had longer epilepsy duration and took a larger number of anti-epileptic drugs. Furthermore, there was a greater probability of suffering from depression and anxiety and a poorer quality of life. After adjusting for these variables, the presence of depression and poorer quality of life maintained an independent association with poorer seizure control. In a review carried out by the Food and Drug Administration it was confirmed that epileptic patients with depression had a higher mean of epileptic seizures per year than epileptic patients without depression26 and this supported the hypothesis that antidepressants could have a protective effect in the development of new seizures.

Recently, studies supporting the bidirectional relationship between epilepsy and depression have been conducted.27 Epilepsy raises the risk of depression due to clinical factors (high frequency of seizure, refractory epilepsy, polytherapy) and due to psychosocial factors such as employment limitations, stress or social stigma resulting from the actual diagnosis of epilepsy. Moreover, patients with a previous diagnosis of depression are at greater risk of presenting with it,28 and it is therefore believed probable that common pathogenic mechanisms exist which facilitate the occurrence of one disease in the presence of the other.29

The significance of identifying depression is that it has a negative impact on the quality of life of patients with epilepsy and this relationship persists, even after controlling other variables such as the frequency of seizure.30

Epilepsy requires multi-disciplinary treatment strategies to address all patient needs, including appropriate control of psychiatric comorbidities and in particular depression and anxiety. It is standard that when a patient with epilepsy is assessed, care focuses on the frequency and severity of the seizure and psychiatric symptoms are frequently underestimated as a result. Approaches solely focusing on seizure control have been proven to be ineffective, and one of the recommended strategies is early determination of psychiatric comorbidities with appropriate screening tools such as the use in our study by medical and nursing staff (GAD7 scale and NDDI-E scale). Once these patients have been identified it is advisable for them to be managed by interdisciplinary teams which include a psychiatrist to confirm the mood disorder diagnosis. Better treatment of epilepsy and mood disorder patients may have a positive impact on seizure control and in the improvement of the patient’s quality of life.

To conclude, there is often a presence of mood changes in epilepsy patients. In our series, depression and poorer quality of life were linked to poorer seizure control.

Conflict of interests

The authors have no conflict of interests to declare.

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Please cite this article as: Fumanal Doménech A, Grau López L, Broto J, Jiménez M, Chies Pérez E, Fagundez Garzón O, et al. ¿Influyen los trastornos del ánimo en el control de crisis de pacientes con epilepsia? Rev Cient Soc Esp Enferm Neurol. 2020. https://doi.org/10.1016/j.sedene.2020.03.001

Copyright © 2020. Sociedad Española de Enfermería Neurológica
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