Introduction
Epilepsy affects all aged people and results in profound physical and psychopathological consequences [
1‐
3]. Notably, comorbid psychiatric conditions are highly prevalent among patients with epilepsy as compared to the general population [
2,
3] suggesting that psychiatric illnesses often accompany the diagnosis of epilepsy [
4], or even precede the onset of the disease [
5]. Moreover, the most common interictal psychiatric disease in epilepsy is depression [
6]. Accordingly, individuals with epilepsy report significantly elevated odds of depression than those without epilepsy, even after adjusting for potential confounders (e.g., age, gender, comorbid physical illnesses [
2]). Among the potential neurobiological determinants, epilepsy-related variables such as duration, frequency and severity of seizures, and medication have been of particular interest [
7]. Therefore, previous investigations have attempted to evaluate the association between the aforementioned risk factors and depression in epilepsy.
Despite depression is a frequent psychiatric condition in individuals with epilepsy, its prevalence is often underestimated [
8]. This evidence seems particularly alarming when considering that some studies reporting depression may exacerbate epilepsy-related symptoms (e.g., fatigue, stress, sleep problems) [
9,
10] and hinder the positive outcomes of epilepsy treatment [
11]. Systematic evidence suggests an overall prevalence of depression of 22.9–23.1% [
12] and a lifetime prevalence for major depression ranging between 8 and 48% in patients with epilepsy [
6]. Depressive symptoms in epilepsy affect patients’ well-being and the clinical course of the disease [
13,
14]. The use of some anti-seizure medications (ASMs) to manage seizures can significantly affect mood by alleviating or exacerbating depressive symptoms [
15]. On the other hand, some ASMs (e.g., GABAergic drugs) have been related to the worsening of mood symptoms in epilepsy [
16,
17].
Predominantly, interest of clinicians focused on identifying valid assessment tools to robustly detect the presence of depressive symptoms among patients with epilepsy [
18]. A recent systematic review on the validity of depression-screening tools in epilepsy reports that Beck Depression Inventory (BDI) [
19] is a complete instrument to evaluate depressive symptoms in people with epilepsy for screening purposes, as compared to other self-report scales [
20]. Studies employing this inventory, and, in particular, its later version (BDI-II) [
21] found that the BDI total score often distinguished depressed from non-depressed participants with epilepsy [
22,
23], confirming its well-recognized sensitivity. Some authors employ a single-item analysis approach in order to investigate the distribution of each specific facet assessed through the BDI and its relationship with epilepsy-related aspects [
24]. The inspection of the single item provides valuable additional information on the core affective, somatic, and cognitive features of depression among individuals with epilepsy.
Hence, in this study, we investigated depressive symptoms in patients with epilepsy visited in a tertiary clinical center, by using the BDI-II with a single-item approach in order to detect the wide spectrum of depressive symptoms in this population of patients. Moreover, considering that gender may influence the prevalence of depression in epilepsy [
25,
26], this study aims to compare depressive symptom patterns according to the BDI-II between female and male patients affected by epilepsy. Consistently with previous evidence [
25], we expected that depressive symptoms would be more accentuated among female patients. Finally, we investigated the possible influence of seizure type, etiology of epilepsy, monthly total seizure count, and ASMs on depressive symptoms.
Discussion
The first aim of the present study was to examine the presence of depressive symptoms in patients with epilepsy visited in a tertiary clinical center, by using the BDI-II with a single-item analysis. This approach is appropriate to examine the distribution of individual item of the BDI-II providing additional information on the core features of depression among individuals with epilepsy [
24].
Results showed that around 39% of participants reported clinically defined depressive symptoms, suggesting that an association between depression and epilepsy should be inferred. This finding is consistent with previous studies reporting similar percentage rates in Italian samples [
23] and with the evidence on the frequency of depression in patients with epilepsy ranging from 9 to 37% [
40]. Indeed, this well-known variability of depressive symptoms reported by patients with epilepsy might be due to the heterogeneity of tools and methods employed to screen for depression in the published literature (e.g., self-reported scales, psychiatric interview; [
41]). This variety often makes comparisons between studies impossible [
40] thus being a barrier to understanding the relationship between depression and epilepsy.
The underling mechanisms explaining the epilepsy–depression link highlight the contribution of both biological and psychosocial factors [
42]. More specifically, the biological determinants of this association (e.g., hippocampal shrinking, amygdala hypertrophy) have been observed in neuroimaging and neurobiological studies and, similarly, the implication of psychological variables (e.g., stigmatization, coping mechanism) in the pathogenesis of depression in epilepsy has been also reported [
43]. Epidemiological studies sustain a bidirectional relationship between epilepsy and depression, as depression may not only co-occur with and follow the onset of epilepsy [
5] but also may increase the risk of developing this disease [
44]. Overall, this evidence seems to suggest an underlying common neurobiological basis [
45].
Results of the current study confirmed what was found in previous evidence [
25], suggesting that depressive symptoms are more accentuated among female patients than male patients presenting epilepsy. Evidence on the general population suggests part of the gender gap might be explained by heightened exposure to severe adversity and by structural social gender inequity [
46]. Consistently, gender was a significant and unique predictor of high BDI-II scores, above and beyond the clinical features of the sample. This evidence was consistent with results from gender comparison and reinforces the idea that being female is a strong depression-predisposing factor in epileptic patients [
47]. A recent meta-analysis highlights that the female hormonal environment could be one explanation of this phenomenon, as the decrease in estrogen increases the likelihood of depression [
8]. Furthermore, females typically face with challenging conditions that may be affected by epilepsy and significantly impact on their perceived quality of life, resulting in high negative emotionality. For example, an increased prevalence of depression during and after pregnancy in women with epilepsy as compared to women with other chronic diseases and women without epilepsy has been observed [
47]. Also, some authors suggest that adverse effects of epilepsy (e.g., stigma, discrimination, vocational difficulties) may prevent the achievement of a job and cause depression in women [
48]. Moreover, females may be more prone to disclosing depressive symptoms than men [
8]. Therefore, future studies should assess factors possibly explaining the gender role in the depression-epilepsy association, and longitudinal research across the lifespan, examining risk factors and transdiagnostic outcomes, is needed.
The present study also examined the associations between depressive symptoms and demographic and clinical characteristics in patients with epilepsy. Differently from previous authors [
49,
50] who found that a shorter epilepsy duration was significantly associated with a lower risk of depression, in the present investigation, high epilepsy duration was determined to decrease depression. This result is consistent with a previous study that found a negative correlation between epilepsy duration and BDI-II scores in patients with temporal lobe epilepsy [
51]. A possible explanation for this rather contradictory result is that adults with long-term epilepsy “come to terms with their ailment over time” [
52 , p.
63]. In this context, it is noteworthy that a previous analysis of 99 adults suffering from intractable epilepsy found an association between longer duration of epilepsy and higher quality of life scores [
53]. A long-term epilepsy may reflect a greater span of time available to face stressful difficulties brought about by this disease. Future studies on the current topic are therefore recommended in order to elucidate if perceived difficulties in coping with epilepsy-related disabilities (e.g., loss of independence) are associated with the duration of symptoms.
The positive unique association found in the present study between the use of psychotropic drugs and depression may indicate that patients with high severity of depression already received psychiatric medications. This finding reinforces the clinical supposition that psychiatric medications cannot present the same effectiveness in patients with epilepsy, thus justifying the need of personalized approaches, counting both pharmacological and non-pharmacological treatments, in patients with epilepsy taking into account that the disease per se can alter the neurobiological networks at the basis of depressive symptoms. Notably, the evidence that, among patients reporting depressive symptoms according to the BDI-II score, almost half (i.e., 57%) did not already receive psychotropic medications might suggest that, in many cases, patients screened as positive for depression with this instrument are under-treated, consistently with previous observations [
54]. This fact is not entirely unfavorable, considering the high rate of false positives for depression associated with the use of the BDI-II [
55]. Conversely, it appeared that depressive symptoms can be overlooked in patients with epilepsy, in particular when the patients are seizure free. Further investigations should comply with the recommendation that the diagnosis of depression and the relative need of a treatment plan must be confirmed with a clinical interview conducted by a trained clinician [
56].
The lack of associations with other epilepsy-related variables confirmed previous studies evidencing no significant changes in epilepsy characteristics (e.g., seizure frequency) in patients treated with antidepressants [
57]. More specifically, in the present study, the seizure frequency was not associated with the severity of depression as indicated by regression coefficients. This result is confirmed by the evidence that the number of seizure-free patients in the current sample was very high (i.e., 76%), thus suggesting that the high prevalence of depressive symptoms found (39%) can only be partially explained by factors related to epilepsy. Previous authors suggested that epilepsy per se is related to the severity of depression, thus encouraging clinicians to treat all patients for depression irrespective of seizure frequency [
54].
In the current sample, the presence of generalized seizure significantly predicted severity of depression. This result did not appear to corroborate previous evidence demonstrating that, in comparison to generalized seizures, focal seizures were associated with a higher risk of depressive symptoms [
58]. On the other hand, this evidence substantiates previous findings in the literature indicating that patients diagnosed with generalized seizure are the most vulnerable to severe depression [
59,
60].
The novelty of this study relies in the single-item analysis documenting that, among all the depressive symptoms, one of the most pronounced was changes in sleeping patterns, confirming that disrupted sleep patterns in epilepsy are commonly described clinically [
61]. High percentage of patients also reported tiredness and loss of energy, suggesting that patients with epilepsy frequently experience extreme and persistent weakness or exhaustion [
62]. Moreover, the high prevalence of all these symptoms may corroborate previous systematic evidence that sleep-related problems and fatigue are intercorrelated symptoms of depression in epileptic condition [
9]. Future studies should extend the above single-item analysis to examine depressive symptoms in specific epilepsy type and in subgroups of patients (e.g., pediatric). Finally, the rate of suicide ideation (i.e., item 9) observed in the present sample (15.7%) supported the prevalence of suicidal attempts found in previous evidence [
63]. This finding encourages the development of appropriate suicide prevention strategies in conjunction with psychiatry and pharmacotherapy programs, especially considering that suicide is frequently underdiagnosed by physicians [
64]. On the other hand, results concerning the depressive symptom rate in epilepsy should be interpreted with caution, since anergy, fatigue, and sleep disturbances are common symptoms reported by patients with epilepsy even in the absence of psychiatric conditions [
9].
Some limitations are acknowledged in the present study including its cross-sectional nature, which does not allow demonstration of causal relationship between predictors and BDI-II scores. Future studies should address this issue, especially considering that no clear results on a directional association exist. Some studies supported the relationship between depression symptom and epilepsy-related symptoms (e.g., seizure frequency) to be bidirectional [
65]. On the other hand, depression appeared to be a prospective predictor for seizure frequency [
66]. Further prospective studies are needed to fill this gap. Another limitation was the relatively small sample size, which might had affected the conclusions of the study in terms of their generalizability. Moreover, the application of subjective self-report instruments to assess depressive symptoms did not permit the exclusion of social desirability in the responses given by participants. Finally, the lack of a control group enabled the comparison between patients with epilepsy and healthy participants on depressive scores.
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