|Ahead of print publication
Comorbid depression and anxiety in patients of epilepsy
Geetanjali Gupta1, Raghav Kesri2, Suchita Goyal3, Sagar Karia4
1 Department of Psychiatry, ESIC Medical College, Faridabad, Haryana, India
2 Department of Medicine, Artemis Hospital, Gurugram, Haryana, India
3 Department of Psychiatry, Raipur Institute Of Medical Science, Raipur, Chattisgarh, India
4 Department of Psychiatry, Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India
|Date of Submission||28-Jul-2021|
|Date of Decision||20-Aug-2021|
|Date of Acceptance||29-Sep-2021|
|Date of Web Publication||15-Mar-2022|
OPD 21, New OPD Building, 2nd Floor, Lokmanya Tilak Municipal Medical College and G.H., Sion, Mumbai - 400 022, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Epilepsy is a common chronic noncommunicable neurological disorder in which brain function is impaired. Epilepsy patients are more prone to comorbidities such as depression, anxiety, psychosis, personality disorders, hypo-sexuality, migraines, and other behavioral disorders. Comorbid depression and anxiety are more common in people with epilepsy than in the general population. Comorbid psychiatric illness in epilepsy has multifactorial etiology, including epilepsy itself, age at onset, duration of epilepsy, treatment of epilepsy, reaction to epilepsy, and any associated brain dysfunction and/or damage. Hence, this study was conducted to check the association of comorbid depression and anxiety with the sociodemographic factors and disease-associated factors in patients with epilepsy. Aim: To study the occurrence of depression and anxiety in patients with epilepsy and their relationship with sociodemographic and disease-associated factors. Materials and Methods: This was a single-centered cross-sectional study, in which 96 patients participated. To assess the severity of depression and anxiety, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were used, respectively. Results: Out of 96 patients, comorbid depression was seen in 35 (36.45%) and anxiety in 28 (29.16%) patients. Conclusions: The present study points out that depression is more prevalent than anxiety in patients with epilepsy and its severity is more if onset age is earlier and duration of illness is more.
Keywords: Age of onset, anxiety, depression, duration, epilepsy
| Introduction|| |
Epilepsy, accounting for 0.75% of the global disease burden, about 35 million out of 50 million do not have adequate treatment available because the clinics do not exist or epilepsy is not seen as a psychiatric disorder or a treatable neurological disease. People with epilepsy (PWE) face barriers to join specific professions, challenges in socialization, work, and self-esteem. This study's focus has been on epilepsy patient's living standards over the past few decades, but progress has slowed and services are still poor. Our study aims to assess the psychiatric (depression and anxiety) comorbidities associated with epilepsy patients. In patients with epilepsy, the most common affective disorder is inter-ictal depression. The recognized symptoms are that of anhedonia, reduced appetite, poor energy, and sleep disturbances. It is more likely to be associated with agitation and psychotic features or impulsive self-harm than the depression seen in the general population. It has been found that significantly lower levels of cerebrospinal fluid serotonin metabolites, 5-hydroxyindolacetic acid in subjects with epilepsy and comorbid depression as compared to patients with depression in the general population.
Various factors increase the risk of depression. It is more prevalent in patients with uncontrolled seizures than patients who are seizure-free. Family history has been observed in over 50% of patients with both epilepsy and depression suggesting a genetic predisposition. Paradoxically, depression can follow both remissions of epilepsy either after epilepsy surgery or after the initiation of an antiepileptic drug. Multiple studies that examined alteration in blood flow, metabolism, MRI volumetrics, and positron emission tomography reported abnormalities in the left (mesial) and frontal regions which established that in patients with left temporal or focal left hemisphere epilepsy, depression was characteristic. Interictal depression affects two-third of patients, especially those with severe and/or frequent seizures. It was used to describe a syndrome comprising eight symptoms, of which the patient must experience minimum three (3/8): Depressive moods, energy, pain, irritability, insomnia, anxiety, fear, and euphoric mood. In severe form, this disorder has been associated with sudden suicidal attempts during episodes of intense depressive mood.
All psychiatric comorbidities in general, and depression in particular is an under-recognized and under-treated psychiatric comorbidity. The major reasons for this are: Failure to recognize or underestimation of the symptoms by the patients, limited access to treatment, and lack of health insurance for psychiatric illnesses. Furthermore, lack of specialists, lack of collaboration among providers, and limited training regarding depression are some health care provider-related issues leading to under-diagnosis and under-treatment of major depression. Depression significantly lowers the quality of life in PWE, but it is a treatable condition. Depression can directly increase seizure frequency. It is important to diagnose and treat depression to prevent suicide. Depression often worsens compliance with anti-epileptic medications.
Anxiety is the dominant symptom of the adjustment disorder which many patients go through when they are first diagnosed with epilepsy. Like depression, anxiety can be seizure related or it can occur in the inter-ictal period. It develops as a result of stressful events. The exact etiology of anxiety in patients with epilepsy is unknown, although it is speculated that it is the result of the unpredictable nature of seizures, a perceived “loss of control,” sudden onset and chance of injury or embarrassment.
Various studies have suggested elevated levels of anxiety, panic attacks, panic disorder, generalized anxiety, and phobia in patients of epilepsy compared with healthy controls., Patients with epilepsy have panic attacks up to six times more frequently than the general population. Of all the types of anxiety disorder, panic is the type most likely to be generated by a seizure– so-called “ictal fear.” In epilepsy, diagnostic delays are common which cause heightened anxiety. After diagnosis, GAD may continue if there is fear of future seizure, fear of disease progression, or fear of specific complications. Specific phobias include fears such as fear of seizures or accidents occurring out of the house-agoraphobia and fear of social embarrassment-social phobia.
Risk factors for anxiety in PWE are female gender, younger chronological age, divorce and separation, low educational attainment, and unemployment. Elderly people who were diagnosed with epilepsy in later life were found to be more anxious and depressed than those diagnosed earlier.
The theory of a common pathophysiological mechanism of anxiety attack and epilepsy is based on the observation that epileptic attack in certain areas of the brain, like amygdale, directly causes paroxysmal anxiety, usually in the form of panic. The amygdala is an important structure in both, the production of anxiety symptoms and epileptic discharges in temporal lobe epilepsy. However, ictal fear also seen with seizures arising in the anterior cingulated or orbitofrontal cortex or other limbic structures, along with temporal lobe epilepsy. A role of GABAA receptors and other neurotransmitter system (especially serotonin, dopamine, noradrenaline) in both epilepsy and anxiety is a further pathophysiological similarity between the two disorders. This theory is supported by the fact that some substances, including GABAergic antiepileptic drugs gabapentin, vigabatrin, tiagabine, valproate, and pregabalin as well as barbiturates, benzodiazepines, and neuroactive steroids, have antiepileptic as well as anxiolytic properties.
Interictal anxiety is difficult to differentiate from independent comorbid anxiety disorder. Studies suggest that kindling mechanisms could be responsible for the development of interictal anxiety. Recurrent epileptic stimulation of the amygdala could give rise to and increased irritability in this region of the brain. Furthermore, interictal anxiety represents a combination of psychological worries about the disorder and its complications. Common concerns focus on the risk of seizure-related injuries or brain damage, memory impairment, the prognosis of the seizure disorder, and issues related to work and employment. In both primary and secondary care, anxiety disorders are often unrecognized and untreated and optimal seizure control is one cornerstone in the management of anxiety in these patients.
| Materials and Methods|| |
This research was performed at the Epilepsy Clinic in the Out-Patient Department (OPD) of a tertiary care private hospital in Mumbai. Those patients who fulfilled the diagnostic criteria of epilepsy according to the International League Against Epilepsy definition of epilepsy, attending the epilepsy clinic in the OPD, were considered for the study. The study was a single-centered, cross-sectional study and was performed after approval from the institutional ethics committee. According to the previous studies, the prevalence of psychiatric illness in patients of epilepsy was 32.5%. N = (Z2 × P[1/P])/e was used for sample size calculation. A sample size total 84 cases would be sufficient to assess the objectives of study at a 5% level of significance, with 80% of power. Considering 10% dropouts, a minimum of a total of 93 patients had to be enrolled in this study. The total duration of the study was 1 year. Initially, 105 male and female patients between 18 and 65 years of age suffering from epilepsy disorder were included. Later, 12 patients were excluded as they either did not consent for the study, or had seizure in the last 1 month, or serious medical disorder which resulted in seizure, substance dependence, neurological disorder, head injury, acute psychosis, or preexisting psychiatric illness, which could affect the assessment.
Semistructured pro forma was used to collect demographic details and questions related to epilepsy such as the age of onset of illness, total duration of illness, frequency of seizure in the last year. Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scales were used to look for anxiety and depression, respectively. Hamilton anxiety rating scale (HAM-A) developed by Dr. Max Hamilton in 1959, was used to estimate the severity of a patient's anxiety, based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints, and behavior at the interview. It takes 15–20 min to complete the interview and scoring. Each item is given a 5-point score-0 (not present) to 4 (severe). The total score is a range of 0–56, categorized as:
- 0–17 indicates mild anxiety
- 18–24 mild-to-moderate anxiety
- 25–30 moderate-to-severe anxiety.
Hamilton depression rating scale (HAM-D) developed by Dr. Max Hamilton in 1960 at the University of Leeds, England. It constitutes of 17 questions which assess symptoms like depressed mood, feelings of guilt, sleep disturbances, weight loss, etc. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0 to 2. Sum the scores range from:
- 0–7 = Normal
- 8–13 = Mild depression
- 14–18 = Moderate depression
- 19–22 = Severe depression
- ≥23 = Very severe depression.
| Results|| |
[Table 1] shows the sociodemographic parameters of the study participants. The study included 96 participants with the age ranging from 18 to 65 years. About 55.2% of the cases were males and 44.8% of the cases were females. [Table 2] shows the phenomenological details of epilepsy in the study population. 54.2% had duration of <5 years of seizures and 59.4% of them had onset after 20 years of age. Majoirty of them (55.2%) were seizure free in the last 1 year. 35 (36.45.9%) patients of epilepsy had comorbid depression. HAM D score increased significantly, in patients as the age of the patient increased, as the duration of epilepsy increased, but not with the age of onset of seizure and with the frequency of seizures. 28 (29.16%) patients of epilepsy were found to have a significant level of anxiety. 20 (20.83%) had mild-moderate and 8 (8.33%) had moderate-severe levels of anxiety). [Table 3] shows the correlation of various factors with HAM D and HAM A score in the total population and in those having comorbid depression and anxiety.
|Table 3: Correlation of depressionand anxiety with various sociodemographic and clinical parameters|
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| Discussion|| |
Epilepsy can occur at any age in life, most often in childhood (about two-thirds of seizures begin in the early years of life). According to statistics from the Epilepsy Foundation, the prevalence is 3% by the time a person reaches at the age of 75. In the present study, majority (30.2%) of the cases belong to the age group of 26–35 years. There is a vast disparity in the studies conducted in the West and the Indian data regarding marital status. The majority of the sample in our study were married (51%), whereas 37.5% were single, 5% were divorced, and 6% were widowed. Western data show that a higher number of patients were either single or were divorced. In India, epilepsy is a ground for divorce or dissolution under the 1954 Special Marriage Act. Majority of participants were married, which might be due to cultural and social stigma associated with divorce in India. In the present study, the majority 34 (35.4%) employed are males, whereas 11 (11.5%) reported being working women, 22 (23%) homemakers, 13 (13.5%) unemployed, 12 (12.5%) students, and 4 (4%) were retired. It has been found that work compromise due to epilepsy affects a significant number of patients 32 (33.3%). Epilepsy is associated with stigma, which makes it difficult for patients with epilepsy to find employment.
In this study, the majority 57 (59.4%) patients were with early onset of epilepsy over 20 years of age followed by 15 (15.6%) were 16–20 years of age, 14 (14.6%) were 11–15 years of age and ten (10.4%) were ≤10 years of age. Therefore, the sample population consisted mainly of adult epilepsy patients. Patients in this study who had epilepsy for the last 5 years or less, 52 (54.2%) followed by 5–10 years 25 (26%), more than 15 years were 13 (13.5%), and 10–15 years were six (6.3%). A similar population was selected by Stefanello et al. where 57% of patients had epilepsy for 5 years or less. In this study profile, 53 (55.2%) patients did not have any seizure in the past 1 year, whereas 18 (18.7%) cases had one seizure, 11 (11.5%) cases had two seizures, five (5.2%) cases had three seizures, three (3.1%) cases had four seizures, four (4.2%) cases had five seizures, and two (2.1%) cases had more than five seizure episodes. Although the frequency of seizures is a risk factor for the development of psychiatric comorbidities in patients of epilepsy. Patients fear that they will lose their job if people find out about their illness, which results in less reporting of both epileptic symptoms and the psychiatric comorbidities associated with them.
The present study shows that 35 (36.45%) of the patients suffered from depression. Kobau et al. in their study reported that 39.7% of patients suffered from depression. In various studies, the current prevalence was found to be between 30% and 35%.,, A study conducted in the US by Blum et al., found a 29% prevalence of depression in epilepsy patients compared with 9% in the common population. The estimated prevalence was found to be 50% in tertiary or specialized clinical centers, against 6%–30% in population studies. Indian study by Arora and Kaur, the prevalence of depression among epileptic patients was found to be 25%. Maheshwari et al., in their study involving 151 patients with epilepsy, 60% of the cases were found to have depression.
It was seen that as the age of the patient increases the HAM-D score and thereby the severity of depression increases. Similar results are also evident from a previous study by Mensah et al. Arora et al. did not find any such association between the age of patients and the severity of depression. Depressive symptoms were found to be slightly more common in males (17.0%) than in females (16.3%), but it was not found to be statistically significant. In this study, the mild four (28.6%) cases, moderate three (21.4%) cases, and severe two (14.3%) cases with the age of onset of epilepsy are reported in between 11 and 15 years out of 14 cases followed by mild one (10%) case, severe one (3.5%) case, very severe one (10%) case, and rest were reported normal for ≤10 years out of ten cases, mild two (13.3%) cases, moderate one (6.7%) case and rest were normal for 15–20 years out of 15 cases and mild nine (15.8%) cases, moderate eight (14%) cases, severe two (3.5%) cases, very severe one (1.8%) case and the rest were normal for >20 years of age out of 57 cases. A significant association was not found in any onset age of epilepsy and depression. As the total duration of epilepsy increases, the HAM-D score increases and the severity of depression increases as well. Out of the 13 patients who had more than 15 years of epilepsy, only two cases were normal. Whereas, five patients had moderate and four had severe depression. Agoub et al. also reported that as the duration of epilepsy increases, the rate to develop depression increases.
A total of 28 (29.16%) patients were found to have a significant level of anxiety, of which 20 (20.83%) patients had mild-moderate levels and eight (8.33%) patients had moderate-severe levels of anxiety. In a study by Jones et al., 30.4% of the study population was found to have comorbid anxiety. Vazquez and Devinsky, suggest that the prevalence rate of anxiety is 10%–25%. Various other studies also report a similar prevalence rate. In this study, no correlation was found between the age of the patient and the HAM-A score. Across various studies, none reports any age group of patients with epilepsy, to be more prone to develop anxiety.
In this study, mild 15 (65.2%) cases and moderate eight (34.8%) cases were reported for 18–25 years out of 23 cases, mild 20 (69%) cases, moderate five (17.2%) cases, and severe four (13.8%) cases for 26–35 years out of 29 cases, mild 17 (73.9%) cases, moderate two (8.7%) cases, severe three (13%) cases, and rest one (4.4%) case is normal for 36–45 years out of 23 cases, mild six (75%) cases and moderate two (25%) cases for 46–55 years out of eight cases and mild nine (69.2%) cases, moderate three (23.1) cases, and severe one (7.7%) case for 56–65 years out of 13 cases, but the difference was not statistically significant. In our study, no correlation was found between the onset age of epilepsy and the level of anxiety symptoms. Mild seven (70%) cases and moderate three (30%) cases of onset age of epilepsy are reported in ≤10 years out of ten cases, mild eight (57.2%) cases, majority moderate five (35.7%) cases and severe one (7.1%) case for 11–15 years out of 14 cases, majority mild 12 (80%) cases and moderate three (20%) cases for 15–20 years out of 15 cases and mild 40 (70.2%) cases, moderate nine (15.8%) cases, and severe seven (12.3%) cases for >20 years of age, one (1.7%) case is reported normal out of 57 cases. Hence, no association existed between the patient's age and the severity of anxiety symptoms. This finding could be accounted by the fact that when an epileptic activity starts in adulthood, the patient is more prone to develop a fear of having an attack in public and may even develop agoraphobia., No correlation was found between the total duration of epilepsy and the HAM-A score or the severity of anxiety symptoms. Mild 27 (75%) cases, moderate six (16.7%) cases and severe three (8.3%) cases, duration of epilepsy are reported in ≤5 years out of 36 cases, mild 26 (63.4%) cases, moderate ten (24.4%) cases, severe four (9.8%) cases and one (2.4%) case was reported normal for 5–10 years out of 41 cases, mild four (66.7%) cases and moderate two (33.3%) cases for 11–15 years out of six cases and mild ten (76.9%) cases, moderate two (15.4%) cases and severe one (7.7%) case for >15 years out of 13 cases. Moderate-to-severe anxiety was seen more in patients who were recently diagnosed with epilepsy (total duration of epilepsy 5 years or less). This might be due to the fact, during the initial few years of the illness, the patient has “anticipatory anxiety” and “ictal fear.”
| Conclusions|| |
Depression (36.45%) was found to be the most common psychiatric comorbidity, followed by anxiety (29.16%) associated with epilepsy. It has been found that the severity of depression increases as the patient ages and the duration of the illness increases.
The present study is a single-center cross-sectional study done in a private hospital; the sample may not be representative of the entire population. The assessment of psychiatric comorbidities was done only once, thus it may under-report the occurrence of psychiatric sequelae occurring later in the disease course as there was no follow-up. Furthermore, the prognosis of those having psychiatry complaints was not assessed.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3]