Stigma and Polytherapy: Predictors of Quality of Life in Patients with Epilepsy from South India.

BACKGROUND: Apart from unpredictable seizures and consequent injuries, people with epilepsy (PWE) confront with psychosocial adjustments. Quality of life (QOL) varies with culture and socioeconomic milieu. Identification of predictors for QOL enables comprehensive and effective care.
OBJECTIVE: The objective of this study was to investigate the role of stigma, demographic, socioeconomic, and clinical factors in QOL among PWE. SUBJECTS AND METHODS: In this prospective observational study, 170 PWE answered QOL in epilepsy-31 (QOLIE-31) and stigma questionnaire. Internal consistency of instruments was evaluated by Cronbach's alpha and reproducibility by intracorrelation coefficient (ICC). Descriptive statistics were calculated, and predictors were identified by regression analysis.
RESULTS: Mean age of the PWE was 34.39 ± 11.49. Cronbach's alpha and ICC of the QOLIE-31 were 0.946 and 0.974 and stigma scale was 0.903 and 0.954, respectively. Mean total QOL was 60.29 ± 14.12. Highest and lowest scores of subscales of QOL were observed in medication effects and social functioning. Mean stigma score of PWE was 22.21 ± 14.64. Majority of PWE had mild stigma (75%) followed by moderate (22%) and high stigma (1%). Stigma score correlated with total and subscales of QOL (P < 0.01). Statistically significant decrease in scores of total and subscales of QOL was observed in high and moderate stigma when compared to mild stigma (P < 0.01). Stigma (standardized beta coefficient = -0.652, P < 0.00) and polytherapy (standardized beta coefficient = -0.180, P < 0.02) were found to be the significant predictors of QOL. Significant decrease in total and subscale scores of QOL was observed in PWE under polytherapy when compared to monotherapy and also in seizure frequent against seizure-free PWE (P < 0.01).
CONCLUSIONS: Besides control of seizures, encouragement of monotherapy and destigmatization campaigns may improve the QOL of PWE.

INTRODUCTION

Ngugi et al. in a meta-analysis have reported that 70 million people in the world have epilepsy and 90% of them were residing in developing countries.[1] Review of epilepsy studies in India has shown that 12 million people are affected by epilepsy. Prevalence and incidence of epilepsy in India ranged from 3 to 11.9/1000 population and 0.2–0.6/1000 population per year, respectively. In terms of demographic and socioeconomic status, epilepsy was found predominantly in male gender, aged, rural residents, and people belonging to low socioeconomic status. The cause of primary epilepsy is yet to be known, while major risk factors for secondary epilepsy were found to be neuroinfections, neurocysticercosis, and neurotrauma along with birth injuries.[2] Epilepsy is defined as the chronic neurological disorder characterized by an enduring predisposition to generate epileptic seizures along with neurobiological, cognitive, psychological, and social consequences.[3]

People with epilepsy (PWE) apart from unpredictability of seizures experience psychosocial problems such as adjustmental demands on personal and work life, family coping, marital discord, economic burden, access to treatment, and stigma.[4] As a consequence of aforementioned reasons, lower quality of life (QOL) was observed not only among PWE but also in comparison of PWE with the patients of other chronic diseases and the general population.[56] QOL may be defined as the perception of a person on his/her health, psychological state, level of independence, relationships, and environment.[7] Control of seizures can be achieved in 70%–80% of PWE, and even in 30%–50% of seizure-controlled PWE, stigma can affect their QOL.[8] Stigma is defined as a social process that is observed when there are elements of labeling, stereotyping, and discrimination because of characteristics previously specified as different and unacceptable which result in social status loss.[910] Various studies conducted in India to assess stigma in PWE had shown higher prevalence of stigma among PWE.[11] Stigma acts as a barrier for PWE to access health care; serves as a source for discrimination in employment, education, marriage, and social relationships; and acts as a deterrent in drug compliance leading to low QOL in PWE.[11] Except three studies,[121314] earlier investigators assessed stigma using knowledge, attitude, and practice questionnaires.[11]

Stigma is influenced by regional and cultural factors,[15] and there is a need for culturally sensitive tools to understand the distribution, determinants, and impact of epilepsy-related stigma.[11] Although a number of studies in India had investigated various risk factors for QOL in PWE,[11] few studies[121314] had attempted to explore the effect of stigma on QOL in PWE in India. Understanding of factors influencing the QOL in PWE will enable for comprehensive and effective care through proper treatment regimens, interventions, and educational materials.[7] In the present study, we have attempted to investigate, apart from clinical, demographic, and socioeconomic factors, the effect of stigma on QOL in PWE representing from South India.

SUBJECTS AND METHODS

Before executing this study, an approval was obtained from the Institutional Ethics Committee.

Sample size and technique

Assuming reliability of 0.7 as acceptable and inter-observer reliability to be 0.8, α = 0.05, and β = 0.2, the calculated sample size was 117.[16] One hundred and seventy PWE, who fulfilled the inclusion criteria of the study, were recruited from the Outpatient Department of Neurology, Sri Venkateswara Institute of Medical Sciences, using a purposive sampling technique.

Inclusion criteria

PWE aged 18–60 years who were diagnosed with epilepsy and were under drug regimen of AED for a minimum period of 1 year and were willing to participate in the study were enrolled in this study.

Exclusion criteria

PWE with psychiatric disorders (mental retardation, schizophrenia, anxiety, obsessive-compulsive disorder, and bipolar disorder), learning disorders (conduct disorders and attention-deficit hyperactive disorder), hospitalized, and who developed seizure after surgery to the brain were excluded from the study.

Based on the history, physical examination, and electroencephalographic and magnetic resonance imaging, epilepsy was diagnosed. Data on age, gender, religion, marital status, residence, smoking, consumption of alcohol, education, occupation, income, and family history of epilepsy were enquired from the PWE and were documented. Data on clinical variables such as age of onset, time of onset, frequency of seizures, duration of seizures, and duration of medication were collected from the case sheets. PWE are grouped into mono (single drug) and polytherapy (two or more drugs) based on the intake of drugs. Using classification proposed by the International League Against Epilepsy,[17] seizures occurring in PWE were categorized into simple partial, complex partial, generalized tonic–clonic seizure, myoclonic, atonic, secondary generalized, and tonic–clonic seizure. PWE were grouped into seizure free (seizure free for at least 1 year) and seizure frequent (based on the occurrence of seizure within the past 1 year).

Instruments

Stigma scale

Stigma scale developed and validated by Fernandes et al.[18] was used for the assessment of stigma in PWE. The original scale was translated into Telugu and then back translated into English by bilingual experts. The Telugu version of Stigma scale was administered to the PWE and responses were documented. Stigma scale was used to assess the perception of stigma. It has five questions with 24 items (related to the opinion about the feeling of PWE on their ability to control the epilepsy, feeling when seeing epileptic seizure, opinion about the difficulties faced by the PWE, opinion on the feeling of epilepsy, and opinion on the prejudice in epilepsy related to relationships, marriage, work, school, and family). Each participant's response is documented on a 4-point rating scale such as not at all, a little, a lot, and totally with marking of score 1–4. Item scores are summed up and linearly transformed on to a 0–100 scale. Zero indicates no stigma, whereas 100 refers to the highest level of stigma.[18] Stigma scale has been validated in Hindi-speaking North Indian populations.[121314] PWE were classified into various groups based on stigma score such as no stigma (0), mild stigma (1–33), moderate stigma (34–65), high stigma (66–99), and maximum stigma (100). Obtained Cronbach's alpha and intracorrelation coefficient for the stigma scale in the present study were 0.903 and 0.954, respectively.

Quality of Life in Epilepsy-31

This scale is derived from QOL in epilepsy inventory-89 developed by RAND organization. In view of easier administration, it is widely used. It contains 31 items and has seven subscales (seizure worry, emotional well-being, energy/fatigue, cognitive functioning, medication effects, social functioning, and overall QOL). Raw scores are obtained using Likert scales and linear transformed on a 0–100 scale. Greater the score, better the QOL. QOL in epilepsy-31 (QOLIE-31) questionnaire has been validated in Marathi-,[1920] Malayalam-,[21] Hindi-,[2223] and Kannada-[24] speaking populations of India. Cronbach's alpha and intraclass correlation coefficient obtained for QOLIE-31 in the present study were 0.946 and 0.974, respectively, which indicated good internal consistency and reproducibility of the instrument for assessment of QOL for the population of the present study.

Statistical analysis

Continuous variables are presented in mean and standard deviation (SD), whereas categorical variables are expressed in proportions. Kolmogorov–Smirnov test was used to check normal distribution of continuous variables. Due to nonrandomness in a large number of variables, Kruskal–Wallis test was employed to compare the means. Analysis of covariance (ANACOVA) was used to compare total QOL and subscale scores after adjusting for seizure frequency. Association between variables was investigated using Spearman's correlation analysis. To evaluate potential independent variables for dependent variables (QOL and stigma), step-wise regression analysis was performed. Significant variables were entered into the final equation to assess the relationship between dependent and independent variables. Internal consistency was evaluated by Cronbach's alpha and reproducibility by interclass correlation coefficient. All computations were carried out using the Statistical Package for the Social Sciences version 20.0 Inc., Chicago, Illinois, USA IBM SPSS, Version 20.0 (Armonk, New York, USA).

RESULTS

The average age of PWE was 34.39 years (SD: 11.49). Majority of the PWE were in the age group of 19–39 years (66%), male (56%), follow Hindu faith (93%), married (65%), stay in rural areas (59%), nonsmokers (91%), and abstain from alcohol (93%). Family history of epilepsy was observed in only 11% of PWE. Majority of PWE had high school education (30%), unemployed (46%), and had monthly income of Rs. 1000–25,000 (86%). The mean age of onset of seizures was 19.9 ± 13.9 years. Majority of PWE had the age of onset of seizures during 0–29 years (73%) and during day time (56%). Generalized tonic–clonic seizure was the predominant type of seizure (74%) observed among PWE. Majority of PWE had seizure free for the last 1 year (54%). Mean duration of medication was 6.9 ± 0.1 years, and a majority (88%) of them were taking medication for 1–15 years. Sixty percent of PWE were taking a single drug, and 30% had seizure-related injuries. Among the type of seizure-related injuries, the predominate type of injury sustained by PWE was tongue/cheek biting (15%) [Table 1].

Table 1

Mean and standard deviation of variables and frequency distribution of demographic and socioeconomic variables among people with epilepsy (n =170)

Mean stigma among PWE was 22.21 (SD: 14.64). Majority of PWE had mild stigma (75%) followed by moderate stigma (22%) and high stigma (1%). Only three PWE had reported to no stigma (1.7%) [Table 2]. Mean total QOL score among PWE was 60.29 ± 14.12. There was higher mean score in medication effects (86.33 ± 17.76), whereas least mean score in social functioning subscales (18.26 ± 3.13) of QOLIE-31 was observed. Except medication effects, in other subscales, the Cronbach's alpha coefficient was above 0.7 [Table 3].

Table 2

Distribution of people with epilepsy based on stigma severity and mean stigma score (n =170)

Table 3

Mean and standard deviation of subscales of Quality of Life in Epilepsy-31 and Cronbach's alpha among people with epilepsy

Stigma score showed correlation with total QOL (r = −0.709) and its subscales such as seizure worry (r = −0.749), emotional well-being (r = −0.668), energy/fatigue (r = −0.479), cognitive functioning (r = −0.517), medication effects (r = −0.527), social functioning (r = −0.502), and overall QOL (r = −0.574) and education (r = −0.217) (P < 0.01) [Table 4]. Mean total QOL score and subscale scores decreased from mild-to-high stigma, and the difference in the means of groups was statistically significant [Table 5]. Intergroup means were compared using post hoc “Tukey” test. Statistically significant difference in the mean scores of mild against moderate and high stigma was observed in total QOL and subscales of QOL (P < 0.05).

Table 4

Relationship between stigma score and subscale and total quality of life scores of Quality of Life in Epilepsy-31

Table 5

Mean and standard deviation of scores of subscales and total quality of life scores of Quality of Life in Epilepsy-31 by stigma severity

Potential predictors of QOL were identified in step-wise regression analysis and entered in the final equation of multiple regression analysis. Stigma score (standardized beta coefficient = −0.652, P < 0.00) and polytherapy (standardized beta coefficient = −0.180, P < 0.02) were found to the significant predictors of QOL [Table 6]. Statistically significant decrease in total and subscale scores of QOL was observed in polytherapy than monotherapy taking PWE [Table 7]. Comparison of total QOL and subscale scores (seizure worry, emotional well-being, energy/fatigue, cognitive functioning, medication effects, social functioning, and overall QOL) between seizure-frequent and seizure-free PWE showed higher mean total and subscale scores in seizure-free PWE when compared to seizure-frequent PWE (P < 0.01). To check whether there is an influence of seizure frequency on total QOL and subscale score due to the presence of 45.9% PWE with a history of frequent seizures, we have compared total QOL and subscale score before and after controlling for seizure frequency using one-way ANACOVA. We found that statistically significant change in mean values of total QOL and subscale scores was observed before and after adjusting with seizure frequency in both seizure-free and seizure-frequent groups, suggesting that there is an influence of seizure frequency on total QOL and subscale scores [Tables 8 and 9].

Table 6

Predictors of quality of life in people with epilepsy

Table 7

Mean and standard deviation of total and subscale scores of quality of life in people with epilepsy on monotherapy and polytherapy

Table 8

Comparison of total quality of life and subscale scores between seizure-free and seizure-frequent people with epilepsy

Table 9

Comparison of total quality of life and subscale scores between seizure-free and seizure-frequent people with epilepsy before and after adjustment with seizure frequency using analysis of covariance

DISCUSSION

PWE face social exclusion due to negative attitudes of people and confront with problems of injury, marriage, employment, and discrimination at workplace. Apart from these, unpredictability of seizure entails PWE to make compromises on psychosocial adjustments. Although seizure control is achieved in 75% of cases, 25% suffer from refractive forms of epilepsy.[25] These clinical and psychosocial challenges lead to the decrease of QOL in PWE. Evaluation of QOL provides subjective assessment of positive and negative aspects of life, if appropriate interventions are applied, it can lead to the improvement of QOL.

Earlier studies conducted on PWE in India using QOLIE-31 showed mean total QOL score ranging from 38.4 to 68.[1920212223] In our study, mean total QOL score was 60.29 which was within the range of scores observed earlier and indicate good total QOL score. Various studies showed high and least scores in various subscales of QOLIE-31 such as highest in cognitive functioning and least score in energy fatigue;[19] highest in emotional well-being and least score in seizure worry;[20] highest in energy/fatigue and least score in overall QOL;[22] and highest in medication effects and least score in seizure worry.[23] With regard to medication effect, the present study is in agreement with earlier study.[23]

In our study, highest score in medication effects and least score in social functioning subscales were observed. Social functioning is the most affected domain of QOL in our study despite PWE on antiepileptic drugs. Earlier, it was observed that treatment alone may not improve the social and psychological functioning of PWE.[26] This suggests that equal importance should be given in improving social functioning in addition to the seizure control because seizure control alone may not improve social limitations and improve QOL. Low social functioning is likely to result due to stigma arising from public appearance and lack of knowledge of family members on stigma. Stigmatized PWE may not also comply with drug regimen. There is a pressing need to address the social functioning aspect of PWE to maximize the QOL.[27] In our study, significant correlation of stigma score with QOL was observed [Table 6]. It was observed that psychosocial variables (psychological distress, loneliness, adjustment and coping, and stigma) influence the QOL, and therefore health professionals should be aware of the significance of the psychosocial functioning of the patients.[28] To know the predictors of social functioning, we employed step-wise regression analysis and found that stigma score (standardized beta coefficient - 0.489) and occupation (standardized beta coefficient - 0.489) (P < 0.01) were significant predictors of social functioning. These results suggest that destigmatization and providing job opportunities may improve the social functioning and QOL of PWE in the present study.

Fernandes et al.[1518] in two separate studies involving PWE and urban individuals of Brazil had reported that mean and median scores of stigma scale were 46 and 49.7, respectively. Two Indian studies available in public domain[1314] used stigma scales of epilepsy developed and validated by Fernanades et al.[18] on the population of same region. Prakesh et al. have studied thirty PWE and reported a mean score of 51.17, while Kumari et al.[13] had studied three groups of 15 individuals each involving new and old cases of epilepsy and age-matched control and reported mean scores of stigma in them as 100, 82, and 78.9, respectively. In the present study, mean and median scores of stigma were 22.21 and 19.4, respectively, and the difference with earlier studies may be due to large number of PWE with mild stigma (75%) in the present study, cultural differences, and also due to larger sample size than earlier studies.[131415] Of the three studies,[131415] only the first study reported seizure frequency in 15 old and 15 newly diagnosed PWE, whereas the latter two studies did not report either mean or frequency of seizures. In the first study,[13] in newly diagnosed PWE, the observed seizure frequency of more than once per week, month, and year was 3, 5, and 7, respectively. In contrast, in old PWE, seizure frequency of more than once per week, month, and year was 1, 3, and 2, respectively. In our study, we have observed seizure frequency in 45.9% of PWE. The frequency of seizures once per month, more than 1/month, <1/week, and <1/day was 31.2%, 12.4%, 1.2%, and 1.2%, respectively.

Studies in developed countries reported 18% prevalence of stigma, whereas in developing countries, it was estimated up to 60%.[8] A study conducted in Mangalore reported that 61% of PWE were stigmatized by epilepsy.[24] In our study, only 1% had highest stigma and 28% had reported moderate stigma. Various factors such as experiences of actual discrimination from society, introverted personality, problem-solving controllability, and emotional subscale of QOLIE-31, in Korea;[29] unemployment and low education in Iran (Ghanean et al., 2013); age group of 30–50 years in India;[23] experience of social isolation, experience of marital problems, and presence of anxiety disorder, in Switzerland;[30] and age ≥50 years, younger age of epilepsy onset, more than 50 seizures to date, generalized tonic–clonic seizures, and a shorter seizure-free period and number of seizures to date, in Croatia were reported.[31] To find the potential predictors of stigma, we have used step-wise regression. In multiple regression analysis, we found that seizure frequency (standardized beta coefficient = 0.239) and polytherapy (standardized beta coefficient = 0.248) (P < 0.001) were significant predictors of stigma in our population. These two variables were found to account for 12.6% variation in the stigma as shown by adjusted R2 (0.126). Among the demographic and socioeconomic variables, stigma score was negatively associated only with education (r = −0.217, P < 0.01). This observation suggests that increasing education levels will decrease the stigma. Association of education with stigma was observed in earlier studies.[1832]

Studies on adult PWE using QOL instruments in Indian populations had identified factors associated with QOL of PWE such as age >30 years, female, being married, presence of anxiety, lack of primary education, being single, separated or widowed, increasing age, low per capita income, having a seizure episode in the past year, previous exposure of knowledge on QOL, reaction to the diagnosis of epilepsy, stress in being alone, feeling of health getting worse, polytherapy, stigma, seizure frequency, workdays lost due to epilepsy in the past 3 months, use of two or more antiepileptic drugs, higher frequency of seizure, long-time gap between onset of seizure, consultation with a neurologist, Engel score of seizure frequency >6, high seizure frequency, anxiety, and depression.[11121321333435363738]

QOL was shown to vary depending on the cultural, economic, and community milieu.[3339] In this study, in multiple regression analysis, stigma (standardized beta coefficient = −0.652, P < 0.00) and polytherapy (standardized beta coefficient = −0.180, P < 0.02) were found to be the significant predictors of QOL.

Significant inverse association between stigma and QOL was observed in PWE in earlier studies.[97121340] In our study also, significant inverse association between stigma and QOL was observed. Majority of PWE in our study had mild stigma (75%), followed by moderate (22%) and high stigma (1%) [Table 2]. Low prevalence of moderate and high stigma may be due to increased awareness regarding epilepsy and its acceptance as medical illness,[19] in agreement with earlier studies in which 60% of patients did not report about stigmatization.[4041] In our study, stigma correlated inversely with total QOL and subscales of QOLIE-31. A significant decrease in total QOL and subscale scores of QOLIE-31 was observed in PWE with mild stigma when compared to moderate and high stigma [Tables 4 and 5]. This suggests that stigma negatively affects the QOL of PWE.

Stigma results from unpredictability of seizures and social exclusion due to negative attitudes of people including difficulties in education, having a family, and finding job, even when it is not contraindicated.[942] Feeling of guilty and depression and hiding about disease from relatives, partners, and employers were observed in stigmatized patients.[94344] Stigmatization was found to be a causative factor for decrease in QOL.[7912134546] By changing patients’ self-esteem and limiting the work opportunities, stigma reduces the QOL in PWE.[946]

Monotherapy is the first line of treatment in epilepsy,[47] whereas polytherapy is advised in case of refractory seizures due to localization-related epilepsy, and there is also an evidence on the practice of polytherapy in peripheral centers in India due to poor control of seizure.[21] Usage of polytherapy in Indian studies ranged from 30% to 48%.[2021234849] In the present study, 41% of PWE were taking polytherapy. Decrease in total and subscale scores of QOLIE was observed in polytherapy when compared to monotherpy taking PWE [Table 7]. Significant association of polytherapy with QOL in PWE was observed in earlier studies.[21484950] Factors such as high cost, adverse reactions, less safety profile, less tolerability, increased comorbid depression, drug toxicity and drug–drug interactions, noncompliance, emotional disturbance, increased conduct disorders, socialized aggression, anxiety withdrawn scales, and difficulties in cognitive function were cited in literature in association with polytherapy and were hypothesized to decrease QOL.[2134485152] In our study, majority of PWE were beneficiaries of free drugs distributed by Friends of SVIMS society in association with SVIMS and who did not report any adverse effects in relation to the drugs.

In PWE, experience of injury, incontinence, fear, and other emotional distress during seizures and intermittent memory deficits, tiredness, and headaches after seizures were reported.[53] Better QOL was observed in seizure-free PWE who had good perception of seizure control and not experienced seizures in public places.[54] Improvement in QOL was observed in PWE who were seizure free for the last 12 weeks of 28-week clinical trial on antiepileptic drugs.[55] In our study, higher mean total QOL and subscale scores were observed in seizure-free PWE when compared to seizure-frequent PWE. In our study, 45.9% of PWE had a history of seizure occurrence. To check whether the seizure frequency influences the QOL, we controlled for the seizure frequency and compared the total QOL and subscale scores in both seizure-frequent and seizure-free PWE. We found that a significant change was observed in mean total QOL and subscale scores before and after controlling seizure frequency in both seizure-frequent and seizure-free PWE, suggesting that seizure frequency influences the QOL in PWE.

To the best of our knowledge, this is the first study which showed the association of stigma and polytherpy as significant predictors of QOL in PWE. Sample may be biased because adult PWE who have access to and who seek medical care at specialized epilepsy clinic at SVIMS were recruited in the study. Exclusion of patients with symptoms of anxiety was done to avoid confounding effect of anxiety which has also been shown to impair the QOL.,[56] Other reasons of exclusion include no intention of studying the role of anxiety and QOL and to avoid inconvenience to patients who are already subjected to two instruments such as QOLIE-31 and stigma scale and to prevent deterioration in the quality of response due to overloading of the information. There is a possibility that exclusion of patients with anxiety disorder may have introduced bias in the sample. Sample may not be representative of adults with epilepsy, and the results are not applicable outside the study population.[7] This is a single-center study involving volunteered patients, having differing etiologies, medication regimens, lifestyles, personalities, and life experiences that may affect study outcomes.[40] Studies involving multicenter and homogeneous patient population are needed to confirm the findings of this study.

CONCLUSIONS

PWE showed good scores in total and subscales of QOL except social functioning. Majority of PWE had mild stigma. Only 22% had moderate, while 1% had high stigma. Stigma correlated significantly with scores of total and subscales of QOL and showed significant decrease in the scores of total and subscale QOL from mild to high stigma. Seizure frequency and polytherapy were found to be significant predictors of stigma. QOL in PWE was found to be affected by stigma and polytherapy. Results of the present study suggest that, besides controlling seizures, encouraging monotherapy and destigmatization campaigns may improve the QOL of PWE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.