Abstract

Objective This study aimed to assess treatment outcome, medication adherence and predictors among epilepsy patients at three low-resource setting hospitals in Mekelle City, Northern Ethiopia.

Design A multicentre hospital-based observational cross-sectional study was conducted.

Setting The study was conducted in three resource-limited tertiary care hospitals in Mekelle City, Northern Ethiopia: Ayder Comprehensive Specialized Hospital, Mekelle General Hospital and Quiha General Hospital.

Participants A total of 351 patients with epilepsy receiving regular follow-up care at adult neurology outpatient clinics in three low-resource setting hospitals were included in the study.

Main outcome measures The study assessed adherence to antiepileptic drugs (AEDs), treatment outcomes and identified independent predictors of these outcomes.

Results A total of 351 study participants were included in the final analysis, with a mean (±SD) age of 37.98±14.27 years. More than one-third (39%) had poorly controlled seizures. Living in urban areas (adjusted odds ratio (AOR)= 3.36, 95% CI 1.1 to 10.4, p=0.037), being government-employed (AOR = 4.0, 95% CI 1.1 to 14.5, p=0.035) and being a student (AOR = 4.0, 95% CI 1.1 to 14.5, p=0.035) were associated with good seizure control. Half of the participants (177, 50.6 %) were non-adherent to their medications. Being a farmer (AOR = 4.2, 95% CI 1.5 to 11.3, p=0.005), a housewife (AOR = 4.9, 95% CI 1.4 to 17.2, p=0.012), absence of seizure-triggering factors (AOR = 3.7, 95% CI 2.34 to 6.06, p<0.001), absence of comorbidities (AOR 1.8, 95% CI 1.11 to 11.28, p=0.008) and good seizure control (AOR= 2.38, 95% CI 1.55 to 3.71, p<0.001) were predictors of adherence to AED treatment.

Conclusions More than two-thirds of patients with epilepsy experienced poor seizure control. Place of residence, employment status and the number of seizure episodes prior to treatment initiation were identified as significant predictors of treatment outcomes. Approximately half of the study participants were adherent to their medications, with employment status, the presence of seizure-triggering factors, comorbidities and seizure control serving as predictors of medication adherence.

Data availability statement

Data are available on reasonable request. The data sets including analysed data and information that support the conclusion are found with the corresponding author on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

STRENGTHS AND LIMITATIONS OF THIS STUDY

• A multicentre study with sufficient sample size increases the representativeness of the findings.

• The high response rate in this cross-sectional study minimises the risk of response bias.

• One limitation of a cross-sectional study is that it cannot establish a cause-and-effect relationship.

• The findings may be limited in their generalisability as only adult epilepsy patients were involved.

Background

Epilepsy is a chronic non-communicable neurological disorder characterised by recurrent seizure attacks resulting from paroxysmal hypersynchronisation and hyperexcitability of neurons within the central nervous system.1 2 The International League Against Epilepsy (ILAE) defines epilepsy as having at least two unprovoked (reflex) seizures occurring in more than 24 hours or one unprovoked seizure with more than a 60% chance of more seizures like the general recurrence risk after two unprovoked seizures occurring in the next 10 years or diagnosis of the epilepsy syndrome.3–5

Epilepsy affects the population of all ages, races, social classes and geographical areas.6 7 Globally, more than 4.6 million new cases of epilepsy are reported annually, with a prevalence of 51.7 million active epilepsy cases, and 82.3 million people diagnosed in their lifetime.8 9 More than 80% of epileptic patients live in low-income and middle-income countries, where a significant proportion of patients cannot access appropriate care.10–15 In Ethiopia, the prevalence of epilepsy is 64 per 100 000 populations, with active epilepsy cases ranging from 5.2 to 29.5 per 1000 people.16 17

Epilepsy is a major health problem in the world, especially in low-income and middle-income countries which negatively affects the physical, mental and social welfare of individuals.18 19 It is also associated with significant mortality and disability as compared with the general population.20 21 The Global Burden of Diseases, Injuries and Risk Factors Study 2010 ranked epilepsy as the second burden of disease based on disability-adjusted life-years.22 23

Medical treatment with AEDs is the primary treatment modality in the majority of epileptic seizures.24–26 The ultimate goal of treatment in epilepsy is to optimise seizure control with minimum AED side effects and maintain the patient’s quality of life.27 28 Seizure control can be achieved in about 70% of epileptics with optimum treatment of AEDs, while the remaining 30% are the most challenging to treat.29 To optimise both the seizure control status and AED adherence, the selection of AEDs should consider the type of epileptic seizures, patient-specific factors such as age, comorbidity, organ function test, childbearing potential and drug-related factors such as cost (insurance coverage), pharmacokinetic and pharmacodynamic profile, safety and dosage regimen.30–32

Despite the high prevalence of epilepsy in resource-limited countries, more than three-fourths of people living with epilepsy in those countries did not receive appropriate treatment, and the availability of AEDs is less than 50%.33–37 Lack of experienced healthcare professionals to diagnose and treat epileptic patients, unavailability of AEDs, cost of treatment and limited and long distance from healthcare facilities are among the factors that contribute to the high treatment gap in low-income and middle-income countries.38 39

Societies living in developing countries also have false perceptions about epileptic seizures and their treatment, often preferring traditional herbal medicines and holy water (administered by religious leaders).40–42 This can lead to poorly controlled repeated active epileptic seizures including status epilepticus, which can cause physical and psychological harm, substantial stigma and discrimination, and sometimes sudden unexpected death from epilepsy. These factors can adversely affect medication adherence and treatment outcomes.16 40 43

Treatment adherence, defined as the extent to which patients can follow the agreed recommendations for prescribed treatments with healthcare providers, is a key component of chronic disease management.44 However, the overall non-adherence to AEDs in epileptic patients ranges from 26% to 79%.45–48 In Ethiopia, the level of AED adherence ranges from 34.1% to 40.27%.49–51 Patients who are non-adherent to their medication can have a threefold increase in mortality, repeated emergency department visits and hospitalisation, and frequent absenteeism from the workplace.52–54 The long-term treatment duration, acute and chronic side effects of AEDs, comorbid psychiatric disorders and poor awareness about the disease condition and its treatment are some of the factors responsible for treatment discontinuation and poor medication adherence, thereby significantly affecting the treatment outcome.55–57

Despite epilepsy being common, there is a higher treatment gap and medication non-adherence in developing nations like Ethiopia. However, there are scarce data regarding treatment outcomes, medication adherence and predictors, particularly in the study setting.58–61 In addition, the studies have been limited to specific geographical areas, predominantly conducted within teaching hospitals. Thus, this study aimed to assess treatment outcomes, medication adherence and predictors at three public hospitals in Mekelle City, Northern Ethiopia.

Methods

Results

Discussion

This multicentre observational cross-sectional study assessed treatment outcomes, medication adherence and predictors among patients living with epilepsy. Out of 351 participants, 61% achieved seizure remission, defined as being seizure-free for at least 1 year. This rate aligns with previous studies done in Ethiopia 60.3%,64 64.6%,63 Nigeria 62.8%,72 China 61.3%73 and Scotland 63.7%.74 However, the seizure-remission rate in this study was significantly lower than in China 80%75 and Ethiopia 78%,76 but higher than in Nigeria77 and rural areas of China,78 where seizure control proportions were 39.2%, 43%, 43.6% and 45%, respectively. Variations in seizure remission rates across these studies may be due to factors such as sample size, research methodology, follow-up durations, inclusion of newly diagnosed epileptic patients, disparities in healthcare access and insurance coverage, the types and availability of AEDs used, and potentially, genetic variations.

Regarding the pattern of seizure remission, 25.4% of participants achieved early remission, 35.6% achieved late remission and 39% had no remission. This contrasts with previous studies in Ethiopia,63 where 46% had early remission, 18% had late remission and 35.4% had no remission, and in China,79 where 51.6% had early remission, and 17.5% had late remission. Differences in study design, duration, participant characteristics and sample size could potentially explain these discrepancies.

The study also assessed seizure-remission and relapse, with 20.8% of participants experiencing seizures after achieving seizure-remission, a lower rate than reported in other studies: 36.6%,73 40%80 and 28.7%.63 This difference may be attributed to longer follow-up periods and large sample sizes in previous studies. This finding implies that there is a high probability of experiencing seizures after seizure remission is achieved. The American College of Neurology indicates that most seizure recurrences occur within the first year, with cumulative incidence increasing over time.81 Therefore, it is important to have sufficient follow-up periods and evaluate the patient’s neurological, cognitive and EEG status before considering discontinuing an AED treatment in epileptic patients.82 83

Determining the predictors of treatment outcomes was another key objective of the current study. The findings revealed that place of residence, employment status and the number of seizure attacks before treatment were predictors of treatment outcome. These findings differed from those of a previous study conducted in Scotland, where a shorter pretreatment duration, good adherence to AEDs and monotherapy were identified as predictors of favourable seizure control.74 Similarly, a study conducted in Ethiopia showed that poor adherence to AEDs and a history of multiple pretreatment seizures were associated with a lower likelihood of seizure remission.76 The differences observed between these studies highlight the importance of considering contextual factors that may influence epilepsy management and treatment outcomes. Factors such as access to healthcare, socioeconomic status and disease severity can vary across settings and play a critical role in shaping the determinants of successful epilepsy treatment.

Similar to previous studies,50 84 85 epileptic patients residing in urban areas were 1.64 times more likely to achieve seizure remission than rural residents. This may be due to patients in urban areas having better access to healthcare services, enabling them to communicate more easily with their healthcare providers. They are more informed about their medical conditions and medications compared with those living in rural areas. In addition, rural residents have more affiliation with religious and traditional medicine, which might affect their healthcare-seeking behaviour and result in poor seizure control.86 87 Therefore, it is important to expand epilepsy care services to primary healthcare facilities and provide comprehensive training to healthcare professionals working in rural areas.

A significant proportion (48.6%) of the study participants with epilepsy were unemployed and experienced poorer seizure control compared with those who were employed. Government employees and students demonstrated better seizure control, with 4 and 3.35 times higher likelihood of seizure remission than unemployed individuals. This finding is consistent with previous studies,88–90 suggesting that employment status may play a role in epilepsy management and treatment outcomes. Unlike other medical conditions, the unpredictable and visible nature of seizures in epileptic patients often leads to significant barriers and social discrimination.88 Many employers are reluctant to hire individuals with epilepsy due to concerns over workplace accidents and high rates of workplace absenteeism.91 92 Moreover, the presence of comorbid mental disorders, low educational background and qualifications also contributes to the high unemployment rate in this population. It is crucial to enhance public awareness about epilepsy, challenge prevailing misconceptions and advocate for equal employment opportunities for people living with epilepsy.16 42

The frequency of seizure episodes before starting AED treatment was another predictor of treatment outcomes. Epileptic patients who experienced more than five seizure episodes before starting AED treatment were less likely to achieve seizure remission than those with fewer seizures before treatment. This finding aligns with previous studies,63 93 implying that the number of seizure attacks before treatment has an impact on the rate of seizure control. One possible explanation for this finding is that frequent and prolonged seizures can cause further structural and neurological damage, potentially leading to the development of new epileptic foci, which can ultimately reduce the rate of seizure control.94 95 Additionally, multiple seizure episodes before AED treatment may inherently alter the target receptors for AEDs and exacerbate the severity of the disease, compromising the response to AEDs.96 Studies suggest that early identification and prompt treatment of epileptic seizures are associated with a higher likelihood of achieving seizure remission and less risk of seizure relapse.97 98

The other aim of our study was to assess medication adherence and associated factors. Only 174 (49.6%) of the study participants were adherent to their medications, which closely aligns with studies conducted in Pakistan, Malaysia and China, which reported adherence rates of 50%, 50.7% and 51.9%, respectively.48 99 100 However, AED adherence in the current study was significantly lower than in studies conducted in India (70%)101 and Pakistan (73.33%).102 The differences in medication adherence between previous studies and our findings may stem from several factors, including variations in sample size, treatment duration, access to healthcare resources, insurance coverage, and sociodemographic, and cultural variations.

Like other chronic conditions, multiple factors determine the adherence status in epileptic patients.103 Unavailability of AEDs 160 (45.58%), feeling hassled to stick with the treatment plan 159 (45.3%), and forgetfulness 145 (42%) were the most reported reasons for non-adherence. This was congruent with other studies104 105 in which forgetfulness, running out of AEDs and missing medication were commonly reported in patients with poor AED adherence. In contrast to this study, previous studies conducted in Saudi Arabia106 and Nigeria107 showed that forgetfulness (64.5%), use of alternative therapies (10%), younger age (≤35 years), use of other concomitant medications, recent episode of the seizures (≤1 month), missing medication, drug-related fatigue and being away from home were significantly associated with AEDs non-adherence. The possible justifications for such inconsistency might be the difference in methodology and tools used to assess medication adherence, healthcare accessibility, medication availability and sociodemographic factors.

Identifying the barriers to AED non-adherence is one strategy to improve the level of medication adherence in people living with epilepsy.108 In the current study, current occupation, comorbidity and seizure-free period were significantly associated with AED adherence (table 4), which were different from studies done in Sudan109 and Ethiopia110 where having depressive and anxiety symptoms, perceived stigma, being single, presence of seizures per month and having ADRs were factors associated with AED adherence.

Nearly half of the study participants were unemployed, with farmers and housewives showing better adherence to AED treatment compared with unemployed patients. The visible and unpredictable nature of seizure attacks causes epileptic patients to become isolated from the social environment. Poorly controlled seizures can disrupt daily tasks, leading to a significantly higher rate of unemployment and underemployment in this population compared with the general population and those with other health conditions.111 112 In addition, employed patients tend to be financially stable, making it easier for them to afford treatment costs, transportation and daily needs compared with those who are unemployed.

Patients without comorbidities were about twice more adherent to their prescribed AEDs as compared with those with comorbidities, which is consistent with other studies.104 110 Comorbidities commonly found in epileptic patients such as anxiety, depression, migraine and other neurodegenerative disorders are significantly related to low mood, lack of interest, fatigue and cognitive impairments which can decrease the motivation of epileptic patients to adhere to their AEDs.113–115 Additionally, many medications used to treat these comorbidities and AEDs have multiple drug–drug interactions and overlapping ADEs, which can contribute to treatment discontinuation.110 This suggests that the treatment of epilepsy should be individualised, with special attention given to epileptic patients with comorbidities.

This multicentre observational cross-sectional study aimed to evaluate treatment response, medication adherence and predictors across multiple centres, using a reasonable sample size and validated assessment tools. However, this study had limitations. If a cohort study design with a longer follow-up had been used, the strength of association among the factors might have been stronger. The study’s generalisability may be limited as it only included adult epilepsy patients; consequently, the results may not apply to paediatric or adolescent populations. The study did not address treatment outcomes and prognosis of drug-resistant epilepsy, which could be a focus for future research.

Conclusions

More than two-thirds of epileptic patients had poor seizure control. Living in rural areas, unemployment and frequent seizure episodes before treatments were predictors of poor treatment outcomes. In addition, half of the study participants had low adherence to their AEDs. Unemployment, frequent seizure episodes before AED treatment, comorbidity and poor seizure control were factors significantly associated with medication non-adherence. These findings highlight the need for targeted interventions to improve treatment outcomes and medication adherence among individuals with epilepsy, particularly those with advanced age, comorbidities and patients with a history of frequent seizures before treatment.

Data availability statement

Data are available on reasonable request. The data sets including analysed data and information that support the conclusion are found with the corresponding author on reasonable request.

Ethics statements

Acknowledgments

The authors would like to acknowledge the study participants for their willingness to participate in this study and for giving their valuable time to respond to the questions. We are also thankful to the data collectors and supervisors, administrators and staff of the three hospitals for their cooperation during the data collection process. Finally, we are grateful to thank the School of Pharmacy, College of Health Sciences, Addis Ababa University for supporting the study.