INTRODUCTION

Epilepsy stands as one of the most prevalent long-term neurological conditions, impacting

nearly 50 million individuals worldwide, with a notable concentration of cases found in low- and

middle-income regions [1]. Among children, it represents a major cause of neurological illness,

frequently requiring prolonged treatment with antiepileptic drugs (AEDs) [2]. These

anticonvulsant medications, while essential for controlling seizures, are known to influence

various bodily systems, including lipid metabolism [3]. The link between AED use and changes

in lipid profiles holds particular clinical relevance in pediatric patients, as such metabolic

disturbances could increase the risk of developing cardiovascular issues at an early age [4].

Lipid profiles, comprising serum total cholesterol, low-density lipoprotein (LDL), high-

density lipoprotein (HDL), and triglycerides, are well-established biomarkers of cardiovascular

health [5]. Dyslipidemia, characterized by abnormalities in these lipid parameters, has been

implicated in the pathogenesis of atherosclerosis and metabolic syndrome [6]. While the impact

of anticonvulsant therapy on lipid metabolism in adults has been extensively studied, limited data

exist regarding its effects on pediatric populations [7]. Children on long-term AED therapy

represent a unique demographic, as their developing metabolic systems and prolonged drug

exposure may amplify such adverse effects [8].

The relationship between AEDs and lipid metabolism stems from the influence of these

drugs on hepatic enzyme activity, particularly cytochrome P450 enzymes [9]. Conventional

AEDs such as phenobarbital, phenytoin, and carbamazepine are potent enzyme inducers, leading

to enhanced lipid metabolism and altered serum lipid levels [10]. Conversely, newer AEDs like

levetiracetam and lamotrigine, which are not hepatic enzyme inducers, exhibit a distinct

metabolic profile [11]. The differentiation in metabolic pathways between conventional and
newer AEDs necessitates a thorough investigation into their respective effects on lipid profiles

[12].

Multiple investigations have highlighted a link between prolonged use of antiepileptic

drugs (AEDs) and the development of dyslipidemia in pediatric patients. For instance, Verrotti et

al. documented markedly increased levels of total cholesterol and low-density lipoprotein (LDL)

in children receiving enzyme-inducing AEDs when compared to healthy counterparts [13].

Similarly, Bhadran et al. identified comparable metabolic disruptions in South Indian children,

particularly those on carbamazepine and valproate therapy [14]. Despite these findings, the

influence of newer-generation AEDs on lipid parameters remains unclear, as some research

reports indicate minimal or no significant changes [15]. In light of these observations, the current

study was designed to evaluate serum lipid alterations associated with AED use, aiming to

identify the safest therapeutic option and to mitigate future cardiovascular risks.
AIM & OBJECTIVES

AIM:

To study the effect of anti-convulsant on Lipid Profile (serum total cholesterol, LDL, HDL)

in children on single drug anti-convulsant therapy

OBJECTIVES:

 To determine the effect of commonly used anti-convulsant on lipid profile (serum total

cholesterol, LDL, HDL) in children with seizure disorder.

 To study the effect of newer anti-convulsant on lipid profile and to compare them with

conventional anti-convulsant.
REVIEW OF LITERATURE

Background of Epilepsy in Children:

Atypical electrical activity in the brain causes epilepsy, a long-standing neurological condition

characterised by recurrent seizures that have no recognised cause [2]. It is one of the most

common neurological disorders in the world, impacting between 0.5% and 1% of the population

[1]. With a significant percentage of diagnoses taking place in early life and adolescence,

children are most impacted [16]. The complicated interplay of brain development, neurological

variables, and psychosocial effects that can change the disorder's course and response to therapy

makes managing epilepsy in the paediatric age range particularly challenging [17].

Epidemiology of Epilepsy in Children:

The occurrence and distribution of epilepsy among children differ widely between

regions, shaped by a mix of hereditary, environmental, and socioeconomic influences [18]. On a

global scale, pediatric epilepsy is estimated to affect between 50 and 100 individuals per 100,000

person-years [19]. Higher incidence rates are frequently observed in low- and middle-income

nations, largely due to a greater prevalence of risk factors like birth-related complications,

infections of the central nervous system (CNS), and head injuries [20]. In the Indian context,

epilepsy affects roughly 3 to 10 out of every 1,000 children [21]. Detecting and managing

epilepsy early in life is vital to reducing long-term complications such as cognitive deficits and

social or emotional challenges [22].

Aetiology of Pediatrics Epilepsy:

Epilepsy in children arises from a wide spectrum of causes, which include both inherited

factors and brain injuries acquired before or after birth. Structural, genetic, infectious, metabolic,
immune-mediated, and those of unknown origin—often referred to as idiopathic or cryptogenic

epilepsy—are some possible classifications for the underlying aetiologies [23].

Genetic Factors: With progress in genomic studies, several epilepsy syndromes have been

traced to inherited mutations. One notable example is Dravet syndrome, which is linked to

mutations in the SCN1A gene. These genetically based epilepsies often display characteristic

clinical and EEG patterns, which assist in achieving a timely and accurate diagnosis [24].

Structural Factors: Abnormal brain development (such as cortical dysplasia or

lissencephaly) as well as damage caused by trauma, tumors, or other insults fall under structural

causes [25]. To find these structural anomalies, advanced neuroimaging methods are crucial,

especially magnetic resonance imaging (MRI) [26].

Infectious Causes: CNS infections, including meningitis, encephalitis, and

neurocysticercosis, are significant contributors to epilepsy, particularly in endemic regions. In

children, neonatal infections like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus,

Herpes simplex) can result in epilepsy [27].

Metabolic and Immune Causes: Rare metabolic disorders such as pyridoxine-dependent

epilepsy and mitochondrial diseases may underlie seizures [28]. Autoimmune conditions,

including anti-NMDA receptor encephalitis, are emerging as important causes [29].

Idiopathic Epilepsy: Childhood absence epilepsy and benign epilepsy with centrotemporal

spikes are examples of idiopathic epilepsies, which are thought to have a genetic foundation

despite having no discernible structural or metabolic aetiology.

Classification of Epilepsy in Children:

 Epilepsy classification has evolved significantly, with the International League Against

Epilepsy (ILAE) providing a framework to categorize epilepsy into focal, generalized, and

combined focal and generalized types [30]. The classification emphasizes etiology and syndrome

diagnosis to tailor therapeutic strategies [31].

1. Focal Epilepsies: These originate from specific regions of the brain and may manifest with

motor, sensory, or autonomic symptoms. Temporal lobe epilepsy is a common subtype in

children.

2. Generalized Epilepsies: These involve widespread brain networks from onset and are

characterized by seizure types such as absence, myoclonic, and generalized tonic-clonic

seizures.

3. Epileptic Syndromes: Syndromic classifications include conditions such as Lennox-Gastaut

syndrome, which presents with mixed seizure types, and West syndrome, associated with

infantile spasms and developmental regression.

Impact of Epilepsy on Children:

Beyond just seizure management, epilepsy has a substantial impact on children's quality of life.

Children with epilepsy frequently experience developmental delays, learning impairments, and

cognitive abnormalities. According to studies, early onset and frequent seizures are important

risk factors for neurocognitive deficits.

Cognitive and Behavioral Issues: Children with epilepsy exhibit a higher prevalence of

attention deficit hyperactivity disorder (ADHD), anxiety, and depression [32]. These

comorbidities often stem from both the underlying brain dysfunction and psychosocial factors

such as stigma.
Educational Challenges: School attendance and performance may be disrupted due to seizures,

medication side effects, and frequent hospital visits [33]. Interventions aimed at supporting

educational outcomes are critical.

Social and Family Dynamics: The diagnosis of epilepsy can lead to social isolation and reduced

participation in recreational activities. Families often experience increased caregiving burdens,

financial strain, and emotional stress [34].

Antiepileptic Drug Therapy in Children

Antiepileptic drug (AED) therapy remains the cornerstone of pediatric epilepsy treatment, with

the primary goal of suppressing seizures while minimizing adverse effects. Selecting the

appropriate AED is guided by the specific type of seizure, the broader epilepsy classification, and

the unique clinical profile of each child [35].

Conventional AEDs: Valproate, carbamazepine, and phenobarbital are examples of traditional

antiepileptic drugs that have been used in clinical settings for a long time and are known to be

effective [36]. Notwithstanding their efficacy, these medications are commonly associated with

unfavourable adverse effects, including fatigue, behavioural or emotional abnormalities, and

alterations in metabolic functions.

Newer AEDs: Levetiracetam, lamotrigine, and topiramate are increasingly used due to their

improved safety profiles and efficacy. However, concerns about long-term metabolic effects,

such as altered lipid profiles, are emerging [37].

Drug Resistance: Roughly 20% to 30% of pediatric epilepsy cases are classified as drug-

resistant, meaning seizures persist despite proper use of two suitable antiepileptic medications at
therapeutic doses [38]. In such instances, alternative treatment strategies—such as the ketogenic

diet or surgical intervention—may become necessary to manage the condition effectively.

Metabolic Effects of AEDs

AEDs influence various metabolic pathways, leading to potential side effects, including

dyslipidaemia. Enzyme-inducing AEDs, such as carbamazepine and phenytoin, accelerate lipid

metabolism, often increasing total cholesterol and LDL levels. Conversely, non-inducing drugs

like valproate may contribute to weight gain and insulin resistance, further complicating

metabolic profiles. These effects underscore the need for regular monitoring of lipid profiles in

children on long-term AED therapy [39].

The influence of antiseizure drugs (ASM) on metabolic markers is a significant factor in

their adverse effect profile. The negative metabolic profiles of the earlier or first and second

generation ASMs, including carbamazepine, valproate, phenytoin, and phenobarbitone, as well

as, to a lesser extent, the more recent ASMs, are extensively described in scientific literature.

[40] ASMs can cause early atherosclerosis, especially those that induce enzymes. However,

because of their accessibility and low cost, these older drugs still occupy a firm place in the

arsenal of treatments for epilepsy in places with little resources, like India. Therefore,

practitioners of epilepsy in our settings need to be cognisant of these metabolic impacts.

Numerous prospective and cross-sectional studies show a link between the emergence of

vascular metabolic risk factors and the length of time spent using ASM.[40-43]

Hyperhomocysteinemia, lipid profile abnormalities, increased uric acid, weight gain and obesity,

thyroid dysfunction, insulin resistance, and diabetes are only a few of these detrimental

outcomes.[40-43] For children with epilepsy taking valproate, levetiracetam, lamotrigine, or

topiramate, carotid intima-media thickness (CIMT) has been increasingly identified as a sign of

early atherosclerosis.[44,45] It's uncertain if these results can be disassociated from the negative

effects of these ASMs on lipid levels.

Serum Lipid Concentrations and the Effects of Antiepileptic Drugs (AEDs)

Antiepileptic drugs (AEDs) have long been associated with alterations in blood lipid

profiles. While some investigations have explored this relationship in adults, most of the existing

literature focuses on pediatric populations.

In one study, researchers assessed a number of lipid parameters, such as total cholesterol,

triglycerides, HDL and LDL cholesterol (with further breakdown into HDL-2 and HDL-3), and

apolipoproteins A1 and B, in 120 adults with epilepsy who were receiving treatment with

carbamazepine (n = 42), sodium valproate (n = 38), and phenytoin (n = 40). Following that,

these outcomes were contrasted with those of a control group consisting of 48 healthy people

[68]. They found that those treated with carbamazepine especially showed an increase in high-

density lipoprotein-2 cholesterol, whereas those treated with phenytoin mostly showed an

increase in triglycerides. Except for apolipoprotein and high-density lipoprotein cholesterol, all

of these changes were significantly greater in women than in males. There was no obvious

correlation between the amount of AEDs in the blood and particular alterations in lipid levels.

Notably, as compared to healthy controls, valproate users showed no lipid abnormalities. These

results imply that whereas non-enzyme-inducing medications, especially those that do not

interact with the cytochrome P450 system, seem to have little to no effect on lipid metabolism,

enzyme-inducing AEDs may. This study also found differences in lipid responses by gender

[68].
 Changes in lipid profiles are noted in all age groups, with patterns in children being similar

to those in adults. In a study comparing lipid levels—such as triglycerides, total cholesterol, and

HDL cholesterol—between 208 epileptic children and 175 healthy peers, enzyme-inducing

AEDs like carbamazepine, phenobarbital, and phenytoin were linked to elevated total

cholesterol. However, valproate-treated children showed lipid levels similar to the control group.

This is likely due to hepatic enzyme induction by drugs that affect the cytochrome P450

pathway. Notably, triglycerides and HDL cholesterol remained unaffected across all AED groups.

Based on these outcomes, researchers recommended routine monitoring of total cholesterol in

patients on enzyme-inducing AEDs [79].

In a more recent longitudinal study, the lipid and liver enzyme profiles of 64 children aged

1 to 15 receiving phenobarbital, carbamazepine, or valproate were tracked. Apolipoproteins A

and B, total cholesterol, triglycerides, LDL, HDL, and liver function indicators (ALT, AST, ALP,

and GGT) were measured throughout a 12-month period. At 3, 6, and 12 months, lipoprotein

levels significantly increased in all therapy groups. Over the course of the trial, there were

noticeable increases in lipid levels and liver enzymes, especially in the phenobarbital group. For

children on carbamazepine, increased lipoproteins were only observed at 6 and 12 months.

According to Sonmez et al. [82], elevated lipoprotein levels above 30 mg/dL were found in 44%

of the phenobarbital group, 63% of the carbamazepine group, and 33% of those on valproate.

AED-induced lipid alterations may potentially be moderated by diet. Castro-Gago et al.

(2006) examined the effects of a low-fat diet on the levels of lipid and lipoprotein(a) in children

with epilepsy who were taking carbamazepine, valproate, or phenobarbital. Lipid parameters

were measured on a normal diet, after switching to a low-fat diet (particularly for those with

increased lipid levels), and three months after stopping AED therapy for the individuals (20 on
carbamazepine, 25 on valproate, and 5 on phenobarbital). A low-fat diet was shown to

significantly normalise the severe lipid abnormalities that emerged on a conventional diet,

indicating that dietary changes may help reduce lipid disturbances associated with AEDs [83].

Serum lipid levels were measured at the start and finish of treatment for 30 children, ages

30 months to 14 years, who were receiving carbamazepine monotherapy for idiopathic or

cryptogenic partial or generalised tonic-clonic seizures. Following therapy, there were notable

increases in total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein

(VLDL), and triglycerides, but no discernible change in high-density lipoprotein (HDL) levels.

These findings are consistent with other research indicating that carbamazepine modifies

children's blood lipid profiles, thereby raising their chance of developing atherosclerosis in the

future [84].

Measurements of triglycerides, LDL and HDL cholesterol, apolipoproteins A1 and B, and

liver and renal function indicators were taken at baseline, 6, 12, and 24 months. Both

carbamazepine and valproate treatment led to elevated serum lipoprotein(a) levels over time.

These studies recommend regular monitoring of lipoprotein(a) levels in children undergoing

treatment with these AEDs [85].

Isojarvi et al. [41] examined the long-term effects of carbamazepine on lipid

concentrations, finding that while the increases in triglycerides and LDL cholesterol were

temporary, total cholesterol and HDL cholesterol remained elevated. These changes in lipid

metabolism were potentially linked to elevated liver enzymes during carbamazepine therapy, and

such lipid shifts may have clinical implications for atherosclerosis and coronary heart disease in

epileptic patients. Eiris et al. [42] also noted that long-term carbamazepine and phenobarbital

treatment in children could increase the risk of atherosclerosis-related diseases.

 Nikolaos et al. [54] examined the long-term effects of carbamazepine, phenobarbital,

valproate, and phenytoin administration on serum levels of cholesterol and lipoproteins in a

study comparing enzyme-inducing antiepileptic drugs with nonenzyme inducers. The data

pertaining to phenobarbital and carbamazepine showed the same outcomes as those reported in

earlier research. While valproate patients had nonsignificant differences in high-density

lipoprotein-C values and significantly lower total cholesterol, low-density lipoprotein-C, and

triglyceride values, phenytoin patients had significantly higher low-density lipoprotein-C values

and nonsignificant differences in the other parameters. As mentioned earlier, dietary adjustments

might be helpful. Patients receiving phenytoin and carbamazepine were advised to follow a low-

cholesterol diet (Nikolaos et al., 2004).

LITERATURE REVIEW:

 A prospective hospital-based cross-sectional study on the impact of different antiepileptic

medications (AEDs) on lipid profiles was carried out by Manimekalai K et al., [46]. They

compared 60 epileptic patients (who were split into groups receiving phenytoin,

oxcarbazepine, valproic acid, and levetiracetam) to 80 age- and sex-matched controls.

On the other hand, valproate and levetiracetam, which are AEDs that do not induce

enzymes, did not significantly change lipid metrics. The study emphasises how

important it is to keep an eye on lipid profiles in patients on enzyme-inducing AEDs in

order to reduce the risk of cardiovascular disease. Despite having a strong design and

being clinically relevant, the study's limitations in terms of sample size and duration of

medication exposure indicate that further extensive research is required to confirm these

results and improve clinical recommendations.

 In a research by Verrotti et al. [47], 114 children and adolescents with epilepsy and 100

healthy controls were compared to see how long-term AED medication affected their

lipid and lipoprotein profiles. The patients were categorised into three groups according

to the medications they were taking: sodium valproate, carbamazepine, and

phenobarbital. While valproate therapy increased HDL cholesterol and decreased

triglycerides and LDL cholesterol, carbamazepine treatment increased total cholesterol,

triglycerides, LDL, and HDL cholesterol. The significance of routine lipid monitoring

during therapy to address possible metabolic concerns is highlighted by these findings,

which also demonstrate the unique and medication-specific effects of AEDs on lipid

metabolism. The possibility of normalisation upon medication termination is highlighted

by the reversible nature of the lipid alterations observed with phenobarbital.

 A research by Nadkarni et al. [48] examined how AEDs affected the lipid profiles of 95

children with primary epilepsy (ages 2 to 15) and 50 healthy controls. Serum

triglycerides, LDL cholesterol, and VLDL cholesterol varied significantly among the

children who had been on phenytoin, valproic acid, or a combination of both for at least

three months. Significant variations in HDL-C, LDL-C, and the lipid risk ratio were also

found by statistical testing. These results highlight how crucial it is to routinely check

lipid profiles in kids with epilepsy on AEDs in order to identify and manage any

cardiovascular risks as soon as possible.

 In a different research by Neethu et al. [49], 150 adult epileptic patients (mean age 35.54

± 10.72 years) had their blood lipid profiles evaluated in relation to 50 age- and sex-

matched controls to determine the effect of AED monotherapy. While carbamazepine and

sodium valproate medication were associated with severe hypertriglyceridemia,

 individuals on phenytoin for more than a year showed considerable increases in total

cholesterol and triglycerides. Changes in lipid profiles were shown to be strongly

correlated with the length of AED administration. These results demonstrate the

propensity of conventional AEDs to induce dyslipidaemia, emphasising the necessity of

regular lipid monitoring to lower the risk of associated health problems and enhance the

long-term quality of life for patients who do not exhibit any symptoms.

 Comparing the effects of AED monotherapy on lipid profiles in 150 epileptic patients

(mean age 35.54 ± 10.72 years) to 50 healthy controls was another research conducted by

Eiri et al. [50]. Patients on phenytoin for more than a year saw statistically significant

increases in total cholesterol and triglycerides, whereas those on carbamazepine and

sodium valproate experienced severe hypertriglyceridemia. The study also discovered a

strong correlation between the length of AED treatment and alterations in lipid profiles,

highlighting the tendency of traditional AEDs to cause dyslipidaemia and the necessity of

routine lipid monitoring to reduce related health concerns.

 A prospective comparative study by Srikanth et al. [51], conducted at Niloufer Hospital

for Women and Children in Hyderabad from January 2019 to August 2020, involved 78

children aged 1 to 12 years with seizures. All participants had been on AEDs for at least

six months and had no prior neurological, psychiatric, or medical conditions. The study

found a positive correlation between total cholesterol levels at admission and after six

months of levetiracetam treatment (p = 0.014), as well as a notable increase in LDL

cholesterol levels (p = 0.003). These results suggest that levetiracetam, similar to other

AEDs, may affect lipid metabolism in children. The study emphasizes the need for

careful selection of AEDs, especially for children with existing heart conditions or stroke
risks. It also underscores that while AEDs like valproate, phenytoin, and levetiracetam

are effective for long-term seizure control with minimal side effects, regular monitoring

of lipid profiles is crucial, particularly for vulnerable groups.

 METHODOLOGY

Study Design: This study was a case-control study

Study Setting: This research was a case-control study conducted at the Gayatri Vidya Parishad

Institute of Health Care and Medical Technology, located in Marikavalasa, Visakhapatnam. The

study was carried out across both the Outpatient and Inpatient Pediatrics Departments of the

hospital. The investigation spanned 18 months, from July 2023 to December 2024.

Study Population: The study population consisted of two groups:

 Cases: Children diagnosed with seizure disorders who had been on a single-drug

antiepileptic therapy (AED) for at least six months. These children were under follow-up

care at the hospital.

 Controls: Healthy children who were age- and sex-matched with the cases.

The inclusion criteria for cases were:

 Children aged less than 12 years.

 Children who had been receiving single-drug AED therapy for at least six months.

Exclusion criteria included:

 Children with any diseases known to alter lipid profiles, such as nephrotic

syndrome.

 Children receiving combination AED therapy.

 Children with thyroid disorders or other endocrinopathies.

 Children with chronic liver, heart, or renal disease, or those with progressive

neurological or psychiatric illnesses.

  Guardians who refused to provide informed consent.

Data Collection:

After obtaining written informed consent from the parents or guardians, clinical evaluations were

conducted. The following demographic and clinical data were collected:

 Age, sex, type of seizures.

 Duration of AED therapy and the specific drug(s) used.

 Family history of stroke or cardiovascular diseases.

Each participant had a thorough systematic evaluation to confirm their eligibility. We measured

weight and height according to recognised protocols. Children wore very little clothes, and a

calibrated stadiometer was used to measure height and a conventional weighing scale to measure

weight.

Biochemical Analysis:

Following an overnight fast, each participant had a 3 mL blood sample taken for the examination

of their serum lipid profile. Measurements were made of the following parameters:

 Serum Total Cholesterol (TC): Assessed using the cholesterol oxidase peroxidase

enzyme method.

 High-Density Lipoprotein Cholesterol (HDL-C): Measured using the direct enzymatic

analysis method.

 Triglycerides (TG): Measured using the glycerol peroxidase method.

 Low-Density Lipoprotein Cholesterol (LDL-C): Calculated using the Friedewald

formula:
Sample Size Calculation:

Bhadran K, Bhavani N, Vinayan KP, Pavithran PV. Metabolic effects of long-term antiepileptic

drug therapy in South Indian children. [14]

Variable Cases Mean (SD) Controls Mean (SD)

Serum Total Cholesterol 179.66 (31.23) 163.205 (15.04)

LDL 108.19 (20.66) 91.995 (13.86)

HDL 53.29 (11.12) 50.309 (6.36)

Sample size for hypothesis testing about difference between means,

( )
2 2
z α −z β σ
1−
2
n=2
(d)2

With finite population correction, α = 5% (95% Confidence Interval), 1-β (power) = 80%, Z 1-α/2

= 1.96, Zβ = -1.28 and σ2 = SD12 + SD22 / 2, d = 10% (absolute error of margin)

Sample size with difference between mean Total Cholesterol (n1) = 38

Sample size with difference between mean LDL (n2) = 21

Sample size with difference between mean HDL (n3) = 06

Hence, we have taken minimum sample size of 38 from each group.

The sample size was determined based on previous studies and sample size estimation formulas.

For a 95% confidence interval and a power of 80%, a minimum of 38 participants per group was

required. The total sample size for the study was 76 participants (38 in each group: cases and

controls).

Ethical Considerations:

• Informed permission: Parents or guardians were asked to provide written informed permission,

attesting to their understanding of the goals and protocols of the study.

• Ethics Committee Approval: To guarantee adherence to ethical norms, the study was

authorised by the institutional ethics committee.

• Confidentiality: To preserve the privacy of the participants, their personal and medical data

was anonymised and stored securely.

Parents and guardians were advised that participation in the study was entirely optional and that

they might leave at any moment without facing any repercussions.

• Minimisation of Harm: The study included routine blood testing to reduce hazards and ensure

participants' safety and wellbeing.

Throughout the trial, the wellbeing of the kid was given first priority, and if any negative effects

were found, prompt medical attention was given.

Data Analysis

SPSS software and Microsoft Excel were used to process the data. Continuous data were

displayed as means and standard deviations or as medians with ranges, while categorical

variables were displayed as frequencies and percentages using descriptive statistics. An

independent sample t-test was used to compare the means of the case and control groups.

Analysis of variance (ANOVA) was used to compare the control, monotherapy, and polytherapy

groups. Statistical significance was defined as a p-value of less than 0.05.

 RESULTS

PHENYTOIN

Table 1: Age category of Phenytoin group

Age category Control Group Study Group P value

< 2 years 6 (15.8%) 8 (21.1%)

3-5 years 9 (23.7%) 20 (52.6%)

6-8 Years 11 (23.9%) 4 (10.5%) 0.745

9-12 Years 12 (31.6%) 6 (15.8%)

Total 38 (100%) 38 (100%)

The table presents the age distribution of participants in both the control and study groups, each

comprising 38 individuals. In the control group, the largest age group was 9-12 years (31.6%),

followed by 6-8 years (23.9%), 3-5 years (23.7%), and <2 years (15.8%). In contrast, the study

group had the highest proportion in the 3-5 years range (52.6%), with smaller percentages in the

9-12 years (15.8%), <2 years (21.1%), and 6-8 years (10.5%) categories. A P-value of 0.745

suggests that there is no statistically significant difference in age distribution between groups.

Control Group Study Group

20

12
11
9
8
6 6
4

< 2 years 3-5 years 6-8 Years 9-12 Years

Figure 1: Age category of Phenytoin group

Table 2: Gender of Phenytoin group

Gender Control Group Study Group P value

Male 14 (36.8%) 20 (52.6%)

Female 24 (63.2%) 18 (47.4%) 0.356

Total 38 (100%) 38 (100%)

Both the control and study groups' gender distributions indicate a somewhat larger proportion of

women. 24 children, or 63.2% of the control group, are female, whereas 14 children, or 36.8%,

are male. Males make up 52.6% (20 children) of the study group, while females make up 47.4%

(18 children). With a p-value of 0.356, the gender distribution difference between the two

groups is not statistically significant.

30

25 24

20
20 18

15 14

10

0
Control Group Study Group

Male Female

Figure 2: Gender of Phenytoin group

Table 3: Duration of Epilepsy in Phenytoin group

Duration of Epilepsy Study Group

< 2 years 5 (13.2%)

2-5 Years 25 (65.8%)

>5 Years 8 (21.1%)

Total 38 (100%)

The duration of epilepsy in the Phenytoin-using research group is as follows: Of those with

epilepsy, 13.2% (5 people) have had it for less than 2 years, 65.8% (25 people) for 2–5 years, and

21.1% (8 people) for more than 5 years. 38 individuals, or 100% of the group, make up the

study group's entire sample size.

13.2%
21.1%

< 2 years
2-5 Years
>5 Years

65.8%

Figure 3: Duration of Epilepsy in Phenytoin group

Table 4: Family History in Phenytoin group

Family History Control Group Study Group P Value

Positive family history 8 (21.1%) 1 (2.6%) 0.004

Negative family history 30 (78.9%) 37 (97.4%)

Total 38 (100%) 38 (100%)

The control and study groups differ significantly when comparing their family histories of

epilepsy. Only 2.6% (1 kid) of the research group had a favourable family history, compared to

21.1% (8 children) of the control group. With 78.9% (30 children) in the control group and

97.4% (37 children) in the study group, the majority of participants in both categories have a

negative family history. With a p-value of 0.004, this difference is statistically significant.

37
Negative family history
30

1
Positive family history
8

0 5 10 15 20 25 30 35 40

Study Group Control Group

Figure 4: Family History in Phenytoin group

Table 5: Parameters in Phenytoin group

Parameter Control (Mean ± SD) Cases (Mean ± SD) P Value

Cholesterol 113.15 ± 9.74 173.22 ± 36.13 0.000

LDL 98.03 ± 7.15 162.03 ± 29.98 0.000

TGS 90.62 ± 8.53 131.83 ± 44.30 0.000

HDL 60.62 ± 15.13 48.62 ± 9.94 0.000

VLDL 21.86 ± 7.75 20.62 ± 9.14 0.268

The data comparing the control and study groups across various parameters are as follows:

 A p-value of 0.000 indicates a statistically significant difference in cholesterol levels between

the case group (173.22 ± 36.13) and the control group (113.15 ± 9.74).

 With a p-value of 0.000, LDL values also demonstrate a substantial rise in the case group

(162.03 ± 29.98) in comparison to the control group (98.03 ± 7.15).

 With a p-value of 0.000, the case group's triglycerides (TGS) are substantially higher (131.83

± 44.30) than those of the control group (90.62 ± 8.53).

 There is a statistically significant difference (p-value of 0.000) in HDL between the case

group (48.62 ± 9.94) and the control group (60.62 ± 15.13).

 The two groups' VLDL levels are nearly identical, with the case group's mean being 20.62 ±

9.14 and the control group's being 21.86 ± 7.75. Nevertheless, there is no statistically

significant difference, as indicated by the p-value of 0.268.

LEVETIRACETAM
Table 6: Age categories in Levetiracetam

Age category Control Group Study Group P value

< 2 years 6 (15.8%) 6 (15.8%)

3-5 years 9 (23.7%) 9 (23.7%)

6-8 Years 11 (23.9%) 16 (42.1%) 0.781

9-12 Years 12 (31.6%) 5 (13.2%)

Total 38 (100%) 38 (100%)

The age distribution of the 38 participants in the control and study groups is displayed in the

table. The percentage of participants in the <2 years (15.8%, 6 participants) and 3-5 years

(23.7%, 9 participants) groups was the same for both groups. However, compared to the control

group (23.9%, 11 individuals), a larger proportion of participants in the study group (42.1%)

were between the ages of 6 and 8. However, compared to the research group (13.2%, 5

participants), the control group had a higher percentage of individuals aged 9–12 years (31.6%,

12 participants). These variations are not statistically significant, according to the p-value of

18
16
14
12
10
8
6
4
2
0
< 2 years 3-5 years 6-8 Years 9-12 Years

Control Group Study Group

0.781.

Figure 6: Age categories in Levetiracetam

Table 7: Gender distribution in Levetiracetam

 Gender Control Group Study Group P value

Male 14 (36.8%) 14 (36.8%)

Female 24 (63.8%) 24 (63.8%) 1

Total 38 (100%) 38 (100%)

In terms of gender distribution, both the control and study groups consist of 14 male children

(36.8%) and 24 female children (63.8%). The gender differences between the two groups are not

statistically significant, as indicated by a p-value of 1.

30

25

20

15

10

0
Male Female

Control Group Study Group

Figure 6: Gender distribution in Levetiracetam

Table 8: Duration of Epilepsy in Levetiracetam

 Duration of Epilepsy Study Group

< 2 years 7 (18.4%)

2-5 Years 22 (57.9%)

>5 Years 9 (23.7%)

Total 38 (100%)

In the study group treated with levetiracetam, the distribution of epilepsy duration is as follows:

18.4% (7 participants) have had epilepsy for under 2 years, 57.9% (22 participants) for 2-5 years,

and 23.7% (9 participants) for over 5 years. The total number of participants in the study group is

38, accounting for 100% of the sample.

>5 Years < 2 years

24% 18%

< 2 years
2-5 Years
>5 Years
2-5 Years
58%

Figure 7: Duration of Epilepsy in Levetiracetam

Table 9: Family History in Levetiracetam

 Family History Control Group Study Group P Value

Positive history 4 (10.5%) 0 (0%) 0.0001

Negative history 34 (89.5%) 38 (100%)

Total 38 (100%) 38 (100%)

In the control group, 10.5% (4 participants) had a positive family history of epilepsy, while

89.5% (34 participants) had no such history. In comparison, all participants in the study group

(100%, 38 individuals) had a negative family history, with none reporting a positive history. The

p-value of 0.0001 shows a statistically significant difference between the two groups regarding

family history of epilepsy.

40 38

35 34

30

25

20

15

10

5 4
0
0
Control Group Study Group

Positive family history Negative family history

Figure 8: Family History in Levetiracetam

Table 10: Parameters in Levetiracetam

 Parameter Control (Mean ± SD) Cases (Mean ± SD) P Value

Cholesterol 118.88 ± 14.36 125.98 ± 11.31 0.084

LDL 87.40 ± 12.85 89.99 ± 12.37 0.451

TGS 90.52 ± 6.67 88.67 ± 6.57 0.289

HDL 56.50 ± 10.26 52.25 ± 5.59 0.217

VLDL 30.16 ± 4.71 29.31 ± 7.00 0.741

The comparison of biochemical parameters between the control and study groups for

Levetiracetam shows the following results:

1. Cholesterol: The study group's mean cholesterol level is somewhat higher at 125.98 ±

11.31 than the control group's, which is 118.88 ± 14.36. With a p-value of 0.084, this

difference is not statistically significant.

2. LDL: There is no discernible difference between the study group's mean LDL level of

89.99 ± 12.37 and the control group's mean LDL level of 87.40 ± 12.85 (p-value =

0.451).

3. Triglycerides (TGS): The study group's mean triglyceride level is somewhat lower at

88.67 ± 6.57 than the control group's, which is 90.52 ± 6.67, but the difference is not

statistically significant (p-value = 0.289).

4. HDL: The research group's mean HDL level was 52.25 ± 5.59, whereas the control

group's was 56.50 ± 10.26. With a p-value of 0.217, the difference is not statistically

significant, nonetheless.

5. VLDL: There is no statistically significant difference between the two groups' VLDL

levels, which are nearly comparable at 30.16 ± 4.71 in the control group and 29.31 ± 7.00

in the study group (p-value = 0.741).

SODIUM VALPROATE
Table 11: Age categories in Sodium Valproate

Age category Control Group Study Group P value

< 2 years 11 (28.9%) 5 (13.2%)

3-5 years 12 (31.6%) 9 (23.7%)

6-8 Years 7 (18.4%) 12 (31.6%) 0.514

9-12 Years 8 (21.1%) 12 (31.6%)

Total 38 (100%) 38 (100%)

For Sodium Valproate, the age distribution between the control and study groups was observed

as follows: In the control group, 28.9% of children were less than 2 years old, 31.6% were in the

3-5 years category, 18.4% were in the 6-8 years category, and 21.1% were in the 9-12 years

category. In contrast, the study group consisted of 13.2% children under 2 years, 23.7% between

3-5 years, 31.6% between 6-8 years, and 31.6% between 9-12 years. The P-value of 0.514

indicates no statistically significant difference between the two groups in terms of age

distribution.

Control Group Study Group

12

12

12
11

8
7
5

< 2 years 3-5 years 6-8 Years 9-12 Years

Figure 9: Age categories in Sodium Valproate

Table 12: Gender in Sodium Valproate

Gender Control Group Study Group P value

Male 20 (52.6%) 22 (57.9%)

Female 18 (47.4%) 16 (42.1%) 0.954

Total 38 (100%) 38 (100%)

Regarding gender distribution, in the control group, 52.6% of children were male and 47.4%

were female. In the study group, 57.9% of children were male and 42.1% were female. The P-

value for gender distribution is 0.954, which shows no significant difference between the control

and study groups in terms of gender.

Control Group Study Group

25
22
20
20
18
16
15

10

0
Male Female

Figure 10: Gender distribution in Sodium Valproate

Table 13: Duration of Epilepsy in Sodium Valproate

 Duration of Epilepsy Study Group

< 2 years 6 (18.4%)

2-5 Years 24 (57.9%)

>5 Years 8 (23.7%)

Total 38 (100%)

In the sodium valproate group, the duration of epilepsy is as follows: 18.4% (6 individuals) have

had epilepsy for less than 2 years, 57.9% (24 individuals) for 2-5 years, and 23.7% (8

individuals) for more than 5 years. The study group consists of 38 participants, representing the

entire sample.

16%
21%

< 2 years
2-5 Years
>5 Years

63%

Figure 11: Duration of Epilepsy in Sodium Valproate

Table 14: Family History in Sodium Valproate

Family History Control Group Study Group P Value

Positive history 8 (21.1%) 0 (0%) 0.004

Negative history 30 (78.9%) 38 (100%)

Total 38 (100%) 38 (100%)

In the control group, 21.1% (8 individuals) reported a positive family history of epilepsy, while

78.9% (30 individuals) had a negative family history. In contrast, the study group had no

participants with a positive family history, with 100% (38 individuals) reporting a negative

family history. The p-value of 0.004 indicates that this difference in family history between the

two groups is statistically significant.

40 38

35
30
30

25

20

15

10 8

5
0
0
Control Group Study Group

Positive family history Negative family history

Figure 12: Family History in Sodium Valproate

Table 15: Parameters in Sodium Valproate

Parameter Control (Mean ± SD) Cases (Mean ± SD) P Value

Cholesterol 107.15 ± 9.22 107.74 ± 8.32 0.412

LDL 95.34 ± 7.91 96.53 ± 6.97 0.841

TGS 89.47 ± 4.46 91.77 ± 8.02 0.214

HDL 47.02 ± 4.65 46.67 ± 5.22 0.541

VLDL 18.63 ± 6.09 21.26 ± 7.30 0.074

For Sodium Valproate, the following results were observed when comparing the control and

study groups:

1. Cholesterol levels: The mean cholesterol level in the control group was 107.15 ± 9.22,

and in the study group, it was 107.74 ± 8.32. The P-value of 0.412 indicates no

significant difference.

2. LDL levels: The control group had a mean LDL of 95.34 ± 7.91, while the study group

had 96.53 ± 6.97. The P-value of 0.841 shows no significant difference.

3. TGS levels: The control group had a mean TGS level of 89.47 ± 4.46, and the study

group had 91.77 ± 8.02. The P-value of 0.214 suggests no significant difference.

4. HDL levels: The mean HDL level in the control group was 47.02 ± 4.65, while in the

study group, it was 46.67 ± 5.22. The P-value of 0.541 indicates no significant

difference.

5. VLDL levels: The control group had a mean VLDL of 18.63 ± 6.09, while the study

group had 21.26 ± 7.30. The P-value of 0.074 suggests a marginal difference between the

two groups, but it is not statistically significant.

Table 16: Comparison of sex in children taking antiepileptic drugs

Gender Male Female

Phenytoin 14 (36.8%) 24 (63.8%)

Sodium valproate 22 (57.9%) 16 (42.1%)

Levitaracetam 14 (36.8%) 24 (63.8%)

The gender distribution across the different treatment groups is as follows:

 Phenytoin: 36.8% (14 males) and 63.8% (24 females).

 Sodium Valproate: 57.9% (22 males) and 42.1% (16 females).

 Levetiracetam: 36.8% (14 males) and 63.8% (24 females).

Male Female

24 24
22

16
14 14

Phenobarbitone Sodium valproate Levitaracetam

Figure 13: Comparison of sex in children taking antiepileptic drugs

Table 17: Comparison of total cholesterol levels in children taking antiepileptic drugs

Total Cholesterol Levels Mean ± SD

Phenytoin 173.22 ± 36.13

Sodium valproate 107.74 ± 8.32

Levitaracetam 125.98 ± 11.31

The total cholesterol levels across the three treatment groups are as follows:

 Phenytoin: Mean total cholesterol level of 173.22 ± 36.13.

 Sodium Valproate: Mean total cholesterol level of 107.74 ± 8.32.

 Levetiracetam: Mean total cholesterol level of 125.98 ± 11.31.

 The Phenytoin group has the highest mean total cholesterol level (173.22), suggesting

that this treatment may be associated with an increase in cholesterol levels.

 Both the Sodium Valproate and Levetiracetam groups have significantly lower mean

cholesterol levels, with Sodium Valproate at 107.74 and Levetiracetam at 125.98. This

suggests that these medications may have a cholesterol-lowering effect compared to

Phenytoin.

Table 18: Comparison of LDL-C levels in children taking antiepileptic drugs

 LDL-C LEVELS Mean ± SD

Phenytoin 162.03 ± 29.98

Sodium valproate 96.53 ± 6.97

Levitaracetam 89.99 ± 12.37

The LDL-C (Low-Density Lipoprotein Cholesterol) levels across the three treatment groups

are as follows:

 Phenytoin: Mean LDL-C level of 162.03 ± 29.98.

 Sodium Valproate: Mean LDL-C level of 96.53 ± 6.97.

 Levetiracetam: Mean LDL-C level of 89.99 ± 12.37.

 The Phenytoin group has the highest mean LDL-C level (162.03), suggesting that this

treatment may significantly increase LDL cholesterol levels, which is a risk factor for

cardiovascular diseases.

 Both the Sodium Valproate and Levetiracetam groups show much lower mean LDL-C

levels, with Sodium Valproate at 96.53 and Levetiracetam at 89.99, indicating that these

treatments might have a cholesterol-lowering effect, particularly on LDL-C levels.

Table 19: Comparison of triglyceride levels in children taking antiepileptic drugs

TRIGLYCERIDE LEVELS Mean ± SD

 Phenytoin 131.83 ± 44.30

Sodium valproate 91.77 ± 8.02

Levitaracetam 88.67 ± 6.57

The triglyceride levels across the three treatment groups are as follows:

 Phenytoin: Mean triglyceride level of 131.83 ± 44.30.

 Sodium Valproate: Mean triglyceride level of 91.77 ± 8.02.

 Levetiracetam: Mean triglyceride level of 88.67 ± 6.57.

 The Phenytoin group has the highest mean triglyceride level (131.83),

 Both the Sodium Valproate and Levetiracetam groups have lower mean triglyceride

levels, with Sodium Valproate at 91.77 and Levetiracetam at 88.67, indicating a

potentially cholesterol-lowering effect and a more favorable lipid profile.

 In summary, Phenytoin appears to be associated with higher triglyceride levels compared

to Sodium Valproate and Levetiracetam, which show more favorable effects on

triglyceride levels.

Table 20: Comparison of HDL-C levels in children taking antiepileptic drugs

HDL-C LEVELS Mean ± SD

Phenytoin 48.62 ± 9.94

Sodium valproate 46.67 ± 5.22

 Levitaracetam 52.25 ± 5.59

The HDL-C (High-Density Lipoprotein Cholesterol) levels across the three treatment groups

are as follows:

 Phenytoin: Mean HDL-C level of 48.62 ± 9.94.

 Sodium Valproate: Mean HDL-C level of 46.67 ± 5.22.

 Levetiracetam: Mean HDL-C level of 52.25 ± 5.59.

 The Levetiracetam group has the highest mean HDL-C level (52.25).

 The Phenytoin group has a slightly lower mean HDL-C level (48.62) compared to

Levetiracetam, but still within a relatively healthy range.

 The Sodium Valproate group has the lowest mean HDL-C level (46.67), although the

difference is minimal compared to Phenytoin.

Table 21: Comparison of VLDL-C levels in children taking antiepileptic drugs

VLDL-C LEVELS Mean ± SD

Phenytoin 20.62 ± 9.14

Sodium valproate 21.26 ± 7.30

Levitaracetam 29.31 ± 7.00

The VLDL-C (Very Low-Density Lipoprotein Cholesterol) levels for the three treatment groups

are as follows:

 Phenytoin: 20.62 ± 9.14

 Sodium Valproate: 21.26 ± 7.30

 Levetiracetam: 29.31 ± 7.00

Key points include:

 Levetiracetam has the highest mean VLDL-C level (29.31), indicating that it may

elevate VLDL-C, a form of "bad" cholesterol, which could increase the risk of

cardiovascular problems.

 Phenytoin and Sodium Valproate have lower mean VLDL-C levels (20.62 and 21.26,

respectively), suggesting a potentially lower risk of cardiovascular issues linked to this

type of cholesterol.

 Levetiracetam shows the greatest variability in VLDL-C levels, with a standard

deviation of 7.00, followed by Sodium Valproate (7.30) and Phenytoin (9.14), indicating

moderate fluctuations in these groups.

In summary, Levetiracetam is associated with the highest VLDL-C levels, which may raise

concerns about lipid metabolism and cardiovascular health, while Phenytoin and Sodium

Valproate are linked with more favorable lipid profiles.

DISCUSSION
 This study aimed to assess the influence of anticonvulsant treatments on lipid profiles in

children with seizure disorders. It specifically examined the effects of three widely prescribed

antiepileptic drugs—Phenytoin, Levetiracetam, and Sodium Valproate—on serum lipid markers

such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density

lipoprotein cholesterol (HDL-C), triglycerides (TGs), and very low-density lipoprotein

cholesterol (VLDL-C). The study also took into account demographic data, clinical

characteristics, and family history to identify factors that may affect lipid metabolism in children

undergoing treatment.

Taking into account a number of clinical, family-related, and demographic characteristics,

the findings provide significant new information on the effects of anticonvulsant treatment on

lipid profiles in paediatric patients. To determine their wider importance and get a greater

understanding of the patterns that have been identified, these findings are contrasted with those

from other studies.

The lipid alterations observed with phenytoin and carbamazepine may be attributed to

enzyme induction. Both drugs are inducers of the CYP51 enzyme, a key player in cholesterol

biosynthesis, particularly the CYP51A1 isoform (lanosterol 14α demethylase), which catalyzes

the removal of the 14α methyl group from lanosterol, ultimately producing oxysterols that

convert into cholesterol in mammalian tissues [52,53]. Enzyme-inducing AEDs are likely to

enhance lipid synthesis. Chronic use of AEDs like phenytoin and phenobarbitone, metabolized

by microsomal enzymes, may also reduce the conversion of cholesterol to bile acids due to

enzymatic competition, leading to increased serum cholesterol levels [54]. Mintzer et al.

demonstrated that switching epileptic patients from enzyme-inducing AEDs to non-inducing

drugs such as lamotrigine and levetiracetam resulted in a significant decrease in serum

cholesterol within six weeks [55].

Age Distribution

The age distribution across different groups in the study highlights variations in the

representation of age categories among the control and study groups for three antiepileptic drugs:

Phenytoin, Levetiracetam, and Sodium Valproate.

In the Phenytoin group, the control group had the largest proportion of participants aged

9-12 years (31.6%), followed by those aged 6-8 years (23.9%), 3-5 years (23.7%), and <2 years

(15.8%). The study group, however, showed a concentration in the 3-5 years category (52.6%),

with smaller proportions in the 9-12 years (15.8%), <2 years (21.1%), and 6-8 years (10.5%)

categories.

For the Levetiracetam group, the distribution was more consistent between control and

study groups for <2 years (15.8%) and 3-5 years (23.7%). But the study group had more

participants between the ages of 6 and 8 (42.1%) than the control group (23.9%), and the control

group had more individuals between the ages of 9 and 12 (31.6%) than the study group (13.2%).

In the Sodium Valproate group, the control group showed the highest proportion in the <2

years (28.9%) and 3-5 years (31.6%) categories, with smaller numbers in the 6-8 years (18.4%)

and 9-12 years (21.1%) categories. Conversely, the study group had the highest proportions in

the 6-8 years (31.6%) and 9-12 years (31.6%) categories, with fewer participants in <2 years

(13.2%) and 3-5 years (23.7%).

 The control and study groups show comparable demographic characteristics for all three

drugs, according to the P-values seen across the treatment groups, which also imply that there are

no appreciable variations in the age distribution.

This result is consistent with study by Smith et al. [57], who observed that in studies on

paediatric epilepsy, age had no discernible impact on lipid metabolism. Similarly, Anju Aggarwal

et al. [58], in their study on carbamazepine's effects on serum lipids and liver function, found no

major age differences between the cases and controls (mean ages of 8.3±2.8 years and 8.4±2.6

years, respectively). In Pooja Dewan et al.'s [59] research on phenytoin and valproate, the

average age was 7.5±4.4 years across 79 children, with 27 in the valproate group, 25 in the

phenytoin group, and 27 in the control group. Similarly, Nadkarni et al. [48] included 95 children

(mean age 7.36±2.81 years) and 50 controls (mean age 6.27±2.73 years), showing minimal age

variation between the groups.

Gender Distribution

The gender distribution across the control and study groups for the three antiepileptic

drugs showed minor differences, none of which were statistically significant. In the Phenytoin

group, the control group had a higher proportion of females (63.2%) compared to males (36.8%),

while the study group had more males (52.6%) than females (47.4%), with a P-value of 0.356

indicating no significant difference. In the Levetiracetam group, the gender ratio was the same in

both the control and study groups, with 63.8% females and 36.8% males, resulting in a P-value

of 1. For Sodium Valproate, the control group had 52.6% males and 47.4% females, while the

study group had 57.9% males and 42.1% females, with a P-value of 0.954, showing no

significant gender difference. In all cases, the gender distribution was relatively balanced, with

no notable differences between the control and study groups.

The results of the gender analysis showed no discernible changes in lipid fractions, which is

consistent with other studies like the one conducted by Kumar et al. [60], which reported no

gender-related differences in lipid outcomes in children with epilepsy. In a similar vein, Magkos

et al. (2018) found that in children receiving anticonvulsant medication, gender has no

discernible impact on lipid metabolism. These findings are consistent with research that suggests

female hormones, such as oestrogen, provide a preventive impact against atherosclerosis through

reverse cholesterol transport, and that lipid alterations in men may be more closely linked to

AED doses [56]. These consistent findings demonstrate that changes in lipid profiles throughout

epilepsy therapy are not significantly influenced by gender.

Duration of Epilepsy

The duration of epilepsy varied across the study groups for the three antiepileptic drugs. In

the Phenytoin group, most participants in the study group (65.8%) had epilepsy for 2-5 years,

followed by 21.1% with a duration of more than 5 years, and 13.2% with less than 2 years.

Similarly, in the Levetiracetam group, the majority of participants (57.9%) had epilepsy for 2-5

years, 23.7% for more than 5 years, and 18.4% for less than 2 years. The Sodium Valproate

group exhibited a comparable pattern, with 57.9% of the study group having epilepsy for 2-5

years, 23.7% for more than 5 years, and 18.4% for less than 2 years. These distributions indicate

that the majority of participants in all study groups had a mid-range duration of epilepsy (2-5

years), with smaller proportions reporting shorter or longer durations. This consistent pattern

across groups reflects a relatively similar epilepsy duration profile among the participants

receiving different medications.

There were no discernible variations in the length of epilepsy across the groups (p=0.649).

According to Praveen D. et al. [62], the length of epilepsy had no effect on alterations in lipid

profiles in children.

Family History

Significant differences between the control and study groups were seen in the family history of

epilepsy for each of the three antiepileptic medication categories. Just 2.6% of research

participants had a positive family history of epilepsy, but 21.1% of control individuals in the

Phenytoin group had. No one in the trial group claimed a positive family history, but 10.5% of

controls in the Levetiracetam group did. With 21.1% of the control group having a favourable

family history compared to none in the research group, a similar pattern was seen in the sodium

valproate group.

The majority of research participants had no family history of epilepsy overall, and all three

groups showed significant differences (P-values: 0.004 for phenytoin, 0.0001 for levetiracetam,

and 0.004 for sodium valproate). According to these findings, the research groups were more

likely than the control groups to have a bad family history.

Comparing these results to previous research, a number of studies have indicated that family

history has a significant role in changes in lipid profiles. Children with a family history of

cardiovascular disease had significantly higher lipid levels when receiving anticonvulsant

treatment, especially when using medications like phenytoin and valproate, according to Bhadran

et al. [63]. This aligns with our study's findings, where phenytoin, an enzyme-inducing drug, was

associated with increased total cholesterol and LDL levels. However, Bhadran et al. [63]
highlighted family history as a major factor influencing lipid changes, which contrasts with our

study’s primary focus on the drug’s direct impact.

In a similar vein, Katalinic et al. [64] found that after long-term anticonvulsant medication,

individuals with a family history of cardiovascular illnesses and dyslipidaemia had more notable

changes in their lipid profiles. This is consistent with our finding that phenytoin may exacerbate

lipid profiles, particularly in kids who have a family history of lipid problems.

A research by Chaves et al. [65], on the other hand, discovered a reduced correlation between

anticonvulsant-induced dyslipidaemia and family history, particularly in children receiving

levetiracetam or other more recent anticonvulsants. In contrast, our study demonstrated that

youngsters taking levetiracetam, independent of their family background, did not exhibit any

appreciable alterations in their lipid profiles.

In conclusion, despite the fact that family history was not a primary focus of this study, its results

are consistent with previous research indicating that lipid profiles during anticonvulsant

medication may be influenced by family history. Family history alone does not seem to have as

much of an effect on lipid levels as older anticonvulsants like phenytoin. To further understand

how these variables interact, future studies might examine the combined effects of long-term

anticonvulsant usage and family history on lipid metabolism.

Lipid Profile Analysis

Across the three categories of antiepileptic medications, there were significant variations in

the levels of LDL and cholesterol between the study and control groups. With a statistically

significant P-value of 0.000, the study group's average cholesterol level in the Phenytoin group

was substantially higher (173.22 ± 36.13) than that of the control group (113.15 ± 9.74).
Additionally, the study group's LDL values were significantly higher (162.03 ± 29.98) than those

of the control group (98.03 ± 7.15), with a P-value of 0.000, suggesting a substantial difference.

Despite being somewhat higher than the control group (118.88 ± 14.36) in the

Levetiracetam group, the study group's mean cholesterol level (125.98 ± 11.31) was not

statistically significant (P-value: 0.084). Similarly, the study group's LDL values were somewhat

higher (89.99 ± 12.37) than those of the control group (87.40 ± 12.85), although the difference

was not statistically significant (P-value: 0.451).

The cholesterol levels of the study group (107.74 ± 8.32) and the control group (107.15 ±

9.22) for the sodium valproate group were not significantly different, with a P-value of 0.412.

The study group's LDL levels were 96.53 ± 6.97 and the control group's were 95.34 ± 7.91,

resulting in a non-significant P-value of 0.841.

Overall, the Phenytoin group exhibited significantly higher cholesterol and LDL levels in

the study group, indicating a possible effect of the drug on lipid metabolism. In contrast, the

Levetiracetam and Sodium Valproate groups showed minimal or no differences between the

study and control groups.

Shah et al. [66] conducted a study showing a reduction in cholesterol levels in children

treated with enzyme-inducing anticonvulsants like phenytoin and carbamazepine. They

suggested that these drugs, by stimulating hepatic enzymes, may alter lipid metabolism, leading

to lower cholesterol levels. This finding aligns with our study, where significant reductions in

both cholesterol and LDL levels were noted in children on anticonvulsants. Shah et al. [66]

proposed that this reduction in cholesterol could be a compensatory response to increased hepatic

clearance, potentially mitigating cardiovascular risks in the long term.

 When Garcia et al. [67] looked at how anticonvulsant medication affected children's lipid

profiles over time, they found that LDL levels significantly decreased. Their research, which

included both more recent pharmaceuticals like valproate and older enzyme-inducing

anticonvulsants, showed that long-term usage of these treatments may affect not only cholesterol

levels but also other lipoprotein fractions like LDL-C, a crucial marker of the risk of

cardiovascular disease. This is consistent with our research, which indicates that long-term

anticonvulsant treatment may result in a protective reduction in LDL-C, lowering the risk of

atherosclerosis and cardiovascular issues.

However, Nadkarni [48] discovered that children using anticonvulsants had somewhat

higher LDL-C levels, while this difference was not statistically significant (p=0.051). This may

indicate disparities in patient characteristics or individual differences in lipid responses to

various anticonvulsant treatments. Although LDL-C was clearly and statistically significantly

reduced in our study, Nadkarni's results suggest that anticonvulsants may sometimes have a less

noticeable impact on lipid metabolism.

Dewan et al. [59] examined the lipid profiles of children treated with various

anticonvulsants and found significantly higher LDL-C levels in children on phenytoin compared

to those on valproate or the control group. They suggested that phenytoin, as an enzyme-

inducing drug, might increase LDL-C levels due to its impact on lipid metabolism. However, our

study observed a reduction in both total cholesterol and LDL-C in children treated with

phenytoin. This difference could be due to variations in therapy duration, sample size, or lipid

profile assessment methods. It’s also important to consider that phenytoin's effects on lipid levels

can vary among individuals, influenced by factors like diet, genetic predisposition, and other

medications.
 Pita-Calandre E et al. [68] studied the effects of carbamazepine and phenytoin on lipid

profiles, finding that carbamazepine increased HDL2 cholesterol levels, a more protective form

of HDL, while phenytoin raised triglyceride levels, a common effect of many anticonvulsants,

particularly enzyme-inducing ones. Their study highlights the varied effects of different

anticonvulsants on lipid metabolism, with carbamazepine having a more beneficial impact on

HDL levels, while phenytoin increased triglycerides. Although our study did not specifically

focus on HDL2, we observed significant changes in lipid profiles in phenytoin-treated children,

particularly in total cholesterol and LDL-C, which are consistent with Pita-Calandre E's findings

regarding the triglyceride-increasing effects of phenytoin.

A research by Gopi Srikanth et al. [69] indicated that valproate did not result in significant

changes in total cholesterol (p=0.796) after six months of therapy, supporting the idea that

anticonvulsant medicines can considerably influence lipid profiles. This is consistent with our

results, which showed that children treated with valproate did not exhibit any appreciable

alterations in their lipid levels. In line with our finding that children using phenytoin had lower

cholesterol levels, Gopi Srikanth et al. [69] also observed that phenytoin did not substantially

change total cholesterol (p=0.065). Additionally, the study found that levetiracetam, a more

recent anticonvulsant, had little impact on lipid levels. This finding was consistent with our own,

which also found that levetiracetam did not significantly alter lipid profiles.

Gopi Srikanth et al. [69] found no evidence of a significant rise in LDL-C levels in children

using levetiracetam (p=0.319), phenytoin (p=0.122), or valproate (p=0.143). Our findings

supported this pattern, showing that children treated with valproate and levetiracetam did not

significantly alter their LDL-C levels, but children treated with phenytoin had a statistically

significant reduction in LDL-C levels. This disparity might result from variations in the study's
methodology, sample size, or length of therapy. Furthermore, the levetiracetam group's absence

of notable LDL-C alterations is consistent with its designation as a more recent anticonvulsant,

which is characterised by a better safety record and less effects on lipid metabolism.

In conclusion, although our research revealed a protective decrease in LDL-C and total

cholesterol levels in kids undergoing anticonvulsant treatment, the impact on lipid profiles varies

according on the drug, length of treatment, and patient characteristics. The findings are in line

with recent research examining how anticonvulsants, especially older, enzyme-inducing

medications like phenytoin, affect cholesterol levels. The disparity in results, however,

emphasises how crucial it is to monitor lipid profiles individually in children on long-term

anticonvulsant treatment, as some may be more susceptible to lipid imbalances and

cardiovascular problems.

HDL Levels

For the three antiepileptic medications, there were variations in HDL levels between the control

and study groups, but none of the differences were statistically significant. With a significant P-

value of 0.000, the study group's mean HDL level (48.62 ± 9.94) was lower than that of the

control group (60.62 ± 15.13) in the Phenytoin group, indicating that Phenytoin may lower HDL

levels. Although the study group's mean HDL level (52.25 ± 5.59) was somewhat lower than the

control group's (56.50 ± 10.26) in the Levetiracetam group, the P-value of 0.217 showed no

discernible difference. With the study group's HDL levels at 46.67 ± 5.22 and the control group's

at 47.02 ± 4.65, the sodium valproate group's levels were almost identical and did not differ

significantly (P-value: 0.541).

In conclusion, HDL levels among research participants were significantly lower in the Phenytoin

group and comparatively unchanged in the Levetiracetam and Sodium Valproate groups,

indicating that these medications may have less of an impact on this lipid parameter.

Contrasting with our results, Pooja Dewan et al. [59] found higher HDL-C levels in children

treated with phenytoin compared to both controls and those treated with valproic acid. This

indicates that phenytoin may have an opposite effect on HDL-C, potentially increasing it, while

other anticonvulsants generally lower HDL-C. Additionally, studies by Nikkila et al. [72] and

O'Neill et al. [73] also noted elevated HDL-C levels in phenytoin-treated patients, suggesting it

may have a positive effect on HDL levels.

However, Nadkarni et al. [48] observed significantly lower HDL-C levels in children receiving

AEDs compared to controls, with a P-value of 0.000, indicating a clear link between AED

therapy and decreased HDL levels. This highlights the potential variation in the impact of

anticonvulsants on HDL levels depending on the specific drug and patient factors. Finally, Gopi

Srikanth et al. [51] did not report detailed changes in HDL levels but noted that overall lipid

profile effects were minimal across different AEDs, which contrasts with the more substantial

effects observed in other studies. These inconsistencies underscore the complexity of how

anticonvulsant therapy affects lipid metabolism in children and the need for further research to

better understand these relationships.

Triglyceride Levels:

The Phenytoin group's triglyceride (TGS) levels varied significantly from those of the other

medication groups, which showed rather constant levels. With a highly significant P-value of

0.000, the study group's mean triglyceride level (131.83 44.30) was significantly higher than that
of the control group (90.62 8.53). This suggests that phenytoin may significantly raise

triglyceride levels, which could have a detrimental effect on lipid metabolism.

Although the study group's mean triglyceride level was somewhat lower (88.67 ± 6.57) than the

control group's (90.52 ± 6.67) in the Levetiracetam group, the difference was not statistically

significant (P-value: 0.289). In a similar vein, the study group's mean triglyceride level in the

sodium valproate group was somewhat higher (91.77 ± 8.02) than that of the control group

(89.47 ± 4.46), although there was no discernible difference (P-value: 0.214).

These findings imply that whereas levetiracetam and sodium valproate have no effect on

triglyceride levels, phenytoin is highly linked to higher triglyceride levels. This calls into

question how phenytoin affects cardiovascular health and lipid metabolism.

There may be a trend towards greater triglycerides with AEDs, but not necessarily clinically

significant in smaller trials, according to the Nadkarni research [48], which also reported slightly

higher triglyceride levels in the case group. However, the results were not statistically significant

(p=0.154).

Contrasting with our findings, Gopi Srikanth et al. [51] observed a significant rise in triglyceride

levels in children treated with valproate (p=0.001), suggesting that valproate may have a more

pronounced effect on triglycerides. They also noticed a near-significant increase in triglyceride

levels in children on phenytoin (p=0.053) and a significant rise in levetiracetam-treated children

(p=0.013), further highlighting the variability of AEDs in their effects on triglyceride levels.
SUMMARY:

 Among individuals taking Phenytoin, 65.8% had been diagnosed with epilepsy for a duration

of 2 to 5 years, in contrast to 57.9% in both the Levetiracetam and Sodium Valproate groups.

 A vast majority of patients in the Phenytoin group (97.4%) reported no family history of

epilepsy. Similarly, none of the participants in the Levetiracetam and Sodium Valproate

groups reported a positive family history. These differences were statistically significant

when compared to their respective control groups (P-values: 0.004, 0.0001, and 0.004,

respectively).

 The Phenytoin group exhibited a notably higher average total cholesterol level (173.22 ±

36.13 mg/dL) compared to the control group (113.15 ± 9.74 mg/dL), with a highly significant

P-value of 0.000.

 With a P-value of 0.000, the Phenytoin group's mean LDL cholesterol was substantially

higher (162.03 ± 29.98 mg/dL) than the controls' (98.03 ± 7.15 mg/dL).

 Phenytoin users had significantly lower HDL cholesterol levels (48.62 ± 9.94 mg/dL) than

control subjects (60.62 ± 15.13 mg/dL), a difference that was statistically significant (P =

0.000).

 With a P-value of 0.000, triglyceride levels were substantially higher in the Phenytoin-treated

group (131.83 ± 44.30 mg/dL) than in the control group (90.62 ± 8.53 mg/dL).

 However, users of levetiracetam did not show any statistically significant differences in the

components of their lipid profiles when compared to controls. For instance, total cholesterol
 levels in the study group were 125.98 ± 11.31 mg/dL, whereas those in the control group

were 118.88 ± 14.36 mg/dL (P = 0.084).

 Lipid readings varied very little in those using sodium valproate, and these differences were

not statistically significant. Their triglyceride levels were 91.77 ± 8.02 mg/dL vs 89.47 ±

4.46 mg/dL (P = 0.214), and their cholesterol levels were 107.74 ± 8.32 mg/dL versus 107.15

± 9.22 mg/dL in the control group (P = 0.412).

CONCLUSION:

This study compared the effects of Phenytoin, Levetiracetam, and Sodium Valproate on

demographic, clinical, and biochemical parameters in children with epilepsy. Demographic

distributions were balanced across groups, with no significant differences in age or gender.

Phenytoin was associated with significantly elevated cholesterol, LDL, and triglyceride levels,

suggesting a higher cardiovascular risk, while Levetiracetam showed favorable HDL levels but

elevated VLDL, raising potential concerns about lipid metabolism. Sodium Valproate

demonstrated the most stable lipid profile with no significant abnormalities, suggesting a safer

cardiovascular profile. Additionally, study groups exhibited a significant reduction in positive

family history of epilepsy, particularly in those receiving Levetiracetam and Sodium Valproate.

These findings highlight the need to consider metabolic impacts when choosing antiepileptic

treatments.
RECOMMENDATIONS:

1. Regular Monitoring: Monitor lipid profiles and liver enzymes regularly for children on

long-term AED therapy to detect early signs of dyslipidemia and hepatic dysfunction.

2. Individualized Treatment: Tailor AED prescriptions based on the child's health status

and the potential side effects of each drug.

3. Longer Studies: Conduct larger, longitudinal studies to explore long-term metabolic and

hepatic effects of AEDs.

4. Genetic Screening: Consider genetic screening for children with a family history of

epilepsy to better understand their risks and personalize treatment.

LIMITATIONS:

1. Small Sample Size: The study’s small sample size may limit the applicability of the

findings to the broader population.

2. Short Duration: The study’s 6-month duration limits its ability to assess long-term

effects of AED therapy.

3. Other Confounding Factors: The study did not account for lifestyle factors or other

health conditions that may affect lipid and liver enzyme levels.

4. Lack of AED Specificity: The study did not analyze individual AEDs in detail, which

could provide more targeted insights into their specific effects.