Vol.

3 Issue 1, January-March 2010 ISSN 0974-2441

Utilization pattern of antiepileptic drugs and

RESEARCH ARTICLE

their adverse effects, in a teaching hospital

Shobhana Mathur, Sumana Sen *, L Ramesh, Satish Kumar M

Department of Pharmacology, Deccan College of Medical Sciences, Hyderabad - 500058, A.P., India.

Address for correspondence: Dr. Sumana Sen, Department of Pharmacology, Deccan College of Medical Sciences,
Kanchanbagh, Hyderabad - 500058, A.P., India. E-mail: [email protected]

The overall aim in treating epilepsy should be complete control of seizures, without causing any untoward reaction due
to the medication. Many of the drugs currently available for epilepsy cause side effects. This study attempts to get an
insight into the utilization pattern of anti-epileptic drugs (AEDs) in different types of epilepsy, to identify the extent of
poly-pharmacy and to evaluate the adverse drug reactions reported. In a prospective study spanning 8 months (January
to August 2008) we analyzed the prescription data of 278 patients of seizures from neurology out patient department
(OPD) of Owaisi hospital, general medicine and pediatric O.P.D.s of Princess Esra hospital, Hyderabad. The
demographic data, type of seizures, anti-epileptic drugs prescribed and adverse drug reactions (ADRs) reported by the
patients were recorded. A total of 278 prescriptions were analyzed and adverse drug reactions reported by the patients
were recorded. Idiopathic generalized epilepsy was the commonest type of epilepsy (34.53%) and Phenytoin was the
commonest drug prescribed (60.41%) for it’s treatment, followed by Sodium Valproate (20.83%). Symptomatic
epilepsy comprised the second commonest category of seizures (26.25%). Phenytoin (57.53%) followed by Sodium
Valproate (27.39%) were the most commonly prescribed drugs to treat it. Monotherapy was given in 53.95% of
patients. The overall incidence of adverse drug reactions (ADRs) was 4.67%. Unlike previous studies Phenytoin was
the most frequently prescribed AED followed by Sodium Valproate. In contrast to other studies, our study revealed
frequent use of Topiramate as an adjuvant. Carbamazepine and Phenytoin accounted for most of the ADRs. Drowsiness
was the commonest ADR reported.

Keywords: Antiepileptic drugs, Drug utilization, Epilepsy, Adverse drug reactions.

INTRODUCTION idiosyncratic reactions like bone marrow

Epilepsy is a common neurological disorder depression (carbamazepine) to acute myopia
which demands immediate medical attention and glaucoma (topiramate). Monotherapy is the
and often long term therapy. The incidence is usual dictum, but polytherapy is needed for
approximately 0.3 – 0.5% in different world patients with multiple seizure types or
populations with a prevalence rate of five to ten refractory disease [3, 4, 5]. The current study
per thousand people. The overall aim in treating attempts to analyze the pattern of drug
epilepsy should be complete control of seizures, utilization in different types of epilepsy. The
without causing any untoward reaction due to extent of polytherapy is also looked into. The
the medication. A large number of drugs are adverse drug reactions reported by the patients
currently available for the treatment of epilepsy. and their impact on the continuation of anti-
Older/conventional drugs like phenytoin, epileptic therapy are evaluated.
carbamazepine, valproic acid and ethosuximide
are commonly used as first line drugs. They are Objectives of the study
relatively less expensive than the newer anti-
epileptics. Drugs like gabapentin, lamotrigine, Get an insight into the utilization pattern of
vigabatrin, topiramate, tiagabine and zonisamide anti-epileptic drugs (AEDs) in different types
are the newer ones and currently used as add-on of epilepsy and to identify the extent of poly-
or alternative therapy.They have lesser adverse pharmacy.
effects and have few, if any, drug interactions [1, 2].
Evaluate the adverse drug reactions caused by
Some side effects may be common with the the anti-epileptic drugs.
above mentioned drugs and include sedation and
ataxia. They can be diverse as well, ranging from MATERIALS AND METHODS

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Vol.3 Issue 1, January-March 2010 ISSN 0974-2441

In a prospective study spanning eight months ability scale.

(January to August 2008) we analyzed the 3) Whether the suspected drug was stopped after the
prescription data of 278 patients of seizures from ADR.
neurology out patient department (OPD) of Owaisi 4) Whether any treatment was given for the ADR.
hospital and the general medicine and pediatric 5) The drug(s) most commonly causing ADRs.
OPDs of Princess Esra hospital, Hyderabad. Current
diagnosis was made by the doctor in charge of the RESULTS
patient.
Prescribing indicators
Inclusion criteria: Patients with seizures, of both
sex and all age groups, who are prescribed an anti- 1) Average number of anti-epileptic drugs (AEDs)
epileptic drug, are included in the study. prescribed per patient. This is calculated as:
436
Exclusion criteria: Patients with status epilepticus Avg. no. of AEDs/patient = = 1.56
and seizures associated with acute conditions like 278
paralytic stroke are excluded. The demographic 2) The types of seizures encountered in this study
data, type of seizures, the anti-epileptic drugs and their frequency are shown in Table 1.
prescribed and the adverse drug reactions (ADRs)
reported by the patients were recorded. Table 1. Seizure types and their frequency
Seizure type Cases out of 278 %
The data thus obtained was analyzed to arrive at Idiopathic generalized epilepsy 96 34.53
prescribing indicators, patient indicators and Symptomatic epilepsy * 73 26.25
adverse drug reaction profile [6]. Simple Febrile seizures 48 17.26
Complex partial seizures 18 6.47
Seizures with mental
Prescribing indicators include 16 5.75
retardation (cerebral palsy)
Complex febrile seizures 9 3.23
1) Average number of anti-epileptic drugs (AEDs) Simple partial seizures 8 2.87
prescribed per patient. This is calculated as: Absence seizures 6 2.15
Juvenile myoclonic seizures 1 0.35
Post partum epilepsy 1 0.35
Total no. of AEDs prescribed for
Benign Rolandic epilepsy 1 0.35
all patients
Eating (reflex) epilepsy 1 0.35
Avg. no. of AEDs/patient =
*Seizures due to structural lesions of brain such as stroke,
Total no. of patients
cerebral bleed trauma, granuloma, cerebral atrophy, cyst,
tumor etc.
2) Most commonly prescribed anti-epileptic drug(s)
in this study and the commonest drug(s) The most commonly prescribed anti-epileptic drugs
prescribed for each seizure type. (AEDs) in our study were Phenytoin 42.44%
3) Number of AEDs prescribed using generic followed by Sodium Valproate 23.74%. The drug(s)
names. prescribed in each type of seizure is shown in table 2.

Patient indicators include 3) Number of AEDs prescribed in generic name:

Diazepam – 72 cases, Midazolam – 26 cases.
1) Total number of male and female patients.
2) Average age of male and female patients. Patient indicators
3) Number of patients receiving monotherapy and
multiple anti-epileptic drugs respectively. 1) Total number of patients in the study = 278
a) Number of male patients = 173 (62.23%)
Adverse drug reaction (ADR) profile includes b) Number of female patients = 105 (37.77%)
1) The incidence and type of adverse drug reaction. Male 173
2) The causality relationship of the ADR with Ratio = = = 1.64
suspected drug according to Naranjo ADR prob- Female 105

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Table 2. Types of seizures and drugs prescribed

Commonest drug prescribed Second commonest drug
Other drugs
Seizure type alone or in combination (% of prescribed alone or in
prescribed
cases) combination (% of cases)
Clobazam
Topiramate
Midazolam
Idiopathic generalized
Phenytoin (60.41) Sodium valproate (20.83) Carbamazepine
epilepsy
Phenobarbitone
Clonazepam
Oxcarbazepine
Topiramate
Midazolam
Symptomatic epilepsy Phenytoin (57.53) Sodium valproate (27.39) Carbamazepine
Oxcarbazepine
Clonazepam
Phenytoin
Midazolam
Simple febrile seizures Clobazam (79.16) Diazepam (66.66)
Phenobarbitone
Lorazepam
Topiramate
Oxcarbazepine
Complex partial seizures Carbamazepine (55.55) Sodium valproate (27.77)
Clonazepam
Phenytoin
Topiramate
Seizures with mental
Sodium valproate (25) Carbamazepine
retardation Phenytoin (50)
Midazolam (25) Clobazam
(cerebral palsy)
Diazepam
Phenytoin (44.44) Sodium valproate (33.33)
Complex febrile seizures ---
Diazepam (44.44) Clobazam (33.33)
Phenytoin (25)
Simple partial seizures Carbamazepine (50) Sodium valproate (25) ---
Diazepam (25)
Carbamazepine (33)
Topiramate (83.33) (as
Absence seizures Sodium valproate (33) ---
adjuvant drug)
Phenytoin (33)
Juvenile myoclonic
Sodium valproate (100) --- ---
seizures
Post partum epilepsy Carbamazepine (100) --- ---
Benign Rolandic
Carbamazepine (100) --- ---
epilepsy
Eating (reflex) epilepsy Oxcarbazepine (100) --- ---

2) Age range of patients = 7 months to 70 years. Phenytoin and Carbamazepine contributed equally
a) Average age of male patients = 22.21 years. to the occurrence of adverse effects (six cases
b) Average age of female patients = 22.98 years. each). None of the patients received any treatment
3) Incidence of mono and polytherapy (Table 3). for adverse effects.

Table3. Incidence of mono and polytherapy DISCUSSION

Type of therapy Percentage
No. of patients receiving single AED 150(53.95 %) In this study, idiopathic generalized epilepsy was
No. of patients receiving two AEDs 114 (41.00 %) the commonest type of epilepsy 34.53% and
No. of patients receiving three AEDs 14 (5.03 %)
phenytoin was the commonest drug prescribed
60.41% for it’s treatment, followed by sodium
Adverse drug reaction (ADR) profile
valproate 20.83%. Symptomatic epilepsy
comprised the second commonest category of
13 patients out of a total of 278 reported ADRs
seizures 26.25%. It included seizures due to
(incidence = 4.67%) as shown in the Table 4.
structural lesions of the brain such as stroke, cerebral
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Vol.3 Issue 1, January-March 2010 ISSN 0974-2441

Table 4. Adverse drug reactions

No. of Suspected Causality Whether treatment with
ADR reported
patients drug relationship AED continued / stopped
3 Drowsiness, subtle imbalance Phenytoin Possible Continued
2 Gum swelling Phenytoin Possible Continued
1 Decreased memory and learning Phenytoin Possible Continued
Carbamazepine (6 cases) Possible Continued (5 cases)
7 Drowsiness Stopped (1 case)
Topiramate (1 case) Possible Continued

bleed, trauma, granuloma, cerebral atrophy, cyst, clonic seizures, usually during sleep. This case was
tumour etc. Phenytoin 57.53% followed by Sodium treated with carbamazepine which is commonly
Valproate 27.39% was the most commonly used for this seizure type [9].
prescribed drugs. Phenytoin was widely prescribed
in our study, unlike another South Indian study by We recorded one case of eating epilepsy which is a
Radhakrishnan et al. where it was underutilized, type of reflex epilepsy. In this condition, seizures
inspite of being less expensive [4]. Simple febrile can be provoked habitually by an external stimulus
seizures were treated with diazepam in the acute (like eating) or internal mentalprocesses. Reflex
stage and therapy was maintained with Clobazam. epilepsies may manifest as either focal onset or
The latter drug is preferred as maintenance therapy primary generalized seizures [10]. Among the
to prevent recurrence. It has fewer side effects like prescribed AEDs, Diazepam (72 cases) and
ataxia and drowsiness compared to Diazepam and Midazolam (26 cases) were the only drugs
also ensures better patient compliance [7]. In cases prescribed by generic names.
of complex febrile seizures Diazepam/ Phenytoin/
Sodium Valproate were used in the acute stage and Diazepam, lorazepam and midazolam were the
Clobazam was used for maintenance therapy. drugs used for acute control of different types of
seizures. Single AED was prescribed in 53.95% of
Among the newer AEDs Topiramate was most patients. The remaining patients required
commonly used as an adjuvant drug. It was most polytherapy. A combination of two AEDs was
often combined with Sodium Valproate (18 cases) prescribed in 41% of patients while 5.03% were on
followed by combination with Carbamazepine (four a combination of three AEDs.
cases), Oxcarbazepine (four cases) and Phenytoin
(two cases). Topiramate was the commonest The overall incidence of adverse drug reactions
adjuvant drug and recorded maximal use in absence (ADRs) was not very high in our study (13 patients
seizures. Though the efficacy of Topiramate is out of 278 i.e. 4.67%). Phenytoin and
similar to the conventional drugs, it was preferred Carbamazepine contributed equally to the
because of lesser incidence of adverse effects [8]. occurrence of ADRs (six patients each).Drowsiness,
imbalance, gum swelling, decreased memory and
We encountered use of Phenytoin and learning were the ADRs reported by patients on
Carbamazepine in two cases each of absence Phenytoin. Most of these correspond well with the
seizures, which is not in accordance with the known adverse effect profile of Phenytoin [11]. Since
standard treatment protocol. In case of partial Phenytoin was the only AED in the prescriptions of
seizures (both simple and complex) Carbamazepine these patients, the reported adverse effects can be
was the commonest first line drug, which conforms attributed to it. Drowsiness was reported by six
with standard treatment guidelines. patients taking Carbamazepine as monotherapy. In
one case, drowsiness was possibly due to
We came across one case of benign rolandic Topiramate as the patient reported it only after it
epilepsy. A typical attack involves twitching, was added to Carbamazepine. The patient did not
numbness or tingling of the child’s face or tongue report drowsiness with the use of Carbamazepine as
(partial seizure) which often interferes with speech a single drug previously. Overall, drowsiness was
and may cause drooling. These seizures last less the most frequent adverse effect in our study which
than two minutes and the child remains fully is similar to the finding in a previous study [4].
conscious. Sometimes the child may also have tonic-

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Vol.3 Issue 1, January-March 2010 ISSN 0974-2441

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Phenytoin was the most frequently prescribed AED a pharmacoepidemiolgic study in Oman. Journal of
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The overall incidence of adverse drug reactions was
not very high. Drowsiness was the commonest ADR
reported. Carbamazepine and Phenytoin accounted
for most of the ADRs. Treatment with antiepileptic
drugs was continued in all cases except one, as the
nature of adverse reaction was not considered
serious. None of the patients received any treatment
for adverse effects.

ACKNOWLEDGEMENTS

We thank the consultant neurologist of Owaisi

hospital Dr. V S Prasad for his kind help and
cooperation in conducting this study.

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