Original Articles

Clobazam for the treatment of

intractable childhood epilepsy

Mohammed M. Jan, MBChB, FRCP(C), Ali O. Shaabat, MD, FRCP(C).

ABSTRACT

Objective: Clobazam is a newer 1,5-benzodiazepine and were on multiple anti-epileptic drugs (mean 2.3, +/-
used for the treatment of epilepsy. It is better tolerated and SD 1). Fourteen (45%) children had Lennox-Gastaut
less sedating than other benzodiazepines. It has yet to gain Syndrome. After the introduction of clobazam, 11
wide use for epilepsy in the Middle East. Our objective is (35.5%) became completely seizure free and 14 (45%) had
to report our experience with clobazam for the treatment of >50% seizure reduction. Side effects were reported in 7
childhood epilepsy. (22.5%) in the form of excessive sedation, vomiting,
irritability, behavioral change, and ataxia. In 4 children
Methods: A cohort of children with intractable epilepsy, these side effects resolved either spontaneously or with
defined as recurrent seizures after at least 3 anti-epileptic dose reduction.
medication trials, were included prospectively. Clobazam
was added to a maximum dose of 2 mg/kg/day. Follow-up Conclusion: Clobazam is a well tolerated, safe, and very
by two pediatric neurologists was performed. Therapeutic effective antiepileptic drug. It has a broad spectrum of
response was recorded as complete (no seizures), good antiepileptic activity, minimal side effects, and is relatively
(>50% seizure reduction), fair (<50% seizure reduction), inexpensive. Wider use of this drug is recommended in
or none. children with intractable epilepsy.

Results: Thirty one children (21 males - 10 females), Keywords: Clobazam, child, intractable, epilepsy, seizures.
aged 2 months-15 years (mean 4.6 years) were followed
for 3-12 months. Most children (68%) had daily seizures Neurosciences 2000; Vol. 5 (3): 159-161

lobazam is a newer benzodiazepine used for the clearance and increase carbamazepine levels.10-12 Few
C treatment of epilepsy. It is a 1,5-
1 side effects have been reported in up to 25% of
benzodiazepine that is better tolerated and results in patients, mainly sedation, behavioral change,
less sedation when compared to the other memory defects, and tolerance. 4,8
benzodiazepines.2-4 The half life of clobazam is 18 Although clobazam is cheaper than the other new
hours and up to 42 hours for its active metabolite.4 anti-epileptic drugs and is readily available in the
Several studies examined the efficacy of clobazam in Middle East, it is not widely used for epilepsy and its
partial and generalized seizures.5-8 The Canadian use has been primarily in the field of psychiatry as an
Clobazam Cooperative Study Group reported a 50% anxiolytic agent. We report our experience with
improvement in 40% of patients with intractable clobazam for the treatment of childhood epilepsy.
seizures.8 In other studies up to 21% of children
became seizure free and half had at least 50% seizure
reduction.9 The drug had a low incidence of drug Methods. A cohort of children with intractable
interactions, however, enzyme inducers can lower its epilepsy was included prospectively. Patients were
serum level. Clobazam can reduce phenytoin hepatic identified through referrals and consultations to the

From the Department of Pediatrics (Neurology), King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia.

Published simultaneously with special permission from Saudi Medical Journal.

Address correspondence and reprint request to: Dr Mohammed M. S. Jan, The Department of Pediatrics (Neurology), King Abdulaziz University
Hospital, PO Box 6615, Jeddah 21452, Kingdom of Saudi Arabia. Tel. + 966 2 640 1000 Ext 20208. Fax. + 966 2 640 3975.

159
 Clobazam for childhood epilepsy ... Jan & Shaabat

Table 1 - Causes of intractable epilepsy in the study cohort (n=31). females, aged 2 months-15 years (mean 4.6, SD 3.1
years). Twenty-four (77%) children had mental
retardation. Fourteen (45%) children had Lennox-
Diagnosis Number (Percentage) Gastaut Syndrome with multiple seizure types, 9
(29%) had partial seizures with or without secondary
generalizations, 4 (13%) had myoclonic epilepsy, and
Cerebral Palsy 7 (23%)
4 (13%) had isolated generalized tonic clonic
Idiopathic Epilepsy 6 (19%) seizures. The underlying causes of their epilepsy are
Syndromic/CNS Malformation 5 (16%) summarized in Table 1. The most common diagnosis
was cerebral palsy (23%). Idiopathic epilepsy
Cryptogenic Epilepsy 4 (13%) (normal development and central nervous
Neurodegenerative Disorder 3 (10%) examination (CNS)) and cryptogenic epilepsy
(abnormal development and CNS exam with no
Post-meningitis or Post-encephalitis 3 (10%) recognized disease) were present in 19% and 13% of
CNS Tumor 1 (3%) the children (Table 1). The age of seizure onset
ranged between 1 month – 6 years (mean 1.8, SD 1.7
Post-traumatic Epilepsy 1 (3%)
years). The duration of epilepsy prior to the
Mesial Temporal Sclerosis 1 (3%) initiation of clobazam ranged between 2 months – 10
years (mean 2.9, SD 2.5 years). Most children (68%)
had daily seizures and were on multiple anti-epileptic
Pediatric Neurology Service at King Abdulaziz drugs (range 1-5, mean 2.3, +/- SD 1). Eleven
University Hospital (KAUH) from August 1, 1998 to (35.5%) children were on 3 or more antiepileptic
July 31, 1999. King Abdulaziz University Hospital drugs. Clobazam was added to the other antiepileptic
is a multispecialty adult and pediatric hospital drugs with a final dose ranging between 5-40 mg/day
providing primary care to the Jeddah area, as well as divided twice per day. After the introduction of
secondary and tertiary care for most of the regional clobazam, 11 (35.5%) children became completely
population of western Saudi Arabia. King Abdulaziz seizure free, 14 (45%) had >50% seizure reduction, 4
University Hospital is the main teaching center of (13%) had <50% seizure reduction, and 2 (6.5%) had
western Saudi Arabia and is linked to King no response. None of the children had worsening of
Abdulaziz University Medical School. Patient and their seizures. Table 2 shows a summary of the
disease related data were collected during the initial seizure count before and after clobazam. Children
visit. Intractable epilepsy was defined as recurrent with Lennox Gastaut Syndrome had a relatively less
seizures that failed to respond to at least three anti- favorable response as more children continued to
epileptic medication trials singly or in combination have daily seizures when compared to those with
despite of using maximum doses or doses resulting in other seizure types (3/14 vs 1/17, p=NS). The
therapeutic drug levels. After obtaining verbal number of anti-epileptic drugs also decreased after
consent, clobazam was added to the other anti- the introduction of clobazam to 1-3 (mean 1.7, SD
epileptic drug therapy at a starting dose of 0.25 mg/ 0.5). Only one child was on 3 anti-epileptic drugs.
kg/day (minimum starting dose of 2.5 mg/day). Electroencephalograms (EEG) were recorded before
Clobazam was gradually increased by doubling the starting the clobazam and repeated while the child
dose every 5-7 days until the minimum effective dose was on it in 10 children. Nine (90%) of these children
was reached (achieving a seizure free outcome) or up showed marked EEG improvement in terms of
to a maximum dose of 2 mg/kg/day. Follow up by epileptiform discharges and 8 out of these 9 were
two pediatric neurologists was performed to seizure free. No side effects were noted in 24
document therapeutic response and occurrence of (77.5%) children. The remaining 7 (22.5%) children
side effects. Therapeutic response was recorded as
complete (no seizures), good (>50% seizure Table 2 - Seizure count before and after the initiation of clobazam.
reduction), fair (<50% seizure reduction), or none (no
response).
The data was tabulated using Epi Info, version 6
13,14 , and the results were examined by Chi-square Seizure Count Before Clobazam On Clobazam
Number (%) Number (%)
statistics to identify the magnitude of significant
associations when present. A p-value less than 0.05 Daily 21 (68%) 4 (13%)
was considered statistically significant.
Weekly 7 (22%) 6 (19.5%)

Results. Thirty-one children with intractable Monthly 3 (10%) 10 (32%)

epilepsy were identified and followed for 3-12 None 0.00 11 (35.5%)
months. There were 21 (68%) males and 10 (32%)

160 Neurosciences 2000; Vol. 5 (3)

 Clobazam for childhood epilepsy ... Jan & Shaabat

had some side effects including; excessive sedation this drug is recommended in children with intractable
in 4, vomiting in one, irritability and behavioral epilepsy.
change in 2, and ataxia in one child. The sedation and
ataxia were transient and resolved in 4 children either Acknowledgments. We wish to thank the pediatric
spontaneously or with dose reduction. Clobazam had consultants at King Abdulaziz University Hospital who
to be withdrawn in 3 children due to repeated participated with their referred patients. We particularly would
like to thank Dr. Saad Al-Saadi, Dr. Wasim Anshasi, Dr. Hussein
vomiting or behavioral changes. Bamashmous, and Dr. Amal Al-Dabbag.

Discussion. The study results confirm several References

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