Transcript Evidenced Based Journal Club – 20th June 2007

Evidenced Based Journal
Club – 20th June 2007
A brief overview of:
Banu et al, Side effects of phenobarbital and
carbamazepine in childhood epilepsy:
randomised controlled trial
BMJ, doi:10.1136/bmj.39022.436389.BE
Dr Roland Morley
Goals of Study
• Is phenobarbital associated with more
behavioural side effects than
carbamazepine?
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Study Structure
• Double blind RCT
• Children’s hospital in
Bangladesh
• 12 month follow up
• Intention to treat analysis
• Comparison of behaviour
before and after treatment
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Inclusion
• n=108 recruited by referral
• Children with “active epilepsy”:
• ≥2 generalised tonic-clonic, partial (focal) or
2ndry generalised seizures in last 12 months
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Exclusion
• Absence, myoclonic or severe malignant
epilepsy
• Major motor and cognitive impairments
• Current treatment with antiepileptics
General Assessment
• History
• Examination – CNS and general
• Multi-disciplinary developmental:
– including psychological and IQ
• EEG
Behavioural Assessment
• Participants ≤ 2 years:
– Bayley scale of infant development
• Participants >2 yrs to 3 yrs 11 mths:
– Richman behavioural assessment
questionnaire
• Participants > 5 years:
– Connors’ rating scale
Classification of Participants
• International League Against Epilepsy
research guidelines to classify patients:
• Symptomatic
• Without other impairment
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Randomisation
• Blinded researcher to physician by telephone:
– Oral Phenobarbital (once a day):
• Starting dose 1.5mg/kg OD
• Increased to 3mg/kg OD at 2 weeks
• Titrated until seizures controlled or max dose 4mg/kg
Vs
– Oral Carbamazepine (in 2 divided doses) :
• Starting dose 5mg/kg
• Increased to 16mg/kg at 2 weeks
• Titrated until seizures controlled or max dose 20mg/kg
Follow Up
• 2 weeks, 1 month, 3 months, 6 months, 1 year:
– “depending on therapeutic response and travel”
• Compliance assessed
• Uncontrolled / intolerant of treatment:
– Switch to new drug
– Remove from behaviour outcome analysis
Outcomes
• Behaviour
• “Seizure remission”:
– No seizures in last quarter of 12 month follow up
• Drug Efficacy
– Time to first seizure
– Time to withdrawal from treatment due to side effects
– Date of last follow up
Behaviour Change
• At 1 year follow
up:
– No Change
– Improved
– Deteriorated:
• Acceptable to
parents
• Unacceptable to
parents
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STUDY HEADLINE RESULTS
Behavioural difference within
treatment groups
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• Neither drug shows significant deterioration in
behaviour at 1 year
• 2-5 age group shows significant improvement
Behavioural difference between
treatment groups
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• No significant difference between
treatments
Seizure Remission - No seizures in
last quarter of 12 month follow up
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• Mean time without seizures:
• Phenobarb = 102 days
• Carbamaz = 74 days
No Correlation between
behavioural problems and variables
at one year
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Appendix
• Slides for reference now follow for
discussion
Flow Through Trial
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Demographics
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Demographics
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Outcome
by drug
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