Correlation between Daytime Sleepiness and Antiepileptic Drugs in Generalized Tonic Clonic Epilepsy Patients in Epilepsy Outpatient Clinic at Neurology Department University of Sumatera Utara, Medan, Indonesia
Correlation between Daytime Sleepiness and Antiepileptic Drugs in
Generalized Tonic Clonic Epilepsy Patients in Epilepsy Outpatient Clinic at
Neurology Department University of Sumatera Utara, Medan, Indonesia
Silvana Asrini, Aldy S. Rambe, dan Darulkutni Nasution
Department of Neurology, North Sumatera Medical Faculty
And Haji Adam Malik Hospital
Medan, Indonesia
Abstract: Drowsiness is frequently reported in patients taking antiepileptic drugs (AEDs), but it
seems more prominent with some AEDs, and it is invariably enhanced by drug combination. This
study was aimed to assess correlation between daytime sleepiness and AEDs in generalized tonic
clonic epilepsy patients. A cross sectional study with subjects consisted of 40 consecutive adult
patients with generalized tonic clonic epilepsy, receiving AEDs monotherapy or polytherapy was
performed. Each patient was asked regarding the type and the dose of AEDs. Patients were selfrated their own degree of sleepiness by using Epworth Sleepiness Scale and Stanford Sleepiness
Scale. In this research, 27 (67.5%) patients took monotherapy (phenytoin or carbamazepine), 13
(32.5%) patients took polytherapy (phenytoin-carbamazepine, phenytoin-phenobarbital or
phenytoin-valproic acid). Correlation between daytime sleepiness and AEDs in generalized tonic
clonic epilepsy patients was significant (p < 0.05). Epworth Sleepiness Scale and Stanford
Sleepiness Scale showed that there was a different level of sleepiness in each kind of AED. Most
subjects reported that they had moderate and severe daytime sleepiness after taking combination
of phenytoin and carbamazepine. Daytime sleepiness in patients receiving AEDs polytherapy
was higher than monotherapy (p < 0,05). There is a significant relationship between AEDs and
daytime sleepiness in patients with generalized tonic clonic epilepsy (p < 0.05). Sleepiness is
relatively higher in AEDs polytherapy than in monotherapy.
Keywords: antiepileptic drugs - daytime sleepiness – epilepsy
Abstrak: Mengantuk sering dilaporkan pada pasien yang mengkonsumsi obat anti epilepsi (OAE),
tetapi terlihat lebih menonjol pada beberapa OAE, dan bertambah lagi dengan kombinasi obat.
Penelitian ini bertujuan untuk menilai hubungan antara daytime sleepiness dan OAE pada pasien
epilepsi umum tonik klonik. Suatu penelitian potong lintang dengan subjek yang terdiri dari 40
pasien dewasa epilepsi umum tonik klonik secara konsekutif, yang mendapat OAE monoterapi
atau politerapi. Setiap pasien ditanya mengenai tipe dan dosis OAE. Pasien disuruh menilai
sendiri tingkat mengantuknya dengan menggunakan Epworth Sleepiness Scale dan Stanford
Sleepiness Scale. Pada penelitian ini, 27 (67,5%) pasien menggunakan monoterapi (fenitoin atau
karbamazepin), 13(32,5%) pasien menggunakan politerapi (fenitoin-karbamazepin, fenitoinfenobarbital atau fenitoin-asam valproat). Hubungan antara daytime sleepiness dan OAE pada
epilepsi umum tonik klonik adalah signifikan (p < 0.05). Epworth Sleepiness Scale dan Stanford
Sleepiness Scale telah menunjukkan bahwa terdapat perbedaan tingkat rasa mengantuk pada
masing-masing OAE. Kebanyakan subjek melaporkan bahwa mereka memiliki daytime sleepiness
yang sedang dan berat setelah mengkonsumsi kombinasi antara fenitoin dan karbamazepin.
Daytime sleepiness pada pasien yang mendapat OAE politerapi lebih tinggi dibanding monoterapi
(p < 0,05). Terdapat hubungan yang signifikan antara OAE dan daytime sleepiness pada pasien
epilepsi umum tonik klonik. Rasa mengantuk relatif lebih tinggi pada OAE politerapi dibanding
monoterapi.
Kata kunci: obat anti epilepsi – daytime sleepiness – epilepsi
99
Majalah Kedokteran Nusantara Volume 41 y No. 2 y Juni 2008
Silvana Asrini dkk.
INTRODUCTION
Sleep is important for the general health of
all, but is particularly essential for individuals with
epilepsy. In these patients, a complex relationship
1
exists between seizures and sleep. Historically,
Hippocrates and Aristotle, the interrelationship
2
between epilepsy and sleep has been noted.
Individuals with epilepsy commonly report
excessive daytime sleepiness (EDS) and fatigue
that are typically attributed to the effects of
seizure or antiepileptic drugs (AEDs). However,
in patients with epilepsy, sleep is disrupted by
frequent arousals, awakenings, and stage shift,
3-5
even in the absence of seizures and AEDs.
Drowsiness is frequently reported in patients
taking antiepileptic drugs (AEDs), but it seems
more prominent with some AEDs, and it is
invariably enhanced by drug combination. It is
well known that sleepiness is highly related to
6
polipharmacy, particularly with older AEDs.
A number of the older epilepsy drugs have
adverse effects on sleep and daytime vigilance.
Recent studies suggest that some of the newer
AEDs may be neutral or even have positive effects
on sleep consolidation and alertness. Whether
primary sleep disorders are a significant cause of
EDS in patients with epilepsy remains to be
7
determined.
This study was aimed to assess correlation
between daytime sleepiness and AEDs in
generalized tonic clonic epilepsy patients.
METHODS
Subjects
A cross sectional study with subjects
consisted of 40 consecutive adult patients with
generalized tonic clonic epilepsy, who visited
Epilepsy Outpatient Clinic Haji Adam Malik
Hospital, Tembakau Deli Hospital and Kesdam I
Putri Hijau Hospital, from December 2005
through March 2006. All subjects fulfilled
inclusion criteria: (a) age > 15 years: (b) have been
used AEDs more than 3 months: (c) seizure-free
more than 3 months. Exclusion criteria included
(a) use of sedatives, hypnotics, anxiolitics and
antihistamines drugs: (b) evidence of sleep
disorders: (c) epilepsy patients with alcoholic and
other drug abuse: (d) psychiatric disorders: and (e)
patients with consciousness, auditory, aphasia and
visual disorders.
Correlation between Daytimes Sleepiness…
Procedure
After giving written informed consent,
subjects were interviewed by physician. Each
subject was asked to fill up questionnaire which
adaptation from Epworth Sleepiness Scale (ESS)
and Stanford Sleepiness Scale (SSS). The ESS is an
eight-item survey designed to ascertain sleep
propensity during activities of daily living. Subjects
rate the chance of dozing in each of eight activities
of daily living from 0 (never) to 3 (high). The
scores for the eight activities are tallied, producing
a total score ranging from 0 to 24, with a score
until 6-7 (normal), 8-12 (mild), 13-17 (moderate)
and score > 18 indicating severe daytime
3
sleepiness. The SSS is an eight-item survey
designed to ascertain sleep propensity during
subject was interviewed. Subjects was asked to
choose one of the item. Score > 3 (severe) and
Generalized Tonic Clonic Epilepsy Patients in Epilepsy Outpatient Clinic at
Neurology Department University of Sumatera Utara, Medan, Indonesia
Silvana Asrini, Aldy S. Rambe, dan Darulkutni Nasution
Department of Neurology, North Sumatera Medical Faculty
And Haji Adam Malik Hospital
Medan, Indonesia
Abstract: Drowsiness is frequently reported in patients taking antiepileptic drugs (AEDs), but it
seems more prominent with some AEDs, and it is invariably enhanced by drug combination. This
study was aimed to assess correlation between daytime sleepiness and AEDs in generalized tonic
clonic epilepsy patients. A cross sectional study with subjects consisted of 40 consecutive adult
patients with generalized tonic clonic epilepsy, receiving AEDs monotherapy or polytherapy was
performed. Each patient was asked regarding the type and the dose of AEDs. Patients were selfrated their own degree of sleepiness by using Epworth Sleepiness Scale and Stanford Sleepiness
Scale. In this research, 27 (67.5%) patients took monotherapy (phenytoin or carbamazepine), 13
(32.5%) patients took polytherapy (phenytoin-carbamazepine, phenytoin-phenobarbital or
phenytoin-valproic acid). Correlation between daytime sleepiness and AEDs in generalized tonic
clonic epilepsy patients was significant (p < 0.05). Epworth Sleepiness Scale and Stanford
Sleepiness Scale showed that there was a different level of sleepiness in each kind of AED. Most
subjects reported that they had moderate and severe daytime sleepiness after taking combination
of phenytoin and carbamazepine. Daytime sleepiness in patients receiving AEDs polytherapy
was higher than monotherapy (p < 0,05). There is a significant relationship between AEDs and
daytime sleepiness in patients with generalized tonic clonic epilepsy (p < 0.05). Sleepiness is
relatively higher in AEDs polytherapy than in monotherapy.
Keywords: antiepileptic drugs - daytime sleepiness – epilepsy
Abstrak: Mengantuk sering dilaporkan pada pasien yang mengkonsumsi obat anti epilepsi (OAE),
tetapi terlihat lebih menonjol pada beberapa OAE, dan bertambah lagi dengan kombinasi obat.
Penelitian ini bertujuan untuk menilai hubungan antara daytime sleepiness dan OAE pada pasien
epilepsi umum tonik klonik. Suatu penelitian potong lintang dengan subjek yang terdiri dari 40
pasien dewasa epilepsi umum tonik klonik secara konsekutif, yang mendapat OAE monoterapi
atau politerapi. Setiap pasien ditanya mengenai tipe dan dosis OAE. Pasien disuruh menilai
sendiri tingkat mengantuknya dengan menggunakan Epworth Sleepiness Scale dan Stanford
Sleepiness Scale. Pada penelitian ini, 27 (67,5%) pasien menggunakan monoterapi (fenitoin atau
karbamazepin), 13(32,5%) pasien menggunakan politerapi (fenitoin-karbamazepin, fenitoinfenobarbital atau fenitoin-asam valproat). Hubungan antara daytime sleepiness dan OAE pada
epilepsi umum tonik klonik adalah signifikan (p < 0.05). Epworth Sleepiness Scale dan Stanford
Sleepiness Scale telah menunjukkan bahwa terdapat perbedaan tingkat rasa mengantuk pada
masing-masing OAE. Kebanyakan subjek melaporkan bahwa mereka memiliki daytime sleepiness
yang sedang dan berat setelah mengkonsumsi kombinasi antara fenitoin dan karbamazepin.
Daytime sleepiness pada pasien yang mendapat OAE politerapi lebih tinggi dibanding monoterapi
(p < 0,05). Terdapat hubungan yang signifikan antara OAE dan daytime sleepiness pada pasien
epilepsi umum tonik klonik. Rasa mengantuk relatif lebih tinggi pada OAE politerapi dibanding
monoterapi.
Kata kunci: obat anti epilepsi – daytime sleepiness – epilepsi
99
Majalah Kedokteran Nusantara Volume 41 y No. 2 y Juni 2008
Silvana Asrini dkk.
INTRODUCTION
Sleep is important for the general health of
all, but is particularly essential for individuals with
epilepsy. In these patients, a complex relationship
1
exists between seizures and sleep. Historically,
Hippocrates and Aristotle, the interrelationship
2
between epilepsy and sleep has been noted.
Individuals with epilepsy commonly report
excessive daytime sleepiness (EDS) and fatigue
that are typically attributed to the effects of
seizure or antiepileptic drugs (AEDs). However,
in patients with epilepsy, sleep is disrupted by
frequent arousals, awakenings, and stage shift,
3-5
even in the absence of seizures and AEDs.
Drowsiness is frequently reported in patients
taking antiepileptic drugs (AEDs), but it seems
more prominent with some AEDs, and it is
invariably enhanced by drug combination. It is
well known that sleepiness is highly related to
6
polipharmacy, particularly with older AEDs.
A number of the older epilepsy drugs have
adverse effects on sleep and daytime vigilance.
Recent studies suggest that some of the newer
AEDs may be neutral or even have positive effects
on sleep consolidation and alertness. Whether
primary sleep disorders are a significant cause of
EDS in patients with epilepsy remains to be
7
determined.
This study was aimed to assess correlation
between daytime sleepiness and AEDs in
generalized tonic clonic epilepsy patients.
METHODS
Subjects
A cross sectional study with subjects
consisted of 40 consecutive adult patients with
generalized tonic clonic epilepsy, who visited
Epilepsy Outpatient Clinic Haji Adam Malik
Hospital, Tembakau Deli Hospital and Kesdam I
Putri Hijau Hospital, from December 2005
through March 2006. All subjects fulfilled
inclusion criteria: (a) age > 15 years: (b) have been
used AEDs more than 3 months: (c) seizure-free
more than 3 months. Exclusion criteria included
(a) use of sedatives, hypnotics, anxiolitics and
antihistamines drugs: (b) evidence of sleep
disorders: (c) epilepsy patients with alcoholic and
other drug abuse: (d) psychiatric disorders: and (e)
patients with consciousness, auditory, aphasia and
visual disorders.
Correlation between Daytimes Sleepiness…
Procedure
After giving written informed consent,
subjects were interviewed by physician. Each
subject was asked to fill up questionnaire which
adaptation from Epworth Sleepiness Scale (ESS)
and Stanford Sleepiness Scale (SSS). The ESS is an
eight-item survey designed to ascertain sleep
propensity during activities of daily living. Subjects
rate the chance of dozing in each of eight activities
of daily living from 0 (never) to 3 (high). The
scores for the eight activities are tallied, producing
a total score ranging from 0 to 24, with a score
until 6-7 (normal), 8-12 (mild), 13-17 (moderate)
and score > 18 indicating severe daytime
3
sleepiness. The SSS is an eight-item survey
designed to ascertain sleep propensity during
subject was interviewed. Subjects was asked to
choose one of the item. Score > 3 (severe) and