Background
An epileptic seizure is a transient occurrence of signs and/or symptoms
due to abnormal excessive or synchronous neuronal activity in the
brain.1The definition of epilepsy requires at least
one seizure and evidence of persistent changes in the brain, which
increases the likelihood of seizures in the future. The prevalence of
men is slightly higher than that of women. 1, 2The
International League against Epilepsy (ILAE) Commission on
Classification and Terminology, classify seizures into: Focal seizures
that can be further described as having motor, sensory, autonomic,
cognitive, or other features, Generalized seizures that can be
subdivided into: Absence (Typical, Atypical), Tonic clonic, Clonic,
Tonic, A tonic, Myoclonic, and Types that may be focal, generalized, or
unclear (Epileptic spasms). 1In most surveys,
approximately 60% of epilepsy will have no identifiable cause, the main
Investigations of a patient with suspected epilepsy are:
Electroencephalography (EEG) and neuroimaging (MRI, SPECT, and
PET).2The management of patients with epilepsy is both
challenging and rewarding, The main goal of AEDs therapy is to eliminate
seizures without causing side effects.3Since 1960s and
1970s sodium valproate (valproate) and carbamazepine became the standard
treatments for epilepsy, which they still are.4The
introduction of new AEDs and the increased emphasis on maximizing the
quality of life for patients with epilepsy have led to a new set of
goals for the treatment of seizures. These goals have evolved from
complete control of seizures, whether side effects occurred, to enabling
patients with epilepsy to lead lifestyles consistent with their
capabilities.3The choice of AEDs following a new
diagnosis of epilepsy can be complex and is affected by age,
co-morbidity, concomitant medication, possibility of pregnancy and the
individual’s epilepsy classification.4Treatment
usually starts with one drug at a low dose. The dose is then increased
slowly. In most patients, epilepsy remits over a period of years and
drug therapy may be withdrawn slowly.5The principal
antiepileptic drugs used to treat patients with epilepsy are
carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam,
oxcarbazepine, phenobarbital, phenytoin, primidone, tiagabine,
topiramate, valproate, and zonisamide.6Current
guidelines recommend valproate (VPA) as a treatment of first choice for
patients with generalized onset seizures whilst carbamazepine (CBZ) is
recommended as the first line treatment for patients with partial onset
seizures.7-8 Several terms are used to describe health
problems reported by patients taking AEDs, e.g. “adverse events,”
“adverse effects,” “side effects” and “adverse drug reaction”.
These terms are often used interchangeably, but they are
not.9 World Health Organization (WHO)’s definition of
an adverse drug reaction, which has been in use for about 30 years, It
is ”a response to a harmful and unexpected drug, and it occurs at a dose
that humans usually use to prevent, diagnose, or treat disease or change
physiological functions.” 10The terms “adverse
reaction” and “adverse effect” are interchangeable, except that an
adverse effect is seen from the point of view of the drug, whereas an
adverse reaction is seen from the point of view of the patient.11 -9There are several ways in which adverse effects
have been classified. The classification “dose-related” or
“idiosyncratic” is most commonly used. 12Adverse
effects are a leading cause of treatment failure with antiepileptic
drugs. Not only do they cause 25% of patients to stop treatment
prematurely, they also prevent a fully effective dose from being reached
and impair patient compliance with treatment.13Furthermore, adverse effects of antiepileptic drugs
are a major source of disability, morbidity, and mortality.13The main reason for changing AEDs is lack of
efficacy, but significant side effects are also an important reason for
modifying treatment in those patients who reported higher levels of
discomfort.14 With certain modification on the
definition of the international conference on harmonization Guideline
(ICH) E2A, we can define “cosmetic effect” as any negative
(unfavorable) effects or positive (favorable) effects on the beauty,
that is associated with the use of a medicinal product, Provided that a
causal relationship between them is at least a reasonable possibility. A
previous studies done showed the adverse effects of anti-epileptic drugs
in the self-administered Adverse Event Profile tend to segregate into
five classes. These include 1) Cognition/Coordination (unsteadiness,
double or blurred vision, difficulty in concentrating, shaky hands,
dizziness, and memory problems); 2) Mood/Emotion (feelings of
aggression, nervousness or agitation, and depression); 3) Sleep
(tiredness, restlessness, upset stomach, sleepiness, and disturbed
sleep); 4) Weight/Cephalgia (weight gain and headache); and 5)
Tegument/Mucosa (hair loss, problems with skin, and trouble with mouth
or gums.15The two classes of Tegument/Mucosa and
Weight/Cephalgia with exclusion of headache can be regarded as cosmetic
effects. 16-1 7, 18 Weight gain and loss of hair
commonly occur with sodium valproate while loss of weight occurred with
levetiracetame.Gum hypertrophy,hirstism and acne are famous side effects
of phenytoin. carbamazepine, phenytoin, phenobarbital, and lamotrogine
can cause maculopapular rashes. 18