Cosmetic effects of anti-epileptic drugs among adult Sudanese epileptic patients

Background and aims: Adverse effects are leading causes of treatment failure with antiepileptic drugs(AEDs).We studied the cosmetic effects of AEDs and their association with medications adherence and quality of life . Methods The study was performed on Sudanese epilepsy patients attending Daoud charity (June-September2014). Five main variables were used(1)Cosmetic effects prole;(2) Morisky Medication Adherence Scale (MMAS-8);(3)WHO Quality of Life Brief-26;(4)Socio-demographic data ,and (5)Epilepsy related data. A senior neurologist assessed the cosmetic effects through clinical examination of the patients. Consents have been obtained from all patients. Result of was valproate.(26.2%)of Neither of life nor score were correlated with any the of 0.05).A signicant positive correlations was found between the from the last and the quality of life score (P = 0.03). The Gum overgrowth was correlated with hirsutism and Acne(P > 0.05).


Introduction
An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. 1 The de nition 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. 1,2 The International League against Epilepsy (ILAE) Commission on Classi cation 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, Atonic, Myoclonic, and Types that may be focal, generalized, or unclear (Epileptic spasms). 1 In most surveys, approximately 60% of epilepsy will have no identi able cause, the main Investigations of a patient with suspected epilepsy are: Electroencephalography (EEG) and neuroimaging (MRI, SPECT, and PET). 2 The management of patients with epilepsy is both challenging and rewarding, The main goal of AEDs therapy is to eliminate seizures without causing side effects. 3 Since 1960s and 1970s sodium valproate (valproate) and carbamazepine became the standard treatments for epilepsy, which they still are. 4 The 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 or not side effects occurred, to enabling patients with epilepsy to lead lifestyles consistent with their capabilities. 3 The 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 classi cation. 4 Treatment 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. 5 The principal antiepileptic drugs used to treat patients with epilepsy are carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproate, and zonisamide. 6 Current guidelines recommend valproate (VPA) as a treatment of rst choice for patients with generalized onset seizures whilst carbamazepine (CBZ) is recommended as the rst 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 de nition 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." 10 The 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 -9 There are several ways in which adverse effects have been classi ed. The classi cation "dose-related" or "idiosyncratic" is most commonly used. 12 Adverse 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. 13 Furthermore, adverse effects of antiepileptic drugs are a major source of disability, morbidity, and mortality. 13 The main reason for changing AEDs is lack of e cacy, but signi cant side effects are also an important reason for modifying treatment in those patients who reported higher levels of discomfort. 14 With certain modi cation on the de nition of the international conference on harmonization Guideline (ICH) E2A, we can de ne "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 Pro le tend to segregate into ve classes. These include 1) Cognition/Coordination (unsteadiness, double or blurred vision, di culty 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. 15 The two classes of Tegument/Mucosa and Weight/Cephalgia with exclusion of headache can be regarded as cosmetic effects. 16 Sudan is now the third largest country in Africa and also the third largest country in the Arab world (estimated population is little over 30 million people) Omdurman is the largest city in Sudan and Khartoum State, lying on the western banks of the River Nile, together With Khartoum and Khartoum Bahri; it forms the cultural and industrial heart of the nation.
Banat charity Neurological Referral Clinic is a charity clinic, in which neurologists, psychiatrists, physicians, and medical registrars tend to see patients every week at Friday, which is the weekend, and many patients attend this clinic; they are from Khartoum state, but also many of them from deferent states of Sudan. Also the clinic is attended by medical students. All interviewers are doctors graduated from faculty of medicine, or a 5 th year medical student and above.
Data analysis: All collected data were entered into the computer using the statistical package program for social science (SPSS) to analyze the data via simple descriptive statistics. (Analyzer is specialized personnel in SPSS).
Ethical concern: Consent was obtained from: All patients, and from the local ethical committee acid. Gingival hyperplasia, hirsutism and acne were the most commonly reported in patients taking phenytoin(2%,p0.oo1).One of our patient who used to take lamotrogine had loss of weight. One patient on phenobarbitone and one on carbamazipine had skin eruption. Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with sodium valprote compared with all other AEDs (2.3% P 0.001). Neither of life score, nor adherence score were correlated with any of the cosmetic effects of AEDs (P > 0.05).A signi cant positive correlations was found between the duration from the last attack and the quality of life score (P = 0.03).

Discussion
Epilepsy is a relatively common condition characterized by a tendency for recurrent seizures, which is due to the disturbance of spread of electrical discharge of the cortical neurons. 19 Epilepsy is either: idiopathic when there is no underlying cause or secondary if there is an underlying cause egg brain tumors, stroke.
Clinically seizures are divided into two basic categories, generalized and focal. As many as 80% of epilepsy patients can be controlled with anti-epileptic drugs. The type of medication prescribed depends on the type of seizure, the underlying cause of the epilepsy, the age of the patient, possible side effects, and the availability of the medication. Treatment usually starts with a low dose and then gradually increases. In most patients, the epilepsy will subside after a few years and medications can be stopped gradually.
Phenytoin is effective for the treatment of focal and tonic clonic seizures.Carbamazepine is effective in the treatment of focal and generalized tonic-clonic seizures, while phenobarbital is as effective as phenytoin and carbamazepine in clearing focal and generalized tonic-clonic seizures. On the other hand, sodium valproate is effective for all types of epilepsy patients. The occurrence of adverse effects unrelated to the dose, is particularly prominent during the initiation of therapy (especially with carbamazepine and valproic acid), but disappear as tolerance develops. For this reason, therapy with these drugs should be started on low doses and the dose slowly titrated up to the recommended maintenance over several weeks. 20 Cosmetic effects of AEDs are of particular concern among women because they can damage body image and self-esteem. Like what was mentioned in the literature maculopapular rashes were noted in 3% of our patients started on carbamazepine, phenytoin, phenobarbital, and lamotrigine. 22 Rarely severe mucocutaneous reactions such as Stevens-Johnson syndrome, and toxic epidermal necrolysis can occurred with the use of these antiepileptic drugs. 23 Patient taking phenobarbital can have many skin reactions, including: morbilliform, urticaria, erythema multiforme, photosensitivity, acneiform rash, and purpura. Skin eruptions are signi cantly more likely if lamotrigine is given with valporic acid, especially if the recommended dose is exceeded.Adverse effects of Lamotrigine may include serious toxic epidermal necrolysis, in which alopecia is a well-known phenomenon. The occurrence of carbamazepine-induced alopecia is at or below 2%. 24 Hair loss is a side effect of patients taking aromatic anticonvulsants, but it rarely occurs after such drugs are discontinued during recovery from anticonvulsant hypersensitivity syndrome. 24 Epilepsy has diverse effects on the overall wellbeing or subjective quality of life (QOL) of the patients.25 QOL in epilepsy is associated with several factors. These factors include clinical variables (for example, seizure frequency, severity, illness duration, treatment side effects and psychiatric co-morbidities), social disadvantages (for example, divorce, unemployment, social stigma, and illness intrusion into social life), and family circumstances (such as family caregiver characteristics and social support). 25 Adverse effects of antiepileptic drugs have emerged as one of the strongest predictors of impaired health-related quality of life, independent of seizure outcome. 26 Declarations Consent for publication Not applicable.
Availability of data and materials The materials datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.