Citation

Ahmadabadif F, Fattahzadeh G, Atalu A, Badihi P (2019) Investigating the Effects of Phenytoin, Phenobarbital, Topiramate, Carbamazepine and Sodium Valproate on the Neurotransmitter Speed in Treated Seizure Children. Int J Neurol Neurother 6:093. doi.org/10.23937/2378-3001/1410093

Research Article | OPEN ACCESS DOI: 10.23937/2378-3001/1410093

Investigating the Effects of Phenytoin, Phenobarbital, Topiramate, Carbamazepine and Sodium Valproate on the Neurotransmitter Speed in Treated Seizure Children

Farzad AhmadabadiF1, Ghasem Fattahzadeh2, Abolfazl Atalu2* and Pooya Badihi3

1Department of Pediatrics, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

2Department of Neurology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

3School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

Abstract

Anticonvulsants such as phenytoin, phenobarbital, topiramate, carbamazepine and valproate due to their beneficial effects and economic benefits in compare to new drugs are used more but these drugs are not harmless and sometimes had dangerous, safe and reversible side effects. Reduction of the nervous conduction velocity (NCV) is the common side effect of these drugs and it is of clinically importance if it is severe especially in treated children. Therefore, it is necessary to evaluate and compare the effect of each drug on NCV. The aim of this study was to investigate the effects of antiepileptic drugs on NCV. In this quasi-experimental study, 125 children with seizure were randomly selected and divided into six equal size groups which received phenytoin, phenobarbital, topiramate, valproate, carbamazepine and one group as control which no received anti-epileptic drug. Sensory and motor neural conduction velocity were measured and recorded for all children in groups. Collected data were analyzed by statistical methods in SPSS version 19. All of anticonvulsants were reduced the NCV in children but among all drugs, phenobarbital and phenytoin had the least and most impact on the NCV. The changes in NCV were not related to the age and gender of children. Results showed that the anticonvulsants had similar impact on NCV in generally but future studies are recommended by considering the other effective variables on response to drug.

Keywords

Seizure, Anticonvulsants, Nerve conduction velocity (NCV), Epilepsy

Introduction

About one percent of the world's population had epilepsy. Epilepsy attacks are the second most common neurological disorder after stroke. Today standard treatments have managed to control nearly 80% of patients. Seizures are short term episodes as a result of abnormal discharge of brain neurons. Various causes such as infection, neoplasm or trauma may be involved in these attacks. Epilepsy is one of the most common diagnoses seen by pediatric neurologists. One percent to two percent of the pediatric population has epilepsy [1]. Almost 4-10% of children experience at least one seizure. The prevalence of epilepsy in children is about 1-2%. The goal of treatment in children is to maintain optimal functional status. About in 60% of children, the seizure was controlled by using an appropriate primary drug and the results are satisfactory. We know that while 80% of people with epilepsy live in low- and middle-income countries, most of them do not have access to treatment [2]. Seizure is one of the most common diseases in children age group which was controlled by the availability of anticonvulsants, and due to the impact of anticonvulsants which act through the action on the membrane potential, it seems that these medications can affect the NCV [3-6]. Of course, in the poisoning with some medications such as phenytoin, the NCV has decreased. On the other one, one of the effective factors on the NCV was ambient temperature while some anticonvulsants can increase fever in body [7-10]. Also, consumers of anticonvulsants in neurological examinations show declining deep reflexes [11].

Anticonvulsants such as phenytoin, phenobarbital, topiramate, carbamazepine and valproate due to their beneficial effects and economic benefits in compare to new drugs are used more but these drugs are not harmless and sometimes had dangerous, safe and reversible side effects. Reduction of the nervous conduction velocity (NCV) is the common side effect of these drugs and it is of clinically importance if it is severe especially in children and need for more attention of physician in clinically using of these drugs. The aim of this study was to investigate the effects of antiepileptic drugs on NCV.

Materials and Methods

This was a quasi-experimental study. In this study, children aged 2-15 years with one of generalized or partial seizures requiring anticonvulsant drugs (Phenytoin, phenobarbital, Topiramate, carbamazepine, sodium valproate) selected and randomly divided into 5 groups each with 25 patients and each group received a drug. We also selected a control group without any drug use. Children were excluded from the study if they had any disruptive factors which affect NCV. At base line an NCV was performed for all groups. In this study the NCV were measured in the upper limbs in the median and ulna nerves and in the lower limbs in Peroneal and sural nerves by the EMG-NCV, Micromed device (made in Italy) and 6 months later these measurements was performed again and the necessary data were collected. After collecting NCV information along with age, sex and type of drug, data were analyzed by statistical methods in SPSS version 19.

Ethical approve

This study ethical approves by ethical committee of Ardabil University of Medical Sciences and registered by code REC.ARUMS.1397.675. In this study parents of children were informed and the consent form was completed for them.

Results

The average age of children was 5.5 ± 2.9 years in range of 2 to 11. Of all children, 68 (45.4%) were boy and 82 (55.6%) were girls. All of used drugs compared to the control group, significantly reduced sensory and motor NCV of upper and lower limbs nerves.

The phenytoin as an anti-seizure drug compared to the control group significantly reduced the motor and sensory NCV in the upper and lower limbs for nerves Median, Sural and Peroneal but the difference between phenytoin at baseline and control in Ulnar nerve wasn't significant (Table 1).

Table 1: Compare the mean of NCV in treated patients with phenytoin by type of nerve. View Table 1

The phenobarbital as an anti-seizure drug compared to the control group significantly reduced the motor and sensory NCV in the upper and lower limbs for nerves Median, Sural and Peroneal but the difference between phenobarbital at baseline and control in Ulnar nerve wasn't significant (Table 2).

Table 2: Compare the mean of NCV in treated patients with phenobarbital by type of nerves. View Table 2

The topiramate as an anti-seizure drug compared to the control group significantly reduced the motor and sensory NCV in the upper and lower limbs for nerves Median, Sural, Ulnar and Peroneal (Table 3).

Table 3: Compare the mean of NCV in treated patients with topiramate by type of nerves. View Table 3

The sodium-valproate as an anti-seizure drug compared to the control group significantly reduced the motor and sensory NCV in the upper and lower limbs for nerves Median, Sural, Ulnar and Peroneal (Table 4).

Table 4: Compare the mean of NCV in treated patients with sodium valproate by type of nerves. View Table 4

The carbamazepine as an anti-seizure drug compared to the control group significantly reduced the motor and sensory NCV in the upper and lower limbs for nerves Median, Sural, Ulnar and Peroneal (Table 5).

Table 5: Compare the mean of NCV in treated patients with Carbamazepine by type of nerves. View Table 5

The effect of anticonvulsants on the motor and sensory NCV of the upper and lower limbs was not related to the gender and age of children.

By comparing the effect of phenytoin and phenobarbital on NCV, we seen that in the median nerve phenytoin significantly reduced the NCV more than phenobarbital. Comparing the effect of phenobarbital and topiramate on NCV, we see that topiramate significantly reduced the NCV in the median nerve more than phenobarbital. Comparing the effect of phenobarbital and valproate on NCV, we see that valproate sodium significantly reduced the NCV in median nerve more than phenobarbital. Comparing the effect of phenobarbital and carbamazepine on NCV we see that carbamazepine significantly reduced the NCV in the median nerve more than phenobarbital.

Discussion

In a similar study in 1990, Krause, et al. suggested that anticonvulsants reduced the NCV in the median and peroneal nerves [3]. A study by Danner, et al. found that carbamazepine as an anti-seizure drug more than phenytoin reduced the NCV which was similar to our study results [12]. According to the results of Freeman, et al. research on the subject of polyneuropathy treatment, the mean of decrease in NCV for placebo was higher than that of topiramate. Secondary measurements showed that the NCV was not reduced for treated patients with topiramate [13]. Swift, et al. showed that there was no relationship between phenobarbital or phenytoin levels in blood and the duration of their use and abnormality of electrical findings as well as environmental neuropathy [14]. According to research by Chokroverty, et al. the NCV in the posterior tibial nerve was significantly reduced in patients who had been treated with phenytoin for more than 10 years or those who had a drug level of more than 20 mug/ml in their blood [15]. In a study by Danner, et al. the results show that carbamazepine reduce the NCV after 4 weeks treatment [16]. The result of Danner, et al. study showed a significant decrease in NCV in seizure patients who receiving anticonvulsants compared to the control group which was similar to our study results [17]. In research by Castro, et al. the NCV in patients receiving anticonvulsants is significantly reduced compared to the control group (healthy people) [18]. According to research by Ramirez, et al. long term use of phenytoin causes the destruction of nerve cells and their demyelination and reduces NCV and 16 months after the drug cut, the nerve cells are restored [19]. Studies by Traccis, et al. showed that long term treatment with carbamazepine reduced the sensory and motor NCV of the environmental nerves [20]. Zebrowska, et al. concluded in their research that by using 300-400 mg of phenytoin every day, the NCV in the environmental nerves will not decrease [21]. The present study showed that all of the anticonvulsants used in this study reduced the motor and sensory NCV of the upper and lower limbs. This difference was statistically significant for each drug compared to the control group. About Phenytoin and carbamazepine results showed that the difference in NCV in baseline and six months late was significant.

Geraldini and Taylor in their study showed that gender was not related to the effect of anticonvulsant drugs on NCV in patients [5,22]. Krause, et al. in their study stated that the gender of patients was ineffective in the motor and sensory NCV of median and perineal nerves but the NCV in the median nerve in men was lower than women [3]. Boylu and Shorvon and Encinoza similar to our study, in their research stated that the gender of the patients did not affect the NCV [4,6,23].

The findings of this study were in line with other studies which showed that the gender of patients did not affect the motor and sensory NCV in patients treated with anticonvulsants. Boylu and Shorvon and Encinoza in their research showed that age of the patients did not affect the NCV [4,6,23]. The results of this study similar to other studies, showed that there was no relation between the age of patients and their sensory and motor NCV reduces when taking anticonvulsants.

Danner, et al. found that anticonvulsants reduce NCV but of them carbamazepine reduces NCV more than phenytoin [12]. Swift, et al. in their studies showed that there is no relation between the level of phenobarbital or phenytoin in blood and the duration of their use and the abnormality of electrical findings as well as environmental neuropathy [14]. The results of Mervaala, et al. showed that the effects of phenytoin and carbamazepine on the NCV were similar to others. The effect of sodium valproate on reducing NCV is less than the other two drugs [24]. Zafeiridou, et al. in their study showed that phenytoin even at below concentrations has neurological complications [25]. Hamed, et al. showed that among the anti-seizure drugs, phenytoin had the most complications of neuropathy. environmental neuropathy is almost reported in carbamazepine treatment and environmental neuropathy also common in the administration of other anticonvulsants such as sodium valproate and topiramate [26]. Uemura, et al. Stated that the rate of decreased NCV is higher in phenytoin than carbamazepine [27]. According to Ay, et al. study, both carbamazepine and valproate sodium cause environmental neuropathy and there was no significant difference in the side effects of neuropathy between two drugs [28]. In this study similar to previous studies, phenobarbital decreases the rate of NCV less than other drugs and phenytoin more than other drugs reduced the NCV. But differences in the results of the effects of carbamazepine can be due to the variability of its blood level and previous studies have been carried out to evaluate the blood levels of drugs and starting an anticonvulsant medication as a first line of treatment may also be involved. Also the racial and age differences in response to drugs should not be over looked and this topic due to neurological complications especially in children is very important.

Conclusions

All of the anticonvulsants used in the study, reduced the motor and sensory NCV of the upper and lower extremities of the nerves. The gender of patients did not affect the sensory and motor NCV of the seizure patients treated with anticonvulsants. There was no significant correlation between the age of patients and their sensory NCV when taking anticonvulsant drugs. Anticonvulsant medications were similar in the reduction of NCV but among them phenobarbital was less effective than other drugs and phenytoin reduced NCV more than others. It is suggested that studies be conducted on the basis of the blood levels of drugs in the future.

Conflict of interest

None-declared.

Financially support

This study results of a Medical Doctoral thesis which approved by Ardabil University of Medical Science and author would like to thanks all patients participated in the study.

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Citation

Ahmadabadif F, Fattahzadeh G, Atalu A, Badihi P (2019) Investigating the Effects of Phenytoin, Phenobarbital, Topiramate, Carbamazepine and Sodium Valproate on the Neurotransmitter Speed in Treated Seizure Children. Int J Neurol Neurother 6:093. doi.org/10.23937/2378-3001/1410093