Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.     

Lamotrigine in the treatment of epilepsy in people with intellectual disability

Information about the mechanism of action and pharmacology of lamotrigine is summarized. A brief review of the literature on the use of this drug in people with intellectual disability is followed by a suggested framework for evaluating antiepileptic drugs in this population. The role of lamotrigine is systematically examined against the suggested framework. This leads to the conclusion that lamotrigine is a very favourable drug for treating epilepsy in people with intellectual disability because it has a broad spectrum of action, is effective in treating subtle seizures, shows no loss of effect with time, is not usually sedative, does not produce difficult-to-manage adverse effects, appears to have no direct adverse behavioural effects and is available in a range of 'patient friendly' preparations. However, it is important to use the drug wisely. This implies starting with low doses of lamotrigine and escalating the dose slowly to avoid adverse effects, especially rash, and being aware of drug interactions which could cause difficulty, including the prolongation of half-life with valproate, the pharmacodynamic interaction when it is added to carbamazepine and the pharmacokinetic interactions of lamotrigine with a number of antiepileptic drugs.     

Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy

PURPOSE: To determine whether levetiracetam (LEV) affects plasma concentrations of carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. METHODS: The potential for interaction of LEV with other antiepileptic drugs (AEDs) was assessed using plasma drug levels obtained in a randomized placebo-controlled phase III trial of adjunctive LEV in children receiving one or two concomitant AEDs. Multiple plasma AED levels at baseline and during adjunctive treatment with LEV or placebo were compared by repeated measures analysis of covariance and mean concentration ratios (treatment/baseline) were estimated with their 90% confidence intervals (CI). RESULTS: The study population included 187 children receiving any concomitant AED alone or in combination. The geometric mean concentrations at baseline and during LEV treatment were carbamazepine 8.4 microg/ml versus 8.1 microg/ml (coefficient of variation, CV = 30%; n = 35); valproic acid 83.8 versus 82.5 microg/ml (CV = 38%; n = 23); topiramate 7.3 versus 7.2 microg/ml (CV = 82%; n = 28); lamotrigine 8.2 versus 7.7 microg/ml (CV = 62%; n = 22). For each AED, the mean concentration ratios (LEV/baseline) and their 90% CIs showed that AED concentrations were unaffected by concomitant LEV administration. No differences were observed between LEV and placebo. CONCLUSIONS: LEV does not affect plasma concentrations of carbamazepine, valproic acid, topiramate, or lamotrigine in children with epilepsy.     

A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy

Antiepileptic drugs (AEDs) can affect bone metabolism, but the exact mechanisms or differences in individual drugs are still unknown. The purpose of this study was to prospectively investigate the alterations in bone mineral density (BMD) and markers of bone metabolism induced by different AEDs in Koreans with epilepsy. Subjects included 33 drug-naïve, newly diagnosed patients with epilepsy aged between 18 and 50. BMD at right calcaneus and various markers for bone metabolism were measured before and after 6 months of AED monotherapy including carbamazepine, valproic acid, and lamotrigine. Carbamazepine caused a significant decrease in BMD, which was accompanied by a decrease in the level of vitamin D (25-OHD₃). BMD and vitamin D were not affected by 6 months of valproic acid or lamotrigine therapy. Interestingly, valproic acid and lamotrigine, but not carbamazepine, significantly increased osteocalcin, a marker of bone formation. All AEDs almost doubled the parathyroid hormone level, whereas urinary Pyrilinks, a marker of bone resorption, was not affected by those AEDs. These findings suggest that carbamazepine, a hepatic enzyme-inducing drug, decreases BMD.     

Oxcarbazepine in the treatment of epilepsy in children and adolescents with intellectual disability

Oxcarbazepine is similar to carbamazepine in its mechanisms of action and antiepileptic efficacy, but has better tolerability and fewer interactions with other drugs. Very few data are available on the usefulness of oxcarbazepine in patients with intellectual disability and epilepsy. From January 1991 until October 1994, the present authors treated 40 patients with intellectual disability and epilepsy under the age of 18 years with oxcarbazepine. The mean age at onset of epilepsy was 12 months (range = 0-132 months). All patients had previously been intractable to antiepileptic drugs (including carbamazepine in 29 patients). The age at onset of oxcarbazepine therapy ranged from 0.8 to 17.1 years (mean = 6.2 years). Thirty-one patients (78%) received other antiepileptic drugs simultaneously with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 18.8 months. The mean maximum oxcarbazepine dose was 49 mg kg(-1) day(-1) (range = 21-86 mg kg(-1) day(-1). A reduction in seizures of at least 50% during oxcarbazepine treatment was observed in 14 out of 28 (50%) patients with localization-related epilepsy and in 5 out of 12 (42%) patients with generalized epilepsy. Efficacy was transient in three patients. An increase of atypical absences was observed in one child and an emergence of drop attacks in another. Side-effects were observed in 16 (40%) patients; in eight (20%), these lead to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for children and adolescents with intellectual disability and epilepsy.     

Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients

Multiple factors-including the efficacy of the antiepileptic drug for the particular seizure type, availability of pediatrics-friendly formulations, the ease of dosing and titration, and tolerability issues, such as possible drug interactions and adverse events-affect the selection of the best antiepileptic drug for a child with epilepsy. Behavioral problems are common in children with epilepsy and can be aggravated or initiated by antiepileptic drug therapy. The types and frequencies of antiepileptic drug-associated behavioral events can influence a clinician's drug selection, drug management, and counseling of parents. Unfortunately, appreciating differences among antiepileptic drugs in behavioral adverse event profiles is problematic because, among other reasons, methodologies for reporting, collecting, and analyzing adverse events are not uniform across trials, and there is marked heterogeneity in study design among trials. This review summarizes incidence rates for behavioral and psychiatric adverse events taken from studies of children with epilepsy. These rates are reported for the 10 most commonly prescribed antiepileptic drugs (valproic acid, carbamazepine, phenobarbital, lamotrigine, phenytoin, levetiracetam, oxcarbazepine, topiramate, zonisamide, and gabapentin), grouped according to their predominant mechanism of action. Despite the numerous methodologic inconsistencies, some similarities in adverse event profiles among antiepileptic drugs that share mechanisms of action are apparent. Moreover, the overwhelming body of data on the behavioral effects of phenobarbital should convince clinicians that, whenever possible, it should not be used as the initial-or even the second-monotherapy in children with epilepsy.     

Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet

This study was performed to evaluate carnitine deficiency in a large series of epilepsy children and adolescents treated with old and new antiepileptic drugs with or without ketogenic diet. Plasma free carnitine was determined in 164 epilepsy patients aged between 7 months and 30 years (mean 10.8 years) treated for a mean period of 7.5 years (range 1 month-26 years) with old and new antiepileptic drugs as mono or add-on therapy. In 16 patients on topiramate or lamotrigine and in 11 on ketogenic diet, plasma free carnitine was prospectively evaluated before starting treatment and after 3 and 12 months, respectively. Overall, low plasma levels of free carnitine were found in 41 patients (25%); by single subgroups, 32 out of 84 patients (38%) taking valproic acid and 13 of 54 (24%) on carbamazepine, both as monotherapy or in combination, showed low free carnitine levels. A higher though not statistically significant risk of hypocarnitinemia resulted to be linked to polytherapy (31.5%) versus monotherapy (17.3%) (P=.0573). Female sex, psychomotor or mental retardation and abnormal neurological examination appeared to be significantly related with hypocarnitinemia, as well. As to monotherapy, valproic acid was associated with a higher risk of hypocarnitinemia (27.3%) compared with carbamazepine group (14.3%). Neither one of the patients on topiramate (10), lamotrigine (5) or ketogenic diet (11) developed hypocarnitinemia during the first 12 months of treatment. Carnitine deficiency is not uncommon among epilepsy children and adolescents and is mainly linked to valproate therapy; further studies are needed to better understand the clinical significance of serum carnitine decline.     

Juvenile absence epilepsy exacerbated by valproic acid

Valproic acid is commonly and effectively used in the treatment of idiopathic generalized epilepsies, including juvenile absence epilepsy. Although several adverse effects are associated with this drug, it has only rarely been known to exacerbate seizures. Similar to antiarrhythmic drugs aggravating particular arrhythmias, antiepileptic drugs can paradoxically induce new seizure types or exacerbate existing ones. This reaction is better known with carbamazepine and phenytoin, but is less common with broad-spectrum antiepileptic drugs such as valproic acid. This report describes a case of paradoxical, intravenous valproic acid-induced seizure exacerbation in a child with juvenile absence epilepsy, documented by video-electroencephalography.     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

Two antiepileptic drugs for intractable epilepsy with complex-partial seizures

The value of adding a second antiepileptic drug in intractable epilepsy with complex-partial seizures was studied in a long-term prospective trial in 30 adult patients who failed to respond to the maximum use of carbamazepine, phenytoin, phenobarbital or primidone as the first drug. Based on the individual previous history of one-drug treatment, the most promising antiepileptic drug (carbamazepine, clobazam, clonazepam, phenobarbital, phenytoin, primidone, valproic acid) was added, if necessary until clinical toxicity occurred. A reduction of the seizure frequency by more than 75% was seen in only four patients (13%) exposed to a second drug in the event of failure of optimum one-drug treatment. The remaining majority of patients (87%) did not benefit from the second drug; in three patients the seizure frequency increased by more than 100%. The common practice of adding another drug in difficult-to-treat cases may need to be reconsidered until further evidence is presented that two drugs are more beneficial than one drug in the treatment of intractable epilepsy.     

Thyroid hormones in epileptic children receiving carbamazepine and valproic acid

Carbamazepine and valproic acid are effective antiepileptic drugs for treating many types of epilepsy. Although they are well tolerated, many effects on endocrine function have been reported. Changes in serum thyroid hormones levels in 37 children with epilepsy during carbamazepine and valproic acid therapy were analyzed, and the thyroid hormone concentration after thyrotropin-releasing hormone test was evaluated. Serum thyroxine and free thyroxine levels were significantly lower in patients treated with carbamazepine and carbamazepine plus valproic acid than in the control subjects; serum thyroxine and free thyroxine concentrations were unaffected by valproic acid monotherapy. Serum triiodothyronine and free triiodothyronine concentrations were similar in the three groups of patients studied. Thyroid-stimulating hormone serum levels were normal in all patients, and the thyrotropin responses to the thyrotropin-releasing hormone were similar to control group. Our data suggest that children treated with carbamazepine may have subclinical signs of hypothyroidism, and these changes are more evident if carbamazepine is given in association with valproic acid, while no alteration in thyroid hormones can be found with valproic acid monotherapy. Thyroid-stimulating hormone and thyrotropin-releasing hormone levels do not seem to be affected by these drugs, suggesting that hypothalamic function is not affected in these children.     

Effect of antiepileptic drugs on bone density in ambulatory patients

BACKGROUND: Long-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density. METHODS: A cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy-vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients. RESULTS: Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide. CONCLUSION: Epilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.     

Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy

BACKGROUND: In the face of availability of newer antiepileptic drugs (AEDs) such as lamotrigine and topiramate, there is need to reassess the role of older AEDs in the treatment of juvenile myoclonic epilepsy (JME). OBJECTIVES: To explore whether lamotrigine and topiramate monotherapy or polytherapy can be effective options in the treatment of JME, and to determine whether older AEDs, such as phenytoin and carbamazepine, have a role in the treatment of JME. DESIGN: A retrospective cohort study. SETTING: A large academic teaching hospital. PATIENTS: Seventy-two consecutive JME patients treated with valproic acid, lamotrigine, topiramate, phenytoin, or carbamazepine between April 1, 1991, and March 31, 2001. METHODS: We compared the efficacy of valproic acid, lamotrigine, and topiramate monotherapy or polytherapy in the control of different seizure types of JME, and compared their efficacy and tolerability with the efficacy and tolerability of phenytoin and carbamazepine. RESULTS: Seizure outcome did not differ when patients receiving valproic acid monotherapy (n = 36) were compared with those receiving lamotrigine monotherapy (n = 14), and when patients receiving valproic acid polytherapy (n = 22) were compared with those receiving lamotrigine polytherapy (n = 21) or topiramate polytherapy (n = 15) (P>.05 for all). The combined data of myoclonic seizure control by all 3 AEDs were poorer when compared with the combined data of generalized tonic-clonic seizure control by all 3 AEDs (P =.03), but not when compared with the combined data of absence seizure control by all 3 AEDs (P =.43). Valproic acid, lamotrigine, and topiramate, when compared with phenytoin or carbamazepine, demonstrated significantly better control of myoclonic seizures (P<.01 for all), but not of generalized tonic-clonic seizures (P>.11 for all). CONCLUSIONS: Lamotrigine and topiramate are effective alternative options to valproic acid in the treatment of JME. Lamotrigine is an effective option as monotherapy and polytherapy. Topiramate is an effective option as polytherapy, but more data are needed to determine if it is an effective option as monotherapy. More effective therapy is needed to improve myoclonic seizure control. Older AEDs, such as phenytoin and carbamazepine, may not be indicated in JME patients.     

Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines

BACKGROUND: Until the early 1990s six major compounds (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid) were available for the treatment of epilepsy. However, these drugs have pharmacokinetic limitations, teratogenic potential, and a negative effect on cognitive functions that impairs the quality of patients' lives and limits the use of these drugs in some patients. In addition, 20-30% of patients are refractory to these drugs. RECENT DEVELOPMENTS: The development of ten new antiepileptic drugs (vigabatrin, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin) has expanded treatment options. The newer drugs may be better tolerated, have fewer drug interactions, and seem to affect cognitive functions to a lesser extent than old drugs. Guidelines on the use of new antiepileptic drugs have been developed in the USA and in the UK. Both guidelines offer a clear picture of the efficacy, safety, and tolerability of the new antiepileptic drugs and agree on their use as add-on treatment in patients who do not respond to conventional drugs. The guidelines differ in the type and strength of recommendations. Whereas the US guidelines recommend treatment in newly diagnosed epilepsy with a standard drug or a new drug depending on the individual patient's characteristics, the UK guidelines recommend that a new antiepileptic drug should be considered only if there is no benefit from an old antiepileptic drug, an old drug is contraindicated, there is a previous negative experience with the same drug, or the patient is a woman of childbearing potential. WHERE NEXT: The limited amount of information on the new antiepileptic drugs may explain the discrepancies among the two guidelines and between these and other recommendations. Comparative, pragmatic, long-term and open trials should be done to show long-term efficacy and comparative features of the new antiepileptic drugs, and to better assess the effect on quality-of-life, cost-effectiveness, tolerability, and teratogenic potential. In addition, the conflicts should be resolved between the needs of the regulatory bodies and those of the treating physicians. Finally, there is a need for trial designs to be standardised.     

Extended-release formulations in epilepsy

In the past years, the extended-release antiepileptic drug formulations have been developed and then approved for the treatment of many types of epilepsy. Among these extended-release formulations of antiepileptic drugs, the main drugs are valproic acid, carbamazepine, and phenytoin. This review analyzes the chemical and structural characteristics of the extended-release formulations of these 3 antiepileptic drugs, analyzing their bioequivalence and the studies about their clinical use. The results of these studies are encouraging and suggest a good tolerability and efficacy of these extended-release formulations, although larger studies are needed.     

Premenstrual dysphoric disorder in women with epilepsy: relationships to potential epileptic, antiepileptic drug, and reproductive endocrine factors

The purpose of this prospective observational investigation was to determine whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity of PMDD symptoms differ between women with epilepsy and controls without epilepsy and whether there exists a relationship between the severity of PMDD symptoms and some epileptic, antiepileptic drug, and reproductive endocrine features. The results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD severity scores may be greater in people with right-sided than in those with left-sided epilepsy, and in people with temporal than in those with nontemporal epileptic foci. PMDD severity scores may be greater with anovulatory cycles, and scores may correlate negatively with midluteal serum progesterone levels and positively with midluteal estradiol/progesterone ratios. Mood score may vary with particular antiepileptic drugs, favoring carbamazepine and lamotrigine over levetiracetam. PMDD severity scores may correlate directly with carbamazepine levels, whereas they correlate inversely with lamotrigine levels.     

Interactions between antiepileptic drugs,and between antiepileptic drugs and other drugs

Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P‐glycoprotein) and can reduce the efficacy of co‐administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥200 mg/day) and perampanel (at doses ≥8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen‐containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of sodium channel blocking antiepileptic drugs.     

Drug selection for the newly diagnosed patient: When is a new generation antiepileptic drug indicated?

Abstract. Treatment options in epilepsy have increased dramatically since the early 1990s with the introduction of nine new generation antiepileptic drugs (AEDs) (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide). This makes drug selection much more complicated and challenging. This review discusses drug selection in patients with newly diagnosed epilepsy and in particular the role of new AEDs in this population. The choice of treatment should always be based on a careful comparison of the risk-benefit ratio for the different treatment options and the outcome of such evaluation may be different in patients with new onset compared with chronic epilepsy. Efficacy, tolerability and safety are the main criteria for selection of AEDs and any first line drug for patients with newly diagnosed epilepsy must have demonstrated satisfactory efficacy as monotherapy in that patient population. So far, of the new AEDs only lamotrigine, oxcarbazepine and topiramate have documentation sufficient to be granted licence for use as monotherapy in most European countries. Because the new generation AEDs have failed to demonstrate improved effectiveness as monotherapy, old generation AEDs such as carbamazepine and valproate remain drugs of first choice for partial and generalised seizures, respectively. However, there are special situations and populations where a new AED may be a reasonable first line drug. These include vigabatrin in West syndrome associated with tuberous sclerosis, lamotrigine as alternative to valproate in idiopathic generalised seizures in women of childbearing potential and lamotrigine for the treatment of epilepsy in the elderly population. The role of the new generation AEDs is likely to become more prominent as more experience is gained.     

Adjunctive lamotrigine for refractory epilepsy in adolescents with mental retardation

Epilepsy is a major comorbid condition in adolescents with mental retardation and is often characterized by multiple seizure types that are refractory to treatment. This study (n = 22) describes a subanalysis of data from a larger multicenter study of adjunctive lamotrigine therapy in patients with mental retardation and refractory epilepsy and focuses on the outcome measures of seizure reduction, safety and tolerability, and impact on behaviors in adolescents with mental retardation and refractory epilepsy. The study kept baseline antiepileptic drugs constant and titrated lamotrigine over 8 weeks to the target dose, followed by an 8-week maintenance phase and then a 12-week optimization phase during which all antiepileptic drugs and lamotrigine could be altered as clinically indicated. Sixty percent of subjects had a 50% decrease in seizures by the end of the maintenance phase and a mean 39% reduction in seizure frequency by the end of the maintenance phase (25% by end of study) compared with baseline. Global improvements were observed in most patients, with statistically significant improvements in the Aberrant Behavior Checklist and the Habilitative Improvement Scale, which is predictive of less need for supportive care in activities of daily living and thus enhanced potential for greater independence. Lamotrigine-associated improvements in behavior can be attributed to improved control of seizures, a reduction in concomitant antiepileptic drugs, and/or direct mood-stabilizing and behavior-enhancing properties independent of the antiseizure effects of the drug. The results of this study suggest that lamotrigine is an important treatment option in adolescents with mental retardation and comorbid epilepsy.     

Carbamazepine in the treatment of epilepsy in people with intellectual disability

Carbamazepine is a major antiepileptic drug which is primarily used to treat epileptic patients suffering from partial seizures with or without secondary generalization, but which also has applications in those suffering from primary generalized tonic-clonic seizures. Besides its antiepileptic effect, carbamazepine is also indicated in the treatment of trigeminal and occipital neuralgia, and in manic depressive disorders. Because of its minimal unwanted effects on cognition and behaviour, carbamazepine is an excellent drug for the treatment of people with intellectual disability and epilepsy. Carbamazepine is still one of the most commonly prescribed medications in the treatment of epileptic disorders.