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PubMed2002

Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain.

Nitric oxide synthase inhibitors have been regarded as potentially beneficial for psychiatric disorders such as depression and schizophrenia, though little is known about how nitric oxide synthases are affected by psychotropic drugs in the brain. Using reverse transcription-polymerase chain reaction analysis, we investigated the effects of short- and long-term oral treatments with several psychotropics on type II nitric oxide synthase gene expression in the rat brain. With maprotiline and fluvoxamine, enzyme mRNA levels were higher after a 28 day treatment than after 1 and 4 day treatments. Zonisamide, carbamazepine and diazepam also increased mRNA, though differences in levels between 1, 4 and 28 day treatments were not significant. These results suggest that psychotropics modulate the gene expression of type-II nitric oxide synthase in the brain.

Animals↗
PubMed2001

Refractory grand mal seizures with onset during infancy including severe myoclonic epilepsy in infancy.

In 1978, Dravet proposed a clinical entity called severe myoclonic epilepsy in infancy (SMEI). In the same year, a patient group, which was later called high voltage slow wave-grand mal syndrome (HVSW-GM), is reported in Japan. Both syndromes are very similar, except for seizure manifestation: generalized tonic-clonic convulsions (GTC) with myoclonic and other polymorphic seizures in SMEI vs. GTC only in HVSW-GM. To study the pathophysiology of these refractory epilepsies, the author formulated new clinical diagnostic criteria common to both syndromes as follows: GTC with onset before the age of 1 year as the principal seizure type; an epilepsy entity unclassifiable either as partial or generalized by all the clinical data including EEG findings; mental and motor dysfunction absent prior to seizure onset but appearing later; absence of epileptiform activities on EEG in the initial stage; stubborn refractoriness to conventional antiepileptic medication. Twenty-two patients meeting all of five clinical criteria above mentioned were recruited in the study. Detailed analysis of clinico-electrical features and long-term follow-up of these patients led the author to the conclusion that GTC in combination with seizures of other types will contribute to an unfavorable pathophysiological or prognostic conditions, and, especially when GTC exists in combination with myoclonic seizures, the severity of epilepsy will increase. The author claimed that the three clinical entities, SMEI, HVSW-GM, and their variant form, share certain characteristics in common and may constitute a unique epilepsy syndrome for which a new name of infantile refractory grand mal syndrome (IRGMS) was offered. This is a more basic concept with broader spectrum than SMEI, encompassing not only SMEI but also related borderlands like HVSW-GM. More recently, the author observed that early zonisamide medication within 1 year after seizure onset may improve seizure prognosis in IRGMS, by preventing the development of myoclonic seizures.

Anticonvulsants↗
PubMed2006

Post-anoxic myoclonus: a case presentation and review of management in the rehabilitation setting.

Post-anoxic myoclonus is a rare movement disorder manifested by diffuse action-triggered jerking movements that may result in significant disability. The incidence of this disorder is not clearly established, but over 122 cases have so far been reported in the literature. The pathogenesis is not entirely known, although it has been hypothesized that particular susceptibility of the Purkinje cells of cerebellum to anoxic injury may play a key role. A case is presented of an independently living 60-year-old woman admitted to the rehabilitation unit with diffuse myoclonus after sustaining a cardio-pulmonary arrest. She presented with severe jerking movements in all extremities with startle to noise and exacerbations upon attempting any purposeful actions. The patient's myoclonus was controlled by a variety of anti-epileptic medications. The patient initially responded to a combination of divalproex sodium and zonisamide, but relapsed in several weeks, requiring addition of levetriacetam and clonazepam. At a 1-year follow-up she demonstrated a significant improvement in ambulation and self-care activities. This case illustrates that, although patients with post-anoxic myoclonus cannot be fully cured, their quality of life can be significantly improved by rehabilitation interventions.

Anticonvulsants↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed1996

The effects of antiepileptic drugs on cognition in normal volunteers.

The effects of antiepileptic drugs on cognitive function in 48 healthy volunteers were assessed using event-related potentials (ERP) and the Attention Index included in the Wechsler Memory Scale, revised edition (WMS-R). The study was conducted over 1 week, using a double-blind design. Four drugs, carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and zonisamide (ZNS) were tested. Using an auditory oddball task, ERP measurements were made under two conditions with different tone intensities: Condition 1 used 70 db SPL; and Condition 2 used 30 db SPL. Results showed that CBZ prolonged target N1 and P3 latencies in Condition 1, and reduced frequent N1 amplitude in Condition 2, which suggests that CBZ may cause a change in sensory memory and prolong stimulus evaluation time. It is suggested that under a low stimulus intensity level, the sensory function itself was affected. Phenytoin was found to prolong target N1 latency in Condition 2, which also indicates a change in the sensory memory function. However, VPA did not significantly affect ERP components, except for the shortened frequent N1 latency, which could not be explained due to the limited information. It was found that ZNS augmented P3 amplitude in Condition 2, and reduced scores on the Attention Index. It is suggested that the augmentation of P3 amplitude was caused by the reduction of processing negativity as a result of the detrimental effect of ZNS on subjects' attention. However, the apparent difference between the ERP and behavioral indices suggests that caution should be exercised in assessing the results obtained only from ERP measurements.

Adult↗
PubMedDate not supplied

Electrochemistry of anticonvulsants: electron transfer as a possible mode of action.

Reduction potentials were determined for various anticonvulsants, including progabide, SL 75.102, CGS 9896, pyridazines, zonisamide, 1,2,3-triazoles, and copper complexes. The values generally were in the range of about -0.1 to -0.6 V for the protonated drugs and the metal complexes. Reduction potentials provide information on the feasibility of electron transfer (ET) in vivo. If the value is relatively positive (greater than about -0.6 V), the agent can act catalytically as an electron acceptor from an appropriate cellular donor. A concomitant favorable influence on abnormal neuronal processes associated with epilepsy could occur. We describe ET as a possible mode of action of anticonvulsants as well as some antiepileptic agents with no electrochemical data based on this hypothetical ET approach.

Anticonvulsants↗
PubMed1994

Antiepileptic drugs in development: prospects for the near future.

Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. Although these drugs all have some CNS side effects, especially when administered in combination with other AEDs, they also all have low toxicity profiles. The availability of AEDs with different mechanisms of action may facilitate rational polytherapy. FBM is not teratogenic in animals. Half-life of FBM in humans is 11-28 h. Daily FBM dosages are 15-45 mg/kg in children and 2,400-4,800 mg in adults. Side effects include insomnia and anorexia, with weight loss. FBM increases phenytoin (PHT) and valproate (VPA) concentrations, and FBM concentration may be affected by other drugs. It is available in the United States for treatment of Lennox-Gastaut syndrome and partial seizures in adults. GBP is very water soluble. Half-life of GBP in humans is 5-7 h and daily dosages range from 900 to 2,400 mg in adults. Few side effects have been observed. GBP is not metabolized by the liver and has no drug interactions. It is available in the United Kingdom and the United States. LTG has no teratogenicity in animal models. Half-life of LTG in humans depends on co-medication: with enzyme inducers it is 15-24 h, and with VPA it is approximately 60 h. LTG dosages are 100-600 mg/day in adults. LTG is available in Europe. OCBZ is rapidly metabolized to 10,11-dihydro-10-hydroxy-carbazepine (MHD), the active compound. Animal studies have shown similar efficacy but superior toxicity to carbamazepine (CBZ) in animal models. For MHD, half-life ranges from 10 to 15 h in patients. OCBZ dosages range from 300 to 1,800 mg/day. VGB is a potent, irreversible inhibitor of GABA transaminase which elevates GABA levels in the CNS. Daily dosages of 2,000-4,000 mg of VGB are needed in adults. Although intramyelinic edema has developed in rats and dogs, it has not yet presented in other mammals or humans. ZNS is a sulfonamide effective in animal models of epilepsy. Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.

Acetates↗
PubMed1996

Clinical administration of new antiepileptic drugs: an overview of safety and efficacy.

Gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide are all administered as add-on therapy for treatment of patients with refractory epilepsy. To date, no comparative randomized trials have been performed that could potentially allow an evidence-based choice to be made between these antiepileptic drugs (AEDs). We report a series of meta-analyses of placebo-controlled, randomized add-on trials in patients with partial epilepsy. Results of these meta-analyses are compared, thus giving broad estimates of the comparative efficacy and tolerability of these AEDs. The efficacy outcome is the odds ratio for the number of patients with a > or = 50% reduction in seizure frequency. Reported side effects are also used as tolerability outcomes, and study withdrawal is used as a global outcome measure. Results are summarized as odds ratios with 95% confidence intervals (CIs). When each outcome is compared among drugs, the 95% CIs overlap. Therefore, no conclusive evidence of a difference in efficacy or tolerability between these AEDs was derived, even though the apparently most effective agent (topiramate) may be twice as effective as the apparently least effective agent (lamotrigine). Comparative randomized studies are needed to further evaluate these drugs.

Acetates↗
PubMed1997

The new antiepileptic drugs: a systematic review of their efficacy and tolerability.

PURPOSE: Gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS) are all in use as "add-on" treatment for patients with refractory epilepsy. There have been no comparative randomized controlled trials allowing an evidence-based choice between these drugs. We report a series of meta-analyses of randomized placebo-controlled add-on trials in which these drugs have been tested in patients with partial epilepsy. This work provides an estimate of each drug's efficacy and tolerability compared with placebo. These estimates are compared across drugs to give broad estimates of comparative efficacy and tolerability. METHODS: Trial reports were found by searching Medline, by searching through journals by hand, and by contacting the pharmaceutical industry. The outcomes chosen were the proportion of patients who (a) have a > or = 50% reduction in seizure frequency (50% responders); (b) withdrew from the study (any reason); or (c) reported the following side effects: ataxia, dizziness, fatigue, nausea, or somnolence. Overall odds ratio (OR) with 95% confidence intervals (CIs; 50% responders) or 99% CIs; side effects) were calculated. RESULTS: Twenty-nine trials were included, representing 4,091 randomized patients. The ORs for 50% response (95% CI) were GBP, 2.29 (1.53-3.43); LTG, 2.32 (1.47-3.68); TGB, 3.03 (2.01-4.58); TPM, 4.07 (2.87-5.78); VGB, 3.67 (2.44-5.51); and ZNS, 2.7 (1.36-4.47). ORs for discontinuation were GBP, 1.36 (0.75-2.49); LTG, 1.19 (0.79-1.79); TGB, 1.81 (1.21-2.70); TPM, 2.56 (1.64-4.00); VGB, 2.58 (126-5.27); and ZNS, 4.23 (1.71-10.49). CONCLUSIONS: We have clear evidence that each of these drugs is better than placebo at preventing seizures. When results are compared across drugs, the confidence intervals overlap, and we have no conclusive evidence of differences in efficacy or tolerability. Despite this, the agent that appears most effective may be twice as effective as the agent that appears least effective, and the agent that appears most likely to cause discontinuation may be 4 times more likely to do so than the treatment that appears least likely to do so. Comparative randomized studies are needed further to evaluate these drugs.

Acetates↗
PubMed1999

Comparative anticonvulsant and mechanistic profile of the established and newer antiepileptic drugs.

Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory-mediated neurotransmission, or reduction of excitatory-mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic-based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. For many of the newer AEDs, several molecular mechanisms of action have been identified. For example, felbamate (FBM), lamotrigine (LTG), zonisamide (ZNS), topiramate (TPM), oxcarbazepine (OCBZ), and possibly gabapentin (GBP) share a similar mechanism with that defined for phenytoin (PHT) and carbamazepine (CBZ), i.e., a voltage- and use-dependent block of voltage-sensitive sodium (Na+) channels. In addition to their effects on Na+ currents, TPM, ZNS, and FBM also appear to act as allosteric modulators of the GABA(A) receptor, whereas GBP appears to increase brain GABA levels. GBP, ZNS, FBM, LTG, and OCBZ attenuate voltage-sensitive calcium (Ca2+) channels, albeit through different mechanisms and with different classes of Ca2+ channels. FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA- and AMPA/kainate-mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.

Animals↗
PubMed1999

The clinical pharmacokinetics of the new antiepileptic drugs.

Because pharmacokinetics is a major determinant of the magnitude and duration of pharmacologic response, understanding the kinetic properties of the new antiepileptic drugs (AEDs) is essential for the correct use of these compounds in clinical practice. After oral administration, absorption is rapid and relatively efficient for the new AEDs, the most notable exception being gabapentin, whose bioavailability decreases with increasing dosage. None of the new AEDs is extensively bound to plasma proteins except for tiagabine, which is over 95% protein-bound. The route of elimination differs to an important extent from one compound to another, and elimination half-lives range from over 30 h for zonisamide to 5-7 h for gabapentin. For all drugs that are metabolized, half-life is shortened and clearance is increased when patients receive concomitant enzyme-inducing agents such as barbiturates, phenytoin, and carbamazepine. Lamotrigine metabolism is markedly inhibited by valproic acid, and felbamate may increase the serum levels of most other AEDs. Felbamate, topiramate, and oxcarbazepine may also reduce the efficacy of the contraceptive pill by stimulating its metabolism.

Acetates↗
PubMed2000

Developmental and therapeutic pharmacology of antiepileptic drugs.

We investigated the clinical effects and plasma levels of zonisamide (ZNS) in children with cryptogenic localization-related epilepsies. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long as compared with that of other common antiepileptic drugs. The peak-to-trough plasma level ratios during a day were as small as 1.28 +/- 0.15 in children taking a daily dose of 8 mg/kg of ZNS once a day as a single drug. The plasma level (microg/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels both increased with advancing age, but the peak-to-trough plasma level ratios were maintained almost uniformly throughout the pediatric age period. A wide range of the plasma levels was associated with complete freedom from seizures. The range of the plasma levels in patients who did not respond to ZNS was higher than that in the controlled group. However, the clinical effects of ZNS were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15-40 microg/ml. Any patient who receives polytherapy is at risk to develop 1 or more drug interactions. Concurrent administration of carbamazepine (CBZ) decreases plasma concentrations of ZNS. However, ZNS does not alter plasma concentrations of CBZ or its primary metabolite, carbamazepine-10,11-epoxide (CBZ-E). It is evident that the concurrent administration of lamotrigine (LTG) affects plasma concentrations of CBZ-E, while plasma CBZ levels remain unaltered. However, the effect of LTG on plasma concentrations of CBZ-E is small, and none of the study patients showed toxic plasma concentrations of CBZ-E or associated clinical toxicity. Drug-protein binding interactions are another source of side effects. A simultaneous administration of valproic acid increases the total plasma CBZ-E levels relative to the CBZ dose associated with the raised free fractions of CBZ and CBZ-E. The high free plasma concentrations of CBZ-E above 1.5 microg/ml may be responsible for the side effects.

Adolescent↗
PubMed2002

Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes.

In the present study, we investigated the effects of 14 endogenous steroids on the CYP3A4-mediated drug metabolism by human liver microsomes in vitro. Nevirapine (NVP) 2-, 12-hydroxylations, carbamazepine (CBZ) 10,11-epoxidation, triazolam (TZM) 1'-, 4-hydroxylations, erythromycin (EM) N-demethylation, and 2-sulphamoylacetylphenol (SMAP) formation from zonisamide (ZNS) were investigated. The activities of the NVP 2-, 12-hydroxylations, the CBZ 10,11-epoxidation, and the TZM 4-hydroxylation were activated by endogenous androgens, such as androstenedione (AND), testosterone, and dehydroepiandrosterone. However, these androgens inhibited EM N-demethylation, TZM 1'-hydroxylation, and SMAP formation. To understand the mechanisms of these effects of androgens on CYP3A4 activities, we performed a kinetic analysis of the metabolism of CBZ and ZNS in the presence or absence of AND using the modified two-site equation model. The addition of AND to the reaction mixture caused a drastic increase in the activity of CBZ 10,11-epoxidase, especially at a low substrate concentration, and resulted in a change in the kinetics from the sigmoid to Michaelis-Menten type. On the other hand, the metabolism of ZNS was strongly inhibited by AND, although no allosteric change was observed in this case. These data demonstrate that endogenous steroids, especially androgens, strongly affect CYP3A4-mediated drug metabolism in vitro. The postulated mechanisms of the interactions between AND and CBZ or ZNS are discussed.

Adult↗
PubMed2002

Protein-losing cytomegalovirus gastritis in a patient with Stevens-Johnson syndrome.

We present a case of protein-losing cytomegalovirus gastritis in a previously immunocompetent 14-year-old Japanese girl that occurred during treatment of drug (zonisamide)-induced Stevens-Johnson syndrome with hepatic failure. Her hepatic failure and symptoms of Stevens-Johnson syndrome were successfully treated with intravenous prednisolone and infusion of fresh-frozen plasma or albumin, as the occasion demanded. However, during the course of treatment, she complained of severe epigastralgia together with hypoproteinemia, and cytomegalovirus gastritis was found by endoscopic and histological examinations. The possible mechanism by which cytomegalovirus gastritis occurred in the present case and effective diagnostic procedures are discussed.

Adolescent↗
PubMed2006

Pharmacologic treatment of obesity.

Obesity is strongly associated with conditions such as hypertension, diabetes mellitus and osteoarthritis that have known adverse health outcomes. The rising prevalence of obesity threatens to overburden our health care system. As a result, the need for safe and effective treatment options is urgent. Unfortunately, pharmacologic treatment options have been disappointing either because of poor side effect profiles or limited long-term efficacy. Our goal is to review currently available pharmacologic treatments and the data supporting their use so that practicing physicians may better incorporate them into a comprehensive, long-term treatment strategy for their patients. We focus on orlistat and sibutramine as these are the two medicines approved by the FDA for long-term treatment of obesity. In addition, we review briefly agents approved for short-term use as well as agents such as zonisamide and topiramate which have shown some promise as weight loss agents in specific clinical circumstances. Finally, we highlight one medicine currently in phase III clinical trials, an endocannabinoid receptor antagonist. Given the overwhelming research focus on this disease, it is likely that the coming years will bring more treatment options, raising the chance that our patients will have meaningful and sustained weight loss.

Anti-Obesity Agents↗
PubMed2002

Using the new antiepilepsy drugs in children.

New epilepsy treatment options are becoming available to physicians and may help provide safe and effective seizure management in patients for whom traditional drug therapies have been unsuccessful. Presented here is a brief discussion on the screening models used to test drugs for efficacy against various seizure types and the mechanisms of action and pharmacology of antiepilepsy drugs. This is followed by a more detailed review of the clinical pharmacology of the latest three antiepilepsy drugs introduced to the United States: levetiracetam, oxcarbazepine, and zonisamide. All three appear to have advantages over some traditional antiepilepsy drugs and with more clinical experience may replace them in certain seizure types or epilepsy syndromes.

Anticonvulsants↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗