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PubMedDate not supplied

Felbamate, gabapentin and topiramate as adjuvant antiepileptic drugs in experimental models of epilepsy.

Newly diagnosed epileptic patients start their medication with monotherapy. Around 30% of epileptic patients require more than one antiepileptic drug. Results from experimental studies provide evidence that administration of two antiepileptic drugs may result in antagonistic, additive, or supra-additive (synergistic) anticonvulsant effects. If adverse effects of a synergistic combination also show supra-additive summation then the protective index may not change. In this context, drug combinations, possessing synergistic anticonvulsant effects and additive (or infra-additive) toxicity, are of clinical interest. Recent experimental data indicate that topiramate and gabapentin generally potentiate the protective activity of conventional antiepileptic drugs against maximal electroshock-induced convulsions in mice. The anticonvulsant action of carbamazepine, diphenylhydantoin, phenobarbital, and valproate was not modified in this test by felbamate at subprotective doses against threshold electroconvulsions. Interestingly, conventional antiepileptics (at subeffective doses) enhanced the protection offered by felbamate. It may indicate that beneficial effects of a drug combination may be observed at only some drug ratios.

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PubMedDate not supplied

[Gabapentin in children and adolescents with epilepsy].

OBJECTIVE: We analyze the studies published on gabapentin (GBP) in children and adolescents with epilepsy, both clinical studies, in which it is used to treat patients with partial seizures refractory to treatment with other drugs, and in other studies of its use as monotherapy. PATIENTS AND METHODS: We report the results of a multicentric observational study carried out in Spain using GBP as monotherapy for 52 adolescents with partial seizures with no previous treatment (32) or as a second alternative treatment (20). RESULTS: We showed evident clinical efficacy, with a reduction of >50% in the frequency of seizures in 79% of the cases and abolition of seizures in 60%, after six months of treatment with GBP. At the same time the drug is very well tolerated, with adverse effects in 7.7% of cases. The drug was only suspended on account of adverse effects in one patient (1.9%). Simultaneously all the basic items of the QOLIE 10 questionnaire were improved after six months of treatment. CONCLUSION: GBP is an effective drug which is well tolerated by children and adolescents with partial crises, when used in polytherapy or as monotherapy.

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PubMedDate not supplied

[Gabapentin in the treatment of epilepsy in the elderly].

INTRODUCTION: Epilepsy is the third most common neurological disease in the elderly. Diagnosis of epilepsy in this age is increasing because more people are reaching older age and physician awareness about this disorder is higher than in the past. Seizures are suspected in patients with episodic impairment of consciousness and neurological function, but in addition, seizures can be the cause of fluctuating cognitive derangement and nocturnal episodes of neurological dysfunction. DEVELOPMENT: The etiological spectrum of epilepsy in the elderly is different than in younger adults because of a higher prevalence of cerebrovascular disease and degenerative disorders of the central nervous system. The selection and dosage of antiepileptic drugs requires proper attention to special pharmacokinetic and pharmacodynamic situations that are common in older individuals. Changes that occur with advanced age are responsible of distinct pharmacokinetics, decreased tolerability to antiepileptic drugs, concomitant systemic diseases. In addition poor compliance and polypharmacy can complicate therapy. CONCLUSIONS: Gabapentin has favourable pharmacokinetic properties: lack of hepatic metabolism, no protein binding, and easy to calculate regimen for patients with renal failure. For these reasons is a good candidate drug for treatment of seizures in the elderly.

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PubMedDate not supplied

[Safety and tolerability of gabapentin].

OBJECTIVE: To review the information available regarding the safety and tolerability of gabapentin (GBP) in the treatment of epilepsy. PATIENTS AND METHODS: We reviewed the reports in the literature on the safety, adverse effects and tolerance of GBP as treatment, used as monotherapy or associated with other drugs, in epilepsies in patients of all age groups, including children, adults and the elderly. RESULTS: All published studies confirm that GBP is a well tolerated drug when used for monotherapy or associated with other antiepileptic drugs. The commonest adverse effects seen were somnolence, fainting, ataxia, nystagmus, tremor and headache. However, their incidence was low and intensity mild. There was no clear relationship between the dose given and appearance of side effects, except for fainting and somnolence. CONCLUSIONS: GBP is a drug which is free of unwanted side effects. Its safety and tolerability profile is excellent for treatment of simple and complex partial crises, with or without generalization in epileptic patients of all ages.

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PubMed2002

[Characteristics and indications of gabapentin].

Gabapentin is a drug that shares a similar structure to that of GABA, although its mechanism of action cannot be explained solely by a direct gaba mimetic effect. It is well absorbed when administered orally and displays linear kinetics up to doses of 1,800 mg/day. It is been found to be effective both in added therapy and in mono therapy, and is particularly useful in special populations like the elderly and children, as well as patients suffering from liver diseases. Its safety profile and the absence of interactions make it a suitable drug for the treatment of recently diagnosed epilepsies, both in mono therapy and in bi therapy.

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PubMed2002

Gabapentin and lamotrigine in Indian patients of partial epilepsy refractory to carbamazepine.

52 patients (25 males and 27 females) suffering from refrectory partial seizures, of not more than two years duration and on carbamazepine monotherapy were enrolled in this study. Patients were randomly put on gabapentin (19 males and 8 females) or lamotrigine (6 males and 19 females) as add on therapy. The efficacy of the drugs was assessed by the seizure frequency, pattern of seizures and seizure free interval. The safety was evaluated from the biochemical investigations and the adverse effects observed or reported by the patients during the course of the study. The average frequency of basal partial seizures was 6.26+3.86 and 5.04+2.47 which decreased significantly (p<. 001) after 12 weeks of add on therapy to 1.75+2.16. and 1.68+2.94 in the GBP and LTG group respectively. However, there was no significant difference between the two drugs after 12 weeks of add on therapy. The PCB (primary change in basal seizure frequency) values decreased to -72+34.92 and -76.22+29.68 in the GBP and LTG group respectively. The difference in these two groups was not significant. The responder rate was 77.7% and 92% respectively in GBP and LTG group respectively. GBP was found to be more effective in partial seizures with secondarily generalization while LTG was effective in all subtypes of partial seizures. The abnormal scalp EEG was recorded in 33.3% (9 of 27 patients) in GBP group and 40 %( 10 of 25 patients) in LTG group and it did not revert to normal in 33.3% and 40% of patients in either of groups (GBP/LTG). Minor side effects which were self limiting were noticed in 80% in groups I and 74% were groups II.

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PubMed2001

Improvement of acquired pendular nystagmus by gabapentin: case report.

Acquired Pendular Nystagmus (APN) may cause distressing visual symptoms in patients who are already suffering a severe general disease. Averbuch-Heller et al. conducted the first double-blind controlled study on treatment for APN. They showed that gabapentin substantially reduces pendular nystagmus and significantly increases visual acuity in the majority of patients. We present a patient with APN due to multiple sclerosis who suffered severe oscillopsy and reduction of visual acuity and who substantially benefited from a trial treatment with this agent.

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PubMed2003

Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy.

BACKGROUND AND PURPOSE: Proton MR spectroscopy has revealed impaired neuronal integrity in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). We hypothesized that the N-acetylaspartate (NAA)-creatine (Cr) ratios in the motor cortex and adjacent brain could reflect the therapeutic effectiveness of gabapentin (GBP) treatment in ALS. METHODS: Eight patients with ALS underwent MR spectroscopy before and 26.5 days +/- 8.8 after starting GBP. In 10 patients with ALS who were not treated with GBP, paired spectra were obtained 21.4 days +/- 7.2 apart. Fourteen healthy subjects underwent a single MR spectroscopic examination. The NAA/Cr ratio was measured in the precentral gyrus, the postcentral gyrus, the superior parietal lobule, the supplementary motor area, and the premotor cortex. RESULTS: The NAA/Cr ratio was decreased in the precentral and postcentral gyri of patients with ALS compared with healthy controls. In those with ALS, the change in the NAA/Cr ratio was not different between treated patients and untreated patients in any of the regions studied. CONCLUSION: No improvement in neuronal integrity was detected in motor and nonmotor cerebral regions after GBP treatment. This result agrees with that of prior investigations showing the equivocal clinical effectiveness of GBP for ALS and supports the validity of the NAA/Cr ratio as a surrogate of therapeutic effectiveness.

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PubMedDate not supplied

Effects of gabapentin and antidepressant drug combinations on convulsions and memory in mice.

In epileptic patients, neurobehavioral problems such as cognitive impairment, depression, and psychosocial impairments have been described, which may have a pathological and/or iatrogenic basis. For this reason additional treatment is required, beside antiepileptic drug (AED) therapy, to correct the accompanying neurological deficits. However, the rationale behind use of antidepressants along with antiepileptics has been questioned due to proconvulsant effects of the former. In the present study, the effect of gabapentin (GBP) on seizure score and memory is evaluated when it is given alone and in combination with some antidepressants, such as sertraline (SERTR) and alprazolam (ALP). Pentetrazole (PTZ)-induced convulsion and spontaneous alternation behavior (SAB) models were used to study the anticonvulsant effect and effect on memory, respectively. Results showed that addition of SERT to GBP or ALP resulted in reduction of anticonvulsant efficacy of these drugs. However, the combination of GBP + SERT + ALP was superior as far as effect on seizure severity and memory was concerned.

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PubMedDate not supplied

[The safety and tolerability profile of gabapentin in optimal doses].

INTRODUCTION: Gabapentin (GBP) is an amino acid that is structurally analogous to GABA with the capacity to cross the blood-brain barrier and an antiepileptic action. It is indicated in the treatment of partial seizures with or without secondary generalisation. It has been suggested that the dosages used in pilot studies were not suitable to achieve optimal efficiency. AIMS: The aims of this study were to investigate the safety and tolerability of GBP with doses above those initially advocated in the literature. DEVELOPMENT: We review its pharmacological characteristics and analyse the results of different placebo-controlled, open, short and long-term trials, both in monotherapy and associated to other antiepileptic drugs. CONCLUSION: Enough evidence was found to allow us to state that the efficiency of GBP can be increased with the utilisation of higher doses than those recommended to date, without the risk of generating unacceptable side effects at the same time.

Adult↗
PubMed2004

[Gabapentin (Neurontin) and cancer pain: a pilot study].

Gabapentin (GBP) is a new antiepileptic agent with an original spectrum of activity. Its mechanism of action has not yet been fully elucidated but appears not to involve binding to GABA receptors despite being a structural analogue of GABA and is distinct from tricyclic antidepressants (TCAs). It has been shown to modulate high threshold calcium currents in brain neurons. As some other anticonvulsants, GBP has been recently proposed for the treatment of noncancer neuropathic pain like diabetic neuropathy and post herpetic neuralgia (double blind studies with placebo). We prospectively followed 20 cancer patients with advanced disease suffering from neuropathic pain. All were already treated for their pain syndrome. We started with 300 mg of GBP given orally in order to reach a dose of 900 mg on D3. All coanalgesics were stopped before entering the study. The only relevant side effect due to GBP was somnolence, otherwise time limited. GBP treatment was associated with a decrease of opioids doses in 9 patients and a decrease of VAS for pain intensity in all cases. Furthermore, the need of rescue doses decreased in all cases but 2. GBP appears to be one of the most effective drugs for the treatment of neuropathic pain. It is well tolerated and its effectiveness appears shortly after its administration. A synergistic action with opioids is suggested. Despite the small number of patients, our study suggests that GBP could be a treatment of neuropathic pain in cancer. Comparative trials should be performed with other neuropathic pain drugs including TCAs and antiepileptic drugs, especially carbamazepine.

Adult↗
PubMedDate not supplied

[Improvements in the symptoms of olivopontocerebellar atrophy with gabapentin].

INTRODUCTION: Olivopontocerebellar atrophy (OPCA) is a degenerative disease of the nervous system (NS) which currently has no known cure. The neuronal depopulation it brings about produces a number of neurochemical alterations, including a reduction in levels of gamma-aminobutyric acid (GABA) in tissues and in cerebrospinal fluid (CSF). The drug gabapentin (GBP) has proved to be capable of increasing the concentration of this neurotransmitter in the central nervous system, and of improving the cerebellar ataxia in other diseases with a similar neurochemical substrate. CASE REPORTS: We describe two sporadic cases of OPCA, who were administered GBP. In one of the cases, the ataxia was noticeably reduced after taking one 400 mg dose. In the other case, a considerable improvement was observed in a very intense cerebellar dysarthria, and there was less oscillopsia with better vision, following administration of GBP for a period of over 12 months. CONCLUSIONS: GBP has proved to be capable of slowing down the motor disorders reported by patients in the course of OPCA. We discuss how such effects are due to the increased levels of GABA in the NS triggered by the drug. Finally, we suggest that the administration of GBP could constitute an effective symptomatic treatment for the ataxia and the dysarthria caused by OPCA, and that the improvement in symptoms following single doses of GBP could be valuable in cases of OPCA, as well as other types of ataxia, that are ideal for taking advantage of the stimulus of the GABAergic neurotransmission.

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PubMed2006

[Efficacy, safety and effect on the quality of life of gabapentin in adult epilepsy--results of a prospective open-label quasi naturalistic Hungarian multicenter study (phase human-IV)].

PURPOSE: To evaluate the efficacy and safety of gabapentin (GBP) in idiopathic or crypto/symptomatic partial epilepsy in adults. METHODS: We performed a prospective open label add-on study in pharmacoresistant patients with simple or complex partial or generalized seizures of partial onset (at least four seizures per month). GBP was added to no more than two baseline antiepileptics and the efficacy was rated primarily according to the seizure frequency. The secondary efficacy parameters were the change in the seizure severity scores (measured by the NHS3 scale) and in the quality of life (measured by the QUOLIE-31 questionnaire). GBP was added up to 1500-1600 mg per day in the titration period than an individual optimalization was allowed in any further visits. The follow-up period was three months. POPULATION: Fourteen Hungarian epilepsy out-patient unit participated in the study. 72 patients were enrolled, GBP was applied in 63 persons (ITT population) and 57 completed the study. RESULTS: A more than 50% decrease in seizure frequency was found in more than 70% of the patients in the third month. Among them just every third patient became seizure-free. Significant improvement appeared also in the severity of seizures and in the total score of the quality of life questionnaire. There was no difference either according to the etiology of the epilepsy or the seizure types. GBP was tolerated excellently. There was no need to decrease of the dosage of GBP and the side effects were mild and of transitory nature. CONSEQUENCES: GBP appears to be a valuable antiepileptic drug considering its high efficacy and extremely favourable tolerance. While GBP also decreases the severity of the seizures, its complex effects result an improvement in the quality of life of the patients. The positive effects have been durable during the follow-up. Open label naturalistic studies of larger population are needed to clear the special indications of GBP in chronic partial epilepsies.

Adult↗
PubMedDate not supplied

Gabapentin synergistically interacts with topiramate in the mouse maximal electroshock seizure model: an isobolographic analysis.

The anticonvulsant effects produced by topiramate (TPM) and gabapentin (GBP)--two second-generation antiepileptic drugs, in numerous fixed-ratio combinations of 8:1, 4:1, 2:1, 1:1, 1:2, 1:4 and 1:8 were examined by isobolographic analysis in the mouse maximal electroshock seizure (MES) model. Results indicate that the combinations of TPM and GBP at the fixed-ratios of 2:1, 1:1, 1:2, 1:4 and 1:8 resulted in supra-additive (synergistic) interaction against MES-induced seizures. Moreover, the combinations of TPM and GBP (at their median effective doses) did not affect motor performance of animals challenged with the chimney test and had no impact on neuromuscular tone in the grip-strength test. Additionally, GBP had no impact on total brain TPM concentrations, and simultaneously, TPM did not alter brain GBP concentrations, indicating that the interaction between drugs was pharmacodynamic in nature. In conclusion, supra-additive interaction of TPM with GBP against MES-induced seizures, lack of motor coordination and neuromuscular tone impairments as well as lack of pharmacokinetic interactions between TPM and GBP in preclinical study, strongly support the combined application of both antiepileptic drugs in patients with refractory partial epilepsy.

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PubMed1994

Gabapentin--a new antiepileptic drug.

Gabapentin (Neurontin--Parke-Davis) is a new antiepileptic drug. Like lamotrigine, which we reviewed 2 years ago, it is marketed for the add-on treatment of patients with partial or secondarily generalised (tonic-clonic) seizures that are inadequately controlled with standard antiepileptic drugs.

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PubMed1994

Guidelines for treating epilepsy in the age of felbamate, vigabatrin, lamotrigine, and gabapentin.

For the first time in 15 years, new antiepileptic medications are available for the treatment of patients with seizure disorders. These drugs have demonstrated efficacy in animal models of epilepsy and in controlled clinical trials. Felbamate was licensed in 1993 for use as adjunctive therapy or monotherapy in adults with partial or tonic-clonic seizures and as adjunctive therapy for children with the Lennox-Gastaut syndrome. Gabapentin was approved January 1994 as adjunctive therapy in patients 12 years or older with partial seizures, with or without secondary generalization. Lamotrigine is expected to be approved this year for the treatment of partial and tonic-clonic seizures in adults. Last, a new drug application has been filed for vigabatrin this year, with possible licensing next year. These four anticonvulsants present new options in the treatment of patients with refractory epilepsy and are not merely congeners of previously available treatments. They have unique clinical spectrums and are reported to be safer and better tolerated than conventional therapy. Trials to compare their use with that of conventional therapy have not been done, and their use in the initial treatment of patients with epilepsy is not completely clear.

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PubMed1995

[Refractory epilepsy in adults and the new antiepileptic drugs: the role of gabapentin].

The features of refractory epilepsies and the role of functional surgery and new antiepileptic drugs is reviewed. Among the latter, gabapentin, a drug with peculiar pharmacokinetic properties, is highlighted as a therapeutic alternative in refractory epilepsies and eventually for epileptic patients without previous treatment. A new type of relationship between the pharmaceutical industry and physicians, that privileges clinical research, is discussed.

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PubMed1996

[Gabapentin (Neurontin): a new possibility in the add-on therapy of partial epilepsies].

Gabapentin is a new antiepileptic drug for add-on therapy in patients above the age of 12 years with otherwise refractory partial seizures. Its unknown molecular mode of action is probably related to amino-acid-related binding sites in the brain. There are no hints to toxicologic effects or damage of the hematopoietic system, liver, or kidney in man. With the exception of a rather short elimination half life and dose-limited abortion, the pharmacokinetic data are very favourable. Due to lack of protein binding and metabolization, there are no major interactions with antiepileptic or other drugs. Efficacy has been demonstrated in three multicenter, placebo controlled trials involving a total of 705 patients. Secondarily generalized seizures seem to be the most likely to respond to 900 to 1800 mg/day, followed by complex partial and simple partial seizures. Tolerance is good, and serious side effects have not been observed up to now.

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