topiramate and Learning-Disabilities

Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre.. Sixty-four patients (36 men, 28 women, aged 16-65 years) were begun on adjunctive TPM after a 3-month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6-month period at optimal TPM dosing. These were seizure freedom or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study.. Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy.. TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population.

Topics: Adolescent; Adult; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Learning Disabilities; Male; Middle Aged; Prospective Studies; Topiramate; Treatment Outcome

Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Dopamine Uptake Inhibitors; Frontal Lobe; Fructose; Learning Disabilities; Male; Memory Disorders; Neuroprotective Agents; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Topiramate

28 male Long-Evans rats prepared with lesions of the middle cerebral artery displayed deficits in spatial navigational learning in a simple version of the Morris Water Maze task not seen in animals prepared with the same injury but administered 4 treatments with topiramate after surgery.

Topics: Animals; Cerebral Hemorrhage; Disease Models, Animal; Fructose; Learning Disabilities; Male; Maze Learning; Neuroprotective Agents; Rats; Rats, Long-Evans; Topiramate

The aim of this audit was to ascertain outcomes for people who had taken or who were still taking three "new generation" broad-spectrum antiepileptic drugs (AEDs), namely lamotrigine, levetiracetam and topiramate. Thirteen percent of people became seizure free and approximately, one-third had a reduction of greater than 50% in their seizures. Two-thirds of people were still taking their audit AED. In addition, approximately one-third of people with a learning disability derived substantial benefit, although the rate of seizure freedom was lower. All three AEDs were most successful at treating primary generalised epilepsy and least successful with symptomatic generalised epilepsy. With some reservations the data suggests that levetiracetam and topiramate are the most efficacious AEDs, but topiramate is the least well tolerated. These results mean consideration of a "general prescribing policy" is important when using and choosing these AEDs. We conclude that lamotrigine, levetiracetam and topiramate are useful additions to the armamentarium of AEDs.

Topics: Adult; Aged; Anticonvulsants; Cohort Studies; Drug Utilization; Epilepsy; Epilepsy, Generalized; Female; Fructose; Hospitals, General; Humans; Knowledge Bases; Lamotrigine; Learning Disabilities; Levetiracetam; Male; Medical Audit; Middle Aged; Patient Dropouts; Piracetam; Topiramate; Triazines; United Kingdom

To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention.. All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression.. Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy.. A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Chronic Disease; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Learning Disabilities; Male; Middle Aged; Prognosis; Proportional Hazards Models; Survival Analysis; Topiramate