PubMed Health⌕ Search

Biomedical subjects

I E Leppik

Publications and source records attributed to I E Leppik.

At least 19 recordsLinked to original sources
PubMed1999

Safety of tiagabine: summary of 53 trials.

We reviewed the clinical safety of tiagabine HCl (TGB), a selective CNS GABA uptake inhibitor, in nearly 3100 patients from 53 separate clinical trials. TGB was found to have no clinically important effect upon hepatic metabolic processes, serum concentrations of concomitant antiepileptic drugs (AEDs), laboratory values, or important interactions with any common non-AEDs. Adverse effects were usually mild and involved the nervous system. TGB is safe and well-tolerated as add-on therapy for the treatment of partial seizures.

Adolescent↗
PubMed1998

Tiagabine for complex partial seizures: a randomized, add-on, dose-response trial.

OBJECTIVE: To determine the efficacy and tolerability of tiagabine, a new antiepileptic drug (AED) that inhibits gamma-aminobutyric acid (GABA) uptake, at 3 dose levels vs placebo as adjunctive therapy in patients with intractable complex partial seizures (CPS). DESIGN: Randomized, double-blind, placebo-controlled study with a parallel-group, add-on design, starting with a 12-week unblinded baseline phase followed by a 20-week double-blind treatment phase. SETTING: Twenty-one US medical centers. PATIENTS: Patients (N = 297) aged 12 to 77 years, previously diagnosed as having CPS and receiving stable regimens of 1 to 3 hepatic enzyme-inducing AEDs; divalproex sodium or valproic acid was allowed in combination with any of these drugs. INTERVENTIONS: Placebo or tiagabine 4 times a day at 16, 32, or 56 mg daily. MAIN OUTCOME MEASURES: Median change in 4-week CPS frequency and adverse events. RESULTS: Median decreases in 4-week CPS frequency for the 32-mg (-2.2) and 56-mg (-2.8) tiagabine groups were significantly greater than for the placebo (-0.7) group (P = .03 and P < .03, respectively); 20% and 29% of patients in the 32- and 56-mg groups had a 50% or greater reduction in the frequency of CPS vs 4% in the placebo group (P = .002 and P < .001, respectively). Adverse effects were similar for placebo and tiagabine except for a significantly greater incidence of dizziness in the 32-mg tiagabine group, tremor in the 32- and 56-mg groups, abnormal thinking (usually mental lethargy or difficulty concentrating) in the 56-mg group, and depressed mood in the 16- and 56-mg groups. CONCLUSIONS: Tiagabine is efficacious and well tolerated as adjunctive therapy for CPS; there is a clear dose-response relationship.

Adolescent↗
PubMed1998

Quality of life of people with epilepsy in the United States.

Health care provision in the United States is driven by the fact that most health insurance is commercial and private. This leads to the tendency to view patients as units that will produce a future cash yield. The quality of life (QOL) movement in the United States is in some ways a response to this view and has a role in convincing insurers that new treatments and techniques are worth increased expenditure. In the case of epilepsy, QOL research has become essential in improving the quality of care offered to people with epilepsy. In this review, some of the outcomes of using the Quality of Life in Epilepsy questionnaire are reviewed, the preliminary data from a community-based study of people with epilepsy are described, and recent studies comparing QOL in epilepsy and other neurologic and nonneurologic diseases are discussed. This review illustrates the complexity of QOL issues and the need for the widespread use of QOL measures in people with epilepsy.

Adolescent↗
PubMed1998

Antiepileptic drug use in nursing home residents: effect of age, gender, and comedication on patterns of use.

PURPOSE: Examine antiepileptic drug (AED) use in nursing homes by age, gender, and use of comedication that can interact with AEDs. METHODS: Two point-prevalence evaluations of AED use from computerized medical records of nursing home residents throughout the United States (set 1, 43,757; set 2, 41,386) 65 years and older serviced by PHARMERICA. RESULTS: 10.5% of residents received an AED. Of the age group 65-84 years, 15 % received an AED compared with 6.1% of those 85 years or older (p < 0.001). Gender differences were present; 13.4% of the male residents and 9.4% of the female residents were treated with an AED (p < 0.001). The most frequently prescribed AEDs were phenytoin, carbamazepine, clonazepam, or phenobarbital. The average number of routine medications taken by AED recipients was 5.6, greater than the average of 4.6 for other residents. CONCLUSIONS: AEDs are extensively prescribed for elderly nursing home residents. Men and persons aged 65-85 years were more likely to receive AEDs than were women or those older than 85 years. AED recipients receive more routine medications than do other residents, including co-medications that alter hepatic metabolism and clinical response. The reasons for age and gender differences are unclear and require further study.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Tiagabine therapy for complex partial seizures. A dose-frequency study. The Tiagabine Study Group.

OBJECTIVE: To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment. DESIGN: Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period. SETTING: Twenty-six centers throughout the United States. PATIENTS: Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study. INTERVENTIONS: Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose. MAIN OUTCOME MEASURE: The median change in the 4-week rate of CPSs from baseline to experimental period. RESULTS: The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events. CONCLUSIONS: Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.

Adolescent↗
PubMed1997

Intramuscular fosphenytoin (Cerebyx) in patients requiring a loading dose of phenytoin.

Fosphenytoin (Cerebyx), is a water soluble prodrug that is rapidly and completely converted to phenytoin. This study reports the injection-site tolerance and safety of intramuscular fosphenytoin (> 10 mg/kg doses) in 60 patients requiring a phenytoin loading dose. Patients received injections at single or multiple sites with volumes ranging from 4 to 30 ml per injection site. The majority of patients had no irritation (erythema, swelling, tenderness, bruising) or complaints of discomfort related to fosphenytoin injection either after injection (95%) or at follow-up (88%). Irritation, when reported, was mild in all cases. Forty of 60 patients (67%) reported transient side effects, primarily involving the central nervous system, such as nystagmus, dizziness or ataxia, which are commonly associated with phenytoin therapy. All patients received prescribed doses; no patient had an injection(s) stopped due to intolerance or side effects. No serious adverse events occurred with intramuscular fosphenytoin. In this study, intramuscular fosphenytoin was demonstrated to be a safe and well tolerated, and in many instances, a preferable alternative to other means of phenytoin loading.

Adolescent↗
PubMed1996

Familial cerebral cavernous angioma: a gene localized to a 15-cM interval on chromosome 7q.

Cerebral cavernous angiomas are collections of closely clustered vessels without intervening normal brain parenchyma, with microscopic evidence of hemorrhage, frequently multiple; they are best visualized with magnetic resonance imaging. Familial cerebral cavernous angioma occurs as an autosomal dominant disorder, although carriers of the gene are often asymptomatic. Recently, a gene responsible for familial cerebral cavernous angioma in a large Hispanic kindred was mapped to human chromosome 7q11-22, representing a large segment of DNA containing approximately 33 cM (about 33 million base pairs). This distance did not allow more restricted isolation of the region containing the familial cerebral cavernous angioma gene. In this report, we present a large white kindred with familial cerebral cavernous angioma and confirm the mapping to 7q11-22, including the genetic markers D7S558/D7S1789 and D7S804. Recombination between several markers in the region suggests that the candidate region is distal to D7S804. Combining our results with those previously published, we suggest that the gene is likely to reside within a 15-cM region bounded by markers D7S660 and D7S558/D7S1789. These results should assist the further refinement of the candidate region for familial cerebral cavernous angioma and facilitate the search for the gene.

Brain↗
PubMed1996

Cost of refractory epilepsy in adults in the USA.

A cost of illness of refractory epilepsy was developed based on estimates supplied by an expert panel of physicians and a review of the current literature. The basic elements of model can be divided into two main components: direct and indirect costs. Direct costs include the medical resource utilization patterns associated with epilepsy care while the indirect costs represent lost productivity associated with the disease. The results of the analysis indicate that an estimated 24,578 incident cases of epilepsy incur a total of $318,582,669; while our prevalence estimates indicate that 335,167 individuals incur a total of $3,905,183,463, in a given year. Direct medical costs account for one-third of the total costs while indirect costs constitute the remaining two-thirds.

Adult↗
PubMed1996

Rational monotherapy for epilepsy.

At the present time monotherapy is preferable to polytherapy if the epilepsy can be controlled with a single drug. However, persons with intractable epilepsy may need more than one antiepileptic drug to attain the best seizure control with the fewest side-effects. Although clinical studies have not been performed to identify the best combinations, rational polytherapy would imply combining antiepileptic drugs with different mechanisms of action.

Anticonvulsants↗
PubMed1995

Familial cerebral cavernous angioma: clinical analysis of a family and phenotypic classification.

Only a few large families with cerebral cavernous angiomas (CCA) have been reported. We studied 47 members of a four-generation kindred with familial CCA. Thirteen members are affected; of these, eleven (85%) have epilepsy, five (38%) have hearing loss, three (23%) have clinically significant cerebral hemorrhages, one has dementia and progressive pseudobulbar palsy, one has a compressive myelopathy, one has asymptomatic cerebral cavernous angiomas identified by MRI, and another has an adrenal angioma found at autopsy. We developed a phenotypic classification to be used in future gene mapping studies. This classification is based on clinical symptoms, age at onset, concurrent diagnoses, and magnetic resonance imaging (MRI) findings. In the context of this family, this system assigns each member a probability of affectedness that can be used for linkage analysis. We suggest that patients with epilepsy may experience transient poor seizure control due to bleeding from an angioma, and drugs that may induce bleeding from the angiomas, such as valproic acid, should be avoided.

Adolescent↗
PubMed1995

Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing antiepilepsy drugs.

The effect of hepatic enzyme-inducing antiepilepsy drugs (AEDs) on the clinical pharmacokinetics of tiagabine, a new AED, was studied in the steady-state condition. Patients with epilepsy entered this two-day study on a previously stable regimen of one to three enzyme-inducing drugs (phenytoin, phenobarbital, carbamazepine, and/or primidone) and tiagabine.HCl (24, 40, 56, or 80 mg daily). Patients were confined on both days, and serial blood samples were collected. Plasma tiagabine concentrations were determined by high-performance liquid chromatography; pharmacokinetic parameters were calculated using noncompartmental methods. Tiagabine pharmacokinetics were linear at all doses, as substantiated by the lack of significant differences among groups for dose-adjusted Cmax, Cmin, and AUC0-6. Some diurnal variation occurred, as evidenced by a statistically significant time effect for dose-adjusted AUC0-6. The effect was small, however, and possibly not clinically relevant. The harmonic mean half-lives of 3.8 to 4.9 h were remarkably constant across dosages and shorter than those of historical control subjects not taking enzyme-inducing AEDs suggesting that epilepsy patients not taking enzyme-inducing AEDs may require lower tiagabine.HCl doses to achieve the plasma levels observed in patients taking these drugs.

Adolescent↗
PubMed1995

Felbamate.

After the first year of clinical experience, felbamate (FBM) appears to be a valuable antiepileptic drug (AED) for the treatment of intractable epilepsy. However, many patients experience side effects that may discourage continued usage. These may be decreased by using a slower dose-escalation schedule and/or by being more aggressive in decreasing co-medication. The most common troublesome side effects are nausea and insomnia. With the recent observation of aplastic anemia, FBM should be considered only for persons with intractable epilepsy under the care of a physician familiar with FBM. Nevertheless, many patients have benefited significantly from FBM and have made a decision to continue receiving FBM at the presently known risk profile. A few more years of experience may be needed to more accurately determine the final place of FBM in the treatment of epilepsy.

Adult↗
PubMed1995

Tiagabine: the safety landscape.

Tiagabine (TGB) hydrochloride is a potential new antiepileptic drug (AED) undergoing clinical development. Experience in humans amounts to 1,810 patient-years of exposure. TGB was found to be tolerated in an integrated safety analysis of five double-blind, add-on therapy trials involving approximately 1,000 patients with epilepsy with difficult-to-control seizures with existing AEDs. Discontinuation resulting from adverse events were infrequent, occurring in 15% of patients receiving TGB compared to 5% receiving placebo. The most frequently reported adverse event was dizziness, which was usually transient and did not require medical intervention. Adverse events that were statistically significantly more common with TGB than placebo were dizziness, asthenia, nervousness, tremor, diarrhea, and depression (not major depression). Adverse events were usually mild to moderate in severity and transient, and most were associated with dose titration. The incidence, type, and severity of adverse events in long-term studies were comparable with those in short-term studies. Serious adverse events were uncommon and no idiosyncratic events were reported.

Adolescent↗
PubMed1995

Involuntary movement disorders associated with felbamate.

Two children developed involuntary movements while taking felbamate as an adjunct to their antiepileptic regimen. One exhibited choreoathetosis and the other an acute dystonic reaction. In both children the symptoms resolved with no recurrence after felbamate discontinuance.

Adolescent↗
PubMed1994

Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics.

OBJECTIVE: To evaluate antiepileptic (AE) use by nursing home residents. DATA SOURCES: Medical records for 996 residents from six Minnesota nursing homes (5% of the nursing home residents in the Minneapolis-St Paul area) compared with medication records of 45,405 nursing home residents nationwide serviced by Pharmacy Corporation of America, Boulder, Colo. STUDY SELECTION: Reports comparing pharmacokinetics in younger adults and elderly volunteers or patients with epilepsy who were given AEs. DATA SYNTHESIS: Among Minnesota nursing home residents, 7.7% were taking AEs. Usage in a national survey was 10.1%. A review of published studies involving small numbers of elderly subjects or patients given phenytoin sodium, valproic acid, or carbamazepine demonstrates decreased protein binding and intrinsic clearance and increased half-life with advancing age. Concomitant drugs, especially those with central nervous system effects, can lower the concentration at which AEs cause dose-related side effects, thereby narrowing therapeutic ranges. CONCLUSION: Approximately 10% of nursing home residents receive AEs, usually with other maintenance medications. In 82% of residents receiving an AE, the indication was treatment of a seizure disorder. Other indications included aggressive behavior, essential tremors, and neurologic pain. Age-related alterations in AE pharmacokinetics result in protein-binding changes and decreases in drug elimination. Measurement of unbound drug concentrations may be helpful when altered binding is suspected or clinical response does not correlate with total AE concentration. Concomitant drugs pose the risk for significant drug interactions and adverse reactions. An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions.

Age Factors↗