Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy.

Tiagabine blocks the uptake by neurons or glia of synaptically released GABA resulting in prolonged GABAergic activity and decreased likelihood of epileptic seizures. We evaluated the cognitive and quality of life effects of tiagabine in a double-blind, add-on, placebo-controlled, parallel, multicenter, dose-response efficacy study in patients with focal epilepsy whose complex partial seizures were difficult to control. One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments: placebo (n = 57), 16 mg/d tiagabine (n = 34), 32 mg/d tiagabine (n = 45), or 56 mg/d tiagabine (n = 26) at a fixed-dose for 12 weeks after a 4-week dose titration period. Eight cognitive tests and three measures of mood and adjustment were administered during the baseline period and again during the double-blind period near the end of treatment (or at the time of dropout). The patient groups were similar at entry into the study. Results showed no clinically important changes with the addition of tiagabine on the test battery. Although this is an encouraging finding, it remains for future investigations to determine the cognitive and behavioral effects of tiagabine either as monotherapy or in relation to other antiepileptic drugs.

Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy.

We evaluated the psychological effects of the antiepilepsy drug vigabatrin in a randomized multicenter double-blind placebo-controlled parallel group study that compared 3 grams oral vigabatrin with placebo as daily add-on therapy in patients with focal epilepsy whose complex partial seizures were difficult to control. Testing at baseline and after 12 weeks of vigabatrin (n = 83) or placebo (n = 85) used eight measures of cognitive abilities and three of mood and adjustment. The vigabatrin and placebo groups were highly similar at entry into the study. At the end of the study, there were no differences between the vigabatrin and placebo groups on any cognitive variable or on any measure of mood and adjustment. Analysis of the results related to relief from seizures demonstrated only chance findings. In a similar manner, there were no relationships between vigabatrin serum levels at the end of the study and changes on measures of abilities and adjustment. Vigabatrin appears to be a useful antiepilepsy drug with little impact upon tests of either cognitive abilities or quality of life.

Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, and mood.

The effects of tiagabine (TGB) on abilities and on adjustment and mood are as yet incompletely understood. These effects were compared with those of phenytoin (PHT) and carbamazepine (CBZ) in an add-on study. Patients included in the analysis were adults with uncontrolled partial seizures who at study entry were on CBZ alone (n=153) or on PHT alone (n=124). Of the patients receiving CBZ, 82 were randomized to add-on TGB and 71 were randomized to add-on PHT during the double-blind period. Of the patients receiving PHT, 58 were randomized to add-on TGB and 66 were randomized to add-on CBZ. Eight tests of mental abilities and three of mood and adjustment were given prior to assignment of add-on treatment and after up to 16 weeks of add-on treatment. For the baseline CBZ group, analyses were done to search for differential changes from baseline in the test scores of the add-on TGB and add-on PHT groups, and for the baseline PHT group in the add-on TGB and add-on CBZ groups. In the baseline CBZ group, no differences in test scores were found between PHT and TGB. In the baseline PHT group for the area of abilities, patients treated with TGB had improved verbal fluency, as well as quicker responses on a test of perceptual/motor speed compared with patients treated with CBZ. For the baseline PHT group in the area of adjustment and mood, patients treated with TGB reported less positive mood and more financial concerns compared to patients treated with CBZ. Overall, add-on TGB showed few or no differences in comparison with add-on CBZ and add-on PHT.

Cognitive abilities and adjustment with gabapentin: results of a multisite study.

The cognitive and quality of life effects of gabapentin are not yet well explored. While preliminary work in the area has provided positive findings, a large double-blinded study has been needed to explore this area more thoroughly. From 24 sites in North America, 201 adults were studied who had uncontrolled complex partial seizures with or without secondary generalization. Attempts were made to convert each patient from one or two marketed antiepileptic drugs (AEDs) taken in baseline to gabapentin monotherapy (600, 1200, or 2400 mg/day). Tests of cognitive abilities and adjustment were administered at the end of the 8-week baseline period and at the end of the 26-week double-blind treatment period. Analyses of baseline to treatment period changes were conducted for each dose group in comparison with a reference group of placebo-treated patients from another study. In the area of cognitive functioning, no changes in any of the gabapentin groups were found in comparison with the reference group. In the area of adjustment and mood, however, improvement with gabapentin administration was noted on several variables pertaining to emotional and interpersonal adjustment. These results are consistent with findings from previous studies.

Effect of task complexity on mental performance during immersion hypothermia.

The effect of task complexity on the decrement in mental performance during immersion hypothermia was studied. Psychometric tests of varying length and complexity were administered: 1) prior to cold water immersion (baseline); 2) soon after immersion to the neck in cold (8 degrees C) water but prior to any decrease in core temperature; and 3) after 55 to 80 min of immersion when core temperature had decreased 2-4 degrees C. Results indicated that tests placing relatively minimal cognitive demands on individuals, such as auditory attention, the Benton visual recognition test and forward digit span, were unaffected by either initial cold water immersion or central cooling. On the other hand, tests requiring relatively greater mental manipulation and short term memory (i.e., backward digit span) or processing and analysis (i.e., Stroop test) showed a slight improvement upon cold water immersion (perhaps related to increased arousal and/or learning) but a significant decrement following central cooling of 2-4 degrees C. Thus, relatively simple tasks were unaffected by central cooling, whereas more complex tasks were adversely affected. Cold water immersion itself did not interfere with performance of any tasks. Central nervous system cooling probably interferes with mental processing although discomfort and/or the physiological and physical effects of cold on the neuromuscular aspects of speech, required for responses to some of the tasks, may also affect performance.

Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and quality of life in epilepsy.

Vigabatrin (VGB) prevents seizures by irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase and a resulting increase in GABA levels. We evaluated the cognitive and quality-of-life (QOL) effects of VGB in a double-blinded, add-on, placebo-controlled, parallel group dose-response study of patients with focal epilepsy whose complex partial seizures (CPS) were difficult to control. In a single investigation, patients were randomly assigned to placebo (n = 40), 1 g VGB (n = 36), 3 g VGB (n = 38), or 6 g VGB (n = 32), treated for 12 weeks after a 6-week dose escalation period, and tested at the end of the baseline period and at the end of the treatment period with eight cognitive measures and three tests of mood and adjustment. The patient groups were highly similar at study entry. Results at the end of the study showed substantial relief from seizures. The Digit Cancellation Test showed decreases in performance with increasing doses of VGB. Performance on no other test showed any decrement with increasing dosage. Relief from seizures was not associated with changes on the psychological tests. VGB is a useful antiepileptic drug (AED) that has little impact on tests of either cognitive abilities or QOL, even at a high dose.

Effects of tiagabine monotherapy on abilities, adjustment, and mood.

PURPOSE: We evaluated the dose-related impacts of tiagabine (TGB) on cognition and mood in a monotherapy study. METHODS: Patients were 123 adults with uncontrolled partial seizures, each treated with a single currently available antiepileptic drug (AED) for management of clinical epilepsy. They completed a battery of neuropsychological tests during an 8-week prospective baseline period and once again at the end of the 12-week fixed-dose period (or earlier if they dropped out of the study). Sixty-six patients were randomized to 6 mg/day TGB and 57 were randomized to 36 mg/day TGB. RESULTS: Few changes in either abilities or adjustment and mood were noted when all patients were considered as a single group. However, analysis of both dose and attainment of TGB monotherapy showed that patients receiving TGB monotherapy did best, improving particularly in the areas of adjustment and mood with low-dose TGB and in the area of abilities with high-dose TGB. Patients who did not attain monotherapy showed no change except that the high-dose group did not perform as well on measures of mood and adjustment. Baseline AED and changes in seizure control did not affect the results. CONCLUSIONS: Patients' attainment of TGB monotherapy was associated with their achievement of positive changes of varying degree on psychological tests. Failure to attain TGB monotherapy was associated with no changes on the tests except in patients receiving high-dose TGB where it appeared that some alterations in mood might have been avoided if a slower titration schedule had been used.