ABSTRACT
Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.
Subject(s)
Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Nipecotic Acids/administration & dosage , Adolescent , Anticonvulsants/adverse effects , Anticonvulsants/blood , Child , Epilepsy/blood , Epilepsy/psychology , Female , Humans , Male , Nipecotic Acids/adverse effects , Nipecotic Acids/blood , Prospective Studies , Single-Blind Method , TiagabineABSTRACT
In a multicentre, double-blind, parallel-group, placebo-controlled trial, a three-times daily regimen of tiagabine was evaluated as add-on therapy in 154 adult patients with refractory partial seizures. A total of 77 patients were randomised to treatment in each arm. Tiagabine HCl was titrated from an initial dose of 12-30 mg/day over 4 weeks. During the 12-week fixed-dose period, there was a significant reduction in the median 4-weekly seizure rate for all partial seizures and simple partial seizures (P < 0.05 in each case). Furthermore, the proportion of patients with a reduction of 50% or more in all partial seizures was higher in the tiagabine group than in the placebo group (14 versus 6%), though the difference did not achieve statistical significance. The difference with respect to simple partial seizures was significant (21 versus 6%, P < 0.01). The percentage of patients achieving an increase of at least 50% in the proportion of days free of all partial seizures was significantly greater in the tiagabine group compared to placebo (14 versus 4%, P<0.01). Tiagabine did not appear to influence the plasma concentrations of other concomitant antiepileptic drugs and was generally well tolerated, with most drug-related adverse events being mild or moderate in severity. The most common adverse events were dizziness, asthenia, headache and somnolence. Adverse event incidence was similar between tiagabine and placebo groups, except for dizziness which was more common with tiagabine (29 versus 10%, P < 0.01). Tiagabine had no significant effects on laboratory tests or vital signs. The present study shows that tiagabine, at a dose of 10 mg administered three-times daily, which is at the lower end of the usual recommended dose range (30-50 mg/day, tiagabine base), is generally well tolerated and demonstrates efficacy for the treatment of refractory partial seizures.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Nipecotic Acids/therapeutic use , Adolescent , Adult , Aged , Anticonvulsants/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Electrocardiography , Electroencephalography , Epilepsies, Partial/physiopathology , Epilepsy, Complex Partial/drug therapy , Epilepsy, Complex Partial/physiopathology , Female , Humans , Male , Middle Aged , Neurologic Examination , Nipecotic Acids/adverse effects , Placebos , TiagabineABSTRACT
A total of 149 patients in 7 centers in Denmark, Norway and Sweden entered a 6-week double-blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients (65 years of age or older) who might also suffer from somatic disorders and/or senile dementia. Results of ratings on the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram-treated patients improved more than the placebo-treated patients. Results of ratings on the Gottfries-Bråne-Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram-treated subgroup of patients with dementia than in the placebo-treated subgroup.
