Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter y-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting >50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy. (7 Neurol Neurosurg Psychiatry 1994;57:921-924)
Tiagabine is a novel antiepileptic drug which acts by decreasing gamma aminobutyric acid uptake in astrocytes and neurones. Here the first case of deliberate overdose with this compound in a patient on concomitant phenytoin is reported. On admission to hospital his conscious level deteriorated to grade III coma. No changes in the electrocardiogram were noted. Recovery from the initial effects was rapid, and there were no sequelae. Plasma levels of tiagabine (3.1 micrograms/ml) 4 hours after ingestion were 30 times higher than at typical steady state during therapeutic dosing. The effects of poisoning with current first-line antiepileptic drugs are reviewed. The newer agents, particularly those with greater biochemical specificity, may be safer in overdose than the more established anticonvulsants.
Old age is recognized to be the commonest time in life to develop epilepsy. There is a perception that older patients are more sensitive to the deleterious cognitive effects of antiepileptic drugs (AEDs). Elderly patients (median age 70 years, range 60-88 years) taking anticonvulsant monotherapy (10 carbamazepine [CBZ], 8 sodium valproate [VPA], 5 phenytoin [PHT]) took an extra dose of their usual medication (200mg CBZ, 500mg VPA, 100mg PHT) and matched placebo each for a month in random order. The concentrations of AEDs were higher after 7 and 28 days of active treatment compared with placebo (7 days: CBZ 9.5 vs. 7.8 mg L(-1), p < 0.05; VPA 97 vs. 64 mg L(-1), p < 0.05; PHT 13 vs. 11 mg L(-1), p < 0.05; 28 days: CBZ 9.4 vs. 7.7 mg L(-1); p < 0.01, VPA 85 vs. 60 mg L(-1), p < 0.05; PHT 16 vs. 13 mg L(-1), p < 0.05). Despite these increases in concentration, there were no significant changes in attention, reaction time, finger tapping, memory, side-effect scale or sedation scoring during the active phases compared with placebo phases for the three drugs analysed together and separately. Elderly patients taking standard AEDs as monotherapy did not develop cognitive impairment when the dose was modestly increased within the target range for each drug.
Background Safety systems are socio-cultural in nature, characterised by people, their relationships to one another and to the whole. This study aimed to (1) map the social networks of New Zealand’s quality improvement and safety leaders (2) illuminate influential characteristics and behaviours of key network players (3) make recommendations regarding how networks might be optimised. Methods Instrumental case study using mixed methods. Purposeful sampling was applied to collect survey data from delegates at two national safety and quality forums (n=85). Social network questions asked respondents who influenced their safety work. Key network players were identified and invited to participate in a semi structured interview (n=7). Results Key players described safety systems in humanistic terms. Safety influence was determined to be a responsive relational process. Adaptive leaders broker relationships between multiple perspectives and contexts, which is essential for safe healthcare. Conclusion Influential safety approaches appreciate the human contribution to safety. Designing the health system to adapt and respond to the needs of people, teams, and communities, rather than the unilateral needs of the system is essential. Adaptive leadership will assist in achieving these aims and will likely be embraced by New Zealand health professionals.
The incidence and prevalence of epilepsy increase substantially with old age. Despite this, the investigation and management of this patient population remains a grey area. Four hundred and eleven (53%) consultant geriatricians responded to a questionnaire exploring their approach to seizures in the elderly in order to establish an overview of current clinical practice. Between one and five patients presenting with seizures, predominantly aged between 75–85 years, were reviewed monthly. Seventy per cent of geriatricians undertook to investigate the patients themselves with biochemical and haematological profiles performed by most. Electroencephalography and computerized tomographic scanning were routinely requested by a quarter of responders. Only 58% would themselves initiate therapy with antiepileptic drugs, with 16% of consultants starting treatment following the first seizure, 59% after a second and 5% after a third. Phenytoin was first choice for generalized tonic-clonic seizures with carbamazepine preferred for partial seizures. If good control was not obtained, 67% would substitute another first line drug, while 27% would add in a second. Less than 3% would use the new anticonvulsants lamotrigine or vigabatrin. Sixty per cent monitored anticonvulsant concentrations in patients with poor control or suspected toxicity. A wide variability was seen in the current approach to seizures in the elderly, which reflects a lack of established practice. Epilepsy clinics for the elderly would encourage structured research into the many unanswered questions affecting the care of older people with seizures.
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