Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin.

PURPOSE: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared. METHODS: In a double-blind parallel-groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for < or =48 weeks. RESULTS: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme-inducing drug, whereas those taking LTG did not. CONCLUSIONS: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.

Neurological complications associated with pregnancy.

Prospective multidisciplinary audit from both hospital and community has identified neurological complications persisting for more than 6 weeks in association with pregnancy and delivery. They occurred at a frequency of 1 in 2530 deliveries in the North West Thames Region. Extradural analgesia was considered contributory to a neurological disorder in one of 13,007 patients. The woman had prolonged paraesthesiae along a nerve root. The types of sensory, motor and sympathetic neurological problems presented ranged from transient problems to more serious disorders resulting in death in one case. Seven of 19 patients had a continuing neurological disability for more than 1 yr. Although obstetrics may be associated with lumbar and sacral neurological disorders, problems occurred with the same frequency in the upper as in the lower half of the body. Significant morbidity is not being recognized in hospitals where women are being delivered and it is within the community that these disorders are recognized. This has implications for training, audit and risk assessment.

Is there a place for placebo controlled trials of antiepileptic drugs?

In many patients who develop epilepsy the disease is short lived and the overall number of seizures small. The role of anticonvulsant drugs in such patients is uncertain. If treatment is merely suppressive and the disease self limiting then treatment may not be necessary in some patients. If, on the other hand, early treatment prevents the subsequent evolution to chronic epilepsy then it is imperative. To resolve this issue it is essential to undertake placebo controlled trials, in which a group of patients with newly diagnosed epilepsy is given active treatment and compared with a similar group given placebo alone.

Phenytoin monotherapy for epilepsy: a long-term prospective study, assisted by serum level monitoring, in previously untreated patients.

Of 31 previously untreated patients with grand mal and/or partial seizures referred to a neurological clinic and treated with phenytoin monotherapy, assisted by serum level monitoring, 26 have been followed up for a mean of 42 months. Seizures were completely controlled in 80%. Failure of optimum phenytoin monotherapy occurred in 12%. The degree of seizure control was significantly related to phenytoin serum levels. The success of monotherapy was probably related to availability of serum level monitoring and to the study of a previously untreated population with a relatively short history of epilepsy. The main reasons for failure of monotherapy were poor compliance and the presence of additional neuropsychiatric handicaps, which commonly occur together. The place for polytherapy in the event of failure of monotherapy has still to be defined.