Concomitant use of divalproex sodium and lamotrigine in developmentally disabled patients with epilepsy: a retrospective evaluation of efficacy and tolerability

Objective. Epilepsy in institutionalized severe developmentally disabled patients poses a therapeutic challenge. Frequently these patients have multiple seizure (sz) types that are often intractable. Both divalproex sodium (VPA) and lamotrigine (LTG) have demonstrated efficacy. We sought to examine the efficacy of this specific combination in a group of institutionalized, developmentally disabled patients with epilepsy.Methods. Medical and pharmacy records of all patients with developmental disabilities and intractable seizures were reviewed to identify those who had received VPA and LTG. This retrospective evaluation was structured with respect to time frame and outcome measure. Phase 1 consisted of baseline monotherapy with VPA. Phase 2 consisted of titration/dose escalation. Phase 3 was treatment observation period with the combination of both. Seizure frequency and adverse effect data were obtained from nursing or residential staff records. Primary outcome measures were change in seizure frequency between Phases 1 and 3. Additional measures were percentage of patients seizure-free and those with >75% reduction in seizures. A Wilcoxan signed rank test was used for statistical analysis.Results. Of 293 patients, 25 (12M/13F, 31.7+/-10.2 years) had VPA monotherapy following which LTG was added. Mean doses of VPA and LTG were 1474+/-728 and 165+/-111mg/day, respectively. Baseline seizure frequency ranged from 1 to 25 per month. Mean seizure frequency significantly decreased (6.5+/-vs2.0+/-4.0seizures/month, P<0.001). Sixty-four percent of these patients had >/=75% reduction in seizures 28% became seizure-free.Conclusions. The combination of VPA and LTG appears efficacious in this group of developmentally disabled patients with intractable seizures. Rash, which has been associated with this combination, was notably absent and this may reflect the slower titration schedule used.     

Assessment of Seizure Severity with Adjunctive Lamotrigine Therapy: Results from a U.S. Observational Study

THE ADJUNCTIVE LAMICTAL (LAMOTRIGINE) IN EPILEPSY: Response to Treatment (ALERT) study was an observational study designed to assess the safety of lamotrigine in patients with refractory partial seizures when used in a general practice setting. We measured the impact of adjunctive lamotrigine therapy for 16 weeks on the severity of seizures using the Liverpool Seizure Severity Scale (LSSS). This questionnaire was scored using a revised scoring procedure that assesses the impact of treatment on the patients "most severe seizure." Data from the LSSS were also compared with physician-rated changes of seizure severity. Patients who completed 16 weeks of lamotrigine treatment showed a significant reduction in LSSS scores when compared with patients who discontinued lamotrigine (change scores: patient's taking lamotrigine at Week 16, 9.2 +/- 23.4; patients who discontinued lamotrigine by Week 16, 0.8 +/- 23.4, P < 0.05). These findings were supported by significant reductions in physician ratings of seizure severity in patients who completed 16 weeks of lamotrigine therapy. Seizure severity is an important outcome in the study of antiepileptic medication. Data from this observational study suggest that lamotrigine is effective in reducing seizure severity when used as an adjunctive therapy in patients with refractory partial seizures.     

Adjunctive lamotrigine XR for primary generalized tonic-clonic seizures in a randomized, placebo-controlled study

Efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for primary generalized tonic-clonic (PGTC) seizures in epilepsy were evaluated. Patients (n = 153) ≥ 13 years old diagnosed with epilepsy with PGTC seizures were randomized to once-daily adjunctive lamotrigine XR or placebo in a double-blind, parallel-group trial comprising a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase. Lamotrigine XR was more effective than placebo with respect to median percentage reduction from baseline in weekly PGTC seizure frequency (primary endpoint-19-week treatment phase: 75.4% vs 32.1%, P<0.0001; escalation phase: 61.9% vs 30.6%, P = 0.0016; maintenance phase: 89.7% vs 33.3%, P<0.0001). Lamotrigine XR was more effective than placebo with respect to the percentage of patients with ≥50% reduction in PGTC seizure frequency. Significant separation from placebo for ≥50% reduction in PGTC seizures was observed beginning on treatment day 8. The most common adverse event was headache (lamotrigine XR 14%, placebo 16%).     

Lamotrigine add-on therapy for childhood-onset refractory epilepsy: comparison of the efficacy between 3 months and 6 months after initiation

We investigated the effect of lamotrigine (LTG) add-on therapy in 50 patients with childhood-onset refractory epilepsy (25 males and 25 females): 15 with localization-related epilepsy, 33 with generalized epilepsy, and 2 with undetermined epilepsy. Twenty-four patients had experienced a period of West syndrome during their clinical course. Age at the start of LTG therapy ranged from 2 years 6 months to 41 years 2 months: <16 years in 43 and > or = 16 years in 7. Seizure frequency was > or = 1 per day in 36 patients (72%) and > or = 1 per week in 14 (28%). We increased the LTG dosage every two weeks in accordance with usage recommendations. We evaluated efficacy at two points: 3 and 6 months after the start of LTG. At the 6-month point, seizure freedom was achieved in 2 patients (4%), > or = 50% seizure reduction in 14 (28%), 25 to 50% seizure reduction in 20 (40%), no effect in 6 (12%), and aggravation in 4 (8%). Only 4 patients (8%) stopped LTG therapy within 6 months due to LTG-related mild skin rash in 2 and suspicion of seizure aggravation in the other 2. In terms of seizure types, seizure freedom or > or = 50% seizure reduction was achieved in 29% for epileptic spasms, 32% for tonic seizures, and 29% for partial seizures. A comparison between the 3- and 6-month points revealed that the efficacy level was increased or maintained in 77% of the patients and decreased in 23%. In most cases, the highest level of efficacy appeared within 3 months with doses that were smaller than maintenance doses. Observed CNS-related adverse effects included somnolence in 16 patients, irritability in 14, and sleep disturbance in 11. Positive psychotropic effects in daily activities were seen in 28 patients (56%). These effects appeared regardless of the change in seizure frequency with doses that were smaller than maintenance doses.     

Efficacy and safety of levetiracetam as adjunctive treatment of refractory partial seizures in a multicentre open-label single-arm trial in Korean patients.

This prospective, open-label study evaluated the efficacy and safety of adjunctive levetiracetam (LEV) in Korean adults with uncontrolled partial epilepsy. Study patients had to have an average of at least 1 and not more than 14 partial seizures per month (averaged over a 3-month historical baseline) despite the use of one or two AEDs. Patients initially received LEV 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted, respectively. Seizure count and adverse events (AEs) were recorded by patients. Global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated. A total of 100 patients were enrolled and 92 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 43.2%. The >or=50% and >or=75% responder rates were 45.4% and 36.1%, respectively. Seizure freedom throughout the 16-week treatment period was observed in 17 patients. On investigator's GES, 81 patients were considered improved, with 41 patients showing marked improvement. Most QOLIE-31 scales improved significantly. Treatment-emergent AEs were reported in 59 patients. Three most common AEs were somnolence (36%), dizziness (12%), and headache (8%). Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy.     

The Use of Sertraline in Patients with Epilepsy: Is It Safe?

Purpose. The purpose of this study was to assess the impact of the selective serotonin-reuptake inhibitor (SSRI) sertraline (SRT) on the severity and frequency of seizures of patients with epilepsy.Methods. We prospectively assessed the seizure frequency of 100 consecutive patients with partial (n = 95) and primary (n = 5) generalized epilepsy during a trial with SRT for the treatment of a depressive (n = 97) or obsessive-compulsive (n = 3) disorder. We compared the monthly seizure frequency recorded while on SRT with those logged during the 3 and 12 months preceding the start of SRT. A definite causality between seizure worsening and SRT was considered in the following circumstances: (1) occurrence of de novo generalized tonic-clonic seizure (GTC); (2) recurrence of a GTC following a period of at least 1 year without this seizure type; and (3) an increase in the monthly seizure frequency beyond the maximal recorded monthly frequency during both 3- and 12-month periods preceding SRT. A probable causality between SRT and seizure worsening was considered in the case of an increase in monthly seizures beyond the maximal frequency recorded during the 3-month, but not the 12-month, period preceding SRT.Results. Six patients (6%) experienced an increase in seizure frequency after starting SRT. One and five patients met criteria for definite and probable causality between SRT and seizure worsening, respectively. Adjustment of antiepileptic drug doses resulted in a return to baseline seizure frequency in the latter five patients; four patients were kept on SRT at the same doses. The SRT dose of these six patients was significantly lower (57.1 +/- 23.8 mg/day vs 111.8 +/- 56.8 mg/day; F = 6.35, P = 0.01) than that of the other 94 patients.Conclusion. SRT can be safely used in the vast majority of patients with epilepsy.     

Gabapentin as add-on therapy in children with refractory partial seizures: a 24-week, multicentre, open-label study

The efficacy and safety of gabapentin as add-on therapy for refractory partial seizures in 237 children, aged 3 to 12 years were evaluated over a 6-month period. All children received gabapentin at 24 to 70 mg/kg/day. Efficacy variables included the percent change in seizure frequency and the responder rate (defined as those patients who showed >50% reduction in seizure frequency). For all partial seizures, the median percent change in seizure frequency was -34% and the overall responder rate was 34%. Simple partial seizures showed a median reduction of -53%; complex partial seizures, -38%; and secondarily generalized tonic-clonic seizures, -35%. Thirteen patients (5%) withdrew during the 6-month period because of adverse events. Concurrent antiepileptic medication remained unchanged in 185 patients (78%), was decreased in 27 (11%), and increased in 25 (11%) patients. This 6-month follow-up study has demonstrated that gabapentin was well tolerated and appeared to show a sustained efficacy in a large population of children with refractory partial and secondarily generalized tonic-clonic seizures.     

Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.     

Treatment of seizures with medroxyprogesterone acetate: preliminary report

Medroxyprogesterone acetate (MPA), a synthetic progesterone, was added to the antiepileptic drug regimen of 14 women who had uncontrolled seizures. Of the 11 women who developed amenorrhea, 7 reported fewer seizures during MPA therapy. Overall reductions in seizure frequency averaged 30% (n = 11), declining from a baseline 8.3 +/- 5.8 seizures per month to 5.1 +/- 4.1 seizures per month (p = 0.02). No serious side effects were encountered, but spotting was common. These preliminary data suggest further evaluation of MPA for catamenial seizures.     

Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy]

The study was designed to evaluate optimal use of add-on lamotrigine in the treatment of children and adults with refractory epilepsy of any type. Because of the available evidence from controlled studies, indicating the large spectrum of action of lamotrigine, we designed this prospective study to investigate the efficacy and safety of lamotrigine in everyday clinical practice, to collect useful information on its action in specific epilepsy syndromes and on the clinical results of specific co-medications. We studied 566 patients with a diagnosis of refractory epilepsy of any type currently receiving stable conventional regimens of antiepileptic therapy. Efficacy analysis was limited to 510 patients (388 patients aged 12 years or more, 122 patients aged 2 to 12 years) for which the exact number of seizures could be evaluated. Seizure characteristics were: simple and/or complex partial seizures in 298 (58p. cent) patients, partial seizures with secondary generalisation in 85 (17p. cent), generalised seizures of any type in 226 (44 percent). Syndromic diagnosis was partial symptomatic or cryptogenic epilepsy in 302 patients (59 percent), generalised symptomatic or cryptogenic epilepsy in 116 (23 percent) and idiopathic generalised epilepsy in 50 (10 percent). The percentage of patients who achieved at least 50 percent reduction in the frequency of seizures was evaluated around 40p. cent for all epilepsy categories, and up to 61 percent in idiopathic generalised epilepsies. Response to treatment with lamotrigine was usually obtained by the end of titration (4 weeks) and remained stable at 48 weeks. Thirty-three patients (7 percent) remained seizure-free at 48 weeks. In the group of patients with partial epilepsy, 19p. cent presented a more than 75 percent reduction in seizure frequency. A more than 50 percent reduction in secondary generalisation of partial seizures was observed in 45 percent of the patients. Efficacy results were similar in both the adult and paediatric age groups. They were better for patients receiving valproate co-medication (45 percent of the responders) as compared to other co-medications (37 percent of the responders), suggesting a synergistic action. Safety has been evaluated for all the patients having received lamotrigine (n=566). The incidence of adverse events attributed to lamotrigine was similar to the results of controlled studies, with somnolence reported in 10p. cent, a cutaneous reaction in 8 percent and episodes of transitory diplopia in 8 percent. A cutaneous reaction was more frequent in patients receiving carbamazepine (10 percent) as compared to valproate comedication (5 percent). However, the adverse event was sufficiently serious to necessitate hospitalisation in 3 patients receiving valproate. Dose escalation was not respected in two. Rash was reversible in all of the patients following discontinuation of the drug. The results of this study contribute to the overall understanding of the spectrum of lamotrigine effectiveness across seizure types and epileptic syndromes. Lamotrigine was well tolerated in children and adults.     

Generalized Tonic-Clonic Seizures in Patients with Complex-Partial Seizures: Natural History and Prognostic Relevance

Clinical course and long-term seizure prognosis were studied in 155 patients with complex-partial seizures during a follow-up of 10.1 +/- 1 (SD) years. In 79% of the patients generalized tonic-clonic seizures were recorded, mostly within the first 3 years of epilepsy but occurring as late as 20 years after the onset of epilepsy. Seizure control was defined as complete absence of all seizures, including auras, for a minimum of 2 years. Seizure control occurred in 20 of 32 patients (63%) with complex-partial seizures only and in 76 of 123 patients (62%) with complex-partial seizures and generalized tonic-clonic seizures. The onset of the epilepsy with generalized tonic-clonic seizures or complex-partial seizures did not influence the therapeutic outcome despite differences in their natural history. A family history of epilepsy and other generalized seizures (e.g., absence) were more frequent in patients with generalized tonic-clonic seizures at the onset of epilepsy. Seizure control was significantly lower (44%) in patients with a history of a maximum frequency of one or more generalized tonic-clonic seizures per month when compared to patients (79%) with a total of less than six generalized tonic-clonic seizures (p less than 0.05). The frequency of generalized tonic-clonic seizures is of predictive value for the seizure prognosis of patients with complex-partial seizures.     

Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomized, double-blind, placebo-controlled, parallel-group phase III study

Purpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial‐onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel‐group study had an 8‐week, single‐blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once‐daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double‐blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400‐mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200‐mg (p = 0.0003) and 800‐mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log‐transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once‐daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.     

Long-term tolerability and efficacy of lamotrigine in infants 1 to 24 months old

This open-label study was designed to evaluate the long-term tolerability and efficacy of lamotrigine in 1- to 24-month-old infants with partial seizures. The study enrolled both lamotrigine-na?ve patients and patients who had been previously exposed to lamotrigine in a randomized, double-blind, placebo-controlled study. Patients (n = 204) received lamotrigine according to a dosing schedule that depended on prior experience with lamotrigine and concurrent antiepileptic drug therapy for up to 48 weeks or their second birthday, whichever occurred last. Total duration of lamotrigine exposure (which included exposure during the placebo-controlled study in lamotrigine-experienced patients) was >/=24 weeks in 92% of patients, >/=48 weeks in 70% of patients, and >/=72 weeks in 20% of patients. A total of 20 (10%) patients (8 lamotrigine-na?ve patients and 12 lamotrigine-experienced patients) transitioned to lamotrigine monotherapy. The most common adverse events were pyrexia (45% of patients), upper-respiratory tract infection (28%), and ear infection (22%). The only adverse event considered reasonably attributable to study medication in >2% of patients was irritability (n = 10; 5% of patients). No cases of serious rash were reported. The median percent reduction from baseline in partial seizure frequency in the sample as a whole was 74%. Seizure frequency was reduced by >/=50% from pre-lamotrigine baseline in 62% of patients in the sample as a whole, 60% of the lamotrigine-na?ve subgroup, and 63% of the lamotrigine-experienced subgroup. In the sample as a whole, 13% of patients were seizure free during the Treatment Phase. Investigators considered clinical status at the last clinic visit to be improved (mildly, moderately, or markedly) relative to prelamotrigine clinical status in 76% of patients (150/197) and to be unchanged in 19% (37/197). In this study-the first large prospective investigation of the long-term tolerability and efficacy of an antiepileptic drug in a patient population 2 years and younger-lamotrigine administered for up to approximately 72 weeks was well tolerated and associated with good seizure control.     

Rectal diazepam gel for treatment of acute repetitive seizures. The North American Diastat Study Group.

The purpose of these investigations was to determine from combined data the response to rectal diazepam (DZP) gel (Diastat [Athena Neurosciences, South San Francisco, CA]) in home treatment of children with episodes of acute repetitive seizures (ARS). A subset of patients aged 2-17 years were selected from two prospective placebo-controlled studies of children and adults. In both studies a prospective, double-blind, placebo-controlled design was used. The treatment groups (68 DZP; 65 placebo) did not differ significantly in age, race, seizure type or etiology, or in the median number of ARS episodes per month before study entry. DZP-treated children demonstrated a significant reduction in median seizure frequency compared with the placebo group (0.00 vs 0.25 seizures per hour, P = 0.001). Significantly more DZP-treated children remained seizure free during the observation period (40 vs 20, P = 0.001). Somnolence was the only adverse effect present significantly more often in the DZP-treated children (25.0% vs 7.7%, P = 0.0095). There were no instances of serious respiratory depression. Rectal DZP was demonstrated to be an effective and safe treatment to abort an episode of ARS in a child and, additionally, lessened the likelihood of seizure recurrence within the next 12 hours.     

Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory partial-onset seizures: a multicenter, open-label single-arm study

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam as add-on therapy in patients with refractory partial-onset seizures in a protocol designed to reflect clinical practice. METHODS: All patients in this open-label, single-arm study entered an 8-week baseline period followed by a 4-week titration period and a 12-week maintenance period. Patients initially received levetiracetam 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of levetiracetam could not be increased but could be decreased once if tolerability warranted. Seizure count and adverse events were recorded by patients in a diary. Quality of life and global evaluation of disease evolution were also evaluated. RESULTS: Ninety-nine patients were enrolled and 91 completed the study. A steady dose was maintained over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving 1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency of partial-onset seizures was observed over the entire treatment period. The median partial-onset seizure count decreased from 2.3 per week during the baseline period to 1.3 per week over the treatment period. A total of 42.4% of patients were responders (> or = 50% reduction from baseline in weekly seizure frequency) over the treatment period; two patients were seizure-free from the first day of treatment throughout the treatment period. The most frequent drug-related adverse events were fatigue (27.3% of patients), somnolence (11.1%), headache (8.1%), and dizziness (8.1%). CONCLUSION: Levetiracetam as add-on therapy at doses up to 3000 mg/day effectively reduced the frequency of partial-onset seizures in patients with refractory epilepsy and was well-tolerated in this study, bridging conditions of placebo-controlled clinical trials and clinical practice.     

A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.

The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour.     

Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study

PURPOSE: Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. METHODS: This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. RESULTS: Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CONCLUSIONS: CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.     

Efficacy and Tolerability of Vigabatrin in Children with Refractory Partial Seizures: A Single-Blind Dose-Increasing Study

Summary: The efficacy and tolerability of vigabatrin (VGB) in children with refractory partial epilepsy were assessed in a single-blind, add-on, fixed-sequence, placebo-controlled trial. After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure-free (n = 3) or improved markedly (n = 8), treatment was completed at a dose <80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21,12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number of patients who had <50% reduction in seizure frequency after 2, 4, and 6 months was 28, 33, and 35, respectively. Eight patients became seizure-free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no signscant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment. Increased appetite and sedation were observed in 17 and 11% of cases, respectively. VGB is effective in the management of refractory partial epilepsy in children, and in some patients a positive dose-response relationship appears to occur over the assessed dosing range.     

Topiramate in patients with learning disability and refractory epilepsy

PURPOSE: Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre. METHODS: Sixty-four patients (36 men, 28 women, aged 16-65 years) were begun on adjunctive TPM after a 3-month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6-month period at optimal TPM dosing. These were seizure freedom or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study. RESULTS: Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy. CONCLUSIONS: TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population.     

Effect of trained Seizure Alert Dogs on frequency of tonic-clonic seizures.

We have previously reported that dogs can be trained to recognize specific changes preceding an epileptic seizure in humans. Such dogs can provide an overt signal that acts as a useful warning to the human. Early observations suggested that seizure frequency might also be reduced. We report a prospective study of 10 consecutive referrals to our Seizure Alert Dogs service of people with tonic-clonic seizures. Seizure frequency was monitored over a 48 week period including 12 weeks baseline after entry, a 12 week training period, and 24 weeks follow up. Comparing baseline seizure frequency to the last 12 weeks of follow up, there was a 43% mean reduction in seizure frequency ( P= 0.002). Nine out of /10 subjects showed a 34% or greater reduction, 4 /10 showed a 50% or greater reduction, and only one showed no improvement. Although a significant drop in seizure frequency was seen during the first 4 weeks of training ( P= 0.0078) a further drop occurred between the first and last 4 week period of training (P = 0.038) and this final improvement was maintained for the whole 24 week follow up.