Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group.

The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.     

Tiagabine Monotherapy in the Treatment of Partial Epilepsy

Summary: Three studies were conducted to assess tiagabine (TGB) hydrochloride monotherapy in patients with partial seizures. The first was a double-blind, placebo-controlled trial of 11 patients (seven TGB, four placebo) undergoing evaluation for epilepsy surgery. Baseline antiepileptic drug (AED) therapy was discontinued abruptly before monotherapy. Although 24-h seizure rates increased during monotherapy in both groups, patients receiving TGB experienced fewer seizures than placebo patients. Subsequent studies (an open-label, dose-ranging study; n = 31 and a double-blind, randomized comparison of 6 and 36 mg/day TGB; n = 102 and 96, respectively) involved discontinuation of baseline AEDs. In the dose-ranging study, 19 of 31 patients (61%) converted to TGB monotherapy, with a mean final dose of 38.4 mg/day (range 24–54 mg/day) in those who completed the study ( n = 12). In the low- vs. high-dosage study, median 4-week complex partial seizure rates decreased significantly in patients from both dose groups who completed the monotherapy period ( p <0.05 compared with baseline). In the intent-to-treat analysis, significantly more patients in the high-dose group experienced a reduction in seizures of at least 50% compared with the low-dose group ( p = 0.038). Overall, the types of adverse events with TGB monotherapy were similar to those observed in add-on trials. These initial trials in difficult-to-treat epilepsy patients indicate that TGB monotherapy may provide a new approach to the treatment of patients with partial seizures refractory to other AEDs.     

Conversion to High Dose Gabapentin Monotherapy in Patients with Medically Refractory Partial Epilepsy

Summary: Purpose: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,0004,800 mg/ day) in patients with medically refractory partial epilepsy.
Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed.
Results: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,4004,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related.
Conclusions: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.     

Gabapentin add-on treatment: how many patients become seizure-free?: An open-label multicenter study

The aim of the study was to find out the percentage of patients with localization-related epilepsy achieving complete seizure control with gabapentin (GBP) add-on therapy. Patients under anti-epileptic drug monotherapy during 8 weeks baseline (BSL) with 6 or more seizures were treated with GBP for 26 weeks up to 2400 mg/day. Patients obtaining complete seizure control of all seizures or any partial seizure type during the last 8 weeks were calculated. Seizure frequency was compared between BSL and last 8 weeks. In all, 110 patients were enrolled (92 completed, 18 discontinued): mean age of the completers: 37.6 years (range 16–72), median seizure frequency per 28 days at BSL: 6.8 (2.5–24.5), mean duration of epilepsy: 17.6 years (0.2–51.4), mean duration with GBP for completers: 182.8 days (144–187). Complete seizure control of all seizures was achieved in 8.7% of patients (simple partial seizures: 13.3%, complex partial seizures 24.3%, secondarily generalized seizures: 61.5%): 38% of the patients became seizure-free in at least 1 seizure-type; 40% experienced adverse events. Assessment for quality of life (QoL) and trough plasma levels of GBP did not correlate with the good effect of GBP.     

Valproate Monotherapy in 30 Patients with Partial Seizures

This retrospective pilot study describes 30 patients diagnosed and treated for complex partial seizures (CPS) and simple partial seizures (SPS) with and without generalization who received valproate (VPA) monotherapy after lack of response or allergic reaction for carbamazepine (CBZ), phenytoin (PHT), or phenobarbital (PB). Seizures were tabulated daily on seizure calendars by the patients. Three time periods were examined for seizure frequency, 90 days before VPA treatment and 90 and 180 days after VPA treatment. Twenty-two were "controlled" or "improved" (reduction of seizure activity by greater than or equal to 51%) 6 months following the initiation of VPA. VPA was particularly effective in 17 patients who had secondarily generalized tonic-clonic seizures (GTCS) as a subtype of partial seizures. Failure of response to VPA in eight patients appears to be related to their type of partial seizure (SPS or CPS alone, without GTCS) and duration of uncontrolled recurrent seizures. Etiology and compliance were not related to treatment failure. This study supports the need for a double-blind controlled trial with VPA in patients with partial seizures.     

Relationship of Carbamazepine Reduction Rate to Seizure Frequency During Inpatient Telemetry

Summary: To establish guidelines for medication reduction during inpatient telemetry, the records of 18 children and young adults with refractory partial seizures undergoing carbamazepine (CBZ) reductions during continuous video/EEG telemetry were reviewed. Six patients were receiving CBZ monotherapy, and 12 patients were treated with an additional antiepileptic drug (AED) maintained at baseline dosage during CBZ taper. Despite relatively rapid mean reductions in dosage of 44% by day 2 of taper, no patients experienced frequent repetitive seizures or status epilepticus (SE). Seizure rate during the entire CBZ reduction period correlated significantly with rate of drug reduction. Linear regression analysis showed drug reduction rate to be a good predictor of seizure rate. Fourteen patients experienced at least three seizures during CBZ taper. On the average, the third seizure occurred on day 5 of taper at a percentage of dose seduction of 79%. In 8 patients, CBZ concentrations were measured both before taper and ≤24 h after the third seizure. For these patients, seizure rate also correlated significantly with reduction in CBZ level. We conclude that manipulation of CBZ dose reduction rate is important in maximizing seizure frequency during telemetry and, in our patients, a relatively rapid rate of dose reduction was safe and effective in promoting seizure recordings.     

Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy. 012 Study group

Patients from 12 countries reporting two or more partial seizures per month despite treatment with optimal doses of CBZ were randomised to additional vigabatrin (VGB, 2-4 g daily) or sodium valproate (VPA, 1-2 g daily) using a double-blind, double-dummy design. The study included a 6 month retrospective baseline on unchanged CBZ dosage, a month's prospective baseline, a short titration phase, and an assessment period lasting 3 months on duotherapy. CBZ was withdrawn over a further 2 months in responders ( > or = 50% monthly seizure reduction compared with baseline), who continued on alternative monotherapy for 3 or more months. If seizure control deteriorated, CBZ was reinstated and these patients were also followed up for 3 months. A total of 215 patients (108 VGB, 107 VPA) reporting a mean of seven partial seizures per month fulfilled the criteria for the intention-to-treat analysis. 53 and 51% of patients in the VGB and VPA group respectively achieved a monthly reduction in seizure numbers > or = 50%, respectively. 27 and 31% maintained alternative monotherapy. Overall, 17% (7% monotherapy, 10% duotherapy) of the VGB treated patients and 19% (8% monotherapy, 11% duotherapy) of the VPA group remained seizure-free during the final 3 month treatment period. VGB and VPA, which increase neuronal inhibition mediated by gamma aminobutyric acid, can be added to or substituted for CBZ when this Na+ channel blocker fails to control partial seizures. This lends credence to the hypothesis in support of a mechanistic approach to the management of 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.     

Gabapentin in childhood epilepsy: a prospective evaluation of efficacy and safety

PURPOSE: To evaluate the efficacy and safety of gabapentin (GBP) in partial epilepsy in children. METHODS: We performed a prospective open label add-on study in 52 children and adolescents (age 1.8-17.5 years, mean 11.1 years) with refractory partial seizures. Gabapentin was added to one other baseline drug and the efficacy was rated according to seizure type and frequency. RESULTS: The GBP dose ranged from 26 to 78 mg/kg per day (mean 52 mg/kg per day) and was well tolerated in most patients. The seizure frequency remained unchanged in 34 patients (65%). We saw a provocation of seizures in three children (6%). Initially 15 patients (29%) benefited from GBP: five (10%) with a seizure reduction of 50-74%, seven (13%) with a reduction of 75-99% and three (6%) became seizure free. All but three experienced a development of tolerance within the next weeks to months. CONCLUSIONS: Although gabapentin seems also to be safe in children, the efficacy in refractory partial seizures was disappointing.     

Improved quality of life in patients with partial seizures after conversion to oxcarbazepine monotherapy

OBJECTIVE: Quality of life (QOL) was assessed in patients who switched to oxcarbazepine monotherapy because of the lack of efficacy or poor tolerability of their current antiepileptic drug (AED). METHOD: This open-label, single-arm study consisted of patients aged 12 >or= years with partial onset seizures. Oxcarbazepine (8-10mg/kg/day for children, 600 mg/day for adults) was titrated up over 4 weeks while the existing AED was tapered off. QOL was evaluated at baseline and end of study (Week 16) using the validated-in-epilepsy QOLIE-31 questionnaire. RESULTS: For all patients who completed the QOLIE-31 at baseline and completion, a statistically significant improvement was noted for both the composite and multi-item subscale QOL scores (P<0.05 vs baseline). Statistically significant mean percentage improvements of >or=10% from baseline (range=10.8-50.1%) were also noted. Significant improvements were seen in health-related QOL for patients who experienced seizure freedom or >or=50% reductions in seizure frequency with oxcarbazepine monotherapy. CONCLUSIONS: Patients with partial seizures who switched to oxcarbazepine monotherapy showed statistically significant, clinically relevant improvements in QOL.     

The use of lamotrigine monotherapy in children with newly diagnosed partial epilepsy

Lamotrigine (Lamictal, Glaxo Wellcome) is a drug which is used as add-on therapy in patients with refractory epilepsy. Several previous studies have demonstrated the efficacy of lamotrigine monotherapy, but only few have been done in pediatric patients. The aim of our study was the assessment of efficacy and tolerability of lamotrigine monotherapy in children with newly diagnosed partial epilepsy. Lamictal was used in 19 children (11 boys and 8 girls), aged 3-16 years. 17 patients demonstrated complex partial seizures (with or without secondarily generalisation), 2 children had simplex partial seizures. Symptomatic epilepsy was diagnosed in 10 patients and cryptogenic epilepsy in 9 cases. The drug was administered at the dose of 3.87 +/- 1.02 mg/kg/day during 24 weeks. Three children withdrew from the study because of adverse events: one patient developed rash, two ones seizure exacerbation. Lamictal produced of at least 50% reduction in seizure frequency in 12 (63.15%) children, included 10 seizure-free patients. One third patients experienced EEG improvement. The most common adverse effects were gastrointestinal and sleep disturbances, infections, dizziness, all of them were mild and transient and observed more often in children under 12 years of age. Lamotrigine monotherapy is effective and safe for treatment of newly diagnosed cryptogenic and symptomatic epilepsy with partial seizures but further studies are necessary specially in young children.     

Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.     

Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study

PURPOSE: Monotherapy has been the gold standard in epilepsy treatment for the last 20 years, partly because of the reputation for increased toxicity of polytherapy. However, monotherapy and polytherapy have not been compared in a double-blind clinical trial. Open trials that compared the two treatments were not optimally designed and compared the two at unequal drug loads (i.e., at nonequivalent dosages). We report on a double-blind clinical trial in which a combination of carbamazepine (CBZ) and valproate (VPA) was compared with CBZ monotherapy. Patients started with equal drug loads, and neurotoxicity was the primary outcome measure. METHODS: The 130 adult patients with untreated generalized tonic-clonic and/or partial seizures were randomized to equal drug loads of either monotherapy (400 mg CBZ per day) or polytherapy (200 mg CBZ plus 300 mg VPA per day). Outcome was measured by seizure counts, clinimetric epilepsy scales, and neuropsychological tests at baseline, at 2 and 12 months, and irregularly between 2 and 12 months. RESULTS: No statistical differences were found between the two treatments in the reduction of seizure frequencies, in overall neurotoxicity, or in overall systemic toxicity. The frequencies and clinimetric scores of certain adverse effects did differ (e.g., more monotherapy patients remained sedated, and more polytherapy patients gained weight). Fewer polytherapy patients withdrew because of adverse effects (14 vs. 22%), although this did not reach statistical significance (p=0.15). Neuropsychological assessment did not show significant differences. CONCLUSIONS: No differences were found in overall neurotoxicity between monotherapy and polytherapy.     

Clinical experience with open-label topiramate use in infants younger than 2 years of age

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0-10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and a s monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation.     

Felbamate monotherapy: controlled trial in patients with partial onset seizures.

Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p less than 0.001, chi-square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.     

Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed. RESULTS: A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy. CONCLUSIONS: Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.     

Long-term outcome of vagus nerve stimulation for refractory partial epilepsy

We assessed 1- and 2-year outcomes of specific seizure types, quality of life, depression, and anxiety among patients treated with vagus nerve stimulation (VNS) for refractory partial epilepsy. Patients completed a seizure questionnaire, the Quality of Life in Epilepsy-89 (QOLIE-89) questionnaire, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) at baseline and 1 year, and 2 years after activation of VNS. VNS was associated with >or=50% reduction in total seizure frequency in 54% of patients at 1 year and 61% of patients 2 years post-VNS activation compared with baseline. No statistically significant changes from baseline to 12 or 24 months were found in mean quality of life, depression, or anxiety measures in the overall study population. Patients with at least 50% reduction in seizures had significant improvement in anxiety at 12 and 24 months compared with patients who did not have the same degree of seizure reduction.     

Gabapentin to control seizures in children undergoing cancer treatment

Hepatic clearance of chemotherapy drugs is increased by many antiepilepsy drugs. At our institution, new-onset seizures in children on chemotherapy are treated with gabapentin, a nonhepatic enzyme inducer. The charts of all children given gabapentin for seizures were reviewed. At a median follow-up of 34 months, seizures were controlled in 74% of 50 children given gabapentin monotherapy as initial treatment: 91% of the leukemia group, 57% of the brain tumor group, and 75% of the other tumor group. Seizures were controlled in 49% of 59 children in whom gabapentin was added to other antiepilepsy drugs: 43% of the leukemia group, 53% of the brain tumor group, and 50% of the other tumor group. More than one seizure at presentation, focal neurologic deficits, high-dose methotrexate, brain irradiation, and T2-weighted signal abnormality around the brain tumor cavity predicted uncontrolled seizures. Only 8 children (7%) reported adverse effects, and the drug was discontinued in two. Gabapentin effectively controls seizures in children receiving chemotherapy and is well tolerated.     

Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?

OBJECTIVES: To assess clinical trials for evidence that antiepileptic drugs (AED) aggravate partial seizures. To determine if the methodology used to examine drug efficacy can also be used to examine seizure aggravation. BACKGROUND: It is widely accepted that AED aggravate epilepsy in some patients. However, there is little published objective or quantitative evidence. Most reports concern generalized epilepsies. METHODS: Pharmaceutical companies responsible for the development of five of the new AED were asked to provide data concerning seizure increases during randomized placebo-controlled, add-on clinical trials in patients with uncontrolled partial seizures. Seizure frequency in individual patients taking drug or placebo was compared with the baseline pretreatment seizure frequency. The counterpart of the 50% reduction used in efficacy analyses is a 100% increase, because both represent a twofold change. A dose-response relationship was also explored. RESULTS: More than 40% of subjects in clinical trials of tiagabine (TGB), topiramate (TPM), and levetiracetam (LEV) experienced an increase in seizures while taking a placebo. Seizure increases were no more likely to occur when taking any of the three drugs than taking placebo. A doubling or more of seizure frequency was less likely to occur with TPM or LEV than with placebo but more likely with TGB. However, for TGB, this did not reach significance. There was some evidence for a dose-response effect with TGB but a negative effect with TPM (aggravation less likely with increasing dose). Data on gabapentin and lamotrigine were not provided. CONCLUSIONS: Many patients with partial seizures experience an increase in seizures when a new AED is added to their therapy. However, it occurs no more frequently when taking drug than placebo. It probably represents the spontaneous fluctuation of seizure frequency. When a patient who has started a new AED deteriorates, this is not necessarily a drug effect.     

Long-Term Efficacy and Safety of Zonisamide Monotherapy in Epilepsy Patients

Background and purpose

Zonisamide (ZNS) is a useful antiepileptic drug with a broad therapeutic spectrum. However, there is limited information on the long-term use of ZNS as a monotherapy. This study investigated the long-term effects of ZNS as a monotherapy for the treatment of epilepsy.

Methods

We retrospectively analyzed the records of epilepsy patients treated with ZNS monotherapy at our clinic. We identified outcomes for patients treated with ZNS monotherapy for a minimum of 6 months. Efficacy was quantified as the percentage change in seizure frequency, and safety was assessed by the frequency and types of adverse events.

Results

Sixty patients who received ZNS for a minimum of 6 months were included. The mean duration of treatment was 19.8 months (range, 6-37 months), and the mean ZNS dosage was 255 mg/day (range, 100-500 mg/day). Twenty-seven patients (45%) were seizure-free, and an additional 20 patients (33%) had above 50% seizure frequency reduction at the last follow-up visit. Partial seizures with or without secondary generalization and generalized seizures were well controlled by ZNS, whereas complex partial seizures were not. Forty-eight patients (80%) reported mild-to-moderate adverse events, including memory loss (35%), attention deficit (27%), and weight loss (20%).

Conclusions

Long-term ZNS monotherapy is effective at treating a broad spectrum of seizure disorders, except complex partial seizures. However, a specific adverse event, such as cognitive impairment, is common and long-lasting.