The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood.

PURPOSE: Lamotrigine (LTG), vigabatrin (VGB) and gabapentin (GBP) are three anti-epileptic drugs (AEDs) used in the treatment of children with epilepsy for which long-term retention rates are not currently well known. This study examines the efficacy, long-term survival and adverse event profile of these three agents used as add-on therapy in children with refractory epilepsy over a 10-year period. METHODS: Three separate audits were conducted between February 1996 and September 2000. All children studied had epilepsy refractory to other AEDs. Efficacy was confirmed if a patient became seizure free or achieved >50% reduction in seizure frequency for 6 months or more after starting therapy. Adverse events and patient survival for each drug were recorded at the end of the study period. RESULTS: Between September 1990 and February 1996, 132 children received LTG, 80 VGB and 39 GBP. At the 10-year follow-up audit, 33% of the children on LTG had a sustained beneficial effect on their seizure frequency in contrast to 19% for VGB and 15% for GBP. No significant difference in efficacy was found in children with partial seizures. Children with epileptic encephalopathy (EE) including myoclonic-astatic epilepsy and Lennox-Gastaut Syndrome (LGS) achieved a more favorable response to LTG. The main reasons for drug withdrawal were lack of efficacy for VGB, apparent worsening of seizures for GBP and the development of a rash for LTG. CONCLUSIONS: Lamotrigine is a useful add-on therapy in treating children with epilepsy. It has a low adverse event profile and a sustained beneficial effect in children with intractable epilepsy.     

The New Antiepileptic Drugs and Women: Efficacy, Reproductive Health, Pregnancy, and Fetal Outcome

Summary: As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues in clude gender-specific efficacy and tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs ap pear to be at risk for compromised bone health, for dis turbances in fertility, menstrual cyclicity, ovulatory func tion, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabap-entin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development pro cess had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy ex posures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential infor mation about teratogenic effects be acquired in an accept ably short time.     

Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy

PURPOSE: This randomised, double-blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy. METHODS: Patients with partial seizures with and/or without secondary generalization or primary generalized tonic-clonic seizures were randomized to either GBP or LTG. During 2- and 6-week titration periods, respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the subsequent 24-week maintenance phase, the dose could be adjusted based on seizure control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300 mg/day for LTG. The primary end point was time to exit, a composite of efficacy and tolerability. Evaluable patients were used for the primary efficacy analysis, whereas tolerability was examined on an intent-to-treat basis. RESULTS: A total of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the evaluable population. Nineteen patients in each group had an exit event. The median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was estimated as 1.043 (90% confidence intervals, 0.602-1.809). Overall, 106 (71.6% of the evaluable population) GBP-treated and 96 (67.1%) LTG-treated patients completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%) taking LTG remained seizure free during the final 12 weeks of treatment. Only 14 (8.9%) GBP-treated patients and 15 (9.9%) LTG-treated patients withdrew because of study drug-related adverse events. CONCLUSIONS: GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.     

Long-term retention rates of new antiepileptic drugs in adults with chronic epilepsy and learning disability

We compared the long-term retention rates of several newly licensed antiepileptic drugs (AEDs) in a residential community of adults with chronic epilepsy and learning disability. Data relating to duration of therapy, maximum dose, and tolerability of six new AEDs-gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TIA), and topiramate (TPM)-were collected. Drug retention at 2 years was 85% (OXC), 57% (LTG), 56% (LEV), 45% (TPM), 24% (TIA) and 15% (GBP). OXC was used mainly as a substitute for carbamazepine. LTG, LEV, and TPM were all associated with retention rates higher than those of GBP or TIA. TPM had the highest rate of adverse event development at the maximum tried dose (60%), whereas LEV had the lowest (16%). Experience from this single epilepsy community study indicated limited impact for GBP or TIA but higher retention of OXC, LEV, LTG, and TPM in patients with chronic epilepsy and learning disability.     

Comparison of the efficacy and tolerability of new antiepileptic drugs: what can we learn from long‐term studies?

OBJECTIVE: A review of long-term open-label studies was performed with the aim of detecting differences in efficacy and/or tolerability of new antiepileptic drugs (AEDs). METHODS: From more than 500 open studies conducted to evaluate the efficacy and tolerability of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB), tiagabine (TGB), topiramate (TPM) or zonisamide (ZNS), we selected all studies that reported or allowed us to calculate the number of patients who achieved seizure freedom for 6 months and/or the number of patients withdrawing for adverse effects and/or the number or percentage of patients continuing treatment after 1 year. RESULTS: No studies were found in which this information was available for OXC, PGB, TGB or ZNS. The number of patients who achieved seizure freedom for 6 months was reported in four studies each for GBP and TPM, five studies for LTG, and eight studies for LEV. The best efficacy profile using this end point was found for LEV, followed by TPM, LTG, and GBP. Twenty-two studies reported the number of patients withdrawing due to adverse effects. LEV was the best-tolerated AED, a little ahead of LTG, and significantly better than GBP or TPM . TPM was by far the least well-tolerated drug. Information concerning patients continuing treatment after 1 year was reported in two GBP studies, two TPM studies, six LEV studies and five LTG studies. GBP had a very low retention rate (between 20% and 25% of patients continued the drug), while TPM and LTG had a retention rate of 40-60% and LEV had a retention rate of 60-75%. CONCLUSION: One limitation of these rankings is that their statistical value is limited because of the indirect nature of the comparisons. Anyhow, this review covers the main studies published thus far on this subject and provides full updated information on the current literature about these drugs.     

Prognostic factors affecting long-term retention of topiramate in patients with chronic epilepsy

PURPOSE: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. METHODS: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. RESULTS: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. CONCLUSIONS: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.     

Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy

PURPOSE: We sought to determine the long-term retention rates of lamotrigine (LTG), gabapentin (GBP), and topiramate (TPM) therapy for patients at a tertiary referral clinic for chronic, refractory epilepsy. METHODS: We analyzed 424 consecutive patients with chronic, refractory partial and/or generalized epilepsy who were started on LTG, 158 patients who were started on GBP, and 393 patients who were started on TPM. The percentages of patients who continued therapy with LTG, GBP, and TPM were estimated with the use of Kaplan-Meier survival analysis. Factors that influence retention were analyzed with the use of Cox regression analysis. RESULTS: Kaplan-Meier survival analysis showed that at 3 years, 30% continued therapy on TPM compared with 29% on LTG and fewer than 10% on GBP. Adverse events resulted in therapy withdrawal in 40% of patients on TPM compared with GBP (37%) and LTG (22%). Perceived lack of efficacy led to treatment withdrawal in 39% of patients on GBP compared with 34% on LTG and 19% on TPM. Cox regression estimated that a fourth or fewer of patients with chronic partial epilepsy are likely to continue therapy with a new antiepileptic drug beyond 5 years. CONCLUSIONS: The impact of these new antiepileptic drugs on the long-term course of chronic partial epilepsy is likely to be small, as approximately three of four patients will discontinue therapy. More patients appear to continue on TPM compared with LTG or GBP, with a possible reason being better perceived efficacy of TPM, despite having the highest incidence of adverse events.     

Pharmacokinetic Profile of Topiramate in Comparison with Other New Antiepileptic Drugs

Summary: Antiepileptic drugs (AEDs) in broad use today have a number of pharmacokinetic liabilities, including a propensity for clinically meaningful drug interactions. Therefore, new AEDs with improved pharmacokinetic characteristics would be welcomed. The pharmacokinetic proftles of six newer AEDs—topiramate (TPM), gaba-pentin (GBP), vigabatrin (VGB), lamotrigine (LTG), ox-carbazepine (OCBZ), and felbamate—were reviewed. Some of these AEDs offer an improvement in one or more pharmacokinetic parameters compared with traditional AEDs, with TPM, GBP, VGB, and OCBZ demonstrating the most advantageous overall pharmacokinetic profiles.     

Utility of the Lethargic (lh/lh) Mouse Model of Absence Seizures in Predicting the Effects of Lamotrigine,Vigabatrin, Tiagabine,Gabapentin, and Topiramate Against Human Absence Seizures

Summary: Purpose: Traditional methods of preclinical screening have predicted the effects of a putative antiepi-leptic drug (AED) against human absence seizures by testing its efficacy against clonic seizures in the high-dose pen-tylenetetrazole (PTZ) model. This high-dose PTZ model correctly predicted the efficacy of ethosuximide (ESM), benzodiazepines, and valproate (VPA) and the lack of efficacy of phenytoin (PHT) and carbamazepine (CBZ). However, the high-dose PTZ model erred in predictions for (a) phenobarbital (PB) (PTZ: efficacy; human: noneffi-cacy); (b) lamotrigine (LTG) (PTZ nonefficacy; human: efficacy); (c) vigabatrin (VGB) (PTZ: nonefficacy; human: proabsence effect); and (d) tiagabine (TGB) (PTZ efficacy; human: possibleproabsence). It also appears to have erred in predictions for gabapentin (GBP) (PTZ efficacy) and topiramate (TPM) (PTZ: efficacy). Because the lh/lh genetic model of absence seizures correctly predicted effects of ESM, clonazepam, VPA, PHT, CBZ, and PB against human absence seizures, we performed this study to test the predictive utility of the lWZh model for LTG, VGB, TGB, GBP, and TPM. Methods: Bipolar recording electrodes were implanted bilaterally into frontal neocortex of 8–week-old male lWZh mice. With the exception of VGB, vehicle or drugs were administered intraperitoneally (i.p.) on alternating days, and an EEG was used to record effects on seizure frequency. With VGB, vehicle was administered i.p. on day 1, and gradually increasing doses of VGB were administered on successive days. Drug and vehicle effects were compared in corresponding lfi-min epochs of the 150–min period after administration. Results: LTG (4.8–144 μmol/kg) significantly (p < 0.04) reduced seizure frequency (by 6.5%) compared with vehicle. In contrast, VGB (0.35–11 mmol/kg) and TGB (0.27–27 μmol/kg) significantly increased seizure frequency (300– 700%) and seizure duration (1,700–1,800%; p ≤ 0.001). GBP (18μmol/kg to 1.8 mmol/kg) and TPM (8.9–29.5 pmol/kg) had no significant effect on seizure frequency. Conclusions: In contrast to the high-dose PTZ model, the lh/lh model correctly predicted the antiabsence effect of LTG, the possible proabsence effects of VGB and TGB, and the lack of effect of GBP and TPM. The lWlh model appears to be superior to the high-dose PTZ model in predicting efficacy of putative AEDs against human absence seizures.     

The New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability

: Purpose: Gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS) are all in use as “add-on” treatment for patients with refractory epilepsy. There have been no comparative randomized controlled trials allowing an evidence-based choice between these drugs. We report a series of meta-analyses of randomized placebo-controlled add-on trials in which these drugs have been tested in patients with partial epilepsy. This work provides an estimate of each drug's efficacy and tolerability compared with placebo. These estimates are compared across drugs to give broad estimates of comparative efficacy and tolerability. Methods: Trial reports were found by searching Medline, by searching through journals by hand, and by contacting the pharmaceutical industry. The outcomes chosen were the proportion of patients who (a) have a 350% reduction in seizure frequency (50% responders); (b) withdrew from the study (any reason); or (c) reported the following side effects: ataxia, dizziness, fatigue, nausea, or somnolence. Overall odds ratio (OR) with 95% confidence intervals (CIS; 50% responders) or 99% CIS; side effects) were calculated. Results: Twenty-nine trials were included, representing 4,091 randomized patients. The ORs for 50% response (95% CI) were GBP, 2.29 (1.53–3.43); LTG, 2.32 (1.47–3.68); TGB, 3.03 (2.01–4.58); TPM, 4.07 (2.87–5.78); VGB, 3.67 (2.44–5.51); and ZNS, 2.7 (1.36–4.47). ORs for discontinuation were GBP, 1.36 (0.75–2.49); LTG, 1.19 (0.79–1.79); TGB, 1.81 (1.21–2.70); TPM, 2.56 (1.64–4.00); VGB, 2.58 (126–5.27); and ZNS, 4.23 (1.71–10.49). Conclusions: We have clear evidence that each of these drugs is better than placebo at preventing seizures. When results are compared across drugs, the confidence intervals overlap, and we have no conclusive evidence of differences in efficacy or tolerability. Despite this, the agent that appears most effective may be twice as effective as the agent that appears least effective, and the agent that appears most likely to cause discontinuation may be 4 times more likely to do so than the treatment that appears least likely to do so. Comparative randomized studies are needed further to evaluate these drugs.     

An Overview of the Efficacy and Tolerability of New Antiepileptic Drugs

Summary: To evaluate the efficacy and tolerability of recently developed antiepileptic drugs (AEDs), a systematic review of placebo-controlled, randomized controlled trials (RCTs) of the AEDs as add-on therapy in refractory partial epilepsy was conducted. Two or more RCTs meeting our inclusion criteria were found for gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS). The outcome selected for estimation of efficacy was the proportion of patients experiencing a ≥50% reduction in seizure frequency from baseline. Tolerability was estimated on the basis of rates of patient withdrawal from study for any reason. Efficacy and tolerability odds ratios (ORs) and 95% confidence intervals (95% CIs) for each measure were generated for each trial included in the analysis, and overall efficacy and tolerability ORs were calculated for each AED across all trials and drug dosages evaluated. Because 95% CIs for both efficacy and tolerability overlapped for the six drugs, conclusive evidence of between-drug differences in effectiveness or safety were not obtained from the analysis. However, the data suggest that the drug with the highest OR for efficacy (TPM) may be approximately twice as effective as the AED with the lowest OR for efficacy (GBP), and that the treatment that appears to most frequently cause withdrawal (ZNS) may be about four times more likely to do so that the AED with the lowest withdrawal rate (LTG). RCTs comparing newer AEDs with the older standard drugs and with each other are needed to further evaluate their relative utility.     

Role of Vigabatrin and Lamotrigine in Treatment of Childhood Epileptic Syndromes

Summary: Purpose: Vigabatrin (VGB) and lamotrigine (LTG) are two new antiepileptic drugs (AEDs) with different mechanisms of action for treatment of refractory epilepsies. Previous reports have indicated efficacy of both drugs in a number of epileptic syndromes.
Methods: We compared these new AEDs drugs to determine their respective efficacy against different types of epileptic syndrome and to develop a rational approach to their use. We reviewed the charts of 105 children, with partial and generalized epilepsies.
Results: VGB was to be significantly more effective in children with partial epilepsies, and LTG was more effective in those with generalized epilepsies.
Conclusions: VGB and LTG have different therapeutic profiles. Combination treatment with the two drugs may represent rational polytherapy for patients with epilepsy resistant to treatment with either drug alone or as add-on to other AED treatment.     

Effect of antiepileptic drugs on spontaneous seizures in epileptic rats

The present study investigated whether spontaneously seizing animals are a valid model for evaluating antiepileptic compounds in the treatment of human epilepsy. We examined whether clinically effective antiepileptic drugs (AEDs), including carbamazepine (CBZ), valproic acid (VPA), ethosuximide (ESM), lamotrigine (LTG), or vigabatrin (VGB) suppress spontaneous seizures in a rat model of human temporal lobe epilepsy, in which epilepsy is triggered by status epilepticus induced by electrical stimulation of the amygdala. Eight adult male rats with newly diagnosed epilepsy and focal onset seizures were included in the study. Baseline seizure frequency was determined by continuous video-electroencephalography (EEG) monitoring during a 7 days baseline period. This was followed by a 2-3 days titration period, a 5-7 days treatment period, and a 2-3 days wash-out period. During the 5-7 days treatment period, animals were treated successively with CBZ (120 mg/kg/day), VPA (600 mg/kg/day), ESM (400 mg/kg/day), LTG (20 mg/kg/day), and VGB (250 mg/kg/day). VPA, LTG, and VGB were the most efficient of the compounds investigated, decreasing the mean seizure frequency by 83, 84, and 60%, respectively. In the VPA group, the percentage of rats with a greater than 50% decrease in seizure frequency was 100%, in the LTG group 88%, in the VGB group 83%, in the CBZ group 29%, and in the ESM group 38%. During the 7 day treatment period, 20% of the VPA-treated animals and 14% of the CBZ-treated animals became seizure-free. These findings indicate that rats with focal onset spontaneous seizures respond to the same AEDs as patients with focal onset seizures. Like in humans, the response to AEDs can vary substantially between animals. These observations support the idea that spontaneously seizing animals are a useful tool for testing novel compounds for the treatment of human epilepsy.     

A Pharmacoepidemiologic Study of Factors Influencing the Outcome of Treatment with Lamotrigine in Chronic Epilepsy

PURPOSE: To identify prognostic factors for freedom from seizures and long-term retention of treatment in patients receiving lamotrigine (LTG). METHODS: A multicenter, retrospective, case record study of 1,050 patients with chronic epilepsy was carried out. Logistic regression and Cox regression analyses were used to identify clinical features associated with freedom from seizures and retention of treatment, respectively. Long-term retention rates of LTG therapy were estimated using Kaplan-Meier survival analysis. RESULTS: The 1,050 patients with chronic epilepsy were included in the study. Patients with generalized epilepsy (p = 0.01), who were not receiving carbamazepine (CBZ; p = 0.02) were more likely to become seizure-free. Sixty percent of patients continued on LTG therapy >1 year and estimated retention at 8 years was 38%. Patients with generalized epilepsy (p = 0.002), patients receiving concurrent sodium valproate (VPA; p < 0.0001), those not previously exposed to gabapentin and vigabatrin (p < 0.0001), and those in whom the starting dose was lower (p < 0.0012), were more likely to remain on long-term treatment with LTG. The relationships with exposure to other antiepileptic drugs remained significant in patients with focal and with generalized epilepsy when considered separately. CONCLUSIONS: The best results from LTG treatment in terms of freedom from seizures and long-term retention of treatment were obtained in patients with generalized epilepsy. Retention of treatment was enhanced by VPA not only in generalized but also in focal epilepsy. The importance of a low starting dose of LTG was again confirmed. The apparent negative effect of CBZ in patients taking LTG merits further investigation.     

Pharmacological outcomes in newly diagnosed epilepsy

The response to antiepileptic drugs (AEDs) has been examined in 780 adult and adolescent patients with newly diagnosed epilepsy presenting with a range of seizure types and epilepsy syndromes over a 20-year period. Carbamazepine (CBZ, n=312), sodium valproate (VPA, n=315), and lamotrigine (LTG, n=249) were the most common AEDs prescribed as monotherapy. More patients with localization-related epilepsies became seizure free with LTG (63%) than with CBZ (45%, P=0.006) or VPA (42%, P=0.006). For idiopathic generalized epilepsies a greater proportion of patients achieved control with VPA (68%) than with CBZ (31%) or LTG (45%). In particular, more patients with juvenile myoclonic epilepsy responded to VPA (75%) compared with LTG (39%, P=0.014). Seizure freedom was achieved with modest or moderate daily doses (median CBZ 400mg, VPA 1000 mg, (LTG) 150 mg) of all three AEDs in the majority of patients achieving remission. Time to first seizure did not differ among these three drugs when given as first treatment. Adverse effects leading to withdrawal were more frequent with CBZ (16%) than with VPA (7%, P=0.03) or LTG (7%, P=0.018). In patients failing initial monotherapy, response to a combination of two AEDs (27%) was not different from that with alternative monotherapy (32%). The majority of patients with newly diagnosed epilepsy responding to treatment did so rapidly and completely with moderate doses of AEDs, with no differences in time to first seizure.     

Overview of the Safety of Newer Antiepileptic Drugs

Summary: Standard antiepileptic drugs (AEDs) are associated with a wide variety of acute and chronic adverse events and with many interactions with each other and with non-AEDs that complicate patient management. The safety and interaction profiles of the newer AEDs have also been intensively studied. Safety data are available for six of the newer AEDs, lamotrigine (LTG), vigabatrin (VGB), gabapentin (GBP), tiagabine (TGB), felbamate (FBM), and topiramate (TPM). The potential for the most recently developed AEDs for producing rare idiosyncratic reactions cannot be ascertained until additional patient exposures have been reported from careful postmarketing surveillance.     

Comparative retention rates and long-term tolerability of new antiepileptic drugs.

OBJECTIVE: Retention rates of five new anti-epileptic medications (AEDs) were compared in order to evaluate their long-term tolerability and efficacy. METHOD: We acquired the retention data on levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), topiramate (TPM), and zonisamide (ZNS) from the electronic database. The data included patient's age, gender, seizure type, current and previous medications, dosage, main reasons for discontinuation, and duration of therapy. The retention rates of these AEDs were evaluated at 4, 12, 24, 52, and 104 weeks. RESULTS: A total of 828 new AED exposures were obtained (LEV=196, LTG=251, OXC=97, TPM=156, ZNS=128) from patients with partial or generalized epilepsy. At 2 years, retention rate was highest with LTG (74.1%), followed by ZNS (60.2%), OXC (58.8%), LEV (53.6%), and TPM (44.2%). When these AEDs were discontinued, it was mainly due to inefficacy (29.5%) and sedating side-effects (20.5%), and commonly within 6 months into therapy. Several important AED specific side-effects leading to discontinuation were identified, including behavioral or irritability from LEV, rash from LTG and OXC, nausea from OXC and ZNS, hyponatremia from OXC, and kidney stones from TPM and ZNS. CONCLUSION: Comparing retention rates of new AEDs can provide useful insight into their tolerability and efficacy. This study showed highest retention rate with LTG, which was significantly different from ZNS (p=0.0025), LEV (p<0.0001), OXC (p=0.0024), and TPM (p<0.0001). Beside ineffectiveness, other leading causes of discontinuation were adverse behavioral effects with LEV, rash with LTG and OXC, and sedation for TPM and ZNS.