Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial.

OBJECTIVE: To evaluate treatment satisfaction, level of anxiety, confidence about traveling with midazolam nasal spray (MDZ-NS), and health-related quality of life in patients with seizure clusters and their caregivers after repeated, intermittent use of MDZ-NS in the outpatient setting. METHODS: We analyzed the psychosocial outcome data from a phase 3, open-label extension trial (ARTEMIS-2; P261-402; NCT01529034) in patients 12 years of age and older with seizure clusters on a stable regimen of antiseizure medications. Caregivers administered MDZ-NS 5 mg when patients experienced a seizure cluster. A second dose could be given if seizures did not terminate within 10 min or recurred from 10 min to 6 h. Treatment Satisfaction Questionnaire for Medication (TSQM), the Intranasal Therapy Impact Questionnaire (ITIQ), and the Short Form-12 Health Survey version 2 (SF-12v2) were self-administered by patients and/or caregivers at prespecified visits. RESULTS: Of the one hundred and seventy-five patients enrolled in ARTEMIS-2, 161 (92.0%) received ≥ 1 dose of MDZ-NS and had a post-treatment seizure-related assessment and were included in the Efficacy Evaluable Set in this analysis, with a total of 1,998 treated seizure clusters over a median duration of 16.8 months. All TSQM scales showed improvement from the baseline of the double-blind ARTEMIS-1 trial (NCT01390220) to the last visit in ARTEMIS-2, indicating greater satisfaction with MDZ-NS across all domains, with a mean change from baseline of 8.8, 6.1, 4.3, and 6.2 for effectiveness (n = 135), side effects (n = 139), convenience (n = 139), and global satisfaction (n = 138), respectively. Change from baseline in TSQM scores generally increased with repeated MDZ-NS use. In both patients and caregivers, anxiety generally lessened with repeated MDZ-NS use, with a mean improvement in ITIQ scores in patients' anxiety since receiving MDZ-NS from 2.5 (n = 138) to 3.5 (n = 145) from visit 1 to the last visit (and from 2.6 [n = 156] to 3.6 [n = 160] for caregivers), respectively. From visit 1 (screening and enrollment in ARTEMIS-2) to visit 10 (after 16 seizure cluster episodes treated with MDZ-NS), the proportions of patients and caregivers who answered "strongly agree" or "agree" for confidence about traveling with an intranasal spray remained ≥ 79% and generally increased over repeated MDZ-NS use. Small positive mean changes in SF-12v2 scores from baseline to the last visit were observed in both patients and caregivers, respectively, for the domains of physical functioning (0.9, 1.1), role-physical (2.4, 0.3), bodily pain (1.7, 0.3), general health (0.6, 1.2), and role-emotional (2.1, 0.3), and in the physical health component (1.6, 1.0). CONCLUSION: Patients and caregivers perceived MDZ-NS favorably, with improvement from baseline on perceived effectiveness, side effects, convenience, and global satisfaction in the TSQM. This is supported by progressively lower anxiety and higher confidence levels about traveling with MDZ-NS over repeated intermittent use in the ITIQ. The positive mean changes observed in SF-12v2 scores from baseline to the last visit were small in magnitude. Limitations of this exploratory analysis include the open-label trial design and that these questionnaires have not been directly validated in epilepsy to identify clinically important changes; however, this does not mean these findings are not clinically meaningful. Overall, MDZ-NS is a socially acceptable drug device for outpatient treatment of seizure clusters that has the potential to improve quality of life and overall independence.

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.

OBJECTIVE: A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters. METHODS: Patients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded. RESULTS: Of 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. SIGNIFICANCE: In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.

Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: A comparative study of Asian and non-Asian populations.

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4-6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: -30.32%, P = 0.0017; -30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non-Asian population (-35.07%, P = 0.0001; -37.78%, P < 0.0001; -34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, -37.37%, P = 0.0139; non-Asian, -27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non-Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non-Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.

Short-term efficacy and tolerability of rufinamide adjunctive therapy in children with refractory generalised epilepsy.

We evaluated the efficacy and tolerability of rufinamide adjunctive therapy in children with refractory generalised epilepsy. The study cohort consisted of 20 patients with Lennox-Gastaut syndrome, 5 with Dravet syndrome, and 28 with unclassified refractory generalised epilepsy. Patients with more than 50% seizure reduction at three and six months were defined as responders. The overall response rate was 37.7% at three months and 34.0% at six months. At three months, patients with Lennox-Gastaut syndrome (40.0%) and epilepsy with spasms/tonic seizures (38.5%) showed higher response rates than those with Dravet syndrome (20.0%) and epilepsy with myoclonic seizures (20.0%). High response rates in patients with Lennox-Gastaut syndrome (30.0%) and epilepsy with spasms/tonic seizures (38.5%) were sustained throughout the six-month study. The accuracy of, and differences between, responder rates should, however, be interpreted with caution due to the small number of patients. Overall, rufinamide appeared to be effective and reasonably well tolerated in this group of children with refractory generalised epilepsies, although a subgroup of patients with Dravet syndrome and epilepsy with myoclonic seizures were less responsive to rufinamide treatment.

Idiopathic (primary) generalized epilepsy. Traditional versus new antiepileptic drugs.

Idiopathic generalized epilepsies (IGE) are genetic based seizures with normal neurologic exam, intelligence, and imaging studies. Based on the age of onset and prominent seizure type, different syndromes were identified. The purpose of this study is to summarize the characteristics, prognosis, and choices of antiepileptic drugs (AED) in common syndromes of IGE. In addition, we review the updated role of new AEDs in specific syndromes of IGE. The first choice AED is usually valproate. Most drug trials on the effects of new AEDs compared them with placebo and not valproate. However, some of the broad spectrum new AEDs may be considered as the first choice in specific conditions. In true refractory patients, combination therapy and vagal nerve stimulation could be the next option. In the proper management of IGE, neurologists should consider the predominant seizure type, patient gender, co-morbidities, and antiepileptic drugs that may aggravate a specific seizure type.

[Effect of topiramate for patients with intractable epilepsy].

The effects of topiramate (TPM) were evaluated in 51 patients with intractable epilepsy. Callosotomy and hemispherotomy were performed in 16 patients and one patient before the administration of TPM, respectively. The 50% responder rate (50%RR) was recorded in 39% of the total patient population and in 58% of patients with symptomatic location-related epilepsy (SLE). TPM was most effective for frontal lobe epilepsy (FLE), and the 50%RR was recorded in 88% of those patients. TPM (50%RR) was more effective in secondary generalized seizures (in 75%) and complex partial seizures (in 67%) in comparison to that of tonic-clonic seizures (in 44%) and drop attacks (in 29%). Seventy-one percent of the patients with atypical absence seizures increased seizure frequency. The 50%RR was recorded in 22% of the patients who underwent epilepsy surgery, and 29% of those patients also showed seizure aggravation due to TPM. These results suggest the efficacy of TPM for intractable epilepsy.

[Optimal Use of Perampanel in the Treatment of Patients with Epilepsy Based on the Clinical Evidence and Characteristics].

Perampanel (PER) has been used clinically as monotherapy and adjunctive therapy for focal seizures and as adjunctive therapy for generalized tonic-clonic seizures in epilepsy patients in Japan. In recent years in Japan and worldwide, clinical studies have been conducted on patients with various seizure types of epilepsy. The results have shown that PER has broad spectrum properties. The pooled analysis of controlled trials (PERMIT study) showed PER efficacy in patients with status epilepticus, myoclonic seizures, and absence seizures. In addition, PER has been shown to be safe and effective in patients with juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, and elderly-onset epilepsy that are often difficult to treat with narrow-spectrum ASM. In this review article, we summarize the latest findings on PER, and overview the broad spectrum characteristics of PER. In addition, we discuss the optimal use of PER for patients with epilepsy, focusing on low-dose initiation and on slow titration of PER to minimize adverse events. (Received December 7, 2021; Accepted March 29, 2022; Published July 1, 2022).

[Short-term and long-term efficacy of topiramate in refractory generalized epilepsy of children].

Topiramate (TPM) was administered to 25 children with intractable generalized epilepsy. A > or =50% decrease in seizure frequency was observed in 56% and 45% of children at two months and one year after initiation of TPM therapy, respectively. However, efficacy of TPM for Lennox-Gastaut syndrome was low. TPM therapy was discontinued in five of 25 children at 3-5.5 months due to lack of efficacy or aggravation of seizures. No serious adverse effects were observed during TPM therapy. The present study revealed that TPM has clinical efficacy in the treatment of children with intractable generalized epilepsy.

[Peculiarities of pathogenesis, clinical picture and new approaches to the treatment of symptomatic epilepsy in the elderly and geriatric patients].

The purpose of this work was to find out single pathogenetic mechanisms of epilepsy development in elderly patients with chronic brain blood-circulation deficiency. There were results of 49 patients' clinical study aged 64-86, suffering from epilepsy with the disease onset after 60. The correlation between the degree of atherosclerotic lesions of brain vessels and epileptic activity presented in EEG is given in the paper. The clinical example of successful treatment of hemodynamic-valuable stenosis of carotic artery in patients with symptomatic post-stoke epilepsy is supplied. The question of drug ethiopathogenic treatment and anti-convulsant application in elderly patients is discussed.

[Epilepsies and their medical treatment]. / Epilepsien und ihre medikamentöse Behandlung.

During the last decade, medical treatment of epilepsies has not progressed a lot regarding its efficacy, but options have widened considerably. Second generation antiepileptic drugs (AED) have advantages in pharmacokinetics, show an overall better tolerability as compared to old AED, and use new mechanisms of action. This offers the opportunity to invidualization of patient treatment. Whereas several drugs released since 2000 have already established their role in differential treatment of epilepsies, the role of new substances like lacosamide, eslicarbazepine, and retigabine will become clear during the years to come. Presently, new antiepileptic drugs play a key role in the initial treatment of epilepsies, in difficult-to-treat epilepsy syndromes, and recently also in intravenous epilepsy treatment. These treatment options have emerged not only in monotherapy, but also in combination therapy, where the lower tendency of interactions in new antiepileptic drugs like lacosamide, levetiracetam, pregabalin, and zonisamide offers particular advantages.

Some treatments cause seizure aggravation in idiopathic epilepsies (especially absence epilepsy).

Seizure aggravation by antiepileptic drugs (AEDs) is a rare phenomenon, occurring mostly in generalized epilepsies treated with drugs that are more efficacious against partial seizures. Its frequency is greatly overestimated by doctors and especially by patients. There are many other reasons for seizures to deteriorate but they are often not considered. Seizure aggravation by AEDs is important to recognize but equally important not to overdiagnose. It can largely be prevented by accurate syndromic diagnosis and the treatment of generalized epilepsies with drugs that are effective against primary generalized seizures and avoiding those that are not.

[Sulthiame treatment for patients with intractable epilepsy].

We examined the antiepileptic effect and side effects of sulthiame in 28 patients with intractable epilepsy. The patients' ages ranged from 6 months to 34 years (mean: 8 years 7 months), and 26 of them were under 18-years-old. Nineteen patients had severe physical and mental disabilities. Sixteen patients had generalized seizures, and 12 had partial seizures. Sulthiame was administered at the dose of 50-300 mg/day (4-14 mg/kg body weight) as add-on therapy in all except one patient. Among the 28 patients, two with complex partial seizures (7%) became seizure-free. Eight patients (29%) (6 patients with generalized seizures and 2 patients with partial seizures) showed seizure reduction by > 50%. Among these 10 patients who showed positive responses, six developed tolerance within 2-5 months. Side-effects were observed in 5 patients, including enuresis, drowsiness, and drooling, none of which caused discontinuation of treatment. Therefore, we conclude that sulthiame is an effective and safe antiepileptic drug for the treatment of intractable epilepsy.

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy.

INTRODUCTION: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.

Status epilepticus due to tiagabine ingestion.

Tiagabine, in excess dosing scenarios, has been rarely documented to cause status epilepticus. We describe such a case that was not responsive to benzodiazepines, but only to propofol infusion.

The course of epilepsy and seizure control in pregnant women.

To investigate the course of epilepsy and seizure control during pregnancy. 105 pregnant women with epilepsy were studied prospectively during the period from 2013 to 2017. The average age at the onset of epilepsy was 17.4 ± 0.5 years. Seizures during pregnancy were observed in 76 (72.4 ± 4.4%) women. Eleven (10.5 ± 3.0%) women had their first seizure during current pregnancy. Among those 94 women who were diagnosed with epilepsy before pregnancy, 29 (30.9 ± 4.8%) remained seizure free; seizure frequency increased in 27 (28.7 ± 4.7%), decreased in 24 (25.5 ± 4.5%) women, in 14 (14.9 ± 3.7%) remained unchanged. Among 15 women who were seizure free for the 1 year prior to pregnancy 11 (73.3 ± 11.4%) women remained seizure free during pregnancy. The worsening in seizure control during pregnancy occurred in 22 (35.5 ± 6.1%) of 62 women with focal epilepsy and 5 (15.6 ± 6.4%) of 32 with idiopathic generalized epilepsy (OR 2.97, 95% CI 1.0-8.81). Non-compliance with the antiepileptic drug therapy was observed in 20 (19.0 ± 3.8%) pregnant women, seizure frequency increased in 18 (90.0 ± 6.7%) of them compared with 5 (9.8 ± 4.2%) of 51 of those who followed correct antiepileptic drug regimen (p < 0.001). The risk of seizures during pregnancy was lower in women who were seizure-free for the 1 year prior to pregnancy; focal epilepsy was associated with an increased risk of seizure relapse during pregnancy; non-compliance with the antiepileptic drug therapy and inappropriate treatment may lead to worsening of seizure control and to the status epilepticus during pregnancy.

A Randomized Controlled Trial of Phenobarbital and Levetiracetam in Childhood Epilepsy.

Levetiracetam has been introduced for the control of seizures besides phenobarbital as monotherapy in children with epilepsy. This study was aimed to compare the effectiveness of these two drugs for the control of seizures in epilepsy. This randomized controlled trial was done to assess the efficacy and tolerability of levetiracetam compared to phenobarbital in childhood epilepsy and was conducted in Institute of Pediatric Neurodisorder and Autism (IPNA), Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh among children between 1 month to 15 years who were diagnosed as cases of epilepsy (idiopathic focal, generalized, focal with secondary generalization) according to ILAE to assess the effect of Levetiracetam (n=50) and Phenobarbital (n=68) from May 2015 to July 2016. The children were followed up for 12 months at 3 months interval to compare the seizure remission and side effects of Levetiracetam and Phenobarbital. The children in levetiracetam group was about 10 months older along with older age of onset of seizure (p=0.02) than those of phenobarbital group (p=0.03 and 0.02 respectively). GTCS was the most common type of seizure in both groups. During 3 months of intervention 55.8% patients of levetiracetam group achieved 50-75% seizure remission compared to 44.2% in phenobarbital group, at 6 months period 75-100% seizure remission observed among 57.4% patients of levetiracetam group compared to 42.6% of phenobarbital group (p=0.06), which continued to increase at 9 months in levetiracetam (n=33, 55.9%) compared to phenobarbital (n=26, 44.1%) and this value is statistically significant (p=0.05). No further improvement observed at 12 months follow up. Behavioral problem was reported among 4 patients of phenobarbital group without any evidence of cognitive deterioration, only 3 patients of levetiracetam experienced irritability, but no children of both group discontinued treatment due to side effects. Levetiracetam mono-therapy is more effective in controlling seizures in focal, generalized and focal with secondary generalization epilepsy compared to phenobarbital with minimum side effects.

Corpus callosotomy via laser interstitial thermal therapy: a case series.

Corpus callosotomy has been used as a form of surgical palliation for patients suffering from medically refractory generalized seizures, including drop attacks. Callosotomy has traditionally been described as involving a craniotomy with microdissection. MR-guided laser interstitial thermal therapy (MRg-LITT) has recently been used as a minimally invasive method for performing surgical ablation of epileptogenic foci and corpus callosotomy. The authors present 3 cases in which MRg-LITT was used to perform a corpus callosotomy as part of a staged surgical procedure for a patient with multiple seizure types and in instances when further ablation of residual corpus callosum is necessary after a prior open surgical procedure. To the authors' knowledge, this is the first case series of corpus callosotomy performed using the MRg-LITT system with a 3.3-year average follow-up. Although MRg-LITT is not expected to replace the traditional corpus callosotomy in all cases, it is a safe, effective, and durable alternative to the traditional open corpus callosotomy, particularly in the setting of a prior craniotomy.

[Pathomorphosis of idiopathic generalized epilepsy. Juvenile forms]. / Patomorfoz idiopaticheskoi generalizovannoi épilepsii. Iuvenil'nye formy.

AIM: To investigate the pathomorphosis of idiopathic generalized epilepsy (IGE) in the aspect of prognosis. MATERIAL AND METHODS: The study involved 1480 patients with epilepsy including 281 patients with IGE. RESULTS AND CONCLUSION: 'Juvenile' forms were diagnosed in 228 patients. Relapse of seizures in anamnesis occurred in 19% out of 105 patients with juvenile myoclonic epilepsy (JME). Remission was achieved in 59.2% out of 76 patients with long-term follow-up. Out of 35 patients with juvenile absence epilepsy (JAE), relapse of seizures in anamnesis occurred in 25.7%. Out of 24 patients with long-term follow-up, remission was achieved in 70.8%. Out of 88 patients with IGE with generalized tonic clonic-seizures, relapse of seizures in anamnesis occurred in 15%. Out of 60 patients with long-term follow-up, remission was achieved in 86.7%. The main features of epilepsy pathomorphosis in all groups of patients were the decrease of informativeness of routine EEG, reduction in the frequency and duration of seizures, occurrence of seizures in the discontinuation of therapy and/or under the influence of provoking factors.

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.

Perampanel for the treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.

INTRODUCTION: The non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs. AREAS COVERED: Data sources included MEDLINE, EMBASE, Google Scholar and ClinicalTrials.gov, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015). EXPERT OPINION: A placebo-controlled clinical phase III study including 164 patients (≥ 12 years) with pGTCS in idiopathic generalized epilepsies (IGE) demonstrated efficacy of PER in reducing pGTCS with good tolerability profile, and without aggravating absence seizures or myoclonic seizures. Dizziness, the main adverse event (AE), can be avoided by bedtime administration. Psychiatric AEs ranging from mild depression to aggression and suicidal attempts should be especially monitored in patients with a history of psychiatric disorders. Co-administration of enzyme inducing antiepileptic drugs (AEDs) might decrease PER plasma levels and make dose adjustment necessary. A reduced efficacy of progesterone-containing oral contraceptives should be considered when administering PER to young women. There is lack of evidence on PER treatment in pregnancy. Although no teratogenic effects were observed in animal models, PER is not recommended for women of childbearing age without contraception.