Mechanisms of neurodevelopmental toxicity of topiramate.

Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate on the neuromolecular mechanisms by which prenatal exposure may perturb neurocognitive development. Specifically, we explore the potential role of topiramate's pharmacological interactions with ligand- and voltage-gated ion channels, especially GABAergic signaling, its effects on DNA methylation and histone acetylation, whether topiramate induces oxidative stress, and its association with fetal growth restriction as possible mechanisms contributing to neurodevelopmental toxicity. Resolving this biology will be necessary to reduce the risk of adverse pregnancy outcomes caused by topiramate or other ASMs.

Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: Perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.

Medications for Obesity: A Review.

Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia. Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16 964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants). Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.

Structural insights into the allosteric effects of the antiepileptic drug topiramate on the CaV2.3 channel.

The R-type voltage-gated calcium channel CaV2.3 is predominantly located in the presynapse and is implicated in distinct types of epileptic seizures. It has consequently emerged as a molecular target in seizure treatment. Here, we determined the cryo-EM structure of the CaV2.3-α2δ1-ß1 complex in the topiramate-bound state at a 3.0 Å resolution. We provide a snapshot of the binding site of topiramate, a widely prescribed antiepileptic drug, on a voltage-gated ion channel. The binding site is located at an intracellular juxtamembrane hydrophilic cavity. Further structural analysis revealed that topiramate may allosterically facilitate channel inactivation. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of topiramate on CaV and NaV channels, elucidating a previously unseen modulator binding site and thus pointing toward a route for the development of new drugs.

Acupuncture plus topiramate placebo versus topiramate plus sham acupuncture for the preventive treatment of chronic migraine: A single-blind, double-dummy, randomized controlled trial.

BACKGROUND: Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. METHODS: This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100 mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. RESULTS: Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. CONCLUSIONS: Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. TRIAL REGISTRATION: ISRCTN.org Identifier 13563102.

Clinical effectiveness and predictors of response to topiramate plus lifestyle modification in youth with obesity seen in a weight management clinical setting.

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response. Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data. Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point. Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.

Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

PURPOSE: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. METHODS: We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. RESULTS: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. CONCLUSIONS: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Topiramate treatment during adolescence induces short and long-term alterations in the reproductive system of female rats.

Topiramate (TPM) is an antiepileptic drug used for treating epilepsy in children, and migraine in teenagers. In this context, preclinical studies with adult female rats observed reproductive system abnormalities following treatment with TPM. Additionally, exposure to endocrine disruptors during developmental plasticity periods, such as childhood and adolescence, may influence characteristics in the adult individual. This study evaluated whether treatment with TPM during developmental periods influences the reproductive system of female rats either immediately or in adult life. Female Wistar rats were treated with TPM (41 mg/Kg/day) by oral gavage from postnatal day (PND) 16-28, or PND 28-50, which correspond to childhood and adolescence, respectively, and euthanized either 24 h after the final administration or during adulthood. Treatment with TPM during adolescence induced short-term increase in uterus and ovary weights and reduction in endometrial stroma thickness. Adult animals treated during adolescence displayed reduced primordial ovarian follicles' numbers, and increased primary and pre-antral ovarian follicles' numbers. Treatment during childhood induced no short or long-term differences. These results indicate TPM treatment during adolescence is capable of inducing short and long-term alterations on the reproductive system of female Wistar rats.

The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults. METHODS: Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy. RESULTS: Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95 th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment. CONCLUSION: In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.

Topiramate-induced ocular complications: case series.

Several ocular adverse effects have been attributed to Topiramate, a sulfonamide derivative. It can cause problems in the eye such as choroidal effusion syndrome, acute angle closure glaucoma, myopic shift, visual field defects, and Myokymia. If not identified early, it can be vision-threatening. It is commonly used for migraine prophylaxis, partial onset, and generalized tonic-clonic seizures. It has also been prescribed for bipolar disorder and alcoholism. The risk of adverse reactions with this drug is 3%. The prognosis is favorable if it is discontinued early and prompt therapy is initiated. OBJECTIVE: This article reported a case series of topiramate-induced ocular complications. MATERIALS AND METHODS: The patients presented with high intraocular pressure and blurred vision following a topiramate prescription for headache. CONCLUSION: Timely recognition and intervention can prevent potential visual loss in such cases.

Three Patients of the Early Onset Epileptic Spasms without Hypsarrhythmia.

Epileptic spasms without hypsarrhythmia occur when patients do not display hypsarrhythmia on electroencephalogram (EEG) at the onset and throughout the clinical course. We report three patients of epileptic spasms in patients with early onset, all of whom experienced other types of seizures.We detail three patients (two boys and one girl) of epileptic spasms without hypsarrhythmia, occurring between 1 and 3 months of age, with no abnormalities detected on neurometabolic analysis and brain magnetic resonance imaging. Long-term video-EEG monitoring revealed epileptic spasms with focal onset seizures in two patients, and epileptic spasms followed by generalized tonic-clonic seizures in one patient. Hypsarrhythmia was never observed in repeated EEG examinations. Two patients achieved seizure freedom and improved development through treatment with topiramate alone or in combination with valproate, without requiring hormonal therapies or vigabatrin. The remaining patient achieved seizure freedom following administration of antiseizure medications, including topiramate, after a trial of adrenocorticotropic hormone therapy.We report the cases of three patients with early onset epileptic spasms without hypsarrhythmia. All patients achieved seizure freedom after topiramate treatment. Topiramate may be considered as a relatively effective antiseizure medication for early onset epileptic spasms without hypsarrhythmia.

Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs. METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.

Drug-induced lupus erythematosus in childhood: Case-based review.

BACKGROUND: Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than adults. METHODS: In this study, we present four children with DILE and similar published cases through a systematic literature review. RESULTS: We report four children (three girls and one boy) who developed DILE associated with the use of topiramate, doxycycline, etanercept, and ethosuximide. Three of them were positive for anti-histone antibodies. In all patients, the drug was discontinued and symptoms resolved completely. The literature review revealed 48 articles describing 61 children with DILE. In the evaluation of 65 patients (our 4 patients and 61 patients from the literature), the most frequently reported drugs associated with DILE were ethosuximide (n = 13) and minocycline (n = 12). Fever (n = 33), arthralgia (n = 31), rash (n = 30), and arthritis (n = 29) were the most common clinical manifestations. Antinuclear antibody (ANA) was positive in 93.5% of patients and anti-histone antibodies were detected in 72.2% of the patients. As for treatment, the responsible drug was discontinued in all patients, and corticosteroids were initiated in 53.3%. Improvement was achieved in 92.0% of patients. CONCLUSION: For children presenting with SLE features, proper drug history is crucial since DILE may be more frequent than anticipated. An association of the relevant drug with the symptoms, and resolution of symptoms on drug withdrawal provides evidence for the diagnosis of DILE.

Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Comparative analysis of adverse drug reactions associated with new antiseizure medications from the Korea Adverse Event Reporting System database.

OBJECTIVE: This study aimed to compare and characterize the safety profiles of new antiseizure medications (ASMs) using a nationwide pharmacovigilance database from a long-term perspective in Korea. METHODS: We reviewed adverse event reports from the Korea Adverse Event Reporting System database between January 2013 and December 2022 for descriptive analysis of six new ASMs (lacosamide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, and zonisamide). We investigated the frequency and characteristics of adverse drug reactions (ADRs) based on the MedDRA terminology, system organ classes, and modified WHO classification. RESULTS: We identified 5,733 reported cases of ADRs. The commonly reported ADRs associated with total ASMs were rash/urticaria (1,822, 31.8 %), dizziness (409, 7.1 %), somnolence/drowsiness (311, 5.4 %), and hepatotoxic effects (273, 4.8 %). Type B (idiosyncratic) effects (2,932; 51.1 %) were more commonly reported than Type A (related to known drug mechanisms) effects (2,613; 45.6 %). Skin and subcutaneous tissue disorders and type B effects were most commonly reported for lamotrigine and oxcarbazepine, whereas nervous system disorders and type A effects were most commonly reported for lacosamide, topiramate, and zonisamide. The pediatric group (<18 years) exhibited skin and subcutaneous tissue disorders and type B effects relatively more frequently than the adult and older adult groups. CONCLUSION: Hypersensitivity skin reactions and type B effects remained significant ADRs in the new ASMs; however, type A effects were more commonly reported in some ASMs. The pediatric group showed a higher rate of type B effects. Overall, new ASMs should also be used with caution.