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.

Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure.

BACKGROUND: Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use. METHODS: We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control. RESULTS: The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score-adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine. CONCLUSIONS: The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.).

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: a 12 week, randomized, double-blind, pilot study.

Topiramate (TPM), a GABA/glutamate modulator, has shown positive results for treating alcohol use disorder (AUD), but causes significant cognitive adverse effects. TPM causes cognitive side effects by reducing glutathione levels in the frontal lobe. N-acetyl cysteine (NAC) increases level of intracellular glutathione. We hypothesized that combining NAC with TPM may mitigate the possible cognitive side effects of TPM, as well as working synergistically in reducing alcohol consumption more efficaciously than using TPM alone. A 12-week, double-blind randomized trial assessing the effects of combining NAC (1200 mg/day) with TPM (200 mg/day) vs TPM alone (i) cognitive side effects caused by TPM, (ii) percentage of heavy drinking days (PHDD) and percentage of days abstinent (PDA) using weekly calendar, and (iii) craving outcomes using the obsessive-compulsive drinking scale. Seventeen participants were randomized into the study (nine received TPM + NAC and eight matching TPM + Placebo). Cognitive adverse events were not significantly different between the treatment arms (P = 0.581). There was no difference in PHDD (P = 0.536) and in PDA over the entire study period (P = 0.892). However, both treatment groups at study end, compared with the baseline, significantly reduced their PHDD and increased their PDA. As for cravings: TPM + NAC group has shown higher level in automaticity of drinking (P = 0.029) and interference due to drinking (P = 0.014) subscales compared with the TPM + Placebo group. No difference was observed between groups in terms of Drinking Obsessions and Alcohol Consumption subscales. This pilot study indicates that combining NAC with TPM is overall safe, but the addition of NAC has no significant benefit over placebo in the incidence of TPM-related cognitive impairment, and alcohol drinking. Furthermore, craving outcomes may become worse with the addition of NAC.

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial.

Importance: Cryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence. Objective: To determine whether topiramate can slow decline in intraepidermal nerve fiber density (IENFD) and/or neuropathy-specific quality of life measured using the Norfolk Quality of Life-Diabetic Neuropathy (NQOL-DN) scale. Design, Setting, and Participants: Topiramate as a Disease-Modifying Therapy for CSPN (TopCSPN) was a double-blind, placebo-controlled, randomized clinical trial conducted between February 2018 and October 2021. TopCSPN was performed at 20 sites in the National Institutes of Health-funded Network for Excellence in Neurosciences Clinical Trials (NeuroNEXT). Individuals with CSPN and metabolic syndrome aged 18 to 80 years were screened and randomly assigned by body mass index (<30 vs ≥30), which is calculated as weight in kilograms divided by height in meters squared. Patients were excluded if they had poorly controlled diabetes, prior topiramate treatment, recurrent nephrolithiasis, type 1 diabetes, use of insulin within 3 months before screening, history of foot ulceration, planned bariatric surgery, history of alcohol or drug overuse in the 2 years before screening, family history of a hereditary neuropathy, or an alternative neuropathy cause. Interventions: Participants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day. Main Outcomes and Measures: IENFD and NQOL-DN score were co-primary outcome measures. A positive study was defined as efficacy in both or efficacy in one and noninferiority in the other. Results: A total of 211 individuals were screened, and 132 were randomly assigned to treatment groups: 66 in the topiramate group and 66 in the placebo group. Age and sex were similar between groups (topiramate: mean [SD] age, 61 (10) years; 38 male [58%]; placebo: mean [SD] age, 62 (11) years; 44 male [67%]). The difference in change in IENFD and NQOL-DN score was noninferior but not superior in the intention-to-treat (ITT) analysis (IENFD, 0.21 fibers/mm per year; 95% CI, -0.43 to ∞ fibers/mm per year and NQOL-DN score, -1.52 points per year; 95% CI, -∞ to 1.19 points per year). A per-protocol analysis excluding noncompliant participants based on serum topiramate levels and those with major protocol deviations demonstrated superiority in NQOL-DN score (-3.69 points per year; 95% CI, -∞ to -0.73 points per year). Patients treated with topiramate had a mean (SD) annual change in IENFD of 0.56 fibers/mm per year relative to placebo (95% CI, -0.21 to ∞ fibers/mm per year). Although IENFD was stable in the topiramate group compared with a decline consistent with expected natural history, this difference did not demonstrate superiority. Conclusion and Relevance: Topiramate did not slow IENFD decline or affect NQOL-DN score in the primary ITT analysis. Some participants were intolerant of topiramate. NQOL-DN score was superior among those compliant based on serum levels and without major protocol deviations. Trial Registration: ClinicalTrials.gov Identifier: NCT02878798.

Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study.

Objective: To assess the efficacy, safety, and tolerability of topiramate for the treatment of posttraumatic stress disorder (PTSD) in civilians.Methods: This 12-week double-blind, randomized, placebo-controlled study enrolled 72 outpatients (aged 19-64 years) with a DSM-IV-TR diagnosis of non-combat-related PTSD and a score ≥ 50 on the Clinician-Administered PTSD Scale (CAPS). The primary efficacy endpoint, percent change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance. Safety assessments included monitoring of vital signs, physical examinations, clinical laboratory parameters, electrocardiograms, and adverse events (AEs). The study was conducted from October 2001 to March 2004.Results: The intent-to-treat (ITT) population (N = 68; mean age = 35 years; 87% women; 74% White) showed greater percent reduction in total CAPS scores with topiramate versus placebo (39.5% vs 29.5%), but the difference was not statistically significant (P = .31). Similarly, higher reductions with topiramate versus placebo were seen in the CAPS subscale scores for symptoms of reexperiencing (43.6% vs 34.8%), avoidance/numbing (38.3% vs 30.6%), and hyperarousal (36.6% vs 21.4%). However, these differences were not statistically significant. Six patients in the topiramate arm had a final CAPS score < 20, whereas only 2 in the placebo arm achieved the result (P = .075). The median final topiramate daily dose was 100 mg/d (range, 25-400 mg/d), and mean ± SD treatment duration was 55 ± 32 days, showing the tolerability of the medication. In topiramate-treated patients, treatment-emergent AEs included paresthesia, headache, fatigue, and insomnia; treatment-limiting AEs included influenza-like symptoms, agitation, cognitive problems not otherwise specified, and somnolence. However, a higher rate of AE-related discontinuation was seen in the placebo group than in the treatment group (26% vs 18%).Conclusions: In this 12-week civilian PTSD study, topiramate improved the primary and secondary outcome measures at a higher rate than did placebo, but the difference did not reach statistical significance. Further adequately powered studies may be warranted.Trial Registration: Clinical Trials.gov identifier: NCT00208130.Prim Care Companion CNS Disord 2023;25(5):23m03555. Author affiliations are listed at the end of this article.

Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report.

OBJECTIVES: Hypercalcemia has been reported as an uncommon complication of the ketogenic diet (KD). Here we present a toddler whose hypercalcemia persisted for 2 months after stopping the KD. CASE PRESENTATION: A 2 year 11-month-old child with global developmental delay, infantile spasms, neuromuscular weakness with limited mobility, tracheostomy and ventilator dependence, and oropharyngeal dysphagia with G-tube dependence presented with hypercalcemia in the setting of recurrent vomiting. At presentation, the patient was adherent to a KD and taking topiramate since infancy for intractable seizures. His laboratory parameters at presentation showed hypercalcemia (11.9 mg/dL), hypercalciuria, acute renal failure, low alkaline phosphatase (76 IU/L [110-302 IU/L]), parathyroid hormone (PTH) <6 pg/mL (18-80 pg/mL), normal thyroid function, cortisol and vitamin D level. The patient's hypercalcemia persisted post-discontinuation of the KD and topiramate. PTH-related protein was mildly elevated at 15.3 pmol/L. Follow-up laboratory and imaging studies ruled out malignancy. He was managed with calcitonin 4 u/kg/dose Q12H × 1 day and 8 u/kg/dose Q8H × 1 day, hydration and low-calcium formula. Post-discontinuation of the KD, normalization of alkaline phosphatase levels preceded the normalization of calcium on day 55 and PTH on day 85. CONCLUSIONS: Hypercalcemia may persist for an extended period after weaning from a KD; lab parameters may mimic that of hypophosphatasia as previously described in the literature. Normalization of alkaline phosphatase, a marker of bone turnover, indicates recovery from the adynamic state induced by the KD and typically precedes the normalization of calcium and PTH.

European Headache Federation (EHF) critical reappraisal and meta-analysis of oral drugs in migraine prevention - part 3: topiramate.

OBJECTIVE: Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate. METHODS: A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework. RESULTS: Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)]. CONCLUSIONS: There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.

Risk factors of hyperammonemia in epilepsy patients with valproic acid therapy.

BACKGROUND: Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of VPA therapy, early recognition of VHE and identifying its risk factors are important because VHE can lead to loss of consciousness and increased seizure frequency. PURPOSE: The purpose of our study is to evaluate the risk factors of hyperammonemia in epilepsy patients during treatment with VPA therapy. METHODS: We reviewed the medical records of 1084 adult patients with epilepsy and enrolled 116 patients with VPA therapy who had results of blood levels of ammonia over a 3-year period. Hyperammonemia was defined as a blood ammonia level exceeding 80 µg/dL. Correlations of blood levels of ammonia with dosages and blood levels of VPA were evaluated. We further performed univariate and multivariate linear regression analyses to identify risk factors for hyperammonemia in epilepsy patients treated with VPA therapy. RESULTS: Blood levels of ammonia were well correlated with dosages of VPA (p = 0.036), but not with blood levels of VPA (p = 0.463). Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs). Hyperammonemia was also associated with the use of topiramate and phenobarbital. In multivariate analysis, we identified total drug load of ASMs (p = 0.003) and use of topiramate (p = 0.007) as independent predictors of hyperammonemia. Four patients (4/116, 3.4 %) had clinical symptoms of VHE. Three of them had hyperammonemia while the other patient had normal blood level of ammonia with a high blood level of VPA. CONCLUSION: Our study shows that higher total drug loads of concurrent ASMs and use of topiramate were independent risk factors of hyperammonemia in epilepsy patients with VPA therapy. Although the incidence of VHE was not high in our study, clinicians should be aware of this potential adverse effect of VPA therapy, especially in patients with polytherapy of ASMs including topiramate.

Presumed topiramate-induced retinopathy in a 58-year-old woman.

We present a case of presumed topiramate-induced retinopathy in a 58-year-old woman who presented with progressive, bilateral visual loss following a 3- to 4-year history of oral topiramate intake for migraine. She reported difficulty with light adaptation, hemeralopia, and color desaturation. Her best-corrected visual acuity was 1/60 (20/1200) in the right eye and 6/18 (20/60) in the left eye, and she performed poorly on Ishihara color plate testing. Anterior segment examination was normal; dilated funduscopy showed mild macular pigmentary changes. Optical coherence tomography revealed subtle thinning and reduced reflectivity of the subfoveal ellipsoid zone and interdigitation zone bilaterally, associated with increased foveal autofluorescence. Humphrey visual field 24-2 revealed central defects. Electrodiagnostic testing showed a reduced and delayed b-wave and a normal a-wave on photopic full-field electroretinogram (ERG), with normal scotopic responses; multifocal ERG revealed reduced responses in the inner 10° in both eyes. She underwent extensive investigations including whole-body computed tomography and positron emission tomography scan, magnetic resonance imaging of the brain, uveitis screening, retinal autoantibody testing, and genetic testing on the retinal dystrophy panel to rule-out other causes for her presentation, all of which were normal or negative.

Antiseizure medications as migraine preventatives: a call for action for a teratogenic and neurodevelopmental risk removal.

INTRODUCTION: A recent study has demonstrated an increased risk of neurodevelopmental disorders, including autism spectrum disorder, in individuals exposed to either valproate or topiramate monotherapy. Regulatory bodies have initiated a review to reassess the safety of topiramate exposure during pregnancy. These novel findings raise concerns regarding the recommendation of antiseizure medications in women of childbearing potential. This manuscript highlights current research defining concerns specific to the use of valproate and topiramate in women of childbearing potential. AREAS COVERED: This manuscript summarizes recent findings regarding the safety of valproate and topiramate when compared to alternative therapies for the preventative treatment of migraine in women of childbearing potential. The studies included in this review were selected following a comprehensive literature review of multiple relevant databases. All studies that were published within the past 15 years were considered for inclusion. EXPERT OPINION: The use of valproate and topiramate in women of childbearing potential should be highly discouraged. Our recommendations include a review of current prescribing guidelines, further public education regarding the neurodevelopmental and congenital risks associated with the use of valproate and topiramate, and an appeal for further research defining the safety of alternative medications for migraine prevention when intrauterine exposure is possible.

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis.

OBJECTIVE: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. RESULTS: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. CONCLUSIONS: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.

Pharmacokinetics and Safety of Coadministered Atogepant and Topiramate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, and topiramate, a commonly used oral antiepileptic, are approved as preventive migraine treatments. Given the distinct mechanisms of action of these treatments, it is possible that they may be coprescribed for migraine. This open-label, single-center, 2-cohort, phase 1 trial evaluated the potential pharmacokinetic (PK) 2-way drug-drug interactions (DDIs), safety, and tolerability of atogepant and topiramate in healthy adults. Participants received atogepant 60 mg once daily and topiramate 100 mg twice daily. Cohort 1 (N = 28) evaluated the effect of topiramate on the PK of atogepant; cohort 2 (N = 25) evaluated the effect of atogepant on the PK of topiramate. Potential DDIs were assessed using geometric mean ratios and 90% confidence intervals calculated for maximum plasma drug concentration at steady state (Cmax,ss ) and area under the plasma concentration-time curve during the dosing interval at steady state (AUC0-tau,ss ). Additional PK parameters were assessed. Atogepant AUC0-tau,ss and Cmax,ss decreased by 25% and 24%, respectively, with topiramate coadministration. Topiramate AUC0-tau,ss and Cmax,ss decreased by 5% and 6%, respectively, with atogepant coadministration. The 25% reduction in atogepant exposure when coadministered with topiramate is not considered to be clinically relevant and would not require dose adjustments.

[Psychiatric Symptoms of Patients With Epilepsy: Characteristics of Psychiatric Adverse Events by Novel Antiepileptic Medications].

Patients with epilepsy often show treatment-related psychiatric symptoms. Among the novel antiseizure medications (ASM), Perampanel (PER), Levetiracetam (LEV), and Topiramate (TPM) have been reported to have a relatively high frequency of psychiatric adverse events. However, these psychiatric symptoms are not identical; PER and LEV show adverse events of irritability and aggression, while TPM shows typical symptoms of depression and schizophrenia. It is important to understand the characteristics of these psychiatric adverse events to design appropriate treatment regimens for epileptic patients. (Received August 1, 2022; Accepted December 24, 2022; Published April 1, 2023).

Dural Venous Sinus Stent Placement Reduces Dosage Requirements for Carbonic Anhydrase Inhibitors in Patients with Idiopathic Intracranial Hypertension.

This retrospective single-center study evaluated the change in required dosage of acetazolamide and topiramate before and after dural venous sinus stent placement (VSSP) for idiopathic intracranial hypertension (IIH). Adults diagnosed with IIH who failed optimized medical management and were treated with VSSP were included. This study comprised 55 patients who underwent VSSP for the diagnosis of IIH. The median preprocedural dosage of acetazolamide and topiramate was 1,000 mg (range, 500-4,000 mg) and 100 mg (range, 0-200 mg), respectively, among patients able to tolerate the medications. The median postprocedural dosage of acetazolamide and topiramate was 375 mg (range, 0-4,000 mg), with a mean reduction of 52.9% (P = .001), and 0 mg (range, 0-200 mg), with a mean reduction of 45.9% (P = .005), respectively. Dural VSSP significantly reduced dosage requirements for acetazolamide and/or topiramate, potentially reducing the morbidity secondary to medication side effects.

The pharmacokinetics of single oral dose extended-release topiramate and adverse effects after multi-dose administration in healthy cats.

Current treatment options for feline epilepsy are limited to medications that require administration of multiple doses per day or administration of a capsule or large tablet. Expanding the current treatment options could improve patient and owner compliance and optimize seizure control. Topiramate has been used sparingly in veterinary medicine, and limited pharmacokinetic studies have focused on immediate release formulations in dogs. If effective and safe, topiramate extended-release (XR) could broaden the current treatment options for feline epilepsy. The aims of this two-phase study were to establish single-dose pharmacokinetics for topiramate XR in cats, identify a dosing regimen that maintains steady-state plasma drug concentrations within a reference range extrapolated from human medicine (5-20 µg/mL), and evaluate the safety of topiramate XR in cats following multidose administration. Topiramate XR administered orally at 10 mg/kg once daily for 30 days was sufficient to achieve the desired concentrations in all cats. While no clinically apparent adverse effects were observed, four out of eight cats developed subclinical anemia, calling into question the safety of topiramate XR with chronic administration. Further studies are necessary to better understand the potential adverse effects and overall efficacy of topiramate XR for the treatment of feline epilepsy.

Alucinaciones como efecto adverso del topiramato / Hallucinations as an adverse effect of topiramate

El topiramato es un fármaco antiepiléptico que bloquea los canales de sodio voltaje-dependientes y potencia la actividad gabaérgica. Entre sus posibles efectos adversos se han descrito algunos muy infrecuentes como las alucinaciones visuales o auditivas. Presentamos un caso de una niña de 7 años con antecedentes de migraña sin aura sin otros antecedentes personales ni familiares de interés que, tras 15 días de tratamiento preventivo con topiramato, desarrolló alucinaciones, cambios de humor bruscos, negativismo e ideas de muerte. Dada la clínica no explicable por otra circunstancia o fármaco se retiró el topiramato con desaparición completa de los síntomas a los 20 días, sin reaparición de estos. Las alucinaciones son un efecto adverso muy inusual del topiramato. El mecanismo fisiopatológico podría estar relacionado con su efecto sobre la actividad GABA. Existen muy pocos casos de este efecto adverso descritos. En pacientes pediátricos solo se han descrito dos casos, siendo este el primer caso descrito en el contexto de tratamiento profiláctico de la migraña (AU)

Topiramate is an antiepileptic drug which blocks voltage-gated sodium channels and enhances GABAergic activity. We report the case of a 7-year-old girl with a medical history of migraine without aura who, after fifteen days of preventive treatment with topiramate developed visual and tactile hallucinations. She also presented sudden mood swings, negativism and even death ideation. She had no other personal or family medical or psychiatric history. Due to the symptomatology, Topiramate was stopped, with a complete disappearance of symptoms twenty days after its suspension, and without the recurrence of them.Hallucinations are a very unusual side effect of Topiramate. There are very few cases of this adverse effect described in the literature. In pediatric patients, there were only two cases, this being the first case described in the context of prophylactic treatment of migraine. (AU)