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Background: Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA). Methods: We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan–Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline. Results: This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025–1.048). Conclusions: Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder characterized by seizures that cause neurobiological and behavioral impairment. Caffeine (CAF), which is the most widely consumed stimulant in the world, is reported to influence epileptic seizures and antiepileptic drugs, especially topiramate (TPM). The aim of the study was to optimize the zebrafish larvae pentylenetetrazol-induced seizure model for the study of CAF and TPM interactions, which include the determination of dose space, and the delivery of an analytical method for monitoring CAF, TPM, and CAF metabolite paraxanthine (PAR) in Zebrafish larvae. Methods: The zebrafish larvae, 4 days post-fertilization, were incubated for 18 h with CAF, TPM, or CAF + TPM, with subsequent locomotor activity assessment. Seizures were evoked by adding PTZ solution to obtain a final concentration of 20 mM. Subsequently, the liquid chromatography–mass spectrometry (LC–MS/MS) analytical method was used to simultaneously assess the levels of both CAF and TPM in the larvae. CAF (50 mg/L) and TPM (75 μM) given separately decreased the average larvae locomotor activity compared to the PTZ group but, however, were not able to lower it to the control level. Co-administration of 25 mg/L CAF and 50 μM TPM suppressed the activity to the same level. Adding 25 μM TPM to 50 mg/L CAF decrease the measured CAF level in the larvae. Until proven otherwise, CAF consumption should be regarded as a potential determinant in the modulation of TPM's efficacy in the management of epileptic seizures. The optimized model will contribute to the standardization of studying CAF and TPM interactions and building the understanding of the molecular bases of the interaction. [ABSTRACT FROM AUTHOR]

Nucleus accumbens plays an important role in opioid addiction. Topiramate, increases postsynaptic gamma-aminobutyric acid receptor activity and antagonizes glutamatergic activity. Brain-derived neurotrophic factor (BDNF), which plays a key role in synaptic plasticity, is produced from proBDNF. The aim of this study is to investigate the effects of 100 µM topiramate applied into the lateral ventricle or nucleus accumbens on naloxone-induced morphine withdrawal and the BDNF/proBDNF ratio in the frontal cortex. In the study, 36 adult male Wistar rats weighing 250–350 g were used. Morphine dependence was created with morphine pellets following guide cannula implantations. Withdrawal findings were evaluated in naloxone-induced morphine withdrawal syndrome following topiramate administration, and locomotor activity measurements were performed simultaneously. The brains of sacrificed animals were removed for determination of BDNF/proBDNF ratio. Topiramate administered by either route significantly suppressed the number of jumps in morphine withdrawal. Topiramate applied into the nucleus accumbens significantly reduced stereotypical behavior in morphine withdrawal, but did not cause any changes in other locomotor activity behaviors. Topiramate applied into the lateral ventricle significantly decreased the BDNF/proBDNF ratio, whereas administered into the nucleus accumbens significantly increased this ratio. The findings of this study indicate that topiramate administered into the lateral ventricle and nucleus accumbens reduces naloxone-induced morphine withdrawal symptoms, stereotypical locomotor activity, and changes the BDNF/proBDNF ratio. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people globally. In this review we summarised the evidence from randomised controlled trials of gabapentin used as monotherapy for the treatment of focal epilepsy, both newly diagnosed and drug-resistant, with or without secondary generalisation. OBJECTIVE: To assess the effects of gabapentin monotherapy for people with epileptic focal seizures with and without secondary generalisation. METHODS: We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 24 February 2020) on 25 February 2020. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRA), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We also searched several Russian databases, reference lists of relevant studies, ongoing trials registers, conference proceedings, and we contacted trial authors. RESULTS: We found five randomised controlled trials (3167 participants) comparing gabapentin to other antiepileptic drugs (AEDs) and differing doses of gabapentin as monotherapy for newly diagnosed focal epilepsy and drug- resistant focal epilepsy with or without secondary generalisation. Two review authors independently applied the inclusion criteria, assessed trial quality, risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence and present seven patient-important outcomes in the "Summary of findings" tables. The quality of evidence was very low to moderate due to poor reporting quality, poor trial design, and other risks of bias, such as selective presentation of findings and potential heavy industry input. Better quality research may change our certainty in the effect estimates. None of the included trials reported on the number of people with 50% or greater reduction in seizures and time to withdrawal (retention time) in an extractable way. Gabapentin-treated participants were more likely to withdraw from treatment for any cause (285/539) than those treated with lamotrigine, oxcarbazepine, or topiramate pooled together (695/1317) (RR 1.13, 95% CI 1.02 to 1.25; 3 studies, 1856 participants; moderate-certainty evidence), but not carbamazepine. Fewer people treated with gabapentin withdrew from treatment owing to adverse events (190/525) than those treated with carbamazepine, oxcarbazepine, or topiramate (479/1238), (RR 0.79, 95% CI 0.69 to 0.91; 1763 participants, 3 studies; moderate-certainty evidence), but not lamotrigine. CONCLUSION: Gabapentin as monotherapy probably controlled seizures no better and no worse than comparator AEDs (lamotrigine, carbamazepine, oxcarbazepine, and topiramate). Compared to carbamazepine, gabapentin was probably better in retaining people in studies and preventing withdrawals due to adverse events. The most common side effects associated with gabapentin were ataxia (poor co-ordination and unsteady gait), dizziness, fatigue, and drowsiness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Topiramate, an approved antiepileptic drug, was found effective in treating aggressive symptoms in humans and rodents. However, the effects and mechanisms of Topiramate on aggressive behavior are still unclear. Our previous study indicated that intraperitoneal administration of Topiramate successfully decreased aggression and reinforced sociability in socially aggressive mice, and increased cFos-expressing neurons in the anterior cingulate cortex (ACC). In addition to its pharmacological properties, previous studies have approved the neuroprotective effects of Topiramate. These suggest a potential effect of Topiramate on ACC's structure and function. Objectives and Results: In the present study, we first investigated the structural characteristics of ACC in the social isolation-induced aggression paradigm. The results showed that hyper-aggressive behavior in socially aggressive mice was associated with several structural alterations in ACC: increased neuron death combined with decreased neuron density, increased damaged neuronal morphology and increased neuroinflammation markers. Based on these observations, we next investigated the potential neuroprotective effect of Topiramate against structural alterations of ACC observed in socially aggressive mice. Results indicated that intraperitoneal administration of Topiramate (30 mg/kg) decreased aggression and enhanced sociability without affecting locomotor activity. Interestingly, the anti-aggressive effect of Topiramate was associated with decreased neuronal death, ameliorated damaged neuronal morphology, and decreased reactive microglia markers in ACC. Conclusions: Our results provide insights into the structural alterations of ACC in aggressive socially aggressive mice. Moreover, the present study suggested that the anti-aggressive effect of Topiramate could be related to its neuroprotective effects against the structural alterations of ACC. [ABSTRACT FROM AUTHOR]

Background: Because neuropathic pain is currently a poorly understood medical condition, there is a need to identify a more effective therapeutic drug with a low toxicity profile. Purpose: To address the behavioural, oxidative stress, and cytokine-mediated inflammatory pathways involved in sciatic nerve, the current study protocol used Chronic Constriction Injury (CCI) and Streptozotocin (STZ) induced neuropathic pain methods. Materials and Methods: Following CCI to the sciatic nerve and administration of STZ 60mg/kg, rats develop painful neuropathy characterized by hyperalgesia, allodynia, oxidative stress, neuroinflammation, and increased total calcium levels. Results: Topiramate (20, 40, and 80 mg/kg) treatment for two weeks beginning on the 15th day of CCI surgery and ending on the 29th day of diabetes confirmation significantly and dose dependently reduced the development of allodynia and hyperalgesia. Furthermore, topiramate treatment produced significant dose-dependent antioxidant and anti-inflammatory effects by restoring the balance of oxidative stress and decreasing the levels of inflammatory markers such as TNF-a, IL-1, and IL-6, as well as total calcium in sciatic nerve homogenate. Conclusion: To summarize, the treatment with different doses of topiramate produces analgesic, antioxidant, and anti-inflammatory effects in a dose dependent manner, owing to the increased curiosity to understand the underlying pain producing mechanism and its translation into signs and symptoms of CCI and STZ induced neuropathy. [ABSTRACT FROM AUTHOR]

Jeavons syndrome is a common, often misdiagnosed or overlooked epileptic syndrome presenting with a triad of eyelid myoclonia with or without absence seizures, eye closure-induced EEG paroxysms, and photosensitivity. We present a seven-year-old female who presented with eyelid myoclonia evident since birth with absence seizures and migraines with associated photosensitivity. An EEG with photic stimulation confirmed the diagnosis of Jeavons syndrome. Genetic testing showed a heterozygous mutation in the PLCB1 gene which has been linked to early onset epilepsies and encephalopathic epilepsies. This mutation and her clinical presentation identifies another etiology of Jeavons syndrome and confirms it can begin from birth. Its presence highlights the importance of genetic testing in epileptic patients to better understand the links between genetics and epilepsy syndromes so appropriate treatment can be initiated. [ABSTRACT FROM AUTHOR]

Background and Aims: Previous findings have been equivocal as to whether a single‐nucleotide polymorphism (rs2832407) in GRIK1, which encodes a glutamate receptor subunit, moderates the effects of topiramate treatment for drinking reduction. We leveraged intensive longitudinal data to provide greater precision and allow an examination of intermediate outcomes addressing this question. We used data from a randomized controlled trial (RCT) to test the hypotheses that topiramate treatment reduces daily heavy drinking, desire to drink and positive alcohol expectancies and that these effects are stronger in rs2832407*C‐allele homozygotes. Design: Secondary data analysis of a randomized controlled trial. Setting: University of Pennsylvania Treatment Research Center in the United States. Participants/Cases: Participants were 164 individuals (70.1% male, mean age = 51.42, 36.0% rs2832407*C‐allele homozygotes) who sought to reduce or stop drinking. Intervention and Comparator: Participants were assigned to medication (topiramate or placebo), with stratification by genotype group (CC versus AA/AC) and treatment goal (reduce versus abstain). Measurements During the 12‐week treatment period, participants completed daily interactive voice response (IVR) surveys. Findings On any given day during treatment, participants who received topiramate had lower odds of IVR‐reported heavy drinking [odds ratio (OR) = 0.259, b (standard error, SE) = −1.351 (0.334), P < 0.001] and lower levels of desire to drink [b (SE) = −0.323 (0.122), P = 0.009] and positive alcohol expectancies [b (SE) = −0.347 (0.138), P = 0.013] than those who received placebo. Participants who received topiramate also reported greater reductions in positive alcohol expectancies during the first 2 weeks of treatment than those who received placebo [b (SE) = −0.028 (0.008), P = 0.001], but topiramate did not impact the daily rate of change in heavy drinking or desire to drink. Genotype did not moderate the effects of topiramate on any outcomes examined (P > 0.05). Conclusions: Topiramate is an effective medication for individuals seeking to reduce heavy drinking. The effects are not moderated by the single‐nucleotide polymorphism rs2832407. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to investigate the effects of topiramate on pancreatic islets of Langerhans cells in Methotrexate-related pancreatic injury. Materials and Methods: The study was conducted between 04 July - 24 July 2022 in the Animal Research Unit of Recep Tayyip Erdogan University. Male Spraque-Dawley rats were divided into 3 groups with 8 animals in each group. Control group (C) (Only 0.9% saline was administered). A single dose of 20mg/ kg Methotrexate was administered to the MTX group (MTX). The TPM group (TPM) was administered 100 mg/kg/day Topiramate by oral gavage for a total of 14 days, 7 days before and after Methotrexate administration. All subjects were euthanized by anesthesia 16 hours after the last Topiramate dose. Results: We observed widespread edematous areas and necrotic cells in the islets of Langerhans in the MTX. We found that necrotic cells and edematous areas were decreased in the TPM compared to the MTX. We found fewer β cells showing insulin positivity in the MTX compared to the controls (p<0.05). We observed an increase in insulin-positive β-cells in the TPM compared to the MTX (p<0.05). We observed a significant decrease in the number of cells showing glucagon positivity in the MTX compared to the controls (p<0.05). We observed an increased number of α cells showing glucagon positivity in the TPM compared to the MTX (p<0.05). We found that the HDS increased from 0(0-1) in the control group to 6(6-8) in the MTX (p<0.05). It was found as 2(2-3) in the TPM (p<0.05). Conclusion: Our study shows that topiramate has a protective effect on pancreatic islet cells. [ABSTRACT FROM AUTHOR]

Management of patients with BMI≥50 kg/m2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage. Patients with BMI≥50 kg/m2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston–Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46–15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP. By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were −24.44 (−34.46,−14.43)/−28.60 (−40.74,−16.46) in the PT + SG group versus −11.81 (−17.58,−6.05)/−13.89 (−21.32,−6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01). Patients with BMI≥50 kg/m2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this. • We studied blood pressure effects of Phentermine/Topiramate and Sleeve Gastrectomy. • Blood pressure improved with use of Phentermine/Topiramate with Sleeve Gastrectomy. • Antihypertensives were not needed with Sleeve Gastrectomy and Phentermine/Topiramate. • 41% of patients with Sleeve Gastrectomy alone continued antihypertensive medication. [ABSTRACT FROM AUTHOR]

Objective: To examine group differences in self‐reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self‐reported and "nosology‐derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD‐3]) migraine days. Background: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology. Methods: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self‐reported migraine days at trial completion (summed from trial weeks 20–24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD‐3 criteria for migraine without aura, and examined the association between self‐reported and "nosology‐derived" migraine days. Results: Results showed no significant differences between groups in self‐reported migraine days over the course of the trial. Self‐reported and "nosology‐derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001). Conclusion: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self‐reported migraine days over the course of the trial (about 3.8 days less). The strong association between self‐reported and "nosology‐derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed. [ABSTRACT FROM AUTHOR]

Obesity has become an epidemic and a worldwide problem and its treatment is ever-evolving. Apart from diet and exercise, medication and surgery are other options. After disappointing side effects of various obesity drugs, new treatments showed promising results. This review discusses the following anti-obesity drugs: liraglutide, semaglutide, tirzepatide, orlistat, as well as the phentermine/topiramate and bupropion/naltrexone combinations. These drugs have been approved by the Food and Drug Administration (FDA) for weight reduction except for tirzepatide which is still under evaluation. Efficacy and tolerable safety profiles of some of these drugs contribute to the management of obesity and reduce the complications associated with this chronic disease. [ABSTRACT FROM AUTHOR]

BackgroundTopiramate is an effective treatment for alcohol use disorder (AUD) and has also been used in the care of mild traumatic brain injury (mTBI). This pilot study aimed to obtain a preliminary assessment of topiramate's efficacy in reducing alcohol use and post-concussive symptoms, and its potential negative impact on cognitive function in 32 Veterans with co-occurring AUD and mTBI.MethodsThis was a prospective 12-week, randomized, double-blind, placebo-controlled pilot study of flexible-dose topiramate or placebo. Primary outcome was reduction of drinking days per week within the topiramate arm. Secondary outcomes included between group comparisons of alcohol use and craving, post-concussive symptoms, and cognitive function.ResultsDrinking days per week significantly decreased within both the topiramate and placebo arm. There were no significant treatment-by-week interactions on alcohol use/craving, or post-concussive symptoms in intent-to-treat analyses. In per-protocol analyses, topiramate significantly reduced number of drinks per week compared with placebo. Topiramate transiently impaired verbal fluency and working memory. Processing speed, cognitive inhibition, and mental flexibility significantly improved between weeks 1 and 12, regardless of treatment arm.ConclusionsSignificant improvement occurred in both the topiramate and placebo groups over 12 weeks of treatment in alcohol use and post-concussive symptoms. Among treatment completers there was greater reduction of alcohol use in the topiramate arm. Topiramate was also associated with negative but transient effects on cognitive function. Results suggest both a possible benefit for topiramate treatment in reducing alcohol use and some potential for negative cognitive effects in Veterans with AUD and mTBI.

ObjectivesTo evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis.MethodsIn a prospective cohort, patients with hyperacusis were treated with a multi-modal step-wise migraine prophylactic regimen (nortriptyline, verapamil, topiramate, or a combination thereof) as well as lifestyle and dietary modifications. Pre- and post-treatment average loudness discomfort level (LDL), hyperacusis discomfort level measured by a visual analogue scale (VAS), and scores on the modified Khalfa questionnaire for severity of hyperacusis were compared.ResultsTwenty-two of the 25 patients (88%) reported subjective resolution of their symptoms following treatment. Post-treatment audiograms showed significant improvement in average LDL from 81.3 ± 3.2 dB to 86.4 ± 2.6 dB (P < .001), indicating increased sound tolerability. The VAS discomfort level also showed significant improvement from a pre-treatment average of 7.7 ± 1.1 to 3.7 ± 1.6 post-treatment (P < .001). There was also significant improvement in the average total score on modified Khalfa questionnaire (32.2 ± 3.6 vs 22.0 ± 5.7, P < .001).ConclusionsThe majority of patients with hyperacusis demonstrated symptomatic improvement from migraine prophylaxis therapy, as indicated by self-reported and audiometric measures. Our findings indicate that, for some patients, hyperacusis may share a pathophysiologic basis with migraine disorder and may be successfully managed with multimodal migraine prophylaxis therapy.

Abstract Background Depression is a common disorder that affects patients' quality of life and incurs health system costs. Due to the resistance to treat depression, better understanding of neurophysiology was considered; one of the implications is the glutamatergic system. This study aims to systematically review clinical trials investigating the antidepressant effects of kainate receptor antagonists. Methods The study protocol was registered in PROSPERO (CRD42021213912). Scopus, ISI, Embase, PubMed, Cochrane Library, Google Scholar, and two trial registries were searched for randomized controlled trials on the effectiveness of topiramate, phenobarbital, and other ten barbiturates in depression. The difference with control groups in terms of changing depressive symptoms was the primary outcome. Results Nine trials were identified, in which 784 patients were studied. The efficacy of thiopental was comparable to that of imipramine, with fewer side effects. When administered with electroconvulsive therapy, it had fewer to similar effects and fewer side effects than ketamine. Both monotherapy and adjunctive therapy with topiramate were effective and tolerable in treating depressed patients. Phenobarbital had therapeutic effects compared to imipramine and amitriptyline with fewer side effects. Conclusion Regarding the glutamatergic hypothesis of depression and obtained promising results, further studies of kainate receptor antagonists in high‐quality trials are recommended. Given the high prevalence of depression in epileptic patients, more problems with its treatment, and the fact that the studied agents were anticonvulsants, it is recommended that future studies prioritize depressed‐epileptic patients.

Тhe paper of Shohin I.E., Ramenskaya G.V., Medvedev Yu.V., Yarushok T.A., Sheveleva M.A.1 is devoted to development and validation of HPLC method determination of topiramate in rabbit plasma with precolumn derivatization. Topiramate was extracted from plasma by dichloromethane. Derivatization was performed by dansyl chloride in borate buffer. HPLC analysis was performed on C18 column (3 μm, 4,6 x 75 mm). Acetonitrile – 25 mM phosphate buffer pH 2.50 (30:70) at 1.0 mL/min was used as mobile phase. The standard curve was linear over the range 0.95 μg/ml to 47.32 μg/ml of topiramate in plasma. Within-run precision was 1.55 % to 2.12 % and between-run precision was 1.67 % to 8.09 % determined on spiked samples. The accuracy of the method was 1.14 % to 19.62 % (within-run) and 1.74 % to 19.25 (between-run). The lower limit of quantification was 0.95 μg/ ml. The method was applied to preclinical pharmacokinetics study of topiramate drug products in rabbits.

The mitochondrial isoforms VA/VB of metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) are involved in metabolic processes, such as de novo lipogenesis and fatty acid biosynthesis. We review the drug design landscape for obtaining CA VA/VB-selective/effective inhibitors, starting from the clinical observations that CA inhibitory drugs, such as the antiepileptics topiramate and zonisamide, or the diuretic acetazolamide induce a significant weight loss. The main approaches for designing such compounds consisted in drug repurposing of already known CA inhibitors (CAIs); screening of synthetic/natural products libraries both in the classical and virtual modes, and de novo drug design using the tail approach. A number of such studies allowed the identification of lead compounds diverse from sulphonamides, such as tropolones, phenols, polyphenols, flavones, glycosides, fludarabine, lenvatinib, rufinamide, etc., for which the binding mode to the enzyme is not always well understood. Classical drug design studies of sulphonamides, sulfamates and sulfamides afforded low nanomolar mitochondrial CA-selective inhibitors, but detailed antiobesity studies were poorly performed with most of them. A breakthrough in the field may be constituted by the design of hybrids incorporating CAIs and other antiobesity chemotypes.

Abstract Objective HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication. Methods Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment. Results Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50–100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p

Background: Topiramate (TPM) may reduce olanzapine (OLZ)-related weight gain and metabolism abnormalities in patients with schizophrenia. However, differences in the efficacy of OLZ-related weight gain and metabolism abnormalities between TPM and vitamin C (VC) are not clear. This study aimed to investigate whether TPM is more effective than VC in reducing OLZ-induced weight gain and metabolic abnormalities in patients with schizophrenia and explore their patterns. Methods: This was a 12-week longitudinal comparison study in OLZ-treated patients with schizophrenia. Twenty-two patients who received OLZ monotherapy plus VC treatment (OLZ+VC group) was matched to 22 patients who received OLZ monotherapy plus TPM treatment (OLZ+TPM group). Body mass index (BMI) and metabolism indicators were measured at baseline and 12-weeks follow-up. Results: A significant difference in triglyceride (TG) levels at different time points (pre-treatment: F=7.89, p=0.008; 4-weeks treatment: F=13.19, p=0.001; 12-weeks treatment: F=54.48, p < 0.001) was found. Latent profile analysis demonstrated that a 2-class model for OLZ+TPM group (high vs. low BMI in the first 4 weeks) and OLZ+VC group (high vs. low), respectively. Conclusion: Our findings suggested that TPM could better mitigates OLZ-induced increase in TG levels. The trajectories of change also differed in all metabolic indexes over time between the two groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Topiramate or (2,3:4,5-bis-O-methylethylidene-β-d-fructopyranose sulfamate) is classified as a sulfamate-substituted monosaccharide derived from fructose and is one of the most efficient antiepileptic drugs. Oral medicated jelly is an easily swallowed dosage form for administration to dysphagic patients including pediatrics or geriatrics. For this study, medicated jellies with topiramate were developed and characterized employing currently used gelling agents: sodium alginate, gelatin and pectin. Moist binary mixtures between topiramate and each component used in jellies were prepared before the jellies formulations to determine the substance compatibility. Topiramate, moist binary mixtures and oral medicated jellies were analyzed by FTIR–UATR spectroscopy, UV–Vis spectroscopy and thermogravimetry to evaluate the thermal behavior and possible interactions between compounds. [ABSTRACT FROM AUTHOR]

The article focuses on if topiramate, a migraine and other headache drug, reduces the efficacy of oral contraceptives. It reports the findings of a retrospective cohort study that compared the rates of accidental pregnancies among women taking combined oral contraceptives with topiramate versus other headache therapies, and the findings revealed no significant difference in contraception failure rates among the two groups.

Objective: To conduct a pilot study to examine topiramate for the treatment of weight gain associated with olanzapine in manic adolescents with bipolar disorder. Methods: We conducted a 12-week double-blind randomized placebo-controlled pilot study of topiramate (300–400 mg/day) versus placebo in manic youth (ages 10–18 years) with bipolar disorder who were treated with olanzapine (10–20 mg/day). The primary outcome measure was gender- and weight-normed change in body mass index (BMI z-score). Results: Thirty manic adolescents were treated with olanzapine and were randomized to either topiramate (n = 16) or placebo (n = 14). There was a significantly greater increase in BMI z-scores in the placebo group (0.28 standard deviations [SDs]) compared with the topiramate group (0.10 SDs) when analyzed by longitudinal regression (p = 0.049). The placebo group had greater increases in raw BMI and weight (2.25 kg/m2 and 6.9 kg, respectively) compared with the topiramate (0.99 kg/m2 and 2.9 kg) group (p = 0.011 for BMI, p = 0.016 for weight). The most common adverse events in the topiramate group were headache (n = 7, 44%), gastrointestinal upset (n = 3, 19%), and muscle stiffness (n = 3, 19%). Conclusions: Topiramate may minimize the weight gain associated with olanzapine treatment in adolescents with bipolar disorder. Moreover, topiramate in combination with olanzapine was well tolerated. Larger studies that are adequately powered are necessary to determine the efficacy of topiramate for second-generation antipsychotic-related weight gain. Trial Registration: ClinicalTrials.gov Identifier number NCT00394095. [ABSTRACT FROM AUTHOR]

Background. Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and new antiepileptic drugs (AEDs). In this meta-analysis, we aimed to assess the effects of new AEDs on Hcy. Methods. PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to June 2022 for articles that focused on the effects of new AEDs on Hcy. A meta-analysis was performed using Stata 16.0 software. The results were presented as the mean difference (MD) and corresponding to 95% confidence intervals (CIs) comparing epileptic patients with new AEDs to the control subjects. Results. A total of 11 studies were included in the meta-analysis. Hcy was markedly increased in the new AEDs group compared with the control group (MD = 2.220, 95% CI: 0.596–3.844, P = 0.007), with a high degree of heterogeneity (I2 = 99.5%). In the drugs subgroup, the oxcarbazepine (OXC) (MD = 2.30, 95% CI: −1.11–5.72, P = 0.187) and lamotrigine (LTG) (MD = 1.14, 95% CI: −0.209–2.482, P < 0.001) groups had no significant differences when compared with the control group. The levetiracetam (LEV) (MD = 1.81, 95% CI: 1.03–2.18, P < 0.001) and topiramate (TPM) (MD = 6.922, 95% CI: 0.788–13.055, P = 0.027) groups were significantly higher than the control group. Conclusions. The new AEDs, especially TPM and LEV, may increase the plasma of Hcy. The role of Hcy in patients with epilepsy who are given TPM and LEV should not be ignored in clinical situations. Patients with epilepsy who also have a high-risk vascular profile are recommended to use OXC and LTG. [ABSTRACT FROM AUTHOR]

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2–4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase (CA) I with a Topiramate (TPM) complex was investigated on the basis of a Quantum Mechanics/Molecular Mechanics (QM/MM) approach. The QM part was treated using Density Functional Theory (DFT) while the MM was simulated using Amberff14SB and GAFF force fields. In addition, the TIP3P model was applied to reproduce the polar environment influence on the studied complex. Next, three snapshots (after 5 ps, 10 ps, and 15 ps of the simulation time) were taken from the obtained trajectory to provide an insight into the non-covalent interactions present between the ligand and binding pocket of the protein. Our special attention was devoted to the binding site rearrangement, which is known in the literature concerning the complex. This part of the computations was performed using ω B97X functional with Grimme D3 dispersion corrections as well as a Becke–Johnson damping function (D3-BJ). Two basis sets were applied: def2-SVP (for larger models) and def2-TZVPD (for smaller models), respectively. In order to detect and describe non-covalent interactions between amino acids of the binding pocket and the ligand, Independent Gradient Model based on Hirshfeld partitioning (IGMH), Interaction Region Indicator (IRI), Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbitals (NBO) methods were employed. Finally, Symmetry-Adapted Perturbation Theory (SAPT) was applied for energy decomposition between the ligand and protein. It was found that during the simulation time, the ligand position in the binding site was preserved. Nonetheless, amino acids interacting with TPM were exchanging during the simulation, thus showing the binding site reorganization. The energy partitioning revealed that dispersion and electrostatics are decisive factors that are responsible for the complex stability. [ABSTRACT FROM AUTHOR]

The article presents the discussion on role of hormonal contraception in preventing ectopic pregnancies and reducing ovarian cancer risk. Topics include thrombosis risks with various progestogens, use of depot medroxyprogesterone acetate (DMPA) for treating leiomyoma, as well as interactions between topiramate and etonogestrel serum levels; and Individuals being obese reaching only half the effective pharmacokinetic dose compared to those with normal BMI increasing the risk for failure.

Objective: For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy‐to‐use and easy‐to‐prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)–approved excipient meglumine. Methods: During formulation development, we compared the solubility of TPM in bi‐distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine‐based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine‐induced SE. Results: The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether‐β‐cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co‐administered with another ASM for SE treatment. The tolerability studies of the meglumine‐based TPM solution and meglumine‐based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine‐induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway. Significance: In conclusion, the novel meglumine‐based solution of TPM presented here may be well suited for clinical development. [ABSTRACT FROM AUTHOR]

Introduction: Prader–Willi Syndrome (PWS) is a rare genetic condition, which affects one in 25,000 births and results in various phenotypes. It leads to a wide range of metabolic and endocrine disorders including growth delay, hypogonadism, narcolepsy, lack of satiety and compulsive eating, associated with mild to moderate cognitive impairment. Prognosis is especially determined by the complications of obesity (diabetes, cardiorespiratory diseases) and by severe behavioral disorders marked by impulsivity and compulsion. This heterogeneous clinical picture may lead to mis- or delayed diagnosis of comorbidities. Moreover, when diagnosis is made, treatment remains limited, with high interindividual differences in drug response. This may be due to the underlying genetic variability of the syndrome, which can involve several different genetic mutations, notably deletion or uniparental disomy (UPD) in a region of chromosome 15. Here, we propose to determine whether subjects with PWS differ for clinical phenotype and treatment response depending on the underlying genetic anomaly. Methods: We retrospectively included all 24 PWS patients who were referred to the Reference Center for Rare Psychiatric Disorders (GHU Paris Psychiatrie and Neurosciences) between November 2018 and July 2022, with either deletion (N = 8) or disomy (N = 16). The following socio-demographic and clinical characteristics were recorded: age, sex, psychiatric and non-psychiatric symptoms, the type of genetic defect, medication and treatment response to topiramate, which was evaluated in terms of eating compulsions and impulsive behaviors. We compared topiramate treatment doses and responses between PWS with deletion and those with disomy. Non-parametric tests were used with random permutations for p-value and bootstrap 95% confidence interval computations. Results: First, we found that disomy was associated with a more severe clinical phenotype than deletion. Second, we observed that topiramate was less effective and less tolerated in disomy, compared to deletion. Discussion: These results suggest that a pharmacogenomic-based approach may be relevant for the treatment of compulsions in PWS, thus highlighting the importance of personalized medicine for such complex heterogeneous disorders. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of tiapride and topiramate on patients with Tourette syndrome (TS). Methods: This retrospective analysis included 126 children diagnosed with TS at Children's Hospital of Chongqing Medical University from 2019 to 2021, with treatment including tiapride (n = 60) and topiramate (n = 66). Their tic severity values were assessed with the Yale Global Tic Severity Scale (YGTSS). Furthermore, behavioral and emotional problems were assessed with the Conner's Parent Rating Scale (CPRS) and the Children Behavior Checklist (CBCL). Results: Compared with premedication, the scores of tic severity were significantly decreased in both tiapride and topiramate groups after treatment, especially topiramate. Moreover, it was noted that five subscores of CPRS were significantly reduced in TS patients thanks to medication. However, there was no significant difference in CBCL after treatment, in both tiapride and topiramate groups. Conclusions: Tiapride and topiramate were proven to be effective on tics and some behavioral/emotional problems in TS patients, and topiramate may provide better treatment. [ABSTRACT FROM AUTHOR]

For the first time in 15 years the American Academy of Pediatrics (AAP) has issued comprehensive guidance on overweight and obesity, and recommends "immediate, intensive treatment for children and teens who are at or above the 85th percentile of body mass index (BMI) for their age and sex." [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The mechanisms of treatment-resistant epilepsy remain unclear. We have previously shown that frontline administration of therapeutic doses of lamotrigine (LTG), which preferentially inhibits the fast-inactivation state of sodium channels, during corneal kindling of mice promotes cross-resistance to several other antiseizure medicines (ASMs). However, whether this phenomenon extends to monotherapy with ASMs that stabilize the slow inactivation state of sodium channels is unknown. Therefore, this study assessed whether lacosamide (LCM) monotherapy during corneal kindling would promote future development of drug-resistant focal seizures in mice. Male CF-1 mice (n = 40/group; 18–25 g) were administered an anticonvulsant dose of LCM (4.5 mg/kg, i.p.), LTG (8.5 mg/kg, i.p.), or vehicle (0.5% methylcellulose) twice daily for two weeks during kindling. A subset of mice (n = 10/group) were euthanized one day after kindling for immunohistochemical assessment of astrogliosis, neurogenesis, and neuropathology. The dose-related antiseizure efficacy of distinct ASMs, including LTG, LCM, carbamazepine, levetiracetam, gabapentin, perampanel, valproic acid, phenobarbital, and topiramate, was then assessed in the remaining kindled mice. Neither LCM nor LTG administration prevented kindling: 29/39 vehicle-exposed mice were kindled; 33/40 LTG-exposed mice were kindled; and 31/40 LCM-exposed mice were kindled. Mice administered LCM or LTG during kindling became resistant to escalating doses of LCM, LTG, and carbamazepine. Perampanel, valproic acid, and phenobarbital were less potent in LTG- and LCM-kindled mice, whereas levetiracetam and gabapentin retained equivalent potency across groups. Notable differences in reactive gliosis and neurogenesis were also appreciated. This study indicates that early, repeated administration of sodium channel-blocking ASMs, regardless of inactivation state preference, promotes pharmacoresistant chronic seizures. Inappropriate ASM monotherapy in newly diagnosed epilepsy may thus be one driver of future drug resistance, with resistance being highly ASM class specific. [ABSTRACT FROM AUTHOR]

Background: Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid–base balance differ in the presence of an AUD or by topiramate dosage. Methods: Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score‐matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test–Consumption (AUDIT‐C) scores in the EHR. Analysis also included a three‐level measure representing mean daily dosage. The topiramate‐associated changes in serum bicarbonate concentration were estimated in difference‐in‐differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis. Results: The cohort comprised 4287 topiramate‐treated patients and 5992 propensity score‐matched controls with a mean follow‐up period of 417 days. The mean topiramate‐associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate‐treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis. Conclusions: The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider. [ABSTRACT FROM AUTHOR]

Youth with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity, early adiposity rebound, and increased abdominal adiposity compared to unaffected youth. Current obesity management in CAH largely focuses on lifestyle modifications. There is evidence that topiramate therapy is effective in reducing body mass index (BMI), as well as visceral adipose tissue (VAT), in unaffected adolescents with exogenous obesity. However, little is known about the efficacy of topiramate in patients with classical CAH. We report on a 17-year-old female with severe obesity and salt-wasting CAH due to 21-hydroxylase deficiency, who demonstrated reductions in BMI, as well as abdominal visceral and subcutaneous adipose tissue (SAT) while on topiramate therapy. The patient was diagnosed with classical CAH as a newborn with a 17-hydroxyprogesterone 11,000 ng/dL. She had a BMI over the 95th percentile at 3 years of age, followed by unremitting obesity. At 17 years old, she was started on topiramate to treat chronic migraines. Following three years of topiramate therapy, her BMI z-score decreased from +2.6 to +2.1. After four years of therapy, her waist circumference decreased from 110 to 101 cm, abdominal VAT decreased substantially by 34.2%, and abdominal SAT decreased by 25.6%. Topiramate therapy was associated with effective weight loss and reduced central adiposity in an adolescent with classical CAH and severe obesity, without any side effects. Further study is warranted regarding topiramate therapy in obese youth with classical CAH and increased central adiposity, who are at higher risk for significant morbidity. [ABSTRACT FROM AUTHOR]

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Fluorescent probes have supplanted more conventional techniques in many experiments due to their versatility, sensitivity, and measurability. Topiramate, the objective compound lacks fluorogenic or chromophoric moieties rendering its direct analysis impractical. Without these groups, the molecule lacks the ability to fluoresce or absorb light in its natural state when subjected to a source of ultraviolet radiation. Tagging with a tracking reagent or fluorescent probing can overcome this phenomenon. Under the specific conditions In this study, a new, eco-friendly, practically applicable, and specific fluorometric approach to the assay of none fluorescent drug, topiramate was proposed. The planned analytical approach is dependent on the integration of fluorescence probes through the use of the o-phthalaldehyde reagent to yield a potent fluorescent product that can be measured fluorimetrically. Topiramate's unsubstituted amine moiety can condense with o-phthalaldehyde and thiol moiety in a buffered solution. After being excited at 339 nm. the product was measured at em 440 nm. This technique provides linearity within a concentration scale of 0.1–0.9 µg mL−1. The system quantum yield was evaluated by a comparative method. Also, the probe validation was analyzed in accordance with the standards set by the International Council for Harmonization (ICH). Excipients had no appreciable impact on the proposed probe's performance when testing topiramate in both batch powder and commercially available products. The results show remarkable consistency with the documented reference method with no obvious discrepancies between the two. Finally, the planned system was evaluated from the environmental side through different ecological metrics such as National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI), and Analytical GREEnness measure (AGREE) and showed a high degree of greenness (ES: 93/100; AGREE 0.75/1 and full green NEMI pictograms).

In many experimental applications, fluorescent probes (fluorophores or just fluors) have replaced more traditional methods because of their adaptability, sensitivity, and quantifiability. The target analyte molecule (Topiramate) does not include any fluorogenic or chromophoric groups; hence it has no fluorescence in its native state or light absorptive power when exposed to ultraviolet light, thus; it is impossible to analyze it directly and must be undergone chemical mutagenicity in its molecular structure. This phenomenon can be achieved through fluorescent probing or labeling with tagging reagent. Consequently, the current analytical methodology depends on the fluorescence probe development via the ninhydrin reagent's utility to birth a condensed fluorescent derivative that can be tracked fluorimetrically. The final product was monitored at λem 482 nm after excitation at λex 381 nm. Under appropriate conditions, topiramate's primary amine group can condense with ninhydrin (β-diketone) and phenylacetaldehyde in a buffered solution. A new, green, feasible, and selective fluorometric strategy for topiramate assay has been presented in this work. The method offers linearity at a topiramate concentration range of 0.5 – 8 μg mL−1. The method's quantum yield was rated, and the validation parameters were examined following the International Council for Harmonisation (ICH) rules. Finally, the proposed probe was efficiently employed in the topiramate testing in the batched powder and available dosage form with high accuracy, and there was no significant effect with the existence of excipients. The findings indicate an impressive alignment with the reference documented method, showing no major variations in precision and accuracy.