Topiramate Group Research Articles

Efficacy and Tolerability of Erenumab and Topiramate for Prevention of Chronic Migraine: A Retrospective Cohort Study

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals’ quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations.

Does Topiramate Add-On Enhance the Response to the MATRIX Program in Individuals with Methamphetamine Use Disorder? A Double-Blinded Randomized Placebo-Controlled Trial

Background: Methamphetamine dependence significantly impacts individuals and society. Treating methamphetamine use disorder is challenging due to limited evidence on effective pharmacotherapies and their interaction with nonpharmacologic interventions. This study evaluated the efficacy of topiramate compared to placebo in treating methamphetamine use disorder among participants in a Matrix program. Methods: Participants were recruited from the Addiction Center of Iran Psychiatric Hospital between January 2020 and June 2023 and randomly assigned to receive either topiramate or a placebo for 12 weeks, alongside Matrix program sessions. Blinding was maintained for participants, personnel, outcome assessors, and statisticians. Main outcomes included craving, desire to use, positive urine amphetamine toxicology rates, and depression severity. Craving was assessed using the Visual Analog Scale (VAS) and the Substance Craving Questionnaire–brief (SCQ-B). The desire to use was evaluated with the Addiction Severity Index (ASI), while depression severity was measured using the Beck Depression Inventory. Data analysis utilized IBM SPSS Statistics® 20.0, employing various statistical tests for comparison. Results: Both groups exhibited improvement in craving as per VAS scores (p=0.007), with greater reduction in the topiramate group; however, no significant difference was found between groups (p=0.06). The negative urine toxicology rates showed no significant difference (Hazard ratio=1.15, 95% CI: 0.75, 1.78). Depression scores decreased in both groups without significant between-group differences (p=0.78). Conclusion: The findings do not support the efficacy of topiramate in enhancing outcomes within a Matrix program for individuals with methamphetamine use disorder.

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

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

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

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

Treatment compliance, treatment patterns, and healthcare utilization in epilepsy patients with first add-on antiepileptic drugs: A nationwide cohort study

ObjectiveThis study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy. MethodsWe conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs. ResultsAmong 6,746 patients who initiated AED add-on therapy, 65.5% were persistent on their index AED add-on from the index date until the end of the follow-up period, and the mean persistent time on the index add-on was 307.3 ± 92.3 days. A total of 76.8% patients were adherent, with a medication possession ratio (MPR) ≥80%, and the mean MPR was 88.9 ± 25.4%. Persistence and adherence to the index AED add-on were relatively higher among patients prescribed lamotrigine, levetiracetam, oxcarbazepine, and perampanel than those prescribed carbamazepine, topiramate, or valproate. A total of 41.0% of the patients changed their index AED add-on during the follow-up period. The carbamazepine, topiramate, and valproate groups had higher rates of change than the other AED groups. HCRU and costs tended to be lower in the lamotrigine, levetiracetam, oxcarbazepine, and perampanel groups. Furthermore, perampanel showed the lowest HCRU and costs for all-cause cases as well as the lowest length of stay and outpatient visits for epilepsy-related cases. ConclusionIn this population-based study, the use of lamotrigine, levetiracetam, oxcarbazepine, or perampanel as the first add-on therapy in patients with epilepsy contributed to better treatment compliance and lower HCRU and costs than that of carbamazepine, topiramate, or valproate.

Vascular dysfunction programmed in male rats by topiramate during peripubertal period

AimThe present study evaluated whether topiramate (TPM) treatment during the peripubertal period affects vascular parameters of male rats and whether oxidative stress plays a role in these changes. Main methodsRats were treated with TPM (41 mg/kg/day, gavage) or vehicle (CTR group) from the postnatal day (PND) 28 to 50. At PND 51 and 120 the rats were evaluated for: thoracic aorta reactivity to phenylephrine, in the presence (Endo+) or absence of endothelium (Endo-), to acetylcholine and to sodium nitroprusside (SNP), aortic thickness and endothelial nitric oxide synthase (eNOS) expression. In serum were analyzed: the antioxidant capacity by ferric reducing antioxidant power assay; endogenous antioxidant reduced glutathione, and superoxide anion. Results were expressed as mean ± s.e.m., differences when p < 0.05. Statistics: Two-way ANOVA (and Tukey's) or Student t-test. Key findingsAt PND 51, the contraction induced by phenylephrine in Endo+ ring was higher in TPM when compared to CTR. At PND 120, the aortic sensitivity to acetylcholine in TPM rats was reduced in comparison with CTR. The aortic eNOs expression and the aortic thickness were similar between the groups. At PND 51 and 120, TPM group presented a decrease in antioxidants when compared to CTR groups and at PND 120, in TPM group the superoxide anion was increased. SignificanceTaken together, the treatment of rats with TPM during peripubertal period promoted permanent impairment of endothelial function probably mediated by oxidative stress.

Flunarizine versus topiramate in migraine prophylaxis and their effect on psychomotor ability: A prospective open-label study

Background: About 9% of the overall population suffers from migraine headaches, with a female majority. For the prevention of migraines, the two most often prescribed drugs are topiramate (TPM) and flunarizine. Regarding TPM and flunarizine’s long-term efficacy, safety, and adverse effects on migraine prevention, little is known. To evaluate the effectiveness of flunarizine against TPM in migraine prophylaxis and its impact on psychomotor ability, the current study was designed. Aims and Objectives: The aim of the study was to compare the efficacy of flunarizine and TPM in the prophylaxis of migraine and to assess change in the psychomotor ability of the brain using different psychomotor analysis scoring systems. Materials and Methods: A comparative, open-label, and prospective study was carried out on patients with chronic migraine from the outpatient department of the neurology department at Uttar Pradesh University of Medical Sciences, Saifai, Uttar Pradesh, with flunarizine and TPM treatment (n = 20/group) for 2 months. Data regarding patient’s scores of headache severity on the Visual Analogue Scale (VAS), digit later substitution test, 6 letter cancellation test, digit span test, mathematical ability test, and flicker fusion apparatus test were recorded and analyzed. Results: When compared to the baseline, the mean±standard deviation pain severity score on the VAS was 2.9 ± 0.8 in the flunarizine group and 3.7 ± 1.4 in the TPM group, with a P &lt; 0.001. Furthermore, the flunarizine group showed less decline in performances in the scores of each psychomotor test as compared with the scores of the TPM treatment group when baseline values were compared at 1 and 2 months. Conclusion: Flunarizine is well tolerated, has a better safety profile, and has less cognitive decline as compared to TPM.

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome

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. 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. 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. Participants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day. 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. 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. 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. ClinicalTrials.gov Identifier: NCT02878798.

Study of Effectiveness of Prophylactic Treatment for Vestibular Migraine Patients

Abstract Objectives To evaluate effectiveness of prophylactic drugs in treatment of VM patients. Second to compare between each drug for its efficacy for treatment of VM patients Subjects and Methods Forty-five subjects divided into 3 groups were included in the present study. Group A, 15 subjects received Cinnarzine with mean age of 37.7 years. Group B, 15 subjects received Inderal with mean age of 38.3 years. Group C, 15 subjects received Topamax with mean age of 39 years diagnosed with vestibular migraine. They were subjected to a Dizziness Handicap Inventory questionnaire (DHI), visual analogue scale (VAS), neurological examination, vestibular office tests, videonystagmography (VNG) and sensory organization test (SOT) of computerized dynamic posturography (CDP) before and after receiving treatment according to grouping. Results 3 months after treatment, the mean number of total vertiginous attacks decreased from (14.5 ±9.2) to (7.3 ± 7.8), from (11.5 ±6.6) to (5.2 ± 4.1) and (13.1 ±8.6) to (4.1 ± 3) in Cinnarzine, Propranolol (Inderal) and topiramate (Topamax) groups respectively. DHI scores decreased from (50 ± 12.7) to (34.7± 12.5), (49.7 ± 11.2) to (32.4± 15.6) and (52.7 ±11.2) to (28.3 ± 9.2) in Propranolol (Inderal) and topiramate (Topamax) groups respectively. Conclusions This study provided that all three drugs are effective for ameliorating vertiginous attacks in VM patients; also, the treatment effects were similar in three groups with no significant difference.

Trajectory of blood pressure after initiating anti-calcitonin gene-related peptide treatment of migraine: a target trial emulation from the veterans health administration

BackgroundCalcitonin 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).MethodsWe 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.ResultsThis 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).ConclusionsOur 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.

A Double-Blind Placebo-Controlled Pilot Study of Topiramate in Manic Adolescents Treated with Olanzapine.

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.

Influence of Tiapride and Topiramate on Tic Severity and Behavioral/Emotional Problems in Children with Tourette Syndrome: A Retrospective Study.

To investigate the effect of tiapride and topiramate on patients with Tourette syndrome (TS). 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). 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. Tiapride and topiramate were proven to be effective on tics and some behavioral/emotional problems in TS patients, and topiramate may provide better treatment.

Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization

Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.

Role of anti-craving drugs baclofen and topiramate in the maintenance of abstinence in alcohol dependence syndrome

Background: Alcohol craving is psychological condition related to motivation. Craving is risk factor for relapse in alcohol dependence syndrome. No gold standard therapy is available; many therapeutic agents are under various evaluation stages. Objectives: To evaluate role of anti-craving drugs baclofen and topiramate in maintenance of abstinence in alcohol dependence syndrome Methods: From March to October 2018, an open-label interventional study with 70 sample size was conducted at Nobel Medical College, following ethical clearance. Age range for inclusion was 20-60, with no history of psychotropic use, whereas history of psychiatric illness and use of substance, excluding nicotine were excluded. After written informed consent patients were admitted for detoxification, and after detoxification, anti-craving therapy was started with topiramate and baclofen and asked for follow-up at two, four, and six weeks. Clinical withdrawal assessment scale was used for withdrawal symptoms and obsessive-compulsive drinking scale (OCDS) for progress in craving. Baclofen at 20 mgs/day, topiramate at 50 mgs/day, were prescribed and increased as required at follow-up. Results: Maximum daily dose of baclofen was 24.29 ± 2.19 mg and topiramate 120 ± 33.21 mg. Baclofen group patients had significant improvement in second week (OCDS T score 16.41± 9.52) while topiramate group showed significant improvement (OCDS T score 17.70 ± 7.57) after four weeks. Major side effects were tremors 8.10% in topiramate group, headache was 5.40% in both groups. Conclusion: Baclofen and topiramate were equally effective at six weeks for controlling cravings. Baclofen started to show significant improvements after two weeks of trial.

What Is the Effect of Topiramate Use on Growth in Children With Epilepsy?

ObjectiveThe literature related to weight loss as a side effect of using topiramate (TPM) in pediatric patients is inconsistent. The aim of this study was to assess the effect of TPM on the growth of pediatric epileptic patients.MethodsThe electronic medical files of 50 pediatric epileptic patients who were prescribed TPM over 5 years were retrospectively reviewed. Cases treated with other antiepileptic drugs were the control group (n=60).ResultsHeight growth was similar in both groups. At the 6-12-month follow-up, there was a decrease in the average BMI in the TPM group of -0.81 kg/m2 (p=0.019) and an increase in the control group of +0.46 kg/m2 (p=0.023). Weight loss was noted in 21/50 (42%) of the TPM group as compared with 13/60 (22%) in the control group (p=0.02). More weight loss was observed in the overweight TPM group in 7/16 (44%) compared to none in the nine cases in the control group (p=0.03). After the one-year follow-up, the average change in weight was +1.73 kg (p=0.0001) and +3.53 kg (p=0.0001) in the TPM and control groups, respectively. In patients with normal initial BMI, the weight increased by +1.3 kg on average, compared to the group with a high initial BMI, which decreased by -2.55 kg.ConclusionTopiramate use has no negative effect on height growth in pediatric patients with epilepsy. While mild weight loss occurs frequently in the first year of treatment, weight gain resumes after the first year except in patients with a high initial BMI

The Promising Effect of Topiramate on Random-Pattern Skin Flap Survival in Rats.

Partial necrosis of skin flaps following plastic and reconstructive surgeries is one of the major problems in these medical interventions. This study was conducted to evaluate the beneficial effects of topiramate an anti-epileptic agent on ischemic random skin flaps. Twenty-four Wistar rats were provided and randomly divided into four experimental groups (control group and low-, intermediate- and high-dose treatment groups). A rat random-pattern skin flap model was performed in all groups, and animals in the low-, intermediate- and high-dose experimental groups were administered topiramate intraperitoneally at doses of 25, 50 and 100 mg/kg, respectively, 1 h before raising the flap and once daily for 7 consecutive days after the initial surgical procedure. Control rats received vehicle according to the same schedule. On postoperative day 7 the flap necrotic area was measured, and tissue samples were stained with hematoxylin and eosin for histological analysis. Furthermore, the oxidative stress in flap tissue was assessed by measuring the activity of superoxide dismutase (SOD), glutathione (GSH) level and the content of malondialdehyde (MDA). Treating animals with 50 and 100 mg/kg topiramate significantly decreased the necrotic flap areas as compared to the control group. Histological studies demonstrated that in intermediate and high dose topiramate groups the inflammatory cell numbers were attenuated and microvessel development were markedly increased. Furthermore, the MDA contents were significantly reduced and GSH levels were significantly increased in these groups as compared to the control group. However, the SOD activity was increased significantly only in high-dose group as compared to the control group. These findings indicated that topiramate in doses of 50 and 100 mg/kg increases random skin flap survival. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats

AimTo determine the effects of valproate (VPA), carbamazepine (CBZ), oxcarbazepine(OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) on ovarian folliculogenesis in young rats. MethodsForty-nine female Wistar rats, aged 21–24 days, were divided equally into 7 experimental groups. These were given tap water over 21–24 days (control group), 300 mg/kg of VPA, 150 mg/kg of CBZ, 150 mg/kg of OXC, 100 mg/kg of TPM, 10 mg/kg of LTG, or 50 mg/kg of LEV daily in 2 doses via oral gavage until the end of puberty. At the end of the study, the estrous cycle of each rat was monitored daily, and those rats in pro-estrus or di-estrus were sacrificed and the ovaries removed. Serial sections obtained from the ovaries were stained with hematoxylin and eosin, and the corpora lutea and follicles were enumerated. Apoptotic cells were detected using the TUNEL technique. Various serial sections were immunohistochemically stained with proliferating cell nuclear antigen (PCNA), growth differentiation factor (GDF)-9, caspase-3, caspase-9, transforming growth factor beta 1 (TGF-1), and epidermal growth factor (EGF), and evaluated and photographed under a light microscope. Key FindingsThe number of corpora lutea was significantly increased in the VPA, CBZ, OXC, and LTG groups compared to the control group (p < 0.001). The number of TUNEL-positive ovarian follicles was 3.3 ± 1.1 (median, 3), 6.1 ± 0.9 (median, 6), and 5.7 ± 0.8 (median,6) in the control, OXC and LEV groups, respectively (p < 0.001). The number of TUNEL-positive granulosa cells was higher in all the groups treated with antiepileptics, with the exception of the TPM group, compared to the control group (p < 0.001). HSCOREs for immunohistochemical staining using PCNA, GDF-9, TGF-1 and EGF were significantly higher in the control group than in the others (p < 0.001). HSCORE for staining using caspase-3 was significantly higher in the VPA, CBZ, OXC and LEV groups, while the HSCORE was significantly lower in the TPM group than in the control group. HSCORE for staining using caspase-9 was significantly higher in the VPA, CBZ and OXC groups, while it was significantly lower in the TPM group than in the control group (p < 0.001). SignificanceExposure to VPA, CBZ, OXC, TPM, LTG and LEV caused different levels of impaired folliculogenesis in young rats.

Randomised, placebo-controlled trial on topiramate add-on therapy for weight reduction and symptomatology in overweight/obese persons with schizophrenia.

Higher cardiovascular mortality is seen with schizophrenia due to the disorder itself and antipsychotic use. South Asians are more vulnerable to developing metabolic disorders than others. Resource-limited settings in South Asia have only a few mental health professionals, and individualised case management is mostly unavailable. Therefore, there is less monitoring and personalised support for diet and physical exercise programmes. Topiramate is useful for weight reduction and improvement of psychopathology in schizophrenia. However, there has been only one previous randomised controlled trial (RCT) done in South Asia, which possesses a quarter of the world's population. We conducted a double-blind RCT in an outpatient setting in Sri Lanka. We compared topiramate 100mg/day with a placebo in overweight/obese adults with schizophrenia who have been on antipsychotics for at least a year. We obtained monthly anthropometric measurements and assessed the symptomatology using the brief psychiatric rating scale (BPRS). Fifty patients each in the topiramate and placebo arms completed the study. Topiramate add-on therapy led to significant weight/Body Mass Index reduction and improved symptomatology as measured by the BPRS compared to the placebo. The topiramate group had significantly more reporting of loss of appetite. According to available data, this is the RCT with most participants assessing the use of topiramate in schizophrenia and only the second in South Asia. Topiramate was shown to be useful for weight reduction and symptomatic improvement in persons with schizophrenia in a resource-limited setting in South Asia.

Post-treatment effects of topiramate on alcohol-related outcomes: A combined analysis of two placebo-controlled trials.

Topiramate reduces drinking and alcohol-related problems and is increasingly being used to treat alcohol use disorder (AUD). In a randomized controlled trial (RCT) of topiramate, rs2832407, a single nucleotide polymorphism (SNP) in the GRIK1 gene moderated topiramate's effects (Study 1). However, a second RCT (Study 2) did not replicate the SNP's moderating effect during treatment. The current analysis combines data from these two studies to examine topiramate's effects on alcohol-related outcomes and on its pharmacogenetic moderation during a 6-month post-treatment period. This analysis includes 308 individuals with problematic alcohol use (67% male; mean age = 51.1; topiramate: 49%, placebo: 51%). It uses generalized linear mixed models to examine changes in self-reported alcohol consumption and alcohol-related problems and concentrations of the liver enzyme γ-glutamyltransferase. The report combines published 3- and 6-month follow-up data from Study 1 with similar, unpublished data from Study 2. Despite robust effects of topiramate on drinking during treatment, the overall multivariate medication effects on outcomes during 3- and 6-month follow-up were not significant (p = 0.08 and p = 0.26, respectively). The moderating effect of the SNP on primary treatment outcomes was also not significant during either follow-up period (p = 0.13 and p = 0.16, respectively). However, during the 3-month post-treatment period, drinks per day was significantly lower in the topiramate group than the placebo group in the rs2832407*CC-genotype group. The robust effects of topiramate on alcohol-related outcomes during treatment diminish substantially once the medication is discontinued. Research is needed both to determine the optimal treatment duration and to identify clinically useful pharmacogenetic moderators of topiramate for treating AUD.

Effects and side effects of migraine prophylaxis in children.

Migraine is the primary cause of headache in children. Most patients can be treated with lifestyle changes and acute attack prophylaxis. Prophylaxis should be considered when symptoms cause frequent school absenteeism, poor quality of life, recurring emergency room visits, and frequent analgesic use. We aimed to compare the efficacy and side effects of drugs used in migraine prophylaxis, chosen according to the clinical and/or demographic characteristics of the patients. One hundred eighty-six patients aged 6-18 years were evaluated and who were diagnosed with migraine according to The International Classification of Headache Disorders, 3rd edition beta version (ICH-3β). Propranolol, topiramate, flunarizine, and cyproheptadine were given as prophylactic treatment. The Pediatric Migraine Disability Assessment Score (PedMIDAS) score, severity, duration, and frequency of the headache attacks were evaluated from the medical records and pre- and post-treatment values were compared. The median age of the patients was 14 years (range, 6-18 years) and the mean duration of headache was 29.6 ± 21.02 months. The mean PedMIDAS score was 29.9 ± 21.2 before and 14.9 ± 12.5 after treatment. Most reduction in the frequency of attacks was observed in the topiramate group. All four drugs significantly reduced the PedMIDAS score. The most common side effect was palpitations. Significant improvement was found in PedMIDAS scores in all drug groups. Topiramate was found to be the most effective drug in reducing the frequency of attacks. All four drugs in this study may be utilized for migraine prophylaxis in terms of effectiveness and safety.