Effects Of Topiramate Research Articles

Erenumab versus topiramate: migraine-related disability, impact and health-related quality of life.

HER-MES was the first head-to-head study of erenumab against topiramate (standard of care). This post hoc analysis of the HER-MES study evaluated the effect of erenumab versus topiramate on patient-reported outcomes at week 24. Adult patients with episodic or chronic migraine (n = 777) were randomized (1:1) to monthly subcutaneous erenumab (n = 389) or daily oral topiramate (n = 388). Migraine-related disability, as measured by the Headache Impact Test 6 (HIT-6) and Short Form 36 Health Survey version 2 (SF-36v2), was analysed in the entire study cohort and true completers. In the erenumab group (vs. topiramate), significant improvements were reported in Headache Impact Test 6 total scores (composite populations, -10.88 vs. -7.72; true completers, -11.92 vs. -10.61) and a higher proportion of patients achieved a ≥5-point reduction from baseline with erenumab (composite populations, 72.2% vs. 53.9%; true completers, 79.64% vs. 71.43%). The adjusted mean change from baseline in the SF-36v2 score was greater with erenumab for both physical component summary (composite population, 5.48 vs. 3.63; true completers, 5.95 vs. 5.23) and mental component summary (composite populations, 1.00 vs. -1.18; true completers, 1.74 vs. -0.33). A higher proportion of patients on erenumab versus topiramate had a ≥5-point improvement in SF-36v2 for the physical component summary (composite populations, 47.7% vs. 37.4%; true completers, 52.1% vs. 48.9%) and mental component summary (composite populations, 25.3% vs. 16.8%; true completers, 27.3% vs. 17.7%). This post hoc analysis demonstrated that patients treated with erenumab had significant improvements in headache impact and quality of life as measured by patient-reported outcomes versus patients treated with topiramate.

Efficacy and Side Effects of Topiramate in Treatment of Children With Pseudotumor Cerebri Syndrome

BackgroundTopiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children. MethodsRetrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded. ResultsA total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss. ConclusionsTopiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.

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

The R-type voltage-gated calcium channel CaV2.3 is predominantly located in the presynapse and is implicated in distinct types of epileptic seizures. It has consequently emerged as a molecular target in seizure treatment. Here, we determined the cryo-EM structure of the CaV2.3-α2δ1-β1 complex in the topiramate-bound state at a 3.0 Å resolution. We provide a snapshot of the binding site of topiramate, a widely prescribed antiepileptic drug, on a voltage-gated ion channel. The binding site is located at an intracellular juxtamembrane hydrophilic cavity. Further structural analysis revealed that topiramate may allosterically facilitate channel inactivation. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of topiramate on CaV and NaV channels, elucidating a previously unseen modulator binding site and thus pointing toward a route for the development of new drugs.

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.

Topiramate inhibits adjuvant-induced chronic orofacial inflammatory allodynia in the rat.

Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund's adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has not been validated with currently used drugs. Here we tested the effects of the adjuvant analgesic/antiepileptic voltage-gated Na+ channel blocker complex mechanism of action topiramate in comparison with the gold standard antimigraine serotonin 5-HT1B/D receptor agonist sumatriptan in this model. CFA was injected subcutaneously into the right whisker pad of male Sprague-Dawley rats (250-300g), then mechanonociceptive threshold values were investigated with von Frey filaments (3, 5, and 7 days after CFA injection). Effects of topiramate (30mg/kg per os) and sumatriptan (1mg/kg subcutaneous) on the adjuvant-induced chronic inflammatory orofacial allodynia were investigated 60, 120, and 180min after the treatments each day. To determine the optimal concentration for drug effect analysis, we tested the effects of two different CFA-concentrations (1 and 0.5mg/mL) on mechanonociceptive thresholds. Both concentrations of CFA induced a chronic orofacial allodynia in 60% of all rats. Although, higher CFA concentration induced greater allodynia, much more stable threshold reduction was observed with the lower CFA concentration: on day 3 the thresholds decreased from 18.30g to approximately 11g (low) and 5g (high), respectively, however a slight increase was observed in the case of higher CFA concentration (on days 5, 7, and 11). In all investigation days, topiramate showed significant anti-allodynic effect comparing the pre and post drug dose and comparing the vehicle treated to the drug treated groups. Sumatriptan also caused a significant threshold increase compared to pre dose thresholds (day 3) and also showed a slight anti-allodynic effect compared to the vehicle-treated group (day 3 and 5). In the present study CFA-induced chronic orofacial allodynia was reversed by topiramate in rats validating the model with the adjuvant analgesic. Other than establishing a validated orofacial pain-related syndrome model in rats, new ways are opened for the repurposing of topiramate.

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling.

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1β signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1β but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1β levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action.

Comparison between the effectiveness of three prophylactic drugs for vestibular migraine; cinnarizine, propranolol, and topiramate: prospective study

BackgroundVestibular migraine (VM) is considered one of the most common causes of episodic vertigo. Acute attacks may interfere or hinder daily activities, and hence decrease the quality of life. Accordingly, this study was designed to evaluate and compare the effectiveness of Cinnarizine, Propranolol, and Topiramate as prophylactic treatment for vestibular migraine, in order to decrease the occurrence of acute attacks. Several medications have been proposed as a prophylactic treatment, but their benefit is still a vast field of study.MethodsForty-five subjects were diagnosed with vestibular migraine. They were divided into 3 groups; each group either received Cinnarzine, Propranolol, or Topiramate. All patients were submitted to thorough history taking for headache and vertiginous attacks, Dizziness Handicap Inventory questionnaire (DHI) -Arabic version, visual analog scale, videonystagmography, and computerized dynamic posturography (CDP) before and after receiving the treatment by 3 months.ResultsTopiramate was significantly superior in reducing the frequency and severity of headache attacks. The three drugs showed improvement but with no significant difference as regards duration and frequency of vertiginous attacks, DHI scores, and CDP. Only 5 patients had non-serious temporary side effects.ConclusionsThe three drugs were effective for ameliorating vertiginous attacks in vestibular migraine patients, but Topiramate was better in the 25 mg twice daily dose.

Psychosocial and pharmacologic interventions for problematic methamphetamine use: Findings from a scoping review of the literature.

Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU. Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature. We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure. This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU.

Ameliorative Effect of Cannabidiol on Topiramate-Induced Memory Loss: The Role of Hippocampal and Prefrontal Cortical NMDA Receptors and CREB/BDNF Signaling Pathways in Rats.

Cannabidiol (CBD) is a promising neurological agent with potential beneficial effects on memory and cognitive function. The combination of CBD and topiramate in the treatment of some neurological diseases has been of great interest. Since Topiramate-induced memory loss is a major drawback of its clinical application and the overall effect of the combination of CBD and topiramate on memory is still unclear, here we investigated the effect of CBD on topiramate-induced memory loss and the underlying molecular mechanisms. A one trial step-through inhibitory test was used to evaluate memory consolidation in rats. Moreover, the role of N-methyl-D-aspartate receptors (NMDARs) in the combination of CBD and topiramate in memory consolidation was evaluated through the intra-CA1 administration of MK-801 and NMDA. Western blot analysis was used to evaluate variations in brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-binding protein (pCREB)/CREB ratio in the prefrontal cortex (PFC) and hippocampus (HPC). While the intraperitoneal (i.p.) administration of topiramate (50, 75, and 100mg/kg) significantly reduced inhibitory time latency, the i.p. administration of CBD (20 and 40mg/kg) could effectively reverse these effects. Similarly, the sub-effective doses of NMDA plus CBD (10mg/kg) could improve the topiramate-induced memory loss along with an enhancement in BDNF and pCREB expression in the PFC and HPC. Contrarily, the administration of sub-effective doses of the NMDAR antagonist (MK-801) diminished the protective effects of CBD (20mg/kg) on topiramate-induced memory loss associated with decreased BDNF and pCREB levels in the PFC and HPC. These findings suggest that CBD can improve topiramate-induced memory impairment, partially by the NMDARs of the PFC and HPC, possibly regulated by the CREB/BDNF signaling pathway.

The Effectiveness of Topiramate in the Treatment of Amphetamine and Methamphetamine Use Disorder: A Randomized Controlled Trial.

Objective: Limited studies have yet evaluated the effectiveness of topiramate in the treatment of amphetamine and methamphetamine addiction. Therefore, the aim of this study was to investigate the effectiveness of topiramate in the treatment of patients with this disorder. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with amphetamine and methamphetamine use disorder, within the age range of 16-60 years, were randomly divided into an intervention group (n = 26) and a placebo group (n = 26). The intervention group was treated with topiramate tablets with a starting dose of 50 mg, which was gradually increased to the target dose of 200 mg. The control group was treated with placebo. The duration of drug intervention in this clinical trial was 12 weeks, and all participants were evaluated before the intervention and 2, 4, 6, 8, 10, and 12 weeks after beginning the intervention. The Beck Depression Inventory, drug use temptation questionnaire, urine test, and side effects questionnaire were used as outcome measures to assess the patients. The data were analyzed using chi-square, independent t-test, and analysis of variance with repeated measurements. Results: There was no significant difference between the intervention and placebo groups in depression at the beginning of the treatment and at the 4th, 8th, and 12th weeks after the intervention (P > 0.05). The urine test also showed no significant difference between the two groups at any of the evaluation stages (P > 0.05). Although there was no significant difference between the two groups in the drug use temptation results at the beginning and the 2nd, 4th and 6th weeks (P > 0.05), the level of drug temptation in the intervention group was significantly lower than the placebo group in the 8th, 10th, and 12th weeks (P < 0.05). Conclusion: Topiramate can be effective in reducing the desire to use amphetamine and methamphetamine. However, further studies are needed to confirm these results.

Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress.

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

Effect of Topiramate on Mitochondrial Biogenesis and Neuroinflammation in Chronic Constriction Injury and Streptozotocin-induced Peripheral Neuropathy

Effect of Topiramate on Mitochondrial Biogenesis and Neuroinflammation in Chronic Constriction Injury and Streptozotocin-induced Peripheral Neuropathy

Study comparing the effect of topiramate and pregabalin on learning and memory with phenytoin in albino rats using morris water maze and elevated plus maze

Epilepsy is a chronic neurological disorder characterized by repeated seizures. Neurocognitive impairment is one of the adverse drug reactions (ADRs) in the case of antiepileptic drugs (AEDs). Phenytoin (PHT), an effective older generation AED, shows decline in cognitive functions such as memory, concentration and motor speed in both healthy volunteers and epileptic patients. Topiramate, has cognitive complaints among the adverse effects reported and include impaired concentration and memory, slowing of thought process, and difficulties in word finding. Another antiepileptic Pregabalin shows that it’s negative effects on cognitive functions are mild. Hence, a comparative assessment of the above group of drugs along with a control group was done using morris water maze and elevated plus maze. Effects on learning and memory was assessed using parameters such as escape latency and transfer latency. Albino rats were taken (24 in number) and assigned into 4 groups with three drug groups and one control group. They were given the respective drugs for a period of 15 days and then checked for escape latency and transfer latency times to assess the effect on “learning”. Thereafter the rats received the drugs for another 5 days after which they were assessed for “memory”. It was seen that phenytoin and topiramate do affect learning in comparison to pregabalin but the result about affecting memory was not conclusive.

Adverse Effects of Topiramate in Neonate with Moderate to Severe Perinatal Asphyxia: A Randomized Controlled Trial

Introduction: A harmful pregnancy condition that harms both the mother and the fetus is perinatal asphyxia. It frequently happens as a result of challenges during labour, including protracted or challenging delivery, concerns with the umbilical cord, placental abnormalities, or maternal health conditions. Topiramate, an anticonvulsant, works through a variety of different methods. Topiramate looks to be effective as a neuroprotective agent as well as an anti-seizure medication in animal models of newborn brain injury. Angiogenesis, neurogenesis, and neuronal anti-apoptotic pathways are all stimulated and regulated by topiramate. In light of this, this observational study was conducted to ascertain Topiramate's negative consequences in kids with mild to moderate neonatal hypoxia. Methods: This observational case-control study was carried out in the Neonatal ward and ICU of Dhaka Shishu Hospital from April 2015 to March 2016. A total of 64 neonates were enrolled in this study and were assigned Group A -the interventional group (n=32) received topiramate and standard treatment protocol, and Group B or the control group (n=32) received only standard treatment protocol. The data were analyzed according to standard procedure. Results: Among the study neonates, based on sex in case and control groups, respectively, seventeen (17,53%) and twenty-one (21,66%) neonates were male, and fifteen (15,47%) and eleven (11,44%) neonates were female. Statistically, the sex distribution between groups was not significant (p=0.44). USG finding of the neonates after treatment was normal in 12 (48%) and 13(41%), and abnormal in 20(32%) and 19 (59%) neonates in the control and case groups, respectively. Out of 27 neonates in the control group, 11 (41%) were neurologically normal, and 16 (59%) had abnormal neurological findings. Out of 29 neonates in the case group, 24 (73%) were neurologically normal, and 5(17%) showed abnormal neurological findings. Statistically, significant variation ..

The Effects of Topiramate on Methotrexate- Induced Pancreatic Injury

Amaç: Bu çalışmada metotreksat ilişkili pankreas hasarında topiramatın pankreasın Langerhans adacık hücreleri üzerine olan etkisinin araştırılması amaçlandı. Gereçler ve Yöntem: Çalışma 04 Temmuz- 24 Temmuz 2022 tarihinde Recep Tayyip Erdoğan Üniversitesi Hayvan Deneyleri ünitesinde gerçekleştirilmiştir. Çalışmada Spraque-Dawley erkek sıçanlar her grupta 8 hayvan olacak şekilde 3 gruba ayrıldı. Kontrol grubuna ait sıçanlara sadece %0.9’luk serum fizyolojik intraperiteonal (i.p.) olarak uygulandı. Metotreksat (MTX) grubuna tek doz 20mg/kg MTX uygulandı. Topiramat (TPM) tedavi grubuna MTX uygulamasından 7 gün önce ve 7 gün sonra olmak üzere toplam 14 gün süreyle günde tek doz TPM 100 mg/kg/gün oral gavaj yoluyla uygulandı. TPM uygulamasından 7 gün, son dozdan 16 saat sonra tüm denekler 50 mg/kg ketamin HCL ve 20 mg/kg ksilazin i.p. uygulanarak uyutuldu. Bulgular: MTX grubunda Langerhans adacıklarında yaygın ödematöz alanlar ve nekrotik hücreler gözlemledik. TPM grubunda MTX grubuna kıyasla nekrotik hücrelerin ve ödematöz alanların azaldığını saptadık. MTX grubunda insulin pozitivitesi gösteren β hücrelerinin kontrol grubuna kıyasla azalmış olduğunu saptadık (p&lt;0.05). TPM grubundaki pankreas dokusuna ait kesitlerde MTX grubuna kıyasla insülin pozitivitesi gösteren β hücrelerinde anlamlı düzeyde artış olduğunu gözlemledik (p&lt;0.05). MTX grubunda kontrol grubuna kıyasla glukagon pozitivitesi gösteren hücrelerin sayısında anlamlı olarak azalma olduğunu izledik (p&lt;0.05). TPM grubunda MTX grubuna kıyasla glukagon pozitivitesini gösteren α hücrelerinin sayısının artmış olduğunu gözlemledik (p&lt;0.05). Histopatolojik Hasar Skoru kontrol grubunda 0(0-1), MTX grubunda 6(6-8)’ya yükseldiğini saptadık (p&lt;0.05). TPM grubunda HHS 2(2-3) olarak gözlemlendi (p&lt;0.05). Sonuç: Çalışmamız topiramatın pankreas adacık hücreleri üzerinde koruyucu bir etkiye sahip olduğunu göstermektedir.

Effects of topiramate on morphological and structural alterations of the anterior cingulate cortex in aggressive socially isolated mice.

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. 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 (30mg/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. 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.

The protective effects of topiramate and spirulina against doxorubicin-induced cardiotoxicity in rats.

Doxorubicin (DOX) is a widely used chemotherapy drug that can cause significant cardiotoxicity, limiting its clinical application. This study aimed to investigate the potential protective effects of topiramate (TPM) and spirulina (SP), either alone or in combination, in preventing DOX-induced cardiotoxicity. Adult Sprague Dawley rats were divided into five groups, including a normal control group and groups receiving DOX alone, DOX with TPM, DOX with SP, or DOX with a combination of TPM and SP. Cardiotoxicity was induced by administering DOX intraperitoneally at a cumulative dose of 16 mg/kg over 4weeks. TPM and/or SP administration started 1week before DOX treatment and continued for 35 days. Body weight, serum markers of cardiac damage, oxidative stress and inflammatory parameters were assessed. Histopathological and immunohistochemical examinations were performed on cardiac tissues. Results showed that TPM and SP monotherapy led to significant improvements in serum levels of cardiac markers, decreased oxidative stress, reduced fibrosis-related growth factor levels, increased antioxidant levels, and improved histopathological features. SP demonstrated more prominent effects in comparison to TPM, and the combination of TPM and SP exhibited even more pronounced effects. In conclusion, TPM and SP, either alone or in combination, hold promise as therapeutic interventions for mitigating DOX-induced cardiotoxicity.

Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

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.

Effects of topiramate therapy on serum bicarbonate concentration in a sample of 10,279 veterans.

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. 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. 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 <2mEq/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. 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.