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Introduction: Pharmacological and other treatments for binge eating disorder (BED) predate its inclusion as the third main eating disorder in the 2013 DSM-5. Currently, second in line to psychological therapy are psychotropics such as antidepressants, anticonvulsants and stimulants., Areas Covered: This review summarizes the evidence and emerging evidence on the pharmacotherapies for BED and their potential for wider use., Expert Opinion: Pharmacotherapy has utility as an alternative or adjunctive treatment for those exhibiting insufficient response to, or not preferencing, psychological interventions. Medications may also benefit individuals with BED and other co-occurring mental health conditions, such as depression and attention deficit hyperactivity disorder. In addition, there are several agents (e.g. glucagon like peptide-1 receptor agonists and the combination of naltrexone-bupropion) displaying promise for weight and binge eating reduction in people with BED and high BMI. Future research should extend the understanding of the role of medication in BED, focusing on their sustained effects over time, when and if they may be ceased, their effectiveness in people with adequate weight, and the risks associated with weight loss in those with BED and high weight.

Topiramate has been found to be effective in reducing alcohol use and may also attenuate anxiety severity in patients with alcohol use disorder (AUD). This study compared the neural response of treatment-seeking patients with AUD on either topiramate or naltrexone during an anticipatory anxiety task. Participants were 42 patients with AUD who were randomized to receive either topiramate (n = 23; titrated dose up to 200 mg/day) or naltrexone (n = 19; 50 mg/day) for 12-weeks as part of a larger randomized controlled trial. Following 6 weeks of treatment, participants completed an anticipatory anxiety task during a functional magnetic resonance imaging (fMRI) session. The task presented a series of high-threat and low-threat stimuli followed by an unpleasant or pleasant image, respectively. Primary whole-brain analyses revealed no significant differences in neural activation between the topiramate and naltrexone groups. Deactivation for safe cues relative to threat cues was observed within the precuneus, inferior parietal lobule and the cingulate gyrus. In the precentral and middle frontal gyri, threat cues elicited greater activation. Exploratory analyses revealed an effect of change in anxiety from baseline to week 6, with a greater reduction associated with a reduced response to threat cues relative to safe cues in the cuneus and lingual gyrus. The current study is the first to examine and compare neural activation during anticipatory anxiety in treatment-seeking individuals on topiramate and naltrexone. This preliminary research contributes to our understanding of the therapeutic mechanisms of these alcohol pharmacotherapies., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press.)

Background: Clinical trials demonstrate the efficacy and tolerability of medications targeting calcitonin gene-related peptide (CGRP) signaling for migraine prevention. However, these trials may not accurately reflect the real-world experiences of more diverse and heterogeneous patient populations, who often have higher disease burden and more comorbidities. Therefore, postmarketing safety surveillance is warranted. Regulatory organizations encourage marketing authorization holders to screen digital media for suspected adverse reactions, applying the same requirements as for spontaneous reports. Real-world data from social media platforms constitute a potential venue to capture diverse patient experiences and help detect treatment-related adverse events. However, while social media holds promise for this purpose, its use in pharmacovigilance is still in its early stages. Computational linguistics, which involves the automatic manipulation and quantitative analysis of oral or written language, offers a potential method for exploring this content., Objective: This study aims to characterize adverse events related to monoclonal antibodies targeting CGRP signaling on Reddit, a large online social media forum, by using computational linguistics., Methods: We examined differences in word frequencies from medication-related posts on the Reddit subforum r/Migraine over a 10-year period (2010-2020) using computational linguistics. The study had 2 phases: a validation phase and an application phase. In the validation phase, we compared posts about propranolol and topiramate, as well as posts about each medication against randomly selected posts, to identify known and expected adverse events. In the application phase, we analyzed posts discussing 2 monoclonal antibodies targeting CGRP signaling-erenumab and fremanezumab-to identify potential adverse events for these medications., Results: From 22,467 Reddit r/Migraine posts, we extracted 402 (2%) propranolol posts, 1423 (6.33%) topiramate posts, 468 (2.08%) erenumab posts, and 73 (0.32%) fremanezumab posts. Comparing topiramate against propranolol identified several expected adverse events, for example, "appetite," "weight," "taste," "foggy," "forgetful," and "dizziness." Comparing erenumab against a random selection of terms identified "constipation" as a recurring keyword. Comparing erenumab against fremanezumab identified "constipation," "depression," "vomiting," and "muscle" as keywords. No adverse events were identified for fremanezumab., Conclusions: The validation phase of our study accurately identified common adverse events for oral migraine preventive medications. For example, typical adverse events such as "appetite" and "dizziness" were mentioned in posts about topiramate. When we applied this methodology to monoclonal antibodies targeting CGRP or its receptor-fremanezumab and erenumab, respectively-we found no definite adverse events for fremanezumab. However, notable flagged words for erenumab included "constipation," "depression," and "vomiting." In conclusion, computational linguistics applied to social media may help identify potential adverse events for novel therapeutics. While social media data show promise for pharmacovigilance, further work is needed to improve its reliability and usability., (©Pengfei Zhang, Brad K Kamitaki, Thien Phu Do. Originally published in JMIR Formative Research (https://formative.jmir.org), 08.11.2024.)

Background: Topiramate 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., Methods: Retrospective 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., Results: A 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., Conclusions: Topiramate 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Topiramate is a drug belonging to the second generation of antiseizure arsenal, used to treat focal onset seizures without generalization, focal-to-bilateral tonic-clonic seizures, and primary generalized tonic-clonic seizures., Areas Covered: The narrative evaluation of topiramate's clinical research that has been published in this article focuses on the medication's effectiveness and safety when used to treat primary generalized and focal-to-bilateral tonic-clonic seizures. From their founding to the present, the databases MEDLINE, SCOPUS, EBSCO, and GOOGLE SCHOLAR were searched., Expert Opinion: Topiramate treatment has the obvious benefit of being effective in treating tonic-clonic seizures; nevertheless, it may have a drawback in that up to 56% of patients discontinue therapy due to its rather poor tolerability, particularly at doses exceeding 600 mg daily. Patients are most bothered by psychiatric and cognitive side effects, and then by appetite and weight decrease. While the onset of anorexia cannot be prevented by changing the dosage regimen, psychiatric and cognitive side effects can be mitigated by slowly titrating the topiramate dose.

Purpose: Uveal effusion syndrome (UES) is an exudative detachment of ciliary body, retina and choroid. Various underlying causes leads to UES-like drugs (topiramate), inflammation and hypotony. Wnt gene involvement has never been associated with UES. We report a case of bilateral UES being misdiagnosed as Vogt-Koyanagi-Harada syndrome (VKH), with Wnt gene dysfunction as the underlying trigger., Observations: A 32-year-old male presented with diminution of vision in his left eye. He was found to have choroidal detachment with retinal detachment in his left eye. Choroidal detachment was noted in the right eye. Various ocular imaging including fundus fluorescein angiography and ocular coherence tomography was done. He was misdiagnosed as a case of VKH syndrome, for which he was treated with systemic immunomodulatory therapy. However, a subclinical response was made to revisit the diagnosis. Ultrasound biomicroscopy showed supraciliary effusion. Systemic and genetic evaluation led to the detection of Wnt10A pathway mutation., Conclusions: UES is an entity of diagnostic challenge. Careful and thorough systemic evaluation is required to clinch the diagnosis. We reported the first case of bilateral UES recalcitrant to corticosteroids, with Wnt10A gene mutation.

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.

Objectives: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet., Methods: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured., Results: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05)., Conclusion: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run., Level I: Randomized clinical trial., (© 2024. The Author(s).)

Migraine is a chronic, recurrent neurovascular disorder characterized by episodes closely associated with neurovascular hypersensitivity. Oxidative stress can worsen the hypersensitive state of the central nervous system, which in turn can trigger pro-inflammatory factors that result in neurogenic inflammation. Topiramate is frequently used as a preventative measure for migraines, but there is currently little empirical data to support its efficacy through pathways related to neurogenic inflammation and oxidative stress. This review provides an overview of current knowledge regarding the etiology, inducements, pathophysiology, and available treatments for migraine, with a focus on the clinical and experimental evidence of neurogenic inflammation and oxidative stress in migraine. It also delves into the antioxidant and anti-inflammatory qualities of topiramate, clarifying the possible ways in which topiramate affects these pathways to lessen migraine symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Meng and Ko.)

Objectives: Behavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD., Methods: We searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines., Results: We identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54-1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone., Conclusion: Anticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low., Competing Interests: DISCLOSURES The authors have no disclosures to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Polycystic ovary syndrome (PCOS) is often linked with obesity, and weight management can improve endocrine and cardiometabolic features., Objective: To evaluate the effects of adding topiramate (TPM) to metformin (MTF) on weight control, hormonal and metabolic outcomes in women with PCOS., Methods: In a randomized, double-blind, placebo-controlled trial, participants with PCOS and body mass index ≥30 kg/m² or ≥27 kg/m² associated with hypertension, type 2 diabetes, or dyslipidemia followed a 20 kcal/kg diet in addition to 850 mg of MTF or a previous MTF regimen. They were randomized to receive either TPM or placebo (P) alongside MTF. Anthropometric measurements, blood pressure, modified Ferriman-Gallwey score (mFGS), and adverse events were assessed every 4 weeks for 6 months., Main Outcome Measures: The primary endpoint was the percent change in body weight from baseline in both groups. Secondary endpoints included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features., Results: Thirty-one participants were in the MTF+P group and 30 in the MTF+TPM group. The MTF+TPM group showed greater mean weight loss at 3 months (-3.4% vs. -1.6%, p=0.03) and 6 months (-4.5% vs. -1.4%, p=0.03). Both groups improved androgens, lipids, and psychosocial scores. Participants with ≥3% weight loss at 6 months improved mFGS (8.4 to 6.5, p=0.026). Paresthesia was more common in the MTF+TPM group (23.3% vs. 3.2%, p=0.026)., Conclusions: Combining TPM with MTF and a low-calorie diet may be an effective, low-cost, easy-to-use, and safe strategy for weight management in women with PCOS, with mild adverse effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37℃), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague-Dawley rats (G3) showed higher plasma C max (504 ng/ml, p < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC 0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Objective: Antipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG)., Methods: The data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence., Results: The drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (-8.0 kg; -16. to -0.21), metformin 750 mg + lifestyle modification (-7.5 kg; -12 to -2.8), topiramate 200 mg (-7 kg; -10 to -3.4), metformin 750 mg (-5.7 kg; -9.3 to -2.1), topiramate 100 mg (-5.7 kg; -8.8 to -2.5), topiramate 50 mg (-5.2 kg; -10 to -0.57), liraglutide 1.8 mg (-5.2 kg; -10., -0.080), sibutramine 15 mg (-4.5 kg; -8.9 to -0.59), nizatidine 300 mg (-3.0 kg; -5.9 to -0.23) and metformin 1000 mg (-2.3 kg; -4.6 to -0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG., Conclusion: Metformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Topiramate (TPM), a carbonic anhydrase (CA) inhibitor, is known for its anti-obesity effect. Even though, nonalcoholic fatty liver disease (NAFLD) is present in 80% of obese patients, TPM's effects on oxidant-antioxidant parameters and CA activity on fatty liver is not known. 24 Wistar albino rats were divided into four groups: control, TPM, diet, and diet + TPM. Diet groups fed with high-fat diet while control and TPM groups received standard chow for six weeks. Than 100 mg/kg/day TPM (po) was added to TPM groups for 21 days. Rats' weight and blood glucose levels were monitored weekly, and at the end of the study liver removed for biochemical and histological analysis. TPM eliminated the increases in weight and blood glucose levels caused by high-fat diet. TPM decreased CA activity in all groups. MDA levels increased significantly in TPM and DT groups ( p  = 0.004; p  = 0.008). GSH levels were decreased in the TPM, D and DT groups ( p  = 0.004; p  = 0.015; p  = 0.003). Similarly, GPx activity levels were significantly decreased in all groups. Histological evaluation revealed notable infiltration, eosinophilia and cytoplasmic vacuolization in the TPM group. Steatosis and NAFLD activity score (NAS) were higher in the diet group. Ballooning, infiltration and NAS were higher in the diet + TPM group compared to control. CA activity negatively correlated with MDA ( p  < 0.001), and positively correlated with GSH ( p  < 0.001). TPM caused oxidant stress and liver damage, which are exacerbated in NAFLD induced rats. Therefore, use of TPM in patients with liver disease should be considered very carefully.

Purpose: Prolonged surgical procedures and some clinical conditions such as surgeries of thoracoabdominal aorta, mesenteric ischemia, cardiopulmonary bypass, strangulated hernias and neonatal necrotizing enterocolitis may cause decreased perfusion and injury of relevant organs and tissues. After reperfusion, injuries may get worse, leading to ischemia–reperfusion (I/R) injury. Reperfusion following arterial clamping allows oxygen to ischemic tissues and produce injury by multiple mechanisms, including neutrophilic infiltration, intracellular adhesion molecules, and generation of reactive oxygen radicals. In this study with the analysis of SOD, MDA and Caspase-3 levels, we aimed to investigate the effect of topiramate on the outcome of I/R occured after abdominal aorta clamping on rats. Materials and Methods: Totaly 24 Sprague–Dawley male rats were randomly divided into three experimental groups; the control group (n = 8), I/R (n = 8) and I/R+ topiramate (n = 8). Topiramate (100 mg/kg/day); 50 mg/kg (single dose) was administered intraperitoneally after being diluted with saline 5 days before I/R. Results: The intestinal tissue of the ischemia group displayed hemorrhage, Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields as a result of aortic occlusion. We also observed that MDA levels and Caspase-3 positivity increased and SOD levels decreased in the small intestine. However, topiramate administration decreased Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields, Caspase-3 positivity, and MDA levels. Conclusion: Our findings suggest that topiramate is effective against aortic occlusion-induced intestinal injury by reducing oxidative stress and apoptosis.

Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies.

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, including weight loss, for patients prescribed this medication. Although the specific mechanism of action concerning weight loss remains uncertain, various hypotheses have been reported. Notably, topiramate may contribute to weight loss by reducing calorie intake, decreasing fat gain, and lowering triglyceride and cholesterol levels. Additionally, its impact on reward pathways associated with food could play a role. Multiple clinical studies have supported the use of topiramate as a weight-loss medication. Notably, the medication demonstrates effectiveness in reducing body weight across different dosages and sustaining weight loss over time, outperforming alternative weight loss methods. Moreover, it was generally well-tolerated in clinical studies, with few side effects observed. In conclusion, topiramate offers promising potential as a weight loss solution and can be a valuable addition to the range of treatment options for combating obesity.

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington’s disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aβ42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3β and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits.

This letter to the editor discusses the treatment of ketamine use disorder using a combination of gabapentin and topiramate. Ketamine is a recreational drug that affects NMDA and GABA receptors. The authors present two case studies where the combination of gabapentin and topiramate successfully reduced ketamine use, cravings, and improved mood stability. The authors suggest that further research is needed to determine the potential efficacy of this treatment for ketamine use disorder. [Extracted from the article]

The article emphasizes holistic obesity management for preventing and treating type 2 diabetes through nutrition counseling, exercise, behavioral strategies, and diabetes education. Topics discussed include the importance of weight management in delaying diabetes progression, treating type 2 diabetes effectively, and reducing cardiovascular risks through lifestyle modifications and targeted interventions.

Inflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. These therapies, in the long term, may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as bodyweight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes the stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for the treatment of IBD in the future. [ABSTRACT FROM AUTHOR]

Idiopathic intracranial hypertension (IIH) is more common in women of reproductive age who have obesity, yet there is little information on its management specifically in pregnancy. Women with IIH should plan their pregnancy including discussing contraception before pregnancy, recognising that hormonal contraceptives are not contraindicated. Potentially teratogenic medications including acetazolamide and topiramate are not recommended during pregnancy or in those with immediate plans to conceive; prescribing acetazolamide in pregnancy must only follow discussion with the patient and their obstetrician. Ideally, patients should aim to achieve disease remission or control before pregnancy, through optimising their weight. Although weight gain is expected in pregnancy, excessive weight gain may exacerbate IIH and increase maternal and fetal complications; evidence-based recommendations for non-IIH pregnancies may help in guiding optimal gestational weight gain. The vast majority of women with IIH can have a normal vaginal delivery, with spinal or epidural anaesthesia if needed, provided the papilloedema is stable or the IIH is in remission. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients. Background: Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet. Methods: This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events. Results: One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (−9.6 vs −7.3 days; p = 0.003) and (−10.1 vs −7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6–9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1–6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported. Conclusion: Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated. [ABSTRACT FROM AUTHOR]

Objective: To understand the metabolic disturbances of stone formers currently taking topiramate and to examine the reversibility of these disturbances with cessation of the medication.Materials and Methods: All progress notes written by 5 endourologists from a single academic center were retrospectively reviewed from January 2010 to July 2020 containing the words "topiramate" or "topamax." Inclusion criteria were age >18 and presence of either a 24-hour urine sample or stone analysis while on topiramate. In addition, a subgroup of 18 patients with 24-hour urine samples before and after stopping topiramate were identified.Results: A total of 93 patients were identified and included for final analysis. Twenty-four hour urine samples were available in 67 patients and showed mean citrate excretion of 331 ± 322 mg/d, mean pH of 6.6 ± 0.5, and mean calcium phosphate supersaturation of 1.9 ± 1.1. In the subgroup analysis urinary citrate excretion increased from 225 mg/d to 614 mg/d (P <.01) and pH decreased from 6.59 ± 0.54 to 6.33 ± 0.47 (P = .06) after stopping topiramate. In addition, 114 stone events occurred in 73 distinct patients, with 50% of stones either pure or majority (≥50%) calcium phosphate by composition.Conclusion: Hypocitraturia and elevated pH is seen during topiramate use with resultant higher rate of calcium phosphate stone formation compared to the general population. Stopping topiramate leads to significant increase in citrate excretion and normalization of pH. These metabolic disturbances appear to be reversible with medication cessation. [ABSTRACT FROM AUTHOR]

Objectives: To explore the prophylactic outcome and tolerability of topiramate in patients suffering from chronic episodes of migraine. Methods: A prospective, non-interventional study was conducted at the Neurology Department of Nishtar Medical University & Hospital Multan from 17th Aug 2020 to 17th Aug 2021. The eligible patients were administered topiramate (flexible dose) for six months while the treatment was continued for another six months upon the advice of the physician. The patients were analyzed for improvement in migraine intensity and adverse effects of the evaluated drug at 2nd, 4th, 8th, 12th weeks, and at 6th, 9th, and 12th months. SPSS version 18 was used for statistical analysis Results: Out of the total of one hundred enrolled patients, 30 discontinued the study due to unavoidable adverse effects, loss in the follow-up period, and other unknown reasons. The median endpoint dose was 45 mg/dl ± 20.5mg/day. Both median days with migraine episodes and median pain intensity score significantly reduced from 7 to 1.5 days and from 16 to 2.75, respectively (p<0.01). Women who were found to have menstruation-related migraines reported a decrease in the median number of migraine episodes from 3.0 to 0.8 (p=0.01). The utilization of triptan reduced significantly along with significant improvement in self-reported impairment of life. Nausea (2.5%) and paresthesia (5.7%) were the most reported adverse effects. Conclusion: Topiramate not only significantly prevents migraine intensity and frequency of episodes but is also well-tolerated. [ABSTRACT FROM AUTHOR]

A case study is for a three and half month‑old girl was admitted to the pediatric neurology clinic because of small head size, restlessness and staring attacks. Topics include Electroencephalography during sleep showed epileptiform activity over the posterior regions of her brain and enlarged subarachnoid spaces; and Reported features of trappopathies include skeletal disorder, spondyloepiphyseal dysplasia tarda and a febrile illness‑induced encephalopathy and neurodevelopmental delay.

Patients with Huntington's disease are a risk group for developing problematic gambling, which is characterised by subjects' inability to stop gambling despite financial, personal or professional problems. Predisposition to pathological gambling and other addictions involves disturbances in the same corticostriatal circuits that are affected in Huntington's disease, and displays similar disinhibition‐related symptoms. The authors present a case of long‐standing pathological gambling, impulsivity and organic mood disorder related to Huntington's disease. [ABSTRACT FROM AUTHOR]

Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), and computational approaches were used to elucidate the molecular aspects of interaction between the antiepileptic drug topiramate and the multifunctional transport protein bovine serum albumin (BSA) under physiological conditions. Topiramate quenched BSA fluorescence in a static quenching mode, according to the Stern‐Volmer quenching constant (Ksv) data derived from fluorescence spectroscopy for the topiramate‐BSA complex. The binding constant was also used to calculate the binding affinity for the topiramate‐BSA interaction. Fluorescence and circular dichroism experiments demonstrate that the protein's tertiary structure is affected by the microenvironmental alterations generated by topiramate binding to BSA. To establish the exact binding site, interacting residues, and interaction forces involved in the binding of topiramate to BSA, molecular modeling and simulation approaches were used. According to the Molecular Mechanics Poisson‐Boltzmann Surface Area (MMPBSA) calculations, the average binding energy between topiramate and BSA is −421.05 kJ/mol. Topiramate was discovered to have substantial interactions with BSA, changing the structural dynamic and Gibbs free energy landscape patterns. [ABSTRACT FROM AUTHOR]

Topiramate is being widely used to prevent migraine headaches and treat epilepsy and mental disorders; however, Oral Lichenoid Lesion (OLL) is one of its rare side effects. The present report has been provided based on a patient case study who had developed OLLs following treatment with topiramate. The patient was a 50-year-old woman referred to a psychiatric clinic with complaints of severe headaches, anxiety, insomnia, and symptoms of Obsessive-Compulsive Disorder (OCD). For this purpose, fluoxetine, topiramate, and nortriptyline were prescribed. Two months after increasing the topiramate dosage to 400 mg per day, she developed OLLs. The Topiramate dose was reduced within two weeks and finally discontinued. The lesions were removed four weeks after the cessation. The patient had no lesions for 6 months. With restarting the drug, the lesion reappeared and finally, ceasing topiramate usage. To conclude, the mentioned lesions are one of the rare complications of this anticonvulsant drug. [ABSTRACT FROM AUTHOR]

Background: Gut microbial dysbiosis and gut-brain axis dysfunction have been implicated in the pathophysiology of migraine. However, it is unclear whether migraine-related cephalic allodynia could induce the alteration of gut microbial composition. Methods: A classic migraine rat model was established by repeated dural infusions of inflammatory soup (IS). Periorbital mechanical threshold and nociception-related behaviors were used to evaluate IS-induced cephalic allodynia and the preventive effect of topiramate. The alterations in gut microbial composition and potential metabolic pathways were investigated based on the results of 16 S rRNA gene sequencing. Microbiota-related short-chain fatty acids and tryptophan metabolites were detected and quantified by mass spectrometry analysis. Results: Repeated dural IS infusions induced cephalic allodynia (decreased mechanical threshold), migraine-like behaviors (increased immobility time and reduced moving distance), and microbial composition alteration, which were ameliorated by the treatment of topiramate. Decreased Lactobacillus was the most prominent biomarker genus in the IS-induced alteration of microbial composition. Additionally, IS infusions also enhanced metabolic pathways of the gut microbiota in butanoate, propanoate, and tryptophan, while the increased tryptophan-related metabolites indole-3-acetamide and tryptophol in feces could be the indicators. Conclusions: Inflammatory dural stimulation-induced cephalic allodynia causes the alterations of gut microbiota profile and microbial metabolic pathways. [ABSTRACT FROM AUTHOR]

Antiepileptic drugs prescribed in the context of migraine have been reported to be potentially linked with an increased risk of suicidal ideation and behavior. Meta-analyses support the evidence that amongst antiepileptic drugs, Topiramate has the greatest potential for facilitating the occurrence of suicidal ideation and behavior. Studies indicate that this occurs via the increased incidence of mood disorders amongst the population with migraines using Topiramate as a treatment, with a slow and progressive onset of suicidal ideation (if any). We discuss the unique case of a 43-year-old man known to have chronic migraines, who presented with intense rapid-onset suicidal ideation and olfactory hallucinations, three weeks after the introduction of Topiramate for chronic migraines. After a negative extensive investigation panel to rule out common organic diseases, Topiramate was ceased. The suicidal ideation and olfactory hallucinations resolved in less than 24 h without further interventions. This case report highlights that rapid-onset suicidal ideation and olfactory hallucinations could be linked as an unusual side effect to the introduction of Topiramate. The removal of Topiramate from the patient's pharmacological treatments prevented further psychological distress linked to ego-dystonic suicidal ideation and a resolution of olfactory hallucinations. He was discharged 48 h later. [ABSTRACT FROM AUTHOR]