Withdrawal Of Topiramate Research Articles

Topiramate: Connecting dot of acute angle closure with myopic shift and missing link with acute anterior uveitis

An interesting case of a 38-year-old male who presented with bilateral, sudden onset, painful diminution of vision. He had raised intraocular pressure (IOP), Oculus Uterque (OU) and bilateral acute onset myopia. Ultrasound biomicroscopy (UBM) revealed bilateral (B/L) ciliochoroidal effusion. This made us revisit his history to justify the acute onset myopia associated with raised IOP, which was established to be Topiramate (TPM) induced. Fourteen days after withdrawal of TPM, he also developed unilateral acute non-granulomatous anterior uveitis that was managed conservatively. Finally, his uncorrected visual acuity was 6/6 OU, and IOP was normal without any drugs. This case illustrates the significance of meticulous history and a step-wise approach to clinch the diagnosis. It is also imperative for clinicians to recognize these conditions and educate patients about the serious adverse effects when prescribing TPM.

Cognitive reawakening and improved quality of life achieved after discontinuing 16 years of anti-seizure treatment with topiramate

ABSTRACT A 42-year-old female patient with epilepsy and a co-morbid migraine suffered from the severe cognitive side effects of topiramate (TPM) for more than 16 years with detrimental consequences for her daily functioning, career, and social interaction. Even a prodromal stage of dementia was suggested, giving rise to fears of developing a neurodegenerative disease. Recently, cognitive monitoring of attention and executive function before and after withdrawal of TPM revealed a significant recovery from the severe negative cognitive side effects of the long-standing and inefficacious antiseizure medication (ASM). Whereas the side effects were reversible after cessation, their consequences for the patient`s biography were permanent. A considerable increase in quality of life, however, was observed without TPM and family members were impressed by the improvements. This case illustrates the potentially severe consequences of negative cognitive side effects which affect daily functioning, career and social life, thus underscoring the importance of being knowledgeable of the potential cognitive risks when prescribing an ASM. Because cognitive side effects may not depend solely on ASM choice and drug load, but also on individual idiosyncratic intolerances, and patients might stay on their treatment for many years, cognitive monitoring is highly recommended.

Spermatorrhea and Loss of Libido Induced by Topiramate: First Case Report and Review of Literature

Topiramate (TPM) is a broad-spectrum antiepileptic drug used for a variety of clinical conditions, including migraine prophylaxis and mood disorders. Spermatorrhea accompanied by loss of libido severely lowers quality of life for men, but had never been reported as a possible adverse effect of TPM. Here, we present a case of a 39-year-old Chinese man who was diagnosed with partial epilepsy and treated with TPM (100 mg/d). Eleven days after initiating TPM treatment, he began to experience spermatorrhea every 2 to 3 days, accompanied by loss of libido, lack of energy, lassitude, irascibility, weakness, poor appetite, frequent urination, and nocturia. The symptoms continued for 2 months. After withdrawal of TPM, symptoms disappeared and did not recur. This is the first case report of TPM-induced spermatorrhea and loss of libido in China. Spermatorrhea and loss of libido are probably rare adverse effects of TPM treatment. When these symptoms occur in a patient taking TPM, the possibility that they are adverse effects to this drug should be considered, and switching the patient to a different drug may be a good option. The underlying mechanism by which TPM induces spermatorrhea may be related to increased serotonin level, and loss of libido may be related to changes in serotonin and hormone levels.

Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.

Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function.

Paradoxical topiramate-induced hyperphagia successfully treated with phentermine in a woman with migraine

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate.

Cognitive adverse events of topiramate in patients with epilepsy and intellectual disability

Topiramate (TPM) is an effective antiepileptic drug (AED). A high proportion of patients, however, experiences cognitive adverse events (CAEs), especially in verbal fluency, memory spans, and working memory. To our knowledge, CAEs of TPM have not been studied systematically in patients with intellectual disability (ID). This may be due to the fact that many of those patients are not able to follow test instructions properly and that neuropsychological instruments are not validated for that group. Cognitive deterioration in patients with ID may thus easily be overlooked. Topiramate is in frequent use in persons with ID. We included 26 consecutive patients with epilepsy and ID in this observational study who had undergone neuropsychological examinations as part of clinical routine before and after the introduction of TPM into the therapeutic regimen (n=4) or before and after the withdrawal of TPM (n=22). Examinations under TPM showed reduced cognitive speed, reduced verbal memory, reduced verbal fluency, and reduced flexibility compared to examinations without TPM. Despite some limitations (especially small sample size, high interindividual variation of the results dependent on the degree of ID, effects of other – limited – changes in the therapeutic regimen), our study indicates that TPM in persons with epilepsy and ID may lead to CAEs comparable to those in persons with normal intelligence. Neuropsychological testing is mandatory in order not to miss CAEs that might severely impair quality of life.

Weight regain after discontinuation of topiramate treatment in patients with migraine: a prospective observational study.

To monitor weight regain after therapy discontinuation in patients with migraine experiencing weight loss during topiramate (TPM) treatment. Patients with migraine without aura were enrolled in this observational prospective study. Weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, and ghrelin, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated before starting TPM (T1), at 3 (T2) and 6 (T3) months of treatment and 6 months after withdrawal of TPM (T4). Weight loss/regain was considered as a change of </>5% of pre-TPM body weight. A total of 241 patients were analyzed. Of these, 87 (36%) patients experienced weight loss on TPM medication. During TPM therapy significant reductions in mean values of weight (p<0.001), BMI (p<0.001), waist circumference (p<0.01), HOMA-IR (p<0.01), and leptin (p<0.01) were observed. After TPM discontinuation, all of these parameters showed a clear trend to increase at T4, achieving pre-TPM values in 27 patients. Among potential predictors, only HOMA-IR before starting TPM (parameter estimate=1.36, effect size=0.75; p=0.006) was significantly associated with weight regain after therapy discontinuation. Loss of body weight is a reversible effect, which at 6 months after TPM discontinuation shows a clear trend to return to baseline values. HOMA-IR is the only predictive factor of weight regain.

Efficacy and safety of topiramate on weight loss: a meta‐analysis of randomized controlled trials

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]-6.12 to -4.56) of additional weight as compared with placebo. According to meta-regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96-200 mg day(-1) , the weight loss was higher in trials with >28 weeks of duration (-6.58 kg [95%CI -7.48 to -5.68]) than in trials with ≤28 weeks (-4.11 kg [95%CI -4.92 to -3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64-2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered.

Successful Treatment of Cerebellar Ataxia and Tremor in Multiple Sclerosis With Topiramate

We describe the clinical efficacy of topiramate for treatment of cerebellar dysfunction in a 33-year-old female patient with relapsing remitting multiple sclerosis. The patient presented severe ataxia and tremor precluding many activities of daily life. Topiramate was administered as a monotherapy and slowly tapered in to 150 mg daily without negative side effects. Treatment was well tolerated and led to a marked and lasting improvement of tremor as well as ataxia during an observation period of 2 years. Upon transient withdrawal of topiramate, ataxia and tremor worsened but were again improved after re-dosing of the drug. Multiple sclerosis immunotherapy was not changed in this period. In conclusion, topiramate may be a new therapeutic option to treat cerebellar tremor and ataxia in patients with multiple sclerosis.

Topiramate as Treatment for Hemifacial Spasm

To report a patient with hemifacial spasm (HFS) which improved with topiramate. A 52-year-old woman diagnosed with migraine, who also had a right HFS, did experience a marked improvement of HFS after introduction of topiramate as prophylactic therapy for her migraine episodes. Topiramate withdrawal led to reappearance of HFS, which improved again after its reintroduction. Topiramate should be considered as a possible therapy for HFS.

Efeitos adversos psiquiátricos desencadeados por Topiramato: relato de dois casos

INTRODUÇÃO: Potencialmente todas as drogas antiepilépticas podem levar a efeitos adversos psiquiátricos em alguns pacientes. Esses efeitos podem estar relacionados à predisposição familiar para doença psiquiátrica, reações idiossincrásicas, regime politerapêutico ou uso de altas doses, deficiência de folato e/ou normalização forçada. O Topiramato (TPM), um novo medicamento antiepiléptico, pode ser utilizado em várias afecções neurológicas e psiquiátricas; é uma droga antiepiléptica (DAE) altamente efetiva, indicada tanto para o tratamento dos pacientes com crises parciais quanto generalizadas. O TPM também tem um alto índice de efeitos adversos, embora estes geralmente estejam relacionados em parte à rápida titulação das doses. OBJETIVO: Relatar o caso de dois pacientes com epilepsia do lobo temporal, em regime politerapêutico, um deles com déficit cognitivo grave, que apresentaram efeitos adversos psiquiátricos com o uso de TPM. RESULTADOS: Os pacientes desenvolveram quadros de agitação psicomotora intensa, alucinações e comportamento agressivo após o uso do TPM e do controle completo das crises. DISCUSSÃO: Esses sintomas psicóticos parecem ter sido decorrentes do uso do TPM, pois sua completa remissão foi obtida após a redução e retirada desse medicamento.

Topiramate withdrawal

Topiramate withdrawal

A Case Of Hyperammonemic Encephalopathy Due To Valproate And Topiramate Combination At High Doses

A 35 years old male patient was admitted for a mental and behavioral disorder during the last two months. He had been treated for intractable epilepsy with valproate for many years. Topiramate was added in the previous year without any adverse reactions. Due to increased seizure frequency, the dosages of both drugs were increased gradually. Following the adjustment of drug regimen as 2000 mgs valproate and 400 mgs topiramate daily, the patient presented an encephalopaty with prominent delta and theta waves in EEG. Either serum liver enzymes or serum valproate levels showed no abnormality, but ammonia level had had rised up to 2 folds of normal. After withdrawal of topiramate and then valproate the symptoms resolved and ammonia level fell into the normal limits. The diagnosis of hyperammonemic encephalopathy due to treatment with the combination of valproate and topiramate was supposed. In our patient, the halopathic features had extraordinarily appeared after elevation of both antiepileptic drugs to high levels, while no adverse reactions had observed with moderately low doses. While treating patients with intractable epilepsy, complications of combinations should be carefully considered in desicion making not only for initiation but also for follow-up of drug adjustments.

Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of Topiramate in epilepsy patients

Rationale: Topiramate (TPM) is a highly effective anticonvulsant drug, but a comparably high rate of cognitive adverse effects have been reported. In this study, we investigated changes in frontal lobe associated cognitive measures after TPM withdrawal in epilepsy patients hospitalized for presurgical evaluation. Methods: Twenty epilepsy patients were administered a brief neuropsychological test battery before and after withdrawal of TPM. Neuropsychological evaluation included a verbal fluency task, verbal (Wechsler’s digits) and spatial spans (Corsi block-tapping) and Trail Making Test (TMT, parts A and B). Median baseline dosage of TPM was 237.5 mg/d, the median retest-interval was 8 days. Results were compared to a matched group of patients, who had been tested and retested before and after reduction of AEDs other than TPM at comparable time intervals. Results: After TPM withdrawal, group performance appeared significantly improved in five of six tests administered. The scores of the control patients remained largely unchanged after drug reduction. After withdrawal, the scores of the TPM group did not differ significantly from the results of the control group whereas pronounced differences had been observed before. Individual improvement became apparent in the majority of patients. Cognitive performance was not correlated to current daily dosages/current blood serum levels of TPM. Conclusion: Withdrawal of TPM causes significant improvement in frontal lobe associated measures like verbal fluency and working memory. As withdrawal was part of the preoperative work-up, and not initiated because of patients’ complaints or hints of intoxication, cognitive impairment due to TPM appears to be easily overlooked and underestimated.

Topiramate: efficacy and tolerability in children according to epilepsy syndromes

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox–Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.

Recovery of cognitive and emotional functioning following withdrawal of topiramate maintenance therapy

The present investigation reports cognitive improvement following withdrawal of topiramate (TPM) maintenance therapy in two patients with intractable seizures. The first patient received a neuropsychological evaluation after 10 months of adjunctive TPM treatment and was reassessed after complete withdrawal. The second patient received a first evaluation without TPM therapy. A reassessment was conducted after 13 weeks of stable TPM add-on therapy, and a third evaluation was performed after TPM withdrawal. During TPM treatment, the first patient demonstrated dysfunction on both verbal and non-verbal measures, suggesting bilateral impairment. Reassessment yielded cognitive improvement, and was consistent with a lateralized lesion as supported by seizure semiology, magnetic resonance imaging (MRI), and electroencephalogram (EEG) data. The second patient showed cognitive and emotional declines during TPM therapy. Reassessment, without TPM, demonstrated recovery on a majority of variables. These results illustrate the risk for considerable cognitive side effects after TPM habituation and support good recovery after withdrawal. Attempting to withdraw TPM and conducting a re-evaluation may be especially justified in the presence of a deflated neuropsychological profile that is inconsistent with a patient's estimated level of cognitive functioning. Reducing the influence of medical effects that could mimic bilateral dysfunction is particularly important in presurgical evaluations.