topiramate and Chronic-Disease

Relative to migraine generally, chronic migraine (CM) imposes greater disability, healthcare utilization and socioeconomic burden. Six therapies currently possess a credible evidence base for prevention/suppression of CM. This review is intended to provide an assessment of their relative utility, defined as a blend of safety, tolerability and efficacy, focusing in particular on their safety and tolerability.Areas Covered: We discuss all six medications currently FDA-approved for migraine prevention which also specifically possess credible evidence of efficacy in treating CM. While we do address the efficacy of each, our primary emphasis involves assessment of safety and tolerability data derived from clinical trials and post-marketing experience.Expert Opinion: Recent research involving CM has led to the identification of highly targeted and typically well-tolerated therapies. For patients who experience obstacles to accessing these newer therapies, topiramate is available as an evidence-based alternative, but contraindications, drug-drug interactions and poor tolerability may limit or prevent its use. Although data to support such intervention presently is limited, clinically challenging CM cases may benefit from combination therapy. 'Real world' studies are needed to evaluate such polytherapy, along with studies intended to assess the long-term safety of the individual therapies and their use during pregnancy and breast-feeding.

Topics: Chronic Disease; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Migraine Disorders; Topiramate

Migraine is highly prevalent and carries a significant personal, social and economic burden. It is the second cause of disability (years living with disability) worldwide and the first cause under 50 years of age. Chronic migraine (occurring for more than 15 days a month) and refractory migraine (treatment resistant), especially when there is also analgesic overuse, are the most disabling forms of migraine. These three disorders (chronic migraine, refractory migraine and medication overuse headache) are particularly difficult to treat. This article reviews their epidemiology, clinical presentation, diagnostic criteria, risk factors, comorbidities and social and personal impact. The therapeutic options available are discussed and focused on a multidisciplinary approach, non-pharmacological interventions treatment of comorbidities and avoiding analgesic overuse. Prophylactic treatments are mandatory and include the oral prophylactic treatments (topiramate), botulinum toxin type A and the novel monoclonal antibodies against calcitonin gene related peptide or its receptor, which are the first migraine preventive medicines developed specifically to target migraine pathogenesis. In refractory cases, multiple therapies are required including neurostimulation.. A enxaqueca é uma cefaleia muito prevalente na população com importantes custos pessoais, sociais e económicos e é a segunda causa a nível mundial de anos vividos com incapacidade. As suas variantes, crónica (aquela que ocorre mais de 15 dias por mês) e refratária (resistente ao tratamento), sobretudo quando se complicam de uso excessivo de analgésicos, embora mais raras, constituem as formas que causam maior incapacidade. Os autores revêm estes três tipos de cefaleias (enxaqueca refratária, enxaqueca crónica e cefaleia secundária a utilização excessiva de analgésicos) que constituem um grupo de cefaleias de difícil terapêutica. São revistos a epidemiologia, os aspetos clínicos, os critérios de diagnóstico, as comorbilidades, os fatores de agravamento e o impacto destas cefaleias sobre a qualidade de vida dos doentes. O tratamento de cada uma destas entidades é abordado, ressalvando a importância de uma abordagem abrangente, considerando o tratamento das comorbilidades, a utilidade de medidas não farmacológicas, o imperativo de evitar o abuso de analgésicos e a necessidade absoluta de tratamento profilático. São revistos os diferentes tratamentos profiláticos disponíveis (e a evidência científica da sua eficácia), tais como os fármacos preventivos orais (neuromodeladores como o topiramato), a toxina botulínica tipo A e os novos medicamentos preventivos para a enxaqueca (anticorpos monoclonais que atuam sobre o péptido relacionado com o gene da calcitonina ou o seu recetor, e que são os primeiros medicamentos preventivos desenvolvidos especificamente para atuar na fisiopatogenia da enxaqueca. Para os casos refratários são consideradas outras alternativas terapêuticas como a neuroestimulação.

Topics: Antibodies, Monoclonal; Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Headache; Headache Disorders, Secondary; Humans; Migraine Disorders; Neuromuscular Agents; Topiramate

Patients with POAG have lower corneal endothelial cell density than healthy controls of the same age. This may be attributed to mechanical damage from elevated IOP and toxicity of glaucoma medications.. Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.. T

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Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment.. Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment.. Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Chronic Disease; Disabled Persons; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

Topics: Animals; Botulinum Toxins, Type A; Chronic Disease; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome

Secondary generalized tonic-clonic seizures (SGTCS) are among the most severe forms of seizures, and the main risk factor for sudden unexpected death in epilepsy (SUDEP). Whether some antiepileptic drugs (AEDs) might be more efficacious than others on SGTCS in patients with drug-resistant focal epilepsy thus represents an important clinical issue for which no data are currently available.. We performed a meta-analysis of randomized controlled trials of adjunctive AED in which information on efficacy outcomes (i.e., responder rate and/or frequency per 28 days relative to baseline) were available both for all seizure types and for SGTCS. The primary analysis evaluated the efficacy of AEDs on all types of seizure and on SGTCS by comparing the responder rates for AED and for placebo.. Responder rate was available both for all seizure types and for SGTCS in 13 of the 72 eligible trials, evaluating 7 AEDs. Only three AEDs--lacosamide, perampanel and topiramate--showed greater efficacy than placebo. However, confidence intervals of relative risks overlapped for all AEDs but pregabalin, which demonstrated significantly lower efficacy than lacosamide, perampanel, and topiramate. Moreover, there was a nonsignificant trend toward a lower relative risk of responder rate for SGTCS than for all seizure types, which appeared related to a greater response to placebo for this outcome.. Indirect comparison of AEDs using randomized placebo-controlled add-on trials does not support robust differences between AEDs to prevent SGTCS. Alternative designs for evaluation of therapeutic interventions in patients at risk for SGTCS-related complications are required.

Topics: Acetamides; Anticonvulsants; Chronic Disease; Death, Sudden; Early Medical Intervention; Epilepsies, Partial; Fructose; Humans; Lacosamide; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Seizures; Topiramate; Treatment Outcome

We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A.

Topics: Amitriptyline; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antihypertensive Agents; Anxiety; Barbiturates; Botulinum Toxins, Type A; Chronic Disease; Contraindications; Depression; Drug Combinations; Ergot Alkaloids; Fructose; Headache Disorders, Secondary; Humans; Migraine Disorders; Narcotics; Risk Factors; Topiramate; Tryptamines

Chronic migraine is defined in different ways. The most commonly used definition is headache on more than 15 days per month in patients with migraine. Chronic migraine is difficult to treat and requires a multidisciplinary approach. Only two pharmacological treatments have been shown to be effective in placebo-controlled randomized trials: topiramate and local injection of botulinum toxin. Both therapies are effective in patients with chronic migraine with and without medication overuse. Many other substances have been investigated in chronic daily headache. All trials were underpowered and, therefore, recommendations concerning possible efficacy are not possible.

Topics: Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Fructose; Humans; Migraine Disorders; Topiramate

Topics: Adolescent; Child; Chronic Disease; Evidence-Based Medicine; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate

Migraine is a common neurological disease affecting about 12% of the population in Western Europe and North America, and causing a considerable burden both to migraineurs and to society. Severe, frequent and disabling migraine attacks, as well as those poorly responsive to acute care medication, require preventive treatment, which is often under-utilized. Antiepileptic drugs are used in the prevention of migraine. We performed a literature search of PubMed through June 2008 for controlled trials of antiepileptic drugs in the prevention of migraine. The search identified 70 papers for a full-text review. The majority of these papers referred to valproate and topiramate, and showed that these drugs are effective and well tolerated in migraine prevention and are suitable for first-line clinical use. On the other hand, acetazolamide, lamotrigine, oxcarbazepine and vigabatrin have been shown to be not effective and gabapentin requires further evaluation. For the rest of the antiepileptic drugs, no data from controlled trials are available.

Topics: Adult; Anticonvulsants; Child; Chronic Disease; Clinical Trials as Topic; Fructose; Humans; Migraine Disorders; Quality of Life; Topiramate; Valproic Acid

Alcoholism remains a serious cause of morbidity and mortality despite progress through neurobiological research in identifying new pharmacological strategies for its treatment. Drugs that affect neural pathways that modulate the activity of the cortico-mesolimbic dopamine system have been shown to alter drinking behavior, presumably because this dopaminergic system is closely associated with rewarding behavior. Ondansetron, naltrexone, topiramate, and baclofen are examples. Subtyping alcoholism in adults into an early-onset type, with chronic symptoms and a strong biological predisposition to the disease, and a late-onset type, typically brought on by psychosocial triggers and associated with mood symptoms, may help in the selection of optimal therapy. Emerging adults with binge drinking patterns also might be aided by selective treatments. Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment. Brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy.

Topics: Adult; Aged; Alcohol Deterrents; Alcoholism; Baclofen; Chronic Disease; Depressive Disorder; Female; Fructose; Humans; Hypothalamo-Hypophyseal System; Limbic System; Male; Naltrexone; Ondansetron; Pituitary-Adrenal System; Prefrontal Cortex; Receptors, Dopamine D2; Receptors, GABA; Topiramate; Young Adult

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

Topics: Analgesics; Anticonvulsants; Chronic Disease; Fructose; Humans; Migraine Disorders; Topiramate

Increasing evidence shows that migraine, typically considered as an episodic disease, is a chronic and, in some patients, progressive disorder. Among neuromodulators used for migraine prevention, topiramate has a high level of evidence-based efficacy. Through its wide range of mechanisms of action topiramate increases the activation threshold resulting in neuronal stabilization and thereby reducing cortical neurons hyperexcitability, which is believed to be an important electrophysiological feature underlying the pathogenesis of epilepsy and migraine. Recent studies show that migraineurs have subclinical structural brain changes and persistent alteration of pain perception, in some cases correlated with the duration of the disease and the frequency of attacks that might play a role in the transformation of episodic migraine to chronic forms. An early and prolonged preventive treatment might reduce the risk of such transformation. Recent evidence suggests that topiramate, by reducing migraine frequency and use of acute medication, may prevent the negative progression of migraine. Furthermore, two recently completed multicenter, randomised, placebo-controlled trials have shown that treatment with topiramate 100 mg/day is effective and well tolerated in patients already progressed to chronic migraine and difficult to treat conditions associated with medication-overuse. Topiramate seems to be a preventive treatment, which might be able to act at different levels of the migraine cycle: reduction of frequency in episodic migraine, prevention, and treatment of chronic migraine.

Topics: Anticonvulsants; Brain; Chronic Disease; Disease Progression; Fructose; Humans; Migraine Disorders; Neurons; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on > or = 15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is approximately 1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.

Topics: Chronic Disease; Fructose; Headache Disorders; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Risk Factors; Topiramate; Treatment Outcome

The onset of a migraine attack is associated with the activation of the trigemino-vascular system. Early intervention with triptans, which inhibit this activation is an effective treatment for migraine attacks. To avoid a cutaneous allodynia it is necessary to introduce as soon as possible the treatment with triptans. Drugs useful in the migraine prophylaxis tend to reduce the neuronal excitability in different areas of the central nervous system. The new definition of a chronic migraine is presented. This chronic migraine is frequently the result of an overuse of triptans. The practical aspects of the therapy of this specific migraine are described.

Topics: Acute Disease; Adrenergic beta-Antagonists; Anticonvulsants; Chronic Disease; Fructose; Humans; Hyperalgesia; Migraine Disorders; Topiramate; Tryptamines

Topics: Amines; Analgesics; Anticonvulsants; Bupropion; Chronic Disease; Cyclohexanecarboxylic Acids; Dopamine Uptake Inhibitors; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Mental Disorders; Pain; Topiramate; Triazines

The need for long-term management of bipolar disorder is evident. Bipolar patients spend more time depressed than manic; however, few agents used for maintenance therapy of bipolar disorder have demonstrated good efficacy in delaying relapse into depression. This article provides a comprehensive review of open-label and randomized, controlled studies examining prophylactic efficacy in bipolar disorder, especially bipolar depression. Lithium, considered the gold standard for bipolar disorder maintenance therapy may be more effective in delaying manic relapse than in delaying depressive relapse. Evidence for the efficacy of divalproex and carbamazepine in delaying depressive relapse is yet to be fully elucidated. Lamotrigine has demonstrated efficacy in delaying time to depressive relapse. Unpublished studies show olanzapine's efficacy in preventing manic recurrence, while its efficacy in preventing depressive recurrence is yet to be proven. As patients with bipolar disorder are prone to experiencing depressive episodes, more attention needs to be focused on preventing depressive relapse. To date, three agents--lithium, lamotrigine, and olanzapine--have been shown to have prophylactic benefits in treating this highly recurrent disorder.

Topics: Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Chronic Disease; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium Carbonate; Randomized Controlled Trials as Topic; Time; Topiramate; Triazines; Valproic Acid

In developed countries, the incidence of epilepsy is 50-100 cases per 100,000 population per year and the prevalence is approximately 5 to 8 cases per 1,000 population. Epilepsy is by far the most prevalent serious neurologic condition. Mortality rates in epilepsy are two to four times those found in matched nonepileptic populations. The prognosis of epilepsy can be classified into at least four categories, with chronic and refractory cases comprising about 40% of all cases. A detailed approach to the management of chronic epilepsy cases is recommended. Approximately 20% of patients cannot achieve seizure control with existing agents and new antiepileptic drugs are required for these patients.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Chronic Disease; Developed Countries; Developing Countries; Drug Therapy, Combination; Epilepsy; Fructose; Humans; Incidence; Middle Aged; Minnesota; Prevalence; Prognosis; Topiramate; Treatment Outcome

Migraine is included in the top-ten disabling diseases and conditions among the Western populations. Non-invasive neurostimulation, including the Cefaly® device, for the treatment of various types of pain is a relatively new field of interest. The aim of the present study was to explore the clinical experience with Cefaly® in a cohort of migraine patients previously refractory or intolerant to topiramate prophylaxis.. A prospective, multi-center clinical study was performed in patients diagnosed with episodic or chronic migraine with a previous failure to topiramate treatment requiring prevention with Cefaly® according to the treating physician's suggestion. A 1-month period of baseline observation was followed by a 3-month period of observation during the use of transcutaneous supraorbital nerve stimulation (t-SNS) with Cefaly® as the only preventive treatment.. A small but statistically significant decline was shown over time in the number of days with headache (HA), the number of days with HA with intensity ≥5/10, and the number of days with use of acute medication after 3 months (p < 0.001 for all of the three changes). Twenty-three patients (65.7%) expressed their satisfaction and intent to continue treatment with Cefaly®. Compliance was higher among satisfied subjects compared to non-satisfied subjects. None of the explored factors were significantly associated with the reason for the failure of topiramate.. Three-months of preventive treatment for episodic or chronic migraine with t-SNS proved to be an effective, safe and well tolerated option for the treatment of patients with migraine who were intolerant or did not respond to topiramate.. ClinicalTrials NCT03125525 . Registered 21 April 2017.

Topics: Adult; Biomedical Research; Chronic Disease; Fructose; Headache; Humans; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain; Patient Compliance; Prospective Studies; Topiramate; Transcutaneous Electric Nerve Stimulation; Treatment Failure; Treatment Outcome; Young Adult

Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification.. To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse.. We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine.. Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903).. Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.. Estudio comparativo de la efectividad del topiramato y la flunaricina en series independientes de pacientes con migraña cronica sin abuso de medicacion.. Introduccion. El topiramato y la onabotulinumtoxina A han mostrado ser eficaces en la migraña cronica con o sin abuso de farmacos segun los criterios recientes de la Clasificacion de Cefaleas de la Sociedad Internacional de Cefaleas. Objetivo. Demostrar que la flunaricina es tan efectiva como el topiramato en la migraña cronica sin abuso de farmacos. Pacientes y metodos. Estudio prospectivo, no aleatorizado, comparativo de dos grupos de pacientes con similar edad y sexo, con migraña cronica sin abuso, tratados preventivamente por primera vez con topiramato o flunaricina. Resultados. A 40 pacientes tratados con flunaricina se les asigno un paciente del mismo sexo y edad tratado con topiramato. La media de reduccion de las migrañas intensas en el grupo del topiramato fue del 59% y en el grupo de la flunaricina, del 58,5% (p = 0,9444); la tasa de respondedores al cuarto mes de tratamiento tampoco mostro diferencias significativas, ya que fue del 75% para el topiramato y del 70% para la flunaricina (p = 0,6236). La media de reduccion de otras cefaleas en el grupo del topiramato fue del 57%, y en el grupo de la flunaricina, del 64% (p = 0,4261); la tasa de respondedores al cuarto mes de tratamiento fue del 76%, similar en ambos grupos. El porcentaje de abandonos del tratamiento fue mayor con el topiramato (19,5%) que con la flunaricina (10%) (p = 0,3493). En ninguno de los dos grupos hubo efectos adversos graves. Un 78,9% de los pacientes que tomo topiramato presento satisfaccion con el farmaco frente al 75% del grupo de la flunaricina (p = 0,7903). Conclusion. La flunaricina mostro ser tan efectiva como el topiramato en el tratamiento de la migraña cronica sin abuso de farmacos.

Topics: Adult; Calcium Channel Blockers; Chronic Disease; Cognition Disorders; Fatigue; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Dropouts; Patient Satisfaction; Prospective Studies; Topiramate; Treatment Outcome

This study aimed to identify predictive factors of outcome in patients with chronic migraine (CM) treated with acupuncture or topiramate in a randomized controlled trial.. Sixty-six consecutive CM patients were treated with either acupuncture (n=33) or topiramate (n=33) in a 12-week period. Data on potential predictive factors were collected at baseline, and secondary data analysis was performed to identify factors associated with treatment response. Treatment prognosis was defined as the change in mean number of moderate/severe headache days per 4 weeks from the 4-week baseline periods.. The median change in mean number of moderate/severe headache days per 4 weeks for patients with higher baseline headache days (>20 d) was significantly greater than that for lower baseline headache days (≤ 20 d) (median ± interquartile range: -12 ± 2 vs. -10 ± 1 d, P=0.01) in acupuncture group. There was a greater change in mean number of moderate/severe headache days per 4 weeks for high moderate/severe headache days (>20 d) than in low days (≤ 20 d) (-12 ± 1 vs. -10 ± 2 d, P=0.015) in acupuncture group. patients with throbbing symptoms had better prognosis with acupuncture than those without throbbing (-12 ± 2 vs. -9.5 ± 2.5 d, P=0.004). Higher score (>5 points) in the general expectations for improvement predicted better response in both treatment groups (>5 vs. ≤ 5 points: -12 ± 2 vs. -9 ± 2 d for acupuncture group; -10 ± 3 vs. -7 ± 4 d for topiramate group; P<0.001).. Some variables can predict outcome in acupuncture or topiramate treatment of CM patients. Identifying predictors of prognosis of both treatments for CM may help improve outcomes in future work.

Topics: Acupuncture Therapy; Adult; Chronic Disease; Disability Evaluation; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Predictive Value of Tests; Prognosis; Surveys and Questionnaires; Topiramate; Treatment Outcome

To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone.. This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (≥10 headaches/month) with topiramate (50-100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks -4 to 0).. A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91).. This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone.. This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy.

Topics: Adolescent; Adult; Aged; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Topiramate; Treatment Outcome; Young Adult

This multi-center pilot study compared the efficacy of onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and widely accepted treatment for prevention of migraine) in individuals with chronic migraine (CM).. A total of 59 subjects with CM were randomly assigned to one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections, Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets. Subjects maintained daily headache diaries over a 4-week baseline period and a 12-week active study period. The primary endpoint was the Physician Global Assessment, which measured the treatment responder rate and indicated improvement in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12, included headache days per month, migraine days, headache-free days, days on acute medication, severity of headache episodes, Migraine Impact & Disability Assessment, Headache Impact Test, effectiveness of and satisfaction with current treatment on the amount of medication needed, and the frequency and severity of migraine symptoms. At 12 weeks subjects were re-evaluated and tapered off oral study medications over a 2-week time period. Subjects not reporting a >50% reduction of headache frequency at 12 weeks were invited to participate in a 12-week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered for this extension from weeks 14 to 26.. This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall, the results were statistically significant within groups but not between groups. By week 26, subjects had a reduction of headache days per month compared with baseline. This was a significant within-group finding.. OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.

Topics: Adolescent; Adult; Aged; Botulinum Toxins, Type A; Chronic Disease; Double-Blind Method; Endpoint Determination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuromuscular Agents; Neuroprotective Agents; Pilot Projects; Prospective Studies; Surveys and Questionnaires; Topiramate; Young Adult

The limitations of antipsychotics for treatment of schizophrenia have led to investigation of the usefulness of pharmacological augmentation strategies. Clinical studies have provided evidence for glutamate abnormalities in schizophrenia. Topiramate is an anticonvulsant drug with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist properties; therefore, the objective of the present study was to explore the therapeutic efficacy of topiramate as an adjunctive medication in schizophrenia.. A 17 week, double-blind, placebo-controlled clinical trial was performed on 80 patients (25 - 65 years) from 2005 - 2007. All were hospitalized in Mashhad psychiatric hospitals with chronic DSM-IV-TR-diagnosed schizophrenia. All participants received up to 300 mg/day of clozapine. In addition, participants randomly received either topiramate (200 - 300 mg/day) or placebo gradually added to their ongoing treatment. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale at baseline and weeks 4, 8, 12, and 17.. During the study, 5 patients from the placebo group and 12 participants from topiramate group were excluded. Clozapine and topiramate group showed significant decreases in all three subscales of PANSS values from baseline, with the maximum efficacy in week 12. However, after tapering topiramate, the general psychopathology sign was the only subscale that showed a significant difference. The clozapine and placebo group showed a significant decrease in all three subscales of PANSS values compared to baseline. The significant efficacy for all subscales was obtained at the end point. No significant differences in PANSS scores from baseline to end point were noted between case and control groups.. Augmentation of clozapine and topiramate did not significantly decline patterns in any of the three subscales of PANSS compared to the clozapine and placebo group. Irct ID: IRCT138904014236N1

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Chemotherapy, Adjuvant; Chronic Disease; Clozapine; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Topiramate; Treatment Outcome

The aim of this study was to investigate the efficacy and tolerability of acupuncture compared with topiramate treatment in chronic migraine (CM) prophylaxis.. A total of 66 consecutive and prospective CM patients were randomly divided into two treatment arms: 1) acupuncture group: acupuncture administered in 24 sessions over 12 weeks (n = 33); and 2) topiramate group: a 4-week titration, initiated at 25 mg/day and increased by 25 mg/day weekly to a maximum of 100 mg/day followed by an 8-week maintenance period (n = 33).. A significantly larger decrease in the mean monthly number of moderate/severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days was observed in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (p < .01) Significant differences favoring acupuncture were also observed for all secondary efficacy variables. These significant differences still existed when we focused on those patients who were overusing acute medication. Adverse events occurred in 6% of acupuncture group and 66% of topiramate group.. We suggest that acupuncture could be considered a treatment option for CM patients willing to undergo this prophylactic treatment, even for those patients with medication overuse.

Topics: Acupuncture; Adult; Aged; Chronic Disease; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain; Pain Measurement; Topiramate; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of topiramate (100 mg/day) compared with placebo for the treatment of chronic migraine.. This was a randomized, placebo-controlled, parallel-group, multicenter study consisting of 16 weeks of double-blind treatment. Subjects aged 18 to 65 years with 15 or more headache days per month, at least half of which were migraine/migrainous headaches, were randomized 1:1 to either topiramate 100 mg/day or placebo. An initial dose of topiramate 25 mg/day (or placebo) was titrated upward in weekly increments of 25 mg/day to a maximum of 100 mg/day (or to the maximum tolerated dose). Concomitant preventive migraine treatment was not allowed, and acute headache medication use was not to exceed 4 days per week during the double-blind maintenance period. The primary efficacy endpoint was the change from baseline in the mean monthly number of migraine/migrainous days; the change in the mean monthly number of migraine days also was analyzed. A fixed sequence approach (ie, gatekeeper approach) using analysis of covariance was used to analyze the efficacy endpoints. Assessments of safety and tolerability included physical and neurologic examinations, clinical laboratory parameters, and spontaneous reports of clinical adverse events.. The intent-to-treat population included 306 (topiramate, n = 153; placebo, n = 153) of 328 randomized subjects who provided at least 1 efficacy assessment; 55.8% of the topiramate group and 55.2% on placebo were trial completers. The mean final topiramate maintenance dose was 86.0 mg/day. The mean duration of therapy was 91.7 days for the topiramate group and 90.6 days for the placebo group. Topiramate treatment resulted in a statistically significant mean reduction of migraine/migrainous headache days (topiramate -6.4 vs placebo -4.7, P= .010) and migraine headache days relative to baseline (topiramate -5.6 vs placebo -4.1, P= .032). Treatment-emergent adverse events occurred in 132 (82.5%) and 113 (70.2%) of topiramate-treated and placebo-treated subjects, respectively, and were generally of mild or moderate severity. Most commonly reported adverse events in the topiramate group were paresthesia (n = 46, 28.8%), upper respiratory tract infection (n = 22, 13.8%), and fatigue (n = 19, 11.9%). The most common adverse events in the placebo group were upper respiratory tract infection (n = 20, 12.4%), fatigue (n = 16, 9.9%), and nausea (n = 13, 8.1%). Discontinuations due to adverse events occurred in 18 (10.9%) topiramate subjects and 10 (6.1%) placebo subjects. There were no serious adverse events or deaths.. Topiramate treatment at daily doses of approximately 100 mg resulted in statistically significant improvements compared with placebo in mean monthly migraine/migrainous and migraine headache days. Topiramate is safe and generally well tolerated in this group of subjects with chronic migraine, a burdensome condition with important unmet treatment needs. Safety and tolerability of topiramate were consistent with experience in previous clinical trials involving the drug.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Chronic Disease; Female; Fructose; Humans; Male; Migraine Disorders; Topiramate

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7,

Topics: Adolescent; Aged; Anticonvulsants; Chronic Disease; Disability Evaluation; Double-Blind Method; Female; Fructose; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Placebos; Topiramate; Treatment Outcome

Topiramate, a novel anticonvulsant, has been reported to rapidly reduce symptoms of posttraumatic stress disorder (PTSD) in an open-label trial. The present study was designed as a test of topiramate's efficacy as adjunctive therapy in a 7-week, randomized, double-blind, placebo-controlled trial.. Forty male veterans with PTSD in a residential treatment program were randomized to flexible-dose topiramate or placebo augmentation. The primary outcome measures were PTSD symptom severity and global symptom improvement.. Baseline Clinician-Administered PTSD Scale scores were 62.1 +/- 13.9 for placebo and 61.0 +/- 22.2 for topiramate. There was a high dropout rate from the study (55% topiramate; 25% placebo), with 40% of topiramate and 10% of placebo dropping because of adverse events (AEs). No significant treatment effects of topiramate versus placebo were observed for the primary treatment outcomes. Subjects reporting central nervous system-related AEs and with higher baseline severity of depression were more likely to discontinue because of AEs.. Primary outcome measures failed to demonstrate a significant effect for topiramate over placebo; however, high dropout rate in the treatment group prohibits definitive conclusions about the efficacy of topiramate in this population.

Topics: Age Factors; Anticonvulsants; Chronic Disease; Combat Disorders; Double-Blind Method; Drug Administration Schedule; Exanthema; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Psychiatric Status Rating Scales; Severity of Illness Index; Stress Disorders, Post-Traumatic; Time Factors; Topiramate; Treatment Outcome; Urinary Tract Infections; Veterans

This open study evaluates the effectiveness and safety of topiramate for the prophylaxis of chronic tension-type headache. Fifty-one patients were enrolled, of whom 46 completed 24 weeks of treatment with topiramate. Daily dosing was titrated from 25 mg to 100 mg by treatment week 4. The primary efficacy parameter was headache frequency at weeks 13-24 compared with baseline. Headache frequency declined from 23.50 +/- 5.32 days (baseline, mean, SD) to 12.58 +/- 6.28 days at weeks 13-24 (P < 0.0001), with frequency of severe headaches dropping from 8.18 to 3.14 days (P < 0.0001). The average headache intensity dropped from 6.13 to 2.07 on the visual analogue scale (P < 0.0001). These parameters were not significantly reduced at weeks 5-12. A 50% reduction in headache frequency was achieved in 73% of patients at weeks 13-24. Also improved were mood, sleep, quality of life (all parameters, P < 0.0001) as well as the Beck Depression Inventory-II (P < 0.0001). In addition, a highly significant weight loss of 2.14 kg (mean) was observed between baseline (71.64 +/- 10.65 kg) and week 24 [69.50 +/- 10.04 kg (SD)] (P < 0.0001). There were only few side-effects, none of these rated severe. The results provide preliminary confirmation of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache.

Topics: Adolescent; Adult; Affect; Analgesics; Anticonvulsants; Chronic Disease; Depression; Female; Fructose; Humans; Male; Medical Records; Middle Aged; Pilot Projects; Prospective Studies; Quality of Life; Sleep; Tension-Type Headache; Topiramate; Treatment Outcome

Chronic migraine (CM) is a disabling condition with not many treatment strategies available. Topiramate is effective in episodic migraine prevention, however little is known about its effect in CM. An open label study was performed. Sixty-four patients diagnosed with CM or probable CM according to the IHS diagnostic criteria were enrolled, 50 patients were available for analysis and an intention-to-treat methodology was applied. The primary endpoint considered was the number of patients with a decrease in headache frequency higher than 50%. The median dose was 100 mg, a reduction in frequency higher than 50% occurred in 33 patients (66%) and 14 (28%) presented a complete response, defined as a frequency reduction higher than 95%. The medication was well tolerated. The most common side effects found were weight loss, paraesthesias, nausea, cognitive dysfunction, fatigue, somnolence, insomnia and depression. Our findings suggest that topiramate is effective in CM prophylaxis.

Topics: Adult; Anticonvulsants; Brain; Chronic Disease; Cognition Disorders; Disorders of Excessive Somnolence; Female; Fructose; GABA-A Receptor Agonists; Humans; Ion Channels; Male; Middle Aged; Migraine Disorders; Nausea; Paresthesia; Receptors, GABA-A; Topiramate; Treatment Outcome

Chronic lumbar radicular pain is the most common neuropathic pain syndrome. This was a double-blind, randomized, 2-period crossover trial of topiramate (50 to 400 mg) and diphenhydramine (6.25 to 50 mg) as active placebo to assess the efficacy of topiramate. Each period consisted of a 4-week escalation, a 2-week maintenance at the highest tolerated dose, and a 2-week taper. Main outcome was the mean daily leg pain score on a 0 to 10 scale during the maintenance period. Global pain relief was assessed on a 6-level category scale. In the 29 of 42 patients who completed the study, topiramate reduced leg pain by a mean of 19% (P = .065). Global pain relief scores were significantly better on topiramate (P < .005). Mean doses were topiramate 200 mg and diphenhydramine 40 mg. We concluded that topiramate treatment might reduce chronic sciatica in some patients but causes frequent side effects and dropouts. We would not recommend topiramate unless studies of alternative regimens showed a better therapeutic ratio.. The anticonvulsant topiramate might reduce chronic lumbar nerve root pain through effects such as blockade of voltage-gated sodium channels and AMPA/kainite glutamate receptors, modulation of voltage-gated calcium channels, and gamma-aminobutyric acid agonist-like effects.

Topics: Adult; Aged; Analgesics; Anticonvulsants; Chronic Disease; Cross-Over Studies; Diphenhydramine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Humans; Intervertebral Disc Displacement; Ion Channels; Low Back Pain; Male; Middle Aged; Patient Compliance; Placebos; Radiculopathy; Receptors, Glutamate; Topiramate; Treatment Outcome

In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD.. Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a >/= 30% reduction of PTSD symptoms.. For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day.. Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

Topics: Adult; Anticonvulsants; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Personality Inventory; Prospective Studies; Psychotropic Drugs; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.

Topics: Adult; Analgesics; Chi-Square Distribution; Chronic Disease; Confidence Intervals; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Multivariate Analysis; Odds Ratio; Topiramate

The hypothesis that exposure to traumatic events may sensitize or kindle limbic nuclei has led to efforts to treat posttraumatic stress disorder (PTSD) with anticonvulsants. Based on the kindling hypothesis of PTSD, this open-label study assesses clinical response to topiramate as a potential treatment for DSM-IV PTSD.. A naturalistic data review was conducted of medical records of all adult outpatients (9 men. 26 women symptomatic for a mean +/- SD of 18 +/- 15 years with DSM-IV chronic civilian PTSD) treated with topiramate, 12.5 to 500 mg/day, as add-on (N = 28) or monotherapy (N = 7). The last 17 patients completed the PTSD Checklist-Civilian Version (PCL-C) before treatment and at week 4. Dosage titration started at 12.5 to 25 mg/day and increased in 25- to 50-mg increments every 3 to 4 days until a therapeutic response was achieved or the drug was no longer tolerated. The mean duration of treatment was 33 weeks (range, 1-119 weeks).. Topiramate decreased nightmares in 79% (19/24) and flashbacks in 86% (30/35) of patients, with full suppression of nightmares in 50% and of intrusions in 54% of patients with these symptoms. Nightmares or intrusions partially improved in a median of 4 days (mean = 11 +/- 13 days) and were fully absent in a median of 8 days (mean = 35 +/- 49 days). Response was seen in 95% of partial responders at a dosage of 75 mg/day or less, and in 91% of full responders at a dosage of 100 mg/day or less. Mean reductions in PCL-C score from baseline to week 4 were highly significant (baseline score = 60 vs. week 4 score = 39, p < .001), with similar reductions in reexperiencing, avoidance, and hyperarousal criteria symptoms. Thirteen patients discontinued for various reasons during the > 2-year study period. Except for a single instance of acute secondary narrow-angle glaucoma, there were no serious side effects.. Topiramate appeared effective as add-on or monotherapy for chronic PTSD. It demonstrated a rapid onset of action and minimally serious, dose-related side effects without the development of tolerance. Double-blind studies are indicated.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Comorbidity; Dose-Response Relationship, Drug; Dreams; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Hallucinations; Humans; Life Change Events; Male; Middle Aged; Personality Inventory; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Chronic Disease; Double-Blind Method; Humans; Migraine Disorders; Topiramate; Treatment Outcome; Valproic Acid

Calcitonin gene-related peptide (CGRP) inhibitors were introduced in the United States (US) in 2018. To understand the changing patterns of preventive treatment following the introduction of these new agents, we must first characterize the patterns which preceded their introduction.. To characterize the burden, unmet need, and treatment patterns in patients with migraine initiating preventive migraine medications before the introduction of CGRP inhibitors in the US.. Between March 2016 and October 2017, we enrolled episodic (EM) and chronic migraine (CM) patients initiating or changing preventive treatment at primary care or neurology clinic visits in the US, in a real-world observational study using a prospective cohort design. At baseline and monthly thereafter for 6 months, we collected data from study sites and patients on migraine frequency, treatment modifications, migraine impact on functioning, and work productivity for a descriptive analysis of migraine patient experience and treatment patterns.. From the sample of 234 completers, 118 had EM (50.4%) and 116 had CM (49.6%). Mean age at enrollment was 41 years (SD = 12) and mean age at first migraine diagnosis was 22 years (SD = 11). Most participants were females (n = 204/234; 87.2%) and white (n = 178/234; 76.1%). The majority (n = 164/234; 70.1%) had not used preventive migraine treatment in the 5 years prior to enrollment (treatment naïve). At baseline, mean monthly migraine days were 9.6 days (SD = 5.0) for the preventive treatment naïve group and 12.4 days (SD = 7.0) for treatment experienced patients. The majority had severe Migraine Disability Assessment (Grade IV, total score ≥21), including 67.1% (n = 110/164) of the preventive treatment naïve and 77.1% (n = 54/70) of the preventive treatment experienced patients. Headache Impact Test total scores indicating severe impairment (score >59) occurred in 88.4% (n = 145/164) of the treatment naïve and 88.6% (n = 62/70) of treatment experienced patients. Mean work productivity loss as measured by the Work Productivity and Activity Impairment questionnaire in the subsample of employed patients was 53.3% loss. The most used acute medications at baseline were nonsteroidal anti-inflammatory agents (n = 124/234; 53.0%), acetaminophen-based products (n = 112/234; 47.9%), and triptans (n = 105/234; 44.9%). The most commonly initiated preventive treatments were topiramate (n = 100/234; 42.7%), tricyclic antidepressants (n = 39/234; 16.7%), beta-blockers (n = 26/234; 11.1%), and onabotulinumtoxinA (n = 24/234; 10.3%). Over the 6-month follow-up period, almost half of patients (n = 116/234, 49.6%) modified their preventive treatment and discontinued treatment (n = 88/312 total modifications; 28.2%) or modified their pattern of use by increasing, decreasing, or skipping doses (n = 224/312 total modifications; 71.8%), often without seeking medical advice. Avoiding side effects was the main reason reported among patients who discontinued (n = 52/88; 59.1%), decreased frequency or dose (n = 37/89; 41.6%), and skipped doses (n = 29/86; 33.7%). Perceived lack of efficacy was another frequent reason reported among those who discontinued (n = 20/88; 22.7%), decreased frequency or dose (n = 15/89; 16.9%), and skipped doses (n = 18/86; 20.9%). Despite initiation of preventive treatment and improvements observed in number of headache and migraine days, migraine patients continued to experience substantial disability, headache impact, and reduced productivity througho. Prior to 2018, the burden of migraine was high for patients initiating preventive treatments. Despite having more than 9 days of migraine per month on average, the majority (70.1%) of patients initiating prevention had been treatment naïve, indicating underuse of preventive treatments. The preventive treatments used in this study were poorly tolerated and were reported by patients to lack efficacy, resulting in suboptimal adherence. The high discontinuation rates suggest that the preventive medications being offered during the period of the study did not meet the treatment needs of patients. In addition, the decisions by about half of patients to alter their prescribed treatment plan without consulting their provider can pose substantial health risks. These findings pertain to the broad set of preventive treatments initiated in this study and do not support inferences about individual preventive treatments, due to limitations in sample size. These findings suggest the need for more effective and better tolerated preventive treatment options.

Topics: Acetaminophen; Adrenergic beta-Antagonists; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Botulinum Toxins, Type A; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Neuromuscular Agents; Outcome Assessment, Health Care; Serotonin 5-HT1 Receptor Agonists; Topiramate

Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA.. We included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16-74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher's exact test.. Response to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33-7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28-8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found.. Polymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.

Topics: Adolescent; Adult; Aged; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Gene Frequency; Genome-Wide Association Study; Humans; Middle Aged; Migraine Disorders; Neuromuscular Agents; Polymorphism, Single Nucleotide; Prospective Studies; Topiramate; Treatment Outcome; TRPV Cation Channels; Young Adult

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM.. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM.

Topics: Adult; Botulinum Toxins, Type A; Chronic Disease; Clinical Trials as Topic; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Outcome Assessment, Health Care; Quality of Life; Time Factors; Topiramate; Treatment Outcome; Young Adult

Topics: Betamethasone; Child; Chronic Disease; Female; Fructose; Humans; Migraine Disorders; Paroxysmal Hemicrania; Topiramate; Treatment Outcome

Cocaine abuse is a major public health problem with multiple-related complications. Indeed, cocaine can affect almost every organ of the human body, but little is known about its effects on the visual system. The main purpose of this work was to study if topiramate was able to reverse changes in retinal metabolism and retinal function induced by chronic cocaine exposure in adult rats.. Sixteen Wistar rats were treated with a daily oral dose of cocaine during 36 days. Sixteen rats receiving NaCl 0.9% served as controls. Eight control and eight cocaine animals were administered topiramate from day 18 to day 36 of the experiment. Malondialdehyde (MDA), glutathione (GSH) and glutamate content, as well as glutathione peroxidase (GPx) activity in retina tissue homogenates were determined. Retinal function was assessed by electroretinogram (ERG).. Glutamate concentration was increased in the retinas of cocaine-treated rats. No changes in oxidative stress parameters were observed in the retinas of cocaine-treated rats when compared with the control ones. Cocaine induced a decrease in the a-wave and b-wave ERG amplitude. The administration of topiramate reversed cocaine-induced increase in glutamate concentration and had little effect on a-wave and b-wave ERG amplitude. Topiramate, a drug used during the last decade for the treatment of epileptic seizures, is able to reverse the cocaine-induced alterations observed in retinal glutamate concentration.. We can conclude that retinal glutamate metabolism and function may be affected by exposure to cocaine. We confirm that topiramate, a treatment recently proposed for cocaine dependence, is also able to recover partially cocaine-induced changes in the retina.

Topics: Animals; Anticonvulsants; Chronic Disease; Cocaine; Cocaine-Related Disorders; Energy Metabolism; Fructose; Male; Oxidation-Reduction; Rats, Wistar; Retina; Topiramate; Vasoconstrictor Agents; Visual Acuity

The prevalence of chronic headaches in children and adolescents is up to 2 % resulting in the beginning of the later typical headache careers of adults. The therapy for chronic migraine with botulinum toxin is now established in adults. However, there is only limited experience in the use of botulinum toxin in paediatric patients.. 10 patients aged 13 - 17 years who suffered from chronic migraine according to the IHS criteria were injected at 31 specific injection points of the head and neck muscles with a total amount of 150 IE of botulinum toxin A (Botox®) according to the approved scheme. The number of headache days per month over the following 9 months was recorded and side effects were retrospectively determined.. The responder rate (that is reduction of headache days per month more than 50 %) was 7/10 at three months after the injection. On average the number of headache days per month was reduced from 19.2 days to a minimum of 10.1 days. After three to six months the number of headache days increased again in all responders. Slight local side effects such as redness or temporary pain were observed in all patients, but severe side effects such as infections, fever, ptosis or allergic reactions did not occur.. This small case series shows that the therapy for chronic migraine with botulinum toxin A can also be effective and safe in adolescents. As many adolescents still suffer from headaches later as adults a link between neuropaediatricians and neurologists is justifiable. An early botulinum toxin therapy followed by the transition of the adolescents would be helpful.

Topics: Adolescent; Adrenergic beta-Antagonists; Botulinum Toxins, Type A; Chronic Disease; Female; Fructose; Humans; Male; Metoprolol; Migraine Disorders; Neurology; Neuromuscular Agents; Neuroprotective Agents; Pediatrics; Retrospective Studies; Topiramate; Transcutaneous Electric Nerve Stimulation; Treatment Outcome

This clinical practice guideline for treatment of DSM-5 feeding and eating disorders was conducted as part of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guidelines (CPG) Project 2013-2014.. The CPG was developed in accordance with best practice according to the National Health and Medical Research Council of Australia. Literature of evidence for treatments of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified and unspecified eating disorders and avoidant restrictive food intake disorder (ARFID) was sourced from the previous RANZCP CPG reviews (dated to 2009) and updated with a systematic review (dated 2008-2013). A multidisciplinary working group wrote the draft CPG, which then underwent expert, community and stakeholder consultation, during which process additional evidence was identified.. In AN the CPG recommends treatment as an outpatient or day patient in most instances (i.e. in the least restrictive environment), with hospital admission for those at risk of medical and/or psychological compromise. A multi-axial and collaborative approach is recommended, including consideration of nutritional, medical and psychological aspects, the use of family based therapies in younger people and specialist therapist-led manualised based psychological therapies in all age groups and that include longer-term follow-up. A harm minimisation approach is recommended in chronic AN. In BN and BED the CPG recommends an individual psychological therapy for which the best evidence is for therapist-led cognitive behavioural therapy (CBT). There is also a role for CBT adapted for internet delivery, or CBT in a non-specialist guided self-help form. Medications that may be helpful either as an adjunctive or alternative treatment option include an antidepressant, topiramate, or orlistat (the last for people with comorbid obesity). No specific treatment is recommended for ARFID as there are no trials to guide practice.. Specific evidence based psychological and pharmacological treatments are recommended for most eating disorders but more trials are needed for specific therapies in AN, and research is urgently needed for all aspects of ARFID assessment and management.. Associate Professor Susan Byrne, Dr Angelica Claudino, Dr Anthea Fursland, Associate Professor Jennifer Gaudiani, Dr Susan Hart, Ms Gabriella Heruc, Associate Professor Michael Kohn, Dr Rick Kausman, Dr Sarah Maguire, Ms Peta Marks, Professor Janet Treasure and Mr Andrew Wallis.

Topics: Anti-Obesity Agents; Antidepressive Agents; Australia; Chronic Disease; Cognitive Behavioral Therapy; Feeding and Eating Disorders; Fructose; Harm Reduction; Humans; Lactones; New Zealand; Obesity; Orlistat; Psychiatry; Societies, Medical; Topiramate

Pediatric patients who are fed primarily via gastrostomy tube (G-tube) may be at increased risk for urolithiasis, but no studies have specifically examined risk factors for stones in this population. We aimed to determine clinical differences between G-tube fed (GTF) patients with and without stones, in hopes of identifying modifiable factors associated with increased risk of urolithiasis.. We conducted a retrospective case-control study, matching GTF patients with urolithiasis (cases) to GTF children without urolithiasis (controls) based on age (±1 year) and gender. Bivariate comparisons and matched logistic regression modeling were used to determine the unadjusted and adjusted associations between relevant clinical factors and urolithiasis.. Forty-one cases and 80 matched controls (mean age 12.0 ± 6.5 years) were included. On bivariate analysis, factors associated with stone formation included: white race, urinary tract infection (UTI), topiramate administration, vitamin D use, malabsorption, dehydration, 2-year duration with G-tube, and whether goal free water intake was documented in the patient chart. On regression analysis, the following factors remained significant: topiramate administration (odds ratio [OR]: 6.58 [95% confidence interval (CI): 1.76-24.59]), UTI (OR: 7.70 [95% CI: 1.59-37.17]), and <2 years with a G-tube (OR: 8.78 [95% CI: 1.27-52.50]).. Our findings provide a preliminary risk profile for the development of urolithiasis in GTF children. Important associations identified include UTI, topiramate administration, and shorter G-tube duration, which may reflect subclinical chronic dehydration. Of these, topiramate use represents the most promising target for risk reduction.

Topics: Adolescent; Age Factors; Anticonvulsants; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Cohort Studies; Enteral Nutrition; Female; Fructose; Gastrostomy; Humans; Male; Retrospective Studies; Risk Factors; Sex Factors; Topiramate; Urolithiasis

Previous magnetoencephalographic (MEG) studies showed different P100m (where 'm' denotes the magnetic counterpart of P100 in conventional visual evoked potentials) responses between episodic migraine (EM) and chronic migraine (CM) interictally. This study investigated the changes of visual P100m in CM patients who remitted to EM from CM after treatment.. At baseline, 25 patients with CM were studied interictally. For each patient, 30 sequential blocks of 50 P100m responses were obtained by MEG. Sub-averaged amplitudes at blocks 2, 9, 16, 23 and 30 were further compared with that at block 1 to assess response habituation or potentiation (i.e. significant decrease or increase at either block vs block 1). The same study was repeated in those patients who remitted from CM to EM after topiramate treatment.. In total, 10 CM patients remitted to EM after treatment. In the follow-up study of these patients during the interictal stage, the P100m at block 1 decreased in amplitude from 53.6 ± 6.6 nAm before remission to 43.0 ± 5.1 nAm (p = 0.028), and the responses at subsequent blocks switched from habituation (amplitude block 30 < block 1 before remission, p = 0.011) to potentiation (block 2 > block 1, p = 0.028).. The pattern of P100m responses to consecutive stimulation changes with the transition from CM to EM. Visual cortex plasticity might be a potential biomarker reflecting clinical remission of CM.

Topics: Adult; Anticonvulsants; Chronic Disease; Evoked Potentials, Visual; Female; Follow-Up Studies; Fructose; Humans; Magnetoencephalography; Male; Migraine Disorders; Neuronal Plasticity; Remission Induction; Topiramate; Visual Cortex; Young Adult

Chronic migraine is a common disabling condition. Severe migraine attacks should be treated with triptans, but these agents are contraindicated in patients with vascular problems and may not be effective or tolerated in around one third of the patients. New acute migraine therapies without vasoconstrictive activity and triptan-specific side effects are emerging. For the prophylaxis of chronic migraine, only topiramate and OnabotulinumtoxinA have been shown to be effective in placebo-controlled randomized trials, so novel therapeutic strategies are needed. The growing understanding of the pathophysiology of chronic migraine will contribute to the identification of new treatment targets.

Topics: Botulinum Toxins, Type A; Chronic Disease; Drug Design; Fructose; Humans; Migraine Disorders; Molecular Targeted Therapy; Neuromuscular Agents; Neuroprotective Agents; Topiramate; Tryptamines

Patients with frequent episodic and chronic migraine, which is often complicated with drug abuse, are resistant to treatment. An objective of the study was to evaluate the efficacy and safety of topalepsin (topiramate) in the preventive treatment of migraine. Thirty patients with frequent episodic and chronic migraine were treated with topalepsin (100 mg daily) during 6 months. After treatment, there was a significant reduction in the number of days with headache and migraine attacks as well as their duration, severity of concomitant symptoms and amount of analgesics used by patients.

Topics: Adult; Analgesics; Anticonvulsants; Chronic Disease; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

Topics: Amitriptyline; Analgesics; Anticonvulsants; Antidepressive Agents, Tricyclic; Chronic Disease; Female; Fructose; Humans; Male; Migraine Disorders; Risk Factors; Topiramate; Tryptamines; Valproic Acid

Lamotrigine (LTG) and topiramate (TPM), two of the most commonly used new-generation antiepileptic drugs (AEDs), have been shown to produce no adverse and impaired cognitive effects in patients with epilepsy, respectively. As seizure-induced neurogenesis might contribute to cognitive deficits that are associated with status epilepticus (SE), we examined whether these two drugs produce differential effects on seizure-induced neurogenesis in the hippocampus of adult rats. Lithium pilocarpine model was used to mimic human temporal-lobe epilepsy. Five hours after SE, LTG and TPM were administered intragastrically twice daily throughout the entire length of the experiment with total daily dose of 20 and 80 mg/kg, respectively. The hippocampal neurogenesis was examined using 5-bromodeoxyuridine and doublecortin immunohistochemistry. Both LTG and TPM treatments significantly inhibited seizure-induced proliferation of neural progenitors in the hippocampus, but did not affect the neuronal differentiation of newborn cells. Long-term treatment with both AEDs decreased the number of spontaneous recurrent seizures after SE and alleviated chronic seizure-induced neuronal injury in the dentate hilus. Eventually, TPM significantly increased the number of newborn neurons in the dentate granular cell layer after seizures likely by promoting the survival of newborn neurons. In contrast, LTG treatment significantly reduced the number of ectopic hilar newborn neurons after seizures. Neither of them prevented the formation of hilar basal dendrites of newborn neurons in the epileptic hippocampus. These results indicate that TPM but not LTG promotes aberrant neuron regeneration in the hippocampus after SE, which might be partially related to their differential effects on cognitive function.

Topics: Adult Stem Cells; Animals; Anticonvulsants; Cell Proliferation; Cell Survival; Chronic Disease; Dendrites; Dentate Gyrus; Disease Models, Animal; Doublecortin Protein; Epilepsy, Temporal Lobe; Fructose; Hippocampus; Lamotrigine; Male; Neurogenesis; Neurons; Rats; Rats, Sprague-Dawley; Seizures; Topiramate; Triazines

Chronic migraine is an important public health problem. The aim of treatment should be to reduce migraine frequency and its negative impact on functioning, as well as to limit the use of acute medications. These goals may be accomplished by introducing effective prophylaxis. The aim of the present article is to critically review the published evidence on the pharmacological prophylaxis of chronic migraine, analysing published double-blind, placebo-controlled studies on adult patients. The results of the review indicate that tizanidine, gabapentin, valproic acid, and particularly topiramate are effective prophylactics against chronic migraine, with improvements in several endpoints that were significantly superior to those achieved by placebo. However, the different results found by different trials, as well as several methodological problems inherent in the trials, suggest the need for further research to provide clear indications from large, multicentre, controlled trials with homogeneous inclusion criteria and adequate endpoints.

Topics: Amines; Analgesics; Chronic Disease; Clonidine; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Double-Blind Method; Fructose; GABA Agents; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid

Management of patients affected by chronic daily headache (CDH) with medication overuse constitutes one of the most important unresolved problems. The uncertainty regarding the classification and the prophylaxis are a remarkable part of this problem. Objectives are to: (1) to evaluate the efficacy of withdrawal therapy following prophylaxis with topiramate and amitriptyline in a population affected by CDH and medication overuse with follow-up at 1 (T1), 3 (T2) and 6 (T3) months; (2) to identify which group of the Silberstein's CDH classification (1994) may benefit from this protocol. Inclusion criteria are patients with CDH (headache for more >15 days/month for at least 3 consecutive months) and medication overuse according with IHS second edition (8.2 group); exclusion criteria are patients with secondary headache. All patients included in the study were hospitalized for 1 week. Type of overuse: combination of medications, 38%; analgesics, 29%; triptans, 29%; opioids, 2%; ergotamines, 2%. During hospitalization the following protocol was applied: desametasone 4 mg i.v./day for 1 week, diazepam 6 mg/day for 10 days and prophylaxis with amitriptylin plus topiramate. This prophylaxis was protracted for at least 6 months. The dosages assumed ranged for amitriptylin from 10 to 20 mg/day and for topiramate from 50 to 100 mg/day. In the last 4 years 105 patients with CDH (age 24-89 years; f 96; m 9) were admitted to the hospital. The protocol was applied in 52 patients (age, 29-65 years; f 49; m 3). At T1, 89% of the patients did not fall again into medication overuse; at T2, 64%; and at T3,45% of the patients remained free from overuse. According to the Silberstein' proposal at T1, 93% of the subjects was affected by transformed migraine; and 7% by tension-type headache. At T3, all the patients free from overuse were affected by transformed migraine. Our data suggest that the patients affected by CDH and medication overuse benefit from withdrawal therapy performed during hospitalization plus prophylaxis with amitriptyline plus topiramate. This combination seems a good pharmacological solution to reduce the risk of relapse.

Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Analgesics, Non-Narcotic; Chronic Disease; Female; Fructose; Headache Disorders; Humans; Male; Middle Aged; Patient Selection; Topiramate; Treatment Outcome

To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ).. Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis.. In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420).. Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Topics: Adult; Anticonvulsants; Chronic Disease; Cohort Studies; Comorbidity; Craniocerebral Trauma; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Drug Utilization; Drugs, Generic; Epilepsy; Female; Fractures, Bone; Fructose; Health Benefit Plans, Employee; Health Care Costs; Hospitalization; Humans; Insurance, Health, Reimbursement; Male; Patient Acceptance of Health Care; Proportional Hazards Models; Quebec; Retrospective Studies; Risk Factors; Topiramate

To explore the option of using anticonvulsant drugs to modulate pain from corneal erosions.. N.M. is a 28-year-old woman with posttraumatic recurrent corneal erosions treated with bandage contact lenses, Muro-128, topical ketorolac, doxycycline, stromal micropuncture, and laser epithelial keratomileusis over the course of 4 years. Because of persistent episodes of corneal pain, she was prescribed topiramate.. Before starting topiramate therapy, N.M. had experienced 3-4 awakenings at night because of pain and 5-6 episodes of spontaneous tearing and pain during the day. She started topiramate at 25 mg orally 4 times a day without significant change in her symptoms. After 1 week, the dose was escalated to 50 mg orally 4 times a day, and within 1 day, she experienced 0-1 awakenings at night. She had approximately 2-3 episodes of pain and tearing during the day. The dose was escalated to 100 mg orally 4 times a day. At that dose, the patient continued to have pain relief but complained of nausea. The patient's topiramate was weaned off to determine whether her symptom relief was caused by the medication or improvement in her condition. Once off the topiramate, N.M.'s nausea resolved but her corneal symptoms returned at the same frequency as before the initiation of topiramate. Therefore, she was restarted on topiramate 50 mg orally 4 times a day with rapid onset of improvement in her symptoms.. Anticonvulsants such as topiramate may be effective in the management of pain caused by recurrent corneal erosions.

Topics: Adult; Anticonvulsants; Chronic Disease; Corneal Diseases; Female; Fructose; Humans; Pain; Topiramate

Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.

Topics: Adult; Analysis of Variance; Chronic Disease; Differential Threshold; Dose-Response Relationship, Drug; Electric Stimulation; Electromyography; Evoked Potentials, Motor; Fructose; Humans; Middle Aged; Motor Cortex; Neuralgia; Neuroprotective Agents; Topiramate; Transcranial Magnetic Stimulation

Topics: Analgesics; Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Fructose; Humans; Migraine Disorders; Topiramate

Potential antiepileptic drugs (AEDs) are typically screened on acute seizures in normal animals, such as those induced in the maximal electroshock and pentylenetet-razole models. As a proof-of-principle test, the present experiments used spontaneous epileptic seizures in kainate-treated rats to examine the efficacy of topiramate (TPM) with a repeated-measures, crossover protocol.. Kainic acid was administered in repeated low doses (5 mg/kg) every hour until each Sprague-Dawley rat experienced convulsive status epilepticus for >3 h. Six 1-month trials (n = 6-10 rats) assessed the effects of 0.3-100 mg/kg TPM on spontaneous seizures. Each trial involved six pairs of TPM and saline-control treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Data analysis included a log transformation to compensate for the asymmetric distribution of values and the heterogeneous variances, which appeared to arise from clustering of seizures.. A significant effect of TPM was observed for 12 h (i.e., two 6-h periods) after a 30-mg/kg injection, and full recovery from the drug effect was complete within 43 h. TPM exerted a significant effect at doses of 10, 30, and 100 mg/kg, and the effects of TPM (0.3-100 mg/kg) were dose dependent.. These data suggest that animal models with spontaneous seizures, such as kainate- and pilocarpine-treated rats, can be used efficiently for rapid testing of AEDs with a repeated-measures, crossover protocol. Furthermore, the results indicate that this design allows both dose-effect and time-course-of-recovery studies.

Topics: Animals; Anticonvulsants; Chronic Disease; Cross-Over Studies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Epilepsy; Fructose; Injections, Intraperitoneal; Kainic Acid; Pilocarpine; Rats; Rats, Sprague-Dawley; Research Design; Sodium Chloride; Status Epilepticus; Topiramate

Topics: Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Incidence; Migraine Disorders; Pregnancy; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Carbonic Anhydrase Inhibitors; Chronic Disease; Dose-Response Relationship, Drug; Erectile Dysfunction; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nitric Oxide; Penile Erection; Regional Blood Flow; Sex Characteristics; Sexual Dysfunction, Physiological; Topiramate

Topics: Adolescent; Anticonvulsants; Bipolar Disorder; Brain; Chronic Disease; Fructose; Humans; Male; Topiramate

To report observations on the efficacy and tolerability of topiramate in a sample of five patients with severe symptoms of bulimia nervosa and comorbid mood and/or anxiety disorders.. Topiramate was added to other psychotropic medication under open-label conditions up to the maximum tolerated dose or until remission of the eating disorder was achieved.. Topiramate almost completely eliminated binging and purging behavior in three of the five patients. Improvement was maintained throughout the period of follow-up for up to 18 months. One patient showed a partial, temporary response, and the fifth was intolerant of the drug and unable to complete an adequate trial.. These results suggest strongly that the efficacy of topiramate in patients with bulimia nervosa with and without comorbid mood and anxiety disorders should be investigated more fully.

Topics: Adult; Anxiety Disorders; Bipolar Disorder; Bulimia; Chronic Disease; Comorbidity; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Recurrence; Topiramate; Treatment Outcome

To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion.. Clonidine is a medication long used to treat hypertension, and it is still used in the treatment of refractory hypertension. Although effective, clonidine use is hindered by adverse effects and its dual mechanism of action.. A 39-year-old white, quadriplegic man with poorly controlled pain displayed many characteristics consistent with autonomic dysfunction (e.g., C4 spinal lesion, orthostatic hypotension, hypertension). The patient was routinely receiving transdermal clonidine and also received transdermal nitroglycerin paste as needed for control of acute hypertensive episodes. On the recommendation of the home healthcare pharmacists, clonidine was discontinued. Since that time, the patient's blood pressure and the use of emergent antihypertensive treatment have decreased significantly (maximum systolic and diastolic BP by approximately 50 and 25 mm Hg, respectively).. Many of the characteristics of autonomic dysfunction, such as refractory hypertension, can seem selective for the use of clonidine and, because of its reliance on central alpha(2)-activity for its hypotensive effects, clonidine may induce hypertension in patients with autonomic dysfunction. Clonidine should be used with great caution when autonomic dysfunction is suspected.

Topics: Adrenergic alpha-Agonists; Adult; Blood Pressure; Chronic Disease; Clonidine; Fructose; Humans; Hypertension; Male; Neuroprotective Agents; Pain; Pain Measurement; Paraplegia; Spinal Cord Injuries; Topiramate

To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis.. Topiramate has multiple mechanisms of action that could potentially contribute to migraine prophylaxis. We conducted a retrospective chart review to assess the efficacy of topiramate as add-on therapy in patients with transformed migraine or cluster headache, and as first-line therapy in patients with episodic migraine.. Patients diagnosed with transformed migraine, episodic migraine, or cluster headache, who received topiramate either as add-on therapy or monotherapy were selected via retrospective chart review. Patients had begun topiramate therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients with transformed migraine and cluster headache, and as a first-line monotherapy in patients with episodic migraine who had no previous prophylactic therapy. The outcome parameters examined included a mean 28-day migraine frequency, migraine severity, number of headache days/month, number of abortive medication tablets/month, patient global evaluation, and the MIDAS scale.. One hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: n = 70; and cluster headache: n = 12) were included in the retrospective analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For patients with transformed migraine, mean migraine frequency decreased from 6.3/28 days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point scale, with 10 representing the most severe pain (P = 0.003). The mean number of headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001). Patient global evaluation indicated substantial or moderate improvement in 53% of patients with transformed migraine who used topiramate as add-on therapy. Mean MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic migraine patients who were administered topiramate as first-line therapy exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one percent of patients reported marked improvement. Nine of the 12 cluster headache patients exhibited substantial or moderate improvement in symptoms, whereas three had no improvement. The most common adverse effects were paresthesias (12%), cognitive effects (11%), and dizziness (6%). Eight patients discontinued topiramate due to adverse effects; cognitive effects were the most common reason. No patient discontinued topiramate treatment due to lack of efficacy. Twelve percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs).. For both patients with transformed migraine (add-on therapy) and patients with episodic migraine (first-line monotherapy), topiramate yielded significant reductions in migraine frequency, migraine severity, number of headache days/month, and use of abortive medications. Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache. Prospective double-blind, placebo-controlled trials will be required to confirm our results.

Topics: Adult; Aged; Anticonvulsants; Chronic Disease; Cluster Headache; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Recurrence; Retrospective Studies; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Chronic Disease; Drug Interactions; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Topiramate; Treatment Failure

Posttraumatic stress disorder (PTSD) is a serious and debilitating mental condition that affects a significant proportion of the general population at some time in their lives. To date, however, the U.S. Food and Drug Administration has approved only 1 pharmacologic treatment for this indication. Additional effective therapies are urgently required to control the destructive symptoms experienced by individuals with PTSD. This article reviews the effects of the novel antiepileptic drug topiramate on 3 patients meeting DSM-IV criteria for chronic PTSD. In these previously treatment-refractory patients, topiramate had a marked effect: reducing and even eliminating trauma-related intrusive memories and nightmares and normalizing depressed mood. Adverse events were effectively controlled with careful drug titration and discontinuation of concomitant therapies. These findings, together with observations in more than 30 additional patients (reported elsewhere), suggest that further study of topiramate as a treatment for PTSD is warranted.

Topics: Adult; Anticonvulsants; Chronic Disease; Dreams; Female; Fructose; Humans; Male; Memory; Middle Aged; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome

To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention.. All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression.. Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy.. A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Chronic Disease; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Learning Disabilities; Male; Middle Aged; Prognosis; Proportional Hazards Models; Survival Analysis; Topiramate

Topics: Adult; Antipsychotic Agents; Body Weight; Chronic Disease; Clozapine; Fructose; Humans; Male; Neuroprotective Agents; Obesity; Schizophrenia, Paranoid; Topiramate; Weight Loss

We sought to determine the long-term retention rates of lamotrigine (LTG), gabapentin (GBP), and topiramate (TPM) therapy for patients at a tertiary referral clinic for chronic, refractory epilepsy.. We analyzed 424 consecutive patients with chronic, refractory partial and/or generalized epilepsy who were started on LTG, 158 patients who were started on GBP, and 393 patients who were started on TPM. The percentages of patients who continued therapy with LTG, GBP, and TPM were estimated with the use of Kaplan-Meier survival analysis. Factors that influence retention were analyzed with the use of Cox regression analysis.. Kaplan-Meier survival analysis showed that at 3 years, 30% continued therapy on TPM compared with 29% on LTG and fewer than 10% on GBP. Adverse events resulted in therapy withdrawal in 40% of patients on TPM compared with GBP (37%) and LTG (22%). Perceived lack of efficacy led to treatment withdrawal in 39% of patients on GBP compared with 34% on LTG and 19% on TPM. Cox regression estimated that a fourth or fewer of patients with chronic partial epilepsy are likely to continue therapy with a new antiepileptic drug beyond 5 years.. The impact of these new antiepileptic drugs on the long-term course of chronic partial epilepsy is likely to be small, as approximately three of four patients will discontinue therapy. More patients appear to continue on TPM compared with LTG or GBP, with a possible reason being better perceived efficacy of TPM, despite having the highest incidence of adverse events.

Topics: Acetates; Adolescent; Adult; Age of Onset; Aged; Amines; Anticonvulsants; Chronic Disease; Cyclohexanecarboxylic Acids; Epilepsy; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Middle Aged; Patient Compliance; Patient Dropouts; Proportional Hazards Models; Survival Analysis; Topiramate; Triazines