topiramate and Cognition-Disorders

Nongenetic biologic and lifestyle-related factors, including age, sex, hepatic/renal function, diet/exercise practices, illness severity, smoking, and alcohol consumption habits can account for the heterogeneity of treatment effects (HTE). However, even when these factors are taken into account, considerable variation remains unexplained and could potentially be attributable to genetic differences between patients. Drug response may be dictated by variation in genes involved in both pharmacokinetic (PK) (absorption, distribution, metabolism, excretion [ADME]) and pharmacodynamic (PD) (receptors, ion channels, enzymes, immune system) pathways. Functional variants of the ADME genes can result in patients being poor, intermediate, efficient, or ultrarapid metabolizers of specific agents, thereby affecting efficacy and/or susceptibility to adverse drug reaction and necessitating individualized dosing. A well-documented example of ADME gene variation is the debrisoquine polymorphism, which is characterized by markedly different metabolism of numerous commonly prescribed drugs based on variants of the cytochrome P450 2D6 gene. Variants of genes regulating PD pathways cause altering of drug target pathways, which may affect efficacy in a more pronounced manner. Examples of gene variants affecting PD pathways include those coding for dopamine metabolism, synthesis, and transport. These gene variants may act independently, in combination with each other, and/or in combination with PK genes to affect drug response, for example to antipsychotic medications. Increased understanding of a patient's genotype and its corresponding effect on drug response would be useful to the practicing clinician in choosing an effective drug and in optimizing the dose in a timely manner.

Topics: Adolescent; Adult; Age Factors; Clinical Trials as Topic; Cognition Disorders; Dose-Response Relationship, Drug; Epilepsy; Female; Fructose; Genetics, Population; Humans; Male; Middle Aged; Pharmacogenetics; Risk Assessment; Sex Factors; Topiramate; Treatment Outcome

The increasing use of anticonvulsant drugs in psychiatry has prompted greater awareness of their effects on a range of psychiatric domains, including cognition. Older versus newer antiepileptic drugs have been reported to either worsen or enhance cognitive performance in clinical populations, and the extent to which cognitive disturbances may reflect iatrogenic factors versus psychopathology is subject to debate. We review current information about the role of anticonvulsants in cognition, with particular emphasis on newer compounds (such as lamotrigine, gabapentin, and topiramate), the cognitive dimensions of affective illness, and the clinical approach to evaluating cognition in psychiatric patients taking anticonvulsant drugs over time.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Mood Disorders; Topiramate; Triazines; Valproic Acid

The aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of ≤400-mg/day USL255, Qudexy® XR (topiramate) extended-release capsules, as adjunctive therapy for partial-onset seizures (POS) in adults.. Patients who completed the 11-week double-blind treatment phase of the phase 3 PREVAIL study were eligible to enroll in this 1-year open-label extension (OLE) study (PREVAIL OLE). The primary objective was to evaluate the safety and tolerability of USL255 (including treatment-emergent adverse events [TEAEs]). The secondary objective was to assess seizure frequency in patients (e.g., median percent reduction from baseline in weekly POS frequency, responder rate [proportion of patients with ≥25%, ≥50%, ≥75%, or 100% reduction from baseline in POS frequency], and seizure-free intervals [proportion of patients who were seizure-free for 4, 12, 24, 36, or 48weeks]). Exploratory clinical-status endpoints included the Global Impression of Change (CGI-C) and Quality of Life in Epilepsy-Problems (QOLIE-31-P) questionnaires. Post hoc analyses evaluated neurocognitive TEAE incidences during the first 11 and entire 55weeks of treatment and efficacy by patient age and drug-resistant status.. Of the 217 patients who completed PREVAIL (USL255, n=103; placebo, n=114), 210 (97%) enrolled in PREVAIL OLE and were included in the ITT population. Across the entire 55-week treatment period, USL255 was generally safe and well tolerated, with low individual neurocognitive TEAE incidences. Seizure reduction was sustained across the year-long study and observed in patient subgroups, including those with highly drug-resistant seizures and those ≥50years of age. Improvements in CGI-C and QOLIE-31-P were also observed.. The results of PREVAIL OLE are consistent with those from PREVAIL and demonstrate that adjunctive treatment with up to 400mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.

Topics: Adult; Aging; Anticonvulsants; Cognition Disorders; Delayed-Action Preparations; Double-Blind Method; Drug Resistant Epilepsy; Epilepsies, Partial; Female; Fructose; Humans; Male; Quality of Life; Seizures; Surveys and Questionnaires; Topiramate; Treatment Outcome

Topiramate is being investigated as a potential pharmacotherapy for the treatment of addictive disorders. However, its cognitive side effects raise concerns about its use, especially in populations with cognitive impairment, such as persons with chronic substance use disorders. This study investigated topiramate's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind, randomized, controlled trial of topiramate for cocaine dependence treatment. After 5 weeks of stabilization on daily oral methadone (M = 96 mg), participants were randomized to topiramate (n = 18) or placebo (n = 22). Cognitive testing took place at 2 time points: study weeks 4 through 5 to assess baseline performance and 10 to 13 weeks later to assess performance during stable dosing (300 mg topiramate or placebo). All participants were maintained on methadone at both testing times, and testing occurred 2 hours after the daily methadone plus topiramate/placebo administration. The topiramate and placebo groups did not differ on sex, level of education, premorbid intelligence, methadone dose, or illicit drug use. Topiramate slowed psychomotor and information processing speed, worsened divided attention, reduced n-back working memory accuracy, and increased the false alarm rate in recognition memory. Topiramate had no effects on visual processing, other measures of psychomotor function, risk-taking, self-control, Sternberg working memory, free recall, and metamemory. These findings indicate that topiramate may cause cognitive impairment in this population. This effect may limit its acceptability and use as a treatment in individuals with chronic opioid and cocaine use disorders, among whom preexisting cognitive impairments are common. (PsycINFO Database Record

Topics: Adult; Cocaine-Related Disorders; Cognition Disorders; Diagnosis, Dual (Psychiatry); Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Methadone; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders; Topiramate

The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.

Topics: Adult; Aged; Alcohol Drinking; Alcohol-Related Disorders; Anticonvulsants; Cognition Disorders; Double-Blind Method; Female; Fructose; Humans; Isoxazoles; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Topiramate; Treatment Outcome; Young Adult; Zonisamide

The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders.. This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity.. Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment.. These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated.

Topics: Adult; Alcohol Drinking; Alcohol-Related Disorders; Cognition Disorders; Craving; Diagnosis, Dual (Psychiatry); Double-Blind Method; Female; Fructose; Humans; Male; Medication Adherence; Middle Aged; Pilot Projects; Stress Disorders, Post-Traumatic; Topiramate; Treatment Outcome; Veterans

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

Topics: Adolescent; Child; Cognition Disorders; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Topiramate

Neuropsychologic data are presented from a randomized, double-blind, placebo-controlled, multicenter study with placebo, topiramate 50 mg/day, and topiramate 100 mg/day. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and cognitive adverse events were used to evaluate neurocognitive effects of topiramate. Topiramate 100 mg/day vs placebo was associated with slight statistically significant score increases, indicating slowing, from baseline vs placebo in three CANTAB measures: five-choice reaction time (P = 0.028), pattern recognition memory mean correct latency (P = 0.027), and rapid visual information processing mean latency (P = 0.040). No other patterns related to topiramate treatment were observed in measurements of learning, memory, and visual information processing, except for potential improvement with topiramate 100 mg/day vs placebo in spatial span total errors (accuracy test) (P = 0.040). The most common cognitive and neuropsychiatric adverse events with a higher incidence in the topiramate 50 and 100 mg/day groups vs placebo were anorexia (9% and 11% vs 3%), insomnia (9% and 3% vs 3%), fatigue (6% and 9% vs 6%), and dizziness (6% and 9% vs 0%). Thus, topiramate 100 mg/day was associated with modest increases in psychomotor reaction times. Learning, memory, and executive function were unchanged. The tolerability profile, including cognitive adverse events, appeared to be acceptable.

Topics: Adolescent; Anorexia; Child; Cognition Disorders; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Reaction Time; Recognition, Psychology; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Space Perception; Topiramate; Visual Perception

This 12-week open label study explored cognitive and seizure outcomes of 53 children treated with topiramate (TPM). The digit symbol test and verbal learning memory test were administered at baseline and study endpoint. Topiramate was started either in monotherapy or add-on therapy. Overall, 57% of children experienced a ≥50% seizure reduction, 36% became seizure free and cognitive testing revealed no significant changes during TPM therapy. Due to the heterogeneity of the study population, post hoc analyses were added to compare patients in initial or conversion to TPM monotherapy as well as patients who continued add-on therapy. Verbal learning memory test parameters showed neither significant differences within any subgroup comparing baseline with endpoint nor significant differences between described subgroups except for one finding. The digit symbol test revealed no differences between each subgroup between baseline and endpoint. Comparing pre-post differences, TPM monotherapy was associated with better cognitive outcomes than treatment in add-on therapy. These results have to be interpreted with caution given the short study duration and the heterogeneity of the study population. Despite these limitations, our overall results suggest that treatment with topiramate is associated with improved seizure control without significant changes in cognitive functions at the low doses tested.

Topics: Adolescent; Anticonvulsants; Body Weight; Child; Cognition Disorders; Dose-Response Relationship, Drug; Epilepsy; Female; Fructose; Humans; Male; Memory Disorders; Neuropsychological Tests; Prospective Studies; Psychiatric Status Rating Scales; Seizures; Severity of Illness Index; Single-Blind Method; Time Factors; Topiramate; Verbal Learning

Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.. This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument.. Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05).. For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Psychometrics; Taiwan; Topiramate; Young Adult

The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Child; Child, Preschool; Cognition Disorders; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Mental Disorders; Prospective Studies; Severity of Illness Index; Statistics, Nonparametric; Topiramate; Treatment Outcome

To evaluate the cognitive and behavioral effects of topiramate (TPM) versus carbamazepine (CBZ) using efficacious doses of each drug as monotherapy for children with benign rolandic epilepsy.. A multicenter, randomized, open-label, observer-blinded, parallel-group clinical trial was conducted. TPM was introduced at a dose of 12.5 mg/day with the minimum target dose of 50 mg/day in patients <30 kg and 75 mg/day in patients >30 kg over 4 weeks. CBZ was started at a dose of 10 mg/kg/day with the minimum target dose of 20 mg/kg/day over 4 weeks. Additional individual escalation was allowed up to a maximum target dose. The primary study end point was change on a neuropsychological test battery after 28 weeks of treatment.. Neuropsychological data were available for 88 patients (45 patients for TPM and 43 patients for CBZ). Of the cognitive variables measured, arithmetic showed significant worsening in TPM (p = 0.037). An additional test, for maze, also showed a significantly greater improvement for CBZ (p = 0.026). Of behavioral variables, no significant changes were found but the scores had a negative trend for the TPM. When 30 patients on the minimum target dose for TPM were compared to 40 patients treated with minimum target CBZ, there was no significant worsening of cognitive and behavioral effects in the TPM.. The pattern of neuropsychometric changes with TPM seemed to be slightly worse overall than CBZ. However, outcome with the minimum target dose did not differ significantly in comparisons between the treatment groups.

Topics: Adolescent; Age Factors; Anticonvulsants; Carbamazepine; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy, Rolandic; Fructose; Humans; Neuropsychological Tests; Personality Inventory; Topiramate; Treatment Outcome

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

Topics: Adult; Anorexia; Anticonvulsants; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nausea; Paresthesia; Patient Compliance; Placebos; Time; Time Factors; Topiramate; Withholding Treatment

To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task-related and resting-state EEG and evoked potential (EP) measures.. We used a double-blind, randomized, crossover design. Healthy adults (N = 29) had two 8-week periods of dose escalation, 4 weeks of drug maintenance (300 mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM) tasks and resting conditions at baseline, at the end of each maintenance phase, and after final washout. RESULTS. LTG did not affect overt performance on the tasks, although it reduced EEG power in both resting and WM task conditions, most prominently in the 6- to 12-Hz frequency range, and attenuated P300 evoked-potential amplitude equally in both WM task loads. TPM slowed responses and increased errors. It also increased EEG power below 6 Hz in all conditions, and reduced the amplitude of a slow wave observed in a difficult version of the WM task.. The drugs produced both task-independent and task-related alterations in neurophysiologic measures. The EEG and EP changes produced by TPM are consistent with an impairment of WM, as evidenced by overt performance deficits on the behavioral tasks. By contrast, the reduction in synchronous cortical activity produced by LTG was not accompanied by cognitive impairment. It is unknown whether such effects would also be observed at lower doses, such as those that often are used in monotherapy for newly diagnosed patients.

Topics: Adult; Anticonvulsants; Cognition; Cognition Disorders; Cortical Synchronization; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Event-Related Potentials, P300; Female; Fructose; Humans; Lamotrigine; Male; Memory; Memory Disorders; Middle Aged; Psychomotor Performance; Task Performance and Analysis; Topiramate; Triazines

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

Topics: Adolescent; Anti-Obesity Agents; Child; Child, Preschool; Cognition; Cognition Disorders; Female; Fructose; Humans; Male; Obesity; Topiramate

To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP).. Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test.. There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP.. Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.

Topics: Activities of Daily Living; Adult; Amines; Anticonvulsants; Brain; Cognition; Cognition Disorders; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Maximum Tolerated Dose; Middle Aged; Neuropsychological Tests; Patient Selection; Reference Values; Risk Factors; Topiramate; Treatment Outcome

Whereas the efficacy of the newer antiepileptic drugs (AEDs) is well established, there remain questions regarding their cognitive side effects. Therefore, we performed a comparative open randomized trial with TPM and TGB as add-on therapy, with particular consideration of cognition, mood, and health-related quality of life (HRQOL).. Forty-one patients with refractory epilepsy were randomly assigned to one of the two treatment groups (TPM vs TGB) and received neuropsychological testing at baseline (T1), after titration (3 months, T2), and during the maintenance phase (another 3 months, T3). Tests included measures of intelligence, attention, working memory, episodic memory, language, and self-report questionnaires regarding mood and HRQOL. Twenty patients (8 TPM, 12 TGB) discontinued the trial for different reasons (no group difference).. Seizure outcome (intention-to-treat analysis) was comparably good in both groups (8.1% seizure free, 29.7% seizure reduction>50%). From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency, language comprehension, working memory, and visual block tapping under TPM and a deterioration in verbal memory (delayed free recall) in the TGB group. These functions remained stable in the maintenance phase. Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM. In the maintenance phase the TGB group reported feeling a lack of energy, whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level.. This study demonstrates the comparable efficacy of TPM and TGB. Consistent with previous reports, TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions, the degree of which may be estimated by the fact that this effect was observed with a very small sample size. In contrast, in patients taking TPM, initially negatively affected HRQOL returns to baseline in the long run on a descriptive level. The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated.

Topics: Adolescent; Adult; Anticonvulsants; Attention; Cognition Disorders; Drug Evaluation; Epilepsy; Female; Fructose; Humans; Intelligence; Male; Memory, Short-Term; Middle Aged; Mood Disorders; Neuropsychological Tests; Nipecotic Acids; Tiagabine; Topiramate; Treatment Outcome; Verbal Behavior

The relative cognitive and behavioral effects of lamotrigine (LTG) and topiramate (TPM) are unclear.. The authors directly compared the cognitive and behavioral effects of LTG and TPM in 47 healthy adults using a double-blind, randomized crossover design with two 12-week treatment periods. During each treatment condition, subjects were titrated to receive either LTG or TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation included 17 measures yielding 41 variables of cognitive function and subjective behavioral effects. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug-free conditions (pretreatment baseline and 1 month following final AED withdrawal).. Direct comparison of the two AEDs revealed significantly better performance on 33 (80%) variables for LTG, but none for TPM. Even after adjustment for blood levels, performance was better on 19 (46%) variables for LTG, but none for TPM. Differences spanned both objective cognitive and subjective behavioral measures. Comparison of TPM to the non-drug average revealed significantly better performance for non-drug average on 36 (88%) variables, but none for TPM. Comparison of LTG to non-drug average revealed better performance on 7 (17%) variables for non-drug average and 4 (10%) variables for LTG.. Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.

Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsy; Female; Fructose; Humans; Lamotrigine; Male; Memory; Memory Disorders; Middle Aged; Mood Disorders; Neuropsychological Tests; Psychomotor Performance; Reaction Time; Reference Values; Topiramate; Treatment Outcome; Triazines; Verbal Behavior

Cognitive effects have been reported during topiramate (TPM) treatment, but effects relative to standard antiepileptic drugs are unclear.. The authors compared TPM and valproate (VPA) added to carbamazepine (CBZ) in adults with partial seizures. A comprehensive neuropsychological test battery including cognitive, mood, and quality of life measures was used in this multicenter, randomized, double-blind study. After a 4-week baseline, study drug was titrated over 8 weeks to target dosages of 400 mg/d TPM, 2,250 mg/d VPA, or placebo and then maintained for an additional 12 weeks. The neuropsychological test battery was administered at baseline and at the end of titration and maintenance periods.. Slightly more patients on TPM dropped out. Neuropsychological data at all three test periods were available for 62 patients. At the end of maintenance, effects of TPM and VPA were comparable, except for two variables (Symbol Digit Modalities Test and Controlled Oral Word Association Test), in which TPM had greater negative effects relative to VPA. The statistical differences appeared to be due in large part to a small subset of patients who were more negatively affected by TPM. Cognitive effects of TPM relative to VPA were greater at the end of titration than at the end of maintenance.. With adjunctive therapy at moderate dose escalation rate, the cognitive effects of TPM are slightly worse overall than VPA in patients who tolerate therapy over several months.

Topics: Adolescent; Adult; Affect; Anticonvulsants; Attention; Behavior; Carbamazepine; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Psychomotor Performance; Quality of Life; Topiramate; Valproic Acid

Topiramate (TPM) is a new antiepileptic drug (AED) that has been found to be associated with a high prevalence of cognitive adverse events (CAEs). The prevalence of psychiatric adverse events (PAEs) has yet to be established. The purpose of this study was to determine the prevalence of PAEs related to TPM when used in polytherapy regimens in a large cohort of adult patients with epilepsy, to identify any association between the occurrences of CAEs and PAEs and to identify predictors of PAEs and CAEs.. Investigators from 16 epilepsy centers (PADS group) prospectively obtained postmarketing safety and efficacy data on 596 patients aged 16 years and older. All data were recorded on standardized data retrieval forms, completed at the initial visit, while follow-up data were obtained every 6 months or at the time of discontinuation.. PAEs were identified in 75 (12.6%) patients: 30 (5%) experienced symptoms of depression and 34 (5.7%) of aggressive behavior and irritability, while 9 patients experienced symptoms of psychosis (1.5%). CAEs were reported by 247 (41.5%) patients. There was a significant association between the occurrences of CAEs and PAEs. A past psychiatric history was a predictor of CAEs, while older age and past psychiatric history were predictors of PAEs.. The use of TPM in polytherapy regimens can cause PAEs and CAEs and their occurrence is significantly correlated. Patients with a past psychiatric history may be at a higher risk for experiencing PAEs and CAEs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cognition Disorders; Epilepsy; Female; Fructose; Humans; Male; Mental Disorders; Middle Aged; Prospective Studies; Risk Factors; Topiramate

In an open study, 37 epilepsy patients were investigated with regard to cognitive impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition to a preexisting antiepileptic medication, TPM administration was started and increased by 25 mg/week. Cognitive side effects noted by the patient or doctor were assessed by a neuropsychological test battery. In 18/37 patients (49%), cognitive deficits consisting of impaired concentration, psychomotoric slowing, memory deficits, and dysphasia were observed. The adverse effects became apparent at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients, the adverse effects led to withdrawal of TPM. In spite of slow titration, the present study showed a higher frequency of cognitive side effects under TPM than was previously reported. In some patients, these side effects led to substantial impairments in daily life and at work. For early recognition of cognitive impairments, neuropsychological baseline and follow-up investigations of verbal fluency, psychomotor processing speed, and verbal memory are recommended.

Topics: Adult; Aged; Anticonvulsants; Cognition Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Neuropsychological Tests; Remission Induction; Topiramate; Treatment Outcome

This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerability and prevents cognitive impairment.. The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach.. For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration.. Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Placebos; Psychomotor Performance; Topiramate; Treatment Outcome; Valproic Acid

To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate.. Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention.. Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug.. Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration.. Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults.

Topics: Acetates; Adult; Affect; Amines; Anticonvulsants; Cognition Disorders; Cyclohexanecarboxylic Acids; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Neuropsychological Tests; Psychomotor Performance; Reaction Time; Single-Blind Method; Topiramate; Triazines; Word Association Tests

To investigate the effects of topiramate (TPM), zonisamide (ZNS), and levetiracetam (LEV) on cognitive network activations in patients with focal epilepsy using an fMRI language task.. In a retrospective, cross-sectional study, we identified patients from our clinical database of verbal fluency fMRI studies who were treated with either TPM (n = 32) or ZNS (n = 51). We matched 62 patients for clinical measures who took LEV but not TPM or ZNS. We entered antiepileptic comedications as nuisance variables and compared out-of-scanner psychometric measures for verbal fluency and working memory between groups.. Out-of-scanner psychometric data showed overall poorer performance for TPM compared to ZNS and LEV and poorer working memory performance in ZNS-treated patients compared to LEV-treated patients. We found common fMRI effects in patients taking ZNS and TPM, with decreased activations in cognitive frontal and parietal lobe networks compared to those taking LEV. Impaired deactivation was seen only with TPM.. Our findings suggest that TPM and ZNS are associated with similar dysfunctions of frontal and parietal cognitive networks, which are associated with impaired performance. TPM is also associated with impaired attenuation of language-associated deactivation. These studies imply medication-specific effects on the functional neuroanatomy of language and working memory networks.. This study provides Class III evidence that in patients with focal epilepsy, TPM and ZNS compared to LEV lead to disruption of language and working memory networks.

Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Sectional Studies; Epilepsies, Partial; Female; Fructose; Functional Laterality; Humans; Image Processing, Computer-Assisted; Isoxazoles; Language; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Oxygen; Retrospective Studies; Topiramate; Zonisamide

The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy.. The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants.. The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills.. Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology.

Topics: Adolescent; Anticonvulsants; Brain; Brain Waves; Child; Cognition Disorders; Electroencephalography; Epilepsy; Female; Fructose; Humans; Intelligence; Male; Neuroimaging; Neuropsychological Tests; Regression Analysis; Retrospective Studies; Sleep; Statistics, Nonparametric; Topiramate; Wakefulness

To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning.. This was a cross-sectional observational study. Children exposed to monotherapy levetiracetam (n = 42), topiramate (n = 27), or valproate (n = 47) and a group of children born to women who had untreated epilepsy (n = 55) were enrolled retrospectively from the UK Epilepsy and Pregnancy Register. Assessor-blinded neuropsychological assessments were conducted between 5 and 9 years of age. Information was collected on demographic and health variables and adjusted for in multiple regression analyses.. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in child cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing dose of valproate, however, was associated with poorer full-scale IQ (-10.6, 95% confidence interval [CI] -16.3 to -5.0, p < 0.001), verbal abilities (-11.2, 95% CI -16.8 to -5.5, p < 0.001), nonverbal abilities (-11.1, 95% CI -17.3 to -4.9, p < 0.001), and expressive language ability (-2.3, 95% CI -3.4 to -1.6, p < 0.001). Comparisons across medications revealed poorer performance for children exposed to higher doses of valproate in comparison to children exposed to higher doses of levetiracetam or topiramate.. Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.

Topics: Adult; Anticonvulsants; Child; Cognition Disorders; Cross-Sectional Studies; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Levetiracetam; Male; Piracetam; Pregnancy; Prenatal Exposure Delayed Effects; Topiramate; Valproic Acid; Young Adult

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

Topics: Adult; Aged; Anticonvulsants; Cognition Disorders; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Topiramate; Young Adult

As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.

Topics: Anticonvulsants; Brain; Cognition Disorders; Consumer Health Information; Diet, Ketogenic; Drug Resistance; Epilepsy; Evidence-Based Nursing; Fructose; Humans; Internet; Levetiracetam; Medical Marijuana; Parents; Piracetam; Topiramate

Topiramate is an antiepileptic drug that has marked treatment-limiting side effects on specific aspects of cognitive performance in both patients and healthy volunteers. Because these severe side effects occur only in certain individuals, identifying genetic or environmental variables that influence cognitive response would be of great utility in determining whether to administer this drug to a patient. We gave an acute 100 mg oral dose of topiramate to 158 healthy volunteers and measured how the drug changed their performance on a diverse battery of cognitive tests. We found a wide range of responses to topiramate, and we demonstrated that not all tests in the battery were equally affected. There was no correlation between the effect of topiramate and either education level or baseline cognitive performance. Of interest, there was an up to 55-fold variation in the topiramate plasma levels of the participants. Our genome-wide association study (GWAS) of cognitive response did not reveal any genome-wide significant associations; the study was powered to find variants explaining at least 25% of the variation in cognitive response. Combining the results of this GWAS with a retrospective study of cognitive complaints in 290 epilepsy patients who received topiramate as part of their treatment also did not result in a significant association. Our results support the need for additional genetic studies of topiramate that use larger sample sizes.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cognition; Cognition Disorders; Educational Status; Epilepsy; Female; Fructose; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Neuropsychological Tests; Topiramate; Young Adult

The aim of this study was to determine the 12-week cognitive changes in topiramate-treated patients recently detoxified from alcohol.. Participants were inpatients with DSM-IV alcohol dependence. All of them were discharged within 14 days after the initiation of topiramate treatment. The topiramate dose range was 50-300 mg/day. The Montreal Cognitive Assessment (MoCA) was used on day 0, day 29, day 57, and day 85. Differences of the MoCA total and seven subtest scores among four time-points were compared.. Thirty-eight participants (36 men and two women) had a mean ± SD age of 43.1 ± 8.6 years old. At enrollment, they were abstinent for a mean ± SD of 11.5 ± 5.3 days. Five, one, and three patients dropped out of the study on day 29, day 57, and day 85, respectively. On day 85, the mean ± SD dose of topiramate was 253.1 ± 60.8 mg/day. Alcohol consumption decreased drastically during follow up. At each time-point, 75%-80% of the participants were continuous abstainers. The mean ± SD MoCA total, language subtest, and delayed recall subtest scores increased significantly from day 0 to day 85, from 22.0 ± 4.7 to 24.7 ± 3.4 (P < 0.01), from 1.1 ± 1.0 to 1.3 ± 1.0 (P = 0.03), and from 2.7 ± 1.7 to 4.1 ± 1.0 (P < 0.01), respectively.. Topiramate-treated patients recently detoxified from alcohol usually have an improvement of their cognitive function, especially in the language and delayed recall domains. This phenomenon may be caused by the greater influence of cognitive recovery associated with decreased drinking as compared with topiramate-induced cognitive impairment.

Topics: Adolescent; Adult; Alcoholic Intoxication; Alcoholism; Cognition; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Neuropsychological Tests; Patient Dropouts; Prospective Studies; Psychomotor Performance; Recovery of Function; Socioeconomic Factors; Topiramate; Treatment Outcome; Young Adult

A 46-year-old man inhaled combustible smoke of unknown chemical composition for 15-20 min in an automobile body shop. Within 1 month, he noted headache, sadness, anergia, anhedonia, agitation, poor sleep and impairment of concentration, attention and learning skills. Three years later, mental status examination showed major depression and cognitive disorder manifested by apprehension, continuous sadness, agitation, exhaustion, difficulty with word finding, bradyphrenia, short-term and long-term memory impairment, and judgement impaired by impulsive and affect-laden reactions without reflection. Impairments were noted on neuropsychiatric tests, and positron emission tomography (PET) scan of the brain with (18)F-fluorodeoxyglucose showed globally decreased and heterogeneous metabolic activity in the entire brain. Treatment included sertraline, methylphenidate, valproic acid and topiramate. At 14 years after smoke inhalation injury, he had persistent cognitive impairment. Repeat brain PET scan showed areas of improvement and deterioration. This case shows long-term brain and psychiatric dysfunction resulting after toxic smoke inhalation, with some areas of the brain having progressive deterioration between years 3 and 14 after smoke inhalation.

Topics: Activities of Daily Living; Brain; Cognition Disorders; Depressive Disorder, Major; DNA Damage; Fluorodeoxyglucose F18; Fructose; Humans; Male; Memory, Long-Term; Methylphenidate; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Oxidative Stress; Positron-Emission Tomography; Radiopharmaceuticals; Sertraline; Smoke Inhalation Injury; Time Factors; Topiramate; Valproic Acid

Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer.

Topics: Animals; Anticonvulsants; Carbamazepine; Catalase; Cognition Disorders; Disease Models, Animal; Drug Interactions; Escape Reaction; Fructose; Glutathione; Kindling, Neurologic; Lamotrigine; Male; Malondialdehyde; Maze Learning; Mice; Oxcarbazepine; Oxidative Stress; Pentylenetetrazole; Seizures; Superoxide Dismutase; Topiramate; Triazines

The cerebellar cognitive affective syndrome (CCAS) represents a spectrum of cerebellar-induced neurocognitive and affective disturbances. In this report a patient is described who developed CCAS under a treatment with standard daily dose of the anti-epileptic drug topiramate (TPM). Cognitive disturbances consisted of impaired visuo-spatial memory, concentration deficits and executive dysfunctions. Behavior and affect were characterized by marked mood-swings and several disinhibited symptoms. After a gradual discontinuation of treatment with topiramate, a complete remission of the cognitive and affective symptoms was observed within 6 weeks. Functional neuroimaging studies by means of SPECT were conducted 2 weeks and 8 months following TPM discontinuation. This case report seems to suggest that functional disruption of the cerebello-cerebral circuitry, leading to CCAS, can follow treatment with topiramate.

Topics: Amines; Anticonvulsants; Carbamazepine; Cerebellar Diseases; Cerebellum; Cognition Disorders; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Middle Aged; Mood Disorders; Neuropsychological Tests; Oxcarbazepine; Syndrome; Topiramate; Treatment Outcome

Methamphetamine-dependent individuals often cite the need to maintain enhanced cognitive performance and attention as a reason for continuing or relapsing to drug-taking. Further, methamphetamine addicts might not comply with taking a potentially therapeutic medication if it had a profound effect on these cognitive processes. Topiramate, a sulfamate-substituted fructopyranose derivative, has been suggested as a putative therapeutic medication for treating methamphetamine dependence. Examination of topiramate's effects on cognitive performance and attention is a clinically and scientifically important component of understanding its potential therapeutic profile. In 10 male and female individuals who met DSM-IV criteria for methamphetamine dependence, we examined the effects of low (50 mg b.i.d.)- and high (100 mg b.i.d.)-dose topiramate - in both the presence and absence of low (15 mg)- and high (30 mg)-dose intravenous methamphetamine--on cognitive performance, attention, and concentration on the rapid visual information processing task and the digit symbol substitution test. Intravenous methamphetamine enhanced cognitive performance, attention, and concentration among recently withdrawn methamphetamine addicts--an effect that hitherto had not been well characterized. Topiramate's cognitive effects were mixed and rather paradoxical, with a tendency to improve attention and concentration both alone and in the presence of methamphetamine while worsening psychomotor retardation. No deleterious interaction occurred between topiramate and methamphetamine on any of these cognitive processes. While clinical studies with topiramate should prepare participants for possible psychomotor retardation, the cognitive effects profile observed would not likely present an important obstacle to compliance in motivated patients. Topiramate's complicated cognitive effects among methamphetamine addicts need more comprehensive examination.

Topics: Adult; Amphetamine-Related Disorders; Area Under Curve; Attention; Central Nervous System Stimulants; Cognition Disorders; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Methamphetamine; Neuroprotective Agents; Psychiatric Status Rating Scales; Psychomotor Performance; Substance Abuse, Intravenous; Topiramate; Visual Perception

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.

Topics: Adult; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Fructose; Humans; Indans; Language Disorders; Male; Middle Aged; Migraine Disorders; Piperidines; Topiramate; Treatment Outcome

Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.. All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.. Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.. cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.

Topics: Adult; Anticonvulsants; Attitude to Health; Child; Cognition Disorders; Drug Utilization; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Levetiracetam; Male; Patient Dropouts; Piracetam; Topiramate

Topiramate is the second antiepileptic drug, after valproate, to be approved by the FDA for prevention of migraine. There is no evidence that it is more effective than a beta-blocker for this indication, and it is much more expensive. Topiramate can cause cognitive impairment and weight loss. No studies have compared it to valproate for this indication.

Topics: Anticonvulsants; Cognition Disorders; Fructose; Humans; Migraine Disorders; Topiramate; Weight Loss

To specify efficacy of topamax in different types of epileptic seizures and its influence on patient's quality of life (QL), the drug was assigned to 38 patients, aged 18-69 years, as mono- and polytherapy (in combination with other anticonvulsive medications). Topamax dosages ranged from 25-50 mg at a base-line to 600 mg. Treatment duration was 6-18 months. Positive effect of different extent was achieved in 95.7% patients. A seizures frequency decreased by 25% in 17.4% patients; by 50%--in 8.7%; by 75%--in 43.5%; a complete disappearance of seizures was detected in 30.4%. The results confirmed the earlier data received by the authors that topamax was most effective in generalized convulsive, partial and secondary generalized seizures. It exerts a less pronounced effect in myoclonic seizures and absences. After topamax treatment, a total QL index measured by WHO questionnaire increased by 5.2%. The drug is well tolerated and does not affect cognitive functions of the patients. It is concluded that currently topamax is one of the most effective antiepileptic medications.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Administration Schedule; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Neuropsychological Tests; Quality of Life; Topiramate

Topics: Anti-Obesity Agents; Anticonvulsants; Cognition Disorders; Epilepsy; Fructose; Humans; Neuroprotective Agents; Obesity; Practice Guidelines as Topic; Practice Patterns, Physicians'; Topiramate

Topics: Acute Disease; Anticonvulsants; Cognition Disorders; Fructose; Humans; Psychiatric Status Rating Scales; Receptors, Glutamate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Topiramate; Valproic Acid

We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy.. Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed.. In Study 1, significant (p < or = 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p < or = 0.05) for tests of fluency, sustained concentration, and visual motor processing speed.. TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.

Topics: Adolescent; Adult; Anticonvulsants; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Psychomotor Performance; Topiramate; Verbal Learning

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

Topics: Adult; Chi-Square Distribution; Cognition; Cognition Disorders; Epilepsy; Female; Frontal Lobe; Fructose; Humans; Male; Middle Aged; Neuropsychological Tests; Preoperative Care; Statistics, Nonparametric; Topiramate

To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE).. We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999.. Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02).. Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor.

Topics: Adult; Anticonvulsants; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Female; Fructose; Hippocampus; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sclerosis; Topiramate

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Child Behavior Disorders; Cognition Disorders; Fructose; Humans; Male; Topiramate

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; Triazoles; Vigabatrin

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Clinical Trials as Topic; Cognition; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Middle Aged; Multicenter Studies as Topic; Product Surveillance, Postmarketing; Prospective Studies; Psychomotor Disorders; Risk Factors; Topiramate

The objective of this study was to examine the factors associated with the occurrence of behavioral and cognitive abnormalities in children treated with topiramate. A retrospective chart review of patients up to 18 years of age who had been treated with topiramate at a tertiary epilepsy center was performed. Behavioral or cognitive abnormalities were observed in 11 (14.6%) of 75 children between 2 weeks and 4 months after initiation of therapy. The mean dosage (4.6 mg/kg daily) at which these abnormalities were observed was similar to the mean final dose (5.8 mg/kg daily) in children without abnormalities. The mean rate of dosage increase was 0.72 mg/kg weekly and 0.7 mg/kg weekly in those with and without abnormalities, respectively. Five of the 11 children with behavioral or cognitive abnormalities had a previous history of behavioral or cognitive abnormalities, but only nine of the 64 children without abnormalities had a previous history of behavioral or cognitive abnormalities (P = 0.03). Lamotrigine was used concurrently in four of the 11 children with behavioral or cognitive abnormalities but in only seven of the 64 children without abnormalities (P = 0.05). Behavioral and cognitive abnormalities in children treated with topiramate do not appear to be related to the rate of dosage increase. A previous history of behavioral problems and the concurrent use of lamotrigine may be predisposing factors.

Topics: Adolescent; Anticonvulsants; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Infant; Lamotrigine; Male; Medical Records; Retrospective Studies; Risk Factors; Topiramate; Treatment Outcome; Triazines

A 3-year retrospective review was undertaken of the use of topiramate in 51 children aged 3-16 years with partial and generalized epilepsies who attended a tertiary referral epilepsy centre in a large children's hospital. The mean follow-up period was 19 months (range 6-33 months). Twenty-six children (51%) were still receiving topiramate at the time of their last review. Fifteen children (29%) showed a greater than 50% reduction in their seizure frequency and four children (8%) became seizure free, three on topiramate monotherapy. The drug appeared to be most effective in children with moderate learning difficulties with 75% showing an improvement in seizure control compared with 25% of children with normal educational functioning. Topiramate was withdrawn in 25 patients. The reasons for withdrawal included adverse effects in 20, lack of effect in three and worsening of seizures in two patients. Adverse side effects were reported in 57% of the 51 patients. The majority of the side effects were related to behavioural and cognitive difficulties, with less-common side effects including anorexia, weight loss and headaches.

Topics: Adolescent; Anticonvulsants; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Drug Tolerance; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Male; Medical Audit; Retrospective Studies; Topiramate; Treatment Outcome

Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Anti-Anxiety Agents; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids; Dizziness; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fructose; Gabapentin; gamma-Aminobutyric Acid; Heart Defects, Congenital; Humans; Lamotrigine; Nausea; Obesity; Stevens-Johnson Syndrome; Topiramate; Triazines; Valproic Acid