topiramate and Anorexia

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

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

Studies of the efficacy of topiramate (TPM) in infants and young children are few. Here we report an open, prospective, and pragmatic study of effectiveness of TPM in terms of epilepsy syndromes, in children aged less than 2 years. The median follow-up period was 11 months. We enrolled 59 children in the study: 22 affected by localization-related epilepsy (LRE), 23 by generalized epilepsy, six by Dravet's syndrome, and eight with unclassifiable epilepsy. TPM was effective (responders showed a decrease of more than 50% in seizure frequency) in 47% of patients, including 13% who were seizure-free at the last visit. TPM was more effective in localization-related epilepsy (48% of responders) than in generalized epilepsy (32% of responders). In the latter group, 19 patients suffered from infantile spasms. Four of six patients with cryptogenic infantile spasms became seizure-free. Of the 13 patients with symptomatic infantile spasms, only one was seizure-free. Results were poor for patients with Dravet's syndrome. In general, TPM was well tolerated. The most frequently reported adverse effects were drowsiness, irritability, hyperthermia, and anorexia. The present study concludes that TPM is effective for a broad range of seizures in infants and young children and represents a valid therapeutic option in this population.

Topics: Anorexia; Anticonvulsants; Epilepsy; Female; Fever; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Sleep Stages; Spasm; Topiramate; Treatment Outcome

The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN).. Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption.. Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline).. Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

Topics: Adolescent; Adult; Aged; Anorexia; Anticonvulsants; Body Weight; Diabetic Neuropathies; Diarrhea; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Pain; Pain Measurement; Respiratory Tract Infections; Sleep Deprivation; Time Factors; Topiramate

A total of 292 adult patients (mean age, 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug (AED) therapy (median baseline seizure rate, 12 seizures/month) were treated with open-label topiramate (TPM) in dosages of 100-1,600 mg/day.. The mean duration of TPM treatment was 413 days (range, 84-804 days), and the mean TPM dosage was 503 mg/day (range, 100-1,600 mg/day; median TPM dosage, 300 mg/day). Seizure reduction was calculated from seizure counts during the last 3 months and last 6 months of TPM therapy compared with baseline.. Overall, >50% of patients achieved > or =50% seizure reduction. More important, 11% of patients were seizure-free for > or =3 months at the last visit; 10% of patients were seizure free for > or =6 months at the last visit. This robust therapeutic response was consistent for patients receiving TPM dosages >400 and <400 mg/day. The most commonly reported adverse events were related to the central nervous system. Over the 2.2-year treatment period, 19% of patients discontinued TPM therapy because of inadequate seizure control; 32% discontinued because of adverse events. Findings from this study show that TPM is a useful agent for long-term seizure control, with some patients becoming seizure free for extended periods despite failing previous AED therapy.

Topics: Adolescent; Adult; Aged; Anorexia; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fatigue; Female; Fructose; Headache; Humans; Incidence; Male; Middle Aged; Placebos; Sleep Wake Disorders; Topiramate; Treatment Outcome; Weight Loss

To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies.. We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period.. A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed.. TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.

Topics: Abdominal Pain; Anorexia; Anticonvulsants; Central Nervous System Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Humans; Incidence; Korea; Placebos; Topiramate; Treatment Outcome

Historically, adrenocorticotropic hormone was used as a first-line treatment for infantile spasms; however, there has been increasing use of topiramate as initial therapy. Here, we report a retrospective study of adrenocorticotropic hormone (ACTH) and topiramate as initial treatment for infantile spasms. The neurology patient database at the Children's Hospital of Philadelphia was searched using the International Classification of Diseases, Ninth Revision code for infantile spasms, and 50 patients were randomly chosen for chart review. We identified 31 patients receiving either adrenocorticotropic hormone or topiramate monotherapy (adrenocorticotropic hormone n = 12, topiramate n = 19) as a first-line treatment for infantile spasms. A total of 26 patients were symptomatic and 5 cryptogenic. Six patients treated with adrenocorticotropic hormone had resolution of clinical spasms and hypsarrhythmia within a month, but 3 relapsed. Of the 19 patients treated with topiramate, 4 patients eventually, though over a period of 0, 1, 8, or 69 months, had resolution of spasms and hypsarrhythmia.

Topics: Adrenocorticotropic Hormone; Age of Onset; Anorexia; Anticonvulsants; Brain; Dose-Response Relationship, Drug; Female; Fructose; Hormones; Humans; Infant; Lethargy; Male; Retrospective Studies; Selection Bias; Spasm; Spasms, Infantile; Topiramate; Treatment Outcome; Tremor

Topics: Anorexia; Anticonvulsants; Antifungal Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Disorders of Excessive Somnolence; Drug Interactions; Fructose; Humans; Male; Middle Aged; Stupor; Topiramate; Triazoles

Topics: Anorexia; Anti-Obesity Agents; Appetite; Conditioning, Psychological; Energy Intake; Energy Metabolism; Fructose; Humans; Male; Topiramate; Weight Loss