topiramate and Drug-Overdose

Multiple new anticonvulsants have been introduced recently and they are supplanting the older medications. Whereas the older drugs have well-recognized side effects, both in typical therapeutic doses and in overdosage, the properties of the newer ones are unique and largely unknown to all but sub-specialists.. This article gives a concise overview of the potential complications of these new medications in both therapeutic use and overdose.. Clinically significant side effects of the new anticonvulsants, such as metabolic acidosis from topiramate, autoimmune reactions from lamotrigine, hyponatremia from oxcarbazepine, or psychosis from levitiracetam can cause serious morbidity and mortality if unrecognized. The effects of these medications in overdose are also largely unknown to most emergency physicians.. This article reviews the major potential side effects of the new seizure medications and the treatment of their overdoses for the practicing emergency physician.

Topics: Acidosis; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Overdose; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Psychoses, Substance-Induced; Seizures; Tiagabine; Topiramate; Triazines

Epilepsy affects 1.2% to 4.4% of the general population. Given the clinical profile of the newer antiepileptic agents, it is likely their usage will increase in the coming years, thus increasing the emergency physician's exposure to these medications and their side effects. Several of these side effects can have high morbidity, such as the aplastic anemia and hepatotoxicity caused by felbamate, and the Stevens-Johnson syndrome associated with lamotrigine. Overdoses of these medications also could increase, as will our knowledge of recognizing and managing them. The clinical spectrum of the newer medications is the treatment of partial seizures. None of the newer medications can be orally loaded nor are they available in an i.v. preparation. Serum drug levels are not available in most institutions and are not routinely measured in the ED. The new preparations of phenytoin, diazepam, and valporic acid add increased efficiency in drug administration, providing a new method for prehospital treatment of seizures and a more tolerable means of administration in the ED.

Topics: Acetates; Administration, Rectal; Age Factors; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Diazepam; Drug Overdose; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Injections, Intravenous; Lamotrigine; Phenylcarbamates; Phenytoin; Propylene Glycols; Topiramate; Triazines; Valproic Acid

Levetiracetam and topiramate are newer anticonvulsants, which is why international data on overdoses of these drugs are lacking. Only a few mild adverse reactions have been noted. These anticonvulsants have been the drug of choice for neurologists. Despite their wide usage, there is a dearth of literature on symptoms and signs of their toxicity. Presented here is the case of a 21-year-old female who overdosed twice on levetiracetam and topiramate. The woman was admitted and discharged after the first overdose. Ten days later, she took multiple tablets of both drugs and was seen again. Amazingly, the woman went home after the incident with no complications at all.

Topics: Anticonvulsants; Antidotes; Charcoal; Drug Overdose; Female; Fructose; Humans; Levetiracetam; Piracetam; Topiramate; Young Adult

Topics: Adolescent; Adult; Analgesics; Botulinum Toxins, Type A; Child; Drug Administration Schedule; Drug Overdose; France; Fructose; Headache Disorders; Headache Disorders, Secondary; Hospitalization; Humans; Incidence; Migraine Disorders; Prevalence; Recurrence; Topiramate; Transcutaneous Electric Nerve Stimulation

Patients with chronic migraine (CM) and medication abuse are difficult to treat, and have a greater tendency towards chronification and a poorer quality of life than those with other types of headache.. To evaluate whether the presence of medication abuse lowers the effectiveness of topiramate.. A series of patients with CM were grouped according to whether they met abuse criteria or not. They were advised to stop taking the drug that they were abusing. Treatment was adjusted to match their crises and preventive treatment with topiramate was established from the beginning. The number of days with headache and intense migraine in the previous month and at four months of treatment was evaluated.. In all, 262 patients with CM criteria were selected and 167 (63.7%) of them fulfilled abuse criteria. In both groups there was a significant reduction in the number of days with headache/month and number of migraine attacks/month at the fourth month of treatment with topiramate. The percentage of reduction in the number of days with headache/month in CM without abuse was 59.3 ± 36.1%, and with abuse, 48.7 ± 41.7% (p = 0.0574). The percentage of reduction in the number of days with intense migraine/month in CM without abuse was 61.2%, and with abuse, 50% (p = 0.0224). Response rate according to the number of days with headache/month in CM without abuse was 69%, and with abuse, 57%. Response rate according to the number of intense migraines/month in CM without abuse was 76.8%, and in CM with abuse, 61% (p = 0.0097).. Topiramate was effective in patients with CM with and without medication abuse, although effectiveness is lower in the latter case.. El abuso de farmacos en pacientes con migraña cronica influye en la efectividad del tratamiento preventivo con topiramato?. Introduccion. Los pacientes con migraña cronica (MC) y abuso de medicacion son dificiles de tratar y tienen peor calidad de vida que otros pacientes con migrañas. Objetivo. Valorar si la presencia de abuso de farmacos disminuye la efectividad del topiramato. Pacientes y metodos. Una serie de pacientes con MC fueron agrupados segun presentasen criterios de abuso o no abuso de farmacos. Se les aconsejo la supresion del farmaco del cual abusaban. Se ajusto el tratamiento de sus crisis y se inicio tratamiento preventivo desde el principio con topiramato. Se valoro el numero dias con cefalea y migrañas intensas en el mes previo y al cuarto mes de tratamiento. Resultados. Fueron seleccionados 262 pacientes con criterios de MC, y de ellos 167 (63,7%) cumplieron criterios de abuso. En ambos grupos hubo una reduccion significativa del numero de dias con cefalea/mes y numero de crisis de migraña/mes al cuarto mes de tratamiento con topiramato. Porcentaje de reduccion de dias con cefalea/mes en MC sin abuso, 59,3 ± 36,1%; y con abuso, 48,7 ± 41,7% (p = 0,0574). Porcentaje de reduccion de migrañas intensas/mes en MC sin abuso, 61,2%; y con abuso, 50% (p = 0,0224). Tasa de respondedores segun numero de dias con cefalea/mes en MC sin abuso, 69%; y con abuso, 57%. Tasa de respondedores segun numero de migrañas intensas/mes en MC sin abuso, 76,8%; y en MC con abuso, 61% (p = 0,0097). Conclusiones. El topiramato fue efectivo en pacientes con MC sin y con abuso de farmacos, aunque con menor efectividad en estos ultimos.

Topics: Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Drug Overdose; Female; Fructose; Headache Disorders; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Substance-Related Disorders; Topiramate; Treatment Outcome; Tryptamines; Young Adult

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Cyclohexanols; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Female; Fructose; Humans; Quetiapine Fumarate; Seizures; Time Factors; Topiramate; Venlafaxine Hydrochloride; Young Adult

We report the case of a 21-year-old man with idiopathic generalized epilepsy who ingested about 8,000 mg of topiramate (TPM) in a suicide attempt. On admission to the hospital he had a nonconvulsive status epilepticus and received 4 mg lorazepam i.v. He recovered rapidly despite an initial TPM concentration of 144.6 microg/ml. To our knowledge, this is the first report of a patient who survived such a high TPM concentration. The case indicates that nonconvulsive status epilepticus could be a manifestation of TPM intoxication.

Topics: Drug Overdose; Fructose; Humans; Male; Status Epilepticus; Suicide, Attempted; Topiramate; Young Adult

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Topics: Acidosis; Adult; Anticonvulsants; Bipolar Disorder; Blood Gas Analysis; Coma; Critical Care; Drug Overdose; Female; Fructose; Gas Chromatography-Mass Spectrometry; Humans; Hypnotics and Sedatives; Lorazepam; Respiration, Artificial; Topiramate

The clinical manifestations of acute topiramate toxicity are described.. Seven cases of acute and acute-on-chronic topiramate toxicity observed in two clinical units of Polish Poison Control Centers in 2004-2005 were analyzed.. The patients were 4 women and 2 men aged between 16 and 38 (mean 21.0 +/- 8.4) years. The doses of topiramate ranged from 10.7 to 218 mg/kg. The most frequent symptom was somnolence (66.7%) and, vertigo, agitation, and mydriasis were less common (33.4%). One patient who was not previously treated with topiramate experienced three secondarily generalized tonic-clonic seizures. Metabolic acidosis, lasting for 3-7 days, was observed in four cases, and did not influence the outcome.. The clinical manifestations of acute poisonings with topiramate ranged from asymptomatic to severe, but no distant sequelae or fatalities were observed. The course of acute poisoning seems to be more severe in patients who were not previously treated with topiramate.

Topics: Acidosis; Adolescent; Adult; Anticonvulsants; Drug Overdose; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Poison Control Centers; Poland; Severity of Illness Index; Sleep Stages; Suicide, Attempted; Topiramate; Young Adult

Topics: Anticonvulsants; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Overdose; Female; Fructose; Humans; Myoclonus; Seizures; Topiramate

Topics: Adult; Anticonvulsants; Drug Overdose; Fructose; Humans; Male; Seizures; Suicide, Attempted; Topiramate; Treatment Outcome

Topiramate is an FDA-approved second generation antiepileptic drug with actions on voltage-dependent sodium and calcium channels and GABA and excitatory amino acid receptors. There has only been one prior pediatric case report of topiramate toxicity. We report a 33-month-old girl with persisting neurologic symptoms after acute ingestion of topiramate.. A 33-month-old girl was found at her sitter'shouse with a bottle of topiramate (100-mg tablets). She presented to the emergency department 3 days post-ingestion. The child appeared confused and was only able to crawl. At one point, she looked directly at mother and asked, "Where is my mommy?" She had visual hallucinations and screamed while pointing to objects on the wall. Neurologic exam was notable for the slurred speech and severe ataxia. All laboratory testing, urine chemical dependency screen, CSF, chest X-ray, head CT, and EEG showed no abnormalities. Topiramate level on the third day post-ingestion was 9.4 mcg/mL, and 4.2 mcg/mL on the fourth day. Patient became oriented to family and regained normal gait on the fourth day. Her slurred speech persisted until the sixth day after ingestion.. Topiramate is an anti-epileptic drug with multifactorial mechanisms of action not entirely understood. We report here a 33-month-old girl with prolonged neurologic symptoms including hallucination, slurred speech, and severe ataxia after acute topiramate ingestion. This is the first pediatric case report of hallucination and prolonged neurologic symptoms with acute topiramate ingestion.

Topics: Acute Disease; Anticonvulsants; Child, Preschool; Drug Overdose; Female; Fructose; Humans; Neurotoxicity Syndromes; Poisoning; Recovery of Function; Topiramate

Topics: Adolescent; Anticonvulsants; Confusion; Drug Overdose; Fructose; Humans; Male; Memory Disorders; Topiramate

According to the best of our knowledge this is the first case of intoxication with topiramate in Polish medical literature. A case of a 15-year-old female who tried to commit suicide with 450 mg of Topamax was described. There were no significant changes in the medical examination as well as biochemical results. An agitation which transformed into bradykinesia and bradyphasia and lasted for about 24 hours were the only complaints of the patient.

Topics: Acute Disease; Adolescent; Anticonvulsants; Depression; Drug Overdose; Epilepsy; Female; Fructose; Humans; Poisoning; Suicide, Attempted; Time Factors; Topiramate; Treatment Outcome

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children < or = 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P <0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P <0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dizziness; Drug Overdose; Female; Fructose; Humans; Male; Poison Control Centers; Psychomotor Agitation; Retrospective Studies; Sleep Stages; Topiramate; United States

To describe an intentional topiramate ingestion by an adolescent and warn of the potential for topiramate abuse.. A 17-year-old female intentionally ingested approximately eight 100-mg topiramate tablets for the purpose of "getting high." Soon after ingestion, she was found at school obtunded and nonresponsive. Upon transfer to the emergency department, she became combative and aggressive with evolving neurologic abnormalities including incoherence, confusion, disorientation, and significant speech impairments including echolalia. Approximately 24 hours after ingestion, the patient had completely recovered without requiring specific treatment or experiencing sequelae.. The clinical effects following acute topiramate intoxication appear consistent with the drug's known pharmacologic properties. There are few other reports of topiramate ingestions and most cases have had mild outcomes.. Due to the multifactorial effects topiramate may have upon the central nervous system and its anorectic effect, abuse of this drug by adolescents should be considered upon presentation of an adolescent with mental status changes.

Topics: Adolescent; Anticonvulsants; Confusion; Drug Overdose; Female; Fructose; Humans; Speech Disorders; Tablets; Topiramate

Topics: Adult; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Drug Overdose; Feeding and Eating Disorders; Female; Fructose; Humans; Substance-Related Disorders; Topiramate; Weight Gain