Drug Treatment Of Seizures

No single drug controls all types of seizures, and different patients require different drugs. Some patients may need multiple medications. (See also Practice Guideline for the treatment of refractory epilepsy from the American Academy of Neurology and the American Epilepsy Society..) Principles of long-term treatment There are some general principles on the use of anticonvulsants: A single drug, usually the one that first or An attempt was made, secondly, controlled seizures in 60% of patients. If the seizures are difficult to control from the outset (in 30-40% of patients), after ? 2 drugs may be required. For stubborn seizures (refractory to an appropriate treatment trial with ? 2 drugs), patients should be referred to an epilepsy center to determine if they are candidates for surgery. Some i.v. or orally administered drugs (eg., phenytoin, valproate) achieve the desired therapeutic range very quickly. Other (z. B. lamotrigine, topiramate) must, considering the lean body mass (body weight minus fat storage) of the patient can be started with a relatively low dose and increased gradually over a few weeks up to the standard therapeutic dose. The dosage should be adjusted to the compatibility of the drug for the patient. Some patients have low blood levels of symptoms of drug toxicity, others tolerate high concentrations without symptoms. If seizures persist, the daily dose is raised in small increments. The correct dosage of each drug is the lowest dose at which the seizures are stopped, with the fewest side effects, regardless of serum levels. Serum levels are indicative only. After the response is known to the drug, it is much more useful to follow the clinical course than to measure the blood levels. If toxicity develops before the seizures are under control, is reduced to just not toxic dose. Then another low-dose drug is added thereto, and gradually increased until the seizures under control. Patients should be closely monitored, since the two drugs interact with an impact on the respective metabolization. The first drug is then slowly reduced and eventually tapered off. A use of several drugs should be avoided as adverse events, low adherence and interactions may occur with other drugs much more often. The addition of a second drug helps about 10% of the patients, the incidence of adverse effects, however, is more than doubled. Blood levels of anticonvulsants is changed by many other medicines and vice versa. Physicians should be aware of all possible drug interactions before prescribing a new drug. If the seizures are under control, the drug should be passed without interruption until the patients are seizure-free for at least 2 years. Then a withdrawal of the drug may be considered. Most of these drugs can be every 2 weeks then tapered by 10%. Recurrences are more likely in patients who have one of the following features: a seizure disorder since childhood requirement of more than one drug to seizure free to be Earlier seizures while taking an anticonvulsant Partial or myoclonic seizures Underlying static encephalopathy abnormal EEG findings in the course of last year Structural lesions (shown using imaged investigations) Approximately 60% of patients with relapses suffered by them within a year, 80% within 2 years. Patients who had a relapse while taking no anticonvulsants, should be treated in the long run. Antileptika for long-term treatment, the preferred drugs vary depending on the type of seizure (see table: drugs for epilepsy). For more product-specific information: Drug treatment of seizures: Specific anticonvulsants. The traditional classification of drugs in older and newer is based on how long they are available. However, some are called. Newer medications for many years available. Broad-spectrum anticonvulsant (effective in partial and various types of generalized seizures) are lamotrigine, levetiracetam, topiramate, valproate and zonisamide. For partial seizures and generalized tonic-clonic seizures, the newer anticonvulsants are (z. B. clobazam, clonazepam, Ezogabin, felbamate, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, zonisamide) no more effective than established drugs. However, the newer drugs call rather less adverse effects produced and are better tolerated. Infantile Spamsmen and atonic myoclonic seizures are difficult to treat. Valproate, vigabatrin or preferably, followed by clonazepam. In infantile spasms, corticosteroids about 8-10 weeks are often effective. The optimal treatment strategy is controversial. It can ACTH, 20-60 units i.m. once a day, tried. A ketogenic diet (high-fat diet that induces ketosis) can help, but it is difficult to sustain. Juvenile myoclonic epilepsy in life-long treatment is usually recommended. Carbamazepine, oxcarbazepine or gabapentin can worsen seizures. Febrile seizures medicines are not recommended, unless the children have a subsequent seizure without febrile illness. Previously, many doctors have given to children with complex febrile seizures phenobarbital or other anticonvulsants to prevent the development nichtfebriler seizures, but this treatment does not seem to be effective, and long-term administration of phenobarbital reduces the ability to learn. For seizures in alcohol withdrawal drugs are not recommended. Instead, rather the treatment of the withdrawal syndrome prevents seizures. The treatment involves a benzodiazepine generally. Drugs for epilepsy type Medical therapy using primary generalized tonic-clonic seizures divalproex (Editor’s note: Divalproex is not available on the German market, active ingredient used here. Valproic acid) valproate first-line monotherapy lamotrigine, levetiracetam, topiramate monotherapy for the second choice or adjuvant therapy Perampanel zonisamide Adjuvant therapy phenobarbital is often seen despite efficacy as monotherapy for the second choice because it sedated and can cause behavioral and learning problems in children Partial seizures with or without secondary generalization carbamazepine lamotrigine, levetiracetam, oxcarbazepine fosphenytoin phenytoin, topiramate first-line monotherapy divalproex ( Editor’s note: Divalproex is on the German market ni cht available active ingredient used here. valproic acid) eslicarbazepine gabapentin lacosamide perampanel pregabalin valproate zonisamide monotherapy for the second choice, or adjuvant therapy clobazam Ezogabin felbamate tiagabine vigabatrin third-line monotherapy or adjuvant therapy phenobarbital is despite effectiveness often seen as less desirable because it sedated and cause behavioral problems in children can Typical absence seizures divalproex (note the Redak tion: Divalproex is on the German market is not available, active ingredient used here. valproic acid) ethosuximide lamotrigine Valproate first-line monotherapy clobazam levetiracetam topiramate zonisamide Also effective atypical absence seizures absence seizures associated with other types of seizures divalproex (Editor’s note : Divalproex is on the German market is not available, active ingredient used here: valproic acid) felbamate lamotrigine, topiramate valproate first-line monotherapy. Clonazepam is also effective, but often development of tolerance reserved acetazolamide refractory cases Infantile spasms atonic seizures Myoclonic seizures divalproex (Editor’s note: Divalproex is on the German market is not available, active ingredient used here: valproic acid.) Valproate Vigabatrin first-line monotherapy; Risk of irreversible visual field defects clonazepam therapy of second choice Tonic and / or atonic seizures in Lennox-Gastaut syndrome divalproex (Editor’s note: Divalproex is on the German market is not available, active ingredient used here: valproic acid.) Lamotrigine, topiramate valproate first-line monotherapy zonisamide clobazam felbamate Sometimes alternative or adjuvant therapy for atonic seizures Juvenile myoclonic epilepsy divalproex (Editor’s note: Divalproex is not available on the German market, active ingredient used here: valproic acid.) Valproate first-line monotherapy lamotrigine, levetiracetam, topiramate zonisamide monotherapy for the second choice, or adjuvant therapy Nichtklassifizierbare seizures divalproex (Editor’s note : Divalproex is not available on the German market, active ingredient used here. valproic acid) valproate first-line monotherapy Lamotrigine monotherapy of 2nd choice levetiracetam topiramate zonisamide third-line monotherapy or adjuvant therapy Adverse effects The various adverse effects of anticonvulsants may influence the choice of Anticonvulsants for an individual patient. For example, are anticonvulsants that lead to weight gain (eg. As valproate) not the best option for obese patients and topiramate or zonisamide may not be suitable for patients with kidney stones. Some undesirable effects of anticonvulsants can be minimized by using a slower dose increase. Overall, the newer anticonvulsants have advantages, such as better compatibility, less sedation and fewer interactions with other drugs. All anticonvulsants may cause an allergic scarlet shaped or measles-like eczema. Some types of seizures may be worsened by anticonvulsant drugs. For example, pregabalin and lamotrigine may worsen myoclonic seizures; Carbamazepine may aggravate small epileptic, myoclonic and atonic seizures. Other undesirable effects vary depending on the drug (Drug treatment of seizures: Specific anticonvulsants) .Antikonvulsiva use during pregnancy antiepileptic drugs are associated with an increased risk of teratogenicity. A fetal Antiepileptikasyndrom (cleft lip, cleft palate, heart malformations, microcephaly, growth retardation, developmental delay, facial anomalies, limb or Fingerhypoplasie) comes in 4% of children of women under a Antikonvulsivatherapie in pregnant women. Because uncontrolled generalized seizures can cause during pregnancy to the injury of the child and the child death is a continuous drug treatment but generally advisable (seizure disorders in pregnancy). Women should be informed about the risks of antiepileptic drugs for the fetus and the risk should be set in relation to other risks: Alcohol is toxic to the developing fetus than any anticonvulsant. The addition of folic acid before conception helps to reduce the risk of neural tube defects and should be all women who are of childbearing age and taking anticonvulsants recommended. Many anticonvulsants lower the folic acid and vitamin B12 serum levels; oral vitamin supplementation can prevent this effect. The risk of teratogenicity is lower in monotherapy and varies depending on Antikonvulsant; none is completely safe during pregnancy (see table: seizure disorders in pregnancy). The risk associated with carbamazepine, phenytoin, and valproate is relatively high; there are indications that they have caused congenital malformations in humans (see Table: Some drugs with adverse effects during pregnancy). The risk of neural tube defects slightly higher in valproate than with other commonly used anticonvulsant drugs. The risk associated with some of the newer drugs (eg. As lamotrigine) appears to be low. Specific anticonvulsants The adult dosage is based on a body weight of 70 kg, unless otherwise stated. Acetazolamide This medicine is used in refractory absence seizures. Dosage Adults: 4-15 mg / kg p.o. 2 times a day (no more than 1 g / day) Children: 4-15 mg / kg p.o. 2 times a day (no more than 1 g / day) Therapeutic and toxic concentrations Therapeutic: 8-14 micrograms / ml (34-59 mmol / l) Toxic:> 25 ug / ml (> 106 mmol / l) to the undesirable effects include kidney stones, dehydration and metabolic acidosis. Carbamazepine This drug is indicated for partial, generalized and mixed seizures, but not in Absence-, myoclonic or atonic seizures. Dosage Adult: 200-600 mg po 2 times daily (starting dose is the same for normal and extended release tablets) children <6 years: 5-10 mg / kg p.o. 2 times daily (tablets), or 2.5-5 mg / kg p.o. 4 times a day (suspension) Children 6-12 years: 100 mg po 2 times daily (tablets) or 2.5 ml (50 mg) p.o. 4 times a day (suspension) Children> 12 years: 200 mg po 2 times daily (tablets) or 5 ml (100 mg) p.o. 4 times a day (suspension) Therapeutic and toxic concentrations Therapeutic: 4-12 micrograms / ml (17-51 mol / l) Toxic:> 14 ug / ml (> 59 mmol / l) are among the undesirable effects double vision, dizziness, nystagmus, gastrointestinal upset, dysarthria, lethargy, a low white blood cell count (3000-4000 / ul) and severe rash (5% of cases). Idiosyncratic adverse reactions include granulocytopenia, thrombocytopenia, hepatotoxicity and aplastic anemia. In carriers of HLA-B * 1502 allele, in particular Asians, the risk of severe rash (Stevens-Johnson syndrome or toxic epidermal necrolysis) is higher than the usual rate of 5%. Therefore, physicians should test for HLA before prescribing carbamazepine, at least for Asians. Blood counts should be monitored routinely during the first year of therapy. Declines in white blood cell count and dose-dependent neutropenia (neutrophil count <1000 / ul) are common. If another medication can not be easily substituted, these effects can sometimes overcome by lowering the dose. Increases the number of leukocytes but very quickly, carbamazepine should be discontinued. Clobazam This drug is indicated for absence seizures; it is indicated as adjunctive therapy in tonic or atonic seizures associated with Lennox-Gastaut syndrome, and in refractory partial seizures with or without secondary generalization. Dosage Adults: 5-20 mg p.o. 2 times daily Children: 5-10 mg p.o. 2 times a day (up to 20 mg po 2 times daily in children> 30 kg) Therapeutic levels are not clearly defined. The adverse effects include drowsiness, sedation, constipation, ataxia, suicidal thoughts, drug addiction, irritability and dysphagia. Clonazepam This drug is indicated for atypical Absence seizures associated with Lennox-Gastaut syndrome, atonic and myoclonic seizures, infantile spasms and possibly absence seizures that are refractory to ethosuximide. Dosage Adults: Initial 0.5 mg p.o. 3 times daily, maintenance dose up to 5-7 mg po 3 times daily (maximum 20 mg / day) Children: Initial 0.01 mg / kg p.o. 2 to 3 times daily (maximum of 0.05 mg / kg / day), increase of 0.25-0.5 mg every 3 days until the seizures are controlled or undesired reactions occur (usual maintenance dose: 0.03 0.06 mg / kg po 3 times daily) Therapeutic and toxic concentrations Therapeutic: 25-30 ng / ml toxic:> 80 ng / ml the adverse effects include somnolence, ataxia, behavioral disorders and partial or complete tolerance to positive effects ( usually in 1-6 months); serious reactions are rare. Divalproex (Editor’s note: Divalproex is not available on the German market, active ingredient used here. Valproic acid) This drug is a compound consisting of Natriumvalporat and valproic acid and has the same indications as valproate, d. h., indicated at absence seizures (typical and atypical), in partial, tonic-clonic and myoclonic seizures, juvenile myoclonic epilepsy, infantile spasms and neonatal or febrile seizures. In addition, it is indicated for tonic or atonic seizures associated with Lennox-Gastaut syndrome. Dosage Adults: 5 mg / kg p.o. 3 times a day with a slow increase in z. For example by 1.67 to 3.33 mg / kg p.o. 3 times a day at weekly intervals, v. a. when more drugs are taken (maximum 20 mg / kg three times daily) children: initial 5 mg / kg p.o. 2- or 3 times daily, increasing to 5-10 mg / kg / day at weekly intervals (usual maintenance dose at 10-20 mg / kg po 3 times a day) may be administered to children delayed released (Slow) -Retardtabletten once daily , The daily dose is 8-20% higher than that for normal tablets. Delayed released Divalproex may have fewer adverse effects, which may improve compliance. Therapeutic and toxic concentrations therapeutic levels: 50-100 ug / ml (347-693 mmol / l), before the morning dose toxic levels:> 150 g / ml (> 1041 mol / l) The adverse effects include nausea and vomiting, gastrointestinal hypersensitivity, weight gain, alopecia reversible (5% of cases), transient drowsiness, transient neutropenia and tremor. An idiosyncratic occurrence hyperammonaemic encephalopathy may occur. Rarely occurs a fatal hepatic necrosis, especially in young neurologically impaired children who are treated with multiple anticonvulsants. The risk of neural tube defects is slightly larger at valproate than with other commonly used anticonvulsant drugs. Since hepatic side effects, should be performed in patients taking divalproex, 1 year every 3 months Leberfunktonstests; increase the serum transaminases or ammonia levels significantly (> 2-fold the upper limit of normal value), the drug should be discontinued. An ammonia increase up to 1.5 times the ULN can be tolerated without risk. Ethosuximide This drug is indicated for absence seizures. Dosage Adults: 250 mg po 2 times a day, increasing in 250 mg increments every 4-7 d (usual maximum: 1500 mg / day) Children 3-6 years: 250 mg po once daily (usual maximum: 20-40 mg / kg / day) Children> 6 years: initial 250 mg po 2 times a day, increasing to 250 mg / day as needed every 4-7 days (usual maximum: 1500 mg / day) therapeutic and toxic concentrations Therapeutic: 40-100 ug / ml (283-708 mmol / l) Toxic:> 100 ug / ml (> 708 mmol / l) Toxic levels are not well founded. The adverse effects include nausea, lethargy, dizziness and headache. Idiosyncratic adverse effects are leucopenia or pancytopenia, dermatitis and systemic lupus erythematosus. Eslicarbazepine This drug is indicated for the treatment of partial seizures as monotherapy or adjunct therapy. First dose 400 mg po once / day, increasing at weekly intervals by 400 mg to 600 mg / day, up to a recommended maintenance dose of 800 to 1600 mg once / day eslicarbazepine <18 years have not indicated for use in patients. The adverse effects include dizziness, diplopia, somnolence, hyponatremia, suicidal ideation and dermatologic reactions including Stevens-Johnson syndrome. Ezogabin This drug is indicated for partial seizures as a third-line monotherapy or adjunctive therapy. Dosage Adult: 200-400 mg po 3 times daily Ezogabine is not indicated for use in patients <18 years. It was observed no significant association between blood levels and pharmacological effects. The adverse effects include urinary retention, neuropsychiatric symptoms (eg. As confusion, psychosis, hallucinations, suicidal thoughts), abnormalities of the retina, QT prolongation, dizziness and drowsiness. Felbamate This drug is indicated for refractory partial seizures and atypical absence seizures associated with Lennox-Gastaut syndrome. Dosage Adults: initial 400 mg po 3 times daily (maximum of 3600 mg / day) Children: Initial 15 mg / kg / day p.o. (Maximum 45 mg / kg / day) Therapeutic and toxic concentrations Therapeutic: 30-60 ug / ml (125-250 mmol / l) Toxic: - The adverse effects include headache, fatigue, liver failure and aplastic anemia rare. Written informed consent of the patient is required. Fosphenytoin This drug is indicated for epilepticus status. The indications are the same as in i.v. phenytoin. These include epilepticus tonic-clonic seizures, complex partial seizures, prevention of seizures after head trauma and convulsive status. Dosage Adults: single dose of 10-20 phenytoin equivalents (PE) / kg i.v. or i.m. (Maximum infusion rate: 150 PE / min) Children: As in adults, heart rate and blood pressure should be monitored when the maximum infusion rate is used, but not with a slower delivery. Therapeutic and toxic concentrations Therapeutic: 10-20 ug / ml (40-80 mmol / l) Toxic:> 25 ug / ml (> 99 mmol / l) are among the undesirable effects ataxia, dizziness, drowsiness, headache, pruritus and paresthesia , Gabapentin This drug is indicated for the adjuvant treatment of partial seizures in patients aged 3-12 years of partial-onset seizures with or without secondarily generalized tonic-clonic seizures in patients aged ? 12 years. Dosage Adults: 300 mg po 3 times daily (usual maximum: 1200 mg three times daily) Children 3-12 years: 12.5 to 20 mg / kg p.o. 2 times daily (usual maximum: 50 mg / kg 2 times a day) children ? 12 years: 300 mg po 3 times daily (usual maximum: 1200 mg three times daily) therapeutic and toxic concentrations were not determined. The adverse effects include drowsiness, dizziness, weight gain and headaches and in patients aged 3-12 years drowsiness, aggressive behavior, mood swings and hyperactivity. Lacosamide This drug is indicated for the monotherapy of second choice or adjuvant treatment of partial seizures in patients ? 17 years old. Dosage Adult: 100-200 mg po 2 times daily lacosamide is not specified <17 years for use in children. Therapeutic and toxic concentrations Therapeutic: 5-10 micrograms / ml Toxic: Not well-founded The adverse effects include dizziness, double vision and suicidal thoughts. Lamotrigine This drug is indicated for the adjunctive treatment of partial seizures in patients ? 2 years, generalized seizures associated with Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures. In patients ? 16 years lamotrigine is used as monotherapy for partial or secondarily generalized seizures to a concomitantly used enzyme-inducing anticonvulsant (eg. As carbamazepine, phenytoin, phenobarbital) or discontinuation of valproate. The metabolism of lamotrigine is increased by enzyme-inducing anticonvulsants and by enzyme-inhibitory anticonvulsants (z. B. valproate) reduced. Valproate inhibits a broad spectrum of liver enzymes. Lamotrigine can develop a special synergistic effect when it is used with valproate. Dosierung für Erwachsene Mit enzyminduzierenden Antikonvulsiva und ohne Valproat: 50 mg p.o. einmal täglich für 2 Wochen, gefolgt von 50 mg p.o. 2-mal täglich für 2 Wochen, dann Steigerung um 100 mg/Tag alle 1–2 Wochen bis zur üblichen Erhaltungsdosis (150–250 mg p.o. 2-mal täglich) Mit Valproat und mit oder ohne enzyminduzierende Antikonvulsiva: 25 mg p.o. einmal jeden 2. Tag über 2 Wochen, gefolgt von 25 mg p.o. einmal täglich für 2 Wochen, dann Steigerung um 25–50 mg/Tag alle 1–2 Wochen bis zur üblichen Erhaltungsdosis (100 mg p.o. einmal täglich bis 200 mg p.o. 2-mal täglich) Dosierung bei Patienten < 16 Jahre Mit enzyminduzierenden Antikonvulsiva und ohne Valproat: Initial 1 mg/kg p.o. 2-mal täglich für 2 Wochen, gefolgt von 2,5 mg/kg p.o. 2-mal täglich für 2 Wochen, dann 5 mg/kg p.o. 2-mal täglich (übliches Maximum: 15 mg/kg oder 250 mg/Tag) Mit enzyminduzi

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