clozapine and Epilepsy--Tonic-Clonic

To inform clinicians about the types of seizures that can be induced by clozapine and to provide recommendations for treatment.. We identified articles on clozapine-induced seizures from a MEDLINE search of the English-language literature from 1978 to July 2006. The frequency of each type of seizure and the dosages of clozapine associated with seizures were compiled. In addition to this review, we report a new case illustrating the challenge of diagnosing subtle seizure activity.. The tonic-clonic variety is the most frequently described clozapine-induced seizure. Myoclonic and atonic seizures together constitute about one-quarter of the reported seizures. The mean dosage of clozapine associated with seizures is not high (less than 600 mg daily).. It may be difficult for clinicians to recognize subtle types of clozapine-induced seizures, such as myoclonic, atonic, or partial seizures. Clinicians should not place excessive reliance on the plasma level of clozapine or electroencephalogram findings to predict the occurrence of seizures. When a first seizure occurs, it is recommended that the dosage of clozapine be reduced or an alternative antipsychotic agent be employed. If a second seizure occurs, an anticonvulsant drug should be started. Special attention should be paid when commencing or discontinuing concurrent medication that may affect the plasma level of clozapine.

Topics: Antipsychotic Agents; Brain; Clozapine; Drug Administration Schedule; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Humans; Middle Aged; Schizophrenia, Paranoid; Severity of Illness Index

Seizures are an important adverse effect of clozapine therapy; a cumulative 10% risk of tonic-clonic seizures is estimated after 3.8 years of treatment. Although the risk of seizures may be increased by rapid upward titration and higher doses, recent data do not clearly confirm the dose-dependent effect. The vast majority of clozapine-related seizures are tonic-clonic, although myoclonic seizures also occur. The role of the EEG in predicting the occurrence of clozapine-induced seizures remains uncertain. In patients with clozapine-related seizures, either reducing the dose or adding an antiepileptic medication usually allows continuation of therapy.

Topics: Anticonvulsants; Clozapine; Dose-Response Relationship, Drug; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Tonic-Clonic; Humans; Incidence; Risk Factors; Schizophrenia

Two patients with prolonged postictal encephalopathy lasting 63 and 72 hours, respectively, following seizures with clozapine are reported. Clozapine alters the EEG in a majority of patients treated, with seizure frequency as high as 5-10% in doses above 600 mg/d. Prolonged postictal encephalopathy following a clozapine-induced seizure has not been previously reported but may be an important side effect of this medication. Pharmacologic and clinical issues are discussed.

Topics: Adult; Bipolar Disorder; Cerebral Cortex; Clozapine; Delta Rhythm; Electroencephalography; Epilepsy, Tonic-Clonic; Follow-Up Studies; Humans; Male; Psychoses, Substance-Induced; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Austria; Clozapine; Epilepsy, Tonic-Clonic; Female; Germany; Hospitals, Psychiatric; Humans; Male; Mental Disorders; Middle Aged; Pharmacovigilance; Risk; Seizures; Switzerland

We evaluated two polymorphisms at CYP1A2 (*1C and *1F) in a sample of 108 European-derived patients with schizophrenia and their influence on the pro-convulsive effect of clozapine. We found the *1F/*1F genotype to be significantly associated with seizures, and no relationship was observed with combinations of *1F and *1C alleles.

Topics: Adult; Antipsychotic Agents; Brazil; Clozapine; Cytochrome P-450 CYP1A2; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Genetic Association Studies; Genotype; Humans; Male; Polymorphism, Genetic; RNA, Messenger; Schizophrenia; White People

Seizures can be a serious adverse effect of clozapine, often a last-resort antipsychotic with unique efficacy for some patients. Several anticonvulsants have been reported to be useful in preventing further clozapine-induced seizures and permitting continued treatment with this medication. The authors describe the first reported successful use of lamotrigine for this purpose.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy, Tonic-Clonic; Humans; Lamotrigine; Lithium Carbonate; Male; Psychotic Disorders; Triazines; Young Adult

Topics: Adolescent; Antipsychotic Agents; Clomipramine; Clozapine; Epilepsy, Tonic-Clonic; Humans; Male; Myoclonus; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Stuttering

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Epilepsy; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Humans; Male; Psychotic Disorders

We describe a case of clozapine-induced seizures in a patient with treatment-resistant schizophrenia. She had previously been treated unsuccessfully with a number of atypical antipsychotic medications, before she was eventually started on clozapine. She experienced two separate episodes of observed fits whilst on an initial daily dose of 125 mg and, subsequently, on a daily dose of 237.5 mg. Following discontinuation of clozapine, she was rechallenged and again was observed to have seizures. Appropriate investigations ruled out any organic cause of the fits and clozapine was successfully restarted, together with sodium valproate. By the time of treatment stabilization, the patient had not experienced any further fits. These findings suggest that clozapine-induced seizures can be successfully treated, that gradual dose titration can reduce the likelihood of further episodes of seizures and that concomitant use of a suitable mood stabilizer/anti-epileptic medication can improve the outcome of treatment-resistant schizophrenia. Furthermore, the concomitant use of fluoxetine and clozapine is discouraged, with citalopram suggested as a suitable antidepressant in those depressed patients receiving clozapine.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Clozapine; Epilepsy, Tonic-Clonic; Female; Humans; Schizophrenia, Paranoid; Valproic Acid

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Schizophrenia, Paranoid; Seizures; Topiramate; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Humans; Schizophrenia

Epileptiform EEG changes, myoclonus, and seizures are reported in some patients treated with clozapine. Although these are undesirable side effects, the excitation of specific neuronal networks by clozapine and other neuroleptics may be important for the therapeutic effect of this class of agents. In these experiments, intraperitoneal clozapine 2-16 mg/kg produced dose-related myoclonic jerks in partially restrained rats. Paroxysmal slow waves and spike activity were recorded from implanted electrodes in amygdala, hippocampus, and cortex following higher doses of clozapine, but the EEG abnormalities were not correlated with the myoclonic jerks. Single doses of chlorpromazine (8 and 16 mg/kg) rarely produced myoclonic jerks but provoked generalized tonic seizures in two animals preceded by multiple myoclonic jerks in one. Myoclonus and seizures reflect increased excitability of the central nervous system. It is possible that clozapine and other neuroleptics exert a therapeutic effect by increasing excitability in critical subcortical areas of the brain.

Topics: Amygdala; Animals; Brain; Brain Mapping; Chlorpromazine; Clozapine; Dose-Response Relationship, Drug; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Evoked Potentials; Hippocampus; Male; Rats; Rats, Sprague-Dawley; Seizures; Synaptic Transmission

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Humans; Lithium Carbonate; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

We reviewed the incidence, clinical features, and management of all clozapine-related seizures in 5,629 patients monitored by the Clozaril Patient Management System, during the first 6 months after marketing. Seventy-one patients had generalized tonic-clonic seizures yielding a frequency of 1.3%. One patient had myoclonic seizures prior to generalization. Seizures tended to occur at low doses (< 300 mg/d) during the titration phase, and at high doses (> or = 600 mg/d) during the maintenance phase. Patients with a history of seizures or epilepsy were more likely to have seizures soon after initiation of therapy, on low doses. Twenty-nine of 37 patients (78%) who had seizures and were rechallenged with clozapine were able to continue the medication with dose reduction and more-gradual dose titration, or with the addition of an antiepileptic medication.

Topics: Adolescent; Adult; Aged; Clozapine; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Tonic-Clonic; Female; Humans; Incidence; Life Tables; Male; Middle Aged; Retrospective Studies; Seizures; Time Factors

Topics: Adult; Clozapine; Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Female; Humans; Schizophrenia, Paranoid

Clozapine is an atypical neuroleptic drug that has proved to be effective in alleviating psychotic symptoms refractory to treatment with standard neuroleptic drugs. In addition to hematological side effects, an increased susceptibility to epileptic seizures during clozapine treatment has previously been described. In this report, we describe the clinical picture and electroencephalographic findings of 12 schizophrenic patients who have had from one to six clozapine-associated epileptic convulsions.

Topics: Adult; Carbamazepine; Clonazepam; Clozapine; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Clozapine; Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Humans; Male; Myoclonus; Posture; Schizophrenia; Seizures

Two patients receiving clozapine developed grand mal seizures. The plasma levels in one of the patients at the time of the seizure were approximately 100% higher than on 12 previous occasions. This finding led to the conclusion and the patient's admission that she had taken an overdose. Plasma levels in the other patient exceeded the range the authors had noted in previous studies. The authors emphasize the usefulness of plasma level monitoring in relation to safety, drug defaulting, and side effects.

Topics: Adult; Clozapine; Dibenzazepines; Epilepsy, Tonic-Clonic; Female; Humans; Middle Aged; Schizophrenia; Suicide, Attempted