olanzapine and Seizures

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Both first-generation and second-generation antipsychotic medications can lower the seizure threshold, increasing the chances of seizure induction. This article reviews the published literature concerning the seizure-lowering effects of first- and second-generation antipsychotic medication. Unfortunately, rigorously controlled studies are relatively infrequent, and case reports form a large part of the available literature, limiting the confidence with which firm conclusions can be drawn. Of the first-generation antipsychotic medications, chlorpromazine appears to be associated with the greatest risk of seizure provocation, although other first-generation antipsychotics also lower seizure threshold. Conversely, molindone, haloperidol, fluphenazine, pimozide and trifluoperazine are associated with a lower risk of seizure induction. Clozapine is the second-generation antipsychotic most frequently associated with seizures, with risperidone appearing to confer a relatively low risk. Other factors such as history of seizure activity, concurrent use of other drugs that lower seizure threshold, rapid dose titration, slow drug metabolism, metabolic factors and drug-drug interactions appear to increase the chances of an antipsychotic medication inducing seizure activity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Topics: Antipsychotic Agents; Benzodiazepines; Brain Neoplasms; Haloperidol; Humans; Hydrocephalus; Immunoglobulins, Intravenous; Intracranial Hypertension; Mental Disorders; Olanzapine; Pirenzepine; Seizures

Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus, the novel antipsychotics are the result of a search to substantially widen the distance between the dose that treats psychosis and the one that produces adverse effects. In vitro binding profiles have been created for the atypical antipsychotics that have been approved by the U.S. Food and Drug Administration (FDA)-clozapine, olanzapine, and risperidone and those that are under FDA review-quetiapine and sertindole. These profiles, which were compared with that of the typical neuroleptic haloperidol, provide guidance for predicting the adverse effects produced by these drugs. Most conventional antipsychotics have central nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia, sedation, and dulling of cognition. Other adverse effects of the typical antipsychotics include the neuroleptic malignant syndrome, orthostatic hypotension, changes in liver function, anticholinergic and antiadrenergic side effects, sexual dysfunction, and weight gain. The newer agents have a lower incidence of EPS and tardive dyskinesia, while weight gain and changes in blood pressure and liver function tests are adverse effects that have been associated with the use of the newer agents. The favorable side effect profile of these new antipsychotics is likely to make patients more willing to continue treatment, and thus these agents represent a step forward in the treatment of patients with severe, chronic mental illness.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Receptors, Neurotransmitter; Seizures; Sleep; Weight Gain

Although neuroleptic drugs have become the mainstay of treating acute and chronic psychosis, they are substantially limited by troublesome side effects. The traditional neuroleptic drugs have a wide array of central nervous system and peripheral system side effects that often lead to problems in management or patient noncompliance. Of particular difficulty are the extrapyramidal symptoms and tardive dyskinesia. However, other side effects of seizures, sedation, neuroleptic malignant syndrome and cardiovascular, hematologic, endocrinological, and weight gain problems remain as clinical management challenges posed by existing antipsychotic drug therapy. Considerable progress has been made in improving the motor side effect profile with the advent of clozapine and risperidone. However, each of these drugs has its own dose-limiting side effect profile. Two new drugs, olanzapine and sertindole, are now added to the pharmacopeia for treating psychosis. They further improve the benefit/ risk ratio because they have even fewer EPS and other side effects. Overall, these new antipsychotic agents greatly improve the treatment of psychosis by reducing drug-induced morbidity and improving the quality of life for patients.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Seizures; Sleep; Weight Gain

One third of epilepsy patients do not become seizure-free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long-term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons.. Epileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno-associated viral vector encoding the inhibitory DREADD hM4D(Gi), preceded by a cell-specific promotor targeting excitatory neurons. The effect of clozapine-mediated DREADD activation on dentate gyrus evoked potentials and spontaneous electrographic seizures was evaluated. Animals were systemically treated with single (.1 mg/kg/24 h) or repeated (.1 mg/kg/6 h) injections of clozapine. In addition, long-term continuous release of clozapine and olanzapine (2.8 mg/kg/7 days) using implantable minipumps was evaluated. All treatments were administered during the chronic epileptic phase and between 1.5 and 13.5 months after viral transduction.. In the DREADD group, dentate gyrus evoked potentials were inhibited after clozapine treatment. Only in DREADD-expressing animals, clozapine reduced seizure frequency during the first 6 h postinjection. When administered repeatedly, seizures were suppressed during the entire day. Long-term treatment with clozapine and olanzapine both resulted in significant seizure-suppressing effects for multiple days. Histological analysis revealed DREADD expression in both hippocampi and some cortical regions. However, lesions were also detected at the site of vector injection.. This study shows that inhibition of the hippocampus using chemogenetics results in potent seizure-suppressing effects in the intraperitoneal kainic acid rat model, even 1 year after viral transduction. Despite a need for further optimization, chemogenetic neuromodulation represents a promising treatment prospect for temporal lobe epilepsy.

Topics: Animals; Anticonvulsants; Clozapine; Dentate Gyrus; Disease Models, Animal; Epilepsy, Temporal Lobe; Evoked Potentials; G-Protein-Coupled Receptor Kinases; Gene Editing; Hippocampus; Male; Olanzapine; Rats; Rats, Sprague-Dawley; Receptors, Neurotransmitter; Seizures

Olanzapine is a second-generation antipsychotic. Incidence of olanzapine-induced seizures (OIS) is low with monotherapy. Combination therapy with another antipsychotic, drug metabolism and old age are risk factors for OIS. Our patient was a 71-year-old man, admitted to the psychiatry unit. He was managed on the lines of bipolar affective disorder current episode depression and dementia. He was started on olanzapine 1.25 mg two times/day. The patient developed generalised tonic-clonic seizure that lasted for around two and a half minutes within 24 hours of olanzapine treatment. His electroencephalogram showed findings that were suggestive of mild slowing. Our case discusses the incidence of OIS on the subtherapeutic dose. This presentation involves multiple risk factors for OIS: a history of stroke, poststroke seizure, old age and cognitive impairment. Due to scarcity of evidence of OIS; mostly with recommended therapeutic dose range physicians may underestimate seizure risk at subtherapeutic doses.

Topics: Administration, Intravenous; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Drug Monitoring; Electroencephalography; Humans; Male; Olanzapine; Risk Factors; Seizures; Treatment Outcome; Valproic Acid

Olanzapine-related seizures have rarely been reported despite associated proconvulsant risk factors described in the literature: myoclonic status, increased frequency of seizures, tonic-clonic seizures, as well as fatal status epilepticus. We present a psychiatric patient who developed repetitive focal motor seizures and lingual dystonia when olanzapine was added for psychomotor agitation and aggressiveness. Olanzapine was immediately suspended and the seizures progressively disappeared. A control EEG showed no paroxysmal discharges. Olanzapine shares some pharmacological similarities with clozapine, a neuroleptic with a high risk of dose-dependent seizures. This adverse effect should be taken into account, and olanzapine should be used with caution if concomitant circumstances decrease the seizure threshold. [Published with video sequence online].

Topics: Antipsychotic Agents; Benzodiazepines; Dystonia; Electroencephalography; Epilepsy, Partial, Motor; Humans; Male; Middle Aged; Olanzapine; Seizures

Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

Topics: Animals; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Disease Models, Animal; Epilepsy; Haloperidol; Mental Disorders; Olanzapine; Quetiapine Fumarate; Rats; Risperidone; Seizures

This is a case of a citalopram and olanzapine overdose causing seizures and severe cardiotoxicity.. A 21-year-old man presented unresponsive, with seizures, to an Emergency Department. The patient's initial electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30 min of arrival, peak citalopram and olanzapine levels were measured to be 522 ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic until 13.6 h and 42.6 h after arrival for citalopram and olanzapine, respectively. The patient developed bradycardia and hypotension that required multimodal therapies including sodium bicarbonate boluses, vasopressors, and transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but not olanzapine, was supratherapeutic.. This case describes cardiotoxicity directly correlated with supratherapeutic citalopram levels in overdose.

Topics: Adult; Benzodiazepines; Bradycardia; Citalopram; Drug Overdose; Electrocardiography; Humans; Hypotension; Male; Olanzapine; Seizures; Selective Serotonin Reuptake Inhibitors; Young Adult

Epileptic seizures associated with intrathecal baclofen (ITB) application have been observed in patients with traumatic brain injury. A higher incidence of seizures has also been reported in patients with multiple sclerosis (MS) receiving ITB. To our knowledge, no case of a first epileptic seizure has been reported in the context of ITB bolus testing in MS. We report a 41-year-old female patient with primary progressive MS receiving olanzapine and oxcarbazepine for psychotic disorder. Five years prior she began to develop severe spastic quadriparesis, rendering her a candidate for ITB treatment. After ITB test bolus application, however, she experienced a first epileptic seizure. Our observation indicates that ITB may trigger seizures in patients with MS. The observed seizure occurred during ITB bolus testing despite antiepileptic co-medication, which concurs with previous reports suggesting that rapid changes in the dose of ITB may carry a higher risk of seizure induction.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Baclofen; Benzodiazepines; Carbamazepine; Female; GABA-B Receptor Agonists; Humans; Injections, Spinal; Multiple Sclerosis, Chronic Progressive; Olanzapine; Oxcarbazepine; Seizures

To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and the oxime HI-6 for reactivation of soman-inhibited acetylcholinesterase. We also investigated whether sub-chronic treatment with the reported neurogenesis enhancer olanzapine would stimulate neurogenesis and possibly normalize the anticipated long-term deleterious effects of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed after 30 min by soman (200 microg/kg s.c.) and atropine sulphate (16 mg/kg i.m.) 1 min thereafter. Soman poisoning led to an elevation of extracellular acetylcholine levels to 1500% over baseline values as assessed by striatal microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24 h post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU labeled. Learning and memory performance were assessed 8 weeks after soman poisoning, followed by analysis of surviving newborn cells (BrdU) and neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a significantly impaired learning ability was found that was paralleled by significantly lower numbers of DCX-positive cells but no changes in the number of BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. We conclude that soman poisoning has long lasting effects on learning ability, a finding that was accompanied by impaired neurogenesis. Although we confirm a correlation between impaired neurogenesis and cognitive deficits, establishing the true causal relationship between these processes in OP exposed animals awaits future research.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Atropine; Benzodiazepines; Cholinesterase Reactivators; Corpus Striatum; Doublecortin Protein; Hippocampus; Male; Maze Learning; Neurogenesis; Olanzapine; Oximes; Pyridinium Compounds; Rats; Rats, Sprague-Dawley; Seizures; Soman

This case report describes the history and hospital course of an otherwise healthy 20-year-old male with bipolar I disorder who developed symptoms of severe lithium toxicity, culminating in a seizure, despite a level of lithium of only 0.8 mEq/L, within the usual therapeutic range. The discussion emphasizes that lithium toxicity is diagnosed by clinical symptoms and can occur even at usual therapeutic blood levels.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Overdose; Humans; Lithium Carbonate; Male; Olanzapine; Seizures; Suicide, Attempted; Young Adult

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model.. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine.. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine.. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Topics: Animals; Benzodiazepines; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Drug Antagonism; Injections, Intraperitoneal; Longevity; Male; Mice; Mice, Inbred Strains; Olanzapine; Poisoning; Seizures; Selective Serotonin Reuptake Inhibitors; Vasoconstrictor Agents

Olanzapine is a widely used second generation antipsychotic drug. Case reports of intoxications have been published, but reports in the literature of non-fatal intoxications of olanzapine containing repeated measurements of serum levels are scarce. Therefore, this case of non-fatal olanzapine intoxication is presented, in which 19 blood samples were drawn during 2 weeks. The highest (initial) measured value was estimated at 800 pg/L. This patient ingested 550 mg of olanzapine resulting in clinical signs of intoxication, including seizures. Because the patient was found the day after the intoxication, the initial concentration had probably been higher. The pharmacokinetics of olanzapine has been described as linear and dose-proportional throughout the therapeutic dosing range. Large overdoses, however, have been described to show non-linear pharmacokinetics. In this study's series of serum concentrations, a two-phase elimination was seen, with an initial elimination half-life of about 24 h during the first 3 days, followed by a second phase with a half-life of about 2.5 days. The patient in this case recovered completely. Because the elimination time after intoxication can be considerably longer than expected, it is recommended that the patient's serum concentrations after intoxication be monitored.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Drug Overdose; Half-Life; Humans; Liver Diseases; Liver Function Tests; Male; Olanzapine; Seizures; Suicide, Attempted

Neuroleptic malignant syndrome (NMS) is an uncommon but sometimes fatal complication of neuroleptics and other medications that involve the central dopaminergic system. Many diagnostic criteria have been proposed for NMS but because of its variable presentation, universal criteria have not been established yet. Hyperthermia, disturbances of consciousness, extrapyramidal and autonomic symptoms are common features of NMS. We report the case of a 36 years old woman suffering from chronic schizophrenia and treated with flufenazine and olanzapine, who presented with series of generalised tonic-clonic seizures as the acute onset of recurrent malignant neuroleptic syndrome. Although atypical neuroleptics were previously thought to have less risk for MNS, combination of conventional and atypical neuroleptics in therapy increases the risk of NMS development and olanzapine might be responsible for the epileptic manifestations at the onset of fulminant NMS.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Drug Therapy, Combination; Early Diagnosis; Electroencephalography; Epilepsy, Generalized; Fluphenazine; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Recurrence; Risk Factors; Schizophrenia; Seizures

Topics: Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Citalopram; Female; Fluoxetine; Humans; Mianserin; Myoclonus; Olanzapine; Poisoning; Seizures; Selective Serotonin Reuptake Inhibitors; Unconsciousness

Topics: Aged; Benzodiazepines; Dopamine Agents; Drug Synergism; Female; Humans; Memantine; Neuroprotective Agents; Olanzapine; Phenylcarbamates; Rivastigmine; Seizures; Sertraline

In most patients diagnosed with psychotic depression or schizophrenia and treated with electroconvulsive therapy, parallelly administered antipsychotic medication cannot be stopped. Antipsychotic drugs can influence both seizure threshold and seizure activity in different ways.. The present study processes the data of 77 patients treated parallelly with electroconvulsive therapy and antipsychotic drugs. Oral doses of the antipsychotic medication administered the day before the electroconvulsive therapy, stimulus intensity, seizure durations, and impedance were analysed from session to session.. One group of antipsychotics (haloperidol, fluphenazine, risperidone, sulpirid) was not found to influence seizure activity: there was no significant difference in EEG and EMG registered seizure duration or in stimulus intensity between the treated and non-treated group. However, significant difference was found between the next treated and non-treated groups in 40% of the sessions in case of olanzapine, in 50% of the sessions in case of clozapine and in 57% of the sessions in case of zuclopenthixol in EEG or EMG registered seizure duration as well as in stimulus intensity. In the third group (quetiapine) there was a significant difference in each session (2nd session: EMG, p=0.02; 5th session: EEG, p=0.05, EMG, p=0.04). Most of the antipsychotics (olanzapine, clozapine, zuclopenthixol) have been shown to possess epileptogenic properties; only quetiapine reduces seizure activity.. In the clinical use of olanzapine, clozopine and zuclopenthixol seems epileptogenic, whereas in the case of quetiapine seizure reducing properties must be taken into account. Together with the consideration of the accompanying somatic and neurologic disturbances and with the concomitant medications this can influence the treatment of choice.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Brain; Clopenthixol; Clozapine; Dibenzothiazepines; Electric Impedance; Electroconvulsive Therapy; Electroencephalography; Electromyography; Female; Fluphenazine; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Seizures; Sulpiride

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Huntington Disease; Olanzapine; Pirenzepine; Seizures

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Electroencephalography; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Seizures; Sex Factors

To report a case involving a witnessed seizure in a patient receiving concurrent olanzapine and quetiapine.. A 27-year-old white woman was observed to have a seizure while receiving a stable dosage of olanzapine 15 mg/d, with the addition of quetiapine 100 mg in the evening 1 day before the occurrence of the seizure. There were no known risk factors for epilepsy.. This case reports a new-onset seizure in the context of concurrent olanzapine and quetiapine use. Interpretation is complicated by recent discontinuation of low-dose clonazepam.. While uncommon, seizures can occur with non-clozapine atypical antipsychotics. Caution is indicated when using these drugs with other agents that may lower the seizure threshold.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Schizophrenia; Seizures

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Olanzapine; Paranoid Disorders; Pirenzepine; Seizures

Topics: Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Clomipramine; Drug Interactions; Drug Therapy, Combination; Humans; Male; Olanzapine; Pirenzepine; Seizures

Olanzapine is similar in structure and pharmacology to clozapine. An increased incidence of electroencephalogram (EEG) abnormalities and seizures has been associated with clozapine but not with olanzapine, although isolated cases of seizures under olanzapine have been observed in high-risk patients.. To evaluate the frequency of epileptic and non-epileptiform EEG abnormalities during treatment with olanzapine.. Using a rating scale of demonstrated reliability, 43 EEGs of patients receiving 10-25 mg/day olanzapine in routine treatment were blindly rated and compared with EEG registrations from the same 43 patients with a different medication.. There was no difference in epileptiform activity between the conditions with and without olanzapine. However, EEG slowing was significantly more frequent with olanzapine than under the other condition. This difference could not be attributed to concomitant medication.. Although epileptiform activity did not increase under olanzapine, unspecific EEG abnormalities may be more frequent than with use of other neuroleptics. Careful surveillance of patients with risk factors for seizures is advisable. Further studies addressing the frequency and clinical relevance of EEG changes under olanzapine are necessary.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Electroencephalography; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Seizures; Statistics, Nonparametric

To report a case of seizures in a patient who started receiving olanzapine, and to review seizure risk associated with antipsychotic use.. A 31-year-old African-American woman with multiple psychiatric and medical disorders, including generalized seizure disorder, experienced seizure activity when switched from haloperidol to olanzapine. Olanzapine was discontinued, haloperidol was quickly titrated to the previous dose, and the patient was started on oral phenytoin with no further seizure activity noted. The patient remained seizure free and phenytoin was discontinued without complications.. Determining causality in this case is complicated by the number of confounding factors that may have contributed to the occurrence of seizures in this patient. These factors include: (1) diagnosis of generalized seizure disorder, (2) diagnosis of organic mental disorder, (3) concurrent pharmacotherapy with medications implicated in lowering the seizure threshold, and (4) abrupt change in pharmacotherapy. The likelihood that a significant drug interaction precipitated seizure activity is doubtful.. Considering all factors related to causality, the likelihood that olanzapine was responsible for precipitating seizure activity in this patient was judged possible. Although premarketing studies have indicated that olanzapine may be associated with minimal seizure liability, this case serves as a reminder that postmarketing surveillance of newly released medications is essential.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Female; Haloperidol; Humans; Olanzapine; Phenytoin; Pirenzepine; Seizures