quetiapine-fumarate and Seizures

Somnambulism, a previously unreported side effect of quetiapine, is described in two cases. Both cases involved individuals who had no prior or family history of somnambulism and had attention-deficit/hyperactivity disorder. The possible significance of this will also be discussed. Somnambulism is a common parasomnia that reflects an impairment in the normal mechanisms of arousal from sleep in which motor behaviors are activated without full consciousness. Motor behaviors are initiated during deep non-rapid eye movement or slow-wave sleep (stages 3-4), and may be limited to relatively simple manifestations, such as sitting up, fumbling with objects or bedclothes, or mumbling.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Humans; Lower Extremity; Magnesium; Male; Middle Aged; Polysomnography; Quetiapine Fumarate; Seizures; Somnambulism

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

The death of a 36-year-old alcoholic man who died after developing seizure activity while being treated with tramadol, as well as with venlafaxine, trazodone, and quetiapine, all of which interact with the neurotransmitter serotonin, is reported. The decedent, who had a history of chronic back pain, alcoholism, depression, mild hypertensive cardiovascular disease, and gastritis, had just been discharged from the hospital after 4 days of alcohol detoxification treatment. During the admission, no withdrawal seizures were noted. The morning after discharge, a witness observed the decedent exhibiting seizure activity and then collapsing. An autopsy was performed approximately 6 hours after death, and the anatomic findings were consistent with seizure activity and collapse, which included biting injuries of the tongue and soft-tissue injuries of the face. Toxicologic analysis identified tramadol, venlafaxine, promethazine, and acetaminophen in the urine; tramadol (0.70 mg/L) and venlafaxine (0.30 mg/L) in the heart blood, and 0.10 mg of tramadol in 40 ml of submitted stomach contents. No metabolites, such as acetate, acetone, lactate, and pyruvate, were found in the specimens that would be characteristically found in a person with alcohol withdrawal syndrome. The threshold for seizures is lowered by tramadol. In addition, the risk for seizure is enhanced by the concomitant use of tramadol with selective serotonin reuptake inhibitors or neuroleptics, and its use in patients with a recognized risk for seizures, i.e., alcohol withdrawal. The cause of death in this individual was seizure activity complicating therapy for back pain, depression, and alcohol withdrawal syndrome. The data in Adverse Event Reporting System of the Food and Drug Administration from November 1, 1997 to September 8, 1999 was reviewed along with a MEDLINE search from 1966 to the present. This case appears to be the first reported death caused by seizure activity in a patient taking tramadol in combination with drugs that affect serotonin.

Topics: Adult; Alcoholism; Analgesics, Opioid; Cyclohexanols; Dibenzothiazepines; Drug Interactions; Fatal Outcome; Humans; Lorazepam; Male; MEDLINE; Mental Processes; Quetiapine Fumarate; Receptors, Serotonin; Seizures; Selective Serotonin Reuptake Inhibitors; Smoking; Tramadol; Trazodone; Venlafaxine Hydrochloride

Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity.. The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence).. We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides.. There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Asthma; Bipolar Disorder; Cardiovascular Diseases; Comorbidity; Comparative Effectiveness Research; Diabetes Mellitus; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Hyperlipidemias; Lithium Compounds; Male; Metabolic Syndrome; Middle Aged; Neoplasms; Quetiapine Fumarate; Seizures; Smoking; Substance-Related Disorders

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Seizures

Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.. We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database.. There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none;. Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Topics: Acetaminophen; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Coma; Diazepam; Droperidol; Drug Overdose; Duloxetine Hydrochloride; Female; Humans; Hypotension; Ibuprofen; Middle Aged; Norepinephrine; Oxycodone; Pregabalin; Quetiapine Fumarate; Seizures; Serotonin; Sympathomimetics; Tachycardia

Lesion-based investigations of psychopathology have preceded contemporary network-neuroscience initiatives. However, brain-lesions detected in routine psychiatric practice are often considered incidental and therefore ignored. Here, we illustrate a strategy to combine individual subject-level lesion information with open-source normative functional-connectomics data to make putative, neuroscience-informed symptom interpretation. Specifically, we report a patient with left precuneus granulomatous lesion and seizures followed by two distinct symptoms - kinetopsia and delusions of nihilism and guilt - which had a differential treatment response. The lesion-based brain-mapping approach could identify correlated (default-mode) and anti-correlated (temporo-parieto-occipital) networks, which enabled a neurobiological formulation of these diverse clinical manifestations.

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Brain Mapping; Brain Neoplasms; Depressive Disorder, Major; Diagnosis, Differential; Electroconvulsive Therapy; Female; Fluoxetine; Granuloma; Humans; Magnetic Resonance Imaging; Middle Aged; Parietal Lobe; Phenytoin; Quetiapine Fumarate; Schizophrenia, Paranoid; Seizures

Topics: Anesthetics, Local; Animals; Antipsychotic Agents; Aripiprazole; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Mice; Mice, Inbred BALB C; Quetiapine Fumarate; Seizures; Survival Rate

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

Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD.

Topics: Animals; Animals, Newborn; Anticonvulsants; Cerebral Cortex; Cognition Disorders; Corpus Callosum; Disease Models, Animal; Malformations of Cortical Development; Maze Learning; Myelin Sheath; Nootropic Agents; Pentylenetetrazole; Quetiapine Fumarate; Rats, Sprague-Dawley; Recognition, Psychology; Seizures; Severity of Illness Index; Spatial Memory; X-Rays

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

Quetiapine, a second-generation antipsychotic, acts at multiple brain neurotransmitter receptors and has the potential for serious complications. Although seizures have been described in the literature, delayed seizure onset has not been reported. We report the first case of delayed seizures after a significant quetiapine overdose.. A 27-year-old female presented to the emergency department following an overdose of approximately 30 g of quetiapine. Twenty-four hours after arrival, the patient had 2 seizures. The patient was then intubated and remained in the ICU for four days. EEG was negative for epileptiform activity. The serum quetiapine levels (MedTox, St. Paul, MN) were 8.67 mg/L on hospital day one and 3.28 mg/L on hospital day three.. Quetiapine poisoning, with serum levels, associated with seizures has been reported in one prior case. Our case report represents late-onset seizures with serum levels above therapeutic range (>1 mg/L). The serum concentrations of quetiapine in this case were consistent with those in postmortem case reports.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Critical Care; Dibenzothiazepines; Drug Overdose; Electrocardiography; Electroencephalography; Female; Humans; Quetiapine Fumarate; Recurrence; Seizures; Time Factors; Treatment Outcome

A 55-year-old man with congenital hemiparesis of the right side, three episodes of generalised tonic-clonic seizure at 16 years of age, and two episodes of severe depression and two episodes of hypomania in the past, presented with severe depression with psychotic symptoms. Computed tomography of the brain showed a grey matter-lined cerebrospinal fluid-filled cleft in the left cerebral hemisphere, involving the temporoparietal region. He was diagnosed to have bipolar II disorder, and was currently severely depressed with psychotic symptoms and schizencephaly. He improved with sodium valproate 1,000 mg/day, quetiapine 450 mg/day and escitalopram 20 mg/day after three weeks without any emergent side effects, and was maintaining well at three months follow-up. Although uncommon, schizencephaly may be considered as one of the differentials in cases of bipolar disorder along with congenital hemiparesis, mental retardation and/or seizures; and neuroimaging should be done to confirm the diagnosis.

Topics: Bipolar Disorder; Brain; Citalopram; Depression; Diagnosis, Differential; Dibenzothiazepines; Humans; Male; Malformations of Cortical Development; Middle Aged; Quetiapine Fumarate; Seizures; Tomography, X-Ray Computed; Treatment Outcome; Valproic Acid

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Topics: Adult; Antipsychotic Agents; Autonomic Nervous System Diseases; Chromatography, High Pressure Liquid; Coma; Depressive Disorder, Major; Dibenzothiazepines; Drug Overdose; Female; Glasgow Coma Scale; Half-Life; Humans; Long QT Syndrome; Parasympathetic Nervous System; Quetiapine Fumarate; Schizophrenia; Seizures; Suicide, Attempted

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Ornithine Carbamoyltransferase Deficiency Disease; Quetiapine Fumarate; Seizures

To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs.. A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome.. Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication.. Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.

Topics: Coma; Cyclohexanols; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Electrocardiography; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Respiratory Insufficiency; Seizures; Serotonin Agents; Serotonin Syndrome; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Brain; Carrier Proteins; Dibenzothiazepines; Disease Progression; Electroencephalography; Female; Genetic Predisposition to Disease; Hallucinations; Humans; Lafora Disease; Mutation; Quetiapine Fumarate; Seizures; Treatment Outcome; Ubiquitin-Protein Ligases

Antipsychotic-induced extrapyramidal side effects have a negative impact on treatment for mental illness. Acute dystonic reactions are uncomfortable and frightening to the patient, and often lead to early discontinuation of drug therapy and worsened long-term outcome. The lower propensity of the atypical antipsychotic agents to cause extrapyramidal symptoms (EPS) has been associated with multiple benefits, including improved adherence. The authors describe a 57-year-old male patient who was in the treatment refractory unit. This patient exhibited extreme sensitivity to antipsychotic agents, experiencing acute dystonic reactions with quetiapine and olanzapine, in addition to older typical antipsychotic agents. The patient has not experienced acute EPS since therapy with aripiprazole was initiated. Further complicating this patient's course is his unusual sensitivity to experiencing dystonic reactions. We have observed acute dystonias in the absence of antipsychotic treatment and in the context of seizure activity (or paroxysmal dyskinetic activity). The true etiology of the latter dystonic activity has not been completely determined due to the patient's unwillingness to cooperate with invasive testing. None of the gene variations tested (CYP2D6 phenotype, two dopamine D2 receptor variants and one D3 receptor variant) appeared to explain the patient's vulnerability to acute dystonic reactions.

Topics: Anticonvulsants; Antipsychotic Agents; Chronic Disease; Cytochrome P-450 CYP2D6; Dibenzothiazepines; Dystonia; Genotype; Humans; Male; Middle Aged; Phenytoin; Psychotic Disorders; Quetiapine Fumarate; Seizures; Valproic Acid

Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs.. We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine.. Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes.. Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Middle Aged; Quetiapine Fumarate; Seizures; Torsades de Pointes

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Dibenzothiazepines; Drug Packaging; Female; Humans; Medication Errors; Piperazines; Quetiapine Fumarate; Seizures; Triazoles

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

The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made.

Topics: Adult; Anticonvulsants; Commitment of Mentally Ill; Dibenzothiazepines; Fantasy; Forensic Psychiatry; Homicide; Hospitalization; Hospitals, Psychiatric; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Seizures; Self Disclosure

To report a case of seizures in a patient with Alzheimer disease, who was receiving quetiapine for psychoses.. A 75-year-old white man with Alzheimer disease was observed to have seizures while receiving quetiapine 500 mg/d and carbamazepine 200 mg/d. He had been taking quetiapine for 18 months prior to the event. No other toxic, metabolic, or anatomic abnormalities were identified to explain the seizures. After cessation of quetiapine treatment, the patient remained seizure free. An objective causality assessment revealed that the adverse drug reaction was possible.. The patient was taking a relatively high dose of quetiapine. An increased risk of seizures has been associated with Alzheimer disease. Using a relatively high dose of quetiapine may have resulted in seizures in our patient with Alzheimer disease.. As with other antipsychotics, quetiapine should be used cautiously in elderly patients with conditions that can lower the seizure threshold, and special monitoring should be performed for this serious adverse effect.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Carbamazepine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Seizures

We describe the effects of quetiapine in overdose.. Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate).. There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours.. Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Topics: Adult; Antipsychotic Agents; Central Nervous System Diseases; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Drug Therapy, Combination; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Length of Stay; Male; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; 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

1. Several neuroleptics inhibited the 3 microM gamma-aminobutyric acid induced-chloride current (GABA-current) on dissociated rat dorsal root ganglion neurons in whole-cell patch-clamp investigations. 2. The IC(50) for clozapine, zotepine, olanzapine, risperidone and chlorpromazine were 6.95, 18.26, 20.30, 106.01 and 114.56 microM, respectively. The values for the inhibitory effects of neuroleptics on the GABA (3 microM)-current, which were calculated by the fitting Hill's equations where the concentrations represent the mean therapeutic blood concentrations, were ranked clozapine>zotepine>chlorpromazine>olanzapine>risperidone. These inhibitory effects, weighted with the therapeutic concentrations of neuroleptics, were correlated with the clinical incidences of seizure during treatment with neuroleptics. 3. Clozapine reduced the picrotoxin-inhibiton, and may compete with a ligand of the t-butylbicyclophosphorothionate (TBPS) binding site. 4. Haloperidol and quetiapine did not affect the peak amplitude of the GABA (3 microM)-current. However, haloperidol reduced the clozapine-inhibition, and may antagonize ligand binding to TBPS binding site. 5. Neuroleptics including haloperidol and quetiapine enhanced the desensitization of the GABA (3 microM)-current. However, haloperidol and quetiapine at 100 microM inhibited the desensitization at the beginning of application. 6. Blonanserin (AD-5423) at 30 and 50 microM potentiated the GABA (3 microM)-current to 170.1+/-6.9 and 192.0+/-10.6% of the control current, respectively. Blonanserin shifted GABA concentration-response curve leftward. Blonanserin only partly negatively interacted with diazepam. The blonanserin-potentiation was not reversed by flumazenil. Blonanserin is not a benzodiazepine receptor agonist. 7. The various effects of neuroleptics on the GABA-current may be related to the clinical effects including modifying the seizure threshold.

Topics: Animals; Antipsychotic Agents; Cells, Cultured; Chloride Channel Agonists; Chloride Channels; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Synergism; gamma-Aminobutyric Acid; Ganglia, Spinal; Haloperidol; Incidence; Membrane Potentials; Piperazines; Piperidines; Quetiapine Fumarate; Rats; Rats, Wistar; Seizures