clozapine and Epilepsy

Psychiatric comorbidities in patients with epilepsy are common. A bidirectional relationship has been well described where not only patients with epilepsy have a higher prevalence of psychiatric comorbidities but also patients with primary psychiatric disorders are at an increased risk of developing seizures. The aim of this review is to highlight the complex relationship between epilepsy and common psychiatric disorders and to answer the question whether psychotropic medications are proconvulsant by reviewing the preclinical and clinical literature. The evidence shows that the majority of psychotropic medications are not proconvulsant when used in therapeutic doses with the exception of a subset of medications, mainly bupropion IR and certain antipsychotic drugs such as clozapine. An effective treatment of psychiatric comorbidities in patients with epilepsy must consider not only the potential therapeutic effect of the drug, but also its potential iatrogenic effects on the seizure disorder.

Topics: Antipsychotic Agents; Clozapine; Epilepsy; Humans; Psychotropic Drugs; Seizures

Clozapine is associated with various haematological adverse effects, including leukopenia, neutropenia, agarnulocytosis, leukocytosis, anaemia, eosinophilia, thrombocytopenia and thrombocythaemia. Recognition and treatment of clozapine-related seizures also will become increasingly important as clozapine use grows in the 1990s. The decision to stop clozapine as a result of haematological adverse effects or seizures is a frustrating one for the clinician, and frequently disastrous for the patient. Cessation of treatment results in relapse. In case that patient is unresponsive to other antipsychotic, restarting clozapine should be consider, despite the risk involved. As the risk of a second agranulocytosis is much higher in those patients, various methods of militating against repeat blood dyscrasias have been treated, including granulocyte colony-stimulating factor and lithium. The decision to restart clozapine should be taken on case-by-case basis and should take into account the likely risks and benefits of restarting. Prior response to clozapine and magnitude of patient deterioration on stopping treatment are important factors to take into this consideration. Clozapine-related seizures did not preclude successful treatment with clozapine. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. With careful haematologyc control, the risk of agranulocytosis can be minimized and in case of clozapine related seizures recommendations include dose reduction, electroencephalogram (EEG), plasma-level monitoring and prophylactic antiepileptic treatment. Re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring.

Topics: Adult; Agranulocytosis; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Humans; Leukopenia; Lithium Carbonate; Psychotic Disorders; Recurrence; Risk Factors; Schizophrenia; Substance Withdrawal Syndrome; Thrombocytopenia

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

Topics: Animals; Apnea; Clozapine; Designer Drugs; Disease Models, Animal; Epilepsy; Ligands; Mice; Mice, Transgenic; NAV1.6 Voltage-Gated Sodium Channel; Oxides; Prosencephalon; Seizures; Sudden Unexpected Death in Epilepsy

In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.

Topics: Animals; Calcium; Clozapine; Disease Models, Animal; Electroencephalography; Epilepsy; Epilepsy, Temporal Lobe; Female; gamma-Aminobutyric Acid; Hippocampus; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Neurons; Pilocarpine; Retroviridae; Seizures

Clozapine (CZP) is an antipsychotic used in resistant psychosis, but has adverse metabolic effects and is associated with new onset or worsening of epileptic seizures (ES). There is not enough information available regarding its effect on metabolic variables and on ES in patients with epilepsy.. To describe the effect of CZP on the metabolic and hematologic profiles, and on ES in patients with epilepsy and with psychosis and/or aggressive behavior.. A case series of patients with epilepsy and psychosis and/or aggressive behavior that received CZP with an 18-week follow-up. Clinical records were assessed from 2008-2018. 30 patients with epilepsy that received CZP were included. A paired analysis (Student’s t-test or Wilcoxon signed rank test) was performed with metabolic variables (glucose, cholesterol, and triglycerides), hematologic variables, weight, body mass index (BMI), and monthly ES before and after CZP administration.. The median age to CZP initiation was 31.9 ± 16.07 years. Median CZP dosage was 193 mg/day. There were changes on BMI (p = 0.001; 3.2 kg/m2 increase, median = 3.08), triglycerides (p = 0.002) and glucose (p = 0.030). Weight increase was 7 kg (p = 0.292; median = 4 kg). Monthly ES mean was decreased from 4.9 (median = 2) to 2.04 (median = 1; p = 0.001).. This study provide information regarding the security profile of CZP in patients with epilepsy with psychosis and/or aggressive behavior. A decrease on monthly ES was observed, as well as moderate increases in triglycerides, glucose and BMI, which coincide with that described by other authors.. La clozapina (CZP) es un antipsicótico efectivo en la psicosis que no responde a otros antipsicóticos, pero tiene efectos metabólicos adversos y se relaciona con la generación de crisis epilépticas (CE). Existe poca información sobre su efecto en variables metabólicas y sobre las CE en pacientes con epilepsia.. Describir el efecto de la CZP en el perfil metabólico, el perfil hematológico y la frecuencia de CE en pacientes con epilepsia y con psicosis o agresividad.. Serie de casos de pacientes con epilepsia y psicosis o agresividad que recibieron CZP con un seguimiento de 18 semanas. Se revisaron los expedientes clínicos de 2008-2018. Se incluyeron 30 pacientes con epilepsia que recibieron CZP. Se hizo una comparación pareada (prueba t de Student o de signo y rango de Wilcoxon), antes y después del inicio de la CZP, de las variables metabólicas (glucosa, colesterol y triglicéridos) y hematológicas, el peso, el índice de masa corporal (IMC) y las CE mensuales.. La edad media al iniciar la CZP fue de 31.9 ± 16.07 años. La dosis media fue 193 mg/día. Hubo incremento en el IMC (p = 0.001; aumento de 3.2 kg/m2; mediana = 3.08), los triglicéridos (p = 0.002) y la glucosa (p = 0.030). La ganancia de peso fue de 7 ± 10.4 kg (p = 0.292; mediana = 4 kg). El promedio de CE mensuales se redujo de 4.9 (mediana = 2) a 2.04 (p = 0.001; mediana = 1).. Este estudio aporta información del perfil de seguridad del uso de CZP en pacientes con epilepsia y psicosis o agresividad. Se observó una disminución en la frecuencia mensual de CE, así como aumentos moderados de los triglicéridos, la glucosa y el IMC, que coinciden con lo descrito por otros autores.

Topics: Clozapine; Epilepsy; Humans; Metabolome; Psychotic Disorders; Seizures

Since the middle of the 19th century, both neurologists and psychiatrists have linked psychosis and epilepsy. Clozapine, the most effective antipsychotic drug, alters electroencephalographic activity and carries a significant risk of causing seizures. Unfortunately, this risk limits the drug's potential use in treating pharmacoresistant psychosis in patients with epilepsy. We present a unique case in which we used clozapine successfully as a last resort treatment for chronic interictal psychosis in a 43-year-old woman with severe pharmacoresistant epilepsy and recurrent status epilepticus. Her psychotic symptoms improved markedly without an increase in the frequency of seizures despite gradual titration of the clozapine dose up to 300 mg daily. Her response demonstrates that, properly monitored, clozapine can be an effective treatment for psychosis even in patients with daily seizures.

Topics: Adult; Antipsychotic Agents; Clozapine; Epilepsy; Female; Humans; Psychotic Disorders; Treatment Outcome

A series of thirty N-(phenoxy)alkyl or N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols has been designed, synthesized and evaluated for anticonvulsant activity in MES, 6Hz test, and pilocarpine-induced status epilepticus. Among the title compounds, the most promising seems R-(-)-2N-{2-[2-(2,6-dimethylphenoxy)ethoxy]ethyl}aminopropan-1-ol hydrochloride (22a) with proved absolute configuration with X-ray analysis and enantiomeric purity. The compound is effective in MES test with ED50=12.92 mg/kg b.w. and its rotarod TD50=33.26 mg/kg b.w. The activity dose is also effective in a neurogenic pain model-the formalin test. Within high throughput profile assay, among eighty one targets, the strongest affinity of the compound is observed towards σ receptors and 5-HT transporter and the compound does not bind to hERG. It also does not exhibit mutagenic properties in the Vibrio harveyi test. Moreover, murine liver microsomal assay and pharmacokinetics profile (mice, iv, p.o., ip) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule.

Topics: Amino Alcohols; Animals; Anticonvulsants; Chemistry, Physical; Dose-Response Relationship, Drug; Drug Design; Epilepsy; Male; Mice; Microsomes, Liver; Molecular Structure; Pilocarpine

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

Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks.. We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years.. The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up.. Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Clozapine; Combined Modality Therapy; Epilepsy; Fatal Outcome; Female; Haloperidol; Humans; Nordazepam; Olanzapine; Patient Compliance; Psychotherapy; Psychotic Disorders; Schizophrenia, Paranoid; Shared Paranoid Disorder; Sibling Relations; Suicide; Valproic Acid

Topics: Brain; Cataplexy; Clozapine; Diagnosis, Differential; Electroencephalography; Epilepsy; Humans; Myoclonus; Serotonin Antagonists; Terminology as Topic

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

Topics: Aged; Antipsychotic Agents; Clozapine; Epilepsy; Humans; Male; Mental Disorders; Middle Aged

Seizures arising from acetylcholinesterase inhibition are a feature of organophosphate anticholinesterase intoxication. Although benzodiazepines are effective against these seizures, alternative anticonvulsant drugs may possess greater efficacy and fewer side-effects. We have investigated in the guinea-pig hippocampal slice preparation the ability of a series of anticonvulsants to suppress epileptiform bursting induced by the irreversible organophosphate anticholinesterase, soman (100 nM). Carbamazepine (300 microM), phenytoin (100 microM), topiramate (100-300 microM) and retigabine (1-30 microM) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 microM) and clomethiazole (100-300 microM) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 microM) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 microM) and gabapentin (100-300 microM) were without effect. These data suggest that several compounds, in particular clomethiazole, clozapine, felbamate, topiramate and retigabine, merit further evaluation as possible treatments for organophosphate poisoning.

Topics: Amines; Animals; Anticonvulsants; Carbamates; Carbamazepine; Chlormethiazole; Clozapine; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Guinea Pigs; Hippocampus; In Vitro Techniques; Levetiracetam; Male; Phenylcarbamates; Phenylenediamines; Piracetam; Propylene Glycols; Soman; Topiramate

There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region.. A retrospective file-review of patients treated in these three settings during the time period March-June 2002 was performed (n = 24). Information was collected using a semistructured proforma.. Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia.. Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side-effects is needed during therapy.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Cognition Disorders; Drug Resistance; Drug Utilization; Epilepsy; Female; Humans; Male; Middle Aged; Personality Disorders; Psychotic Disorders; Retrospective Studies; Schizophrenia; Substance-Related Disorders

Topics: Adult; Antipsychotic Agents; Clozapine; Epilepsy; Humans; Male; Parkinson Disease

Six patients with epilepsy and severe psychosis were treated with the atypical antipsychotic clozapine. The use of clozapine might be complicated in epileptic patients because of an increased risk of seizures. However, none of the reported patients had an increase of their seizure frequency, in contrast, three patients had a substantial reduction of seizures. One patient had a reduction of non-epileptic seizures as well. In the second part of this paper, combinations of clozapine with newer and older anticonvulsants as well as their interactions and associated risks are discussed.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Clozapine; Epilepsy; Female; Humans; Male; Psychotic Disorders; Seizures; Treatment Outcome

Topics: Adult; Clozapine; Epilepsy; Female; Humans; Male; Serotonin Antagonists; Treatment Outcome

Topics: Acetates; Adolescent; Adult; Amines; Anticonvulsants; Antipsychotic Agents; Clozapine; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Epilepsy; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Schizophrenia; Secondary Prevention; Treatment Outcome

Clozapine is an 'atypical' neuroleptic that improves symptoms of many patients with schizophrenia whose illness is resistant to treatment with other neuroleptics. Unlike the 'typical neuroleptics (chlorpromazine, haloperidol), clozapine does not induce extrapyramidal symptoms such as Parkinsonism and tardive dyskinesia in humans or catalepsy in the rat. However, clozapine frequently causes epileptiform EEG changes and causes seizures in 3-5% of patients treated with this drug in therapeutic doses. Clozapine also induces dose dependent myoclonus in the partially restrained rat. In the experiments reported here, partially restrained rats were administered repeated alternate day or weekly low, fixed doses of clozapine (1 mg/kg). This dose initially caused no behavioral change. Following the third and subsequent administrations, the same dose elicited an increasing number of myoclonic seizure-like jerks reaching 140/h following the 15th injection in rats receiving the same low dose of clozapine on alternate days and 160/h following the 9th injection in animals that received the same dose once weekly. These effects are consistent with kindling, i.e. a progressive increase of brain excitability following repeated administration of a fixed subconvulsive dose of an excitatory agent. Clozapine kindled animals exhibited a significantly different pattern of early gene expression in ventral tegmental area, origin of the mesolimbic-mesocortical dopamine system and in the anterior thalamic nuclei, compared with saline treated controls subjected to exactly the same recording conditions. The evidence of central nervous system excitation with clozapine may be important to the unique therapeutic effect of this atypical antipsychotic in the treatment of symptoms, especially the deficit symptoms, of schizophrenia.

Topics: Animals; Behavior, Animal; Brain; Clozapine; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Epilepsy; Gene Expression; Genes, Immediate-Early; Humans; Kindling, Neurologic; Male; Rats; Rats, Sprague-Dawley; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Anticonvulsants; Chronic Disease; Clozapine; Drug Interactions; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Humans; Male; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Anticonvulsants; Clozapine; Drug Interactions; Electroencephalography; Epilepsy; Humans; Schizophrenia

Clozapine is a novel antipsychotic agent effective in treating refractory schizophrenia. Clozapine produces fewer extrapyramidal effects than other neuroleptics, although agranulocytosis and seizures are significant adverse effects. To characterize the spectrum of clozapine-related electroencephalographic abnormalities, we identified 10 patients who had electroencephalograms (EEGs) performed before and during clozapine treatment. These 10 patients represented a subset of individuals participating in an investigational trial. During clozapine treatment, five developed myoclonus and one experienced a generalized tonic-clonic seizure. Records were retrospectively reviewed by an electroencephalographer blinded to the patient's history and medications. All patients had normal EEGs before clozapine treatment. While receiving clozapine (250-900 mg daily), all patients developed background slowing in the theta and often delta ranges. Additionally, 7 patients exhibited bilateral spike, polyspike and slow wave discharges, one with a photoparoxysmal response. Follow-up EEGs performed in 4 of these 7 patients after a decrease in clozapine dosage and/or addition in valproic acid showed diminished epileptiform activity.

Topics: Adult; Clozapine; Electroencephalography; Epilepsy; Female; Humans; Male; Myoclonus; Retrospective Studies; Schizophrenia

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: Clozapine; Electroencephalography; Epilepsy; Evoked Potentials; Female; Humans; Middle Aged; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Carbamazepine; Clozapine; Drug Interactions; Drug Therapy, Combination; Epilepsy; Humans; Male; Microsomes, Liver; Schizophrenia

Topics: Adult; Clozapine; Epilepsy; Female; Humans; Leukocyte Count; Male; Retrospective Studies; Salivation; Schizophrenia

Topics: Adult; Clozapine; Electroencephalography; Epilepsy; Evoked Potentials; Humans; Male; Neurocognitive Disorders; Psychotic Disorders

The main side effects of 7921 hospitalized patients taken clozapine from July in 1980 to October in 1988 were investigated. In these cases, there were 600 patients with the main side effects caused by clozapine. They included 312 patients with leukocytosis (52.0%), 114 patients with leukopenia (19.0%), (included 16 patients with agranulocytosis), 53 patients with EEG abnormal (8.9%), 35 patients with fever (5.9%), 32 patients with EKG abnormal (5.3%), 14 patients with rash (2.3%), 12 patients with epileptic seizure (2.0%), 11 patients with posture hypotension (1.8%), 8 patients with paralytic intestinal obstruction (1.3%), 6 patients with SGPT raised (1.0%) and 3 patients with conscious disturbances (0.5%). The causes and treatments of the main side effects mentioned above were discussed.

Topics: Adolescent; Adult; Aged; Child; Clozapine; Electroencephalography; Epilepsy; Female; Humans; Intestinal Pseudo-Obstruction; Leukocytosis; Leukopenia; Male; Middle Aged

Topics: Clozapine; Delta Rhythm; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Humans; Schizophrenia; Seizures; Theta Rhythm

Using the parameters of the special synchronization of cortical biopotentials, the authors studied changes in the function of the cerebral cortex in patients with the generalized form of epilepsy with a further progression of the disease and under the effect of the typical neuroleptic haloperidol and atypical neuroleptic clozapine. These drugs have been found to act differently on the epileptic process and on the effects of the hyperventilation test, which appears to be due to their differing ability to block receptors of the nigrostriatal and mesolimbic dopaminergic systems. The data have shown that haloperidol increases the risk of the development of epileptic attacks while clozapine reduces epileptic manifestations.

Topics: Anticonvulsants; Cerebral Cortex; Clozapine; Cortical Synchronization; Dibenzazepines; Epilepsy; Haloperidol; Humans; Respiration

Between January 1974 and June 1975 52 in-patients with mania were treated with Clozapine. In one half of the patients this was the only drug throughout. It was so far thought to be indicated mainly for schizophrenics. Its main action mostly was immediate (partly on the first or second day) and was characterised by initial sedation and subsequent improvement of increased motivation and flight of ideas. On the basis of our present experience Clozapine appears to be superior in the treatment of mania in its main and side effects. Patients prefer it often because of the absence of extrapyramidal side-effects. The in-patient treatment was on average much shorter with Clozapine than with other drugs. These first observations demand further tests for this specific indication.

Topics: Adolescent; Adult; Bipolar Disorder; Clozapine; Dibenzazepines; Electroencephalography; Epilepsy; Female; Humans; Length of Stay; Time Factors

Fifty-two mental hospital cases of acute and chronic schizophrenia and gross behaviour disorders were investigated and observed for 6-12 months during treatment with clozapine. Three-quarters of the acute cases recovered with full occupation capacity. Two-thirds of the chronic cases improved markedly. Antisocial behaviour was controlled in 12 out of the 13 behaviour-disordered group. The improvement in initiative and social capacity was striking and appeared to be due to improved awareness of the environment and the acquisition and handling of useful knowledge. The response to clozapine appears to be specific and relapses occurred when maintenance medication was stopped. It is of value in treating temper states in epilepsy and has the advantage of not causing extrapyramidal symptoms and side-effects are slight after the first week. Maximum improvement may not be reached before 8 weeks. Thereafter the maintenance dose can be small and fluctuations in the illness do not seem to occur. The dosage, side-effects and precautions are discussed. A rating system to display the effect of clozapine on individual parameters as well as on the over-all state was devised for this study.

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Clozapine; Dibenzazepines; Epilepsy; Female; Humans; Male; Middle Aged; Recurrence; Schizophrenia; Social Behavior Disorders