Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clozapine, an atypical antipsychotic drug, is widely used in refractory schizophrenia. At New Hampshire Hospital, 7 of the first 35 patients treated (20%) had convulsions. Patterns were tonic-clonic (5), complex partial (2), and myoclonic (3). Seizures were dose-related and may be anticholinergic in etiology. EEG changes are frequent with clozapine, particularly as dosage is increased. Twenty-six of 35 patients (74%) had EEG abnormalities at some time during clozapine treatment. EEG is a sensitive means of detecting clinical toxicity. When EEG abnormalities (slowing, dysrhythmia, or paroxysmal discharges) are detected, immediately lowering the dose by at least 25-50 mg per day and adjusting weekly until EEG returns to baseline can reduce the incidence of seizures.
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PMID:Clozapine-induced seizures and EEG changes. 795 Mar 47

Lilliputian hallucinations have been described in patients with delirium, schizophrenia, seizure disorders, visual disturbances, and brain tumors. The authors report two cases of patients with lilliputian hallucinations, one with AIDS-dementia complex and the other with dementia following head trauma. This is the first time that lilliputian hallucinations have been described in association with such medical conditions.
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PMID:Lilliputian hallucinations and medical illness. 803 94

A schizophrenic patient suffered from an episode of unexpected grand mal seizure following an enflurane unaesthetic for biopsy of an orbital lesion. The seizure was brief and subsided spontaneously. An assessment of the anaesthetic technique and a thorough neurological examination which included a CT scan and an EEG, failed to demonstrate any obvious cause for the convulsion. The patient was not an epileptic and was receiving neuroleptic drugs preoperatively for the treatment of schizophrenia. A synergistic role of enflurane and neuroleptic drugs is producing seizure activity in this patients is a distinct possibility. Caution is therefore recommended when administering enflurane to patients on neuroleptic drugs.
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PMID:Convulsions after enflurane in a schizophrenic patient receiving neuroleptics. 805 10

In order to assess the safety and some efficacy aspects of clozapine under UK conditions, 54 in-patients with severe treatment-resistant schizophrenic disorders were evaluated using several scales before and during treatment. Of the 54 evaluated, 26 completed the 26-week study. Of these patients, 20 showed improvement in psychopathology, often to a marked degree, involving both positive and negative symptoms. Some oral-facial extrapyramidal side-effects decreased as well. Two patients developed neutropenia, but recovered on discontinuation of clozapine. The most frequent adverse event was hypersalivation, and five patients suffered from seizures. It is concluded that clozapine is worth considering for the treatment of severe treatment-resistant patients in the UK.
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PMID:The safety and efficacy of clozapine in severe treatment-resistant schizophrenic patients in the UK. Clozapine Study Group. 807 4

We investigated a possible relation between aura phenomena and psychopathology in patients with seizure disorders. Twenty-one patients with a variety of seizure types (90% with generalized seizures, 72% with complex partial seizures, CPS) were studied. Aura phenomena were evaluated with the Silberman-Post Psychosensory Phenomena Scale; psychopathology was assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), the Minnesota Multiple Personality Inventory (MMPI), and the Washington Psychosocial Seizure Inventory (WPSI). Psychosensory symptoms occurring in the absence of frank seizures, but not those occurring with seizures, were related to increased psychopathology (primarily mood and anxiety related) and greater time in psychiatric treatment. Psychosensory symptoms may reflect ongoing neurophysiologic dysfunction related to epilepsy and may therefore be a useful subject for further study.
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PMID:Aura phenomena and psychopathology: a pilot investigation. 808 22

Prior studies have incompletely established a relationship between epilepsy and schizophrenia, primarily because of methodological difficulties. We undertook a two-part retrospective investigation of neurology clinic patients with epilepsy and schizophrenia. Part I: Interictal schizophrenic disorders occurred in 149 (9.25%) of 1,611 epileptic outpatients, compared with only 23 (1.06%) of 2,167 migraine outpatients. Part II: Among age- and sex-matched groups, we compared 62 epilepsy-with-schizophrenia patients with 62 epilepsy patients on six seizure variables, and we compared them with 62 schizophrenia patients on 10 psychosis variables. The epilepsy-with-schizophrenia group had a later epilepsy age of onset with more complex partial seizures, more patients with auras, and fewer patients with generalized epilepsy. Except for increased suicidal behavior, epileptic patients did not differ from controls on psychosis variables; however, psychotic symptoms often emerged with increased seizure activity. Together these results support a distinct association of schizophrenic disorders with epilepsy, particularly with seizures emanating from the temporal limbic system.
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PMID:Schizophrenia in epilepsy: seizure and psychosis variables. 818 35

Interictal violence among epileptic patients could result from factors other than epileptiform activity. We characterized 44 patients who presented for psychiatric evaluation because of violent behavior. Most violent acts consisted of verbal or minor physical aggression. Twenty (45%) of these patients met criteria for a schizophrenic disorder, and one committed murder during a paranoid schizophrenic relapse. In addition to schizophrenia, the violence patients had significantly more mental retardation when compared with 88 age- and sex-matched epileptic patients without prior violent behavior. However, violent and nonviolent patients did not differ on seizure variables such as type and frequency of seizures, auras, electroencephalographic changes, epilepsy age of onset, or anticonvulsant therapy. These findings suggest that interictal violence is associated more with psychopathology and mental retardation than with epileptiform activity or other seizure variables.
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PMID:Interictal violence in epilepsy. Relationship to behavior and seizure variables. 824 25

This study examines the relationship between epilepsy and psychosis. It compares clinical, EEG, and neuropathologic data from a group of subjects who had both epilepsy and psychosis with similar information from another group of patients who had epilepsy but no evidence of psychotic illness. We examined, blind to clinical diagnosis, gross and microscopic material from whole-brain specimens from 10 patients diagnosed with epilepsy plus schizophrenia-like psychosis, nine subjects diagnosed with epilepsy plus "epileptic psychosis," and 36 individuals with epilepsy (21 from an epileptic colony and 15 from the community at large) who had no history of psychosis (n = 10 + 9 + 21 + 15 = 55). We abstracted case histories without knowledge of pathologic findings. Epileptic colony patients had an earlier age at onset of seizures, while epileptic colony and epileptic psychosis patients had more frequent seizures. Epileptic individuals in the community died at a younger age than did epileptic patients in long-stay hospital care. Psychotic epileptic patients had larger cerebral ventricles, excess periventricular gliosis, and more focal cerebral damage compared with epileptic patients who had no psychotic illness. Epileptic patients with schizophrenia-like psychosis were distinguished from all other groups by a significant excess of pinpoint perivascular white-matter softenings. We found that mesial temporal sclerosis and temporal lobe epilepsy occurred with equal frequency in the psychotic and nonpsychotic groups; generalized seizures occurred more frequently in the psychotic epileptics and the epileptic colony epileptics than in the community epileptic controls.
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PMID:Epilepsy, psychosis, and schizophrenia: clinical and neuropathologic correlations. 829 87

Antipsychotic agents, most often used for treatment of schizophrenia, are sometimes prescribed for the agitated patient with an organic brain disorder. We report the case of a brain-injured patient who was prescribed chlorpromazine for agitation and who developed a delusional state while taking this antipsychotic agent. The emergence of this delusional state coincided with the exacerbation of certain cognitive deficits. Possible mechanisms for this phenomenon are discussed. Caution is advised when prescribing neuroleptics for patients with traumatic brain injury, especially those agents with significant cognitive side-effects or with a significant potential to precipitate seizures.
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PMID:Chlorpromazine-induced psychosis after brain injury. 842 19

The introduction of clozapine has given clinicians a unique agent for treating patients with schizophrenia that is refractory to other neuroleptics. Despite its efficacy, the drug continues to be prescribed with trepidation due to the incidence of agranulocytosis. This article reviews the pharmacokinetic and pharmacological properties of clozapine and the clinical implications for monitoring plasma concentrations. Various assays have been developed for clozapine that include gas-liquid chromatography, radioimmunoassay and high performance liquid chromatography. Only a few studies have examined the pharmacokinetics of clozapine in patients with schizophrenia. These studies have revealed a wide interpatient variability in pharmacokinetic parameters that include: time to reach peak plasma concentrations 1.1 to 3.6h; elimination half-life 9.1 to 17.4h; clearance 8.7 to 53.3 L/h; and a volume of distribution of 1.6 to 7.3 L/kg. Clozapine is metabolised via the hepatic microsomal enzyme system into 2 principle metabolites: demethyl-clozapine and clozapine N-oxide. Urine samples have reported the ratio of clozapine:demethyl:N-oxide to be 1:1:2. The clozapine N-oxide binding affinity with 3H-haloperidol was 4 times lower than clozapine and its conversion back to clozapine is hypothesised. Although the exact pharmacological mechanism of action of clozapine is not fully understood, the drug does possess significant binding affinity for different dopamine receptors, with recent evidence supporting binding to the D4 receptor subtype. Clozapine transiently increases serum prolactin levels with minimal changes in homovanillic acid plasma levels. Limited studies investigating the relationship between clinical response and plasma clozapine concentrations have investigated the range between 100 and 800 micrograms/L. In the treatment of patients with refractory schizophrenia, a minimum concentration of 350 micrograms/L was suggested as needed. The occurrence of agranulocytosis could have a genetic basis and patients should be rigorously monitored during treatment. The incidence of tardive dyskinesia and extrapyramidal side effects is minimal. Clozapine can lower the seizure threshold in a dose- and time-dependent manner. Careful patient selection and monitoring are required when clozapine therapy is used in patients with schizophrenia.
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PMID:Pharmacokinetics and pharmacodynamics of clozapine. 845 23


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