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)

Compared to young adults, elderly individuals with schizophrenia may have a six-fold increase in the prevalence of tardive dyskinesia. The atypical antipsychotic, olanzapine, may offer particular benefit for this population. This is a prospective, open-label trial of olanzapine therapy in elderly schizophrenic patients. Individuals aged 65 years or older with DSM-IV schizophrenia and a history of neuroleptic responsiveness were given olanzapine as an add-on therapy to their existing medication regimen. Other antipsychotic medication was gradually discontinued. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS). Abnormal movements were assessed with the Simpson-Angus Neurological Rating Scale (SA), the Barnes Akathisia Scale (BA), and the Abnormal Involuntary Movement Scale (AIMS). Cognitive status was assessed with the Mini-Mental State Evaluation (MMSE). Twenty-seven individuals received a mean dosage of 8.4 (+/- 4.2) mg/day. Mean age of the group was 70.6 (+/- 4.1) with a range of 65 to 80 years. Patients had a mean of 1.6 (+/- 1.4) significant comorbid medical illnesses. Change in BPRS scores were not significant for the group as a whole, whereas SA score change was substantial, with a pre-treatment mean of 13.7 (+/- 10.3), compared with a mean of 4.8 (+/- 4.1) for those treated with olanzapine (p < .0002). Changes in AIMS and BA score were also significant on olanzapine therapy. MMSE score change was not statistically significant. Comorbid medical illnesses were not adversely affected. Olanzapine is an effective antipsychotic medication in older adults with schizophrenia, and is associated with significant improvement in extrapyramidal side effects. Implications for effect on cognitive status should be explored in larger, long-term trials.
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PMID:Olanzapine therapy in elderly patients with schizophrenia. 1051 58

The acute effects of systemic administration of the antipsychotic drug, zotepine, on extracellular dopamine (DA) in the frontal cortex of freely-moving rats were studied using in vivo microdialysis and compared with the actions of clozapine, olanzapine and haloperidol. Treatment with zotepine (1.0 mg/kg, i.p.) resulted in a prolonged elevation of cortical DA levels for up to 180 min post-drug. A maximal rise of +333% was observed at 120 min post-zotepine treatment. Clozapine (10.0 mg/kg, i.p.) also evoked a rise in extracellular DA which was similar in duration (200 min) to that resulting from treatment with zotepine. A maximal rise of +223% was observed at 100 min post-clozapine treatment. Olanzapine (1.0 mg/kg, i.p.) resulted in an immediate increase in DA levels which was maximal 40 min post-treatment (+280%) with levels returning to pre-injection values by 100 min after dosing. In contrast, haloperidol (0.1 mg/kg, i.p.) had no measurable influence on cortical DA levels. Local perfusion with the NA uptake inhibitor, nisoxetine (10 microM), resulted in an increase in cortical DA levels which was maximal at 100 min post-onset of perfusion (+257% above baseline). Administration of zotepine (1.0 mg/kg, i.p.) during nisoxetine perfusion elevated DA levels to a maximum of +301% above baseline, 60 min post-zotepine. These results show that acute administration of each of three drugs with an atypical antipsychotic profile causes an elevation of cortical DA in freely-moving rats at doses relevant to those derived from animal models which predict antipsychotic activity. As a dysfunction in cortical DA is thought to be involved in both the negative symptoms of schizophrenia and cognitive deficits in schizophrenic patients, it is possible that zotepine's ability to elevate cortical DA levels may underlie its effectiveness in successfully treating these components of schizophrenia. Furthermore, the ability of zotepine to elevate cortical DA is more likely to derive from its inhibition of the NA transporter rather than DA receptor blockade in this region.
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PMID:A comparison of the acute effects of zotepine and other antipsychotics on rat cortical dopamine release, in vivo. 1068 75

The recent introduction of several antipsychotic medications has raised expectations for better pharmacological management of schizophrenia. Although conventional and new neuroleptics (Risperidone, Olanzapine, Seroquel and soon to be released Ziprasidone) are generally comparable in terms of efficacy; the new antipsychotic medications possess a better side-effects profile and are overall, much better tolerated. The reintroduction of Clozapine as an effective antipsychotic for treatment refractoriness has also improved management for a segment of the schizophrenic population who failed to respond adequately to other antipsychotic medications. Such increased benefits from new antipsychotic medications come with a higher acquisition cost that has somewhat strained the historically low psychiatric budgets. The question then was whether the expected benefits of the new antipsychotics can offset the high cost of these medications in the long-term. In that context, quality of life assessment has provided a tool for the comparative analysis of new and conventional antipsychotic medications, particularly regarding their impact on functional status and satisfaction. In a recently concluded study, we demonstrated that the new antipsychotic medications are subjectively much better tolerated and have a more favourable impact on quality of life compared with conventional neuroleptics. The ultimate question is whether such favourable benefits can translate in the future into better compliance with medications and improved long-term outcomes.
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PMID:Quality of life and new antipsychotics in schizophrenia. Are patients better off? 1068 10

Olanzapine (Zyprexa), a neuroleptic, has obtained marketing authorization for treatment of schizophrenia. The clinical file is satisfactory, but in the absence of relevant trials, it has not yet been demonstrated that olanzapine has a specific activity on the positive or negative symptoms of schizophrenia. The global efficacy of olanzapine was not substantially different from that of haloperidol in two of the three comparative trials published to date. The only relevant comparative trial fails to demonstrate the superiority of olanzapine over risperidone. Olanzapine has fewer adverse neurologic effects than haloperidol, but there is no evidence that it differs from other recent neuroleptics in this respect. Olanzapine can have anticholinergic adverse effects and frequently causes weight gain. Active surveillance is required because subclinical cases of elevated transaminase levels, increased blood pressure, and QT prolongation were observed in clinical trials (2500 patients treated).
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PMID:Olanzapine. Keep an eye on this neuroleptic. 1115 1

Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target dose of 10 mg/day is likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results.
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PMID:Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia. 1077 Apr 61

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.
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PMID:Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study. 1079 21

Olanzapine, a serotonin-dopamine receptor antagonist, is one of the novel atypical antipsychotics that is effective against the positive and negative symptoms of schizophrenia with significantly fewer treatment-emergent extrapyramidal symptoms and less akathisia associated with traditional antipsychotics. Compared with traditional agents, olanzapine shows only a few adverse events such as dry mouth, sedation, and increase in appetite. Compared with risperidone, olanzapine causes greater increases in weight gain and body mass index but less hyperprolactinemia. Transient, non-dose-dependent, asymptomatic elevations in liver enzymes have also been noted in olanzapine-treated patients. Because of the comparative efficacy and improved side effect profiles of the atypical antipsychotics, consideration should be given to using the newer agents as preferred treatment for schizophrenia and related psychoses.
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PMID:Adverse events related to olanzapine. 1081 Dec 40

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.
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PMID:Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. 1083 Oct 17

Clozapine is known to induce epileptic seizures and changes in EEG-patterns, including slowing and the appearance of epileptiform activity. Olanzapine, a new antipsychotic drug, shares many pharmacological and clinical properties with clozapine. However, in patients treated with olanzapine, no case of seizure induction has been reported so far, and the EEG has not been studied systematically. We examined the EEGs of patients with schizophrenia treated with either olanzapine (N = 9) or clozapine (N = 9) prior to medication and 3 to 7 weeks afterwards. Clozapine induced significant EEG slowing present in 78% of the patients, and definite epileptiform activity appeared in 33%. Olanzapine also induced significant EEG slowing, but less frequently (in 44% of the patients) and less pronounced than clozapine. Olanzapine had no significant effect an epileptiform activity, but in one patient, an isolated sharp/slow-wave complex was observed. These preliminary data suggest that olanzapine induces EEG slowing to a lower extent than clozapine. Olanzapine's possible effect an the seizure threshold deserves further attention.
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PMID:A comparison of the effects of clozapine and olanzapine on the EEG in patients with schizophrenia. 1085 62

Olanzapine is an atypical antipsychotic with potent antimuscarinic properties in vitro (K(i) = 2-25 nM). We studied in vivo muscarinic receptor occupancy by olanzapine at both low dose (5 mg/dy) and high dose (20 mg/dy) in several regions of cortex, striatum, thalamus and pons by analyzing [I-123]IQNB SPECT images of seven schizophrenia patients. Both low-dose and high-dose olanzapine studies revealed significantly lower [I-123]IQNB binding than that of drug-free schizophrenia patients (N = 12) in all regions except striatum. [I-123]IQNB binding was significantly lower at high-dose than low-dose in the same regions. Muscarinic occupancy by olanzapine ranged from 13% to 57% at 5 mg/dy and 26% to 79% at 20 mg/dy with an anatomical pattern indicating M(2) subtype selectivity. The [I-123]IQNB data indicate that olanzapine is a potent and subtype-selective muscarinic antagonist in vivo, perhaps explaining its low extrapyramidal side effect profile and low incidence of anticholinergic side effects.
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PMID:In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. 1086 86


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