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)

Zotepine was administered to 45 patients suffering from therapy-resistant psychoses hospitalized in eight psychiatric institutes (University Hospital Okayama and affiliated institutions). The psychoses of these patients were characterised by positive symptoms--predominantly hallucinations and delusions--and could not be influenced by a large variety of conventional antipsychotics, such as haloperidol. Previous medications were discontinued or administered together with zotepine. To assess changes in the pattern of symptoms, the Brief Psychiatric Rating Scale (BPRS) was employed over a period of up to 12 weeks at 2-week intervals. Ten patients dropped out of the study because of undesirable effects or for other reasons. 35 patients completed the 12-week study according to schedule. There was a relation between general improvement and certain patient characteristics. Zotepine proved to be effective especially in the catatonic type of schizophrenia, in chronic schizophrenias with acute exacerbation (DSM-III) and in relatively young patients in whom the disease had existed for a short time only. In the 26 patients who were markedly, moderately or slightly improved, BPRS score had dropped significantly after only two weeks of treatment. This points to a rapid onset of the therapeutic action of zotepine.
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PMID:[Effectiveness of zotepine in therapy-refractory psychoses. An open, multicenter study in eight psychiatric clinics]. 168 39

Neuroleptic classifications try to take account of both biological effects (interaction with different neurotransmitters, selectivity of action on dopaminergic structures or dopaminergic subclasses of receptors) and clinical effects (sedative properties, efficacy on positive or negative symptomatology of schizophrenia, antimanic effect). Zotepine blocks mainly dopaminergic, 5-HT 2 and alpha 1 receptors. It should therefore be expected to have sedative properties in humans and to be effective against mania and the positive symptoms of schizophrenia.
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PMID:Classification of neuroleptics--zotepine. 288 76

Zotepine, a new neuroleptic, was administered to 23 hospitalized patients with schizophrenia at doses of 75 to 600 mg/d for 21 to 42 days. Based upon analysis of conventional rating scales we observed a significant improvement (P less than 0.001) during week 1, which compound throughout the study period. After 21 days we identified 17 responders and 6 nonresponders, 2 of whom dropped out of the study because of a tonic-clonic seizure in one case and withdrawal of consent to further participation in the second case. During further treatment the improvement remaind stable in the responder group, while 1 nonresponder improved after 3 weeks of treatment. In 9 patients extrapyramidal symptoms were observed (6 parkinsonism, 2 early dyskinesia, 1 parkinsonism and early dyskinesia), which required sporadic (n = 3) or continuous (n = 2) treatment with biperiden in 5 cases. This low incidence of extrapyramidal symptoms necessitating coadministration of anticholinergic drugs suggests that the risk of inducing parkinsonism and dyskinesias during zotepine treatment is low. Comparison of cortisol, growth hormone and prolactin release in normal controls challenged with 25 mg zotepine showed that only prolactin secretion is increased, while secretion of cortisol and growth hormone remains unaffected. The clinical effects observed in the present study show that zotepine has potential value in the treatment of schizophrenia. The findings warrant further study in controlled trials.
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PMID:Clinical and neuroendocrine effects of zotepine--a new neuroleptic drug. 288 78

We reported the results of a survey of patients who suffered from schizophrenia with predominate hallucinatory and delusional states, and who had been unresponsive to a variety of antipsychotics like haloperidol but responded more favorably to zotepine. In 10 of the 22 zotepine-responsive patients in this study, there was marked improvement with zotepine. Considering the results from previous drug treatment, the phenothiazines (especially levomepromazine) surpassed the butyrophenones in efficacy, suggesting that zotepine might resemble levomepromazine clinically. After administration of zotepine, cenesthesic hallucination, behavior caused by hallucination, egorrhoe, affective symptoms, and catatonic symptoms were markedly improved. However, insight into disease and negative symptoms were minimally improved after administration of zotepine. Zotepine was effective in the refractory psychoses due to its potent action on the delusional dynamics, in spite of producing little marked improvement in such main symptoms as hallucination and delusion. The authors speculate that zotepine's potent activity at serotonin-1 receptors may lead to a beneficial effect in refractory psychoses, just as in the case of its antimanic effect.
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PMID:Effectivity of zotepine in refractory psychoses: possible relationship between zotepine and non-dopamine psychosis. 288 82

Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.
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PMID:Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study. 913 23

A man with schizophrenia received regular haloperidol ester therapy, but his psychotic symptoms were not mitigated. A combination of zotepine and haloperidol was then used to relieve the psychotic symptoms. However, the patient developed spontaneous ejaculations, which occurred many times a day while undergoing haloperidol and zotepine therapy. These events were not preceded by sexual stimulation and were not associated with a pleasurable sensation. The discomfort disappeared after discontinuing zotepine. Zotepine-induced spontaneous ejaculation was, therefore, diagnosed. There are few reports of drug-related spontaneous ejaculation. Clinicians need to recognize the possibility of zotepine-related spontaneous ejaculation because sexual side effects have an impact on medical adherence.
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PMID:Zotepine-induced spontaneous ejaculation. 1900 May 55

Zotepine is a second generation antipsychotic drug, a substituted dibenzothiepine tricyclic molecule, with effects on dopamine, serotonin and noradrenaline receptors. This article reviews the relevant research studies on the drug based on a search of numerous medical databases for research and literature concerning zotepine and adverse reactions reported to the UK Medicines and Healthcare Products Regulatory Agency. There are double-blind trials demonstrating zotepine as an efficacious antipsychotic with a safe side effect profile that compares favourably with other atypical antipsychotics with regard to metabolic effects and movement disorders. There are some open label studies suggesting usefulness in treatment resistant schizophrenia, but larger, double-blind studies are required.
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PMID:Zotepine: a clinical review. 1919 77

Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many adverse effects are noted. Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis, although empirical studies are very limited. Zotepine, an atypical antipsychotic with a pharmacologic profile similar to clozapine, was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan. This 12-week study is the first prospective, randomized, and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine. Fifty-nine patients with schizophrenia, who had taken clozapine for at least 6 months with a Clinical Global Impression-Severity score of at least 3, were randomly allocated to the zotepine and the clozapine groups. At the end of the study, 52 patients (88%) had completed the trial. The 7 withdrawal cases were all in the zotepine group. The final mean (SD) dose of zotepine and clozapine was 397.1 (75.7) versus 377.1 (62.5) mg/d, respectively. Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [mean (SD), 4.7 (8.7) vs -1.3 (6.3); P = 0.005], more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [mean (SD), 1.74 (3.9) vs -0.2 (2.8); P = 0.039], more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [mean (SD), 1.29 (3.5) vs 0.17 (2.1); P = 0.022], an increased use of propranolol (37.1% vs 0%, P < 0.0001) and anticholinergics (25.7% vs 0%, P = 0.008), and an increased level of prolactin (29.6 vs -3.8 ng/ mL, P < 0.0005), compared with the clozapine group. The results suggested that switching from clozapine to zotepine treatment should be done with caution.
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PMID:Switching from clozapine to zotepine in patients with schizophrenia: a 12-week prospective, randomized, rater blind, and parallel study. 2342 95

Acutely ill, schizophrenic patients frequently require management of agitation. This study was conducted to compare the efficacy of oral zotepine and risperidone in hospitalized, acutely ill schizophrenic patients with symptoms of agitation.This was a 6-week, multicenter, randomized, open-label, parallel-group, flexible dosing study. Thirty-nine patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who met the criteria of a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 60 points, PANSS-excitement component (EC) score of greater than or equal to 14 points, and at least 1 PANSS-EC score of greater than or equal to 4 were randomly assigned to either the zotepine or risperidone group. The primary outcome was a comparison of the change in the PANSS-EC total score from baseline to the end of the study between groups.There was no significant between-group difference in dropout rates (zotepine, 15.8% [3/19]; risperidone, 20.0% [4/20]). The mean (SD) daily dose of zotepine from baseline to study end point ranged from 127.6 (62.3) to 236.8 (74.2) mg/d; the corresponding values for risperidone ranged from 3.3 (1.6) to 4.8 (1.7) mg/d. There were no statistically significant differences in patient characteristics, PANSS total score, and PANSS-EC total score between the zotepine and risperidone groups at baseline. Both groups showed significant reductions in the PANSS-EC total scores (zotepine, -10.1 [4.7], P < 0.001; risperidone, -8.0 [5.3], P < 0.001) and PANSS total scores (zotepine, -34.7 [15.8], P < 0.001; risperidone, -28.6 [14.3], P < 0.001). However, there were no significant differences in PANSS-EC total score (P = 0.265) and PANSS total score (P = 0.125) changes from baseline to study end point between the 2 treatment groups. Serum uric acid and prolactin decreased more in the zotepine group than the risperidone group (P < 0.001 and P = 0.018, respectively).Zotepine seemed to be as effective as risperidone in treating hospitalized, acutely ill, schizophrenic patients with agitation, and had the advantages of lowering hyperuricemia and hyperprolactinemia. Double-blind, fixed dose studies with a larger sample size of acutely ill, schizophrenic patients with agitation are needed to confirm the study results.
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PMID:An open-label, randomized, controlled trial of zotepine and risperidone for acutely ill, hospitalized, schizophrenic patients with symptoms of agitation. 2410 Jul 85

Atypical antipsychotic drugs are recommended for the first line treatment of all patients with schizophrenia. This is because it has been demonstrated that atypical antipsychotic drugs are more effective across a broader range of symptoms of schizophrenia than typical antipsychotic drugs and because they are dramatically less likely to cause the extrapyramidal and endocrine side effects that greatly impair quality of life for patients and reduce their willingness to adhere to maintenance treatment. Atypical antipsychotic drugs are not perfect but they are the most effective and the safest treatment for schizophrenia presently available. The atypical antipsychotic drugs currently marketed in Ireland for the first line treatment of schizophrenia include amisulpride, olanzapine, quetiapine, risperidone and ziprasidone. These agents differ somewhat in chemical class, indications, daily dose range, need for titration, daily dosing regimen and available formulations (see Table 1). Clozapine is marketed for patients unresponsive to, or intolerant of, other antipsychotic drugs and must thus be regarded as a second line treatment for schizophrenia. Zotepine is not yet available in Ireland while the marketing of sertindole has been suspended following reports of arrhythmias and sudden cardiac deaths.
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PMID:Antipsychotic drugs: atypical advantages and typical disadvantages. 3044 Feb 29


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