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)

506 patients with schizophrenia, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria, were included in a long term treatment programme with remoxipride, a selective dopamine (D2)-receptor antagonist. This overview includes pooled data from all patients who have been treated long term with remoxipride in clinical trials, focusing on patients treated for more than 6 months (n = 283). Remoxipride was administered in daily doses of 75 to 600mg. The assessment tools were Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Simpson and Angus scale, Abnormal Involuntary Movements Scale (AIMS) for abnormal involuntary movements, adverse events/symptoms using a 26-item checklist, clinical chemistry, and haematology and cardiovascular investigations. The majority of patients had a long duration of illness (median 11 years). 67% of patients (340/506) withdrew from treatment before 12 months and 44% (223/506) stopped treatment before 6 months. The median BPRS total score decreased during the first 3 months from 23 to 12, and this level of improvement was maintained throughout the 12-month period. Treatment-emergent adverse events reported by more than 5% of the patients were insomnia, tiredness, drowsiness and tremor in the group treated for 6 to 12 months. No symptoms, including checklist extrapyramidal symptoms (EPS), were reported by more than 5% of patients treated for 12 months. Low frequencies of EPS according to the Simpson and Angus scale were seen in patients treated for more than 6 months (n = 147). A small but statistically significant reduction of the mean total AIMS score from baseline to last rating was observed. There were infrequent changes in heart rate, resting diastolic blood pressure and electrocardiogram (ECG). Clinical chemistry and haematology data showed no evidence of clinically significant changes over time during the 12 months of treatment. Among 506 patients, 7 suicides and 7 suicide attempts occurred during the study period. Other serious adverse events were abnormal liver function test (2 cases), gastrointestinal, urinary retention, status epilepticus (psychotic polydipsia), granulocytopenia (1 each) and myocardial infarction (5 cases). Remoxipride is of potential value as a drug which is both effective and well tolerated in the long term management of patients with schizophrenia.
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PMID:Tolerability of remoxipride in the long term treatment of schizophrenia. An overview. 832 49

ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.
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PMID:ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group. 869 Aug 31

This open prospective study was undertaken to determine the efficacy and safety of a fixed dose (6 mg) of risperidone in psychotic patients. Hospital in-patients who fulfilled DSM-111-R criteria for schizophrenia, schizoaffective and bipolar disorders were eligible for entry into the study (n = 15). Patients who were on other antipsychotics had a washout period of 1 week before they were started on the drug. A fixed dose of risperidone was administered (6 mg). The Brief Psychiatric Rating Scale (BPRS), Negative Symptom Rating Scale (NSRS) and Abnormal Involuntary Movement Scale were used to measure psychopathology and extrapyramidal side-effects. Five patients dropped out of the study. Two patients became very agitated and potentially aggressive, one patient became very restless and did not respond to benzodiazepines, and one dropped out because of restlessness that did not respond to clonazepam. Of the 10 patients who completed the study, 50 per cent reduction on BPRS and NSRS was achieved by five and six patients respectively. There was a marginally significant trend towards a greater reduction in the magnitude of negative symptoms. Four patients required treatment with anticholinergic drugs. Risperidone was effective in resistent psychotic patients, but agitated and impulsive psychotic patients with positive symptoms may not be best candidates for treatment with risperidone. On average, negative symptoms respond better than positive symptoms.
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PMID:Efficacy and safety of risperidone in psychotic patients: an open study. 872 91

Descriptions of schizophrenia dating to the beginning of this century include mention of abnormal movements which are similar to tardive dyskinesia (TD), currently thought to be sequelae of neuroleptic medication. In order to examine the extent to which such movements might appear in the normal course of schizophrenia, we examined a sample of 22 never-medicated DSM-III-R schizophrenics who presented for treatment at a psychiatric center in Casablanca, Morocco. Duration of illness in this sample ranged from 1 to 10 years. Patients were assessed for choreoathetoid movements using the Abnormal Involuntary Movement Scale (AIMS). Videotaped and live examinations were rated by the investigators. Three patients (14%) met research diagnostic criteria for probable SD. Mild movements in one body part (AIMS = 2) were seen in an additional five (23%) patients. The movements were characteristic of TD, although their somatic distribution differed from previous studies. Total AIMS score increased with age and duration of illness (r = 0.64, P < 0.01). These findings suggest that choreoathetoid movements may appear spontaneously in patients with schizophrenia.
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PMID:Movements in never-medicated schizophrenics: a preliminary study. 874 45

The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe.
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PMID:Amphetamine and negative symptoms of schizophrenia. 874 46

The aim of this study was to evaluate the clinical response to clozapine of 11 treatment-resistant patients with schizophrenia. Nine male and two female inpatients of a state psychiatric hospital, with at least a 2-year history of unresponsiveness to adequate trials of at least three antipsychotics and from chemically distinct groups, were challenged with clozapine. Clinical assessment involved baseline and repeated post-baseline ratings using the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions Scale (CGI), the Nurses Observation Scale for Inpatient Evaluation (NOSIE-30), and the Abnormal Involuntary Movement Scale (AIMS). Progression to lower categories of care was used as an additional outcome measure. Statistically significant reductions were achieved in global symptomatology, positive psychotic symptoms, and hostility. A statistically significant improvement occurred on the Social Interest factor; however, improvements in the remaining negative symptoms were not statistically significant. Reductions in psychopathology enabled eight patients to progress to lower categories of care with five patients moving to community care. The results indicate that clozapine was effective in treating hospital patients with a very severe form of mental illness.
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PMID:Clinical response to clozapine treatment of 11 chronic patients in a state psychiatric hospital. 938 12

Cocaine use is common among individuals with schizophrenia and schizoaffective illness, with a prevalence ranging from 15-60% of patient samples. It is hypothesized that some schizophrenic cocaine abusers may use cocaine as an attempt to improve anhedonic symptoms or combat neuroleptic side-effects. Flupenthixol (FLX) has the distinct advantage of being both a neuroleptic medication and a potential treatment for cocaine abuse. We evaluated the efficacy of FLX in this dually diagnosed population in an open pilot study consisting of a 4-week inpatient phase and a 6-week outpatient phase. Eight individuals were initially cross-tapered off their neuroleptic medication and were given FLX in a dose of 40 mg of the decanoate every 2 weeks. Psychiatric symptomatology was assessed weekly, using the Positive and Negative Symptom Scale (PANSS) and the Beck Depression Inventory (BDI). Medication side-effects were monitored weekly, using the Simpson Neurological Rating Scale and the Abnormal Involuntary Movement Scale (AIMS). Substantial improvement in psychiatric symptomatology was noted when preadmission scores were compared to scores obtained during the last week of study enrollment. On the PANSS, positive symptom scores and negative symptom scores decreased by 31% and 29%, respectively. Similarly, BDI scores decreased by 57%. Comparing preadmission urine results to those for the last 6 weeks of enrollment in the study showed that cocaine-positive urines decreased by 28%, although most of the patients had a reduction of >75%. Missed clinic visits decreased by 26%. Thus, FLX was well-tolerated by schizophrenic cocaine abusers, suggesting that FLX may be useful for the treatment of this dually diagnosed population.
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PMID:Flupenthixol treatment for cocaine abusers with schizophrenia: a pilot study. 974 39

Dopamine receptor antagonism is a common mechanism underlying the therapeutic efficacy of all classical antipsychotic drugs. It is also thought to underlie the propensity of these agents to induce the movement disorder, tardive dyskinesia (TD), in one fifth of chronically exposed schizophrenia patients. We examined the polymorphic serine to glycine substitution in the first exon of the gene encoding the dopamine D3 receptor (DRD3) inn 53 schizophrenia patients with TD, 63 matched patients with similar antipsychotic exposure but no TD and 117 normal controls. There was a difference in allele frequency that was of borderline significance (P = 0.055), due to an excess of the DRD3gly allele (allele 2) in the schizophrenia patients with TD. The difference in genotype distribution among the groups was highly significant (chi2 = 19.1, d.f. 4, P = 0.0008) due to an excess of the DRD3ser-gly genotype in the schizophrenia patients with TD. The difference between the schizophrenia patients with TD and the controls was highly significant (chi2 = 19.0, d.f. 2, P = 0.00007), even after correction for multiple testing, as was the difference between the combined group of schizophrenia patients and the controls (chi2 = 12.2, d.f. 2, P = 0.002). Comparing the schizophrenia patients with and without TD, genotypes containing the gly allele (DRD3ser-gly and DRD3gly-gly genotypes combined) were significantly associated with dyskinesia (OR = 2.62, 95% CI 1.18-5.59, P = 0.02). DRD3 genotype and age at first antipsychotic treatment contributed significantly to total score on the Abnormal Involuntary Movements Scale (AIMS). The contribution of DRD3 to the variance in AIMS total was 5.2% and the total proportion of the variance accounted for by these two variables together was 11.9%. These results support and extend the report by Steen et al (1997) of an association between DRD3 and TD in schizophrenia patients.
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PMID:Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. 1039 14

We evaluated psychiatric symptoms and neurocognitive functioning among 25 institutionalized and 25 outpatient DSM-IV-diagnosed schizophrenia patients, as well as 25 middle-aged and elderly normal comparison subjects. All subjects were assessed with the Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, modified Simpson-Angus Extrapyramidal Symptom Scale, the Abnormal Involuntary Movement Scale, and the Mattis Dementia Rating Scale (DRS). The two patient groups had similar levels of depressive symptoms, but the institutionalized patients had more severe positive and negative symptoms and were on higher doses of neuroleptic medication. The institutionalized patients had significantly more cognitive impairment on the DRS than outpatients and normal comparison subjects, particularly on the subscales of initiation/perseveration, conceptualization, and memory. Results are discussed in terms of the possible neuropathology associated with cognitive impairment in chronic schizophrenia.
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PMID:Cognitive deficits and psychopathology in institutionalized versus community-dwelling elderly schizophrenia patients. 1044 49

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


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