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)

This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment.
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PMID:Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia. 1606 94

Negative and cognitive symptoms of schizophrenia are associated with a hypodopaminergic state in the frontal cortex and do not respond to neuroleptics equally well as positive symptoms. Therefore pharmacological strategies, which increase dopamine metabolism in the mesocortical pathways, may prove beneficial to ameliorate these symptoms. We report on a case of a patient with paranoid schizophrenia, who still presented negative and depressive symptoms during treatment with amisulpride for more than 6 weeks. We prescribed pergolide (a mixed D1/D2 agonist) as adjuvant therapy to treat these symptoms. The patient showed an improvement of global psychopathology, decrease of negative and depressive symptoms, while no changes in positive symptoms nor EPS were present. For this patient, the adjuvant therapy of pergolide to amisulpride constituted a valid pharmacological approach to treat negative and depressive symptoms of schizophrenia, without increasing positive symptoms.
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PMID:Pergolide as adjuvant therapy to amisulpride in the treatment of negative and depressive symptoms in schizophrenia. 1672 3

Risperidone, olanzapine, and clozapine are three atypical antipsychotic medications commonly used in the management of chronic schizophrenia. While they offer advantages with regard to clinical efficacy and side-effect profile, few studies have compared them in a naturalistic prospective observational manner. This study therefore investigated their comparative efficacy over 12 weeks including illness characteristics and adverse effects. One hundred thirty-one patients (76 M, 55 F) with DSMI-V schizophrenia or schizoaffective disorder were treated with risperidone (n = 38), olanzapine (n = 38), or clozapine (n = 55). All patients showed a significant decrease of Positive and Negative Syndrome Scale (PANSS)-positive scores. Decreases in tardive dyskinesia and impulsivity scores were noted with clozapine and olanzapine, respectively. No differences between the medications were noted on depression, anxiety, EPS, or overt aggression scores. Olanzapine and clozapine appeared to be more effective in females. Males showed a decreased sexual performance irrespective of the medication and those treated with risperidone and clozapine showed greater proportional reduction of overt aggression. Clozapine-treated patients showed significant increased weight, increased glucose levels, and lowered sexual performance. Risperidone patients tended to exhibit reduced cholesterol levels. Higher creatine kinase (CK) levels were noted in risperidone-treated patients. While cautious given the nature of the study design, results suggest differences in the response to various atypical antipsychotic medications regarding efficacy and side-effect susceptibility.
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PMID:Comparison between risperidone, olanzapine, and clozapine in the management of chronic schizophrenia: a naturalistic prospective 12-week observational study. 1678 15

Subjects were patients with schizophrenia or schizoaffective disorder enrolled in extension studies (Study A and Study B) after participating in 12-week studies of long-acting injectable risperidone [Kane, J.M., Eerdekens, M., Lindenmayer, J.-P., Keith, S.J., Lesem, M., Karcher, K., 2003. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am. J. Psychiatry 160, 1125-1132; Lindenmayer, J.-P., Eerdekens, L., Berry, S., Eerdekens, M., 2004. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J. Clin. Psychiatry 65, 1084-1089]. Twelve months of treatment were completed by 55% of Study A patients and 52% of Study B patients. The median modal dose of long-acting injectable risperidone was 50 mg/14 days in both studies. Most frequent adverse events were psychosis, headache, insomnia, agitation, and rhinitis. EPS-related adverse events were reported in 33% of patients in Study A and 22% in Study B. Patients with Clinical Global Impressions ratings of "not ill" and "mild" increased from 14% at baseline to 54% at endpoint in Study A and from 42% to 65% in Study B. It is concluded that treatment with long-acting injectable risperidone for 1 year or longer appeared to be safe and well tolerated in patients with schizophrenia or schizoaffective disorder.
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PMID:Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder. 1704 18

A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D2/D3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability.
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PMID:Studies towards the identification of a new generation of atypical antipsychotic agents. 1708 80

The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms. In addition, the effects of flupentixol on mood and cognitive symptoms were explored. In a randomized, double-blind multicenter study, 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol (4-12 mg/d) or risperidone (2-6 mg/d) for up to 25 weeks. In addition to a non-inferiority analysis, a principal component analysis (PCA) of the PANSS was performed post hoc. Regarding negative symptoms, flupentixol proved to be non-inferior to risperidone. Both drugs improved depressed mood with effect sizes favoring flupentixol. PCA suggested a five-factor structure. Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone. EPS scores were rather low and Parkinsonism improved in both groups, but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group, which generally showed significantly more adverse events. Results indicate that the 1st generation antipsychotic flupentixol improves negative, affective and cognitive symptoms in chronic schizophrenia comparable to risperidone. Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range.
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PMID:Efficacy of flupentixol and risperidone in chronic schizophrenia with predominantly negative symptoms. 1741 73

Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.
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PMID:Efficacy of olanzapine versus quetiapine on cognitive dysfunctions in patients with an acute episode of schizophrenia. 1762 25

This study determines the socio-demographic and clinical correlates of suicide attempts in Chinese schizophrenia outpatients and their impact on patients' quality of life (QOL). Two hundred and fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong (HK) and their counterparts matched according to sex, age, age at onset and length of illness were recruited in Beijing (BJ). All subjects at both sites were interviewed by the same investigator using standardized assessment instruments. Basic socio-demographic and clinical data and history of suicide attempts were collected. The lifetime prevalence of suicide attempts was 26.7% in the whole sample and 20% and 33.6% in the HK and BJ samples, respectively. Patients with a history of suicide attempts were less likely to receive depot antipsychotic (AP) medication, more likely to receive clozapine, benzodiazepines (BZD) and higher doses of APs; were younger at onset, had more hospitalizations; had more severe positive, depressive, anxiety and extrapyramidal (EPS) symptoms; were poorer QOL in the physical, psychological, social and environmental domains; and were more likely to be BJ residents. In multiple logistic regression analysis, early age at onset, poor physical QOL, use of clozapine and BZDs, and study site (HK vs BJ) were significant contributors to lifetime suicide attempts. Significant difference was found between matched samples in HK and BJ with respect to suicide attempts. HK is a cosmopolitan city with a Western social structure and mental health system, whereas in BJ more traditional Chinese cultural values predominate, with a mental health policy radically different from that of HK. These differences suggest that socio-cultural factors play a significant role in determining suicide attempts in schizophrenia.
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PMID:Socio-demographic and clinical correlates of lifetime suicide attempts and their impact on quality of life in Chinese schizophrenia patients. 1766 94

Amisulpride is an atypical antipsychotic drug with a unique receptor pharmacology which is dose dependent. It is a standard treatment in dysthymia as well as in psychosis. Amisulpride is efficacious, effective and well tolerated in positive symptoms of schizophrenia: there is extensive evidence that it treats negative symptoms when given in low doses, although relative lack of EPS and an antidepressant effect may contribute. In first-episode patients amisulpride is an option, although there is little comparative work available. Amisulpride has the best evidence as an effective adjunct to clozapine treatment. Regarding intellectual function, amisulpride appears cognitive sparing but the clinical relevance of this remains obscure. There is evidence that amisulpride can improve social function but again there is little comparative work to demonstrate any particular advantages. Regarding the current conventional versus atypical antipsychotic controversy, amisulpride did better in switching studies and meta-analyses than in the single large pragmatic randomized trial reported to date. It is a versatile drug, and may offer advantages over other atypical antipsychotic drugs in the treatment of negative and depressive symptoms, and tolerability advantages such as the avoidance of weight gain. Essentially it rests with the treating clinician to employ a rational psychopharmacological approach towards the individual patient: there will be few circumstances in which amisulpride will not be a likely contender as a treatment choice.
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PMID:Update on the management of symptoms in schizophrenia: focus on amisulpride. 1955 21

A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was conducted in January 2008 for the years 1985-2007. Selected were truly prospective studies of incident cases of TD in a population with at least 80% patients with schizophrenia. Measures of relative risk were collected from the individual studies, either directly or by calculating the relative risk from the cox- or logistic regression coefficient provided in the article. Hazard Ratio's and Odds Ratio's were pooled using fixed and random effect models in case of multiple studies using the same measure of risk and outcome. Only eight studies satisfied the inclusion criteria reporting on 25 different single estimate risk factors. Of 25 risk factors, six concerned replicated estimates suitable for meta-analysis. Of these, non-white ethnic group and early extrapyramidal symptoms qualified as risk factors for the emergence of TD in schizophrenia. The association with older age was suggestive but inconclusive. Despite many reported risk factors for TD in schizophrenia, little conclusive evidence exists to corroborate this. However, the fact that early EPS predicts onset of TD has important clinical and research implications.
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PMID:Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. 1964 70


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