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Extrapyramidal Symptoms (extrapyramidal + symptom)
Selected AbstractsClinical correlates of clozapine prescription for schizophrenia in ChinaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2007Yu-tao Xiang Abstract Aims Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China. Methods Three hundred ninety-eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM-IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule-Brief version. Assessments were performed by the same investigator in both sites. Results Clozapine was prescribed to 15.6% of (n,=,62) patients. There was a wide inter-site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co-prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non-clozapine groups with regard to any of the quality of life domains. Conclusion A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [source] Quetiapine augmentation in depressed patients with partial response to antidepressants,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008James S Olver Abstract Objective Clinical trials suggest between 30,50% of depressed patients have an inadequate outcome to antidepressant pharmacotherapy. Among the approaches to improve outcome has been augmentation with antipsychotic medications. We aim to investigate the efficacy and tolerability of augmentation with quetiapine in depressed patients with a partial response to antidepressants. Methods Patients with a Major Depressive Disorder (DSMIV) who had partial/no response to a stable dose of an Selective Serotonin Reuptake Inhibitors (SSRI)/SNRI were recruited. All patients received add-on quetiapine (200,600,mg nocte) in a 6-week trial. Outcome measures (HAMD, MADRS) were assessed at screening, baseline, weeks 1, 2, 4 and 6. Extrapyramidal symptoms (EPSEs) were assessed at baseline, weeks 2, 4 and 6. A neuropsychological battery of tests was administered at baseline, weeks 3 and 6. Results Nineteen patients entered the trial and 18 completed the trial per protocol. We report a rapid improvement in depression ratings over 6 weeks (p,<,0.0005) and remission rates of 67% at week 1 and 94% at week 6. There was no evidence of EPSE and no worsening (and some improvement) of cognition. Conclusion This suggests clinical benefits of quetiapine augmentation of SSRI/SNRI antidepressants with no worsening, and possible improvements in cognition. Copyright © 2008 John Wiley & Sons, Ltd. [source] Neurological complications of psychiatric drugs: clinical features and management,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Peter M. Haddad Abstract This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunctionMOVEMENT DISORDERS, Issue 9 2006Antje Mueller MD Abstract Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the "Sniffin' Sticks," which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit. © 2006 Movement Disorder Society [source] Effectiveness and tolerability of risperidone in Asian patients with first-episode psychosisACTA PSYCHIATRICA SCANDINAVICA, Issue 2002S. Verma Objectives, To evaluate the effectiveness and tolerability of risperidone in Asian patients with first-episode psychosis and to examine correlates of response in a naturalistic study. Method, Patients with first-episode psychosis were evaluated at baseline and weekly for 6 weeks with the Positive and Negative Scale for Schizophrenia (PANSS), Simpson,Angus Rating Scale (SARS), Barnes Akathisia Rating Scale (BARS), Rating Scale for Side-effects (RSSE), and the Abnormal Involuntary Movement Scale (AIMS). Results, 42 patients with a mean age of 24.85 ± 9.68 years and mean duration of untreated illness of 11.91 ± 22.04 months were recruited. The mean dose of risperidone was 1.82 ± 0.77 mg. The mean reduction in PANSS score was from 67.97 ± 20.02 at baseline to 42.53 ± 14.08 at week 6 (P < 0.005). The incidence of extrapyramidal symptoms was 9.5% and akathisia was 7.1%. 45.2% of patients showed more than or equal 40% reduction in the PANSS score (responders). When responders were compared to nonresponders, the responders had a significantly higher total and positive PANSS score at baseline. Conclusion, Risperidone is an effective and safe antipsychotic in first-episode psychosis. [source] Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic studyEARLY INTERVENTION IN PSYCHIATRY, Issue 1 2010Richard C. Josiassen Abstract Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. Method: In a naturalistic, ,single-blind' design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms. [source] Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational studyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2010Cecilia Adrianzén Abstract Objective To explore the relative association of adverse events with health-related quality of life (HRQL) in patients (N,=,16,091) with schizophrenia, treated with antipsychotic medication. Methods In this post hoc analysis of data from two 3-year observational studies, a mixed effects model with repeated measures was used to evaluate the association between HRQL (EuroQoL visual analogue scale (EQ-VAS)) and pre-specified covariates including: severity of illness, extrapyramidal symptoms, tardive dyskinesia, sexual dysfunction, and clinically significant weight gain (>,7% increase from baseline after ,,3 months of treatment). Results Mean EQ-VAS increased from 47.8,±,21.7 at baseline to 72.4,±,18.4 after 36 months. The rank order of the negative association of adverse events with HRQL was: sexual dysfunction (effect estimate ,4.04; 95% CI ,4.30 to ,3.79), extrapyramidal symptoms (effect estimate ,2.09; 95% CI ,2.43 to ,1.75), and tardive dyskinesia (effect estimate ,0.89; 95% CI ,1.46 to ,0.32). Conclusions Differences were observed in the direction and magnitude of the association between each adverse event and HRQL. Recognition of the relative association of adverse events with HRQL may contribute to improved adherence of patients with schizophrenia to antipsychotic therapy. Copyright © 2010 John Wiley & Sons, Ltd. [source] Risperidone versus olanzapine for the treatment of deliriumHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2010Sung-Wan Kim Abstract Objective This study compared the effectiveness of risperidone and olanzapine in the treatment of delirium. Methods This was a 7-day, randomized, comparative clinical trial of risperidone and olanzapine in patients with delirium. The primary outcome measure was the Delirium Rating Scale-Revised-98 (DRS-R-98). Results We enrolled 32 subjects (median age, 70 years). Significant within-group improvements in the DRS-R-98 scores over time were observed at every time point in both treatment groups; however, differences in the change of the DRS-R-98 score from baseline were not significant between the treatment groups. On the first day after drug treatment, there was a trend toward greater improvement in the DRS-R-98 score in the olanzapine group compared with the risperidone group, but it did not reach statistical significance (p,=,0.076). The response rates did not differ significantly between the two groups (risperidone group: 64.7%, olanzapine group: 73.3%). However, the response to risperidone was significantly poorer in patients ,70 years of age compared with those aged <70 years. There was no significant difference in the safety profiles, including extrapyramidal symptoms (EPSs), between the two groups. Conclusion Risperidone and olanzapine were equally effective in reducing delirium symptoms. The response to risperidone was poorer in the older age group. Copyright © 2010 John Wiley & Sons, Ltd. [source] Efficacy and safety of quetiapine for depressive symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009Kyoung-Uk Lee Abstract Objective To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia. Method Thirty-nine patients fulfilling DSM-IV-TR diagnostic criteria for schizophrenia and had depressive symptoms were studied in a prospective 6-week open-label design using quetiapine monotherapy. The brief psychiatric rating scale (BPRS), 17-item Hamilton depression rating scale (HAMD-17), Simpson,Angus rating scale, and the Barnes Akathisia rating scale (BARS) were used to assess patients at baseline, week 1, 2, 4, and 6. Results Thirty patients (76.9%) completed this study. The dose of quetiapine at endpoint was 583 (±235 SD),mg/day. Treatment with Quetiapine was associated with significantly reduced depressive symptoms (HAMD-17 total score and BPRS depression/anxiety subscale) from the first week of treatment. Changes of mean score from baseline to endpoint were 7.8,±,6.2 for HAMD-17 total score and 3.4,±,3.6 for BPRS depression/anxiety subscale (LOCF, n,=,39, p,<,0.001). Quetiapine was well tolerated, with minimal extrapyramidal symptoms and non-significant increase in body weight (mean increase of 0.8,kg). Conclusions While the interpretation of findings from the open-label design of this study warrants appropriate caution, the results suggest that quetiapine may be an effective and tolerable treatment for depression in patients with schizophrenia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effect of antipsychotic replacement with quetiapine on the symptoms and quality of life of schizophrenic patients with extrapyramidal symptomsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2006Takahide Taniguchi Abstract Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti-parkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients completed the trial and received the assessment. It was found that replacement with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy (n,=,11) but also patients who took QTP together with reduced small doses (4.4,±,4.3,mg/day) of previous drugs (n,=,11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Persistent dystonia induced by fluoxetineINTERNAL MEDICINE JOURNAL, Issue 8 2008. Bilen Abstract Serotonin-selective re-uptake inhibitors are prescribed widely because they are regarded as having less severe side-effects compared with tricyclics and monoamine oxidase inhibitors. With this popularity, increasing attention has been drawn to their adverse effects. Development of extrapyramidal symptoms has been reported in some patients while taking fluoxetine, a commonly used serotonin-selective re-uptake inhibitor. Here, we report a case of persistent dystonia, thought to be associated with short-term fluoxetine use, which required treatment with botulinum toxin type A. [source] Paliperidone palmitate , review of the efficacy, safety and cost of a new second-generation depot antipsychotic medicationINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010L. Citrome Summary Objective:, To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. Data sources:, A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term ,paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. Study selection:, All available reports of studies were identified. Product labelling provided additional information. Data extraction:, Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose,response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4,7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Conclusions:, Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use. [source] Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO): baseline characteristics of pan-regional observational data from more than 17,000 patients,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2009J. Karagianis Summary Objective:, To describe the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) patient population at study entry, focusing on illness burden and prescribing practices across regions. Methods:, The SOHO study was a 3-year, prospective, observational study designed to assess costs and outcomes associated with antipsychotic use in outpatients initiating or changing antipsychotic (with an emphasis on olanzapine compared with other antipsychotics). SOHO was conducted in 10 European countries and 27 other countries as Intercontinental SOHO (IC-SOHO). Data from all countries have been pooled to produce the W-SOHO dataset. Main outcomes measures:, Clinical Global Impression-Schizophrenia (CGI-SCH) severity scores, psychotropic medication use, adverse events, social interaction, housing and employment status, self-perceived health state (EuroQoL EQ-5D scale and Visual Analogue Scale, EQ-VAS), and reasons for initiation/change of antipsychotic. Results:, The W-SOHO database comprises 17,384 patients from six regions; East Asia (n = 1223), Central and Eastern Europe (n = 2175), Northern Europe (n = 4291), Southern Europe (n = 5788), Latin America (n = 2566), North Africa and the Middle East (n = 1341). Overall, patients were 38 ± 13 years old (mean ± SD), moderately ill (mean CGI-SCH overall score of 4.4 ± 1.0) with a median duration of illness of 7 years (interquartile range 1,16 years); 43% were female, 10% were receiving antipsychotic medication for the first time. Adverse events were prevalent across all regions; on average, 50% (range 41,59%) of patients taking antipsychotics exhibited extrapyramidal symptoms at baseline, and 62% (34,67%) of patients reported sexual dysfunction in the previous month. On average, only 19% (16,23%) of patients were in paid employment and as many as 69% were living in dependent housing. Conclusions:, Despite inherent diversity in these patients and the health care systems supporting them, there are striking cross-regional similarities in baseline characteristics for most measures. Not all countries are represented; regional comparisons may not be valid outside of the countries studied. [source] Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2004Peter Paul De Deyn Abstract Objectives Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings. Methods Patients (n,=,652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5,mg/day). Results Mean age was 76.6±10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items,primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5,mg olanzapine group (,6.2,±,4.9) was significantly greater than with placebo (,5.0,±,6.1, p,=,0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz,2.5 olanzapine group (2.8,±,1.4, p,=,0.030) relative to placebo (3.2,±,1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol. Conclusions While 1.0,mg olanzapine did not show significant differences from placebo, the 2.5,mg dose was a reasonable starting dose. Olanzapine at 7.5,mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated. Copyright © 2004 John Wiley & Sons, Ltd. [source] Identification of a new functional target of haloperidol metabolite: implications for a receptor-independent role of 3-(4-fluorobenzoyl) propionic acidJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Hyeon Soo Kim Abstract Haloperidol, a dopamine D2 receptor blocker, is a classical neuroleptic drug that elicits extrapyramidal symptoms. Its metabolites include 3-(4-fluorobenzoyl) propionic acid (FBPA) and 4-(4-chlorophenyl)-4-piperidinol (CPHP). Until now, the biological significance of these metabolites has remained largely unknown. Here, we report that the administration of FBPA to mice effected a suppression of locomotor activity and induced catalepsy in a manner similar to that observed with haloperidol, whereas CPHP had no significant effects. Neither of these two metabolites, however, exhibited any ability to bind to the dopamine D2 receptor. FBPA blocked dopamine-induced extracellular signal-regulated kinase 1/2 phosphorylation, and it specifically affected mitogen-activated protein kinase kinase (MEK)1/2 activity in hippocampal HN33 cells. Moreover, FBPA was capable of direct interaction with MEK1/2, and inhibited its activity in vitro. We demonstrated the generation of haloperidol metabolites within haloperidol-treated cells by mass spectrometric analyses. Collectively, our results confirm the biological activity of FBPA, and provide initial clues as to the receptor-independent role of haloperidol. [source] Drug-induced extrapyramidal reactionsJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1 2002L Teoh Abstract: A child with psychotic symptoms and attention-deficit hyperactivity disorder who developed extrapyramidal symptoms while on a combination of risperidone, methylphenidate, sertraline, tropisetron and ketorolac is described herein. The extrapyramidal symptoms resolved with the administration of benztropine, an anticholinergic drug. Successful treatment of his psychosis was achieved by decreasing the dose of risperidone, followed by slow upward titration. [source] Nursing and extrapyramidal symptoms: a critical commentaryJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 5 2000Liam Clarke [source] What can we do about acute extrapyramidal symptoms?JOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 3 2000R. Gray RN BSC (HONS) Antipsychotic drugs are the most effective treatment for psychotic disorders such as schizophrenia. However, they are known to cause a range of side-effects including acute extrapyramidal symptoms (EPS) that are both distressing and disabling. Mental health nurses play a critical role in both the detection and the management of these symptoms. A review of the literature was conducted to identify strategies for managing acute EPS. Despite a widely held belief that EPS are associated with noncompliance with medication, the data to support this hypothesis are weak. Although akathisia may negatively affect the treatment outcome, there was little evidence to suggest that parkinsonism or dystonia do. Whilst the use of anticholinergic medication may be helpful in treating acute parkinsonism and dystonia they were associated with their own side-effects and the benefit of long-term prophylactic treatment is doubtful. The literature suggests that logical prescribing and rapid detection and management of acute EPS will result in a substantial reduction in the incidence of these disabling side-effects. [source] Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: A meta-analysis,,MOVEMENT DISORDERS, Issue 16 2009Diederik E. Tenback MD Abstract 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. © 2009 Movement Disorder Society [source] Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunctionMOVEMENT DISORDERS, Issue 9 2006Antje Mueller MD Abstract Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the "Sniffin' Sticks," which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit. © 2006 Movement Disorder Society [source] Metric characteristics of the drug-induced extrapyramidal symptoms scale (DIEPSS): A practical combined rating scale for drug-induced movement disordersMOVEMENT DISORDERS, Issue 6 2002Jong-Hoon Kim MD Abstract The metric properties of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were examined in 182 subjects treated with antipsychotics. Inter-rater reliability, test,retest reliability, and concurrent validity with other rating scales for EPS were high. Four factors were identified and the optimal diagnostic cut-off scores were obtained. These results suggest that the DIEPSS is a reliable and valid multidimensional rating scale. © 2002 Movement Disorder Society [source] Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2002C. R. Cabello In a stereological study of the human substantia nigra (SN), the total number of melanin-positive and melanin-negative neurones from 28 male subjects aged 19,92 years was estimated using a uniform sampling design and optical disectors. There was a significant decrease in the total number of melanin-positive neurones as a function of age (r2=0.18, residual-CV=0.35, 2P=0.032). Using the rotator method, the size distribution of the melanin-positive neurones was estimated and showed a significant difference in mean cell volume of melanin-positive neurones between the seven youngest (21,077 µm3) and the seven oldest individuals (32,011 µm3), 2P=0.022. Using a combination of the total number of melanin-positive neurones and their size distribution, the total perikaryon volume of melanin-positive neurones could be estimated and showed no decrease with increasing age (r2=0.01, residual-CV=0.41, 2P=0.62). Age-related decline in dopamine-transporter neurones within the SN might explain the occurrence of extrapyramidal symptoms in many elderly individuals. Although age-related cell hypertrophy is usually considered to be an indication of cell degeneration or necrosis, this might not always be the case. The fact that motor symptoms, although present in many of the elderly, are of a limited nature despite the high percentage of lost neurones could be due to a compensatory increase in the cell body of dopamine-producing SN neurones. Thus, the total amount of cell substance capable of producing the essential transmitters might not be reduced to a critically low level as a result of ageing. [source] Correlation between scores on Continuous Performance Test and plasma concentration for schizophrenic patients on risperidonePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2004PO SEE CHEN md Abstract, The purpose of the present paper was to evaluate the relationship between plasma antipsychotics concentration and cognitive task performance. This may provide valuable information for rational dosage titration. Literature on the relationship between plasma risperidone (RIS) concentration and performance on the Continuous Performance Test (CPT) remains scarce. Ten patients (four male, six female) were given RIS for more than 1 year. Steady-state plasma concentrations of the parent drug RIS and its active metabolite, 9-hydroxy-risperidone (9-OH-RIS), were measured using specific liquid chromatography-tandem mass spectrometry assay. Psychopathology, side-effects of extrapyramidal symptoms (EPS) and CPT were also assessed. A negative correlation was found between CPT performance and the plasma RIS, 9-OH-RIS and its active moiety (RIS + 9-OH-RIS) concentrations. Both RIS and 9-OH-RIS have an impact on the CPT performance of schizophrenic patients. Optimal active moiety plasma concentration for best cognitive performance needs further study. [source] Single- and multiple-dose pharmacokinetics of ziprasidone under non-fasting conditions in healthy male volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue S1 2000J. J. Miceli Aims, To evaluate the pharmacokinetics and tolerability of single and multiple oral doses of ziprasidone in healthy male volunteers, and to determine the influence of ziprasidone on serum prolactin levels. Methods, Single and multiple doses of ziprasidone were given orally (as two divided daily doses), at fixed dosages of 10 and 40 mg day,,1, and using titrated regimens of 40,80 and 40,120 mg day,,1, for 14 days. All dosages were taken immediately after food. The study adopted a randomized, double-blind, placebo-controlled design. Prolactin response, sedative properties, tolerability, and extrapyramidal symptoms were also investigated. Results, Steady-state exposure to ziprasidone was attained after 1 day of dosing. Mean Cmax and AUC(0,12 h) increased with increasing dose, with apparent dose-proportionality between the 20 and 60 mg dose levels. Trough-to-peak ratios at steady state ranged from 2 to 5. Accumulation ratios for the fixed-dose regimens were 1.49 and 1.48 at the 5 and 20 mg dose levels, respectively. Ziprasidone was associated with transient prolactin elevation but levels of prolactin returned to baseline within the dosing interval at steady state. There was a marginal, transient increase in serum prolactin levels which was not dose-related at the 80 and 120 mg day,,1 doses, and which was noted to attenuate with chronic dosing. Ziprasidone was generally well tolerated. The most frequent side-effect was mild or moderate headache. A minority of patients suffered first-dose postural hypotension. Ziprasidone was also associated with a mild sedative effect that became less pronounced as treatment continued. There were no drug-related changes in electrocardiogram or clinical laboratory variables that were of clinical importance. Conclusions, Ziprasidone is characterized by a predictable pharmacokinetic profile resulting in symptoms that reflect its pharmacological action. [source] Creutzfeldt,Jakob disease with PRNP G114V mutation in a Chinese familyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2010Z. Liu Liu Z, Jia L, Piao Y, Lu D, Wang F, Lv H, Lu Y, Jia J. Creutzfeldt,Jakob disease with PRNP G114V mutation in a Chinese family. Acta Neurol Scand: 2010: 121: 377,383. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background,,, Recent evidence has shown clinical phenotypic heterogeneity of inherited prion diseases, even between patients harbouring the same mutation in the PRNP gene. Objective and methods,,, We collected clinical data from a Chinese family with autosomal dominant dementia and screened the PRNP gene on 28 living members. A stereotactic biopsy of the right frontal lobe of the proband was performed. Results,,, The family comprised four affected individuals within two successive generations. The age of onset was in 30 or 40 s, and the duration was about 2,3 years. Clinical features of the affected members included neuropsychiatric disturbances, progressive dementia and extrapyramidal symptoms. Immunostaining for prion protein showed fine granular deposits of PrPsc in the neuropil. The PRNP gene analysis demonstrated a heterozygous G114V mutation in 15 family members. The proband was diagnosed as familial Creutzfeldt,Jakob disease (fCJD). Conclusion,,, This study strengthens the linkage of the G114V mutation to CJD. It supports the worldwide distribution of fCJD despite differences in genetic background. [source] Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposureACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010K. Sikk Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Askmark H, Danfors T, Sörensen J, Thurfjell L, Raininko R, Eriksson R, Flink R, Färnstrand C, Aquilonius S-M. Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure. Acta Neurol Scand: 2010: 121: 237,243. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). Methods,,, Neurophysiological examinations, magnetic resonance imaging (MRI), single-photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. Results,,, Peripheral nervous system was not affected. No patients had reduced uptake of 123I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. Conclusions,,, Presynaptic neurons in the nigrostriatal pathway are intact in Mn-induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse. [source] Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disordersCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2 2005Richard ReadingArticle first published online: 16 FEB 200 Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disorders . SheaS, TurgayA, CarrollA, SchulzM, OrlikH, SmithI & DunbarF. ( 2004 ) Pediatrics , 114 , e634 , e641 . Objective To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioural symptoms in children with autism and other pervasive developmental disorders (PDD). Methods In this 8-week, randomized, double-blinded, placebo-controlled trial, risperidone/placebo solution (0.01,0.06 mg/kg/day) was administered to 79 children who were aged 5,12 years and had PDD. Behavioural symptoms were assessed using the Aberrant Behaviour Checklist (ABC), Nisonger Child Behaviour Rating Form and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events and laboratory tests. Results Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other four subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive and overly sensitive subscales of the Nisonger Child Behaviour Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% vs. 7.7% of subjects (risperidone vs. placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs. 1.0 kg), pulse rate and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. Conclusions Risperidone was well-tolerated and efficacious in treating behavioural symptoms associated with PDD in children. 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