Simpson-Angus Rating Scale Research Articles

Spontaneous Parkinsonism in Antipsychotic-Naive Patients with First-Episode Psychosis

The purpose of this study was to establish rates of spontaneous parkinsonism (SP) among the different types of psychosis. We hypothesized that the rate would be higher among persons with affective symptoms. We included in the study consecutive patients admitted to a first-episode psychosis intervention program. We recorded sociodemographic data from interviews with patients and caregivers and from medical records. We used the Simpson-Angus Rating Scale at baseline to assess parkinsonism and a diagnosis of SP was established if the Simpson-Angus score was > or = 0.3. A total of 174 patients were examined; of these, only 4 (2.3%; 2 Chinese women, 1 Chinese man, and 1 Malay man) had SP. There was a significant difference in the rates of SP in patients with affective psychosis and schizoaffective disorder, compared with those with nonaffective psychoses (15.4% vs 1.2%; chi2 = 10.7, P = 0.001). The 2 groups did not differ significantly in age, duration of untreated psychosis, or sex distribution. The rate of SP in Asian patients with first-episode psychosis was low, and it was significantly higher in those with affective symptoms.

Long-term treatment of adjunctive quetiapine for bipolar mania

This study evaluated the overall effectiveness and tolerability of adjunctive quetiapine as a continuation therapy for the long-term treatment of bipolar mania. Twenty-three patients were enrolled in this study and received quetiapine add-on treatment in combination with their existing or new mood stabilizers. The clinical assessment was carried out using the Young Mania Rating Scale (YMRS), Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale scores-17 item, Simpson–Angus Rating Scale and Barnes Akathisia Rating Scale at the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly from the baseline to the endpoint by 89.7% and 78.3%, respectively ( p < 0.0001; p < 0.0001). By the end of the study, 22 patients showed at least 50% improvement in the YMRS score. This study suggests that quetiapine can be used as an adjunct in the long-term treatment of bipolar mania.

Clozapine Augmented With Risperidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial

The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.

Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study

Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson–Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex.

The influence of olanzapine on facial expression of emotions in schizophrenia – An improved facial EMG study

Background: The purpose of the study was to investigate the facial expression of emotions (FEE) and its correlation to psychopathology in schizophrenic, olanzapine-treated patients, using an improved facial-EMG method. Method: We compared fifteen olanzapine-treated, schizophrenic patients with nineteen healthy subjects over a period of two weeks. Emotions were induced by showing pictures from the International Affective Picture System. The activity of five facial muscles was measured with a new, highly sensitive and discriminative facial EMG, recording pre-visible facial muscle activity. The Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus rating scale for extrapyramidal side effects (EPS) were administered. Results and Conclusion: Unmedicated schizophrenic patients showed fewer joy/smile reactions than the control group. Compared to healthy controls, the relative smile frequency was not significantly changed by olanzapine. The smile frequency and its changes over time are not significantly correlated with the PANSS depressive syndrome. The changes of facial muscle activity do not correlate with EPS (German J Psychiatry 2004; 7: 14-19).

Switching to quetiapine in patients with acute mania who were intolerant to risperidone.

This study evaluated the overall efficacy and tolerability of quetiapine in the treatment of inpatients with acute mania who are intolerant to risperidone in combination with a mood stabilizer. Eighteen patients completed this 3-week trial. The efficacy and tolerability was assessed upon admission, at baseline, and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global impression-severity (CGI-s) scores from the baseline to the endpoint, decreased by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients exhibited at least a 50% improvement in the YMRS and CGI-s scores by the end of the trial. Measurements taken through the Barnes akathisia rating scale (BARS), the Simpson-Angus rating scale (SARS) and the drug attitude inventory shortened version-10 (DAI-10) also showed significant improvement. This study suggests that quetiapine may hold promise as an alternative regimen that does not worsen the psychopathology, particularly for those vulnerable to the side effects of drugs, including atypical agents such as risperidone, in naturalistic treatment settings.

Effectiveness of Second-Generation Antipsychotics in Patients With Treatment-Resistant Schizophrenia: A Review and Meta-Analysis of Randomized Trials

Objective: The authors conducted a review and meta-analysis of studies that compared the efficacy and tolerability of typical and second-generation antipsychotics for patients with treatment-resistant schizophrenia. Method: A systematic search revealed 12 controlled studies (involving 1,916 independent patients), which were included in the review. For the seven studies that compared clozapine to a typical antipsychotic, a meta-analysis was performed to examine clozapine’s effects on overall psychopathology, response rate, extrapyramidal symptoms, and tardive dyskinesia. Results: The meta-analysis confirmed that treatment-resistant schizophrenic patients have more favorable outcomes when treated with clozapine rather than a typical antipsychotic, as reflected by Brief Psychiatric Rating Scale total score, categorical response rate, Scale for the Assessment of Negative Symptoms score, Simpson-Angus Rating Scale score, and compliance rate. Clozapine also conferred benefits on the sickest treatment-resistant ...

Depression in Kraepelinian schizophrenia.

In order to improve our understanding of depression in chronic schizophrenia, depressive symptoms were assessed in institutionalized, so called Kraepelinian, patients with schizophrenia (N = 43). The patients had been ill and dependent on others for at least 5 years. Depressive symptoms as measured by the Hamilton Depression (HAM-D) scale were less prevalent in this population compared to published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients had a HAM-D score >/= 16. There was also a low prevalence of core depressive symptoms (depressed mood, suicidal ideation, and guilt). The relationship of depression to other dimensions of schizophrenia was explored. Depression had a modest positive correlation (r = 0.44) with general psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as measured by BPRS positive subscale or negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS). Depression also showed a modest positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian schizophrenia, depression is not prevalent, even though patients are severely ill both in symptom and functioning domains. The results of our analysis support that Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia. Finally, the low rate of depression observed revives the notion that preservation of core functional abilities is important for a depressive reaction to evolve in schizophrenia.

Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia.

The putative role of dopamine in the pathophysiology of tardive dyskinesia (TD) makes the genes coding for dopamine receptors the appropriate candidates for study. We investigate the association of the polymorphism of the Ser311Cys and Ser9Gly of the dopamine D2 (DRD2) and D3 receptor (DRD3) genes respectively with TD in Chinese patients with schizophrenia. In a case-control study, 117 Chinese patients with TD were compared to 200 patients without TD. Patients were diagnosed to have schizophrenia according to DSM-IV criteria. Dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS), whereas extrapyramidal side-effects (EPSE) were assessed by the Simpson-Angus Rating Scale. Genotype groups were comparable in age, gender, duration of illness, daily neuroleptic and benzodiazepine dose as well as the mean scores for EPSE. We failed to find an association between the polymorphism of the DRD2 gene with TD but found an increased risk of developing TD among those with D3 serine/serine genotype. Our results did not indicate that the D2 genotype has a role in the pathophysiology of TD in Chinese patients with schizophrenia. The association of TD with the serine/serine genotype of the DRD3 may be an epiphenomenon of patients with a subtype of schizophrenia who had more exposure to neuroleptics.

Serum iron levels in schizophrenic patients with or without akathisia

The pathophysiology of akathisia still remains controversial. Iron deficiency was proposed to be an important factor in the development of akathisia. In the present study, it was aimed to compare levels of serum iron and linked variables in chronic akathisic ( n=30), and non-akathisic patients ( n=30) with schizophrenia and healthy controls ( n=30) because of the controversy in the association of iron and akathisia. The Barnes Akathisia Scale for akathisia and Simpson–Angus Rating Scale for extrapyramidal side effects were used. Serum iron and linked variables and hematological profile of the patients and control subjects were determined. Serum iron levels were significantly lower both in akathisic and non-akathisic groups compared to the control group ( P<0.001). Moreover, akathisic patients had significantly lower iron levels than non-akathisic patients ( P<0.05). Total iron binding capacity was significantly higher in patients with akathisia compared to the control group ( P<0.01). Although non-akathisic patients had a mild increase in total iron binding capacity, it was not statistically significant compared to the control group ( P>0.05). Ferritin levels were determined to be significantly lower in both groups compared to the control group ( P<0.01). In addition, there was a significant difference in ferritin levels between the patients with and without akathisia ( P<0.05). In conclusion, our results support the hypothesis that an association between akathisia and iron metabolism exists.

Duration of untreated psychosis and response in first‐episode psychosis

Objective It is suggested that the duration of untreated psychosis (DUP) is directly correlated to the outcome of the illness. This study examines the effect of DUP on the acute response of patients with first‐episode psychosis.Method In this naturalistic study, 55 Asian patients with first‐episode psychosis were assessed weekly for 6 weeks on the Positive and Negative Syndrome Scale (PANSS), Simpson–Angus Rating Scale, Barnes Akathisia Rating Scale and the Abnormal Involuntary Movement Scale. Clinical response was defined as a 20% or greater reduction in PANSS from baseline.Results After 6 weeks, the response rate was 67% (n=37). The responders had a mean DUP of 14.7 ± 20.2 months and a median of 6 months. This was significantly shorter when compared to the mean DUP 37.3 (SD=32.7) months, median of 36 months of the nonresponders (Mann–Whitney U‐test, P=0.37). There was no significant difference in the mean daily dose of antipsychotics, themean Simpson–Angus Scale, the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale scores between the responders and nonresponders.Conclusions The study results suggest that DUP is a predictor of acute response in first episode psychosis.

Effectiveness and tolerability of risperidone in Asian patients with first‐episode psychosis

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 &lt; 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.

Clinical characteristics and associated factors in antipsychotic-induced akathisia of Asian patients with schizophrenia

Objective: We studied the prevalence of akathisia and its relationship to a number of sociodemographic and clinical factors in a population of Chinese inpatients with Schizophrenia. Method: Six-hundred and forty-five patients were recruited for the study. Akathisia was assessed using the Barnes Akathisia Rating Scale (BARS), dyskinesia by the Abnormal Involuntary Movement Scale (AIMS) and extrapyramidal side effects (EPSE) were assessed by the Simpson–Angus Rating Scale (SARS). Results: Only 35 (5%) patients were assessed to have akathisia. There was no gender or ethnic difference in the rates of akathisia. However, the majority of the patients (65%) were receiving an anticholinergic agent at the time of the study. Conclusion: Our findings of an overlap between TD and EPSE support the suggestion that there may be a common vulnerability for these movement disorders. The finding of a low rate of akathisia among our Asian patients suggests an inter-ethnic difference in the vulnerability for the development of akathisia. However, comparing our results with the rates reported from other countries may be hampered by the diagnostic and methodological differences across studies.

Is olanzapine better than haloperidol in resistant schizophrenia? A double-blind study in partial responders

INTRODUCTION : To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. METHOD : In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. RESULTS : The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). CONCLUSIONS : These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111)

Awareness of tardive dyskinesia in Asian patients with schizophrenia.

While ethnocultural differences in risk of tardive dyskinesia (TD) have been suggested, no previous studies have examined whether this factor also plays a role in lack of awareness of TD. This study examined this question in an Asian population with schizophrenia. Six hundred seven patients in a state mental hospital in Singapore were assessed using the Abnormal Involuntary Movement Scale (AIMS) and the Simpson-Angus Rating Scale. Of the 607 patients, 242 (39.9%) met criteria for TD, and 163 (67.4%) patients were not aware of the presence of TD. No significant differences in terms of age, gender, and duration of illness were found between those aware of their TD and those not aware. Daily neuroleptic doses and scores for the AIMS and Simpson-Angus Rating Scale were significantly different, although after logistic regression, only the Simpson-Angus Rating Scale scores remained significant. The finding that a large proportion of our patients lacked awareness of their TD is consistent with other reports in the West and provides evidence that this feature is characteristic of the illness rather than of a specific ethnocultural group. We found an association between lack of awareness and greater severity of extrapyramidal symptoms (EPS), suggesting that there may be a subtype of TD in which lack of awareness and greater vulnerability of developing EPS are features.

Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials.

The authors conducted a review and meta-analysis of studies that compared the efficacy and tolerability of typical and second-generation antipsychotics for patients with treatment-resistant schizophrenia. A systematic search revealed 12 controlled studies (involving 1,916 independent patients), which were included in the review. For the seven studies that compared clozapine to a typical antipsychotic, a meta-analysis was performed to examine clozapine's effects on overall psychopathology, response rate, extrapyramidal symptoms, and tardive dyskinesia. The meta-analysis confirmed that treatment-resistant schizophrenic patients have more favorable outcomes when treated with clozapine rather than a typical antipsychotic, as reflected by Brief Psychiatric Rating Scale total score, categorical response rate, Scale for the Assessment of Negative Symptoms score, Simpson-Angus Rating Scale score, and compliance rate. Clozapine also conferred benefits on the sickest treatment-resistant schizophrenic patients. Patients treated with olanzapine also had more favorable outcomes with regard to categorical response and compliance rates. In the aggregate, the results of a meta-analysis indicated that clozapine exhibits superiority over typical antipsychotics in terms of both efficacy (as measured by improvement in overall psychopathology) and safety (in terms of reduced extrapyramidal side effects). However, the magnitude of the clozapine treatment effect was not consistently robust. Efficacy data for other second-generation antipsychotics in the treatment of patients with refractory schizophrenia were inconclusive. There is, therefore, a growing need to consider new and different treatment strategies, whether they be adjunctive or monotherapeutic, for schizophrenia that continues to be resistant or only partially responsive to treatment.

Chronic late-onset schizophrenia-like psychosis that remitted: revisiting Newton's psychosis?

According to historical records, Sir Isaac Newton developed new-onset psychosis at age 51, which was characterized by persecutory delusions. His psychotic symptoms remitted in less than 18 months, but their etiology has since remained a puzzle. The present case conference involves a present-day individual with late-onset paranoid psychosis with later remission, which has some interesting similarities to, as well as important differences front Newton's illness. Our patient had no history of psychiatric illness until age 52, when he developed paranoid delusions, which included thought broadcasting, auditory hallucinations, blunted affect, and poor insight. His early medical history was remarkable for grand mal seizures between ages 15 and 29. His psychosis improved with the use of antipsychotic medication. Approximately 6 years after its onset, his psychotic illness remitted, and all psychotropic medications were discontinued. Four years later, at the writing of this report, our patient continued to function independently with no psychiatric symptoms. We discuss the differential diagnosis for this chronic late-onset schizophrenia-like psychosis with remission.

Depressive signs and symptoms in schizophrenia: A prospective blinded trial of olanzapine and haloperidol

Methods: This was a 17-country investigation of 1996 patients with schizophrenia or a related diagnosis randomly assigned to a blinded, comparative trial of the novel antipsychotic agent olanzapine (5-20 mg/d) or the conventional D2 antagonist haloperidol (5-20 mg/d). Patients were evaluated with the Positive and Negative Syndrome Scale, the Montgomery-Asberg Depression Rating Scale, and the Simpson-Angus Rating Scale. The trial consisted of a 6-week and a 46-week masked responder maintenance period.

Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients.

This study assessed the prevalence of extrapyramidal signs and spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients and examined the clinical correlates. In a prospective study of the psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive patients for the presence of extrapyramidal signs by using the Simpson-Angus Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale. Fifteen patients (16.9%) had extrapyramidal signs, but only one had spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was correlated with more negative symptoms and poorer treatment outcome that was reflected in a longer time to and lower level of remission. There was no correlation of spontaneous extrapyramidal signs with age of patient, age at onset of psychotic symptoms, or baseline psychopathology. There was no difference between patients with and without spontaneous extrapyramidal signs in terms of the subsequent development of persistent tardive dyskinesia, but the patients with spontaneous extrapyramidal signs were more likely to develop parkinsonian side effects after 8 weeks of antipsychotic treatment. Extrapyramidal signs are present in a proportion of neuroleptic-naive, first-episode schizophrenic patients, which suggests an involvement of these signs in the schizophrenic process that probably reflects basal ganglia pathology. The presence of spontaneous extrapyramidal signs seems to have prognostic significance insofar as it is linked to a poorer outcome and longer time to remission. Spontaneous dyskinesia appears to be a relatively rare finding.

Polymorphic Drug Metabolism in Schizophrenic Patients With Tardive Dyskinesia

The metabolism of many neuroleptics cosegregates catalyzed by the polymorphic cytochrome P450 CYP2D6. The population can be phenotyped into extensive metabolizers (EM) and poor metabolizers (PM) with respect to this enzyme's activity. PM are likely to achieve higher than average concentrations of neuroleptic drugs in plasma, with an increased risk of extrapyramidal side effects, possibly including tardive dyskinesia. Sixteen white schizophrenic patients who had developed tardive dyskinesia during long-term neuroleptic treatment were phenotyped with debrisoquine and genotyped by CYP2D6-specific DNA amplification and EcoRI restriction fragment length polymorphism analysis. Only 1 (6%) of the 16 patients had a PM genotype, 8 (50%) were homozygous, and 7 (44%) were heterozygous EM. None had a CYP2D6 genotype indicative of ultrarapid debrisoquine hydroxylation capacity. The patients were also phenotyped with mephenytoin, a probe drug for another polymorphic cytochrome P450, CYP2C19. One patient was a PM of S-mephenytoin, which corresponds to the frequency found in healthy white volunteers. In conclusion, there was no overrepresentation of PM of debrisoquine or of S-mephenytoin among the 16 patients with neuroleptic-induced tardive dyskinesia. However, the PM of debrisoquine had the highest score on the Simpson-Angus Rating Scale and the second highest on the Abnormal Involuntary Movement Scale, despite a very low neuroleptic dose. Also, the debrisoquine MR correlated significantly with the SARS score (rs = 0.685, p < 0.05, N = 10), indicating a relationship between the degree of impaired CYP2D5 activity and the severity of extrapyramidal side effects during neuroleptic treatment.