Simpson-Angus Scale Scores Research Articles

Evaluation of the Efficacy and Safety of Adding Pregabalin to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Double-blind Placebo-controlled Clinical Trial

Objectives: This study aims to evaluate the efficacy and safety of adding pregabalin to standard antipsychotic treatment in patients with chronic schizophrenia. Methods: In this randomized, double-blind, placebo-controlled clinical trial, participants were 48 male inpatients aged 18-65 years with chronic schizophrenia but with clinically stable conditions. They were randomly divided into two groups of intervention (n=24) and control (n=24). The intervention group received 75 mg of pregabalin per day for three weeks which was increased to 150 mg per day from the fourth week to the end of the study, in addition to standard antipsychotic medication for six weeks. The severity of psychotic symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), and their movement disorder symptoms were evaluated by the Barnes Akathisia Rating Scale (BARS) and Simpson-Angus Scale (SAS) at baseline and at 3th and 6th weeks of the intervention. Collected data were analyzed using repeated measures ANOVA in SPSS v.20 software, considering P<0.05 as the statistically significance level. Results: No significant differences were observed in severity of disease based on the PANSS total score and its three subscales (positive scale, negative scale, and general psychopathology) and in the BARS and SAS scores at the end of 6th week in groups and between the two groups. Conclusion: Adding 150 mg of pregabalin to the standard antipsychotic treatment of patients with chronic schizophrenia is not effective in improving their psychotic symptoms, but it is well tolerated.

CYP2D6 Genotyping and Antipsychotic-Associated Extrapyramidal Adverse Effects in a Randomized Trial of Aripiprazole Versus Quetiapine Extended Release in Children and Adolescents, Aged 12-17 Years, With First Episode Psychosis.

The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.

Paliperidone induced sinus tachycardia in a patient with first episode of psychosis (FEP)

IntroductionThis is a presentation of the FEP of a 23 y.o. patient. The patient had a Duration of Untreated Psychosis (DUP) of 6 months and Duration of Untreated Illness (DUI) of six years. The therapeutic response and the adverse effects of Paliperidone are being described.ObjectivesTo investigate the tolerance of Paliperidone in a patient with FEP.MethodsThe patient was assessed regularly by the psychiatric team consisting of a CT doctor and one General Adult Consultant. Appropriate psychological assessments and investigations took place.ResultsUpon admission the patient appeared guarded. She also presented with weight loss and dehydration. Initial PANSS score was 173, positive subscale 41. The patient was initially treated with monotherapy 6mg of Paliperidone. However, the heart rate was around 100 bpm culminating as high as 156 bpm. The ECG indicated sinus tachycardia. The patient presented with serious EPSs and diarrhea. Simpson-Angus Scale score 10. Metoprolol 25mg was prescribed twice a day. The clinical team proceeded in cross titration replacing Paliperidone with Olanzapine. A brain CT scan was also performed, unremarkable. After 10 days of therapy the PANSS score reduced to 102, positive subscale 21.ConclusionsInitial sinus tachycardia is a common adverse effect of Paliperidone. However in this case the tachycardia was refractory in time even after the 7th day, making an alternative SGA trial necessary.DisclosureNo significant relationships.

T205. LUMATEPERONE IN THE TREATMENT OF SCHIZOPHRENIA: EVALUATION OF EXTRAPYRAMIDAL AND MOTOR SYMPTOMS IN 4 LATE-PHASE CLINICAL TRIALS

BackgroundStandard of care (SOC) antipsychotics exhibit efficacy at high dopamine D2 receptor occupancy (60%-80%), which is associated with increased risk of extrapyramidal symptoms (EPS). Lumateperone (lumateperone tosylate, ITI-007) is a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. Efficacy of lumateperone 42 mg (ITI-007 60 mg) has been established in randomized placebo-controlled trials and, in contrast to other antipsychotics, occurs at low D2 receptor occupancy (40%). In controlled trials, lumateperone 42 mg was well tolerated with a favorable safety profile. An open-label long-term study of patients with stable symptoms of schizophrenia switched from SOC antipsychotics to lumateperone 42 mg further supported the safety and effectiveness of lumateperone treatment.This post hoc analysis evaluated the incidence of EPS across short- and long-term studies of lumateperone in patients with schizophrenia.MethodsEPS data were pooled from 3 short-term placebo-controlled studies of lumateperone 42 mg in patients with an acute exacerbation of schizophrenia (Studies 005, 301, and 302); 2 of the studies (Studies 005 and 302) had risperidone 4 mg as an active control. Data from the open-label 1-year trial (Study 303) in patients who were switched from SOC antipsychotics to lumateperone 42 mg were utilized to evaluate EPS risk with long-term treatment. EPS assessments included incidence and time to onset of EPS-related treatment-emergent adverse events (TEAEs). EPS assessment scales included the clinician-rated Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Rating Scale (BARS), and the Simpson Angus Scale (SAS). Patients without akathisia (BARS ≤2) or parkinsonism (SAS ≤3) at baseline were evaluated for the emergence of BARS-confirmed akathisia (BARS >2) and SAS-confirmed parkinsonism (SAS >3) during treatment.ResultsThe pooled short-term safety population comprised 1,073 patients (placebo, 412; lumateperone 42 mg, 406; risperidone 4 mg, 255). The long-term open-label safety population comprised 239 patients who completed 1 year of treatment. In the pooled controlled studies, rates of EPS-related TEAEs were less for lumateperone 42-mg (3.0%) and placebo patients (3.2%) than risperidone (6.3%) patients. The most common EPS-related TEAE with lumateperone was akathisia (2.0%), which occurred less often than with placebo (2.9%) or risperidone (4.7%). Mean time to onset of EPS-related TEAEs was higher for the lumateperone group (17 days) compared with risperidone (9 days), and similar to placebo (14 days). Benztropine use was similar in lumateperone (2.5%) and placebo groups (2.2%) and higher in the risperidone group (9.0%); propranolol use was similar across groups (2.4–3.4%). Change from baseline in AIMS, BARS, and SAS scores was similar across groups.Similar to short-term treatment, long-term treatment with lumateperone was associated with a low incidence of EPS-related TEAEs (0.8%). In patients switched from SOC treatment to lumateperone 42 mg, the mean time to onset of EPS was 38 days. Initiation rates of benztropine and propranolol were low in the long-term study (1.7% and 0.3%, respectively). There were no notable changes in AIMS, BARS, or SAS scores during the 1-year treatment. In patients without BARS-assessed akathisia at baseline, BARS-confirmed akathisia occurred in 0.3% of patients. In patients without SAS-assessed parkinsonism at baseline, no patients had SAS-confirmed incidences of parkinsonism.DiscussionThis post hoc analysis supports the favorable EPS profile of lumateperone 42 mg in both acute and long-term treatment of patients with schizophrenia.

Randomized Controlled Trial of Paliperidone Extended Release Versus Risperidone for the Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

BackgroundThe efficacy or tolerability of paliperidone extended release (ER) in the treatment of methamphetamine (METH)-associated psychosis (MAP) is unknown. This study was designed to assess the tolerability and efficacy of paliperidone ER and risperidone for the treatment of MAP in China.MethodsThis 25-day randomized clinical trial involved 120 patients with acute MAP symptoms who were randomized to receive either paliperidone ER or risperidone from baseline to day 25 of an inpatient hospital stay. The primary outcome was changes in the severity of psychosis, which were assessed using the Positive and Negative Syndrome Scale (PANSS) total score changes from baseline to endpoint.ResultsOverall, 84% of the patients completed the entire study protocol. The PANSS total score, the Clinical Global Impressions-Severity of Illness scale (CGI-S) score, and a METH craving score assessed by a visual analog scale (VAS) showed statistically significant improvements from baseline for the patients in both groups (p < 0.01). The Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS) scores increased from baseline during treatment in both groups (p < 0.01); there were statistically significant differences between the treatment groups in the SAS scores (p < 0.01). Measures of hypermyotonia, salivation, and dizziness were significantly higher in the risperidone-treated patients than in the paliperidone ER-treated patients (all p < 0.05).ConclusionPaliperidone ER and risperidone had similar efficacy and were generally tolerable in the treatment of MAP; however, paliperidone ER had a more favorable adverse event profile than risperidone, particularly regarding extrapyramidal and prolactin-increasing effects.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01822730. Full date of first registration:03/28/2013.

Measuring movements in adolescents with psychosis using the Microsoft Kinect sensor: a pilot study exploring a new tool for assessing aspects of antipsychotic-induced parkinsonism.

The assessment of motor disturbances in antipsychotic-treated adolescent patients is often limited to the use of observer-based rating scales with interobserver variability. The objectives of this pilot study were to measure movement patterns associated with antipsychotic-induced parkinsonism in young patients with psychosis and initiating/treated with antipsychotics, using a computer application connected with the Microsoft Kinect sensor (Motorgame). All participants were assessed by neurological examination, clinical side effect rating scales (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, Barnes Akathisia Rating Scale, Simpson Angus Scale (SAS), and Abnormal Involuntary Movement Scale), and the Motorgame. Furthermore, speed of information processing and motor speed with subtests from the Brief Assessment of Cognition in Schizophrenia test battery was assessed. We included 21 adolescents with first-episode psychosis (62% treated with antipsychotics; males 38%; mean age 16±1.4years) and 69 healthy controls (males 36%; mean age 16±1.5years). Prolonged time of motor performance (TOMP) in the Motorgame was associated with higher SAS scores for arm dropping (p=.009). A consistent practice effect was detected (p<.001). We found no significant associations between TOMP and age, height, body weight, sex, antipsychotic dosage, or information processing speed. We found an uncorrected significant association between prolonged TOMP and shoulder bradykinesia. The Motorgame was found useful in assessing parkinsonian symptoms in early-onset psychosis and accepted by participants. Future studies of larger cohorts, including patients with high scores in clinical motor side effect scales, are required to establish solid validity of the novel test.

Study on risk factors of extrapyramidal symptoms induced by antipsychotics and its correlation with symptoms of schizophrenia

BackgroundExtrapyramidal symptoms (EPS) are one of the most common and neglected side effects during the treatment of schizophrenia. The risk factors of EPS in Chinese patients with schizophrenia and its...

Aripiprazole for the treatment of psychotic symptoms in patients with dementia with Lewy bodies: a case series.

PurposeThe core features of dementia with Lewy bodies (DLB) are cognitive fluctuations, visual hallucinations, and parkinsonian symptoms. Although there have been several reports on the efficacy of treatments for psychotic symptoms in patients with DLB, little is known regarding the treatment effects of aripiprazole. The aim of this study was to evaluate the efficacy and safety of aripiprazole for the treatment of psychotic symptoms in patients with DLB.Patients and methodsWe employed a 10-week, open-label study design with 11 patients who met the criteria for DLB. The patients had previously experienced persistent or intermittent delusions, hallucinations, or both for at least 1 month. Aripiprazole was initiated at a low dose (3 or 6 mg/day) and titrated to higher doses at 2-week intervals or more rapidly, as needed. The Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression-Severity (CGI-S) were administered at baseline and 1, 2, 4, 8, and 10 weeks later. The Simpson–Angus Scale (SAS), Clinical Dementia Rating (CDR), and Mini-Mental State Examination (MMSE) Scale were evaluated at baseline and at week 10. The NPI, CGI-S, and BPRS scores were compared between the baseline and each assessment point and between each assessment point and the one before assessment point. The SAS, CDR, and MMSE scores were compared between the baseline and the end point.ResultsThe mean NPI and BPRS scores improved until the fourth week; they significantly decreased at each assessment point compared to the previous one. Afterward, improvements slowed and continued without significant decrease. The median SAS scores significantly decreased at the end point compared to the baseline (P<0.05). The median MMSE score was higher at the end point than at the baseline (P<0.05).ConclusionThis study showed that aripiprazole may be effective and well tolerated for the treatment of psychotic symptoms in patients with DLB.

Characterization of neurological soft signs in a Brazilian sample of stable patients with schizophrenia.

Neurological soft signs (NSS) have been considered one of the target features and a potential endophenotype for schizophrenia. The present study aimed to characterize NSS in a sample of patients with chronic schizophrenia and to compare them with healthy control individuals. In this study, we evaluated the presence of NSS in a sample of stable patients (n = 24) diagnosed with schizophrenia according to DSM-IV criteria, recruited at the Schizophrenia Outpatient Clinic of Instituto Raul Soares, Belo Horizonte, state of Minas Gerais, southeastern Brazil. Assessment was made with the Brief Motor Scale (BMS), and extrapyramidal symptoms (EPS) were evaluated with the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). A control group (n = 21) was also submitted to the same battery of tests. We observed a significant difference in relation to BMS and SAS scores (p < 0.0001), revealing that individuals with schizophrenia present more NSS and EPS than healthy ones. BMS total scores correlated positively with SAS scores (r = 0.495, p = 0.014), but not with AIMS scores, indicating that NSS could be influenced by the intensity of EPS. Nevertheless, we observed that this relationship remained only for motor coordination tasks (r = 0.550, p = 0.005), while motor sequencing tasks were not influenced by EPS (r = 0.313, p = 0.136). The results suggest that NSS are more frequent in patients with schizophrenia and that motor sequencing tasks could be more specific to the syndrome.

Effect of integrated yoga on anti-psychotic induced side effects and cognitive functions in patients suffering from schizophrenia.

Background Twenty one (12 females) subjects, diagnosed with schizophrenia by a psychiatrist using ICD-10, in the ages 52.87 + 9.5 years and suffering since 24.0 ± 3.05 years were recruited into the study from a schizophrenia rehabilitation center in Bengaluru. Methods All subjects were taking anti-psychotic medications and were in stable state for more than a month. Psychiatric medications were kept constant during the study period. Assessments were done at three points of time: (1) baseline, (2) after one month of usual routine (pre) and (3) after five months of validated Integrated Yoga (IY) intervention (post). Validated 1 h Yoga module (consisting of asanas, pranayama, relaxation techniques and chantings) was practiced for 5 months, five sessions per week. Antipsychotic-induced side effects were assessed using Simpson Angus Scale (SAS) and Udvalg for Kliniske Undersogelser (UKU) side effect rating scale. Cognitive functions (using Trail making Test A and B), clinical symptoms and anthropometry were assessed as secondary variables. Comparisons between "pre" and "post" data was done using paired samples t-tests after subtracting baseline scores from them respectively. Results At the end of five months, significant reduction in drug-induced Parkinsonian symptoms (SAS score; p=0.001) and 38 items of UKU scale was observed along with significant improvement in processing speed, executive functions and negative symptoms of schizophrenia patients. No side effects of Yoga were reported. Conclusions The present study provides preliminary evidence for usefulness of Integrated Yoga intervention in managing anti-psychotic-induced side effects.

Prevalence and pattern of antipsychotic induced movement disorders in a tertiary care teaching hospital in India – a cross-sectional study

Objectives: To assess prevalence and pattern of movement disorders among patients taking antipsychotic medications.Methods: This cross-sectional, intensive monitoring (patient interview, case record form review and clinical examination) study was conducted in patients taking antipsychotic drugs irrespective of duration for the development of movement disorders. The psychiatrist used Modified Simpson-Angus Scale score (10-item scale), Barnes’ rating scale and Abnormal Involuntary Movement Scale to diagnose parkinsonism, akathisia and tardive dyskinesia, respectively. We assessed movement disorders for the preventability and seriousness.Results: The overall prevalence of antipsychotic induced movement disorders was 5.67% (95% CI: 4.19–7.62). The prevalence of parkinsonism, akathisia and tardive dyskinesia was 5.10% (95% CI: 3.71–6.98), 0.85% (95% CI: 0.39–1.84) and 0.57% (95% CI: 0.22–1.45), respectively. There was a trend of high proportions of movement disorders in extreme of age group, female gender, patients treated with conventional antipsychotics, on poly therapy, patients of epilepsy with psychosis, schizophrenia and bipolar mood disorder. The movement disorder was lowest with quetiapine (2.02%).Conclusions: The higher use of atypical antipsychotics had reduced the occurrence of movement disorders in our setup.

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder.

BackgroundAntipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described.ObjectiveThe objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methodsThe study included 64 male patients (average age 41.38 ± 10.14 years, median age 40 years, lower quintile [LQ] 35 years, upper quintile [UQ] 49 years). Bio-Rad CFX Manager™ software and “SNP-Screen” sets of “Syntol” (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and rs2863170. In every “SNP-Screen” set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels.ResultsResults of this study detected a statistically significant difference in the adverse drug reaction intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 ± 2.24 (10/10) versus 13 ± 2.37 (9/10; p < 0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 ± 1.59 (10/10) versus 6.41 ± 1.33 (9/10; p = 0.006) were revealed.ConclusionPolymorphism of the SCL6A3 gene can affect the safety of haloperidol, and this should be taken into account during the choice of drug and its dosage regimen.

Effectiveness of Yoga in Patients with Functional Psychotic Disorder

Background: The application of yoga as a therapeutic intervention, which began early in the twentieth century, takes advantage of the various psychophysiological benefits of the component practices. The physical exercises (asanas) may increase patient’s physical flexibility, coordination, and strength, while the breathing practices and meditation may calm and focus the mind to develop greater awareness and diminish anxiety, and thus result in higher quality of life. The present study was conducted to evaluate the effectiveness of Yoga in patients with functional psychotic disorder. Materials &amp; Methods: 100 patients with a diagnosis of functional non-affective psychosis were involved in the study. They were divided into 2 groups. Group I (Yoga) – It included 50 patients. Group II (Exercise)- It included 50 patients. The severity of clinical state was measured on Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression Severity (CGIS). Assessment was performed at the time of starting yoga/exercise as well as 2 and 6 weeks thereafter. At these 3 time points, the extra pyramidal (Parkinsonian) side-effects too were measured using Simpson Angus Scale (SAS). Results: Group I had 25 males and 25 females. Similarly group II had 25 males and 25 females. The difference was non significant (P – 1). College literate in group I was 15, in group II was 9. 22 patients and 23 patients were on second generation antipsychotics in group I and group II respectively. Illness duration was 20.4 years and 24.2 years in group I and group II respectively. Positive syndrome score was 19.2 and 19.1 in group I and group II respectively. Negative syndrome score was 16.8 and 17.1 in group I and group II respectively. General psychopathology score was 25.4 and 26.2 in group I and group II respectively. Total HDRS score was 61.8 and 61.2 in group I and group II respectively. Total HDRS Score was 13.8 and 14.2 in group I and group II respectively. Total SAS score was 3.2 and 3.4 years in group I and group II respectively. The difference was non significant (P &gt; 0.05). CGI illness severity score in group I, at baseline, 2weeks and 6 weeks was 6.04, 4.65 and 3.12 respectively. Similarly in group II, it was 6.18, 5.14 and 3.86 at baseline, 2weeks and 6 weeks respectively. The difference was significant (P &lt; 0.05). Positive syndrome score in group I, at baseline, 2 weeks and 6 weeks was 18.98, 13.84 and 7.8 respectively. Similarly in group II, it was 18.5, 14.82 and 9.22 at baseline, 2 weeks and 6 weeks respectively. The difference was significant (P &lt; 0.05). Negative syndrome score was significantly higher at 6 weeks in group II as compared to group I (P &lt; 0.05). General Psychopathology score was statistical significant at 2 weeks (P &lt; 0.05). Total PANSS score was statistical significant at 2 weeks (P &lt; 0.05). There was statistical significant difference (P &lt; 0.05) in HDRSS score in both groups. At 2 weeks the total SAS score was statistical significant among both groups (P &lt;0.05). Conclusion: Yoga may be beneficial in patients with psychotic disorder. This has additional advantage along with standard pharmacological management.

Overcoming Disembodiment: The Effect of Movement Therapy on Negative Symptoms in Schizophrenia-A Multicenter Randomized Controlled Trial.

Objective: Negative symptoms of patients with Schizophrenia are resistant to medical treatment or conventional group therapy. Understanding schizophrenia as a form of disembodiment of the self, a number of scientists have argued that the approach of embodiment and associated embodied therapies, such as Dance and Movement Therapy (DMT) or Body Psychotherapy (BPT), may be more suitable to explain the psychopathology underlying the mental illness and to address its symptoms. Hence the present randomized controlled trial (DRKS00009828, http://apps.who.int/trialsearch/) aimed to examine the effectiveness of manualized movement therapy (BPT/DMT) on the negative symptoms of patients with schizophrenia.Method:A total of 68 out-patients with a diagnosis of a schizophrenia spectrum disorder were randomly allocated to either the treatment (n = 44, 20 sessions of BPT/DMT) or the control condition [n = 24, treatment as usual (TAU)]. Changes in negative symptom scores on the Scale for the Assessment of Negative Symptoms (SANS) were analyzed using Analysis of Covariance (ANCOVA) with Simpson-Angus Scale (SAS) scores as covariates in order to control for side effects of antipsychotic medication.Results:After 20 sessions of treatment (BPT/DMT or TAU), patients receiving movement therapy had significantly lower negative symptom scores (SANS total score, blunted affect, attention). Effect sizes were moderate and mean symptom reduction in the treatment group was 20.65%.Conclusion:The study demonstrates that embodied therapies, such as BPT/DMT, are highly effective in the treatment of patients with schizophrenia. Results strongly suggest that BPT/DMT should be embedded in the daily clinical routine.

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Relating Spontaneously Reported Extrapyramidal Adverse Events to Movement Disorder Rating Scales.

Background:While antipsychotic-induced extrapyramidal symptoms (EPS) and akathisia remain important concerns in the treatment of patients with schizophrenia, the relationship between movement disorder rating scales and spontaneously reported EPS-related adverse events (EPS-AEs) remains unexplored.Methods:Data from four randomized, placebo- and haloperidol-controlled ziprasidone trials were analyzed to examine the relationship between spontaneously reported EPS-AEs with the Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Categorical summaries were created for each treatment group to show the frequencies of subjects with EPS-AEs in each of the SAS and BARS categories at weeks 1, 3, and 6, and agreement between ratings was quantified by means of weighted kappa (κ).Results:In general, we found greater frequencies of EPS-AEs with increasing severity of the SAS and BARS scores. The EPS-AEs reported with a “none” SAS score ranged from 0 to 22.2%, with a “mild” SAS score from 3.3 to 29.0%, and with a “moderate” SAS score from 0 to 100%. No subjects in any treatment group reported “severe” SAS scores or corresponding EPS-AEs. Agreement between SAS scores and EPS-AEs was poor for ziprasidone and placebo (κ < 0.2) and only slightly better for haloperidol. The EPS-AEs reported with “non questionable” BARS scores ranged from 1.9 to 9.8%, with “mild moderate” BARS scores from 12.8 to 54.6%, and with “marked severe” scores from 0 to 100%. Agreement was modest for ziprasidone and placebo (κ < 0.4) and moderate for haloperidol (κ < 0.6).Conclusions:These findings may reflect either underreporting of AEs by investigators and subjects or erroneous rating scale evaluations.

The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial.

Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder. This was a multinational, randomized, double-blind, placebo-controlled, flexible-dose study of cariprazine 3-12mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double-blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. Post-hoc analysis evaluated changes on YMRS single items. In each group, 118 patients received double-blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI-S scores versus placebo, with least square mean differences of -6.1 (p<0.001) and -0.6 (p<0.001), respectively. On each YMRS item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p<0.05). A significantly greater percentage of cariprazine patients than placebo patients met YMRS response (48% versus 25%; p<0.001) and remission (42% versus 23%; p=0.002) criteria at Week 3. Adverse events (AEs) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p<0.05). Based on Barnes Akathisia Rating Scale and Simpson-Angus Scale scores, more cariprazine than placebo patients experienced treatment-emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%). Cariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.

Clinimetric Evaluation of the Simpson-Angus Scale in Older Adults With Schizophrenia

Parkinsonism (or Parkinson's syndrome [PS]) remains common in patients exposed to antipsychotic drugs. One clinical tool used in its detection and follow-up, the Simpson-Angus Scale (SAS), has been under revision lately. We further examined the discriminative power of the SAS to detect PS and its efficacy as a measure of PS intensity in chronic schizophrenia. Fifty-six outpatients between 50 and 75 years of age, under stable antipsychotic drug therapy, provided consent to undergo an evaluation along the SAS and Unified Parkinson's Disease Rating Scale III motor subsection, split according to the presence or absence of PS defined in the UK Parkinson's Disease Society Brain Bank (UKPDSBB) criteria or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. The identification rate for PS was 39.3% based on UKPDSBB criteria applied to the Unified Parkinson's Disease Rating Scale III, compared with 62.5% and 87.5% according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and SAS cutoff value greater than 0.3, respectively. Median SAS scores for PS and PS-free participants were comparable. The SAS yielded high sensitivity (90.9%) but low specificity (17.7%). κ Values generally revealed only slight agreement between the group allocation provided by the SAS and the UKPDSBB criteria. Receiver operating characteristic curve for screening performance of the SAS provided poor prediction of subject status. The SAS lacks specificity and constitutes an imperfect detection and measurement tool for PS in older adults. Raising the cutoff score would avoid inflation in PS identification. The scale is probably best used as a measure of change relative to baseline score following an intervention, but results should be interpreted with caution.

Spontaneous parkinsonism is associated with cognitive impairment in antipsychotic-naive patients with first-episode psychosis: a 6-month follow-up study.

There is now growing evidence that parkinsonism and other extrapyramidal signs are highly prevalent in patients with first-episode psychosis who have never been exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis were enrolled on the study and followed up for 6 months. Seventy-seven completed assessments at 3 time points (baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor abnormalities. The Simpson-Angus Scale (SAS) was used for the assessment of extrapyramidal signs, and each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore the longitudinal relationships between parkinsonism scores and cognitive impairment. Parkinsonism scores showed significant strong longitudinal associations with deficits in memory, executive functioning, and attention. Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high 6-month predictive values for cognitive impairment. In addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia, akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor subscores on the SAS scale. These results emphasize the relevance of the assessment of parkinsonism signs prior to starting to administer antipsychotic drugs, as core manifestations of psychotic illness with a high predictive value for cognitive impairment.

Gray matter abnormalities in schizophrenia patients with tardive dyskinesia: a magnetic resonance imaging voxel-based morphometry study.

ObjectiveThe pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings.MethodHigh resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS).ResultsThe TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = −0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = −0.399, p<0.001), and PANSS general score (r = −0.338, p<0.05).LimitationsThe cross-section design can’t separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype.ConclusionsThe schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively.