Barnes Akathisia Rating Scale Scores Research Articles

Adjunctive Memantine Treatment of Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Study.

This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of memantine augmentation to standard regimen of antipsychotic treatment on psychotic symptoms and cognitive function in individuals with chronic schizophrenia for 8 weeks. Forty stabilized individuals with chronic schizophrenia were randomized in a 1:1 ratio to memantine (20 mg/d) and control (placebo) groups, along with their antipsychotic regimen for 8 weeks. The efficacy of treatment was assessed by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition Scale, and the safety was measured by the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale at baseline and at weeks 4 and 8. No significant differences were observed in demographic or clinical variables between both groups at baseline. During the study, all subscales and total scores of PANSS decreased significantly within both groups, except the subscale score in memantine, which was found to be positive. Reduction in general subscale and total scores of PANSS was significantly higher in the control group compared with the memantine group. All subscale scores of the Brief Assessment of Cognition Scale increased significantly only in the memantine group. The increase in the Verbal Memory, Working Memory, Verbal Fluency Letter, and Verbal Fluency Total subscale scores was significantly higher in the memantine group than in the control group. There was no significant difference in the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale scores between the 2 groups during the study. This study showed that adjunctive memantine to antipsychotic regimen improved the verbal memory, learning, verbal letter fluency, and working memory without improvement on psychotic symptoms in individuals with chronic schizophrenia.

F45. THE EFFICACY AND SAFETY OF BLONASERIN AFTER SWITCHING FROM OTHER ATYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIC INPATIENTS: AN OPEN-LABEL, MULTI-CENTER TRIAL

BackgroundThe aim of this study was to investigate the efficacy and safety of blonanserin treatment after switching from other atypical antipsychotics in schizophrenic inpatients who showed inadequate efficacy and poor tolerability.MethodsA total of 63 schizophrenic inpatients (inadequate response group=45 and poor tolerability group=18) were included in this study. They were already treated with atypical antipsychotics except blonanserin and not favored due to inadequate responses or intolerable adverse effects. Blonanserin was administered during 12 weeks after switching from their previous antispsychotics. Treatment response was evaluated with Brief Psychiatric Rating Scale (BPRS) and CGI-S, and safety profile were measured with Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Extrapyramidal Side effects Scale (SAR)S and Barnes Akathisia Rating Scale (BARS). Drug Attitude Inventory (DAI-10) and Subjective Well-being Under Neuroleptic Treatment (SWN) were used for subjective estimates. Assessments were done at baseline, 1, 2, 4, 8 and 12 weeks after blonanserin treatment. Repeated measures of ANOVA were done to analyze the group (inadequate vs. intolerable group) and time effects.ResultsCGI and BPRS were showed significant treatment responses after switching to Blonaserin. Time effects were significant at 2, 4, 8, 12 weeks after switching and group by time effect were also significant at that time. Mean changes of AIMS, SARS and BARS scores were not significant throughout test trial. Although SWN was significantly improved after switching to Blonaserin, it was not found significant group by time effect.DiscussionThe results suggest that blonanserin may be effective and well tolerable in schizophrenic patients who showed inadequate treatment response or poor tolerability.

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.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Adjunctive Aripiprazole for Schizophrenia or Schizoaffective Disorder Inadequately Treated With Quetiapine or Risperidone Monotherapy

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104). The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia. clinicaltrials.gov Identifier: NCT00325689.

Quetiapine Extended Release

Quetiapine is an atypical antipsychotic agent with well established efficacy and tolerability in the acute and maintenance treatment of adults with schizophrenia. The extended-release formulation of quetiapine (quetiapine XR) was developed to provide more convenient once-daily administration, as well as allowing simple and rapid dose escalation, with the aim of improving compliance (known to be a substantial issue in patients with schizophrenia). In several short-term clinical trials, oral quetiapine XR 400-800 mg once daily was generally effective across a range of symptoms in the acute treatment of schizophrenia. As a long-term maintenance treatment, quetiapine XR prevented relapse in patients with stable disease, with significantly longer times to relapse in patients treated with quetiapine XR compared with placebo. Quetiapine XR was generally well tolerated in clinical trials. According to pooled results from three 6-week trials, events occurring in >or=5% of quetiapine XR recipients with an incidence>or=2-fold that seen in placebo recipients were dry mouth, somnolence and dizziness. A generally low incidence of extrapyramidal symptoms (EPS) is seen in quetiapine XR recipients. The most common potentially EPS-associated adverse events seen with quetiapine treatment were akathisia, restlessness and tremor. Rates of worsening of Simpson-Angus Scale and Barnes Akathisia Rating Scale scores were not dissimilar among quetiapine XR, quetiapine immediate release and placebo.

Taq1A polymorphism in the dopamine D2 receptor gene as a predictor of clinical response to aripiprazole

We investigated whether the clinical response to aripiprazole differed according to the Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene. In this 26-week, prospective, open-label, double-blind, parallel-group study, 90 patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder were recruited and divided into two groups according to their DRD2 genotype (A1A1, n = 14; A1A2+A2A2, n = 76). The efficacy assessment included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) scores. Extrapyramidal symptoms were assessed using the Simpson–Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Rating Scale (BAS). Plasma prolactin levels were also measured. Patients with the A1A1 genotype showed a more favorable therapeutic response to aripiprazole when assessed using the PANSS ratio. The changes in the SAS score from baseline to week 4 also differed according to the genotype group. There were no significant differences in the changes in the CGI, AIMS, and BAS scores or plasma prolactin level between the two genotype groups. The results suggest an association between the DRD2 Taq1A polymorphism status and the variation in the clinical response to aripiprazole.

Efficacy and Tolerability of Oral Paliperidone Extended-Release Tablets in the Treatment of Acute Schizophrenia

To evaluate the efficacy and safety of an extended-release (ER) formulation of paliperidone in patients with an acute episode of schizophrenia, in the dosage range of 3 to 15 mg daily. A pooled analysis of 3 similarly designed 6-week, multicenter, double-blind, randomized, fixed-dose, placebo-controlled studies in 1326 patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score of 70-120) was performed. Patients were randomly assigned to receive 3, 6, 9, 12, or 15 mg daily of paliperidone ER or placebo. Efficacy and safety assessments were performed. The primary endpoint was change in PANSS total score from baseline to endpoint. PANSS total, PANSS subscale factor, and Personal and Social Performance scale scores significantly improved at endpoint for all doses of paliperidone ER relative to placebo (p <or= .001). A significantly greater proportion of paliperidone ER-treated patients at all doses achieved a clinical response compared with placebo (p <or= .001). Treatment-emergent adverse events (TEAEs) occurred in 66% to 77% of patients in the paliperidone ER groups and 66% of patients in the placebo group; serious TEAEs occurred in 6% of patients who received placebo and 5% to 6% of paliperidone ER-treated patients. Regardless of treatment group, median Simpson-Angus Rating Scale global, Abnormal Involuntary Movement Scale total, and Barnes Akathisia Rating Scale scores were 0 at both baseline and endpoint. There were no clinically relevant differences in measures of body weight gain, glucose handling, lipid metabolism, or proportion of patients with abnormal corrected QT intervals on electrocardiography and no important differences between the proportion of patients who received paliperidone ER or placebo who reported potentially glucose- or prolactin-related events. Paliperidone ER given once daily for 6 weeks appears to be a safe, well-tolerated, and effective treatment for patients with acute schizophrenia.

Switching from other antipsychotics to once-daily extended release quetiapine fumarate in patients with schizophrenia

ABSTRACTObjective: To evaluate the clinical benefit, efficacy and tolerability of switching patients experiencing suboptimal efficacy or tolerability with their current antipsychotic to once-daily extended release quetiapine fumarate (quetiapine XR).Research design and methods: 12-week, multicenter, open-label study in adult, in- or outpatients with schizophrenia. Quetiapine XR (mg/day) was initiated during a 4-day cross-titration phase (day 1: 300; day 2: 600; days 4–84: 400-800 [flexible-dosing]). The primary endpoint was the percentage of patients achieving clinical benefit (improvement on the Clinical Global Impression-Clinical Benefit [CGI-CB] scale). Secondary endpoints included CGI-Improvement (CGI-I) and Positive and Negative Syndrome Scale (PANSS) total scores. Tolerability was assessed by adverse events (AEs), Simpson–Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) scores. Changes in rating scale scores were analyzed using analysis of covariance and are presented as least squares mean (LSM) changes using the baseline level as a covariate.Results: Of 477 patients switched to quetiapine XR, 77.6% completed treatment. Following switching, 295 of 470 patients adequate for evaluation (62.8%) achieved a clinical benefit (95% confidence interval [CI] 58.4, 67.1; p < 0.0001). Significant improvements in LSM (95% CI) CGI-I of 2.88 (2.67, 3.08) and the LSM change in PANSS total scores of −12.3 (−14.95, −9.58) were observed (both p < 0.001). Common AEs included somnolence (17.8%), sedation (15.1%), dizziness and dry mouth (14.0% each). The incidence of extrapyramidal symptoms (EPS) was 8.0%. Mean improvements from baseline in SAS and BARS scores were −2.1 and −0.4, respectively (both p < 0.001).Conclusions: Switching to quetiapine XR was associated with clinical benefit and good efficacy and tolerability.

The impact of ω-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: An open-label pilot study

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or ω-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining ω-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of ω-3 fatty acids (180 mg EPA + 120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.

Safety and tolerability of quetiapine in the treatment of acute mania in bipolar disorder

Objective To review the safety/tolerability of quetiapine in four placebo-controlled studies in patients with bipolar I disorder experiencing acute mania. Methods Four double-blind, placebo-controlled studies evaluated quetiapine monotherapy (12 weeks) or quetiapine in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 68.6 μg/mL) (Li/DVP) (3 and 6 weeks) in patients with acute mania. Pooled data from the two monotherapy studies and the two combination therapy studies have been evaluated in the analysis presented here. Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded. Results Most adverse events were mild to moderate. Common adverse events (≥ 5% and at least twice the placebo rate) with quetiapine monotherapy and combination therapy were somnolence, dry mouth, weight gain, dizziness, asthenia, pharyngitis, and postural hypotension. Treatment-related discontinuations due to adverse events were not significantly different between quetiapine and placebo, nor was the incidence of extrapyramidal symptoms (including akathisia) (quetiapine monotherapy 12.9% vs placebo 13.1%; combination therapy 21.4% vs placebo 19.2%). Mean change from baseline to endpoint in SAS and BARS scores was not significantly different between groups. Mean weight change at treatment end with quetiapine compared with placebo was + 1.8 vs − 0.15 kg in monotherapy; and + 1.97 vs + 0.27 kg with combination therapy. No patients discontinued due to weight gain. The effect of quetiapine monotherapy on serum prolactin levels was no different from placebo. Conclusions Quetiapine monotherapy and combination therapy were well tolerated in the treatment of acute mania.

Placebo‐level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania

To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.

Combined Effects of Itraconazole and CYP2D6*10 Genetic Polymorphism on the Pharmacokinetics and Pharmacodynamics of Haloperidol in Healthy Subjects

This study was to evaluate the combined effects of the CYP3A4 inhibitor itraconazole and the CYP2D6*10 genotype on the pharmacokinetics and pharmacodynamics of haloperidol, a substrate of both CYP2D6 and CYP3A4, in healthy subjects. Nineteen healthy volunteers whose CYP2D6 genotypes were predetermined were enrolled (9 for CYP2D6*1/*1 and 10 for CYP2D6*10/*10). Four subjects (1 for CYP2D6*1/*1 and 3 for CYP2D6*10/*10) did not complete the study because of adverse events. The pharmacokinetics of haloperidol and its pharmacodynamic effects measured for QTc prolongation and neurologic side effects were evaluated after a single dose of 5 mg haloperidol following a pretreatment of placebo or itraconazole at 200 mg/d for 10 days in a randomized crossover manner. Itraconazole pretreatment increased the mean area under the time-concentration curves (AUCs) of haloperidol by 55% compared to placebo pretreatment (21.7 +/- 11.3 vs 33.5 +/- 29.3 ng h/mL). The subjects with CYP2D6*10/*10 genotype showed 81% higher AUC compared to that of subjects with CYP2D6*1/*1 genotype (27.6 +/- 22.2 vs 50.2 +/- 47.1 ng h/mL). In the presence of itraconazole, subjects with CYP2D6*10/*10 showed 3-fold higher AUC of haloperidol compared to that of placebo pretreated subjects with CYP2D6*1/*1 genotype (21.7 +/- 11.3 vs 66.7 +/- 62.1 ng h/mL; P < 0.05). The CYP2D6*10 genotype and itraconazole pretreatment decreased the oral clearance of haloperidol by 24% and 25%, respectively, but without a statistical significance. In the subjects with both CYP2D6*10 genotype and itraconazole pretreatment, however, the oral clearance was significantly decreased to 42% of subjects with wild genotype in the placebo pretreatment (4.7 +/- 3.6 vs 2.0 +/- 1.9 L/h/kg; P < 0.05). Barnes Akathisia Rating Scale (BARS) of subjects with CYP2D6*10/*10 in the presence of itraconazole pretreatment was significantly higher than that of subjects with CYP2D6*1/*1 genotype in the period of placebo pretreatment. Except for this, all other pharmacodynamic estimations did not reach to statistical significance although each CYP2D6*10 genotype and itraconazole pretreatment caused higher value of UKU side effect and BARS scores. The moderate effect of CYP2D6*10 genotype on the pharmacokinetics and pharmacodynamics of haloperidol seems to be augmented by the presence of itraconazole pretreatment.

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)