Hillside Akathisia Scale Research Articles

Correction: Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study.

Introduction The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. Methods One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). Results Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). Discussion An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study.

The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Antagonism of the adenosine A2A receptor attenuates akathisia-like behavior induced with MP-10 or aripiprazole in a novel non-human primate model

Akathisia is a subset of the larger antipsychotic side effect profile known as extrapyramidal syndrome (EPS). It is associated with antipsychotic treatment and is characterized as a feeling of inner restlessness that results in a compulsion to move. There are currently no primate models available to assess drug-induced akathisia; the present research was designed to address this shortcoming. We developed a novel rating scale based on both the Barnes Akathisia Rating Scale (BARS) and the Hillside Akathisia Scale (HAS) to measure the objective, observable incidence of antipsychotic-induced akathisia-like behavior in Cebus apella non-human primates (NHPs). To induce akathisia, we administered the atypical antipsychotic aripiprazole (1mg/kg) or the selective phosphodiesterase 10A (PDE10A) inhibitor MP-10 (1–3mg/kg). Treatment with both compounds produced significantly greater akathisia scores on the rating scale than vehicle treatment. Characteristic behaviors observed included vocalizations, stereotypies, teeth grinding, restless limb movements, and hyperlocomotion. Adenosine A2A receptor antagonists have previously been shown to be effective in blocking antipsychotic-induced EPS in primates. The selective A2A receptor antagonist, SCH 412348 (10–30mg/kg), effectively reduced or reversed akathisia-like behavior induced by both aripiprazole and MP-10. This work represents the first NHP measurement scale of akathisia and demonstrates that NHPs are responsive to akathisia-inducing agents. As such, it provides a useful tool for the preclinical assessment of putative antipsychotics. In addition, these results provide further evidence of the utility of A2A receptor antagonists for the treatment of antipsychotic-induced movement disorders.

Akathisia and Suicidal Ideation in First-Episode Schizophrenia

Patients with first-episode schizophrenia (FES) are known to be notably sensitive for developing extrapyramidal adverse effects, but the relation of akathisia and suicidal ideation has rarely been studied. The current report is an ongoing analysis of an 8-week double-blind randomized controlled multicenter trial in 289 FES, comparing risperidone and haloperidol. Assessments were conducted weekly and included the Hillside Akathisia Scale and 21-item Hamilton Depression Rating Scale ratings. Suicidal ideation was significantly associated with clinician observed akathisia, depressed mood, younger age, and use of propranolol. The allocated treatment, anxiety, and nervousness had no influence. The present findings suggest a promoting effect of akathisia on suicidal ideation can not be ruled out in patients with FES.

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, chi2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, chi2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, chi2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.

Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia

This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder. This was a long-term (22-week), randomized, double-blind, parallel clinical trial. Sixty patients (mean age, 35.4 years) were randomly assigned to either olanzapine ( n=30) or fluphenazine ( n=30). They received treatment at three centers in Croatia during a 22-week study period and were assessed weekly for the first 6 weeks and monthly thereafter. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Rating Scale (PANSS) and the Clinical Global Impression (CGI) Severity and Improvement scores. The Hillside Akathisia Scale (HAS), Simpson–Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), vital signs, laboratory tests, and treatment-emergent adverse events were assessed to evaluate safety. The olanzapine group showed significantly greater mean decreases from baseline to endpoint for BPRS total (−25.8 vs. −16.5, P=.035), PANSS total (−45.7 vs. −29.5, P=.037), PANSS positive (−13.0 vs. −7.9, P=.034), and CGI Severity (−2.2 vs. −1.3, P=.031) scores. The olanzapine group showed greater mean decreases on all measures of extrapyramidal symptoms, significantly so for the SAS (−2.1 vs. 1.9, P=.004) and HAS (−3.4 vs. 2.6, P=.028). Patients in the fluphenazine group experienced a higher incidence of treatment-emergent adverse events (76.7% vs. 50.0%, P=.032). Weight gain was the most frequently reported adverse event in the olanzapine group (16.7% vs. 0.0%, P=.020). Akathisia (30.0% vs. 10.0%, P=.053) and insomnia (20.0% vs. 0.0%, P=.010) appeared most frequent in the fluphenazine group. Daily use of anticholinergics and benzodiazepines were both significantly greater for the fluphenazine group ( P=.003 and .04, respectively). No significant changes were observed in vital signs, ECG, or clinical chemistry. The study indicates that olanzapine has advantages in both efficacy and safety compared to fluphenazine; however, the small sample size limits our ability to draw definitive conclusions.

Serum iron and ferritin in acute neuroleptic akathisia

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5±14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56.94±39.54 ng/ml) and iron (88.52±40.0 mg/dl) levels in these patients were within the normal range (ferritin 30–300 ng/dl, iron 80–180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.

Risk factors for the development of neuroleptic induced akathisia

Neuroleptic induced akathisia (NIA) is a common and distressing side effect of antipsychotic treatment. Incidence rates are reported to be between 25% and 75%, depending on criteria used for diagnosis. The results of our four week prospective naturalistic study are based on the assessment of 73 inpatients, which were started on antipsychotic medication in one of the inpatient units of the Department of Psychiatry. NIA was rated with the Hillside Akathisia Scale. Assuming that both, objective as well subjective phenomena are necessary for a valid diagnosis of NIA, we calculated an incidence rate of 22.4%. 75% of all NIA cases occurred within the first three days of antipsychotic treatment. When attempting to determine risk factors for the development of NIA, we found a significant influence of dose increase in the first days of treatment.

A conceptual model of quality of life in schizophrenia: description and preliminary clinical validation.

The utility of quality of life (QOL) as an evaluative tool in clinical psychiatric research and drug trials could be enhanced by developing appropriate conceptual models of QOL, specific for psychiatric disorders. In our proposed model, QOL of individuals maintained on antipsychotic drug therapy for schizophrenia, is viewed as the subject's perception of the outcome of an interaction between severity of psychotic symptoms, side-effects including subjective responses to antipsychotic drugs, and the level of psychosocial performance. In order to test the validity of the model in clinical setting, we selected a sample of 62 schizophrenic patients clinically stabilized on antipsychotic drug therapy, and measured their subjective QOL and other potentially relevant clinical and psychosocial factors. Standardized scales including the positive and negative syndromes scale (PANSS), abnormal involuntary movements scale (AIMS), Hillside Akathisia scale (HAI), and the social performance schedule (SPS) were used for this purpose. Results of a multiple regression analysis using subjective quality of life as the outcome variable, indicated that severity of schizophrenic symptoms (partial R2 = 0.32, p < 0.0001) and subjective distress caused by akathisia (partial R2 = 0.11, p < 0.01) and neuroleptic dysphoria (partial R2 = 0.06, p < 0.05), accounted for nearly half of the variance, while the contribution from the psychosocial indicators was negligible. These results broadly endorse key aspects of the proposed model, and suggest further studies in this direction. These results experiences during antipsychotic therapy can enhance patients' QOL. This conceptual model has been developed with particular focus on the impact of antipsychotic medications on the QOL of persons with schizophrenia. As such, it is more applicable to clinical trials of new antipsychotic medications but may not be broad enough to be applicable for other social or vocational interventions.

The Hillside Akathisia Scale: a reliability comparison of the English and German versions

Akathisia usually consists of two components, subjective restlessness and typical movements such as shuffling of the legs, pacing, shifting weight from one leg to the other, and rocking movements of the trunk. The ability to measure akathisia reliably is essential for the assessment of treatments for akathisia and for the evaluation of drug-induced side effects in general. To date, investigators have generally used self-constructed assessment scales without reporting data about reliability or validity. The Hillside Akathisia Scale (HAS) has two subjective and three objective items for which anchored rating points are provided. Reliability was 0.89 for the HAS total score. Reliability for rating subjective symptoms ranged from 0.86 to 0.92, and the objective scores ranged from 0.51 to 0.89. The correlation between HAS and a global assessment of akathisia (modified CGI) was 0.87. These values compare favorably with the original report on the scale indicating that the Hillside Akathisia Scale can validly quantify akathisia with a satisfactory degree of interrater reliability.