Extrapyramidal Side Effects Scale Research Articles

Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine.

Therapeutic efficiacy of the NMDA antagonist amantadine is reported in three acute neuroleptic free akinetic catatonic patients. Intravenous infusion of amantadine led to the resolution of catatonic symptoms and considerable...

Trihexyphenidyl (Artane) Dependence: A Controlled Investigation between Users and Abusers

This controlled study aims to identify the socioclinical factors predisposing psychiatric patients to abuse trihexyphenidyl (artane) and to document the extrapyramidal symptoms in artane abusers and users. Thirty patients (n=30), with mainly two major functional psychoses and who were abusing trihexyphenidyl, were compared with 90 artane user patients (n=90), who were matched for both the diagnosis and treatment. Besides a detailed clinical interview, each patient was assessed by using DSM-IIIR criteria, Brief Psychiatric Rating Scale, Simpson and Angus Scale, and Abnormal Involuntary Movement Scale. The analysis of data showed that, compared with users, trihexyphenidyl abusers were significantly characterized by being unmarried, unemployed, smokers and having past and concurrent history of multiple drug abuse, and genetic loading of mental disorders. Both groups of patients were prescribed antipsychotic drugs and trihexyphenidyl on a longer basis. Besides other socioclinical parameters, premorbid personalities, stressful life events and extrapyramidals, including tardive dyskinesias, we did not differentiate between the two groups. Artane abusers, when compared with users, were significantly characterized by less negative psychopathology. However, other psychopathological domains, in particular, the positive symptoms and depression, did not differentiate between abusers and users. In conclusion, patients having these socioclinical profiles tend to develop trihexyphenidyl abuse. The mental health professionals should not prescribe trihexyphenidyl indiscriminately or for a long time to such patients, who indeed require long-term antipsychotic maintenance medications.

Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dyskinesia.

This study examined the relationship of neuropsychological deficits and negative symptoms with tardive akathisia in chronic schizophrenic patients. Consecutive volunteers (n = 100) were recruited from Community Health Centres with a DSM-III-R diagnosis of schizophrenic disorder, chronic and on stable medication. Subjects were subgrouped into tardive akathisia (TA), tardive dyskinesia (TD) and control groups using four sets of criteria. Detailed single examinations were performed using the following measures: sociodemographic, illness-related and treatment-related variables, Negative Symptom Rating Scale (NSRS), Abnormal Involuntary Movement Scale (AIMS), Rating Scale for Extrapyramidal Side-Effects (EPSE), Akathisia Rating Scale, Barnes Akathisia Rating Scale, and a brief neuropsychological test battery. Group comparisons and logistic regression analyses were performed in order to test the significance of findings. TA ratings showed a significant association with NSRS subscale scores, and with some neuropsychological test scores (Symbol Digits Modalities Test, and to a lesser extent Trail Making Test and Finger Tapping Test). TD scores showed a consistent association with age, and a less consistent association with gender, and their association with NSRS subscale scores and neuropsychological dysfunction was positive but less significant. Higher EPSE scores predicted TA and limb truncal (LT) dyskinesia. In conclusion, TA showed a more significant association with some clinical indices of organic brain dysfunction than the oral-lingual-buccal-facial dyskinetic syndrome. Prospective studies are necessary to determine whether organicity is a vulnerability factor for TA. Both our data and the published literature suggest that the movement disorder seen in TA and TD is but one feature of complex syndromes that include motor and cognitive features.

ICI 204,636, an Atypical Antipsychotic

ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.

Ball experiments in 32 acute akinetic catatonic patients: deficits of internal initiation and generation of movements.

We undertook ball experiments in 32 akinetic catatonic patients in order to determine specific functional deficits in the motor system in akinetic catatonia. Standardized ball experiments (catching, throwing, stopping, kicking) were conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21. Additionally, associated psychopathology was evaluated using different scales on days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale, the Hamilton-Anxiety Scale, the scale for the assessment of negative symptoms (SANS), and the Simpson scale for extrapyramidal side effects (SEPS). Significantly more patients were able to perform more externally guided tasks (catching, stopping) than internally guided tasks (throwing, kicking). Patients showed significantly more posturing and awkward movements on day 0 than on day 21. There was a significantly positive correlation between hypokinetic extrapyramidal features (SEPS) and negative symptoms with their cognitive alterations (SANS) on day 0. The findings suggest a deficit of internal initiation, as in parkinsonism, as well as a dysfunction in the generation of voluntary movements in akinetic catatonia. We assume an underactivity in the dorsolateral prefrontal cortex and the supplementary motor area with consecutive down-regulation of the cortical-striatal-thalamic circuit, the "motor loop," in catatonia.

Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients

Gender differences in onset of illness, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. Patients with first-episode schizophrenia were examined to determine whether gender differences also occur in these patients. Fifty-four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied beginning in an initial stage of the first hospitalization for psychosis while undergoing treatment with a standardized medication regimen. Before antipsychotic drug treatment and during 1 year of follow-up each patient was rated on the Schedule for Affective Disorders and Schizophrenia--Change Version (psychosis and disorganization items), Scale for the Assessment of Negative Symptoms, Clinical Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and prolactin levels were determined weekly for the first 6 weeks. The female schizophrenic patients had a later onset and better treatment response than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin levels from baseline to weeks 1 through 6 were greater among the women. Gender differences in onset and degree of treatment response in first-episode schizophrenic patients are similar to those of chronic patients and are apparent at early stages of the illness. The greater pharmacologic responsivity of the female patients, as indicated by the neuroendocrine results, is consistent with the gender difference in degree of symptom improvement with medication.

Randomized, Double-Blind, Controlled Trial of Risperidone Versus Clozapine in Patients With Chronic Schizophrenia

This study compares the antipsychotic efficacy and the tolerability of risperidone and clozapine in patients with schizophrenia. Patients were randomized to double-blind treatment with risperidone, 4 mg (N = 20), risperidone, 8 mg (N = 19), or clozapine, 400 mg (N = 20), daily for 28 days. Efficacy was assessed by improvement of psychotic symptoms, measured on the Brief Psychiatric Rating Scale, and Clinical Global Impression. The tolerability was assessed by the Simpson and Angus scale for extrapyramidal side effects (EPS), the Association for Methodology and Documentation in Psychiatry (AMDP) scale for somatic side effects, spontaneous reports of adverse events, clinical laboratory assessments, and vital signs. All treatments reduced psychotic symptoms. The global tolerability was significantly better in the risperidone than in the clozapine-treated patients (p < 0.01). There were no differences between treatments on the AMDP scale. The most frequent spontaneously reported adverse effects were dizziness, fatigue, accommodation disturbance, and EPS in all treatment groups and increased salivation, mainly in the clozapine-treated patients. Although there were no changes in vital signs during risperidone treatment, clozapine was associated with a mean reduction in heart rate of 10 beats/minute. Risperidone tolerability at endpoint was classified as "very good" by 60 and 47% of patients treated with risperidone, 4 and 8 mg daily, respectively; the corresponding figure in clozapine-treated patients was 30%. The results suggest that risperidone is at least as effective as an antipsychotic as clozapine, providing a valuable new approach for the treatment of schizophrenia.

Effect of subtle neurological dysfunction on response to haloperidol treatment in schizophrenia

The primary purpose of this study was to assess whether an interaction between subtle neurological impairment and haloperidol plasma level affects treatment response and, if so, the impact on negative symptoms in particular. Forty-three schizophrenic and two schizoaffective inpatients diagnosed according to Research Diagnostic Criteria were given, at the end of a 1-week placebo period, a baseline evaluation consisting of the Brief Psychiatric Rating Scale (BPRS), Scales for the Assessment of Positive and Negative Symptoms, Quantified Neurological Scale, and the Simpson-Angus Scale for extrapyramidal side effects. Subjects were randomly assigned to one of three haloperidol plasma ranges and treated for 6 weeks. At the end point the BPRS, Scales for the Assessment of Positive and Negative Symptoms, and Simpson-Angus Scale were readministered. Multiple linear regressions were used to assess the extent to which the interaction between neurological abnormality and haloperidol plasma level predicted the end-point symptoms once the baseline symptoms, neurological abnormality, and haloperidol plasma level were accounted for. Those patients with higher levels of overall abnormality on the Quantified Neurological Scale at baseline and with frontal dysfunction in particular, had, with increasing haloperidol plasma levels, more severe negative symptoms at end point. Neurological dysfunction was not related to end-point positive symptoms. The effect was specific to end-point negative symptoms and was independent of extrapyramidal side effects. If confirmed, these findings may indicate that relatively intact frontal function is needed for improvement in negative symptoms and that those patients with schizophrenia who have subtle neurological dysfunction should be treated with lower doses of neuroleptics.

Treatment of extrapyramidal side effects with terguride

Terguride, a partial dopamine agonist, was administered in a 4-week open clinical trial to 17 schizophrenic patients suffering from extrapyramidal side effects of neuroleptic treatment. The neuroleptic dosage was kept constant. The mean final daily dose of terguride reached 3.4 mg (SD = 2.0). Fourteen patients completed the trial. Total scores on the Rating Scale for Extrapyramidal Side Effects and the Brief Psychiatric Rating Scale showed a significant improvement of 69% and 40%, respectively. There was also a significant improvement in all BPRS factor scores.

Relationship between extrapyramidal symptoms and serum anticholinergic levels in treated chronic schizophrenics

Serum anticholinergic levels were measured by radioreceptor assay (RRA) in schizophrenic patients treated for drug-induced Parkinsonism; 68 patients stabilized on a single neuroleptic and an anticholinergic antiparkinsonian agent (benzhexol, benztropine or procyclidine) were assessed using the extrapyramidal side effects (EPS) scale prior to each blood sampling. Serum anticholinergic levels showed a significant inverse correlation with EPS but did not appear to be dose-related in any of the three anticholinergic drug groups. Percentage binding to proteins was significantly less with benztropine than either benzhexol or procyclidine. Serum-free anticholinergic levels correlated significantly with total serum levels in the benzhexol and procyclidine groups but not in the benztropine group. At serum levels above 4.5 pmol/ml atropine equivalents, EPS was significantly less than at levels below that. We discuss the implications of this finding and suggest practical clinical applications of measurement of serum anticholinergic levels. Serum neuroleptic and serum prolactin levels did not correlate with either dose or serum level of anticholinergics.