Doses Of Neuroleptics Research Articles

Clinical Characteristics and Predisposing Factors in Acute Drug-Induced Akathisia

As subtypes of drug-induced akathisia have become accepted and attempts have been made at establishing diagnostic criteria, a prospective study of the clinical features and predisposing factors of acute akathisia is a significant deficiency in the literature. One hundred consecutive inpatients with non-organic psychotic disorders, not receiving neuroleptics or other drugs and free of akathisia and related disorders at admission, were assessed for psychiatric status and movement disorders at baseline and daily for 2 weeks, with detailed examinations on days 7 and 14. Multiple operational criteria for akathisia were used. The following risk factors were examined: age, sex, current neuroleptic dose, rate of increment of dose, drug type, duration of illness, past use of neuroleptics, extrapyramidal side effects score, Zung Depression Scale score, Spielberger State Anxiety Inventory score, psychosis score, and smoking. Using a global rating, mild akathisia developed in 41% and moderate-to-severe akathisia in 21%. The symptoms that best discriminated akathisia from non-akathisia were shifting weight from foot to foot or walking on the spot, inability to keep legs still, feelings of inner restlessness, and shifting of body position in the chair. The subjective and objective symptoms loaded on separate factors. Akathisia ratings had low correlations with the anxiety and Zung scores. Receiver operating characteristic analysis suggested a cutoff score of 4 on our 10-item Akathisia Scale as optimal for the diagnosis of akathisia, with a stricter criterion of scores of 2 or more on both the subjective and objective items being more suitable for research diagnosis. The most significant predisposing factors were the extrapyramidal side effects score and current neuroleptic dose and its rate of increment, with lesser contributions from serum iron status and medication type. Predictability was, however, modest. Acute akathisia is a common syndrome with well-defined clinical features. Its occurrence can be predicted with only modest accuracy.

Predicting Patterns of Clozapine Response in a Group of Chronic State Hospital Schizophrenics

Reports estimate that 30-60% of treatment refractory schizophrenics show at least a 20% decrease in BPRS when treated with clozapine. We assessed 14 schizophrenics refractory to traditional neuroleptics with MRI to determine whether brain morphology predicts the pattern of clinical response to clozapine after 2, 6 and 12 weeks. Baseline assessment revealed this sample of severely impaired schizophrenics (mean BPRS total=63, SD=10; mean preclozapine standard neuroleptic dose=2009 CPZ mg equiv./day and mean 12 week cloz dose=644 mg/day), relative to healthy controls, had reductions of cortical gray matter volume (mean head size- and age-corrected z-score=−1.55) and increases in cortical sulcal (mean z=.653) and ventricular CSF volume (mean z= 1.50); those patients with the highest BPRS total (BPRS tot) and positive symptoms (BPRS pos) tended to have less cortical gray matter volume in the frontal and temporal but not parietal regions (p≤.05), while patients with more negative symptoms (BPRS neg) tended to have smaller lateral ventricular volumes (p≤.05). Significant improvement occurred in BPRS pos at 6 weeks (p≤.05) and in BPRS tot at 12 weeks (p<. 05); paired t-tests for all other BPRS change scores were n.s.. A lower than expected % of subjects achieved a 20% improvement at each time period (0 % at 2 wks, 7 % at 6wks and 14 % at 12 weeks). A cluster analysis of BPRS tot change scores across time periods revealed 3 distinct response patterns: early responders (ER; n=5) improved by 2 weeks, delayed responders (DR, n=5) improved by 6 weeks, and non-responders (NR; n=4) did not improve after 12 weeks. To determine whether these response patterns could be predicted from baseline brain morphology and clinical status, the three groups were compared using non-parametric tests. The ER had significantly less cortical gray matter volume in anterior and temporal regions and more third ventricular CSF volume than either the DR or NR., but DR and NR did not significantly differ. The NR had significantly lower baseline BPRS pos and BPRS tot scores than the DR and the ER; the latter two groups did not statistically differ. In conclusion, the ER had the greatest brain volume deficits and the most severe clinical symptoms at baseline, whereas the NR showed the opposite pattern; the DR showed a mixed pattern, with smaller brain volume deficits but more severe symptoms.

Neuroleptic dose and schizophrenic symptoms. A survey of prescribing practices.

A study was conducted to survey the prescribing practices of neuroleptic doses in 100 consecutively hospitalized DSM-III-R schizophrenic patients. The relationship between doses and clinical and symptomatological variables was subsequently analyzed. Patients were evaluated through the Positive and Negative Syndrome Scale (PANSS). The peak mean dose in chlorpromazine equivalents was 1290 (range 250-7200). Haloperidol was the most commonly employed neuroleptic (67 patients). Neuroleptic doses were correlated with excitement, suspiciousness, hostility, uncooperativeness and poor impulse control. The neuroleptic doses administered in our hospital were similar to those found in other survey reports but higher than those recommended by the controlled dose-response studies. The correlation found between neuroleptic doses and symptoms of disruptive behavior suggests that we employed high-dose practices to treat the disruptive symptoms of schizophrenia. We concluded that it is useful to distinguish between the neuroleptic doses required to control the psychotic episode and those to treat the disruptive behavior.

Treatment of Acute Neuroleptic‐Induced Movement Disorders

Acute extrapyramidal syndromes (EPS), including dystonia, parkinsonism, and akathisia, are associated with the use of virtually all neuroleptic agents. They may be alleviated by reducing the neuroleptic dosage, switching to a lower-potency drug, or administering an adjunctive agent such as an anticholinergic, amantadine, benzodiazepine, or beta-blocker. Akathisia may be only partly dispelled by anticholinergics; alternatives are beta-blockers, benzodiazepines, and clonidine. In patients receiving long-term neuroleptic therapy, both the prophylactic use and the duration of treatment with concomitant anti-EPS drugs are controversial. Administration of prophylactic anti-EPS drugs should be based on the likelihood that the patient will develop EPS, as well as the risk of adverse reactions resulting from extended use of the agents in a specific patient. The decision to continue anti-EPS therapy should be reevaluated frequently, especially in elderly patients.

The Role of Parkinsonism and Antiparkinsonian Therapy in the Subsequent Development of Tardive Dyskinesia

Tardive dyskinesia (TD) is a side effect of prolonged neuroleptic treatment presenting as abnormal involuntary movements. This troublesome disorder occurs in only 15-30% of patients taking neuroleptics, suggesting that these individuals may be physiologically distinct so as to be predisposed. This study analyzed possible factors contributing to TD development. Fifty patients on depot neuroleptics for more than 7.1 years were prospectively examined for TD and drug-induced parkinsonism (DIP) using the Smith-Trims rating scale for an average of 5 years. The patients were assessed for the severity of the movement and if the movement increased or decreased with respect to neuroleptic dosage, anticholinergic dosage, parkinsonism, and other related factors. Both TD and DIP increased over time. In the patients whose dose of neuroleptic decreased, the increase in TD ratings was not significant. Using a forward stepwise regression DIP was found to increase as TD worsened but did not appear to predict subsequent TD development. Anticholinergic treatment showed a less significant correlation with the change in TD. These results have implications for the management of combined TD and DIP presentation.

Preliminary report: Cerebral blood flow abnormalities in older schizophrenic patients

We compared global and regional cerebral blood flow in 11 schizophrenic patients and 11 normal comparison subjects, all over the age of 45 years. The schizophrenic patients had lower global cortical uptake than the control subjects. Among the individual regions of interest, the schizophrenic patients had significant decrements in the left posterior frontal region and in the bilateral inferior temporal regions. The uptake did not correlate with age of onset or duration of schizophrenia, current daily neuroleptic dose, severity of psychopathology, or global cognitive impairment.

Clinical Significance of Diffuse Delta EEG Activity in Chronic Schizophrenia

1) Forty-three chronic schizophrenics with diffuse delta activity (DDA) in their rest-awake EEGs were compared with 23 chronic schizophrenics with normal EEGs. 2) The DDA group was divided into three sub-groups according to the temporal persistence of DDA: brief, intermittent, and prolonged. The intermittent DDA is analogous to intermittent rhythmic delta activity (IRDA). 3) The disorganized type of schizophrenia was frequent in the DDA group and the residual type was frequent in the normal EEG group. 4) The doses of neuroleptics, as well as those of phenothiazines and butyrophenones, were higher in the DDA than in the normal group. 5) The frequency of co-administration of carbamazepine was higher in the DDA than in the normal group, and the rate increased with the degree of abnormality. 6) In a 1 year follow-up of the DDA group, reducing doses of neuroleptics resulted in a tendency for DDA to disappear, and reducing the doses of adjunctive carbamazepine caused DDA to disappear. 7) There was no correlation between DDA and the psychiatric symptoms, intelligence level, or CT findings.

Dopamine D 2 receptor occupancy measured by single photon emission computed tomography with 123I-iodobenzamide in chronic schizophrenia

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide ( 123I-IBZM) was used to study 22 chronic schizophrenic patients. The patients, who were receiving maintenance therapy with typical neuroleptics, had not shown any significant improvement since their admission to the hospital. Basal ganglia/frontal cortex ratios of the uptake of 123I-IBZM did not show significant differences on the basis of neuroleptic dosage in chlorpromazine equivalents. There were, however, significant differences in 123I-IBZM uptake in the basal ganglia among patients characterized by negative, mixed and positive symptoms of schizophrenia. Although only a small number of patients had shown a positive response to treatment by the time of discharge, D 2 receptor blockade was significantly higher in responders than in nonresponders. In addition, there was an inverse correlation between reduced activation as measured by the Brief Psychiatric Rating Scale and the basal ganglia/frontal cortex ratio. These findings suggest a complex pathogenetic link between the blockade of dopamine D 2 receptors and psychopathology in chronic schizophrenic patients. SPECT studies with 123I-IBZM appear to have prognostic value in identifying chronic schizophrenic patients who respond poorly to neuroleptic treatment.

Admissions to a public residential facility for individuals with developmental disabilities: Change in neuroleptic drug use and tardive dyskinesia

Two studies were conducted to assess the change in neuroleptic medication dosages and prevalence of tardive dyskinesia (TD) in new admissions to three California Developmental Centers. The first study involved 636 admissions into Fairview, Porterville, and Sonoma Developmental Centers. Neuroleptic medication use was recorded at admission and one year later. Over that period of time, dose and prevalence of neuroleptic use was found to decrease dramatically. The second study investigated the existence of possible side effects associated with the withdrawal from neuroleptic medication. Persons with developmental disabilities (n=43) admitted to Fairview Developmental Center were examined at admission and every 8 weeks thereafter for the presence of TD. Daily neuroleptic dosages were recorded on five examination dates as well as at admission. Ten months after admission, subjects were grouped on the basis of neuroleptic medication status (withdrawn, reduced, no change). TD was manifested in 63% of the subjects in the completely withdrawn group, 29% of the subjects in the reduced group, and 10% of the subjects in the maintenance group. These studies indicate that new admissions to public residential facilities are likely to be receiving neuroleptic medication, that systematic evaluation will reslts in a majority being withdrawn from medication and that withdrawal TD will develop in most cases.

Effects of neuroleptic reduction in schizophrenic outpatients receiving high doses.

This paper presents an open study which evaluated the clinical effects of a partial and progressive reduction in neuroleptic medication in 32 outpatients suffering from schizophrenia who were receiving high doses (equivalent of > or = 18 mg of oral haloperidol per day; EHL). After an observation period of twelve weeks, each subject's dose of neuroleptics was reduced by 50% at the rate of 10% every four weeks. Patients were receiving a mean of 62 mg per day EHL at the beginning of the study and 30 mg per day EHL at the completion of the study. After the reduction, the following was observed: 1. a significant but modest change in psychopathology: a decrease in negative symptoms and in the total score on Brief Psychiatric Rating Scale; and 2. a significant increase in tardive dyskinesia symptoms. Six subjects relapsed but five of them recovered without increasing their reduced medication. Results of this study are discussed in the context of trying to find a minimal maintenance dose in the treatment of schizophrenia. The relative paucity of change despite a large reduction in medication argues for reevaluation of dosage in patients on high or very high doses of neuroleptics. The results suggest that many patients taking high doses could be maintained on significantly lower doses of neuroleptics. With gradual reduction of medication it would seem that many patients who are receiving a high dose of neuroleptic can achieve a lower dose than their current maintenance level.

Effects of zopiclone on sleep and symptoms in schizophrenia: Comparison with benzodiazepine hypnotics

1. Sleep variables and psychiatric symptoms were investigated in 6 male chronic schizophrenic outpatients. 2. The patients were being treated with benzodiazepine(BZD) hypnotics for more than 8 weeks, and BZDs were replaced with zopiclone (ZPC) 15 mg/day. 3. Polysomnographic examinations, subjective sleep assessments and BPRS scoring were performed during BZD therapy and at the end of 8 weeks of ZPC therapy. 4. The doses of neuroleptics and anticholinergic agents remained fixed throughout the study. 5. The amount of slow-wave sleep (SWS) was markedly small and that of stage 1 sleep was moderately large during BZD therapy. 6. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. 7. There were no significant change in the amount of SWS between the treatment. 8. Half of the patients exhibited a sleep-onset REM period (SOREMP) during ZPC therapy. 9. Both total BPRS score and negative symptom score were lower during treatment with ZPC than BZDs. 10. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZD hypnotics and that reduced SWS and SOREMP may be partly involved in the pathophysiology of schizophrenia.

Lower-Dose Therapy With Traditional Neuroleptics in Chronically Hospitalized Schizophrenic Patients

Several recent studies have shown that relatively low doses and low blood levels of neuroleptics are often as effective as high doses of these drugs both in the treatment of an acute exacerbation of schizophrenia^1-3and in the maintenance treatment of stabilized outpatients with schizophrenia.^4,5Yet, some patients with chronic schizophrenia or related disorders, hospitalized for extended periods, are treated with relatively high doses of neuroleptics for many years. The efficacy of low doses vs standard or high doses of traditional neuroleptics in this group of patients has not been extensively investigated and thus represents an important gap in the low-dose research and treatment strategy. This letter reports an attempt to address this important clinical question. <h3>Patients and Methods.</h3> In the course of clinical management of a service of chronically psychotic female patients, a program of neuroleptic dosage reduction combined with quantitative monitoring of their psychopathologic condition was

Predictors of tardive dyskinesia in first episode schizophrenia

Predictors of tardive dyskinesia were determined utilizing data on 70 patients who have been followed longitudinally in an ongoing prospective study of first episode schizophrenics at Hillside Hospital. TD development was predicted by poorer level of remission from first psychotic episode, longer duration of psychotic symptoms prior to study entry, poorer levels of early adolescent social adjustment, frontal horn enlargement and global impairment on neuropsychological testing. Neuroleptic dose was a trend level predictor of TD development. When level of remission and dose as a time dependent covariate were entered simultaneously, level of remission remained a significant predictor of time to TD (risk ratio =7.34, 95%CI=1.75, 30.87, χ2=7.40, df=1, p=.007) while the effects of dose were eliminated (risk ratio per 2 fluphenazine units = 1.02,95% CI = 0.95, 1.09, χ2 =0.29, df=1, p=.59). Our findings suggest that TD development is primarily a consequence of disease related vulnerability which is manifest with drug exposure, rather than a consequence of increased drug exposure.

Organic factors and the clinical features of late paranoid psychosis: a comparison with Alzheimer's disease and normal ageing

The diagnostic allocation and aetiological basis of paranoid psychoses with late onset is controversial. We examined the clinical features of patients with a diagnosis of paranoid psychosis and we compared their cranial computed tomography (CT) scans and electroencephalographic (EEG) recordings with findings from matched samples of patients with Alzheimer's disease and non-demented elderly controls. During a 5-year period, 81 patients (15 men and 66 women) with a diagnosis of paranoid psychosis and onset after age 50 were referred to our Institute. They represent 5.4% of the patients older than 50 admitted during the same period. More than half of these patients had first-rank symptoms. The ventricles, anterior and sylvian fissures of the paranoid group were larger than in non-demented controls but smaller than in Alzheimer's disease. The posterior dominant alpha EEG rhythm was slower than in normal aging and faster than in Alzheimer's dementia. If paranoid patients with first-rank symptoms were distinguished from the ones without, the former had less severe brain atrophy and faster posterior dominant rhythm, although they received higher doses of neuroleptics. This could be explained by the existence of at least 2 subgroups of late paranoid psychosis: late-onset schizophrenia and organic paranoid syndrome, the former characterized by first-rank symptoms and less severe brain atrophy, the latter by more severe EEG and CT scan changes with a closer resemblance to degenerative brain disease.

Reduced attention‐related negative potentials in schizophrenic adults

Event-related potentials were recorded from outpatient adult schizophrenics receiving maintenance doses of neuroleptics and from normal control subjects during performance of a reaction time task and a complex visual discrimination task, the Span of Apprehension. Difference potentials were computed to isolate endogenous activity associated with the processing demands of the Span task. Schizophrenics produce significantly less early endogenous negative activity than do normal subjects. This processing-related negativity reflects pattern matching activity to an attentional trace during the serial scan of the visual icon. We previously reported an identical reduction in processing-related negativity in childhood-onset schizophrenia, suggesting that this deficit is age independent. Both frontal contingent negative variation and an early frontal P3 were larger in the schizophrenics than in normal subjects, suggesting an inappropriate mobilization of nonspecific attentional resources. A later posterior P3 was significantly smaller in schizophrenics than in normal subjects.

Effects of brief neuroleptic discontinuation in chronic hospitalized schizophernic patients: no evidence for supersensitivity psychosis

As many as one third of patients suffering from schizophrenia have persistent severe psychotic symptoms despite high doses of neuroleptic treattaunt. Increased psychotic symptoms because of receptor sensitization psychosis has been proposed as possible side effects of chronic neuroleptic exposure. As part of a protocol to medicate chronic hospitalized treatment resistant schizophrenic patients (DSM-Ill-R and SADS/RDC) with clozapine, we evaluated the effects of discontinuing treatment with high doses of neuroleptics for evidence of a psychosis. Twenty chronic schizophrenic patients, hospitalized for at least 24 months, were tapered of all their neureleptic medication over an average of 42 days. All patients were on large doses of antipsychotic medication (mean + sd = 2058 4-1243 chlorpromazine equivalents). No significant differences were found in pairwise t-tests to evaluate BPRS scores between baseline, end of taper, one and three weeks medication free periods. Multivariate analysis for testing differences between BPRS subscales (positive, negative, agitation, affective) also showed no significant difference. in treatment-resistant chronic schizophrenic patients there is no evidence that high doses of neuroleptics are beneficial, as evidenced by the absence of any deterioration during a period of neuroleptic taper and withdrawal. There is also no support for the idea of a supersensitivity psychosis as evidenced by the absence of any increase in psychotic symptomatulogy.

The effects of neuroleptic dose adjustment on D2 receptor occupancy and schizophrenic symptomatology, a study using IBZM spect

The effects of neuroleptic dose adjustment on D2 receptor occupancy and schizophrenic symptomatology, a study using IBZM spect

Factors affecting rehospitalisation rates of chronic schizophrenic patients living in the community

Eight patients selected from a depot neuroleptic clinic in the hospital outpatients department were assessed clinically on various demographic and clinical variables with a view to determining the factors that may contribute to high rates of rehospitalisation amongst schizophrenics in remission. It was found that rehospitalisation rates during the preceding 5 years correlated with an early age of onset of illness, severity of positive and affective symptoms, current neuroleptic dose and total AIMS score, all reflecting the severity of underlying psychotic disorder and the neuroleptic treatment required to treat the psychosis. Poor compliance with neuroleptic prophylaxis was not found to be of importance in contributing to high relapse rates in this sample. It was concluded that patients who repeatedly relapse may do so because of the clinical characteristics of their illness.

Relationship between Neuroleptic Dose and Positive and Negative Symptoms

The present study explored possible connections between neuroleptic dose and the positive and negative symptoms of schizophrenic patients. Zero-order correlations between medication dose as measured in CPZ equivalent units and standardized assessments of positive (hallucinations, delusions) and negative (blunted affect, poor rapport) symptoms were carried out on 28 hospitalized schizophrenics. While dose was positively related to over-all negative symptom scores as well as specific negative symptoms, no relation was found with positive scores. The discussion focused on the possibility that negative symptoms might represent medication-induced side effects and the need for further research.

QEEG alpha1 changes after a single dose of high-potency neuroleptics as a predictor of short-term response to treatment in schizophrenic patients

Baseline quantitative electroencephalographic (QEEG) characteristics and their changes after a single test dose of either haloperidol or clopenthixol were investigated in a group of 29 schizophrenics as possible predictors of short-term response to those drugs. On baseline QEEG assessment, responders (R) to subsequent treatment showed fewer slow and more fast activities than nonresponders (NR). A large overlap between R and NR with respect to these measures was observed, however, revealing their practical inadequacy to predict short-term response in individual patients. On the contrary, changes in alpha1, observed 6 hr after the administration of a single test dose of either haloperidol or clopenthixol, discriminated to a very large extent between R and NR, correctly identifying 17 out of 18 R and 8 out of 10 NR. The QEEG test dose procedure might be used in the selection of the most appropriate antipsychotic drug for individual schizophrenic patients.