Sociospatial behavioral relationships among hospitalized psychiatric patients

The present study was an attempt to investigate hypotheses about the interrelationship of brain dysfunction and symptoms of schizophrenia using the Brief Psychiatric Rating Scale (BPRS) and a measure of cerebral ventricular size. The ventricular brain ratio (VBR) was correlated with admission and discharge scores on the BPRS in 46 schizophrenic patients. A significant relationship was found between VBR and discharge BPRS scores. In general, the results were partially supportive of relationships found between neuropsychological data and the BPRS in a previous study, but shed little light on the relationships between brain damage and negative and positive symptoms. Limitations of using the BPRS, as well as possible sampling variations, are discussed.     

Prefrontal sulcal prominence is inversely related to response to clozapine in schizophrenia

The object of this study was to determine if brain computed tomography (CT) scan measures are related to treatment response to clozapine, an atypical antipsychotic drug that is effective in some therapy-resistant schizophrenic patients. Thirty-four therapy-resistant patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) before and after 6 weeks of treatment with clozapine. The patients were classified into Nonresponders, Moderate Responders, and Good Responders based on the percent change in BPRS. Comparison of these groups on prefrontal sulcal prominence (PSP) indicated a statistically significant linear trend, with nonresponders having the highest, moderate responders an intermediate degree, and good responders the least PSP. There were no linear trends for the ventricular-brain ratio (VBR), and no quadratic trends for either brain measure. A similar linear trend relating PSP to four of five BPRS subscales, including both positive and negative symptoms, was observed. The relationship between PSP and treatment response was also assessed with multiple linear regression, and PSP significantly contributed to prediction of BPRS at 6 weeks. The results are discussed with regards to the hypothesis that the effect of clozapine on psychopathology depends on prefrontal cortical function.     

Effect size of symptom status in withdrawal of typical antipsychotics and subsequent clozapine treatment in patients with treatment-resistant schizophrenia

OBJECTIVE: In light of the efficacy of newer antipsychotic agents and the possibility that drug withdrawal may negatively affect subsequent drug response, concern has arisen that the use of placebo in schizophrenia research may be unethical. This study examines the effect size of symptom exacerbation during drug washout with placebo and the effects of drug washout on the efficacy of subsequent drug treatment. METHOD: Fifty patients with treatment-resistant schizophrenia hospitalized on a research unit participated in a double-blind longitudinal study of the effects of drug washout after chronic treatment with a typical antipsychotic and before prospective treatment with clozapine. Brief Psychiatric Rating Scale (BPRS) scores were analyzed to examine drug effects and effect sizes for baseline treatment with a typical antipsychotic (>6 months treatment), drug washout with placebo (mean=34 days), early treatment with clozapine (mean=42 days, mean dose=345.0 mg/day), and optimal clozapine treatment (mean=83 days, mean dose=450.5 mg/day). RESULTS: Patients' BPRS total, positive, and negative symptom scores significantly increased during placebo washout, compared with baseline treatment, and significantly decreased with administration of clozapine, compared with placebo washout and baseline treatment. However, 30% of patients showed some symptom improvement during placebo washout. The effect sizes for the BPRS total score were 0.63 for baseline treatment versus placebo washout, 1.10 for optimal clozapine treatment versus placebo washout, and 0.82 for optimal clozapine treatment versus baseline treatment. CONCLUSIONS: Symptom exacerbation induced by drug withdrawal in patients with treatment-resistant schizophrenia did not impede subsequent responsiveness to clozapine. The effect size for clozapine, compared with typical antipsychotics, suggests that the drug-washout longitudinal design is useful for establishing a drug-free baseline and for investigating drug response, while requiring relatively few subjects.     

Sulpiride and perphenazine in schizophrenia. A double-blind clinical trial

Seventeen patients with acute schizophrenia and 30 with chronic schizophrenia were included in a randomized, double-blind parallel-group trial comparing sulpiride and perphenazine. Patients were evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS) prior to the onset of treatment and 1 and 2 weeks, and 1, 2, 3, and 4 months thereafter. In patients with acute schizophrenia, total BPRS scores declined significantly at the end of the trial compared with pretreatment values in sulpiride-treated patients but not in schizophrenics treated with perphenazine. Differences in response between the groups did not reach statistical significance, however. For patients suffering from chronic schizophrenia, a statistically significant decline was observed in total BPRS scores at 4 months compared with pretreatment scores in both sulpiride and perphenazine groups. There was no significant difference in the treatment response between the groups. Sulpiride appeared to be somewhat more effective than perphenazine for treatment of acute schizophrenia. Efficacy of both compounds was less marked in chronic forms of schizophrenia.     

Early prediction of antipsychotic response in schizophrenia

OBJECTIVE: The authors' goal was to examine the predictive value of early symptom changes indicating response to antipsychotic medication in schizophrenia. METHOD: One hundred thirty-one acutely ill patients with schizophrenia received 4 weeks of fluphenazine treatment. Brief Psychiatric Rating Scale (BPRS) ratings were obtained at baseline and weekly. The authors examined the relationship between changes in BPRS total score and each factor score following 1 week of treatment and ultimate response status, defined as a reduction of 20% or more in total BPRS score. RESULTS: None of the patients who [corrected] displayed an improvement of less than 20% in total [corrected] BPRS score and only 5% [corrected] of the [corrected] patients who displayed a reduction of less than 20% in BPRS thought disturbance [corrected] score after 4 weeks of treatment had been classified as responders at 1 week (i.e., 100% and 95% specificity) [corrected] CONCLUSIONS: These data suggest that patients with minimal improvement in positive symptoms during the first week of treatment with a typical antipsychotic are unlikely to respond to a 4-week trial. These data require confirmation and extension to studies with second-generation antipsychotics.     

Effects of mianserin in chronic schizophrenia.

1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. Twenty inpatients with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 5-HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. There were no significant changes in MHPG levels between the two groups. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment.     

Haloperidol. Plasma levels and prolactin response as predictors of clinical improvement in schizophrenia: chemical v radioreceptor plasma level assays

The relationship between clinical response of schizophrenic patients to haloperidol and (1) blood levels of the medication, determined by both gas-liquid chromatography (GLC) and radioreceptor (RR) assays, or (2) prolactin response to the medication, was examined in an inpatient study using several fixed doses of haloperidol. Regression analysis disclosed a substantial curvilinear relationship between steady-state GLC-determined plasma haloperidol levels and decrease in Brief Psychiatric Rating Scale (BPRS) Psychosis factor scores; however, no substantial relationship was found between clinical response and RR plasma haloperidol levels or serum prolactin response to haloperidol. Our results suggest that steady-state plasma levels of haloperidol determined by the GLC chemical assay are a better predictor of decreases in BPRS Psychosis factor scores than RR assayed plasma haloperidol levels or prolactin response to haloperidol.     

Late life depression

The relationship between TaqI A dopamine D₂ receptor (DRD ₂) polymorphism and therapeutic response to bromperidol, a selective dopamine antagonist, was investigated in 30 acutely exacerbated schizophrenic inpatients. Patients were treated with bromperidol 6–18 mg/day for 3 weeks. Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The TaqI A genotypes were determined with the PCR method. There was no significant difference in the percentage improvement of total BPRS or 5-subgrouped symptoms (positive, negative, anxiety-depression, excitement and cognitive symptoms) after the 3-week treatment between the patients with A1 alleles (n=18) and those with no A1 allele (n=12). Although the present study is preliminary, it is suggested that the TaqI A DRD ₂ polymorphism is not associated with therapeutic response to bromperidol in schizophrenic patients. Received: 27 September 2000 / Accepted: 10 January 2001     

Does akathisia influence psychopathology in psychotic patients treated with clozapine?

BACKGROUND: Akathisia has been reported to predict more severe symptoms and poorer treatment response to typical neuroleptics among patients with schizophrenia. Akathisia has also been associated with symptom exacerbation. This study addressed four questions: 1) Does akathisia predict greater severity in global psychopathology? 2) Is this effect global or specific? 3) Does clozapine treatment alter this relationship? 4) Does severity of psychopathology covary with the level of akathisia? METHODS: Akathisia and clinical symptoms were examined in 33 "treatment refractory" schizophrenic patients treated with clozapine across 16 weeks. Weekly ratings were Barnes Akathisia Rating Scale, Abbreviated Dyskinesia Rating Scale, and Brief Psychiatric Rating Scale (BPRS). Patients were classified as "with" (n = 15) or "without" (n = 18) akathisia. Data analyses involved independent t-test comparisons of selected variables, between-group multivariate analyses of variance across time for BPRS Total scores and Guy's five factors, and partial correlations to assess covariation between BPRS scores and level of akathisia. RESULTS: Akathisia predicted more severe global psychopathology, specific to the Activation (AC) and Thought Disturbance (TH) factors. These relationships did not change with clozapine treatment even when akathisia declined. Interestingly, level of akathisia did not covary with severity of psychopathology. CONCLUSIONS: In this sample, akathisia predicted more severe psychopathology, specific to AC and TH BPRS factor scores. Clozapine treatment did not alter this relationship. Although the presence of akathisia predicted more severe symptoms, the level of akathisia did not covary across time with severity of psychopathology, suggesting an "uncoupling" of these symptom domains.     

首发精神分裂症患者认知功能相关因素的5年随访

目的探讨首发精神分裂症患者在急性期和维持治疗期认知功能与精神症状和社会功能的关系。方法对164例首发精神分裂症患者进行随访观察,于治疗前、治疗12周末、治疗1年末、2年末、3年末、4年末、5年末各做1次韦氏成人智力量表、韦氏记忆量表、铁槽铁钉测验、手指敲击试验、动作功能测验、手功能协调测验、连线测验A和B、威斯康星卡片分类测验(WCST)及言语流利性测验等10项神经心理测查及简明精神症状评定量表(BPRS)、阴性症状评定量表(SANS)、功能总体评定量表(GAF)评定。结果治疗前各项认知功能测查结果与BPRS、SANS、GAF均无显著相关(P>0.05);治疗12周末、治疗1年末、2年末手指敲击测验、动作功能测验、总记忆商(MQ)等与BPRS总分显著相关(P<0.003);治疗12周末、治疗1年末、2年末、3年末、5年末铁槽铁钉测验、手指敲击测验、手功能协调性测验、智商(IQ)、MQ等与SANS、GAF总分显著相关(P<0.003)。结论治疗前首发精神分裂症患者认知功能与阳性症状、阴性症状、社会功能相互独立;维持治疗期随着疾病的演变,它们之间的相关性也在发生着变化。     

利培酮改善颅脑损伤患者精神障碍及促进神经功能恢复的观察

目的：观察利培酮对颅脑损伤所致精神障碍患者精神病量表、神经功能及生存品质（QOL）的影响。方法：98例颅脑损伤患者中65例伴有精神障碍,将其随机分为观察组（33例）及对照组（32例）,另外33例不伴精神障碍患者作为空白组。所有患者入院后根据病情行临床常规治疗。其中观察组使用利培酮及对照组使用舒必利对症处理伴发精神障碍。观察对比所有患者治疗前及治疗后第2、4、8周时的神经功能缺损评定量表（NIHSS）评分、简明精神病量表（BPRS）评分及日常生活能力量表（ADL）评分,以判断患者神经功能恢复情况、治疗效果及QOL。结果：观察组与对照组治疗前NIHSS、BPRS评分均高于空白组,ADL评分低于空白组（P＜0．05）,而两组间比较差异无统计学意义（P＞0．05）。3组患者经治疗后,NIHSS、BPRS评分均随着时间推移逐渐下降,ADL评分均有所上升,且治疗后第2、4、8周与同组治疗前比较,差异均存在显著意义（P＜0．05）;观察组与对照组比较,治疗后第2周NIHSS、BPRS评分差异无统计学意义（P＞0．05）,而治疗后第4、8周观察组NIHSS、BPRS评分明显低于对照组,ADL评分明显高于对照组（P＜0．05）;且治疗后第8周,观察组的NIHSS、BPRS、ADL评分几乎接近空白组,差异无统计学意义（P＞0．05）。结论：利培酮对颅脑损伤所致精神障碍患者具有良好疗效,能促进患者神经功能的恢复,降低精神病评分,改善患者的QOL。     

Auditory evoked potentials in schizophrenic patients before and during neuroleptic treatment

Summary The auditory evoked potential (AEP) components N1 and P2 were investigated under a no-task condition in a group of 14 acutely ill unmedicated schizophrenic patients and compared with the findings in an age- and sex-matched control group. In the patients, N1 latency was significantly increased, P2 latency and N1-P2 interpeak latency were reduced. There were significant relationships between AEP parameters and the psychopathological state evaluated by means of the brief psychiatric ratings scale (BPRS). The N1 and P2 latencies were negatively correlated with the BPRS subscore anergia and positively correlated with agitation. In 8 of the patients, a standardized neuroleptic treatment was started with 10 mg haloperidol/day. After 2 weeks of treatment, BPRS scores and N1 amplitude had significantly decreased. However, there was no relationship between BPRS improvement and N1 amplitude reduction. N1 latency in the unmedicated state was negatively correlated with subsequent therapeutic response measured as proportional improvement of the BPRS score within 2 weeks. Thus, N1 latency may be seen as a psychophysiological measure with prognostic applications.     

Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.     

Does neuroanatomy predict ECT response?

1. 1. Structural neuropathologic abnormalities have been associated with severe psychiatric illnesses, including bipolar disorder, major depressive disorder, and schizophrenia. In the latter, ventricular enlargement has been variably associated with symptom severity and poor treatment response. In patients with severe depressive disorders, the relationship between cortical and subcortical pathology and ventricle enlargement, symptom severity, and response to treatment is far from clear.

2. 2. The present study investigated the relationship between structural CNS pathology, symptom severity and treatment response in patients undergoing ECT. It was hypothesized that patients with greater neuroanatomic abnormalities would demonstrate greater initial symptom severity and poorer response to ECT.

3. 3. The subjects were 57 patients with unipolar or bipolar depression admitted for ECT treatment. Symptom severity was quantified using the Hamilton Depression Rating Scale (HRSD) at baseline and post-ECT.

4. 4. Lateral and third ventricle-brain ratio (LVBR, 3VBR) were determined from CT scans and cortical atrophy was rated by a faculty neuroradiologist.

5. 5. Contrary to our first hypothesis, structural pathology was not associated with baseline symptom severity. In terms of treatment response, the number of treatments required to achieve benefit was correlated with larger 3VBR; CT variables were not related to total post-treatment or change in HRSD score. Third ventricle enlargement may be an index of generalized pathology or regional brainstem abnormalities that influence ECT response rate by limiting individual seizure efficacy or neurochemical responsiveness, thereby necessitating a greater number of ECT treatments, without significant impact on overall response.

     

Therapeutic effects of bromperidol on the five dimensions of schizophrenic symptoms

Therapeutic profiles of bromperidol and their relationship with plasma drug concentration and prolactin response were investigated in 30 acutely exacerbated schizophrenic patients treated with randomly allocated fixed-doses of bromperidol (6, 12 or 18 mg/day) for 3 weeks. The mean values (+/- S.D.) of percentage improvement at 3 weeks in total Brief Psychiatric Rating Scale (BPRS) and five subgrouped symptoms were 59.8+/-29.2% for total, 64.6+/-37.5% for positive, 73.3+/-33.7% for excitement, 80.2+/-45.5% for cognitive, 43.1+/-46.5% for negative and 49.6+/-46.8% for anxiety-depression symptoms, respectively. Twenty (67%) of 30 patients were responders defined as having 50% or more symptom reduction significantly greater in responders than those in nonresponders after 2 weeks. Mean plasma bromperidol concentration in patients with 50% or more reduction in positive symptoms was significantly higher than in the others (8.2+/-4.7 vs. 4.1+/-1.8 ng/ml, P< .05). Percentage improvement in total BPRS at 1 and 2 weeks were correlated well with that at 3 weeks. These findings suggest that an early improvement in positive and anxiety-depression symptoms results in favorable outcome of total response to bromperidol treatment. Plasma drug monitoring may have a limited predictive value for improvement in positive symptoms.     

Symptomatic response to antipsychotics differs between recent onset and recurrent chronic schizophrenic patients.

The symptomatic response to standard antipsychotic treatment was assessed over the first 4 weeks of hospitalisation in 39 patients with DSM-III schizophrenia, active phase, using the Brief Psychiatric Rating Scale (BPRS). While highly significant improvement was noted overall, 36% of patients either did not improve or worsened. Furthermore there was no diminution in the withdrawal-retardation factor of the BPRS. Patients experiencing their first admission to hospital, all with recent-onset illness, were then compared with patients who presented with a recurrence and had illness of at least 3 years duration. Despite similarities in overall response, withdrawal-retardation scores did not diminish in recent-onset patients, in contrast to multiple admissions who demonstrated significant improvement. These findings suggest greater responsiveness of negative symptoms to treatment in patients with longstanding illness, and possibly a poorer prognosis in first admission patients with deficit manifestations.     

Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis in schizophrenia. The objective of this study is to evaluate whether DUP and premorbid level of social functioning are related to treatment response in acute treatment of first-episode schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed with BPRS, SAPS, and SANS on admission and discharge during their first hospitalisation. Percentage of the difference between admission and discharge in total scores of all scales were taken as measures of absolute symptom reduction. The median DUP was 6 months (mean=8.6). DUP was correlated with reduction in BPRS and SAPS scores but not SANS scores. Patients with a short DUP (n=41) also showed a higher reduction in BPRS, and SAPS scores than those with a long DUP. Premorbid Adjustment Scale (PAS) scores were inversely correlated with age at onset and positively correlated with BPRS scores at admission. We did not find any relationship between PAS scores and response to treatment. Our findings suggest that DUP may be an important predictor of response in acute treatment of first-episode schizophrenia and thus, attempts for early diagnosis may also have a positive effect on acute treatment response.     

Age of illness onset and schizophrenic symptomatology during an inpatient washout period

The authors examine the relationship between the age of illness onset and the ability to tolerate a medication-free period in a sample of acutely ill schizophrenic patients. Patients were admitted to an inpatient research unit for the treatment of acute and recurrent psychiatric symptoms. Prior medications were discontinued upon admission to the unit for purposes of clinical research and behavioral assessment uncontaminated by medication side effects. The age of illness onset was significantly and positively correlated with the duration of hospital washout. Furthermore, age of illness onset was significantly correlated with the BPRS total score and the BPRS hostility/suspiciousness factor measured at the end of washout. Our results suggest that early onset schizophrenics deteriorate more rapidly in an acute episode than do their later age of onset counterparts.     

Predicting antipsychotic drug response - replication and extension to six weeks in an international olanzapine study

OBJECTIVE: To use the degree of response after 2 weeks of treatment to predict non-response at 4 to 6 weeks. METHOD: Post-hoc re-analysis of a large multi-centered double-blind trial including 1996 patients with schizophrenia using receiver-operator curves and logistic regression analyses to predict non-response at 4 weeks and at 4-6 weeks from the percentage BPRS change at weeks 1 and 2. The primary non-response criterion was a less than 25% BPRS reduction from baseline. RESULTS: A 0% BPRS reduction at 2 weeks predicted non-response at 4 weeks with a positive predictive value of 77.1%; and sustained non-response at weeks 4, 5 and 6 with a positive predictive value of 75.8%. In a secondary last-observation-carried forward-analysis a less stringent cutoff of < or =15% BPRS reduction was associated with an acceptable positive predictive value (75%), with even higher sensitivity (76%). CONCLUSIONS: Those patients who showed little to no reduction of symptoms at week 2 were unlikely to show even minimal response at weeks 4 to 6. There is increasing evidence that such patients may benefit from a change in treatment.     

Pretreatment EEG predicts short-term response to haloperidol treatment.

This study analyzed the relationship between pretreatment electroencephalogram (EEG) and response to haloperidol medication in a group of acutely exacerbated schizophrenic patients (n = 34). Improvement was assessed after 3 and 6 weeks of treatment; it was measured globally, as decrease in the total score on the Brief Psychiatric Rating Scale (BPRS), as well as multidimensionally through the individual BPRS factors. Relative powers from four clinical EEG frequency bands were employed as predictor variables. Baseline alpha activity was significantly related to clinical response. Higher alpha values were associated with poorer response to treatment. Specifically, improvements on the "thought disturbance" and "hostility-suspiciousness" factors underlied the relationship between the pretreatment EEG and outcome.