Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol

BACKGROUND: Prolactin levels are elevated to varying degrees by antipsychotics. Prolactin elevations may result in sexual and other adverse effects, and they may be related to antipsychotic effects. We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level, to explore the relation between clinical effects and prolactin level, and to determine the relationship between plasma levels of antipsychotics and prolactin level. METHOD: Treatment-resistant patients (133 men, 24 women) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind, randomized, 14-week trial comparing clozapine (N = 40), olanzapine (N = 39), risperidone (N = 41), and haloperidol (N = 37). Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5, 8, 10, 12, and 14 during the trial. Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale. Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available. Data were gathered from June 1996 to December 1999. RESULTS: Risperidone caused significant elevation of prolactin levels (p <.05) that appeared to be dose-dependent. Clozapine and olanzapine were associated with decreases of prolactin, whereas haloperidol led to a minor, nonsignificant increase. Plasma olanzapine and prolactin levels were correlated. Prolactin levels were not related to clinical improvement or extrapyramidal side effects. CONCLUSION: Antipsychotics show major differences in their effects on prolactin, and risperidone has clearly the most robust effect.     

Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder

OBJECTIVE: To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder. METHOD: One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point. RESULTS: Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint. CONCLUSIONS: Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.     

Neurocognitive effects of clozapine,olanzapine, risperidone,and haloperidol in patients with chronic schizophrenia or schizoaffective disorder

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.     

氯氮平合并利培酮治疗难治性精神分裂症

目的：了解氯氮平全早培酮的治疗难治性精神分裂症的疗效和安全性。方法：２６例符合ＣＣＭＤ－２－Ｒ精神分裂症诊断标准且临床判断属于难治性病人,予氯氮平合并利培酮治疗,疗程８周,分别在治疗前及治疗后进行阳性与阴性症状量表（ＰＡＮＳＳ）和不良瓜症状量表（ＴＥＳＳ）评定。结果：合并治疗８周后部是性,阴性及一般精神病理分治疗前后均有显著差异。ＴＥＳＳＵ叫分治疗前后无显著差异。副反应主要为静坐不能,肌张力增高,     

利培桐合并氯氮平治疗难治性精神分裂症观察

目的 观察利培酮合并氯氮平治疗难治性精神分裂症的疗效。方法 对32例难治性精神分裂症用利培酮2－6mg／日、氯氮平50－250mg/日治疗共12周,入组前及治疗后2、4、8、12周经BPRS评定。结果 两药合并治疗对难治性精神分裂症有效率为46．88％,治疗中无因明显副反应而停药者。结论 两药合并治疗难治性精神分裂症不失为一种有效的治疗方法。     

A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder

OBJECTIVE: The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. METHOD: Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks. RESULTS: The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants. CONCLUSIONS: Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.     

Acceptability and disintegration rates of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: To investigate the disintegration profile, acceptability, and tolerability of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder. METHOD: Ten patients stable for at least 10 days on monotherapy with oral risperidone 2 mg to 4 mg taken once daily were switched for 7 days to an equivalent dosage of orally disintegrating risperidone. Visual assessments for time to initial and complete disintegration were collected at each visit. Clinical Global Impression of Severity scores were collected at baseline and at the last visit. Patient acceptance of the new formulation, rated according to a visual analog scale, was obtained at the last visit. RESULTS: All patients maintained stable clinical status. Mean time to initial disintegration was 5.1 seconds, SD 0.8, and mean time to complete disintegration was 29.4 seconds, SD 18.4. The formulation was rated as very acceptable. Adverse events were reported by 5 patients; all were mild. CONCLUSION: The orally disintegrating risperidone tablets were well tolerated and rated as very acceptable by all patients.     

Efficacy and safety of long-acting risperidone in elderly patients with schizophrenia and schizoaffective disorder

BACKGROUND: Elderly patients are often an underserved population in terms of optimizing treatment outcomes. Long-acting risperidone, the first long-acting injectable atypical antipsychotic, can improve outcomes through continuous medication delivery. OBJECTIVE: To assess the efficacy and safety of long-acting injectable risperidone in elderly patients with psychotic disorders. METHODS: This is a subanalysis of 57 patients aged > or =65 years enrolled in an open-label study of long-acting risperidone that included 725 symptomatically stable patients with schizophrenia or schizoaffective disorder. Patients were assigned to receive 25, 50, or 75 mg of long-acting risperidone every 2 weeks for up to 50 weeks. RESULTS: Fifty-seven elderly patients (mean +/- SE age, 70.9 +/- 0.7 years) were enrolled. Mean Positive and Negative Syndrome Scale (PANSS) total scores improved significantly throughout the study and at endpoint (p < 0.001). The PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression) also significantly improved (p < 0.01). Clinical improvement (> or =20% reduction in PANSS total scores) was achieved by 49% of these stable patients, and 55% improved on the Clinical Global Impressions scale. Severity of movement disorders (Extrapyramidal Symptom Rating Scale scores) was reduced significantly. Adverse events reported in >10% of patients were insomnia (14%), constipation (12%), and bronchitis (12%). CONCLUSIONS: Long-acting risperidone was associated with significant symptom improvements in stable elderly patients with schizophrenia or schizoaffective disorder. Treatment was well tolerated.     

The impact of insight on functioning in patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable

This post hoc analysis explored the role of insight as a mediator of functioning in a 52-week, double-blind, international trial of 323 patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable. Measures included the Positive and Negative Syndrome Scale (PANSS) insight item, PANSS factors, Clinical Global Impressions-Severity (CGI-S), Strauss-Carpenter Levels of Functioning (LOF), Personal and Social Performance (PSP) scale, and a cognitive test battery. Correlation/regression analyses examined associations between demographic and clinical characteristics, including insight, and functional measures. Insight scores correlated significantly with CGI-S, PANSS subscales, PSP, LOF, and several cognitive measures. Regression models demonstrated that changes in insight, changes in negative symptoms, and study duration were significantly associated with PSP and LOF total change scores. Findings identified important variables to consider for intervention to improve functioning in schizophrenia.     

利培酮和氯氮平治疗伴抑郁症状的难治性精神分裂症对照研究

目的：比较利培酮和氯氮平对伴抑郁症状的难治性精神分裂症疗效。方法：共70例难治性精神分裂症患者随机服用利培酮和氯氮平治疗。利培酮组34例,氯氮平组36例;伴有抑郁症状者39例,利培酮组17例,氯氮平组22例。治疗12周。分别于治疗前、治疗4、8、12周末采用阳性与阴性症状量表（PANSS）,汉密尔顿抑郁量表（HAMD）及功能大体评定量表（GAF）评定疗效。结果：两组PANSS、HAMD和GAF评分在治疗12周均有显著改善;两组间比较差异无显著性。有、无抑郁症状组在治疗4、8、12周末的HAMD总分与治疗前比较均显著减少。结论：抑郁症状不影响难治性精神分裂症的疗效;利培酮和氯氮平对伴抑郁症状的难治性精神分裂症均有效。     

氯氮平合并改良电抽搐治疗难治性精神分裂症的对照研究

目的评价氯氮平合并改良电抽搐治疗（MECT）难治性精神分裂症的临床疗效及安全性。方法将94例难治性精神分裂症患者按照就诊顺序分为两组,联合治疗组47例,在应用氯氮平的基础上合并MECT治疗,疗程8周;单药治疗组47例,仅给予氯氮平治疗。采用阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）评定疗效和不良反应。结果联合治疗组的显效率为51.1%,单药治疗组的显效率为27.7%。联合治疗组不良反应较少。结论氯氮平合并改良电抽搐治疗难治性精神分裂症有效、安全。     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.     

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder

Background: The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones.

Aims: The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects.

Methods: The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder.

Results: The scale showed good overall reliability, with an internal consistency coefficient of α?=?0.84, an average retest coefficient of rho?=?0.76, and a Spearman–Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho?=?0.231; p?=?.025) between severity of side effects and clozapine dose.

Conclusions: The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.     

利培酮与氯氮平治疗精神分裂症对照研究的Meta分析

目的：进一步认识利培酮与氯氮平治疗精神分裂症的疗效和副作用差异。方法：收集在国内精神科杂志上公开发表的９篇关于利培酮与氯氮平对照治疗精神分裂症研究的文章,并作Ｍｅａｔ分析。结果：利培酮治疗前后自身对照比较：综合检验Ｚ１＝４０．８６,Ｐ〈０．０１,提示利培酮治疗精神分裂症前后症状学变化有非常显著性差异,ｄ＾－＝３．１,表明这种治疗效应极大。与氯氮平对照组的组间比较：Ｚ２＝－４．４１,Ｐ〉０．０５,提     

A 1-year double-blind study of 2 doses of long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder

OBJECTIVE: This study examined the effects of 2 doses of long-acting risperidone injection in patients with schizophrenia or schizoaffective disorder. METHOD: This 52-week, prospective, randomized, double-blind, multicenter, international study included clinically stable outpatients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Settings included physicians' offices and clinics. Patients received a fixed dose of long-acting risperidone (25 or 50 mg) every 2 weeks. Primary outcome was time to relapse, defined as either re-hospitalization or other exacerbation criteria. Other assessments included the Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of Illness scale, and functional and quality-of-life measures. Safety was assessed via treatment-emergent adverse events, laboratory tests, and movement disorder rating scales. Data were collected from December 2002 to September 2004. RESULTS: A total of 324 patients were randomized to 25 mg (N = 163) or 50 mg (N = 161) of long-acting risperidone. Time to relapse was comparable (p = .131) for both groups. Projected median time to relapse was 161.8 weeks (95% CI = 103.0 to 254.2) with 25 mg and 259.0 weeks (95% CI = 153.6 to 436.8) with 50 mg. One-year incidences of relapse were 21.6% (N = 35) and 14.9% (N = 24), respectively (p = .059). Psychiatric hospitalization was the reason for relapse for 16 (10%) in the 25-mg group and 10 (6%) in the 50-mg group. Patients experienced statistically significant but modest improvements at endpoint in most measures (i.e., psychotic symptoms, functioning, movement disorder severity) with both doses, with no significant between-group differences. CONCLUSION: In this 1-year study, long-acting risperidone was associated with low relapse and rehospitalization rates, indicating that doses of 25 to 50 mg are appropriate for long-term treatment in schizophrenia.     

Transcultural differences in suicide attempters: analysis on a high-risk population of patients with schizophrenia or schizoaffective disorder

The aim of the study was to investigate transcultural differences between schizophrenia spectrum disorder patients who did or did not attempt suicide. DSM-IV schizophrenia (N=609) or schizoaffective disorder (N=371) patients who participated in the multicentre International Suicide Prevention Trial (InterSePT) were studied. Patients were sub-divided into 5 groups according to the different geographical regions of recruitment: North America (NA), Europe (EUR), East Europe (EEUR), South Africa (SAf), and South America (SA). The main lifetime clinical variables were compared, within each group, between attempters and non-attempters. The presence of comorbid substance abuse disorder and smoking was associated with suicide attempts in all the geographical groups considered (NA: chi(1)(2)=7.575, p<0.01 and chi(1)(2)=69.549, p<0.0001; EUR: chi(1)(2)=55.068, p<0.0001, and chi(1)(2)=48.431, p<0.0001; EEUR: chi(1)(2)=164.628, p<0.000, and chi(1)(2)=5.127, p<0.01; SA: chi(1)(2)=30.204, p<0.0001 and chi(1)(2)=11.710, p=0.001) except for SAf. For the other clinical variables various differences were found across the different groups. Variables related to suicide behavior were similar across the five groups investigated, with differences only in the age at the first suicide attempt (earlier in the NA sample) and the number of lifetime suicide attempts (higher in the NA sample). Results from this study show that, while some suicide-related clinical characteristics in schizophrenia patients are consistent worldwide suggesting the influence of stable biological traits, other variables may vary across different geographical areas suggesting environmental influences.     

Long-term efficacy and safety of aripiprazole in patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder: 26-week prospective study

Aims:  To date there have been no reports of long-term efficacy of aripiprazole in Asian populations. The aim of the present study was therefore to investigate the long-term efficacy, safety and tolerability of aripiprazole in a large number of patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder in Korea.
Methods:  This study was a prospective, multicenter, single-group, 26-week open study of patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder. A total of 300 Korean patients participated in the study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures included the PANSS positive and negative subscales, Clinical Global Impression–Severity of Illness (CGI-S). Tolerability and safety were assessed by monitoring the frequency and severity of treatment-emergent adverse events, extrapyramidal symptoms (EPS), vital signs, weight, and laboratory tests.
Results:  Aripiprazole produced rapid and significant improvements on all efficacy measures. As evidenced by PANSS total score, PANSS positive subscales and the CGI-S scores, first-episode drug-naïve patients demonstrated significantly greater efficacy relative to patients who had previously experienced one or more episodes of relapse. Aripiprazole was associated with significant decrease of serum prolactin level. The subjects showed mild weight gain.
Conclusion:  Aripiprazole is an effective antipsychotic in the long-term treatment of both positive and negative symptoms. This study extends the findings of previous long-term studies, and has found that there is no significant difference with regard to ethnicity in response to aripiprazole.     

Psychopathy and violent behavior among patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Although a strong association between violence and psychopathy has been demonstrated in nonpsychotic forensic populations, the relationship between psychopathy and violence among patients with schizophrenia has not been thoroughly explored. Patients with and without a history of persistent violent behavior were compared for comorbidity of psychopathy and schizophrenia or schizoaffective disorder. METHODS: Violent and nonviolent patients were identified through reviews of hospital charts and records of arrests and convictions. The Psychopathy Checklist: Screening Version was administered to 51 patients, 26 violent patients and 25 matched nonviolent patients. Analysis of variance was used as the principal statistical method for comparing violent and nonviolent groups. RESULTS: Mean psychopathy scores were higher for violent patients than nonviolent patients. Five of the violent patients (19 percent) had scores exceeding the cutoff for psychopathy, and 13 (50 percent) scored in the possible psychopathic range. All of the nonviolent patients scored below the cutoff for possible psychopathy. Higher psychopathy scores were associated with earlier age of onset of illness and more arrests for both violent and nonviolent offenses. CONCLUSIONS: The comorbidity of schizophrenia and psychopathy was found to be higher among violent patients than among nonviolent patients. Violent patients with schizophrenia who score high on measures of psychopathy may have a personality disorder that precedes the emergence of psychotic symptoms, or they may constitute a previously unclassified subtype of schizophrenia, characterized by early symptoms of conduct disorder symptoms and persistent violent behavior.