Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia.

OBJECTIVE: The authors evaluated the comparative efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular placebo for the treatment of acute agitation in schizophrenia. METHOD: Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales. RESULTS: According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QT(c) interval changes were observed in any patients. CONCLUSIONS: Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.     

Treatment of cognitive impairment in early psychosis: a comparison of risperidone and haloperidol in a large long-term trial

OBJECTIVE: Cognitive impairment is a major determinant of functional outcome in schizophrenia. Treatment of cognitive impairment at the time of the first episode may have the potential to change functional outcomes of the illness. This study examined changes associated with treatment with risperidone compared with haloperidol in aspects of cognitive functioning known to be associated with functional outcomes. The study was conducted in a large group of patients experiencing their first episode of schizophrenia. METHOD: Cognitive assessments were conducted in 533 patients experiencing their first episode of schizophrenia or a related psychosis who had been randomly assigned to receive low doses of risperidone or haloperidol. The cognitive assessments were repeated at several different follow-up intervals; 359 patients were reexamined at the 3-month follow-up. The assessments included examinations of verbal and visuospatial episodic memory, vigilance, executive functioning, processing speed, and verbal fluency. Patients' clinical symptoms were also rated with the Positive and Negative Syndrome Scale. RESULTS: Improvements from baseline were found in the risperidone-treated patients for episodic memory, verbal fluency, vigilance, executive functioning, and visuomotor speed. Haloperidol-treated patients also showed improvements from baseline in episodic memory, vigilance, and visuomotor speed but not in executive functioning or verbal fluency. Comparison of differential treatment effects on a composite measure of cognitive functioning found that risperidone was significantly more beneficial than haloperidol after 3 months of treatment. Changes in Positive and Negative Syndrome Scale scores were correlated overall with improvement in the haloperidol-treated patients but not in the risperidone-treated patients. CONCLUSIONS: Treatment with risperidone at the time of the first episode of schizophrenia is associated with wide-ranging improvements in cognitive functioning. Overall improvement is significantly greater with risperidone than with haloperidol. Further, cognitive improvement associated with treatment with risperidone was not influenced by changes in symptoms, but that relationship was significant in haloperidol-treated patients.     

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia

OBJECTIVE: The efficacy and safety of olanzapine were compared with those of ziprasidone. METHOD: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight. RESULTS: The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level. CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.     

Effective resolution with olanzapine of acute presentation of behavioral agitation and positive psychotic symptoms in schizophrenia

Behavioral agitation and prominent positive psychotic symptoms often characterize the acute presentation of schizophrenia. The clinical treatment goal is a rapid control of these symptoms. The relative efficacy of olanzapine, a novel antipsychotic drug, was compared with that of the conventional antipsychotic drug haloperidol. A post hoc analysis conducted on a large multicenter, double-blind, 6-week study of acute-phase patients with DSM-III-R schizophrenia or schizophreniform or schizoaffective disorders treated with olanzapine (5-20 mg/day) or haloperidol (5-20 mg/day) assessed the treatment effects on agitation (Brief Psychiatric Rating Scale [BPRS] agitation score) and positive symptoms (BPRS positive symptom score). Overall, olanzapine-treated patients experienced significantly greater improvement in behavioral agitation than did haloperidol-treated patients (last observation carried forward [LOCF]; p < .0002). Both groups showed similar reductions in agitation scores during the first 3 weeks of therapy; olanzapine was associated with significantly greater improvements at weeks 4, 5, and 6 (observed cases [OC]). Similarly, patients with predominantly positive psychotic symptoms experienced significantly greater improvement in BPRS positive symptom scores with olanzapine compared with haloperidol (LOCF; p = .013). In olanzapine-treated patients, improvement in BPRS agitation and positive symptom scores was significantly greater at weeks 4, 5, and 6 (agitation scores, p < or = .01; positive symptom scores, p < .05) (OC). These data suggest that olanzapine may be considered a first-line treatment for the patient in an acute episode of schizophrenia.     

Olanzapine versus haloperidol in the treatment of patients with chronic schizophrenia: Results of the Japan multicenter, double-blind olanzapine trial

This randomized double-blind trial was conducted to test the efficacy and safety of olanzapine in Japanese patients with schizophrenia. Importantly, this study also represents the first large clinical trial of olanzapine conducted in an Asian population. Patients (n = 182) were randomly assigned to treatment with olanzapine or haloperidol over a period of 8 weeks. The primary analyses included: (i) a test of non-inferiority of olanzapine compared with haloperidol in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison between the treatment groups in extrapyramidal symptom severity using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to haloperidol in efficacy in treating positive symptoms and significantly superior in treating negative symptoms. Extrapyramidal symptom severity was significantly improved for olanzapine-treated patients versus haloperidol-treated patients. Olanzapine was shown to be more effective and better tolerated than haloperidol in the treatment of Japanese patients suffering from chronic schizophrenia.     

Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia.

BACKGROUND: There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted. METHODS: A subpopulation of patients (n = 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, 6-week study assessing the efficacy and safety of olanzapine and haloperidol were examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted. RESULTS: Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale, and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale total (p = .006), PANSS total (p = .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but significance was not reached in the completers analysis (p = .093). Mean doses (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6 mg/day, respectively. CONCLUSIONS: Olanzapine was superior to haloperidol for key symptom domains and parkinsonian side effects. Implications of these data for the therapeutics of this severely ill subgroup are discussed.     

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.     

Early response to antipsychotic therapy as a clinical marker of subsequent response in the treatment of patients with first-episode psychosis

Early response to antipsychotic medication has been shown to accurately predict later response to continued use of the same treatment in patients with chronic schizophrenia. This study examines whether this predictive pattern exists for patients with first-episode psychosis. We used a data-driven threshold for early response of ≥ 26.2% improvement from baseline on the Positive and Negative Syndrome Scale (PANSS(0-6)) Total score to determine whether response at Week 2 of treatment may predict response at Week 12 in a randomized, double-blind trial of olanzapine versus haloperidol for treatment of patients with first-episode psychosis (N=225). Later response was defined as a ≥ 40% and ≥ 50% improvement in PANSS Total(0-6) score and as remission. At Week 2, 43% (97/225) of patients were identified as early responders. At a threshold for later response of ≥ 50% improvement in PANSS(0-6) Total score, early non-response most strongly predicted later non-response, demonstrating high specificity (74%) and high negative predictive value (80%). As had been seen in the treatment of patients with chronic schizophrenia, early non-response was a robust predictor of subsequent non-response in the treatment of patients with first-episode psychosis.     

Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Risperidone Working Group

An international, multicenter, double-blind study was conducted in 183 patients with a first psychotic episode (provisional schizophreniform disorder or schizophrenia; DSM-III-R) treated with flexible doses of risperidone or haloperidol for 6 weeks. At endpoint, 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinically improved (> or = 50% reduction in Positive and Negative Syndrome Scale total scores). Risperidone was better tolerated than haloperidol: the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients; significantly fewer risperidone-treated patients required antiparkinsonian medication; and significantly fewer discontinued treatment because of adverse events. A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients. Furthermore, the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses (maximum, < or = 6 mg/day) than high doses (maximum, > 6 mg/day) of risperidone or haloperidol. These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications. Studies designed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients.     

An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo,haloperidol, risperidone,or clozapine

BACKGROUND: The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database. METHOD: This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared. RESULTS: A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021). CONCLUSION: This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.     

Suicide and undetermined death by drowning

INTRODUCTION : To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. METHOD : In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. RESULTS : The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). CONCLUSIONS : These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111)     

Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder

CONTEXT: Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance. OBJECTIVE: To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder. DESIGN AND SETTING: Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36). MAIN OUTCOME MEASURES: Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). RESULTS: Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales. CONCLUSIONS: Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.     

The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.     

Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial

OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.     

Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: inverse association with positive symptoms

Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia.     

奥氮平快速镇静疗法与氟哌啶醇肌注治疗急性躁狂发作的对照研究

目的比较奥氮平快速镇静疗法和氟哌啶醇肌注对急性躁狂发作的疗效和安全性。方法52例伴有激越行为的急性躁狂患者,随机分成两组,奥氮平组26例、氟哌啶醇组26例,分别在治疗前、治疗后12h、72h、1周及2周末采用阳性症状与阴性症状量表(PANSS)的兴奋因子分评定疗效,治疗时出现的症状量表(TESS)评定不良反应。结果两组治疗后12h、72h、1周及2周末的PANSS兴奋因子分均较前明显下降,两组对兴奋激越症状均能快速起效,两组疗效相当,各时点两组间比较无显著性差异,但氟哌啶醇组在各时点TESS总分显著高于奥氮平组。结论奥氮平快速镇静疗法和氟哌啶醇肌注治疗对急性躁狂发作患者的兴奋激越症状均有很好疗效,两组疗效大致相当,但前者在安全性方面更有优势。     

The association between psychopathology of first-episode psychosis patients within the schizophrenia spectrum and previous offending

Patients with schizophrenia have been shown to have an increased risk of criminality. The aim was to describe possible psychopathological differences between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis. In a multi-centre study, 16 psychiatric treatment centres included and rated 477 patients with first-episode psychosis over a 2-year period on socio-demography, the Positive and Negative Syndrome Scale, OPerational CRITeria checklist, Global Assessment of Functioning, Premorbid Adjustment Scale and Self-report Insight Scale for psychosis. Data were linked with data concerning criminal and psychiatric history. No key characteristics were found to assist the early detection of criminal persons before first psychiatric hospital contact for a psychotic incident. However, when adjusted for sex, age, abuse, living conditions, marital status, employment status and education, a primarily positive symptomatology was associated with a prior criminal career. The premorbid level of functioning and several function parameters were also significantly associated with criminal history. There are significant differences in psychopathology between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis, and a better screening procedure in the judicial system could detect these individuals earlier and make adequate treatment possible.     

Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis.

OBJECTIVE: Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy. METHOD: Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment. RESULTS: At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6). CONCLUSIONS: These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.     

奥氮平与利培酮治疗青少年首发精神分裂症对照研究

目的比较奥氮平与利培酮治疗青少年首发精神分裂症的疗效和安全性。方法对60例青少年期首发精神分裂症患者随机分为两组,分别给予奥氮平与利培酮治疗8周。于治疗前及治疗后1、2、6、8周末进行阳性和阴性症状量表(PANSS)及副反应量表(TESS)评定。结果奥氮平与利培酮总的疗效无显著性差异,均能快速起效,PANSS总分比较治疗第1周与第2周末奥氮平组显著低于利培酮组,利培酮组锥体外系反应显著多于奥氮平组。结论奥氮平与利培酮均是治疗首发青少年精神分裂症安全有效的非典型抗精神病药物,可根据患者的不同情况分别选择。     

Relationship between premorbid functioning and symptom severity as assessed at first episode of psychosis

OBJECTIVE: Investigating the relationship between premorbid and prodromal status and the clinical manifestations of the first psychotic episode is relevant for understanding the pathophysiology of psychosis and for improving management of the disease. This study examined patterns of premorbid functioning of persons interviewed during their first episode of psychotic illness and examined the relationship of premorbid characteristics with symptom severity and cognitive functioning during the first illness episode. METHOD: The data were derived from the baseline assessments of a multicenter international drug trial that enrolled 535 patients in their first episode of psychosis. Subjects' scores on the Premorbid Adjustment Scale were used to assign them to groups according to whether their premorbid functioning was stable-good, stable-poor, or deteriorating. The three groups' scores on the Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, and a cognitive battery were compared. RESULTS: Almost half of the patients (47.5%) had stable-good premorbid functioning, 37.3% had stable-poor premorbid functioning, and 15.1% had initially good, but later deteriorating, premorbid functioning. Compared to the stable-poor and deteriorating groups, the stable-good group had lower (better) negative syndrome and general psychopathology scores on the Positive and Negative Syndrome Scale and a lower CGI severity scale score. Differences between the stable-poor and stable-good groups were also found on some cognitive measures and on the positive syndrome subscale of the Positive and Negative Syndrome Scale. CONCLUSIONS: More than half of the subjects, who were interviewed during their first episode of psychotic disorder, had evident premorbid behavioral disturbances. Poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first illness episode.