Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. METHOD: In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. RESULTS: From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. CONCLUSIONS: In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.     

The relationship of clozapine and haloperidol treatment response to prefrontal,hippocampal, and caudate brain volumes

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.     

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)     

Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder

BACKGROUND: Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo. METHOD: A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval. RESULTS: Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval. CONCLUSION: Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.     

A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.

BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia. METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12. RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05). CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.     

A comparison of two doses of melperone,an atypical antipsychotic drug,in the treatment of schizophrenia

Melperone at a dose of 300 mg/day has been reported to be as effective as thiothixene and superior to placebo in the treatment of schizophrenia. Limited ability to cause extrapyramidal side effects (EPS) and absence of an effect on plasma prolactin (pPRL) levels suggests that it is an atypical antipsychotic drug. The goal of this pilot study was to determine: (1). the ability of melperone 400 mg/day to produce greater improvement in psychopathology than melperone 100 mg/day; and (2). to compare side effects of these two doses of melperone. Melperone, 100 or 400 mg/day, was administered to 34 acutely hospitalized patients with schizophrenia for 6 weeks in a randomized, double-blind manner. Psychopathology, EPS, pPRL levels, and body mass index (BMI) were evaluated at baseline and 6 weeks. Twenty-seven completed the 6-week treatment. A last carried forward analysis revealed no significant difference in the ability of the two doses of melperone to improve psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS)-Total and Positive subscale, the Scale for the Assessment of Negative Symptoms (SANS), the Schedule for Affective Disorders and Schizophrenia-Disorganization subscale, and the Global Assessment Scale (GAS). Treatment with melperone was not associated with exacerbation of EPS, or an increase in pPRL levels or BMI. The Abnormal Involuntary Movement Scale (AIMS) was not significantly changed by treatment with melperone. These results suggest that melperone was equally effective at doses 100 and 400 mg/day, for ameliorating psychopathology and improving overall psychiatric status in patients with schizophrenia. However, the lack of difference and a placebo control group, as well as modest degrees of change in psychopathology, require caution about assuming efficacy of either dose. The lack of significant side effects such as exacerbation of EPS, pPRL elevation, and weight gain indicates melperone is well tolerated.     

The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy

INTRODUCTION: Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine. DATA SOURCES/STUDY SELECTION: A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score. RESULTS: The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis). CONCLUSION: This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.     

Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers

OBJECTIVE: Despite the clinical observation that antipsychotics can produce negative symptoms, no previous controlled study, to our knowledge, has evaluated this action in healthy subjects. The present study assessed observer-rated and self-rated negative symptoms produced by conventional and second-generation antipsychotics in healthy volunteers. METHOD: The authors used a double-blind, placebo-controlled trial of single doses of haloperidol (5 mg) and risperidone (2.5 mg) in normal subjects. Thirty-two subjects were administered haloperidol, risperidone, and placebo in a random order. Motor variables and observer-rated negative symptoms were assessed after 3-4 hours and subjective negative symptoms and drowsiness after 24 hours. RESULTS: Neither of the active drugs caused significant motor extrapyramidal symptoms after administration. Haloperidol caused significantly more negative signs and symptoms than placebo on the Scale for the Assessment of Negative Symptoms (SANS) and two self-rated negative symptom scales: the Subjective Deficit Syndrome Scale total score and an analog scale that evaluates subjective negative symptoms. Risperidone caused significantly more negative signs and symptoms than placebo on the Brief Psychiatric Rating Scale (BPRS), the SANS, the Subjective Deficit Syndrome Scale total score, and the analog scale for subjective negative symptoms. After control for drowsiness, risperidone but not haloperidol produced more negative symptoms than placebo on the BPRS and the SANS. Significance was lost for the subjective negative symptoms with both drugs. CONCLUSIONS: Single doses of both haloperidol and risperidone produce negative symptoms in normal individuals. Drowsiness may be an important confounding factor in the assessment of negative symptoms in antipsychotic trials.     

Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term,placebo-controlled trials

Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201). Daily aripiprazole doses ranged from 2 to 30 mg. Safety assessments included adverse event (AE) reports, EPS scales, ECGs, weight, and prolactin, glucose and cholesterol levels. Aripiprazole was well tolerated, with similar AE incidence rates to placebo, and lower rates than haloperidol for akathisia, extrapyramidal syndrome and somnolence. Objective EPS assessments demonstrated no significant differences between aripiprazole and placebo on Simpson-Angus Scale (SAS) scores, no dose-dependent effects on Barnes Akathisia scores, and significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores from baseline vs. placebo (p相似文献   

Time course of the changes in antipsychotic-induced hyperprolactinemia following the switch to aripiprazole

Hyperprolactinemia is an important but neglected adverse effect of antipsychotic medication. All first generation antipsychotics and the second generation antipsychotics amisulpride and risperidone have been shown to cause marked elevation in serum prolactin levels, whereas most other second generation antipsychotics and aripiprazole appear to have little or no effect on serum prolactin levels. This study was aimed to assess the time course of changes in antipsychotic-induced hyperprolactinemia during the process of antipsychotic switching to aripiprazole. Twenty-three female schizophrenic subjects with risperidone- or sulpiride-induced symptomatic hyperprolactinemia were recruited into the study and 20 of them completed the trial. We added aripiprazole to the therapeutic dose first, then overlapped the preexisting antipsychotic treatment and aripiprazole, and finally tapered the preexisting antipsychotic treatment. Clinical status was assessed by using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity Scale (CGI-S). Assessment scales and serum prolactin levels were measured at baseline, during the combination treatment period, and four weeks after having completed discontinuation of the preexisting antipsychotic treatment. Switching antipsychotic drugs to aripiprazole was effective in reducing serum prolactin levels and restoring menstruation in schizophrenic patients who received prolactin-raising antipsychotics. Mean serum prolactin levels at baseline, during combination period, and after the switch were 97.0+/-69.0 ng/ml, 27.2+/-10.6 ng/ml (p<0.001, vs. baseline), and 12.2+/-5.3 ng/ml (p<0.001, vs. baseline), respectively. None of the study subjects experienced any serious adverse effects during the switching process. No significant changes were noted in the PANSS and CGI-S scores during the switching process. The prolactin-normalizing effects of aripiprazole are likely caused by the unique characteristics of the dopamine partial agonist with its high affinity for dopamine D2 receptors.     

Lithium addition to neuroleptic treatment in chronic schizophrenia: a randomized,double-blind,placebo-controlled,cross-over study

We studied the effect of lithium addition to neuroleptic treatment in chronic schizophrenia, for which contradictory results have been produced in previous studies. Twenty-one chronic schizophrenic inpatients received lithium in a study with randomized, double-blind, placebo-controlled, cross-over design consisting of 8 weeks each of treatment with lithium capsules and identical placebo capsules. The total Brief Psychiatric Rating Scale (BPRS) scores at week 8 of the lithium treatment were improved significantly compared with those at week 8 of the placebo treatment. Of the BPRS subscales, however, only anxiety-depression improved, whereas none of the subscales for anergia, thought disturbance, activation and hostile-suspiciousness improved. There was no significant difference between the total Scale for the Assessment of Negative Symptoms (SANS) scores at any time during lithium and placebo treatment. These results suggest that the addition of lithium to neuroleptic treatment improves anxiety-depression in chronic schizophrenia.     

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.     

Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study

In a double-blind, placebo controlled study, conjugated estrogens (CE) (0.625 mg/day) were added to a fixed dosage of haloperidol (5 mg daily). Forty-four female inpatients with acute schizophrenia were included in the study and randomized to one of the groups; 40 patients completed the trial. They were followed for 28 days and evaluated periodically with the BPRS, Negative Symptoms Rating Scale, Simpson Angus Extrapyramidal Rating Scale and UKU rating scale. Hormonal concentrations (estradiol, estrone, progesterone, FSH, LH and prolactine) were measured at baseline and weekly throughout the trial. Both groups showed similar clinical improvement during the evaluation, although there was a trend for the CE group to show a better improvement than the placebo group (p < 0.10). Side effects and the use of anticholinergics were similar in both groups. Conjugated estrogens caused elevation only of estrone levels in the CE group; estradiol and prolactin showed a similar profile for both groups. Our negative findings regarding the antipsychotic effect of conjugated estrogens does not preclude, however, a possible efficacy of other estrogens, such as 17-beta-estradiol, in schizophrenia.     

Elevated blood superoxide dismutase in neuroleptic-free schizophrenia: association with positive symptoms

Blood levels of superoxide dismutase (SOD), measured by radioimmunometric assay, were compared in 68 patients with chronic schizophrenia and 50 normal control subjects. Psychopathology in the patients was assessed with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms. Blood SOD levels were significantly elevated in schizophrenia compared with control values. SOD levels showed a positive relationship with the BRPS and the SAPS total score in patients.     

阿立哌唑对利培酮所致高催乳素血症的疗效

目的:探讨阿立哌唑治疗利培酮所致高催乳素血症的有效性和安全性。方法:对19例利培酮所致高催乳素血症的男性精神分裂症患者,合并阿立哌唑10 mg/d。分别于治疗前、治疗2、4、8周检测血清催乳素水平;在治疗前、治疗8周评定阳性与阴性症状量表(PANSS)、临床总体印象量表-疾病严重度(CGI-S)、Barnes锥体外系不良反应量表(SAS)、Barnes静坐不能量表(BAS)和UKU不良反应量表(UKU)。结果:治疗4周催乳素水平显著下降(P<0.001),而治疗4周与治疗8周催乳素水平差异无显著性(P>0.05);研究结束时,所有患者催乳素水平下降超过50%,其中6例降至正常,5例患者催乳素相关症状均有改善;治疗前后PANSS、CGI-S、BAS和SAS评分差异无显著性(P>0.05)。结论:阿立哌唑可有效治疗利培酮所致的高催乳素血症,不良反应少。     

阿立哌唑治疗舒必利所致男性高催乳素血症

目的：探讨阿立哌唑治疗舒必利所致男性高催乳素血症的疗效。方法：将60例舒必利所致的高催乳素血症的男性精神分裂症患者随机分为两组,分别用阿立哌唑（30例）及安慰剂（30例）治疗,疗程8周。分别于治疗前、治疗8周检测血清催乳素（PRL）水平,以简明精神病评定量表（BPRS）评定疗效,以治疗中出现的症状量表（TESS）评定不良反应。结果：治疗8周后,阿立哌唑组PRL较治疗前显著下降（t=24.65,P〈0.01）,男性乳房女性化消失率73.3%,自发泌乳消失率85.0%,对照组PRL治疗前后差异性无显著性（t=1.40,P〉0.05）。结论：阿立哌唑可有效治疗舒必利所致的男性高催乳素血症。     

Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics

The primary aim of our study is to evaluate the level of insight during the switch from a classical antipsychotic drug to a atypical neuroleptic. Twenty-two schizophrenic patients were admitted to the study, 9 were male and 13 were female. Standardized questionnaire were: Scale for Assessment of Negative Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessing the three components of Insight (SAI). All patients were receiving haloperidol at time of recruitment. Eight patients were switched to clozapine, 3 to risperidone and 11 to olanzapine. The global function, measured with BPRS, increased after administration of atypical antipsychotics. The positive and negative symptoms were reduced. The level of insight was increased after the administration of the atypical antipsychotics. The cognitive effect of the atypical antipsychotics changed the level of insight and augmented the compliance.     

Baseline Serum Prolactin in Drug-naive, First-episode Schizophrenia and Outcome at Five Years: Is it a Predictive Factor?

Objective: Serum prolactin is influenced by antipsychotic use but its relationships with psychopathology and general functioning are not clear. This study aimed to assess these relationships.Design: Serum prolactin levels were measured in patients with schizophrenia before being treated with antipsychotics and at various follow-up points.Setting: The study was conducted in a nongovernmental psychiatric treatment center in Mumbai, India.Participants: The participants included 30 male and 30 female drug-na?ve patients with schizophrenia and 31 control participants.Measurements: The severity of psychopathology at baseline, three weeks, six weeks, and five years following treatment was assessed using a modified Brief Psychiatric Rating Scale. The Global Assessment of Functioning questionnaire was used at baseline and five years follow up.Results: Contrary to our hypotheses, prolactin levels in male but not female patients at baseline were twice those of control volunteers. Correlations between prolactin, Brief Psychiatric Rating Scale, and Global Assessment of Functioning measurements were not significant for any time point up to six weeks, but were only significant at the five-year follow-up appointments, indicating that those patients with higher levels of serum prolactin had a better outcome at five years.Conclusion: Baseline serum prolactin levels in drug-naive patients with schizophrenia may be used for long-term prognosis, but are not reliable indicators of psychopathology and prognosis in the short term. Future research is needed to conclude with confidence whether or not prolactin can be used as a biomarker of psychopathological and overall functioning in schizophrenia.     

哌泊噻嗪、氟哌啶醇癸酸酯与氟奋乃静癸酸酯治疗精神分裂症的对照研究

建桐翁正【摘要】目的验证和比较哌泊噻嗪、氟哌啶醇癸酸酯、氟奋乃静癸酸酯三种长效抗精神病制剂对精神分裂症的疗效及副反应。方法采用多中心、开放随机对照研究，以简明精神病评定量表（ＢＰＲＳ）、阳性症状评定量表（ＳＡＰＳ）、阴性症状评定量表（ＳＡＮＳ）、临床疗效总评量表（ＣＧＩ）和副反应量表（ＴＥＳＳ）、锥体外系副反应量表（ＲＳＥＳＥ）综合评定。结果治疗后哌泊噻嗪组患者的ＣＧＩＳＩ与ＣＧＩＧＩ分值和ＳＡＮＳ量表总分均低于其它两组，差异均有显著性（Ｐ＜０．０５），而ＢＰＲＳ和ＳＡＰＳ量表总分治疗结束时三组间差异无显著性（Ｐ＞０．０５）。ＴＥＳＳ总分和ＲＳＥＳＥ总分在整个治疗过程中均以氟奋乃静癸酸酯组最高，哌泊噻嗪组最低。结论三组中以哌泊噻嗪对精神分裂症的疗效较好，对阴性症状的改善优于氟哌啶醇癸酸酯组和氟奋乃静癸酸酯组，对阳性症状的疗效近似。哌泊噻嗪组副反应较少，安全度较好     

Clozapine-induced weight gain predicts improvement in psychopathology

BACKGROUND: Some, but not all, previous studies have indicated that weight gain is associated with greater improvement in psychopathology during clozapine treatment. Possible reasons for the inconsistent results include failure to adjust for initial body weight and level of psychopathology, differences in trial duration, outcome measures, reliability of assessment, concomitant medications and clozapine dosage. The purpose of this study was to test the hypothesis that clozapine-induced weight gain is related to antipsychotic efficacy at 6 weeks and 6 months after adjusting for initial body weight and severity of illness. METHODS: Weight and psychopathology were determined in 74 patients with schizophrenia or schizoaffective disorder at baseline and after 6 weeks and 6 months of open treatment with clozapine monotherapy. The primary measures of psychopathology were the Brief Psychiatric Rating Scale (BPRS) Total and Positive symptoms subscales, Schedule for Assessment of Negative Symptoms (SANS), Schedule for Assessment of Positive Symptoms (SAPS) and Global Assessment of Function Scale (GAFS). RESULTS: Significant improvement in the key measures of psychopathology was noted at 6 weeks and 6 months. Mean weight gains at 6 weeks and 6 months were 3.7+/-5.7 S.D. and 7.3+/-7.9 S.D. kg, respectively, with the increase between 6 weeks and 6 months being significant. Age, but not gender, initial body weight, clozapine dosage or plasma levels predicted weight gain at both time points. At 6 weeks and 6 months, after adjustment for age, initial weight and level of psychopathology, the percentage change in weight significantly predicted the improvement in the BPRS Total and Positive symptoms subscale, the SANS Global score, as well as other measures of psychopathology. CONCLUSIONS: Increase in weight with clozapine predicted improvement in psychopathology. This suggests that effects of clozapine on neurotransmitters which influence weight gain, e.g. 5-HT(2C) and 5-HT(1a) antagonism, in association with individual variations in these receptors and others molecules, e.g. peptides and transporters, due to polymorphisms or post-translational editing of mRNAs, may also contribute to the improvement in psychopathology.