国产利培酮对男性精神分裂症患者催乳素影响的临床研究

目的探讨国产利培酮（索乐）对精神分裂症男性患者血清催乳素（PRL）水平影响。方法将60例符合中国精神疾病障碍分类第3版（CCMD-3）精神分裂症诊断标准的男性患者随机分为利培酮（索乐）组（30例）和氟哌啶醇组（30例）,采用酶联免疫法测定两组治疗前后的PRL水平;采用PANSS量表评定两组临床疗效。结果①两组治疗8周末的PANSS量表评分均显著低于治疗前（P〈0．01）;②治疗前利培酮（索乐）组与氟哌啶醇组的PRL水平差异无统计学意义;治疗后利培酮（索乐）组与氟哌啶醇组的PRL水平均比治疗前升高,但两组间无显著性差异（P〉0．05）。结论国产利培酮（索乐）和氟哌啶醇均能升高患者的PRL水平,但两者差异无显著性。     

Stability of serum neuroleptic and prolactin concentrations during short- and long-term treatment of schizophrenic patients

The potential importance of neuroleptic activity measures in the management of schizophrenia warrants attention to the methods for assessing neuroleptic bioactivity and stability of neuroleptic bioactivity over time. We have carried out measurements of serum neuroleptic and prolactin concentrations in 18 schizophrenic patients treated with haloperidol or thioridazine for up to 1 year. Serum neuroleptic levels were measurd by a radioreceptor assay using porcine striatum. The lower limit of sensitivity of the assay was 0.6 ng haloperidol/ml, the intra- and interassay coefficients of variation 3 and 9%, respectively. A linear correlation was observed between haloperidol dose (5–30 mg/d) and serum neuroleptic activity (r=0.706, P<0.001) and a curvilinear relationship between thioridazine dose (50–600 mg/d) and serum neuroleptic activity in schizophrenic outpatients. There was a positive correlation between serum neuroleptic and prolactin concentrations for the patients taking haloperidol (r=0.620, P<0.001) or thioridazine (r=0.542, P<0.001). In patients taking a constant dose of haloperidol or thioridazine for up to 1 year serum neuroleptic activity remained stable, suggesting the absence of metabolic tolerance; the observation of a decrease of 38±16% (mean ± SD) in serum prolactin concentrations in patients treated with haloperidol but no prolactin decrease with thioridazine suggests that under certain neuroleptic treatment conditions a functional tolerance develops in the tuberoinfundibular dopamine system.     

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence

Rationale Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence.Objective We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects.Methods Basal PRL concentrations were assayed in 141 African–American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables.Results The basal PRL (ng/ml) in CD patients (9.28±4.13) was significantly higher than controls (7.33±2.94) (t=3.77, P<0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P<0.01), ASI-alcohol (r=0.19, P<0.05), and ASI-psychological (r=0.25, P<0.01) composite scores, and with the quantity of cocaine use (r=0.18, P<0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures.Conclusion Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence.     

Gonadal axis hormones in male schizophrenic patients during treatment with haloperidol and after switch to risperidone

Rationale: The atypical neuroleptic risperidone, in addition to its dopamine receptor blocking activity, has a high affinity for serotonergic receptors. Since both dopaminergic and serotonergic neuronal activities participate in regulation of the pituitary – gonadal axis (PGA), it is expected that a switch from treatment with haloperidol to treatment with risperidone should influence plasma levels of PGA hormones. Objective: To study the effects of a drug with dopamine and serotonin receptor blocking activity on PGA hormones in patients who were on treatment with a dopamine receptor blocker. Methods: Plasma levels of testosterone, luteinizing harmone (LH) and follicle stimulating harmone (FSH), as well as prolactin and cortisol, were measured in 16 male schizophrenic patients during treatment with haloperidol (mean dose 23.3 mg daily, SD = 16.9) and 6 weeks later after switching to treatment with risperidone (mean dose 11.8 mg daily, SD = 2.9). Psychopathology was assessed by BPRS. Results: After switching to risperidone, total BPRS score and the scores in its subscales for positive, negative, and general symptoms were all significantly reduced in the order of 35–45%. Prolactin levels were significantly increased from 39.5 ± 22.3 to 58.9 ± 28.5 ng/ml (F = 4.61, P = 0.04), while cortisol, testosterone, LH, and FSH remained unchanged. No significant correlations between prolactin increases and reduction in BPRS or in its subscale scores were found. Conclusions: The results show that blocking of both dopamine and serotonin receptors does not influence the pituitary – gonadal axis but considerably increases prolactin release. Received: 29 June 1998/Final version: 23 October 1998     

9‐Hydroxyrisperidone‐Induced Hyperprolactinaemia in Thai Children and Adolescents with Autism Spectrum Disorder

Although our previous study revealed an association between prolactin level and risperidone dosage, data regarding the plasma concentration of risperidone are lacking. Therefore, this study aimed to investigate the association between plasma drug concentrations of risperidone, 9‐hydroxyrisperidone and serum prolactin level in Thai children and adolescents with autism spectrum disorder (ASD). The individuals for this study were 103 children and adolescents with ASD (90 males and 13 females). In the 12th hour after the last risperidone dose, blood samples were collected for analysis. Serum prolactin, plasma risperidone and 9‐hydroxyrisperidone levels were measured. Patients' clinical data were collected from medical records – age, weight, height, body mass index, dose of risperidone and duration of treatment. Serum prolactin level was significantly positively correlated with plasma 9‐hydroxyrisperidone level (r_s = 0.355, p < 0.001). The median concentration of 9‐hydroxyrisperidone in individuals with hyperprolactinaemia (7.59 ng/ml; IQR 4.86–15.55) was significantly higher than non‐hyperprolactinaemic individuals (5.18 ng/ml; IQR 2.10–8.99) after risperidone treatment (p = 0.006). By multivariate analysis, high prolactin level was correlated to high 9‐hydroxyrisperidone level (p = 0.010). The results of this study showed that serum prolactin levels, especially in autistic individuals with hyperprolactinaemia during risperidone treatment, were significantly correlated with the level of 9‐hydroxyrisperidone. These results suggest that hyperprolactinaemia may develop during risperidone treatment.     

Comparison of prolactin concentrations between haloperidol and risperidone treatments in the same female patients with schizophrenia

The present study aimed to investigate intraindividual changes in plasma prolactin concentrations by switching from haloperidol treatment to risperidone treatment. The subjects were 15 female schizophrenic inpatients who received firstly haloperidol 12 mg/day for at least 2 weeks and, thereafter, risperidone 6 mg/day. Prolactin concentration in plasma during risperidone treatment (median 87.5 ng/ml, range 5.3-298.1 ng/ml) was significantly ( P<0.01) higher than during haloperidol treatment (median 50.7 ng/ml, range 11.6-226.6 ng/ml). In contrast, the ratio of prolactin concentration to nmol/l unit drug concentration (the active moiety: the sum of risperidone and 9-hydroxyrisperidone) during risperidone treatment (median 1.10, range 0.02-3.73) was significantly lower ( P<0.001) than that of haloperidol (median 1.81, range 0.41-8.24). Prolactin concentrations during both treatment phases correlated well in individuals (r=0.619, P<0.05), whereas better correlation was found in the ratio of prolactin concentration to drug concentration (r=0.779, P<0.01). These findings suggest the higher risk of hyperprolactinemia during risperidone treatment than during haloperidol treatment at clinically used dosages. However, from a purely pharmacological point of view, prolactin response per drug concentration was more sensitive during haloperidol treatment than risperidone treatment, probably resulting from the potent and selective antagonistic effect of haloperidol on dopamine D(2) receptor, compared with the broader pharmacological spectrum of risperidone.     

Nitric oxide in patients with schizophrenia: the relationship with the severity of illness and the antipsychotic treatment

Objectives: Past studies regarding the relationship between nitric oxide and schizophrenia have reported controversial results. Consequently, the aims of this study are i) to analyze the differences in nitric oxide concentration between patients with schizophrenia and healthy controls, ii) to investigate the influence of antipsychotic treatment on nitric oxide, iii) to correlate nitric oxide concentration with severity of illness, and iv) to investigate the relationship between nitric oxide and any personality disorder.

Research design and methods: We recruited 24 patients and 24 controls; the sample was divided into three groups of 8 patients, each according to the pharmacological treatment (haloperidol, olanzapine, or risperidone). The severity of illness was assessed by PANSS and personality traits were evaluated by SCID II. A blood sample was taken to assess the plasma concentration of nitrites and nitrates.

Results: Patients presented higher nitrate levels than controls (p < 0.05); subjects under olanzapine reported lower nitrate levels than those treated with risperidone (p < 0.05) or haloperidol (p < 0.001). Nitrate levels were correlated with PANSS total score (rho = 0.748; p < 0.001), but not with SCID II scores.

Conclusions: Despite the fact that this study found a correlation between PANSS score and nitrate levels, it is unclear whether nitric oxide is related to the severity of schizophrenia, because nitrate levels are also affected by antipsychotic treatment.     

鲁拉西酮联合舒必利治疗精神分裂症的临床研究

目的 探讨盐酸鲁拉西酮片联合舒必利片治疗精神分裂症的临床疗效。方法 选取2020年2月-2022年11月在上海市静安区精神卫生中心就诊的120例精神分裂症患者,按照计算机随机排列法分为对照组和治疗组,每组各60例。对照组患者口服舒必利片,首次剂量1片/次,3次/d,治疗7 d后增加至3片/次,3次/d。治疗组患者在对照组基础上口服盐酸鲁拉西酮片,1片/次,1次/d。两组患者连续治疗2个月。观察两组的临床疗效,比较两组的阳性与阴性症状量表(PANSS)评分、精神分裂症生活质量量表(SQLS)评分以及血清中催乳素(PRL)、白细胞介素-6(IL-6)、白细胞介素-17(IL-17)水平。结果 治疗后,治疗组的总有效率为91.67%,对照组的总有效率为78.33%,组间比较差异有统计学意义(P<0.05)。治疗后,两组的PANSS各项评分均显著降低(P<0.05),且治疗组PANSS各项评分较对照组更低(P<0.05)。治疗后,两组的SQLS各项评分显著降低(P<0.05),治疗组SQLS各项评分降低程度高于对照组(P<0.05)。治疗后,两组的血清PRL水平高于治疗前,血清IL-6、IL-17水平低于治疗前(P<0.05);治疗后,治疗组的血清IL-6、IL-17水平低于对照组(P<0.05)。结论 盐酸鲁拉西酮片联合舒必利片可提高精神分裂症的临床疗效,减轻患者精神症状,提高生活质量,减轻炎症反应,且药物安全性良好。     

Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic patients during treatment with neuroleptics and after switch to risperidone

RATIONALE: The pharmacological profile of risperidone is that of an atypical neuroleptic regarding its serotonin 5-HT2A and dopamine D2 receptor blocking properties. Treatment with risperidone, though, results in considerably elevated plasma prolactin (PRL) levels which are not observed with other atypical neuroleptics, such as clozapine, indicating a differentiated action on receptors that are involved in PRL release, mainly dopaminergic and serotonergic. OBJECTIVE: To assess the responsivity of serotonergic and dopaminergic receptors during treatment with neuroleptics and after switch to risperidone, using neuroendocrine paradigms. METHODS: Two neuroendocrine challenge tests, measuring the PRL increases induced by acute administration of serotonergic (clomipramine, 25 mg i.v.) and dopaminergic (haloperidol, 5 mg i.m.) drugs were performed in 13 male schizophrenic patients during treatment with typical neuroleptics and, later, after 6 weeks of treatment with risperidone. The tests were also performed in a group of nine healthy male volunteers. PRL was estimated in blood samples taken every 15 min for 1 h for clomipramine and every 30 min for 2 h for haloperidol. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS). RESULTS: During treatment with neuroleptics (mean dose 1354 mg chlorpromazine equivalents, range 300-2400 mg), i.m. haloperidol caused significant elevations in plasma PRL, which were totally abolished after 6 weeks treatment with risperidone (mean dose 12.1 mg/day, range 8-16 mg/day), indicating complete D2 receptor blockade. In contrast, the PRL increases obtained after clomipramine administration during neuroleptic treatment were preserved after treatment with risperidone. Both PRL response patterns to clomipramine were similar to that of healthy controls. BPRS score was 50.2+/-9.3 points during neuroleptic treatment and was reduced after risperidone to 30.1+/-6.6 points, i.e., 40% in the mean. CONCLUSIONS: During treatment with typical neuroleptics, the PRL responses to clomipramine are normal, and they are preserved after switch to risperidone in doses that cause complete dopamine receptor blockade. Risperidone, a dopamine and 5-HT receptor blocker, does not affect 5-HT receptors that are involved in the PRL release by the 5-HT uptake blocker clomipramine, indicating a different behavior than other atypical neuroleptics such as clozapine or olanzapine, for which a reduction of the PRL release induced by serotonergic agents like fenfluramine or mCPP has been reported. A conclusive identification of the 5-HT receptor subtypes that are involved in this different action cannot be identified at present, but it should be taken into account that risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5-HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors.     

3种抗精神病药物对首发精神分裂症患者血清泌乳素的影响

目的　探讨不同抗精神病药物对首发精神分裂症患者血清泌乳素PRL水平的影响。方法　 6 2例患者随机分为 3组 ,分别采用奎的平、氯丙嗪、利培酮治疗 4周 ,治疗前、后分别评定精神症状并测定PRL水平。结果　治疗前、后精神症状及不良反应在各组间无差异 ,但是治疗后氯丙嗪及利培酮组的PRL水平显著高于奎的平组。治疗前 3组患者的精神症状及不良反应量表分与PRL水平的相关无统计学意义 ,治疗后氯丙嗪组及利培酮组的多项精神症状量表分与PRL水平的负相关有统计学意义 (P <0 .0 5 )。结论　氯丙嗪及利培酮在改善精神症状的同时伴有PRL增高 ,而奎的平无PRL增高。     

奥氮平、氟哌啶醇对精神分裂症病人血清催乳素和生长激素的影响

目的:探讨精神分裂症病人催乳素(PRL)和生长激素(GH)的基础水平与正常人的差异,及奥氮平、氟哌啶醇治疗前后PRL,GH水平的变化。方法:采用放射免疫法测定61例精神分裂症病人治疗前和治疗8wk末的PRL和GH水平,并与30名健康者对照,同时将61例精神分裂症病人分为奥氮平治疗组28例和氟哌啶醇治疗组33例,观察药物对PRL和GH水平的影响。结果:精神分裂症病人的基础PRL,GH水平与对照组差异无显著意义(P>0.05);奥氮平组治疗8wk末PRL,GH均无显著改变(P>0.05);氟哌啶醇组治疗8wk末PRL值为(99±48)μg·L-1,较治疗前(17±10)μg·L-1显著增高(P<0.01),GH值为(1.6±1.4)μg·L-1,较治疗前(2.4±1.6)μg·L-1显著降低(P<0.01)。结论:精神分裂症病人PRL和GH的基础水平与正常群体差异不显著。奥氮平对PRL,GH无明显影响,氟哌啶醇致PRL升高,GH降低。     

Prolactin levels and erectile function in patients treated with risperidone

Treatment with risperidone is associated with prolactin (PRL) elevation, and PRL elevations are associated with erectile dysfunction (ED). We evaluated whether the PRL elevations caused by risperidone treatment of subjects with schizophrenia are associated with objective measures of erectile function. Subjects were hospitalized for 2 nights, and serum measurements of PRL, total testosterone, and free and weakly bound testosterone were performed in the morning and afternoon of each day. Risperidone levels, parent compound, and 9-hydroxy metabolite levels were drawn on the first day. Erectile function assessments, using the RigiScan, an instrument that measures nocturnal penile tumescence and rigidity, were performed on both nights. Consistent with previous reports, the correlation between total risperidone level and PRL was very high (r = 0.92, df = 12, P < 0.0001), but risperidone did not appear to affect either testosterone (r = 0.29, df = 5, P = 0.51) or free and weakly bound testosterone (r = -0.11, df = 10, P = 0.72). Contrary to expectations, PRL levels from the second night were positively correlated with erectile function (r = 0.68, df = 9, P = 0.022). Using objective measures, we were unable to confirm a detrimental association between PRL levels and male erectile function. These results are tentative given the small sample.     

奎硫平与利培酮对女性分裂症患者的血清催乳素影响的对照研究

目的：探讨女性精神分裂症患者采用奎硫平与利培酮治疗过程中,血清催乳素（PRL）的变化。方法：选择符合诊断标准的女性精神分裂症患者64例,随机分为奎硫平组与利培酮组,治疗8周,采用阳性和阴性症状量表（PANSS）在治疗前、治疗第4周和第8周分别评定;在治疗前和治疗第4、8周测定血清PRL浓度。结果：治疗前后两组在PANSS总分上无显著差异（P〉0．05）,治疗前两组血清PRL水平无显著差异（P〉0．05）,奎硫平组治疗后PRL水平变化不明显（P均〉0．05）,利培酮组治疗后PRL水平显著升高（P均〈0．01）。结论：奎硫平不引起明显的PRL升高,而利培酮有较强的致PRL升高的作用。     

Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia

The object of this study is to assess 1) the relationship between plasma antipsychotic drug concentration, serum prolactin levels and the clinical efficacy of risperidone, 2) the relationship between the CYP2D6 polymorphisms and metabolizing of risperidone and 3) the role of 9-hydroxyrisperidone in elevating prolactin levels. One-hundred and eighteen Chinese schizophrenia patients (40 males, 78 females, age 15-60 years) were given risperidone at dosages ranging from 2-8 mg/day for 8 weeks. Clinical efficacy was determined using the Brief Psychiatric Rating Scores (BPRS). Serum prolactin levels were assayed before and after the 8 week treatment and plasma risperidone and 9-hydroxyrisperidone levels were also measured at the end of the 8-week treatment. The results showed there was no significant correlation between the concentration of active moiety and clinical response. Risperidone treatment significantly increased serum prolactin levels. Furthermore, changes of prolactin levels were not correlated with the clinical response. For the risperidone/ 9-hydroxyrisperidone ratio, there was a statistically significant difference among the CYP2D6*1/*1, *1/*10, *10/*10 genotypes (Kruskal-Wallis test, p = 0.012). No significant differences were found in the concentration of 9-hydroxyrisperidone and active moiety among the genotypes. In addition, the concentration of 9-hydroxyrisperidone was not significantly correlated with the increase of serum prolactin. In conclusion, our study has, for the first time, produced evidence that in Chinese schizophrenic patients, the metabolism of risperidone is dependent on CYP2D6. Neither changes in serum prolactin levels nor plasma concentration of active moiety were significantly correlated with clinical efficacy of risperidone. 9-hydroxyrisperidone may not play a predominant role in elevating serum prolactin level.     

Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol – a 123I-IBZM SPECT study

The striatal D₂ dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n = 10). Comparisons were obtained with haloperidol (n = 8), clozapine (n = 6), risperidone (n = 11) and untreated healthy controls (n = 8) of a dataset which has partly been reported previously. ¹²³I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D₂ receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D₂ binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio:1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D₂ binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D₂ receptor occupancy in schizophrenic patients. Received: 21 July 1997/Final version: 27 October 1997     

Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week,randomized, blinded-assessment study

Rationale Conventional intramuscular (IM) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia.Objectives To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder.Methods In a 6-week, multicenter, parallel-group, flexibly dosed study, patients were randomized to ziprasidone (IM up to 3 days, then oral 40–80 mg, b.i.d.) or haloperidol (IM up to 3 days, then oral 5–20 mg/day). Assessments were rater-blinded.Results At the end of IM treatment, patients receiving ziprasidone (n=427) showed significantly improved Brief Psychiatric Rating Scale Total (BPRS total) scores compared with those receiving haloperidol (n=138) [least-squares (LS) mean change –6.14 for ziprasidone versus –4.13 for haloperidol, P<0.0018]. At endpoint, there were no significant between-group differences in BPRS total scores. There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients, both at the end of IM treatment (LS mean change –1.15 for ziprasidone and –0.28 for haloperidol, P<0.0001) and at study endpoint (LS mean change –2.94 for ziprasidone and –2.24 for haloperidol, P<0.0001). Haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint (P<0.0001). They also had significantly higher ratings on the Barnes Akathisia Scale (P<0.0001) and the Movement Disorder Burden Score (P<0.005), as well as higher incidences of movement disorder-related adverse events.Conclusions Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia.Declaration of interest This study was funded by Pfizer Inc.     

奥兰扎平利培酮及氯丙嗪对男性精神分裂症患者催乳素及勃起功能的影响

目的:探讨奥兰扎平、利培酮及氯丙嗪对男性精神分裂症患者催乳素(PRL)水平及勃起功能的影响。方法:60例首发男性精神分裂症患者随机分为奥兰扎平组、利培酮组及氯丙嗪组,检测治疗前、入组4周末及8周末PRL水平,利用男性勃起功能量表评估入组12周末勃起功能状况。结果:入组4周末利培酮组血清PRL水平显著高于氯丙嗪组及奥兰扎平组,氯丙嗪组勃起功能量表分显著低于奥兰扎平组。结论:奥兰扎平对催乳素水平及男性勃起功能的影响相对较小。     

The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects

Rationale Increased activity of the hypothalamic–pituitary–adrenal (HPA) axis is an important aspect of the pathophysiology of major depression and schizophrenia. Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol, little is known about their effect on HPA axis function. Objective Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven healthy male volunteers were studied during four sessions one week apart, orally receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg). Blood samples were taken at hourly intervals from 0900 until 1700 hours. For ACTH, cortisol, and prolactin a significant effect of treatment condition (p≤0.005; p≤0.035; p≤0.0001, respectively) for area under the curve (AUC) was found. In comparison to placebo, quetiapine and olanzapine significantly reduced ACTH (p≤0.002; p≤0.05, respectively) and cortisol (p≤0.005; p≤0.03, respectively). No effect of haloperidol on AUC of ACTH or cortisol levels was observed. In comparison with placebo, haloperidol (p≤0.0001) and olanzapine (p≤0.0001) elevated AUC of prolactin plasma levels, whereas no significant effect was observed for quetiapine as a main effect of treatment condition. The atypical antipsychotics’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals’ blockade of serotonergic receptors, but blockade of adrenergic or histaminergic receptors may play a role as well. The observed HPA-axis down-regulation may be clinically important for the atypicals’ effects on depressive symptomatology and cognitive functioning.     

Olanzapine: an updated review of its use in the management of schizophrenia

Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. CONCLUSIONS: Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.     

精神分裂症患者氨磺必利血药浓度与不良反应、泌乳素水平及认知功能相关性

目的 观察氨磺必利用于精神分裂症患者疗效以及其血药浓度与患者不良反应、泌乳素水平及认知功能相关性。方法 选择2019年7月—2020年6月80例经氨磺必利单药治疗精神分裂症患者,连续治疗8周,分别于治疗后1,2,4,8周末监测患者服药剂量、血药浓度、疗效[阳性和阴性症状量表(positive and negative symptom scale,PANSS)]及不良反应[治疗不良反应量表(treatment emergent symptom scale,TESS)];于治疗第8周末,检测患者血清泌乳素水平,测量认知功能水平变化[用韦氏成人记忆量表(wechslermemoryscale-revisedinChina,WMS-RC)、威斯康星卡片分类测验(wisconsin card sorting test,WCST)],并分析血药浓度与服药剂量、疗效、不良反应、血清泌乳素、认知功能相关性。结果Pearson相关分析法显示,治疗第1周末、第2周末、第4周末、第8周末的血药浓度与PANSS减分率、阳性症状减分率、阴性症状减分率、精神病理减分率、TESS评分均呈正相关(P<0.05)...