Effects of acute olanzapine after sustained fluoxetine on extracellular monoamine levels in the rat medial prefrontal cortex

The combination of selective serotonin reuptake inhibitors with atypical antipsychotic drugs exhibits beneficial effects in treatment-resistant depression. We investigated the effects of a 2-week treatment with a low fluoxetine dose (3 mg/kg per day) plus a single injection of olanzapine (3 mg/kg) on the dialysate concentration of noradrenaline, dopamine and serotonin (5-HT) in the medial prefrontal cortex of the rat. Chronic fluoxetine increased only 5-HT levels whereas single olanzapine administration increased the concentration of catecholamines and decreased that of 5-HT to a comparable extent in vehicle- and fluoxetine-treated rats. Therefore, it is possible that the therapeutic benefit of this pharmacological combination may not be associated to changes in the cortical concentration of monoamines, but to postsynaptic blockade of monoaminergic receptors.     

Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium

Objective

The objective of the study was to assess the efficacy and safety of second-generation antipsychotics olanzapine and risperidone vs. haloperidol in patients of delirium admitted to medical and surgical wards.

Methods

Prospective follow-up single-blind randomized controlled trials were performed. Consecutive patients with delirium referred to the consultation–liaison psychiatry team were eligible for the study. The study sample comprised 64 patients, with 20 subjects in the haloperidol group, 21 subjects in the risperidone group and 23 subjects in the olanzapine group. A flexible dose regimen (haloperidol −0.25 to 10 mg; risperidone −0.25 to 4 mg; olanzapine −1.25 to 20 mg) was used. Delirium Rating Scale-Revised-98 (DRS-R98) was used as the primary efficacy measure, and mini mental status examination (MMSE) was used as a secondary efficacy measure.

Results

There was no significant difference in mean baseline DRS-R98 severity scores and MMSE scores between the three groups. However, there were a significant reduction in DRS-R98 severity scores and a significant improvement in MMSE scores over the period of 6 days, but there was no difference between the three groups. Four patients in the haloperidol group, six subjects in the risperidone group and two subjects in the olanzapine group experienced some side effects.

Conclusions

Risperidone and olanzapine are as efficacious as haloperidol in the treatment of delirium.     

阿立哌唑与奥氮平治疗老年期首发精神分裂症的临床分析

目的比较阿立哌唑与奥氮平治疗老年期首发精神分裂症的疗效和安全性。方法 60例老年期精神分裂症患者随机分为阿立哌唑组和奥氮平组,分别给予阿立哌唑和奥氮平治疗。疗程8周。采用阳性和阴性症状量表(PAN SS)评定疗效,采用副反应量表(TESS)评定治疗后不良反应。结果在阴性症状方面,治疗2周后,阿立哌唑组即有明显改善(t=2.210,P0.05),且与奥氮平组相比较有统计学差异(t=2.021,P0.05),而在阳性症状方面,奥氮平组改善优于阿立哌唑组(t=2.016,P0.05),但在治疗4、6、8周后,两组总体疗效相当,但阿立哌唑组在阴性症状方面改善较奥氮平组有显著性差异(t=3.302,P0.01)。在副反应方面,阿立哌唑组副反应较少。结论阿立哌唑治疗老年期首发精神分裂症疗效好,阴性症状改善优越,安全性高,可推广使用。     

奥氮平治疗急性谵妄的临床疗效观察

目的:研究奥氮平对伴有严重精神症状的急性谵妄患者的临床疗效。方法:76例确诊为急性谵妄的患者随机分为两组,治疗组39人和对照组37人。在积极治疗原发病的同时,治疗组患者合并使用奥氮平治疗,对照组患者合并使用地西泮治疗。于治疗前,治疗2周,4周后分别使用谵妄评定量表(CAM-CR),临床总体印象量表(CGI)和药物副作用量表给予评分。结果:与治疗前相比,研究组在治疗2周后的CAM-CR和CGI量表评分有明显改善(P<0.05),而对照组改善不明显,有的患者症状加重。经过4周治疗后,研究组患者改善更明显(P<0.01),而对照组亦有明显改善(P<0.01),其中对照组有2例患者死亡。研究组与对照组的药物副作用量表评分无明显差异(P>0.05)。结论:奥氮平对于快速治疗急性谵妄患者有较好的疗效。     

小剂量短程奥氮平联合氟西汀治疗老年卒中后抑郁的研究

目的评价小剂量短程奥氮平联合氟西汀治疗老年卒中后抑郁的疗效。方法 72例老年卒中后抑郁患者随机分为两组,每天均给予氟西汀20mg,连续6周,其中治疗组34例早期每晚合用奥氮平2.5～5mg,连续2周。于治疗前后采用汉密尔顿抑郁量表(HAMD)评定临床疗效,采用不良反应量表(TESS)评价其安全性。结果治疗组在治疗后3d、1周、2周、4周、6周时HAMD评分改善的总有效率分别为30.6%、47.8%、76.2%、84.4%和84.6%,而对照组分别为5.8%、18.6%、35.6%、61.2%和79.4%,两组总有效率在治疗3d、1周及2周时差别有显著性(P<0.05)。结论单用氟西汀治疗老年卒中后抑郁起效慢且疗效较低,合并使用小剂量短程奥氮平起效快疗效高,且不增加不良反应。     

Liquid chromatography/tandem mass spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum and cerebrospinal fluid

A validated, accurate and sensitive LC–MS/MS method for determination of olanzapine and its metabolite N-desmethylolanzapine has been developed. The analytes were quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. Olanzapine and desmethylolanzapine were extracted from serum or cerebral spinal fluid samples, 200 μl, with tert-butyl methyl ether using olanzapine-D3 as internal standard. Calibrations for olanzapine and desmethylolanzapine were linear within the selected range of 0.2–30 ng/ml (6–96 nM) in cerebral spinal fluid and for olanzapine in plasma, in the range of 5–100 ng/ml (16–320 nM). The method was successfully used for the analysis of samples from patients treated with olanzapine in the dose range of 2.5–25 mg/day.     

奥氮平联合氟西汀治疗无精神病症状抑郁症

目的：探讨氟西汀联合小剂量奥氮平治疗无精神病症状抑郁症的疗效和安全性。方法：47例无精神病症状的抑郁症患者随机分为对照组（氟西汀）22例和治疗组（氟西汀联合奥氮平）25例,于治疗前、治疗第2周和第4周测评汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和不良反应量表（TESS）。疗效评价以HAMD减分率为标准,不良反应以TESS评分为标准。结果：HAMD、HAMA评分组间比较差异有统计学意义（P〈0．05或0．01）,2组疗效比较差异有统计学意义（P〈0．05）,各时期TESS评分组问比较差异无统计学意义（P〉0．05）。结论：抗抑郁剂联合小剂量奥氮平治疗无精神病性症状抑郁症疗效好,安全性高。     

Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

Backgrounds:

This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin.

Materials and Methods:

Albino rats were divided into three groups, namely vehicle control group (CG), olanzapine-treated group (OZ), and olanzapine plus silymarin (OZS) treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP) were measured in all three groups.

Results:

Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant.

Conclusion:

Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.     

Gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients

We investigated the effect of gender on plasma prolactin levels in 20 Japanese drug-naïve schizophrenic patients [10 male, 10 female, aged 25.4 ± 10.3 (mean ± S.D.), range = 12–46 years] treated with olanzapine. Plasma prolactin levels were measured at baseline, and weeks 3 and 8 after starting titration of olanzapine. Comparisons of plasma prolactin levels between baseline and week 3, and between baseline and week 8 were made by repeated analysis of variance (ANOVA) and paired t-test. Two-way ANOVA showed a significant difference in olanzapine-induced prolactin changes between male and female patients (P = 0.037). In male patients (n = 10), the plasma concentration of prolactin at week 3 was significantly higher than at baseline (P = 0.016), but there was no significant difference between the plasma concentration of prolactin at week 8 and at baseline or week 3 (P = 0.191). In female patients (n = 10), there was a significant change of prolactin between baseline and week 3 (P = 0.005), and between baseline and week 8 (P = 0.047). Our results indicate the possibility of gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients. These gender-based findings may be helpful for clinicians when deciding the frequency of follow-up visits once a patient starts olanzapine therapy.     

Improvement in social functioning in outpatients with schizophrenia with prominent negative symptoms treated with olanzapine or risperidone in a 1 year randomized, open-label trial

GENERAL PURPOSE: To evaluate the social functioning of schizophrenic outpatients after switching to second-generation antipsychotics. METHODOLOGY: Multi-center, randomized, open-label, parallel, flexible-dose, 1-year study of schizophrenic outpatients with prominent negative symptoms (defined as a SANS Global score > or =10), previously treated with conventional antipsychotics. Patients were randomly assigned (1:1 ratio) to treatment with an initial dose of at least 10 mg/day olanzapine (N = 120) or at least 3 mg/day risperidone (N = 115). Dosage could be modified during the study according to clinical criteria. Social functioning was evaluated using the total and subscales scores of the Social Functioning Scale (SFS) (validated Spanish version). Other efficacy measures included the SANS, SAPS, and CGI-S scales. Response was defined in advance as a 30% improvement in the SANS Global score. RESULTS: The mean doses during the trial were 12.2 mg/day (S.D. = 5.8) of olanzapine and 4.9 mg/day (S.D. = 2) of risperidone. There were no significant baseline differences in SFS total scores or other relevant clinical variables. At 1 year, olanzapine-treated patients presented a mean improvement in SFS total scores (7.75) that were significantly higher (p = 0.0028) than for risperidone-treated patients (-0.92). Treatment with olanzapine resulted in a greater numerical improvement than risperidone in all SFS domains and reached statistical significance in such categories as social engagement or withdrawal (p = 0.01), independence (performance) (p = 0.0098), independence (competence) (p = 0.04), recreational activities (p = 0.0391), and occupation/employment (p = 0.0024) in which the greatest difference between the olanzapine and risperidone groups was found (0.86 vs. -3.06). Significantly more patients treated with olanzapine reached or surpassed the SFS typified total scores corresponding to a functional level that is representative of a sample of stabilized Spanish outpatients with schizophrenia without prominent negative symptoms (p = 0.0009). Associated factors were treatment with olanzapine and a 30% improvement or more in SANS global score or SAPS global score. CONCLUSIONS: Long-term treatment with olanzapine was associated with overall greater improvement in social functioning (as measured by SFS) compared to risperidone-treated patients.