齐拉西酮与奥氮平治疗早期精神分裂症的临床效果比较

目的 探讨齐拉西酮和奥氮平对于治疗早期精神分裂症的临床疗效及比较两者的安全性。方法 选取我院2017年9月～2019年2月收治的60例早期精神分裂症患者作为研究对象,采用数字随机法将所有患者分成对照组30例和观察组30例,对照组给予奥氮平治疗,观察组给予齐拉西酮治疗。2周为1个疗程,两组均进行8周4个疗程治疗。比较两组患者于治疗前和治疗后2、4、8周进行阳性和阴性症状量表(PANNS)评分,病情严重程度(SI)、疗效总评(GI)评分和不良反应。结果 治疗2周、4周后,两组患者的PANSS评分和SI、GI评分均较低于治疗前,但两组的PANSS评分和SI、GI评分比较,差异无统计学意义(P0.05);疗程结束后,观察组的患者PANSS评分和SI、GI评分均低于对照组,差异有统计学意义(P0.05);治疗期间,对照组的不良反应发生率高于观察组,差异有统计学意义(P0.05)。结论 对于治疗早期分裂症患者,齐拉西酮的长期治疗效果明显优于奥氮平,且安全可靠,值得临床上进一步推广。     

奥氮平与利培酮治疗首发精神分裂症对照研究

目的 比较奥氮平与利培酮治疗首发精神分裂症的疗效及不良反应。方法 随机将符合CCMD-2R精神分裂症的诊断标准70例患者进入奥氮平或利培酮组接受治疗,分别在治疗0、1、2、4、6、8周评定PANSS和TESS量表,在0、4、8周检查心脑电图和肝肾功能,在0、8周检查血催乳素和空腹血糖。结果 奥氮平与利培酮疗效相当,奥氮平能迅速减轻精神症状,其产生的不良反应少、严重程度轻,很少引起血催乳素变化;利培酮会显著提高血催乳素水平。结论 奥氮平对首发精神分裂症治疗安全有效。     

Length of hospital stay and associated costs for olanzapine vs. haloperidol in the treatment of schizophrenia relapse in Germany

We examined the number of days spent in hospital due to a relapse of schizophrenia and the associated costs for patients treated with olanzapine or haloperidol. Twenty-one German psychiatric hospitals participated in this retrospective study. Data on the last hospitalisation following a relapse of schizophrenia were documented for equal numbers of patients on olanzapine and haloperidol. Matching for time since diagnosis and severity of symptoms was performed. Data were collected on 136 matched pairs. Total length of time spent in hospital was the same on average for patients in both groups (median about 5 weeks), but olanzapine patients spent nearly 1 week less in the in-patient setting than haloperidol patients, resulting in a saving of Euro 411 per patient. Our findings are consistent with those of randomised clinical trials in concluding that olanzapine is preferable to haloperidol in terms of the direct cost of treating schizophrenia. Andrea Spannheimer Kendle GmbH & Co. GMI KG, Stefan-George-Ring 6, 81929 Munich, Germany, e-mail: spannheimer.andrea@kendle.com     

A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism

Objective: Olanzapine is a novel antipsychotic, which is effective against both the positive and negative symptoms of schizophrenia and causes fewer extrapyramidal adverse effects than conventional antipsychotics. The purpose of the present study was to assess the potential for a pharmacokinetic interaction between olanzapine and carbamazepine, since these agents are likely to be used concomitantly in the treatment of manic psychotic disorder. Method: The pharmacokinetics of two single therapeutic doses of olanzapine were determined in 11 healthy volunteers. The first dose of olanzapine (10 mg) was taken alone and the second dose (10 mg) after 2 weeks of treatment with carbamazepine (200 mg BID). Measurement of urinary 6-hydroxycortisol/cortisol excretion was used as an endogenous marker to confirm that induction of CYP3A4 by carbamazepine had occurred. Results: The dose of olanzapine given after a 2-week pre-treatment with carbamazepine was cleared more rapidly than olanzapine given alone. Olanzapine pharmacokinetic values for C_max and AUC were significantly lower after the second dose, the elimination half-life was significantly shorter, and the clearance and volume of distribution were significantly increased. Conclusion: Carbamazepine has been shown to induce several P450 cytochromes including CYP3A4 and CYP1A2. Since CYP1A2 plays a role in the metabolic clearance of olanzapine, the interaction may be attributed to induction of CYP1A2 by carbamazepine, leading to increased first-pass and systemic metabolism of olanzapine. The interaction is not considered to be of clinical significance because olanzapine has a wide therapeutic index, and the changes in plasma concentration of olanzapine are within the fourfold variation that occurs without concern for safety in a patient population. Received: 22 July 1997 / Accepted in revised form: 1 June 1998     

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors

The atypical antipsychotic olanzapine was compared to other atypical as well as typical antipsychotic agents for in vivo occupancy of D₁, D₂, D₃, 5HT₂, and muscarinic receptors in rat brain. Blockade of D₂ receptors was determined by measuring the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). To assess the interaction with phosphoinositide (PI)-coupled 5HT_2A and muscarinic receptors in vivo, we used a novel radiometric technique to measure in vivo PI hydrolysis. The antagonism of olanzapine and other antipsychotic agents on 5HT_2A and muscarinic receptors was determined by in vivo blockade of PI hydrolysis, stimulated by the 5HT₂ agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) or the muscarinic agonist pilocarpine. Olanzapine inhibited 5HT₂, D₂, and D₃ in vivo binding with high potency (ID₅₀ = 0.15, 0.6 and 1.2 mg/kg, IP, respectively), while inhibiting D₁ and muscarinic in vivo binding with much less potency (ID₅₀ > 10 mg/kg, IP). The binding of olanzapine to D₂ receptors in neostriatum was well correlated with the increase of DOPAC (ED₂₀₀ = 0.8 mg/kg, IP) in vivo, indicating dopamine D₂ antagonism. In vivo PI hydrolysis was increased by DOI in frontal cortex and by pilocarpine in hippocampus up to 2- and 7-fold above the basal level, respectively. The agonist-induced increases in PI hydrolysis were fully blocked by the 5HT_2A antagonist MDL100907 and the muscarinic antagonist scopolamine, indicating the mediation by 5HT_2A receptors in frontal cortex and PI-coupled muscarinic receptors (m1, m3, and m5) in hippocampus, respectively. Olanzapine was about 8-fold more potent in vivo in blocking DOI-induced stimulation of PI hydrolysis (ID₅₀ = 0.1 mg/kg, IP) than pilocarpine-induced stimulation of PI hydrolysis (ID₅₀ = 0.8 mg/kg, IP). In conclusion, olanzapine is more potent in blocking the 5HT_2A receptor than D₁, D₂, D₃ and muscarinic receptors in vivo, consistent with its favorable clinical profiles. In addition, the novel in vivo PI hydrolysis assay proved to be a useful and reliable in vivo method to assess the functional efficacy of compounds that interact with the 5HT₂ and muscarinic receptors. Received: 10 February 1998/Final version: 22 April 1998     

奥氮平的国内临床应用概况

目的：总结奥氮平在国内的临床应用情况。方法：汇总国内公开发表的9种杂志中刊登的临床应用文献27篇，综合其治疗方法、疗效和不良反应等情况。结果：经PANSS，BPRS，SANS，SAPS，和TESS等量表测试和临床观察，认为奥氮平对治疗精神分裂症有相当的疗效；临床疗效等同或优于氯氮平、利培酮和舒必利；对精神分裂症的思维障碍和敌对猜疑疗效显著；对精神分裂症的阳性症状、阴性症状有效。不良反应小，安全性高，患者依从性好。结论：奥氮平可选用于精神分裂症等精神病的治疗，是目前比较满意的抗精神病药物。     

奥氮平联合氟西汀治疗精神分裂症阴性症状的对照研究

目的探讨奥氮平联合氟西汀治疗精神分裂症阴性症状的疗效及安全性。方法将以阴性症状为主的精神分裂症患者分为奥氮平合用氟西汀组32例和单用奥氮平组30例，两组均以PANSS量表减分情况评定疗效，TESS量表评定药物不良反应，共观察8周。结果（1）奥氮平合用氟西汀组与单用奥氮平组治疗精神分裂症的有效率为90．63％和73．33％（P〉0．05），显效率为75．00％和40．00％（P〈0．01）。（2）PANSS总分减分及PANSS阴性因子分减分在第2、4、8周末奥氮平合用氟西汀组均优于单用奥氮平组（P〈0．05或0.01）。（3）两组药物的不良反应少，奥氮平合用氟西汀组的体重增加明显低于单用奥氮平组（P〈0．05）。结论奥氮平联合氟西汀治疗能明显改善精神分裂症的阴性症状，且安全性好。     

中药汤剂治疗奥氮平药物副反应的临床经验

目的:分析总结中药汤剂治疗奥氮平药物副反应的临床经验。方法:调查服用奥氮平1月以上的精神病患者,统计服用药物后较常出现的中医证候及舌脉象,类推奥氮平的中医“药毒”特性;将60例受试者随机分为2组,其中奥氮平合并服用中药汤剂的为治疗组,中药汤剂根据辨证论治选用温胆汤、玉女煎、补中益气汤、补脾胃泻阴火升阳汤加减治疗,对照组服用奥氮平合并安慰剂,观察治疗前、治疗1月、2月后中医证候评分及糖脂代谢指标的前后变化及组间差异,对疗效进行评估。结果:服用奥氮平1月前后比较,受试者便秘、纳多、肥胖、口干、脉数、精神疲倦、苔厚腻、肢体乏力、舌红、舌淡、脉滑、舌边齿痕、舌胖大、苔白的中医证候评分较前显著升高,具有统计学差异(P<0.05或P<0.01)。中医辨证分型为痰湿内阻证、胃热伤津证、脾气亏虚证和兼有脾虚、痰湿、胃热证。运用传统中医分析中药药性及功效的方法,类推奥氮平的“药毒”性热,入脾胃经,具有胃热伤津、伤脾生湿的作用。经过2月中药汤剂治疗后,试验组中医证候总分较前显著降低,差异具有统计学意义(P<0.01);试验组与对照组比较治疗后中医证候总分差异有显著性(P<0.01)。治疗后试验组与对照组的空腹血糖、餐后2h血糖、血清胰岛素、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、体重、腰围、腰臀比及BMI值差异有显著性(P<0.05)。结论:临床上依据奥氮平“药毒”特性来辨证论治,运用中药汤剂治疗可以显著减少奥氮平所致的药物副反应。     

Olanzapine-induced mania

This report describes a case of manic symptoms induced by olanzapine in an 85-year-old female with a 3 year history of delusional disorder. She was treated in the past with trifluoperazine and risperidone. Symptoms were severe enough to require detention in hospital. Florid manic symptoms resolved two weeks after stopping olanzapine while only using 1 mg of haloperidol as required.     

Eight-year follow-up of olanzapine therapy in a previous treatment-refractory schizophrenic patient: a case report

The introduction of atypical antipsychotic drugs during the 1990s represented a great step forward in the treatment of schizophrenia and other psychoses. These drugs might more effectively prevent relapse because of their effectiveness against a wider range of schizophrenic symptoms, as well as their improved tolerability, which leads to improved medication compliance. Olanzapine, a thienobenzodiazapine, is an antipsychotic drug with high affinity for the serotonergic receptors 5-HT 2 and 5-HT 6 and high affinity for dopaminergic receptors, mainly D2, D3 and D4, and with a lower propensity to cause extrapyramidal symptoms or increasing prolactin levels. The long-term efficacy and safety of olanzapine for treating treatment-refractory schizophrenia is still being investigated. The authors present a case of a 43-year-old man suffering from chronic treatment-resistant schizophrenia with both positive and negative symptoms, who was successfully treated with olanzapine for 8 years. (Int J Psych Clin Pract 2002; 6: 211-214 )