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。     

奥氮平和利培酮治疗精神分裂症临床对照研究

目的比较奥氮平和利培酮对精神分裂症的治疗效果和安全性。方法以奥氮平与利培酮对120例精神分裂症患者进行为期6周的对照治疗,采用阳性和阴性症状量表（PANSS）评定疗效,用副反应量表（TESS）评定副反应。结果奥氮平组显效率76．7％,有效率95％;利培酮组显效率76．7％。有效率93％。奥氮平的主要副反应为嗜睡,利培酮的主要副反应为锥体外系反应。结论两药治疗精神分裂痘均有良好疗效．且安全性较高。     

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。     

The effect of treatment with risperidone,olanzapine or phenothiazines on cognitive functions in patients with schizophrenia

INTRODUCTION: Theaimofthestudywastocomparetheeffectsofrisperidone, olanzapine and phenothiazines on cognitive functions in schizophrenia during short-term (4 &#45 6 weeks) and long-term (3 &#45 4 months) treatment. METHOD: Seventy patients with schizophrenia were investigated: 30 treated with risperidone, 20 with olanzapine and 20 with phenothiazines, in standard doses. Psychometric measurements were made with the Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests included the Trail Making Test (TMT), the Stroop Test and the Wisconsin Card Sorting Test (WCST). RESULTS: PANSS negative symptoms decreased significantly after risperidone and olanzapine, did not change after short-term, and improved marginally after long-term, phenothiazine treatment. Risperidone treatment resulted in significant amelioration of performance on all neuropsychological tests after both short- and long-term treatment. Olanzapine gave benefit on five out of seven subtests, although in most instances this effect was noted only after long-term treatment. Olanzapine was inferior to risperidone in improving WCST performance. Treatment with phenothiazines brought about improvement on two subtests while the results on three showed significant deterioration. CONCLUSION: The results obtained suggest that novel antipsychotics show differential effect on cognition, with risperidone especially improving working memory; however, their effect on negative symptoms and cognitive functions is better than that of typical neuroleptics.     

利培酮与奥氮平治疗首发精神分裂症的1年随访研究

目的评价利培酮与奥氮平治疗首发精神分裂症的疗效与不良反应。方法本研究为开放性，平行对照，药物剂量可调整的临床试验。采用自然观察研究方法，结合全病程管理模式对研究对象进行1年随访研究。分别有131例和136例首发精神分裂症患者被分入利培酮组和奥氮平组。利培酮组剂量为3—6mg，平均（3．8±1．3）mg，奥氮平组剂量为10—20mg，平均（12．9±5．6）mg。疗效主要统计指标为阳性和阴性症状评定量表（PANSS）的总分值及有效率，持续治疗时间。PANSS减分率≥50％定义为有效。次要统计指标为复发率、复发时间及药物不良反应。用副反应量表（TESS）评估药物不良反应。结果12月末时，利培酮组有85例患者（64．9％）完成随访，奥氮平组为93例（68．4％），两组差异无统计学意义（P〉0．05）。治疗终点利醅酮和奥氮平组有效率分别为62．6％和69．8％，差异无统计学意义（P〉0．05），随访中其他时点（2、3、6、8个月）两组有效率差异亦无统计学意义。12个月末利培酮组和奥氮平组的复发率（14．5％、12．5％）、持续治疗时间（9．5±3．8月、9．7±3．8月）、复发时间（4．0±2．9月、5．1±2．8月）等差异均无统计学意义（均P〉0．05）。不良反应方面，利培酮组锥体外系反应比例高于奥氮平组，奥氮平组体重增加比例高于利培酮组。结论利培酮与奥氮平治疗首发精神分裂症1年疗效均好，利培酮组锥体外系反应发生较多，奥氮平组体重增加较多。     

奥氮平与利培酮治疗难治性精神分裂症的对照研究

目的 比较奥氮平与利培酮对难治性精神分裂症的疗效及安全性.方法 68例难治性精神分裂症患者按照排列表法随机分为奥氮平组[34例,(24.1±5.4)mg/d]和利培酮组[34例,(7.9±1.8)mg/d],疗程均为12周.采用阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)及治疗中需处理的不良反应症状量表(TESS),在治疗前及治疗第1,2,4,8,12周末分别评定疗效和不良反应.结果 (1)奥氮平组PANSS总分、阳性症状分、阴性症状分及一般病理分均从治疗第2周末起较治疗前下降(P<0.05～0.01);利培酮组PANSS总分、阳性症状分、一般病理分从治疗第2周末起,阴性症状分从第4周末起,较治疗前下降(P<0.05～0.01);奥氮平组从治疗第2周末起各时点PANSS总分、阴性症状分均低于利培酮组(P<0.05～0.01).(2)治疗第2周末起,2组临床总体印象量表-严重程度和改善程度(CGI-SI)总分均较治疗前下降(P<0.05～0.01);2组间各时点CGI-SI分的差异无统计学意义(P>0.05).(3)治疗第12周末,奥氮平组、利培酮组临床总有效率分别为65%、41%,差异有统计学意义(P<0.05).(4)奥氮平组、利培酮组不良反应发生率分别为53%(18/34)和59%(20/34),差异无统计学意义(P>0.05);奥氮平组体质量增加发生率高于利培酮组(P<0.05);利培酮组静坐不能、异常泌乳和(或)闭经、肌张力增高的发生率高于奥氮平组(P<0.05).结论 奥氮平对难治性精神分裂症有良好疗效,不良反应轻微.     

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.     

The clinical value of risperidone and olanzapine: A meta-analysis of efficacy and safety

INTRODUCTION: Since 1990 novel antipsychotics have been available to treat schizophrenia. Risperidone and olanzapine have emerged as the two most popular members of this class. The current report aims to synthesize the clinical trial data currently available on these two novel antipsychotics and compare them with conventional products in terms of efficacy and safety. METHODS: Published randomized clinical trials, which included a risperidone or olanzapine arm, were sought through the MEDLINE, EMBASE and PSYCLIT databases. Trials were only excluded due to reporting failures or design incompatibilities (not randomized). A random effects approach was applied to compare information across trials, and meta-regression was used to compare product categories and gain insight into patient factors related to clinical outcomes. Outcome variables measured were total Positive and Negative Symptom Scale (PANSS) score, withdrawals due to inefficacy and use of medication for extrapyramidal symptoms (EPS). RESULTS: Risperidone and olanzapine offer advantages over conventional products in terms of both efficacy and safety. Of the two novel antipsychotics studied, the benefits of risperidone were clearer than those with olanzapine in terms of efficacy; this could not be assessed for safety due to inconsistencies in the reporting of extrapyramidal symptoms between studies. CONCLUSION: Patients receiving novel antipsychotics, particularly risperidone, are likely to gain improved control of symptoms of schizophrenia and are less likely to require medication to counteract extrapyramidal symptoms than patients receiving conventional neuroleptics.     

奥氮平与利培酮对精神分裂症认知功能影响的对照研究

目的 比较两种非经典抗精神病药奥氮平、利培酮对精神分裂症病人认知功能的影响.方法 62例急性发病期的精神分裂症患者(包括首发与复发)为研究对象,随机分为两组,分别予以奥氮平、利培酮治疗12周,在基线和12周末分别用阳性与阴性症状量表(PANSS)及副反应量表(TESS)、韦氏智能测验的数字广度和数字符号测验、连线测验A、连线测验B、MMSE依次评价疗效、安全性、认知功能.结果 12周末时两组的PANSS量表总分和各因子分较基线时有显著差异,治疗后两组之间无统计学差异.12周末与基线时比较奥氮平在数字广度顺背数、数字符号、TMT-A连线时间、TMT-A正确数、TMT-B连线时间、MMSE比较差异有统计学意义(P＜0.05).利培酮组在数字广度、数字符号、TMT-A连线时间、TMT-B连线时间、MMSE上有统计学的差异(P＜0.05).12周末时,两组之间相比较,显示利培酮在数字广度顺背数、TMT-B连线时间比较差异有统计学意义(P＜0.05).两组之间不良反应比较,利培酮组肌强直高于奥氮平组,差异有统计学意义(P＜0.05).结论 奥氮平组和利培酮组治疗精神分裂症疗效相当,改善认知功能疗效相当,利培酮可能在改善注意方面优于奥氮平.     

奥氮平与利培酮治疗老年精神分裂症对照研究

目的 比较奥氮平与利培酮治疗老年精神分裂症的临床疗效和安全性.方法 将60例老年精神分裂症患者随机分为两组,分别给予奥氮平(研究组)和利培酮(对照组)治疗,疗程8周,采用阳性与阴性综合征量表(PANSS)及治疗中需处理的不良反应症状量表(TESS)评定疗效及不良反应.结果 治疗8周后,研究组显效率70.0％,对照组显效率66.7％,两组疗效相仿.两组治疗2周末PANSS总分和各因子分均较治疗前有显著下降(P＜0.01),两组间比较,差异无显著性(P＞0.05);研究组不良反应少而轻,锥体外系反应(EPS)明显低于对照组(P＜0.05).结论 奥氮平和利培酮治疗老年精神分裂症疗效相当,奥氮平不良反应少而轻,安全性好.     

利培酮联合奥氮平治疗脑器质性精神障碍疗效分析

目的探讨利培酮联合奥氮平治疗脑器质性精神障碍的有效性和安全性,评价临床疗效。方法选择我院2011-10—2013-10收治的脑器质性精神障碍患者130例,分为对照组和观察组,对照组63例患者单独口服奥氮平治疗;观察组67例患者采用利培酮联合奥氮平治疗。2组患者均于治疗前及治疗后1、3、5、7周末使用阳性和阴性精神症状量表(PANSS)评定患者精神障碍的缓解情况,比较2组总有效率及不良反应发生率。结果观察组治疗后1周末即显示出明显效果,而对照组则在治疗后3周末才与入组时有显著性差异,且2组间PANSS量表评分及减分率在治疗后1、3、5、7周末差异均有统计学意义(P0.01);观察组总有效率高达95.52%,显著优于对照组的85.71%,2组对比差异有统计学意义(χ2=12.13,P0.01);2组不良反应率分别为34.33%、33.33%,差异无统计学意义(χ2=2.26,P0.05)。结论利培酮联合奥氮平应用于治疗脑器质性精神障碍中,能显著缓解患者的精神症状,且不增加药物的不良反应,值得临床推广。     

奥氮平替换利培酮对催乳素及糖脂代谢的影响

目的探讨用奥氮平替换利培酮治疗精神分裂症后,催乳素水平及糖脂代谢的变化。方法对52例服用利培酮治疗的精神分裂症患者换为奥氮平治疗8周。于基线及换药后第8周测空腹催乳素、胰岛素、血糖、甘油三酯、胆固醇、脂蛋白及体重。结果换用奥氮平8周后,催乳素水平显著下降,胰岛素、甘油三酯、栽脂蛋白A1、载脂蛋白B水平均显著升高,体重显著增加（均P〈0．05）。总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平略有升高,空腹血糖略有下降,但差异均无统计学意义（均P〉0．05）。结论奥氮平替换治疗能够明显的改善利培酮所致的高催乳素血症,但也可能会引起脂代谢异常。     

Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine

This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not significantly different between groups. Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and standing blood pressure than non-switched patients. Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia.     

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.     

Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol

Background Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees. We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract. Methods We measured the plasma prolactin levels at 0, 30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a) 33 patients in a drug-free state, b) 15 patients on treatment with clozapine (range 200–600 mg/day), c) 15 patients on olanzapine (10–30 mg/day), d) 14 patients on risperidone (8–16 mg/day), e) 23 patients on haloperidol (10–40 mg/day), f) 14 patients on sulpiride (600–1600 mg/day). Data were also obtained from a group of 14 healthy male control subjects. The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared. Results The baseline prolactin levels did not differ significantly in the groups of controls (8.3±3.8 ng/ml), drug-free patients (8.0±3.6) and patients treated with clozapine (7.7±3.8), they were moderately elevated in patients treated with olanzapine (16.8±8.9), elevated in patients on haloperidol (34.4±17.3), and they were even higher in the groups of patients treated with risperidone (54.9±22.4) or sulpiride (58.8±27.0). All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls. During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed. The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients. Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors. According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine. This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques. Received: 26 March 2001 / Accepted: 21 June 2001     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.     

奥氮平与利培酮对青少年精神分裂症首发患者糖、脂代谢的影响对照研究

目的探讨奥氮平与利培酮对首发青少年精神分裂症患者空腹血糖及血脂水平的影响。方法70例符合入组标准的精神分裂症患者被随机分为奥氮平组（32例）和利培酮组（38例）。治疗观察6周。两组患者在治疗前及治疗第6周末分别检测空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、身高、体质量并计算体质量指数。结果（1）治疗第5周末，奥氮平组患者的体质量指数、血糖、甘油三脂及低密度脂蛋白胆固醇水平均升高，与治疗前的差异有统计学意义（P〈0．05）；两组患者的体质量指数差值、血糖差值及甘油三脂差值间比较有统计学意义（P〈0．05）。（2）两组患者男女间各项指标差值的比较均无统计学意义（P〉0．05）。（3）奥氮平组患者体质量的增加与血糖、甘油三脂有显著相关关系（P〈0．05）。结论奥氮平对青少年精神分裂症患者糖、脂代谢的影响明显大于利培酮。     

氟伏沙明抑制奥氮平体内代谢的药代动力学研究

目的　探讨细胞色素P450 1A2酶 (CYP1A2 )抑制剂氟伏沙明对奥氮平在体内代谢的影响。方法　 1 2名男性健康志愿者 ,采用自身前后对照设计 ,两次服药间隔 4周 ,口服单剂奥氮平 1 0mg;对照部分采用单剂量奥氮平 ,试验部分是在氟伏沙明连续 9天服用过程中的第 4天合用单剂量奥氮平。高效液相色谱电化学法测定奥氮平血浆浓度。结果　合用氟伏沙明后 ,奥氮平各时点的平均浓度增高 ;奥氮平的峰浓度由 1 9 5μg/L增至 2 9 1 μg/L(1 52倍 ,P <0 0 0 1 ) ,消除半衰期由 32 2h延长为46 1h(1 48倍 ,P <0 0 1 ) ,0～ 1 2 0h药时曲线下面积由 647 5μg·h 1 ·L 1 增至 1 0 55 0 μg·h 1 ·L 1 (1 65倍 ,P <0 0 0 1 ) ;而达峰时间由 3 8h缩短为 2 6h(0 69倍 ,P <0 0 1 ) ,系统清除率由 1 6 4L/h减至 8 5L/h(0 59倍 ,P <0 0 0 1 ) ,表观分布容积由 435 5L降为 2 99 2L(0 70倍 ,P <0 0 1 )。结论　氟伏沙明能明显抑制奥氮平在体内的代谢。CYP1A2可能是催化奥氮平体内代谢的主要氧化酶之一。奥氮平与涉及CYP1A2的药物合用时应注意密切观察、趋利避害     

Drug monitoring of lamotrigine and oxcarbazepine combination during pregnancy

Little is known about pregnancy-induced alterations in the pharmacokinetics of the newer antiepileptic drugs, especially when used in combinations. Two women receiving combination therapy of lamotrigine (LTG) and oxcarbazepine (OXC) were followed prospectively during pregnancy and puerperium. Steady-state concentrations of LTG and the active metabolite of OXC, 10-hydroxycarbazepine (MHD), were measured at regular intervals using a dried blood spot method, and clearances were calculated. A strong effect of pregnancy on the clearance of both LTG and MHD was seen. An increase in seizure frequency occurred in both women. This stresses the importance of therapeutic drug monitoring of LTG and MHD during pregnancy. In case of breakthrough seizures or increased seizure frequency, dosage adjustment of both drugs may be required.