拉莫三嗪对难治性癫痫的治疗作用

目的：评价拉莫三嗪对难治性癫痫的治疗作用和安全性。方法：难治性癫痫病人７６例治疗前３ｍｏ开始填写发作的逐日志，完成后随机分成单盲、安慰剂对照（ｎ＝４４）与双盲、交叉、安慰剂对照（ｎ＝３２）２组，保持原用抗痫药不变，按５０～４００ｍｇ／ｄ（未用丙戊酸者）或２５～２００ｍｇ／ｄ（用丙戊酸者），ｑｏｄ，ｑｎ或ｂｉｄ加用拉莫三嗪，对照组用同等剂量的维生素Ｃ，３ｍｏ为一个疗程。结果：拉莫三嗪有效率为５６％，不良反应较轻。结论：拉莫三嗪治疗难治性癫痫是有效和安全的。     

拉莫三嗪与丙戊酸钠对癫痫患者认知功能影响对比研究

目的:评价拉莫三嗪与丙戊酸钠对癫痫患者认知功能的影响。方法:将82例癫痫患者随机均分为拉莫三嗪组(治疗组)与丙戊酸钠组(对照组),利用简易精神状态检查量表(MMSE),分别于治疗前、用药3个月及用药6个月后对患者认知功能进行神经心理学评估。结果:治疗组在用药3个月及用药6个月时与用药前比较,MMSE分值无明显差异;对照组在用药3个月及6个月时与用药前比较,MMSE分值明显下降。结论:丙戊酸钠对患者认知功能有影响,而拉莫三嗪在治疗前后对患者认知功能无明显影响。     

Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data

Aims To examine the population pharmacokinetics of lamotrigine in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks.
Methods The population consisted of 158 Caucasians and 5 Asians of whom 81 were males and 82 females. Age and weight ranged between 14 and 76 years and 41–107  kg, respectively. A one-compartment compartment model with first-order absorption and elimination was fitted to plasma lamotrigine concentration-time profiles from retrospective drug monitoring, using non-linear mixed effect modelling (NONMEM), with first-order estimation. Oral clearance (CL_o ), apparent volume of distribution ( V  / F ) and absorption rate constant ( K _a ) were the main pharmacokinetic parameters.
Results CL_o was not significantly influenced by body weight, age, gender, oral contraceptives and dose. However, due to auto-induction CL_o increased by 17.3% during the 48 weeks of therapy, from 1.94 to 2.28  l h⁻¹, and was 28.7% lower in Asians than Caucasian. The final magnitude in interpatient variability was 32%. The effect of the covariates weight, age, race and gender on V  / F was examined and none was statistically significant. The final population estimate of V  / F was 77.4  l with an interpatient variability of 34%.
Conclusions In view of the wide therapeutic margin of lamotrigine and the 21% residual variability in plasma concentrations, the modest significant effects of race and auto-induction on clearance are unlikely to be clinically significant and, thus, no dosage adjustment is warranted for these effects.     

拉莫三嗪治疗儿童和成人癫痫的耐受性和安全性评价

拉莫三嗪是临床广泛应用的抗癫痫药物之一。欧洲专家共识2007、中国癫痫诊疗指南、美国神经病学学会和美国癫痫学会均推荐为治疗顽固性部分性癫痫发作、成人或儿童原发性全身性癫痫、儿童和青少年失神发作、青少年肌阵挛性癫痫等的首选药物。本文对拉莫三嗪治疗各种类型癫痫的耐受性和安全性进行总结,从认知、内分泌、性功能、体重和社会心理等方面评价拉莫三嗪治疗的安全性。     

Cytisine inhibits the anticonvulsant activity of phenytoin and lamotrigine in mice

BackgroundCytisine (CYT), the most commonly used drug for smoking cessation in Poland, was experimentally found to induce convulsions. There is a lack of studies on the influence of CYT on the anticonvulsant activity of antiepileptic drugs (AEDs).MethodsThe effects of CYT on the anticonvulsant activity of six AEDs were examined in maximal electroshock (MES)-induced seizures in mice.ResultsSingle intraperitoneal (ip) administration of CYTin a subthreshold dose of 2 mg/kg antagonized the protective activity of ip phenytoin and lamotrigine against MES-induced seizures in mice. Adose of 1 mg/kg did not reverse the protective activity of phenytoin and lamotrigine. CYT in a dose of 2 mg/kg had no effect on the anticonvulsive activity of carbamazepine, oxcarbazepine, phenobarbital, and valproate magnesium.ConclusionCYT ability to antagonize the anticonvulsive activity of phenytoin and lamotrigine can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to these drugs resulting in possible breakthrough seizure attacks.     

Extended-release lamotrigine in the treatment of patients with epilepsy

Importance to the field: Epilepsy is a neurological disorder primarily characterized by recurrent, unprovoked seizures resulting from excessive or synchronous neuronal activity in the brain. Depending on the case definition and population studied, the lifetime prevalence of epilepsy in the USA is estimated to be 1.2 – 2.9%. In general, epilepsy is related to a significant increased risk of mortality and injury. A cornerstone of epilepsy management is use of antiepileptic drugs (AEDs). This review focuses on the AED lamotrigine, with particular emphasis on the extended-release formulation, in the management of patients with epilepsy, and the significant clinical issues that may be relevant with once-daily AED therapy.

Areas covered in this review: An introductory section overviews the prevalence of epilepsy, current treatment recommendations for patients with epilepsy, and unmet needs in epilepsy management. This is followed by an overview of the AED market with currently available and developing compounds, a summary of lamotrigine and extended-release lamotrigine, clinical efficacy and tolerability studies with extended-release lamotrigine, and regulatory issues. The review concludes with an expert opinion summary on the important issue of treatment adherence, the possible role of extended-release lamotrigine in adherence enhancement, and additional research and areas which need further focus for optimal epilepsy outcomes.

What the reader will gain: The reader will gain familiarity with extended-release (once-daily) lamotrigine and clinical issues that may be relevant to once-daily use. Once-daily AED use might be one way to simplify the epilepsy treatment regimen and can pave the way for other approaches that can maximize adherence, such as a frank discussion of risks, benefits, and attitudes towards treatment – all critical components of a strong and positive doctor–patient relationship.

Take home message: The AED lamotrigine is widely used in clinical settings and has become available in a once-daily extended-release version, which may minimize serum concentration fluctuation and presumably would both reduce patient burden and maximize treatment adherence as opposed to the immediate-release version of the compound. Adverse effects and safety concerns between the immediate- and extended-release versions of lamotrigine seem similar based upon interpretation of the limited literature.     

拉莫三嗪在癫痫患者中的效果观察

目的:探讨拉莫三嗪治疗成人癫痫患者的临床疗效,以及对患者生活质量的影响。方法:选取符合标准的癫痫患者60例,其中30例服用拉莫三嗪片患者作为观察组,服用苯巴比妥片的30例患者作为对照组,比较2组患者治疗前、治疗6个月和12个月癫痫发作次数及生活质量。结果:观察组患者癫痫发作次数、临床总有效率及生活质量评分,均优于对照组,差异均存在统计学意义(P<0.05);2组患者均未发生严重并发症,不良反应发生率相似(P>0.05)。结论:拉莫三嗪治疗成人癫痫,可以有效控制患者的临床发作,提高患者生活质量,无严重不良反应,安全有效,值得临床推广应用。     

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children

1   Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication.
2   This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively.
3   Thirty-one children aged 6 months to 5 years were included and received a 2  mg  kg⁻¹ single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean±s.d.) were: 7.7±1.8  h, 21.9±6.8  h, 44.7±10.2  h in the 'inducer', 'other' and 'inhibitor' groups respectively.
4   Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3  mg  l⁻¹. The mean minimum plasma concentration for the three groups was 2.54±1.28  mg l⁻¹ at steady state.
5   Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.     

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Aim:

To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline.

Methods:

LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NONMEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models.

Results:

The final regression model for LTG was as follows: CL (L/h)=1.01^*(TBW/27.87)^0.635*e^−0.753*VPA*e^0.868*CBZ*e^0.633*PB, Vd (L)= 16.7^*(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation.

Conclusion:

A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.     

Antioxidant agents and physiological responses in adult epileptic patients treated with lamotrigine

BackgroundThe aim of our research was to evaluate some biochemical changes in blood during lamotrigine (LTG) monotherapy of adult patients with epilepsy, and to check possible associations between typical selenium status parameters and the frequency of seizures.MethodsThe study was performed by examining aspartate aminotransferase (AspAT), alanine aminotransferase (AlaAT), creatinine, ferric reducing ability of plasma (FRAP), serum uric acid (UA), uric-acid-independent FRAP (UAiFRAP), plasma glutathione peroxidase (GPX3), selenoprotein P (SelP), plasma superoxide dismutase (pSOD), 8-hydroxy-2’-deoxyguanosine (8-OHdG) in serum and urine, serum selenium (sSe) and zinc (sZn), in 22 adult patients with epilepsy and 22 healthy controls. Additionally, the levels of LTG were determined in patients.ResultspSOD activity was higher in the study group (5.32 ± 1.24 U/ml) compared with the controls (4.05 ± 0.92 U/ml, p = 0.008). No other statistical difference between patients and controls was found.ConclusionLack of difference in parameters other than SOD, particularly no difference in 8-OHdG concentrations between the patients treated with LTG compared to the control subjects suggests that these patients are at no particular risk of oxidative DNAdamage. In patients who are well or moderately well clinically controlled, selenium status parameters (sSe, GPX3, SelP) are not directly connected with the frequency of seizures.     

Influence of cirrhosis on lamotrigine pharmacokinetics

AIMS: Lamotrigine, an antiepileptic drug, is cleared from the systemic circulation mainly by glucuronidation. The possibility of changes in the pharmacokinetics of lamotrigine in plasma owing to hepatic dysfunction has been evaluated. METHODS: Thirty-six subjects, including 24 patients with various degrees of liver cirrhosis and 12 healthy volunteers received a single 100 mg dose of lamotrgine. Blood samples were taken for 7 days in all subjects, except nine with severe cirrhosis, who had a 29 day blood sampling period. RESULTS: The pharmacokinetics of lamotrigine were comparable between the patients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interval) in patients with severe cirrhosis without or with ascites (corresponding, respectively, to Child-Pugh grade B and C) to healthy subjects were, respectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects were, respectively, 204% (149%, 278%) and 287% (202%, 408%). CONCLUSIONS: Lamotrigine administered as a single oral dose of 100 mg was well tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pugh Grade B or C cirrhosis. Escalation and maintenance doses should be adjusted according to clinical response.     

不同剂量拉莫三嗪治疗老年癫痫的比较研究

目的 探讨不同剂量拉莫三嗪治疗老年癫痫患者的临床疗效。方法 选择2014年7月—2018年2月洛阳市第三人民医院神经内科诊治的老年癫痫患者88例作为研究对象,根据拉莫三嗪使用剂量分为对照组（40例）和观察组（48例）。对照组患者给予大剂量拉莫三嗪片治疗,拉莫三嗪起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量100 mg/d,维持100 mg/d治疗观察至第8周。观察组患者给予小剂量拉莫三嗪片治疗,起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量50 mg/d,维持50 mg/d治疗观察至第8周。观察两组患者的临床疗效,同时比较两组患者蒙特利尔认知评估量表（MoCA）评分、P300潜伏期、波幅和不良反应情况。结果 治疗后,对照组和观察组总有效率分别为97.5%、97.9%,两组对比差异无统计学意义。治疗后,两组患者的MoCA评分均显著高于治疗前,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后的MoCA评分显著高于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,观察组的P300潜伏期显著降低,波幅明显升高,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后P300潜伏期及波幅显著优于对照组,两组比较差异具有统计学意义（P<0.05）。观察组治疗期间的不良反应发生率为6.3%,显著低于对照组的32.5%,两组比较差异具有统计学意义（P<0.05）。结论 相对于大剂量,小剂量拉莫三嗪治疗老年癫痫患者能达到很好的疗效,能减少不良反应的发生,改善患者的神经电生理功能与认知功能。     

Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy

Objective: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration.

Methods: Formulation was optimized using four-factor three levels Box– Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model.

Results: The NLCs had a mean particle size of 151.6 ± 7.6 nm, polydispersity index of 0.249 ± 0.035, zeta potential of 11.75 ± 2.96 mV and EE of 96.64 ± 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 μgcm^?2h^?1. Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. γ scintigraphy studies further proved high accumulation of drug in brain.

Conclusion: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.     

The effects of lamotrigine on the pharmacokinetics of lithium

AIMS: The treatment of bipolar disorder often includes use of multiple drug therapies. Lithium is one of the most commonly used treatments, but has a narrow therapeutic window. Lamotrigine, an established antiepileptic drug, is emerging as a potentially important new therapy in the treatment of bipolar disorder. The objective of this two-treatment crossover study was to determine whether lamotrigine affects lithium pharmacokinetics. METHODS: Twenty healthy adult men completed the study. Subjects took 2 g lithium gluconate anhydrous every 12 h in the morning and evening for 5 days and in the morning of day 6, with or without 100 mg lamotrigine once daily in the morning for 6 days. Blood and urine samples were collected on day 6 of both treatments to characterize the pharmacokinetics of lithium using noncompartmental methods. RESULTS: The geometric least-square mean ratio for renal clearance of lithium between the combination treatment and lithium alone treatment was 0.93 (95% confidence interval 0.85-1.02). Both treatments were well tolerated. CONCLUSIONS: Lamotrigine does not cause significant change in the pharmacokinetics of lithium.     

视频脑电图监测对癫痫的诊断价值

目的:探讨视频脑电图(VEEG)对癫痫的诊断价值。方法:对39例发作性疾病患者进行VEEG检测,并与普通脑电图(REEG)进行比较分析。结果:REEG监测正常28例(71.8%),异常11例(28.2%),其中痫样放电8例(20.5%),临床发作1例(2.5%)。而VEEG监测正常11例(28.2%),异常28例(71.8%),其中痫样放电24例(61.5%),临床发作10例(33.3%)。结论:VEEG对癫痫发作及非癫痫发作的诊断和鉴别有重要价值。     

Effect of caffeine on the anticonvulsant effects of oxcarbazepine,lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures

Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. Using the mouse maximal electroshock model, the present study was undertaken so as to ascertain whether caffeine affects the anticonvulsant efficacy of the new antiepileptic drugs lamotrigine, oxcarbazepine and tiagabine. The results indicate that neither acute nor chronic caffeine administration (up to 46.2 mg/kg) affected the ED₅₀ values of oxcarbazepine or lamotrigine against maximal electroshock. Similarly, caffeine did not modify the tiagabine electroconvulsive threshold. Furthermore, caffeine had no effect on oxcarbazepine, lamotrigine and tiagabine associated adverse effects such as impairment of motor coordination (measured by the chimney test) or long-term memory (measured by the passive avoidance task). Concurrent plasma concentration measurements revealed no significant effect on lamotrigine and oxcarbazepine concentrations. For tiagabine, however, chronic caffeine (4 mg/kg) administration was associated with an increase in tiagabine concentrations. In conclusion, caffeine did not impair the anticonvulsant effects of lamotrigine, oxcarbazepine, or tiagabine as assessed by electroconvulsions in mice. Also, caffeine was without effect upon the adverse potential of the studied antiepileptic drugs. Thus caffeine may not necessarily adversely affect the efficacy of all antiepileptic drugs and this is an important observation.     

Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime cost–utility analysis

Objective: Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost–utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illness data were drawn from a previous ad-hoc study, and quality-of-life values were obtained by prospectively interviewing a separate group of 81 patients referred to our institution with epilepsy. Results: Our analysis showed that chronic lamotrigine treatment implies an incremental lifetime cost of about $1 600 000 for every 100 patients. Incremental lifetime utility was around 40 quality-adjusted life-years (QALYs) for every 100 patients. On the basis of these data, adjunctive lamotrigine was estimated to cost approximately $41 000 per QALY gained. Sensitivity testing suggested a range of $25 000–$85 000 per QALY gained. Conclusion: Adjunctive lamotrigine (500 mg per day) in refractory epilepsy seems to have a worse pharmacoeconomic profile than many pharmacological treatments commonly used in areas other than epilepsy. Further data are needed to determine if lamotrigine can be equally effective at lower (and less costly) daily doses which could markedly improve its pharmacoeconomic characteristics. Received: 5 September 1996 / Accepted in revised form: 25 September 1997     

拉莫三嗪联合左乙拉西坦治疗小儿难治性癫痫的临床研究

目的 探讨拉莫三嗪与左乙拉西坦联合治疗小儿难治性癫痫的疗效及对患儿血清高迁移率族蛋白1（HMGB1）、神经节苷脂抗体（GM1-A）的影响。方法 回顾性选择2017年6月—2020年6月在昆明市儿童医院治疗的难治性癫痫患儿120例为研究对象,根据患儿的治疗方案分为对照组和试验组。对照组给予左乙拉西坦片治疗,初始剂量为10～20 mg·kg^-1·d^-1,每周增加5～10 mg·kg^-1·d^-1,增加剂量至20～40 mg·kg^-1·d^-1,加量期3～7周,连续治疗6个月。试验组在对照组基础上给予拉莫三嗪片治疗,初始剂量为0.3～0.6 mg·kg^-1·d^-1,12 h服药1次,每周加量0.3～0.6 mg·kg^-1·d^-1,目标剂量5～10 mg·kg^-1·d^-1,治疗6个月。观察两组患者的治疗效果,比较治疗前及治疗6个月后两组患儿认知功能、血清炎症因子水平、血清免疫球蛋白水平、血清HMGB1、GM1-A、神经元特异性烯醇化酶（NSE）、神经肽Y（NPY）水平。记录治疗期间患儿不良反应发生情况。结果 试验组总有效率（88.33%）显著高于对照组总有效率（70%）,两组比较差异有统计学意义（P<0.05）;治疗前两组患儿的言语智商、操作智商评分比较差异无统计学意义（P>0.05）,治疗后两组患儿的言语智商、操作智商评分均显著升高（P<0.05）,且试验组升高更显著（P<0.05）;治疗前两组患儿的免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、免疫球蛋白G（IgG）水平比较差异无统计学意义（P>0.05）,治疗后两组患者的IgA、IgM、IgG水平均显著升高（P<0.05）,且试验组升高更显著（P<0.05）;治疗前两组患儿的GM1-A、NSE、NPY水平比较差异无统计学意义（P>0.05）,治疗后两组患儿的GM1-A、NSE水平均显著下降（P<0.05）,NPY水平均显著升高（P<0.05）,且试验组改善更显著（P<0.05）;治疗前两组患儿的HMGB-1、肿瘤坏死因子-α（TNF-α）、超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）水平比较差异无统计学意义（P>0.05）,治疗后两组患儿的HMGB-1、TNF-α、hs-CRP、IL-6水平均显著下降（P<0.05）,且试验组下降更显著（P<0.05）;两组患儿的不良反应发生率比较,差异无统计学意义（P>0.05）。结论 拉莫三嗪联合左乙拉西坦治疗难治性癫痫的治疗效果较好,可改善患儿的认知功能和免疫功能,降低炎症反应,改善HMGB-1、GM1-A水平,并且安全性较好。     

拉莫三嗪联合氯氮平对慢性精神分裂症患者临床疗效及生物学影响的研究

目的：探讨应用拉莫三嗪联合氯氮平治疗慢性精神分裂症的临床疗效以及对生物学指标,包括血糖、血脂[以总胆固醇（TC）水平计]、体质量及心电图（EKG）的影响。方法：选取某院于2013年6月-2014年6月期间收治的68例慢性精神分裂症患者作为研究对象,并按照随机数字表法将其分为2组,每组34例。对照组患者给予氯氮平以及对症支持治疗,而试验组患者在对照组治疗的基础上加用拉莫三嗪进行治疗。2组患者的疗程均为3个月。治疗后,观察并记录2组患者的临床症状,并在治疗前后检测患者的血糖、TC、体质量、EKG和生活质量评分的变化情况。结果：试验组患者的总有效率为88.24%,显著高于对照组的70.59%（P<0.05）。治疗3个月后,2组患者的精神病理症状评分、阳性症状评分、阴性症状评分和PANSS总分均显著降低,与治疗前相比较差异有统计学意义（P<0.05或P<0.01）;试验组患者在上述各指标方面的改善程度相比对照组更为明显,组间差异有统计学意义（P<0.01）。治疗后,对照组患者血糖、EKG和体质量指标均明显增大,与治疗前相比较差异有统计学意义（P<0.05）;试验组患者的上述指标则稍有降低或未有明显变化,均无统计学意义（P>0.05）,但与对照组相比,组间差异有统计学意义（P<0.05）。治疗过程中,2组患者在便秘、心跳过快、静坐不能、白细胞减少、心电图异常和体质量增加方面相比,组间差异有统计学意义（P<0.05或P<0.01）。治疗后,2组患者的生活质量评分相对治疗前均显著提高（P<0.05）;试验组患者生活质量评分的提高程度相比对照组更为明显,组间差异有统计学意义（P<0.05）。结论：拉莫三嗪联合氯氮平治疗慢性精神分裂症的临床效果良好,并能够显著缓解药物治疗的毒副作用及对患者生物学指标影响,同时还对患者的生活质量具有提高的作用,值得临床推广使用。