氯氮平片辅助治疗PD合并精神障碍患者的有效性及不良反应研究

目的:对氯氮平片在帕金森病(Parkinson’s disease,PD)合并精神障碍辅助治疗中的应用价值予以探讨。方法:选取50例我院2013年1月1日—2019年6月30日接诊的PD合并精神障碍患者进行研究,按照随机数表法分为对照组和观察组。对照组用多巴丝肼,观察组联合氯氮平片,对比治疗效果。结果:观察组疾病治疗总有效率96.00%(24/25)高于对照组68.00%(17/25),差异有统计学意义(P<0.05),不良反应发生率8.00%(2/25)与对照组20.00%(5/25)差异无统计学意义(P>0.05);观察组UPDRD评分、VGI-S评分和BPRS评分明显低于对照组,差异有统计学意义(P<0.05)。结论:氯氮平片辅助治疗PD合并精神障碍患者,既可提高临床疗效,也不会增加用药后不良反应,安全性高,值得推广。     

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Limited options are available for clozapine-resistant schizophrenia and intolerable side effects of clozapine. We conducted a systematic review of randomized-controlled trials (RCTs) to determine the efficacy and safety of aripiprazole augmentation of clozapine for schizophrenia. Electronic databases searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. This review synthesized the data of four short-term (8–24 weeks), placebo-controlled trials (N = 347). The overall relative risk (RR, 95% confidence interval) of discontinuation rates was not significantly different between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean differences (SMDs, 95% CIs) (Z-test; number of study; I²-index) suggested trends of aripiprazole augmentation benefits on overall psychotic [−0.40 (−0.87 to 0.07) (n = 3; Z = 1.68, p = 0.09; I² = 68%)], positive [−1.05 (−2.39 to 0.29) (n = 3; Z = 1.54, p = 0.12; I² = 94%)], and negative [−0.36 (−0.77 to 0.05) (n = 3; Z = 1.74, p = 0.08; I² = 54%)] symptoms. Despite of no benefit on three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and high-density lipoprotein), aripiprazole augmentation was superior for weight change with a mean difference (95% CI) of −1.36 kg (−2.35 to −0.36) (n = 3; Z = 2.67, p = 0.008; I² = 39%) and LDL-cholesterol with a mean difference of −11.06 mg/dL (−18.25 to −3.87) (n = 3; Z = 3.02, p = 0.003; I² = 31%). Aripiprazole augmentation was not correlated with headache and insomnia but significantly associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z = 2.38, p = 0.02; I² = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n = 1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole augmentation of clozapine can minimize the cardiometabolic risk, causes agitation/akathesia, and may be effective in attenuating psychotic symptoms.     

氯氮平撤药致谵妄2例

2例双相障碍患者长期应用氯氮平(分别为100 mg/d,150 mg/d)维持治疗,在骤停氯氮平1天后出现谵妄状态,复用氯氮平后症状迅速缓解。     

齐拉西酮联合小剂量氯氮平对男性难治性精神分裂症患者认知功能的影响

目的：观察齐拉西酮联合小剂量氯氮平对男性难治性精神分裂症患者认知功能的影响及临床疗效、安全性研究。方法：将100例男性难治性精神分裂症患者随机分为两组各50例,治疗组给予齐拉西酮联合小剂量氯氮平治疗,对照组给予氯氮平治疗。两组均于治疗前后采用阳性与阴性症状量表（ PANSS ）、韦氏成人智力量表（ WAIS－RC）、个人与社会功能量表（ PSP）及不良反应发生量表评定认知功能影响及临床疗效与安全性。结果：两组患者在治疗12周后PANSS总分及各因子分均明显下降,且差异具有统计学意义（t＝16．98,P＜0．05）;治疗后,治疗组WAIS－RC评分及PSP评分均显著提高,且两组差异具有统计学意义（t＝4．76,2．54;P＜0．05）;治疗12周后,两组间临床疗效相当,且治疗期间,治疗组不良反应的发生率明显低于对照组,两组差异具有统计学意义（χ2＝4．24,P＜0．05）。结论：齐拉西酮联合小剂量氯氮平治疗男性难治性精神分裂症与单用氯氮平治疗临床疗效相当,但安全性高,且能更好地改善患者的认知功能。     

喹硫平替换氯氮平治疗精神分裂症临床疗效观察

目的探讨分析喹硫平替换氯氮平治疗精神分裂症临床疗效及对患者血清胰岛素、泌乳素与生活质量的影响。方法选取我院在2017年5~11月期间收治的120例经氯氮平治疗出现代谢异常的精神分裂症患者为研究对象,按照随机数字表法分为观察组(n=60)与对照组(n=60)。对照组患者给予单一的氯氮平治疗,治疗后首日将氯氮平日量减少1/4~1/3,此后每周氯氮平日量减1/2,治疗3个月;观察组患者在替换用喹硫平片0.2~0.4 g,分2次服用,一般每隔3 d调整剂量1次,4周加至0.6 g,最大日量不超过1.2 g,疗程为3个月。采用临床总体印象量表(CGI)病情严重程度(SI)进行评分和生活质量量表(SF-12),包括锥体外系副反应量表(RSESE)评定临床疗效,对比分析两组患者血清胰岛素及血糖与泌乳素的变化情况。结果从第2周开始,观察组CGI-SI评分与基线比较,差异有统计学意义(P0.05),第6周末与第2周末比较,第12周末与第6周末比较,差异均有统计学意义(P0.05),而对照组各时间段无明显变化(P0.05);随着治疗时间越长,观察组社会功能改善越明显(P0.05),而对照组各时间段无明显变化(P0.05);两组血清胰岛素、血糖及泌乳素第12周末与基线时比较差异有统计学意义(P0.05),且观察组血清胰岛素从第2周末开始升高比对照组快,血糖从第2周末开始降低比对照组快,泌乳素从第6周末开始与对照组有差异(P0.05);治疗后,两组患者失眠、焦虑激越比较差异无统计学意义(P0.05),头痛、头晕、便秘、肝功能异常差异均有统计学意义(P0.05)。结论对氯氮平治疗出现代谢异常的精神分裂症患者,运用喹硫平替换治疗能改善患者的精神病性症状,且提高了社会功能,更具有安全性,值得推广。     

A three-year naturalistic follow-up of patients receiving clozapine: Report from India

INTRODUCTION: Clozapine is a first-line drug for treatment-resistant schizophrenia, but studies dealing with long-term outcome are lacking, so we decided to carry out such a study. METHODS: Patients with treatment-resistant schizophrenia who were recruited in an open-label study three years ago were re-evaluated using the same parameters: BPRS, PANSS and a side-effect rating checklist. RESULTS: Nineteen out of 25 patients who participated in the initial study were available for re-evaluation. Two patients had changed to conventional neuroleptic medication, and were excluded from the study. A significant reduction in psychopathology was observed in 85% of patients. An improvement in social functioning was evident, with seven patients pursuing a career independently, and another six working with their family members since being started on clozapine. All the patients were on clozapine monotherapy, and the average daily dose was 248.21 mg. No patient required hospitalization and there was no incidence of granulocytopenia. CONCLUSIONS: A significant improvement in the psychopathology and social functioning of patients was observed with much lower doses of clozapine than has been reported elsewhere. The doses used for maintenance were lower than those used in the acute phase of treatment. (Int J Psych Clin Pract 2002; 6: 167-171 )     

The clinical use of plasma clozapine levels in a maximum security setting

Background. Research suggests a correlation between clozapine dose, plasma level and therapeutic response. Plasma clozapine levels may, therefore, be useful in practice. Little evidence exists, however, on the indications for, and outcome of, levels being undertaken or their use in maximum security settings. Objective. To determine if plasma clozapine levels are useful in clinical practice by analysing their use at the maximum-security State Hospital, Carstairs. Methods. All plasma clozapine levels (until March 2004) undertaken at the State Hospital, clinical indication and outcome were analysed by retrospective case note analysis. These results were compared with the published literature. Results. A total of 140 plasma clozapine levels were analysed. The average level was 0.61 mg/l and dose was 622.9 mg/day. The indications for and consequences of levels are demonstrated. A positive correlation of 0.217 was calculated. Conclusion. This paper shows that plasma clozapine levels are most useful in managing side effects and suspected non-compliance. Plasma clozapine levels are, therefore, useful in clinical practice.     

Clozapine-induced elevated C-reactive protein and fever mimic infection

Clozapine-induced fever has been reported frequently, but clozapine-induced elevated serum C-reactive protein (S-CRP) over 100 mg/L with early onset, without associated myocarditis, has not been reported in the literature. In this case report, we present a case of an 80-year-old Slovenian female with dementia and psychotic symptoms who developed elevated S-CRP (122 mg/L) and fever (38.2°C) on the seventh day with 25 mg of clozapine daily, which improved after clozapine discontinuation. The patient did not have symptoms and signs of infection. This case report can be used to remind clinicians of keeping in mind the potential of clozapine associated with very high elevated S-CRP with fever, which can be easily confused with more serious conditions.     

阿立哌唑与小剂量氯氮平治疗难治性精神分裂症对照研究

目的探讨阿立哌唑合并小剂量氯氮平治疗难治性精神分裂症的疗效和安全性。方法将40例难治性精神分裂症患者随机分为A组(阿立哌唑合并小剂量氯氮平,n=20)和B组(单用氯氮平,n=20)。于治疗前和治疗第4、8、12周末采用阳性与阴性症状量表(PANSS)评定临床疗效;使用副反应量表(TESS)评定不良反应,并进行对比分析。结果 2组治疗后PANSS总分较治疗前明显降低,A组显著低于B组,差异有统计学意义。2组治疗12周末有效率分别是80%、50%,差异有统计学意义(χ2=3.95,P<0.05)。2组不良反应比较差异有统计学意义(P<0.05)。结论阿立哌唑合并小剂量氯氮平治疗难治性精神分裂症疗效好,不良反应少且依从性好。