奥氮平与阿立哌唑治疗精神分裂症临床疗效的比较研究

目的比较奥氮平与阿立哌唑治疗精神分裂症的临床疗效。方法选取盐城市盐都区精神病防治院2017年3月-2019年2月收治的精神分裂症患者60例,采用随机数表法分为A组和B组,每组30例。A组给予奥氮平治疗,B组给予阿立哌唑治疗,两组均连续治疗8周。比较两组临床疗效及不良反应发生情况。结果两组总有效率比较,差异无统计学意义(P>0.05)。B组不良反应发生率、严重不良反应发生率低于A组(P<0.05)。结论奥氮平与阿立哌唑治疗精神分裂症的临床疗效相当,但阿立哌唑不良反应少且轻微,安全性高于奥氮平,临床应根据患者特点合理用药。     

阿立哌唑与利培酮治疗精神分裂症患者的疗效及不良反应

目的:观察阿立哌唑、利培酮治疗精神分裂症患者的疗效、不良反应及安全性。方法:将60例符合CCMD-3诊断标准的精神分裂症患者随机分为两组,分别给予患者阿立哌唑、利培酮治疗8周,于治疗前以及治疗2、4和8周采用阳性与阴性症状量表(PANSS)评定患者的疗效,不良反应量表(TESS)评定患者的不良反应。结果:两组患者治疗的疗效相当。利培酮组患者的锥体外系反应、内分泌以及体重增加多于阿立哌唑组。结论:阿立哌唑治疗精神分裂症患者的疗效与利培酮相似,但不良反应更少。     

Clinical evolution of patients treated with aripiprazole long-acting injectable: a preliminary,prospective, observational study

Abstract

Objective: To evaluate the effectiveness of 6-month treatment with aripiprazole long-acting injectable (LAI) in improving psychotic symptoms, social functioning and side effects and reducing co-administered antipsychotic drugs.

Methods: Multicentre, observational, prospective study that enrolled 53 patients with diagnosis of schizophrenia spectrum disorders who initiated or switched to aripiprazole LAI. The effectiveness of aripiprazole LAI was assessed through the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersogelser scale for side effects, the Global Assessment of Functioning and the Clinical Global Impression-Schizophrenia (CGI-SCH).

Results: Upon treatment with aripiprazole LAI, patients significantly improved all the domains of PANSS (p?<?.05). Adverse event severity significantly improved after a 6-month aripiprazole LAI treatment (p?<?.05). Differences from baseline to month 6 in Global Assessment of Functioning score were significant (p?=?.0002). The proportion of severely ill patients decreased upon treatment with aripiprazole LAI (CGI-SCH scale). Prolactin levels were normalised after a 6-month treatment (from 43.0 to 14.7?ng/mL). Co-administered antipsychotic drugs significantly decreased after a 6-month treatment with aripiprazole LAI.

Conclusion: A 6-month treatment with aripiprazole LAI improved the clinical status of our patients without modifying their metabolic profile, and allowed the reduction of co-administered antipsychotic drugs.

• Practice implications

• Long-acting injectable antipsychotics are effective treatment options for the maintenance of patients with schizophrenia and related disorders, and to ensure treatment adherence. This study describes the evolution of patients over six months of treatment with aripiprazole long-acting injectable. The results from this study support previous data on the efficacy and safety of this atypical antipsychotic. This study may be of wide interest to the community of psychiatrists and may help clinicians optimise treatment adherence in patients with schizophrenia spectrum disorders.

• Key points

• Aripiprazole long-acting injectable is an atypical antipsychotic intended to improve treatment adherence and prevent relapses.

• This multicentre prospective study evaluated the effectiveness of aripiprazole long-acting injectable over six months of treatment on the control of a comprehensive set of clinical variables.

• Clinical rating scales showed that treatment with aripiprazole long-acting injectable improved clinical symptoms and social functioning, and reduced the severity of adverse events.

• Aripiprazole long-acting injectable contributed to the maintenance of adequate metabolic profiles and the normalisation of prolactin levels.

• Patients significantly decreased co-administered antipsychotic drugs after 6-month treatment with aripiprazole.

     

Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction

Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.     

阿立哌唑与喹硫平治疗双相抑郁对照研究： 国内文献的Meta分析

目的：分析阿立哌唑与喹硫平治疗双相抑郁的疗效差异,为双相抑郁治疗提供新的证据和方法。方法：通过对国内中文文献的数据检索,对4项阿立哌唑与喹硫平治疗双相抑郁的研究资料进行Meta分析,评价有效率的差异和症状改善的差异。结果：①有效率：通过异质性检验, X2=0.7,df=2,P=0.70,I2=0%, 应用固定效应模型OR=1.13,95%CI=0.63~2.02,Z=0.40,P=0.89,提示阿立哌唑与喹硫平治疗双相抑郁有效率没有显著性差异。②症状学评价：异质性检验,X2=8.44,df=3,P=0.04,I2=64.4%,应用随机效应模型SMD=-0.52,95%CI=-1.24~0.21,合并效应检验：Z=1.39,P=0.16,提示阿立哌唑与喹硫平治疗双相抑郁症状评分差异没有显著性。结论：阿立哌唑与喹硫平治疗双相抑郁疗效相似。     

帕利哌酮缓释片与阿立哌唑对青年女性首发精神分裂症的疗效及社会功能的影响

目的 探讨帕利哌酮缓释片与阿立哌唑治疗青年女性首发精神分裂症的疗效及对社会功能的影响。方法 选取我院2017年5月~2019年2月收治的72例首发精神分裂症青年女性患者,按随机数字表法分为两组,A组35例,B组37例,A组给予帕利哌酮,B组给予阿立哌唑,两组均连续治疗8周。观察两组患者治疗前、后血清催乳素、糖脂代谢、社会功能指标,并评定疗效。结果 治疗第4周,A组PANSS评分显著低于B组（P＜0.05）;治疗第4周、第8周,两组血清PRL,与治疗前相比无显著差异（P＞0.05）;治疗第8周,两组脂代谢指标TG水平,均显著高于治疗前（P＜0.05）;B组糖代谢指标GLU水平,显著高于治疗前（P＜0.05）;治疗第4周、第8周,A组PSP评分显著高于同期B组（P＜0.05）;治疗期间,A组体重增加、镇静不良反应的发生率均显著高于B组（P＜0.05）;B组失眠、焦虑不良反应的发生率显著高于A组（P＜0.05）;A组总有效率80.00%,显著高于B组62.16%（P＜0.05）。结论 帕利哌酮与阿立哌唑治疗青年女性首发精神分裂症对血清催乳素无显著影响,对脂代谢均产生一定的影响,且阿立哌唑还会影响糖代谢水平,引起失眠、焦虑等不良反应,帕利哌酮的社会功能恢复力高于阿立哌唑,起效快于阿立哌唑,但8周后疗效相当,且会引起体重增加、镇静等不良反应。     

Effect of valproate on the plasma concentrations of aripiprazole in bipolar patients

Objective. There is very limited documentation available on the effects of valproate co-medication on the pharmacokinetics of aripiprazole in a naturalistic setting. The aim of the present study was to investigate the effect of co-medication with valproate on serum concentrations of aripiprazole in bipolar disorder patients in a clinical setting. Method. Plasma samples of bipolar disorder patients (n = 69) on a stable dose of aripiprazole 20 mg/day were analyzed by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting. Therapeutic drug monitoring was done for the entire study group before and after valproate co-administration. Results. We observed a statistically significant difference between the aripiprazole monotherapy and aripiprazole-valproate combination with respect to total aripiprazole plasma levels (p < 0.01). However, no statistically significant differences were noted in aripiprazole levels between the first week and the second week of valproate co-administration. Conclusion. In conclusion, concurrent treatment with valproate resulted in changes in the total aripiprazole plasma levels by 23%. But a lower total aripiprazole concentration during co-medication with valproate, caused by protein binding displacement, is reported being clinically insignificant in previous studies. The results from these studies are important in order to clarify clinical safety and efficacy.     

阿立哌唑联用小剂量氯氮平治疗女性难治性精神分裂症对照研究

目的 探讨阿立哌唑联合小剂量氯氮平对女性难治性精神分裂症（TRS）的疗效和安全性。方法 将62例女性TRS患者随机分成研究组和对照组各31例,对照组采用阿立哌唑治疗,研究组采用阿立哌唑联用小剂量氯氮平治疗,观察26周。于治疗前及治疗后第8、12、26周末进行阳性和阴性综合征量表（PANSS）评定;治疗后第1、2、6、12、26周末用治疗中需处理的不良反应症状量表（TESS）评定不良反应。结果 治疗后第8、12、26周末两组PANSS总分均较治疗前下降（P〈0.01）,研究组PANSS总分低于对照组（P〈0.05）。两组间不良反应发生率比较差异无统计学意义（P〉0.05）。结论 阿立哌唑联合小剂量氯氮平治疗女性TRS更有效且安全。     

Aripiprazole augmentation versus antidepressant switching for patients with major depressive disorder: A 6-week,randomized, rater-blinded,prospective study

No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score ≥14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n = 52) or SW (n = 49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of −8.7 (p < 0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p = 0.0086) and remitters (p = 0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings.     

阿立哌唑与奋乃静治疗女性精神分裂症对照性研究

目的比较阿立哌唑与奋乃静治疗女性精神分裂症疗效和安全性。方法将83例女性精神分裂症住院患者随机分为阿立哌唑组（研究组）41例和奋乃静组（对照组）42例。以阳性和阴性综合征量表（PANSS）评定疗效,治疗中需处理的不良反应症状量表（TESS）评定不良反应。结果治疗后第2、4、8周末两组PANSS总分及各因子分与治疗前比较均显著下降（P〈0．05,P〈0．01）。治疗后第8周末研究组PANSS量表阴性症状分显著低于对照组（P〈0．05）。两组不良反应均较轻微,不良反应发生率在两组之间无统计学差异（P〉0．05）。结论阿立哌唑治疗女性精神分裂症安全有效。