阿立哌唑治疗急性复发精神分裂症29例

目的:探讨新型抗精神病药物阿立哌唑治疗急性复发精神分裂症的有效性和安全性。方法:随机入组症状急性恶化或复发的精神分裂症患者30例(脱落1例),纳入分析29例(男15例,女14例),采用阿立哌唑治疗,剂量为(14．4±9．2)mg·d-1,临床观察6周。采用阳性症状与阴性症状量表(PANSS)评定疗效,用不良反应症状量表(TESS)、血生化指标和心电图的改变评价治疗的安全性。结果:①治疗1周后,PANSS阳性、阴性症状分和总分均显著下降(P<0．05);治疗6周后PANSS各分值(阳性症状分为15．5±6．1,阴性症状分为15．1±7．0,总分为60．4±18．1)与基线水平(阳性症状分为26．8±7．1,阴性症状分为22．1±8．4,总分为96．4±21．0)差异显著(P<0．01)。②经6周治疗,基本痊愈6例(20．7％),好转共12例(41．4％),症状无显著变化11例(37．9％),1例患者病情有恶化。③治疗过程中,所有患者TESS总分平均值(2．0±2．3),其中12例患者评分一直为0;主要表现为失眠、静坐不能、食欲减退、便秘、视物模糊。6周的观察中未发现阿立哌唑导致的体重显著增加和心电图的明显改变。结论:阿立哌唑对急性复发的精神分裂症有良好的疗效,而且不良反应较小。     

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review

Importance of the field: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP).

Areas covered in this review: Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency.

What the reader will gain: RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI.

Take home message: Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.     

阿立哌唑治疗老年精神分裂症的疗效和安全性观察

目的:观察阿立哌唑治疗老年精神分裂症的临床疗效和安全性。方法:70例老年精神分裂症患者随机分为以下2组:阿立哌唑组[男性17例,女性18例,年龄(66.2±2.4)岁]和氟哌啶醇组[男性18例,女性17例,年龄(65.4±2.4)岁]。阿立哌唑组和氟哌啶组的起始剂量分别为5~10mg/d和2mg/d,之后视病情分别调整为(12.8±3.3)mg/d和(7.3±3.6)mg/d,共治疗8周。采用阳性症状与阴性症状量表(PANSS)评定临床疗效,用不良反应症状量表(TESS)评定不良反应。结果:阿立哌唑组与氟哌啶醇组的有效率分别为88.6%和85.7%,2组比较差异无统计学意义(P>0.05)。阿立哌唑组不良反应少而轻微。结论:阿立哌唑为治疗老年精神分裂症的有效安全药物。     

A safety evaluation of aripiprazole for treating schizophrenia during pregnancy and puerperium

Introduction: Aripiprazole (ARI) is a second-generation antipsychotic acting as a dopamine-serotonin system stabilizer and partial agonist at D₂ receptors. The drug is indicated in several and severe psychiatric disorders which are particularly frequent in women during the childbearing age.

Area covered: A systematic review of studies investigating the reproductive safety of ARI.

Expert opinion: For first trimester use, reviewed data provide no clear evidence about the safety of the drug for the developing fetus. However, a decline of plasma levels (PLs) throughout the pregnancy compared with PLs before pregnancy was observed. This finding suggests the need to increase the dosage during pregnancy in order to maintain stable PLs. If used during late pregnancy, some signals exist suggesting that ARI may worse neonatal outcomes. Hence, clinicians should consider withdrawing the drug before the last month of pregnancy to reduce the risks of neonatal complications. However, such risks must be weighed against the risks of woman’s symptom deterioration. In any case, parturition should happen in hospitals equipped with well-organized neonatal intensive care units. No information is available on the impact of antenatal exposure to ARI on the main neurodevelopmental milestones. Infant exposure to the drug through maternal milk may increase the risk of insufficient milk production and neonatal somnolence.     

Atorvastatin: safety and tolerability

Importance of the field: Atorvastatin is the most widely used statin administered in a variety of settings, including primary and secondary prevention of cardiovascular events, in the elderly, in patients with chronic kidney disease and in diabetic patients. Therefore, the safety and tolerability of atorvastatin is of paramount importance.

Areas covered in this review: We searched MEDLINE for literature published between 1997 and 2010 on the safety and tolerability of atorvastatin. We retrieved data from randomized controlled trials, meta-analyses, post-marketing studies, reports to regulatory bodies and case reports of rare adverse events.

What the reader will gain: The reader will gain insight into the incidence, severity, prevention and management of the major adverse effects of atorvastatin (i.e., liver function abnormalities and muscle-related side effects) overall and in special populations.

Take home message: The existing data suggest that atorvastatin is generally well tolerated across the range of its therapeutic dosage (10 – 80 mg/day).     

Drug safety and tolerability in prophylactic migraine treatment

Introduction: Migraine is a frequent, disabling primary headache disorder, whose pathomechanism is not yet fully understood. Prophylactic treatment is advisable for migraineurs with severe or highly frequent attacks, which impair the quality of life.

Areas covered: The different types of prophylactic migraine drugs are discussed, with particular regard to potential adverse effects and safety issues. β-Adrenergic blockers, antiepileptic drugs and calcium-channel blockers are drugs widely used for migraine prevention, whereas complementary medicine and onabotulinumtoxin A can be used in selected cases.

Expert opinion: The background of the recurrence and chronification of migraine attacks has not been fully clarified, and causative preventive therapy is therefore not currently available. The tolerability and adverse effects of the currently used medications often limit their use. β-Adrenergic receptor blockers may induce adverse cardiovascular events, whereas flunarizine is frequently associated with a weight gain and depression. As most migraine sufferers are young women of child-bearing age, the use of valproate is limited. Topiramate is associated with central nervous system-related side effects. There is a need for future development of pathomechanism-based preventive drugs, and personalized therapy tailored to the patient.     

Asenapine review,part II: clinical efficacy,safety and tolerability

Introduction: Asenapine is a second-generation (atypical) antipsychotic currently marketed for the treatment of schizophrenia and bipolar mania/mixed episodes.

Areas covered: The purpose of this review is to describe the clinical profile of asenapine.

Expert opinion: Asenapine's efficacy in the treatment of schizophrenia and in the acute management of bipolar manic or mixed episodes, within the recommended therapeutic dose range of 5 – 10 mg twice a day, is evidenced by a broad clinical development program. Asenapine's overall tolerability profile is notable for the potential for sedation (time-limited) and, to a lesser extent, extrapyramidal symptoms/akathisia, dizziness, and oral hypoesthesia. Asenapine's effects on weight and metabolic variables appear modest, as are its effects on the ECG QTc interval and on prolactin.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

阿立哌唑与奋乃静治疗精神分裂症的临床疗效与安全性比较

目的比较阿立哌唑与奋乃静治疗精神分裂症的临床疗效及安全性。方法 94例精神分裂症患者随机分为阿立哌唑组和奋乃静组各47例,分别口服阿立哌唑10～30mg·d~(-1)或奋乃静20～40mg·d~(-1)治疗,疗程为8wk。于基线及服药wk 2、4、6、8末,采用阳性和阴性症状量表(PANSS)评定疗效,副反应量表(TESS)评定不良反应。结果 2组治疗wk 2末起PANSS总分均较治疗前有显著下降(P<0.01),阿立哌唑组PANSS阳性症状、阴性症状和一般病理症状因子分与治疗前比较均有非常显著下降(P<0.01),奋乃静组阴性症状因子分与治疗前比较无显著差异(P>0.05)。治疗wk 8末阿立哌唑组PANSS总分减分率为(68±11)%,奋乃静组为(67±12)%;阿立哌唑组显效率为70%,奋乃静组为68%,2组疗效无显著差异(P>0.05)。阿立哌唑组不良反应发生率较奋乃静组少(26%vs.89%,P<0.01)。结论阿立哌唑治疗精神分裂症疗效与奋乃静相当,不良反应较奋乃静少,能更有效改善阴性症状。     

阿立哌唑治疗精神分裂症的开放性临床验证

目的验证阿立哌唑治疗精神分裂症的有效性及安全性。方法用可变剂量阿立哌唑治疗精神分裂症45例,剂量范围5～30mg/d,疗程共8周;以PANSS量表、临床疗效总评量表(CGI)评定疗效;以治疗药物副作用量表(TESS)评定药物不良反应。结果45例中36例完成8周疗程,9例在4周内停止使用。治疗结束时,显效率为64.4%(29/45),其中临床痊愈31.1%(14/45),显著进步33.3%(15/45),好转22.2%(10/45),无变化13.3%(6/45)。阿立哌唑治疗精神分裂症常见不良反应为焦虑、静坐不能、头晕、乏力、视物模糊、震颤等。结论阿立哌唑治疗精神分裂症有效、安全,不良反应少,可作为临床治疗精神分裂症的一种选择。     

中国HIV-1患者使用利匹韦林为基础抗病毒方案的长期疗效和安全性及耐受性

目的:评估利匹韦林(rilpivirine,RPV)联合2种核苷类逆转录酶抑制剂(NRTIs)对中国HIV-1型感染者的长期安全性、耐受性和疗效.方法:本研究为RPV开放多中心Ⅲ期延长研究TMC278-TiDP6-C222的中国亚组分析,入组患者在既往RPV Ⅱb和Ⅲ期研究结束后签署知情同意自愿纳入延长研究,继续接受R...     

阿立哌唑与利培酮治疗精神分裂症的对照研究

目的：比较阿立哌唑与利培酮治疗精神分裂症的疗效和安全性。方法：对符合《中国精神障碍分类与诊断标准》第3版（CCMD-3）精神分裂症诊断标准的50例患者,随机分为两组,分别给予阿立哌唑和利培酮治疗共8周。采用阳性与阴性症状量表（PANSS）和不良反应量表（TESS）评分。结果：治疗8周后阿立哌唑组和利培酮组的显效率分别为72％和76％,差异无显著性（P〉0．05）。两组治疗后各时点PANSS总分及各因子分也无显著性差异（P〉0．05）。阿立哌唑组的主要不良反应为恶心,厌食,呕吐等消化道症状,而锥体外系反应明显低于利培酮组。结论：阿立哌唑和利培酮对精神分裂症疗效相当,不良反应轻,均为疗效好的抗精神病药,阿立哌唑更适合于锥体外系副作用不能耐受的患者。     

Drug safety evaluation of aripiprazole in bipolar disorder

Introduction: Safety and tolerability of medications are key variables to inform treatment choice for patients with bipolar disorder (BD). This review focuses on the overall tolerability and safety profile of aripiprazole when used for its bipolar disorder indications, which include acute treatment of manic and mixed episodes and maintenance treatment of bipolar I disorder for the oral formulation, agitation associated with bipolar mania for the injectable immediate-release formulation, and maintenance treatment of bipolar I disorder for the long acting once-monthly (AOM) formulation.

Areas covered: The authors reviewed aripiprazole safety in bipolar disorder according to product labeling. English language reports located through PubMed and information available on the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites, with a focus on the safety and tolerability of aripiprazole, were reviewed.

Expert opinion: Compared to many other antipsychotics, aripiprazole has a relatively favorable tolerability profile, with a lower risk for weight gain, dyslipidemia, diabetes, and hyperprolactinemia. Compared to first-generation antipsychotics, and similar to most second-generation antipsychotics, aripiprazole has a reduced propensity for extrapyramidal side effects and a better cardiovascular safety.     

Long-term safety and tolerability of glatiramer acetate 20 mg/ml in the treatment of relapsing forms of multiple sclerosis

?Introduction: Glatiramer acetate (GA) is a first-line therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS). It has a well-characterized long-term safety profile and established efficacy, with over 2 million patient-years of exposure.

Areas covered: To present long-term safety and tolerability findings for GA 20 mg/mL daily in the management of patients with multiple sclerosis (MS). A database analysis of all patients with MS who have ever been exposed to GA 20 mg/mL daily in clinical trials, including patients with up to 20 years of continuous treatment.Total exposure to GA in the clinical trials analyzed was 10,017 patient-years, and treatment duration ranged from 0 to 23.1 years (median 1.8 years). No unexpected adverse events (AEs) were recorded. The most common AEs were injection-site related (ISR), affecting 49% of patients receiving GA in clinical trials. Development of erythema at the injection site was the most common ISR, affecting 29.2% of study patients. Immediate post-injection reactions (IPIRs) were experienced by 24.0% of study patients; dyspnea was the most common IPIR, affecting 12.1% of patients.

Expert opinion: The results of this analysis are consistent with long-term studies showing GA to be safe and generally well tolerated.     

The safety and tolerability of atypical antipsychotics in bipolar disorder

Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.     

阿立哌唑与利培酮治疗精神分裂症的双盲双模拟多中心研究

目的:研究阿立哌唑与利培酮治疗精神分裂症的疗效与安全性。方法:采用CCMD-3精神分裂症的诊断标准,223例精神分裂症患者随机分为阿立哌唑组(109例)和利培酮组(114例),治疗6周。治疗前后用阳性症状和阴性症状量表(PANSS)、临床疗效总评量表(CGI)和副反应量表(TESS)、锥体外系副反应量表(ESRS)评定疗效和安全性。结果:经6周治疗,223例患者完成研究。阿立哌唑组治愈率31.8%,有效率83.3%;利培酮组治愈率39.1%,有效率87.5%(P>0.05)。两组治疗前后PANSS总分、阳性症状、阴性症状、一般精神病理症状评分比较有显著差异(P<0.01)。阿立哌唑组阴性症状分治疗6周末下降较利培酮组明显,有显著差异(P<0.05)。治疗4周末、6周末阿立哌唑组反应缺乏分下降,和利培酮组比较有显著差异(P<0.05)。治疗4,6周末TESS评定阿立哌唑不良反应发生率低于利培酮(P<0.05)。阿立哌唑组主要不良反应是锥体外系副反应、失眠、头昏等。结论:阿立哌唑对精神分裂症患者安全有效。     

苦参素缓释片Ⅰ期耐受性试验

目的：评价健康志愿者对苦参素缓释片单次及连续口服的耐受性和安全性，推荐临床安全有效的用药剂量。方法：研究分为单次给药和多次给药两部分。单次给药组18例健康志愿者随机分为600，900，1200mg 3个剂量组。多次给药组7例志愿者口服药物600mg，bid，连续给药7d。观察临床症状、生命体征和血尿常规、血生化等实验室检查，并监测心电图。结果：单次给药后1，24，72h受试者的生命体征及实验室检查等各项指标测定值均未发现有临床意义的异常变化。多次给药组于服药后d4和d8（停药后1d），发生4例与药物有关的不良反应，均为血清拟胆碱酯酶下降，且为轻度一过性反应，可耐受，于停药后1周自行恢复至原水平。未发现其他有临床意义的异常变化。结论：单次口服苦参素缓释片600～1200mg及连续7d口服600mg，bid，安全酎受。     

阿立哌唑口崩片治疗Tourette综合征临床研究

目的：探讨阿立哌唑口崩片治疗Tourette综合征（Tourette syndrome,TS）的疗效和安全性。方法：对47例TS患者进行为期8周的阿立哌唑口崩片单一治疗,采用耶鲁抽动症状严重程度量表（YGTSS）、副反应量表（TESS）于治疗前和治疗后第2、4、8周末对患者进行评估,并作实验室监测。结果：70.2%的病人疗效显著,87.2%症状改善。有效日剂量为5～30 mg,患者治疗后第2、4、8周末YGTSS得分与治疗前相比均有明显下降,差异有极显著性（P〈0.01）,副反应少且轻微。结论：阿立哌唑能有效改善Tourette综合征的运动及发声抽动症状,且副反应轻微。