Incidence of Drug-Induced Delirium During Treatment With Antidepressants or Antipsychotics: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2016

ObjectivesSuccessful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium.MethodsThis observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics.ResultsA total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID.ConclusionsWith an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.     

Cardiovascular effects of antimuscarinic agents and beta3-adrenergic receptor agonist for the treatment of overactive bladder

Introduction: Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge.

Area covered: The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB. A systematic literature search from inception until December 2017 was performed on PubMed and Medline.

Expert opinion: AMs are generally considered to have good CV safety profile but, however, they may cause undesirable adverse events, such as dry mouth, constipation. CV AEs are rare but noteworthy, the most common CV consequences related to the use of these drugs are constituted by an increase in HR and QT interval. Mirabegron has similar efficacy and tolerability to AMs but causes less adverse events, with either modest hypertension and modest increase in HR (<5 bpm) being the most commonly reported.     

The Safety and Tolerability Profile of Vilazodone,A Novel Antidepressant for the Treatment of Major Depressive Disorder

Objective

Vilazodone is a selective serotonin reuptake inhibitor and 5-HT_1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This report summarizes the safety and tolerability of vilazodone 40 mg/day during short- and long-term treatment of adult MDD.

Methods

Pooled data from two 8-week, double-blind studies of vilazodone (n = 436) vs placebo (n = 433) and data from one 52-week, open-label study (n = 616, vilazodone only) were analyzed. Patients aged 18-70 with DSM-IV-TR-defined MDD received vilazodone or placebo (8-week studies only) once daily, with food, titrated to 40 mg/day over 2 weeks. Safety and tolerability assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and weight.

Results

The most common AEs in all studies were diarrhea, nausea, and headache. Vilazodone-associated AEs in the two 8-week studies, defined as an incidence rate of ≥5% in the vilazodone group and at least twice that for placebo, were diarrhea (28.0% vs 9.2%), nausea (23.4% vs 5.1%), and insomnia (6.0% vs 2.1%), with the majority reported as mild to moderate and <5% of those patients requiring concomitant (directed) treatment for these conditions. Discontinuation rates due to AEs were 7.1% (vilazodone) and 3.2% (placebo) in the 8-week studies and 20.7% in the 52-week study. Vilazodone had no clinically significant effects on vital signs, laboratory tests, or electrocardiograms.

Conclusion

Vilazodone 40 mg/day was well tolerated during short- and long-term MDD treatment in these trials. Safety profiles associated with 8- and 52-week exposure were consistent.     

Quantitative Relationship Between Myocardial Concentration of Tacrolimus and QT Prolongation in Guinea Pigs: Pharmacokinetic/Pharmacodynamic Model Incorporating a Site of Adverse Effect

Clinical cases have been reported of tacrolimus (FK506)-induced QT prolongation. We have previously demonstrated sustained QT prolongation by FK506 in guinea pigs. Herein, we aimed to conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis of FK506, using a model involving the myocardial compartment. The pharmacokinetics of FK506 and its effects on QTc intervals were investigated in guinea pigs. In the pharmacokinetic study, whole blood and ventricular FK506 concentrations were analyzed, using a 4-compartment model during and after intravenous infusion of FK506 (0.01 or 0.1 mg/hr/kg). Subsequently, the concentration–response relationship between ventricular FK506 concentration and change in QTc interval was analyzed, using the maximal effect (E_max) model. Pharmacokinetic profiles of FK506 showed a delayed distribution of FK506 into the ventricle. Furthermore, the observed QT prolongation paralleled the ventricular FK506 concentrations, with no lag-time between the two. The E_max model successfully described the relationship between changes in QTc interval and ventricular FK506 concentrations. In conclusion, the PK/PD model where the myocardial drug concentration of FK506 was linked with its adverse effect could describe, for the first time, the anti-clockwise hysteresis observed in the relationship between blood FK506 concentration and QT prolongation. Such a hysteresis pattern for QT prolongation might be caused, therefore, mainly by the delayed disposition of FK506 to ventricular myocytes.     

心脑血管疾病用药不良反应与药品品种关系的聚类分析

目的寻找心脑血管疾病用药的不良反应与药品品种间聚类关系,促进临床安全合理用药。方法运用数据挖掘技术中的两阶段聚类算法对药品的严重不良反应与药品品种间的关系进行聚类分析。结果由聚类结果可知,在使用心脑血管疾病用药时,出现的严重和新的严重不良反应为肝功能异常、肾功能异常、呼吸困难、横纹肌溶解,导致这些严重不良反应的药物有受体类药物、钙离子拮抗剂、降低胆固醇类药物。结论在选择心脑血管疾病用药时,受体类药物、钙离子拮抗剂、降低胆固醇类药物应慎用、少用,尽量避免严重的不良反应发生。     

新旧《药品不良反应报告和监测管理办法》对比分析

目的探讨新《药品不良反应报告和监测管理办法》的先进性。方法从监管部门职责、不良反应报告和监测过程各个环节,对比分析《药品不良反应报告和监测管理办法》修订前后的差异,阐述其实施的重要意义。结果与原法规比较,新法规明确了省以下监管部门和监测机构的职责,细化、规范了不良反应报告要求,完善、强化了评价与控制措施,引入重点监测,使不良反应被动监测变为主动、被动相结合。结论新法规为及时、全面获取药品不良反应相关信息、科学评价药品安全性问题、有效控制药品风险提供了有力保障。