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 )     

Pharmacokinetics,efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials

Abstract

Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.     

Lacosamide for children with paroxysmal kinesigenic dyskinesia

ObjectivesThis study was performed to evaluate the efficacy and tolerability of lacosamide (LCM) for paroxysmal kinesigenic dyskinesia (PKD) in children.MethodsWe retrospectively reviewed the medical charts of pediatric PKD patients (aged <16 years) treated with LCM. Data regarding demographic characteristics, proline-rich transmembrane protein 2 (PRRT2) gene variant, clinical features of PKD, dose of LCM, efficacy, and adverse events were recorded.ResultsFour eligible patients (3 males, 1 female) were identified, with an age of onset ranging from 8.3 to 14.7 years. PRRT2 variant was evaluated in three children and a c.649dupC variant was identified in one child with a positive family history. Attacks were bilateral in three children and left-sided in one. Two children had a family history of PKD and one child had a family history of benign infantile epilepsy. Treatment with carbamazepine failed in two children due to drowsiness and auditory disturbance. The initial dose of LCM was 50 mg/day in three children and 100 mg/day in one. All patients were attack-free within a few days. The maintenance dose was mostly similar to the initial dose. No adverse events related to LCM were reported during follow-up.ConclusionsLCM is an effective and well-tolerated treatment for PKD in children, and low-dose treatment may be viable.     

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter,cohort study

Objective. The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA).

Methods. The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17–87) years; median (range) disease duration, 8 (0.6–48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2–16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group).

Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM.

Results. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group.

Conclusions. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.     

The utilization of psychopharmacological treatment and medication adherence among Medicaid enrolled children and adolescents with bipolar depression

Background

To examine the psychotropic medication utilization and compare adherence to treatment regimens in pediatric bipolar depression patients.

Methods

2003–2007 MAX data from four geographically diverse states were used. According to the regimen received by the patients (6–18 years) in the first month after the index bipolar depression diagnosis, patients were categorized into six mutually exclusive groups. The month to month change of treatment regimen in each group was then assessed during the 6 month post-index bipolar depression diagnosis. Adherence to each regimen was measured as continuation of the initial regimen, switch to a new regimen, augmentation with medication from a different therapeutic category, and discontinuation of all pharmacotherapies. Repeated measure analysis was conducted to compare the trend of each adherence measure across the study groups.

Results

Of the 5,460 subjects identified, 15.39% received antipsychotic monotherapy, 9.43% received mood stabilizer monotherapy, 5.77% received antidepressant monotherapy, 26.48% received mood stabilizer–antipsychotic polytherapy, 22.51% received antidepressant polytherapy, and 19.89% received antipsychotic–mood stabilizer–antidepressant polytherapy. At the end of the follow-up period, over 50% of the 1st month polytherapy users and less than 50% of the monotherapy users were continuing their initial regimen. Repeated measure analysis using antipsychotic monotherapy as the reference group suggested differences in trend slopes (p<0.05).

Limitations

In absence of structured clinical evaluation, bipolar disorder diagnoses cannot be ascertained in this study.

Conclusions

Bipolar depression patients were predominantly treated with combinations of psychotropic drugs. Potentially questionable practice, such as antidepressant monotherapy was used only in a small fraction of patients. Combination regimens had better adherence as compared to monotherapies.     

Lacosamide monotherapy for the treatment of childhood epilepsy with centrotemporal spikes

ObjectiveChildhood epilepsy with centrotemporal spikes (CECTS) is known as age-limited focal epilepsy syndrome in childhood. Lacosamide is a third-generation antiepileptic drug. This study aimed to evaluate the efficacy of lacosamide monotherapy for the treatment of CECTS.MethodsWe enrolled 18 patients (6 girls and 12 boys) who met the following criteria: 1) the age of onset of the seizures was between 3 and 13 years of age; 2) showing at least hemifacial and/or oropharyngeal seizures; 3) interictal discharges in central and/or middle temporal electrodes; 4) no intellectual disability; 5) treatment duration of lacosamide monotherapy over 6 months. We retrospectively collected and analyzed clinical data and treatment information. We evaluated the seizure occurrences during 0–3, 4–6, and 7–12 months from the treatment initiation and the last 6 months of the follow-up. We also evaluated the outcomes as seizure-free if the patients developed no seizures both over 6 months and 3 times of pretreatment mean seizure interval at the last follow-up.ResultsOf the patients, 39%, 67% and 72% were seizure-free during 0–3, 4–6, and 7–12 months from treatment initiation, respectively. Finally, 83% of the patients achieved seizure freedom. Seizure freedom was achieved in 72% during the first 4 months of treatment. All patients continued lacosamide monotherapy during the study, although four patients showed transient fatigue or somnolence.ConclusionsLacosamide showed good efficacy for controlling seizures with fewer adverse effects, and therefore may be a good candidate as a first-line medication for the treatment of new-onset CECTS.     

替加环素单药与联合方案治疗多重耐药菌感染疗效对比的系统评价#br#

目的 替加环素是一种广谱的新型四环素类抗生素,长期单独使用可能存在耐药菌出现增多的问题。本文将系统性评价以替加环素为基础的联合治疗方案与替加环素单药方案治疗多重耐药菌感染疗效的对比。方法 通过检索PubMed、Embase、the Cochrane Library、CNKI、维普、万方等数据库及手工检索会议论文,寻找有关替加环素单药和联合治疗方案比较的随机对照研究、队列研究、病例丛和个案报道。检索日期截止到2016年12月31日。英文数据库的检索词为“tigecycline”、“tygacil”、“monotherapy”以及“combination”。中文数据库的检索词为“替加环素”、“单药”及“联合”。相关综述研究也一并手工检索。结果 仅1篇符合筛选条件的相关RCT研究。最终纳入9项对比研究(含1510个事件)和22项非对比性研究(含26个事件)。对比研究显示基于替加环素的联合治疗方案与替加环素单药治疗方案相比疗效上无显著差异。然而26例个案报道中23例显示替加环素联合的治疗方案临床效果会更佳。此外,研究还显示,与替加环素组合的治疗方案中最常见的抗菌药物是多黏菌素、碳青霉烯类、氨基糖苷类和氟喹诺酮类。结论 替加环素为基础的联合方案似乎更优于单药方案,常见有效的联合药物为多黏菌素、碳青霉烯类、氨基糖苷类和氟喹诺酮类。未来需要进行更多的前瞻性、随机对照、双盲研究来探索联合治疗方案和单药治疗方案疗效对比以及何种药物与替加环素的联合会更适宜。     

含多粘菌素E多药联合方案与单药方案的有效性和安全性Meta分析

目的:系统评价多粘菌素E与其他抗菌药物的联合治疗方案(联合方案)与单药治疗方案(单药方案)的有效性和安全性。方法:计算机检索PubMed,Embase和Cochrane Library,查找其联合方案与单药方案的临床对照研究文献。检索时限截至2013年5月,按纳入与排除标准筛选文献,采用RevMan 5.0统计软件进行Meta分析。结果:共纳入14篇相关文献,其中死亡率结果共纳入5篇文献,单药方案的死亡率显著大于联合方案的死亡率(OR:2.30,95%CI:1.28,4.13,P=0.005);临床疗效共纳入11篇文献,总体结果显示,单药方案优于联合方案[OR=1.59,95%CI:1.03,2.45,P=0.04],但亚组分析结果显示,前瞻性研究中,单药方案与联合方案没有显著性差异(OR:1.02,95%CI:0.53,1.94,P=0.96);微生物结果共纳入4篇文献,结果显示,单药方案与联合方案的微生物根除结果无显著性差异(OR:1.25,95%CI:0.66,2.36,P=0.50);肾毒性结果共纳入4篇文献,联合方案的肾毒性与单药方案的无显著性差异(OR:0.90,95%CI:0.31,2.61,P=0.85)。结论:联合方案在临床结果和微生物根除结果与单药方案相当,但在提高患者生存率上,联合方案要优于单药方案。多药联合治疗不增加多粘菌素E的肾毒性。