Conventional intramuscular sedatives versus ziprasidone for severe agitation in adolescents: case-control study

Objective  

The objective of this study was to compare intramuscular (IM) ziprasidone to conventional IM medications (haloperidol combined with lorazepam) for the treatment of severe agitation in adolescents (age 12–17).     

A naturalistic evaluation of intramuscular ziprasidone versus intramuscular olanzapine for the management of acute agitation and aggression in children and adolescents

OBJECTIVE: The aim of this study was to compare the efficacy and safety of intramuscular ziprasidone versus intramuscular (i.m.) olanzapine in treating aggression in youth. METHODS: A retrospective chart review of 100 hospitalized patients less than 18 years of age treated with either i.m. ziprasidone or i.m. olanzapine for agitation or aggression was conducted. Comparisons were performed using statistical analysis of data collected from medical records. RESULTS: Baseline demographics were similar in the i.m. olanzapine and ziprasidone treatment groups regarding age and ethnicity; however, gender differences did reach statistical significance (p < 0.001). Dosing between children and adolescents significantly differed in the olanzapine group, whereas dosing was comparable in the ziprasidone group. No significant differences between the olanzapine and ziprasidone treatment groups were noted regarding length of stay, efficacy of the study medications, number of restraints, and duration of restraints. Ziprasidone subjects received significantly more doses of emergency medication during their hospital stay and significantly more doses of ziprasidone were administered with concomitant lorazepam or antihistamines. CONCLUSIONS: The results suggest i.m. ziprasidone and intramuscular olanzapine may be equally effective in treating aggression in youth. These agents may also be similar with regard to safety because no clinically significant adverse events were reported for either treatment group. The possibility of poor documentation of adverse events and side effects prevents formulating definitive conclusions regarding safety from this study.     

Intramuscular ziprasidone for acute agitation in adolescents

Several neuropsychiatric disorders in children and adolescents often present with aggressive behavior. In fact, aggression is one of the most common reasons for psychiatric admission for inpatient hospitalization. Psychotropic medication can be helpful in reducing the need for more restrictive interventions, such as seclusion or restraint. The use of "as needed " (PRN) medications has been reported to decrease seclusion and restraint in a university-affiliated hospital setting. In our study, we report the cases of 3 youngsters whose escalating aggression responded to intramuscular ziprasidone with an immediate calming effect and good clinical outcome.     

齐拉西酮注射液治疗精神分裂症急性兴奋临床研究

目的观察齐拉西酮注射液治疗精神分裂症患者急性兴奋的疗效和安全性。方法将急性精神分裂症兴奋患者71例分为两组,治疗组36例予齐拉西酮肌内注射,对照组35例予氟哌啶醇肌内注射,患者入组后即给予齐拉西酮注射液10mg或氟哌啶醇注射液5-10mg肌内注射,4-6h后可重复使用,齐拉西酮及氟哌啶醇每日总量均不超过40mg/d,观察疗程均为3天。采用阳性和阴性症状量表（PANSS）中兴奋因子（PANSS-EC）的变化评定临床疗效,副反应量表（TESS）评定不良反应。于治疗前、治疗第2、6、24、48、72小时分别评定PANSS-EC,副反应量表（TESS）,治疗前及治疗结束时分别评定血、尿、生化常规及心电图。结果治疗72小时,齐拉西酮组的PANSS-EC总分明显降低,PANSS-EC减分率为（71±27）%,临床总有效率为52.7%;氟哌啶醇组的PANSS-EC减分率为（67±24）%,临床总有效率为45.7%,两组的差异均无统计学意义（P均〉0.05）;齐拉西酮组总的不良反应发生率41.7%,氟哌啶醇组为54.3%,两组的差异无统计学意义（P〉0.05）;齐拉西酮组的心脏不良反应发生率19.4%,氟哌啶醇组为14.3%,两组的差异无统计学意义（P〉0.05）;氟哌啶醇组的锥体外系的发生率明显高于齐拉西酮组,差异有统计学意义（P〈0.05）。结论齐拉西酮注射液治疗精神分裂症急性兴奋疗效肯定,安全性高。     

齐拉西酮与氟哌啶醇注射液治疗精神分裂症急性激越症状的临床对照研究

目的评价齐拉西酮与氟哌啶醇注射液治疗精神分裂症急性激越症状的临床疗效和安全性。方法采用最小不平衡指数法将94例具有急性激越症状的精神分裂症患者分为齐拉西酮组和氟哌啶醇组各47例。齐拉西酮组给予齐拉西酮注射液,起始剂量为10~20mg,根据病情需要4~6h后可重复使用,最大剂量不超过40mg/d;氟哌定醇组给予氟哌定醇注射液,起始剂量为5~10mg,4~6h后可重复使用,最大剂量不超过30mg/d。均臀大肌深部注射,疗程3天。采用阳性与阴性症状量表兴奋因子(PANSS-EC)评定疗效,采用副反应量表(TESS)评定副反应。结果齐拉西酮组与氟哌啶醇组PANSS-EC减分率差异无统计学意义[(45.29±13.84)%vs.(47.56±14.49)%,t=0.068,P0.05]。齐拉西酮组与氟哌啶醇组临床总有效率差异无统计学意义(53.19%vs.48.94%,χ2=0.072,P0.05)。齐拉西酮组与氟哌啶醇组不良反应发生率差异有统计学意义(29.8%vs.49.8%,χ2=9.035,P0.05)。结论齐拉西酮注射液治疗精神分裂症急性激越症状的效果与氟哌啶醇相当,安全性优于氟哌啶醇。     

国产齐拉西酮与氟哌啶醇注射液治疗精神分裂症急性激越症状的对照研究

目的 评价国产齐拉西酮注射液治疗精神分裂症急性激越症状的疗效和安全性.方法 将231例精神分裂症患者随机分为齐拉西酮组(115例)和氟哌啶醇组(116例),进行多中心随机单盲对照研究.患者入组后即给予齐拉西酮注射液10～20 mg或氟哌啶醇注射液5～10 mg肌内注射,4～6 h后可重复使用.齐拉西酮每日总量不超过40 mg,氟哌啶醇每日总量不超过30 mg,每日注射均不超过3次,疗程均为3 d.于治疗前、治疗第2,6,24,48,72小时采用阳性和阴性症状量表(PANSS)、阳性和阴性症状量表兴奋因子(PANSS-EC)、治疗时需处理的不良反应量表、锥体外系副反应量表评定疗效及副反应.结果 治疗第72小时,齐拉西酮组的PANSS-EC总分明显降低,PANSS-EC减分率为(68±25)%,临床总有效率为47.8%;氟哌啶醇组PANSS-EC减分率为(65±23)%,临床总有效率为37.1%;两组的差异均无统计学意义(P均＞0.05).齐拉西酮组的不良反应发生率为37.4%,氟哌啶醇组的不良反应发生率为50.0%,两组的差异无统计学意义(P＞0.05).氟哌啶醇组锥体外系的发生率明显高于齐拉西酮组,差异有统计学意义(P＜0.05).结论 国产齐拉西酮注射液治疗精神分裂症的急性激越症状有明显疗效,不良反应少.     

A retrospective chart review of intramuscular ziprasidone for agitation in children and adolescents on psychiatric units: prospective studies are needed

OBJECTIVE: Our primary objective was to evaluate the effectiveness and tolerability of intramuscular ziprasidone for impulsivity and agitation in psychiatrically hospitalized children and adolescents. Our secondary objective was to examine demographic and clinical factors associated with treatment response. METHOD: We conducted a retrospective chart review of children and adolescents admitted to Cincinnati Children's Hospital Medical Center (CCHMC) psychiatric units between January 1, 2002, and July 11, 2005, who received intramuscular ziprasidone. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of ziprasidone. The Behavioral Activity Rating Scale (BARS) was used retrospectively to assess clinical response. Regression analyses were performed to evaluate the effect of demographic factors (age, gender, and ethnicity) and primary psychiatric diagnoses on treatment response. Electrocardiogram (ECG) data was inadequate. RESULTS: Fifty nine children and adolescents received a total of 77 injections of intramuscular ziprasidone for acute agitation. The mean +/- SD BARS score decreased from 6.5 +/- 0.7 to 3.1 +/- 1.3. The most common side effect was drowsiness or falling asleep (n = 46, 60%). Three (4%) could not be roused after the injection. CONCLUSIONS: Intramuscular ziprasidone may be helpful for agitation but often caused oversedation. Safety data, including ECGs, is needed in controlled prospective studies.     

The utility of intramuscular ziprasidone in the management of acute psychotic agitation.

Many psychiatric illnesses, including chronic schizophrenia, bipolar disorder, and dementia, are characterized by episodes of acute agitation, making administration of oral agents difficult or impossible. Ziprasidone, the first atypical antipsychotic available in both intramuscular (IM) and oral formulations, has demonstrated significant control of acute agitation within 15 minutes, as seen in two 24-hour studies in patients with schizophrenia. Improvement was maintained for > or = 4 hours, and a low incidence of extrapyramidal symptoms, akathisia, and dystonia as well as no excessive sedation were observed Also, two 7-day studies (n = 132 and n = 306) and one 6-week study (n = 567) of sequential IM/oral ziprasidone versus IM/oral haloperidol in patients with psychotic disorders found IM ziprasidone more effective than IM haloperidol within 3 days of IM treatment; both drugs produced further comparable improvements in efficacy parameters after transition to oral therapy. IM ziprasidone was associated with a lower incidence of movement disorders than was haloperidol in all of these studies. Overall, discontinuations were similar for IM ziprasidone and haloperidol in the comparative trials, including the sequential IM/oral studies. However, in the 6-week sequential IM/oral trial, the rate of discontinuation due to adverse events was twice as high among haloperidol vs ziprasidone patients. This report focuses on the pharmacology, clinical efficacy, and tolerability of IM ziprasidone, and provides an overview of the utility of other commonly used antipsychotics in the management of acute psychotic agitation.     

齐拉西酮注射液与氟哌啶醇注射液治疗精神分裂症急性激越症状的对比研究

目的验证甲磺酸齐拉西酮注射液治疗精神分裂症急性激越症状的临床疗效和安全性。方法将64例具有急性激越症状的精神分裂症患者随机分为齐拉西酮组（研究组,32例）和氟哌啶醇组（对照组,32例）,进行开放式临床对照研究,患者入组后即给予臀大肌深部注射齐拉西酮注射液10mg或氟哌定醇注射液5~10mg,6~8小时后可重复使用;甲磺酸齐拉西酮和氟哌啶醇每日总量均不超过30mg,每日注射不超过3次,疗程3天。采用阳性和阴性症状量表（PANSS）、阳性与阴性症状量表兴奋因子（PANSS-EC）、临床总体印象量表（CGI）评分评价疗效;采用药物不良反应量表（TESS）、锥体外系副反应量表（SAS）评价副反应。结果治疗72小时后,齐拉西酮组和氟哌啶醇组的PANSS-EC总分均明显减低,齐拉西酮组PANSS-EC减分率为（47.79±12.94）%,氟哌啶醇组为（47.79±11.49）%,差异无统计学意义（t=0.063,P〉0.05）。齐拉西酮组临床总有效率为46.9%;氟哌啶醇组为40.6%,差异无统计学意义（χ2=0.063,P〉0.05）。齐拉西酮组不良反应发生率为28.1%,氟哌啶醇组65.6%,差异有统计学意义（χ2=9.035,P〉0.05）。结论甲磺酸齐拉西酮治疗精神分裂症的急性激越症状疗效明显,耐受性良好。     

Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation

BACKGROUND: Although agitation associated with psychosis is a common presentation in the psychiatric emergency service, there is no consensus concerning the best treatment. Standard treatment often consists of intramuscular (i.m.) injection of high-potency neuroleptics, sometimes combined with benzodiazepines. The objective of this study was to determine the relative efficacy, safety, and tolerability of oral risperidone versus intramuscular haloperidol, both in combination with lorazepam, for the emergency treatment of psychotic agitation in patients who are able to accept oral medications. METHOD: A convenience sample of psychotic patients admitted to a large psychiatric emergency service who required emergency medication for the control of agitation and/or violence was offered risperidone (2 mg liquid concentrate) and oral lorazepam (2 mg) as an alternative to standard care at the institution, haloperidol (5 mg i.m.) and lorazepam (2 mg i.m.). Subjects who refused the oral medications were given the intramuscular treatment as a component of routine care. RESULTS: Thirty patients were enrolled in each treatment group. Although men were significantly more likely to choose oral medication (chi2 = 5.165, p < .023), other demographic characteristics did not differ significantly between the 2 treatment groups. Both groups showed similar improvement in agitation as measured by 5 agitation subscales of the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, and time to sedation. No patients receiving risperidone demonstrated any side effects or adverse events, while 1 patient receiving intramuscular treatment with haloperidol developed acute dystonia. One subject receiving risperidone required subsequent treatment with haloperidol for ongoing agitation. CONCLUSION: Oral treatment with risperidone and lorazepam appears to be a tolerable and comparable alternative to intramuscular haloperidol and lorazepam for short-term treatment of agitated psychosis in patients who accept oral medications.     

Electrocardiographic changes in children and adolescents treated with ziprasidone: a prospective study

OBJECTIVE: To assess the electrocardiographic safety profile of low-dose ziprasidone (< or =40 mg/day) among pediatric outpatients treated for up to 6 months. METHOD: This was a prospective, open-label trial involving 20 subjects with a mean age of 13.2 +/- 3.0 years. Subjects received a mean ziprasidone dose of 30 +/- 13 mg/day and were followed for 4.6 +/- 2.0 months, receiving a median of nine electrocardiograms each (range 2-11; total, 176). RESULTS: There were statistically significant changes from baseline to peak values in heart rate, PR, and QTc intervals, but not in QRS complex width. The mean QTc prolongation was 28 +/- 26 milliseconds and not related to dose (r = 0.16, p = .07). The peak QTc of three subjects reached or exceeded 450 milliseconds; one subject experienced a 114-millisecond prolongation. There was poor agreement (kappa = 0.25) between automated and manual identification of long QTc intervals (> or =440 milliseconds). CONCLUSIONS: These preliminary findings, occurring at doses low by current treatment standards, suggest that close electrocardiographic monitoring is warranted when prescribing ziprasidone to children, particularly at higher doses or when combined with other QTc-prolonging agents.     

A retrospective study of the safety of intramuscular ziprasidone in agitated elderly patients

OBJECTIVE: Authors evaluated the safety of intramuscular ziprasidone for use in acute agitation in an elderly population. METHOD: Medical records were reviewed retrospectively to identify consecutive patients who were admitted to our neuropsychiatry service with the presenting complaint of dementia (DSM-IV) with agitation and who were given intramuscular ziprasidone and then administered an electrocardiogram (ECG) (N = 23). Some patients also had a baseline ECG (N = 14). QTc intervals were recorded, and significance was defined as a QTc of > or =450 ms or a 10% prolongation from baseline. A paired-samples t test was performed to compare the baseline and postmedication QTc intervals. Confounding factors were examined, and cardiac events (torsades de pointes, cardiac arrest) were recorded. RESULTS: There was no significant difference in the QTc interval between the baseline and the post-ziprasidone values. One patient had a QTc greater than 500 ms and 25% over baseline, and therefore the medication was discontinued. The mean prolongation of the QTc interval was only 0.5 ms. There were no episodes of torsades de pointes. Other medications that the patients were taking did not appear to affect the QTc interval in an expected manner. CONCLUSION: Larger studies need to be done to evaluate the safety of intramuscular ziprasidone in agitated elderly patients, a population with an increased risk of QT prolongation and torsades de pointes because of their age, comorbid conditions, and concomitant use of multiple medications.     

严重脑白质疏松症相关因素的病例对照研究

目的探讨严重脑白质疏松症的相关因素。方法按照筛选标准连续收集2015年4月-2016年2月武汉大学中南医院神经内科住院患者,通过头部核磁共振评估脑白质疏松症Fazekas评分并收集相关临床资料,并应用非条件Logistic回归来分析严重脑白质疏松症的相关因素。结果共纳入608例患者,包括Fazekas评分为0的对照组415例和Fazekas评分为3~6的病例组193例。多因素Logistic回归结果提示:高龄(G3 vs G1:OR10.81,95%CI 2.76~42.38,P=0.001;G4 vs G1:OR 28.40,95%CI 7.02~114.95,P0.05;G5 vs G1:OR 68.79,95%CI 14.22~332.92,P0.05)、脑动脉粥样硬化(OR 1.98,95%CI 1.07~3.65,P=0.029)和高血压病(OR=4.84,95%CI=2.65~8.85,P0.05)与严重脑白质疏松症之间呈显著正相关。结论高龄、脑动脉粥样硬化和高血压病可能是严重脑白质疏松症的独立危险因素。     

齐拉西酮合并氯硝西泮治疗急性期伴激越精神分裂症患者的对照研究

目的:评估齐拉西酮合并氯硝西泮治疗精神分裂症患者急性期兴奋激越的有效性和安全性。方法:120例中度急性期伴激越患者,随机分为齐拉西酮合并氯硝西泮治疗组和奥氮平治疗组,分别在治疗基线、第4天、第7天、第14天和第28天进行疗效和安全性评估。共脱落22例,98例纳入分析。结果:①阳性与阴性症状量表(PANSS)的减分值在两组药物之间差异无统计学意义(F=0.264,P=0.608);兴奋条目总分的时间变化趋势差异有统计学意义(F=194.984,P=0.000),而在两组药物之间差异无统计学意义(F=0.047,P=0.828);②两组间体质量、三酰甘油和胆固醇差值比较差异有统计学意义(F=4.274,P=0.041;F=4.967,P=0.028;F=3.991,P=0.049),奥氮平组体质量、血脂变化高于齐拉西酮组;③两组不良反应量表(UKU)比较,时间趋势有统计学差异(F=4.9,P=0.002),分组因素无统计学差异(F=1.425,P=0.236)。结论:齐拉西酮合并氯硝西泮治疗急性期伴有兴奋激越的精神分裂症患者的疗效与奥氮平相当,但对体质量和血脂的影响小于奥氮平。     

Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits

OBJECTIVE: Since use of multiple drugs to treat psychiatric patients is increasing, and research on this practice is rare, the authors carried out a retrospective case-control study of multiple versus single antipsychotic treatment in psychiatric inpatients. METHOD: Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex, diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge. RESULTS: Initial doses were closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5 days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were similar (within 11%) for both treatments. CONCLUSIONS: Short-term treatment with multiple antipsychotics was associated with major increases in drug exposure, adverse events, and time in the hospital but with no apparent gain in clinical benefit. These findings require further testing in controlled prospective studies.     

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia

OBJECTIVE: The efficacy and safety of olanzapine were compared with those of ziprasidone. METHOD: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight. RESULTS: The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level. CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.