Maciulis Valentinas, Bitter Istvan, Milasiunas Raimundas, Dembinskas Algirdas, Radavicius Liaudminas, Kaunas Algirdas, Dossenbach Martin, Walker Daniel
Psychiatric Clinic, Vilnius University, Vilnius, Lithuania.
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
Curr Ther Res Clin Exp. 2004 Jan;65(1):57-69. doi: 10.1016/S0011-393X(04)90005-7.
The atypical antipsychotic olanzapine has been approved for the treatment of schizophrenia in Europe since 1996 but has been used primarily as a second-line treatment to the less expensive typical agents. However, similar to other atypical antipsychotic drugs, olanzapine has a lower risk of inducing extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, and sexual dysfunction compared with the typical antipsychotic drugs.
The aim of this study was to determine whether patients with schizophrenia who have a poor response to their present antipsychotic therapy would show improvement when switched to olanzapine.
This 13-week, multicenter, open-label, nonrandomized trial was conducted at 5 centers in Lithuania. Patients were started on oral olanzapine 10-mg tablets once daily, which could be adjusted by 5 mg/d in the dosing range of 5 to 20 mg/d. The primary efficacy measure was the total score on the Brief Psychiatric Rating Scale (BPRS), which was extracted from the Positive and Negative Syndrome Scale (PANSS). Efficacy response rate was defined a priori as the percentage of patients achieving ≥40% improvement in the BPRS total score. Secondary assessments included the PANSS total and BPRS and PANSS subscales and scores on the Clinical Global Impression-Severity of Illness (CGI-S), the CGI-Global Improvement (CGI-I), and the Patient Global Impression-Improvement (PGI-I) tests. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events (AEs) according to the Udvalg fuer Kliniske Undersogelser (UKU) Side Effect Rating Scale and laboratory analyses.
Twenty-four patients (13 men [54.2%]; mean [SD] age, 32.4 [8.1] years) entered the study. Twenty-three (95.8%) of the 24 patients completed the study. The mean (SD) daily dosage of olanzapine was 11.40 (2.18) mg/d. The total mean (SD) BPRS score improved significantly from 37.8 (7.9) to 19.5 (13.7) (P < 0.001). The response rate was 58.3% (14/24 patients). The mean positive and negative BPRS scores and the mean total and subscale PANSS scores all improved significantly from baseline (P < 0.001). The mean (SD) CGI-S score improved significantly from 4.8 (0.8) at baseline to 3.5 (1.1) at end point (P < 0.001). Twenty-two patients (91.7%) showed improvement on the CGM scale. Similar improvement was found on the PGM scale. Treatment-emergent AEs occurred in 7 patients (29.2%). Improvement was found on 31 of the 48 UKU scale items; no change was shown on 15 items; and slight worsening was shown on 2 items. No clinical abnormalities were detected during the study.
In this study of Lithuanian patients with schizophrenia, significant improvement was shown in all efficacy measures. In addition, olanzapine was well tolerated in these patients.
非典型抗精神病药物奥氮平自1996年起在欧洲被批准用于治疗精神分裂症，但主要作为较便宜的传统药物的二线治疗药物使用。然而，与其他非典型抗精神病药物类似，与传统抗精神病药物相比，奥氮平诱发锥体外系症状、迟发性运动障碍、抗精神病药物恶性综合征和性功能障碍的风险较低。
本研究旨在确定目前抗精神病治疗反应不佳的精神分裂症患者改用奥氮平后是否会有所改善。
这项为期13周的多中心、开放标签、非随机试验在立陶宛的5个中心进行。患者开始口服奥氮平10毫克片剂，每日一次，剂量可在5至20毫克/天的范围内以5毫克/天的幅度进行调整。主要疗效指标是简明精神病评定量表（BPRS）的总分，该量表取自阳性和阴性症状量表（PANSS）。疗效反应率预先定义为BPRS总分改善≥40%的患者百分比。次要评估包括PANSS总分、BPRS和PANSS子量表，以及临床总体印象-疾病严重程度（CGI-S）、CGI-总体改善（CGI-I）和患者总体印象-改善（PGI-I）测试的得分。耐受性主要通过根据乌普萨拉监测中心（UKU）副作用评定量表评估治疗中出现的不良事件（AE）的发生率以及实验室分析来衡量。
24名患者（13名男性[54.2%]；平均[标准差]年龄，32.4[8.1]岁）进入研究。24名患者中有23名（95.8%）完成了研究。奥氮平的平均（标准差）日剂量为11.40（2.18）毫克/天。BPRS总分平均值（标准差）从37.8（7.9）显著改善至19.5（13.7）（P<0.001）。反应率为58.3%（14/24名患者）。BPRS阳性和阴性平均分以及PANSS总分和子量表平均分均较基线有显著改善（P<0.001）。CGI-S平均分从基线时的4.8（0.8）显著改善至终点时的3.5（1.1）（P<0.001）。在CGM量表上，22名患者（91.7%）显示有改善。在PGM量表上也发现了类似的改善。7名患者（29.2%）出现了治疗中出现的AE。在UKU量表的48个项目中，31项有改善；15项无变化；2项有轻微恶化。研究期间未检测到临床异常。
在这项针对立陶宛精神分裂症患者的研究中，所有疗效指标均显示出显著改善。此外，这些患者对奥氮平耐受性良好。
