Leucht S, Hartung B
Klinikum rechts der Isar der TU-München, Klinik für Psychiatrie und Psychotherapie, Ismaningerstr. 22, München, Germany, 81675.
Cochrane Database Syst Rev. 2006 Apr 19(2):CD002832. doi: 10.1002/14651858.CD002832.pub2.
Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As far as we are aware, its use is limited to Germany, Poland, the former Yugoslavia and the Netherlands.
To examine the effects of perazine for those with schizophrenia, and schizophrenia-like psychoses.
We searched the Cochrane Schizophrenia Group's register which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile (last update of the review March 2005). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials.
We selected all randomised controlled trials that compared perazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses.
We independently (SL, BH) inspected citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We excluded data if loss to follow up was greater than 50%. For homogeneous dichotomous data we calculated the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity.
We included six trials with a total of 288 participants. In only one trial with 95 participants, perazine appeared superior to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important global improvement' (n=95, RR 0.43 CI 0.2 to 0.8, NNT 4 CI 2 to 13), but there was no statistically significant difference in most measures of mental state. Perazine did not induce more general adverse events than placebo, but more participants received at least one dose of antiparkinson medication (n=95, RR 4.50 CI 1.0 to 19.5, NNH 6 CI 4 to 33). Five small trials comparing perazine with other antipsychotics, including in total only 193 participants, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible in most occasions. A similar number of participants receiving perazine or comparator antipsychotics left the studies early (n=193, RR 0.85, CI 0.5 to 1.4). The results on efficacy were controversial and need further assessment by randomised controlled trials. No obvious differences in adverse events between perazine and other antipsychotics could be derived from the limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a suitable way for use in meta-analysis, but three small comparisons with the atypical antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n=111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n=111, RR 0.47 CI 0.1 to 3.5), parkinsonism (n=81, RR 1.21 CI 0.5 2.8) or tremor (n=40, RR 0.80 CI 0.3 to 2.6) with perazine.
AUTHORS' CONCLUSIONS: The number, size and reporting of randomised controlled perazine trials is insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics, and this should be clarified in larger, well-designed trials.
奋乃静是一种用于治疗精神分裂症患者的老一代吩噻嗪衍生物,据称其锥体外系不良反应水平较低。据我们所知,其使用仅限于德国、波兰、前南斯拉夫和荷兰。
研究奋乃静对精神分裂症患者及类精神分裂症精神病患者的疗效。
我们检索了Cochrane精神分裂症研究组的注册库,其中包括来自生物医学文摘数据库、护理学与健康照护领域数据库、Cochrane图书馆、荷兰医学文摘数据库、医学索引数据库、心理学文摘数据库、拉丁美洲及加勒比地区健康科学数据库、德国心理学文摘数据库、社会学文摘数据库和社会科学文献数据库的相关随机对照试验(该综述的最后更新时间为2005年3月)。我们检索了所有纳入研究的参考文献以寻找更多试验。我们联系了制药公司和试验的作者。
我们选择了所有将奋乃静与其他治疗方法用于精神分裂症和/或类精神分裂症精神病患者的随机对照试验。
我们独立地(SL、BH)检查了文献引用,如有可能还检查了摘要,并订购论文以便重新检查和质量评估。我们独立提取数据。如果失访率大于50%,我们将排除数据。对于同质二分数据,我们基于意向性分析计算相对危险度(RR)、95%置信区间(CI),并在适当情况下计算需治疗人数(NNT)。对于连续数据,我们计算加权均数差(WMD)。我们检查了所有数据的异质性。
我们纳入了6项试验,共288名参与者。仅在一项有95名参与者的试验中,在5周时,就“无重要总体改善”这一结果而言,奋乃静似乎优于“活性安慰剂”(曲米帕明)(n = 95,RR 0.43,CI 0.2至0.8,NNT 4,CI 2至13),但在大多数精神状态测量指标上无统计学显著差异。奋乃静诱发的一般不良事件并不比安慰剂多,但更多参与者接受了至少一剂抗帕金森药物(n = 95,RR 4.50,CI 1.0至19.5,NNH 6,CI 4至33)。5项比较奋乃静与其他抗精神病药物的小型试验,总共仅193名参与者,报告不完整,结果呈现方式各异,因此大多数情况下无法进行荟萃分析。接受奋乃静或对照抗精神病药物的参与者提前退出研究的人数相近(n = 193,RR 0.85,CI 0.5至1.4)。疗效结果存在争议,需要通过随机对照试验进一步评估。从有限的数据中无法得出奋乃静与其他抗精神病药物在不良事件方面的明显差异。两项与氟哌啶醇的比较未以适合荟萃分析的方式呈现锥体外系副作用,但三项与非典型抗精神病药物佐替平及氨磺必利的小型比较显示,使用奋乃静时静坐不能(n = 111,RR 0.31,CI 0.1至1.1)、运动障碍(n = 111,RR 0.47,CI 0.1至3.5)、帕金森症(n = 81,RR 1.21,CI 0.5至2.8)或震颤(n = 40,RR 0.80,CI 0.3至2.6)的风险并未更高。
关于奋乃静的随机对照试验数量、规模和报告情况不足以就这种抗精神病药物的特性得出确凿结论。奋乃静可能与某些非典型抗精神病药物有类似的锥体外系副作用风险,这一点应在规模更大、设计良好的试验中予以明确。