Kishimoto Taishiro, Robenzadeh Alfred, Leucht Claudia, Leucht Stefan, Watanabe Koichiro, Mimura Masaru, Borenstein Michael, Kane John M, Correll Christoph U
To whom correspondence should be addressed; Division of Psychiatry Research, the Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, US; tel: (718) 470-4812, fax: (718) 343-1659, e-mail:
Schizophr Bull. 2014 Jan;40(1):192-213. doi: 10.1093/schbul/sbs150. Epub 2012 Dec 17.
While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs).
Systematic review/meta-analysis of RCTs that lasted ≥ 6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence.
Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at the longest time point (studies = 21, n = 4950, relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.80-1.08, P = .35). The finding was confirmed restricting the analysis to outpatient studies lasting ≥ 1 year (studies = 12, RR = 0.93, 95% CI:0.71-1.07, P = .31). However, studies using first-generation antipsychotic (FGA)-LAIs (studies = 10, RR = 0.82, 95% CI:0.69-0.97, P = .02) and those published ≤ 1991 (consisting exclusively of all 8 fluphenazine-LAI studies; RR = 0.79, 95% CI: 0.65-0.96, P = 0.02) were superior to OAPs regarding the primary outcome. Pooled LAIs also did not separate from OAPs regarding any secondary outcomes. Again, studies using FGA-LAIs and those published ≤ 1991 were associated with LAI superiority over OAPs, eg, hospitalization and drug inefficacy.
In RCTs, which are less representative of real-world patients than naturalistic studies, pooled LAIs did not reduce relapse compared with OAPs in schizophrenia patients. The exceptions were FGA-LAIs, mostly consisting of fluphenazine-LAI studies, which were all conducted through 1991. Because this finding is vulnerable to a cohort bias, studies comparing FGA-LAI vs second-generation antipsychotics-LAI and LAI vs OAP RCTs in real-world patients are needed.
长效注射用抗精神病药物（LAIs）有望降低精神分裂症的高复发率，但近期的随机对照试验（RCTs）对LAIs优于口服抗精神病药物（OAPs）的益处提出了质疑。
对持续时间≥6个月的比较LAIs和OAPs的RCTs进行系统评价/荟萃分析。主要结局是研究定义的最长时间点的复发；次要结局包括3、6、12、18和24个月时的复发、全因停药、因不良事件停药、药物无效（即复发+因无效停药）、住院和不依从。
在21项RCTs（n = 5176）中，在最长时间点预防复发方面，LAIs与OAPs相似（研究 = 21，n = 4950，相对风险[RR] = 0.93，95%置信区间[CI]：0.80 - 1.08，P = 0.35）。将分析限制在持续时间≥1年的门诊研究中，这一结果得到了证实（研究 = 12，RR = 0.93，95% CI：0.71 - 1.07，P = 0.31）。然而，使用第一代抗精神病药物（FGA）-LAIs的研究（研究 = 10，RR = 0.82，95% CI：0.69 - 0.97，P = 0.02）以及1991年及以前发表的研究（仅包括所有8项氟奋乃静-LAI研究；RR = 0.79，95% CI：0.65 - 0.96，P = 0.02）在主要结局方面优于OAPs。汇总的LAIs在任何次要结局方面也未与OAPs区分开来。同样，使用FGA-LAIs的研究以及1991年及以前发表的研究与LAIs优于OAPs相关，例如住院和药物无效。
在RCTs中，与自然主义研究相比，其对真实世界患者的代表性较差，汇总的LAIs与精神分裂症患者的OAPs相比并未降低复发率。例外情况是FGA-LAIs，主要由氟奋乃静-LAI研究组成，这些研究均在1991年之前进行。由于这一发现容易受到队列偏倚的影响，因此需要在真实世界患者中比较FGA-LAI与第二代抗精神病药物-LAI以及LAI与OAP RCTs的研究。
