Keio University School of Medicine, Tokyo, Japan.
J Clin Psychiatry. 2013 Oct;74(10):957-65. doi: 10.4088/JCP.13r08440.
Recent, large, randomized controlled trials (RCTs) showed no benefit of long-acting injectable (LAI) antipsychotics over oral antipsychotics in preventing relapse in schizophrenia, nor did a recent meta-analysis incorporating these studies. However, RCTs might enroll a disproportionate number of patients with better treatment adherence and lower illness severity. Mirror-image studies, which compare periods of oral antipsychotic versus LAI treatment in the same patients, might therefore better reflect the real-world impact of LAIs.
A systematic literature search without language restriction was conducted using MEDLINE/PubMed, Cochrane Library, Web of Science, PsycINFO, and CINAHL until May 31, 2012. Search terms included synonyms of (1) antipsychotic(s) AND (2) schizophrenia and related disorders AND (3) depot, (long-acting) injection(s), microsphere, decanoate, palmitate, enanthate.
Of 5,483 identified citations, 607 articles were fully inspected, and 582 were ineligible. Finally, 25 mirror-image studies from 28 countries that followed 5,940 patients with schizophrenia for ≥ 12 months (≥ 6 months each on oral antipsychotic and LAI treatment) met the inclusion criteria and were analyzed.
Coprimary outcomes were hospitalization risk and number of hospitalizations. Secondary outcomes included hospitalization days and length of stay.
LAIs showed strong superiority over oral antipsychotics in preventing hospitalization (16 studies, N = 4,066; risk ratio = 0.43; 95% CI, 0.35-0.53; P < .001) and in decreasing the number of hospitalizations (15 studies, 6,342 person-years; rate ratio = 0.38; 95% CI, 0.28-0.51; P < .001). This strong advantage was also observed for secondary outcomes and in multiple clinically relevant subpopulations and treatment groups.
Results from mirror-image studies in patients eligible for clinical use of LAIs showed strong superiority of LAIs compared to oral antipsychotics in preventing hospitalization. The results were in contrast to the recent meta-analysis of RCTs, which showed no superiority of LAIs. Given the possible biases in mirror-image studies, such as expectation bias, natural illness course, and time effect, a cautious interpretation is required. Nevertheless, the population in mirror-image studies better reflects the population receiving LAIs in clinical practice.
最近的几项大型随机对照试验（RCT）显示，长效注射抗精神病药（LAI）在预防精神分裂症复发方面并不优于口服抗精神病药，最近一项纳入这些研究的荟萃分析也未显示出这一点。然而，RCT 可能会招募到更多治疗依从性较好、疾病严重程度较低的患者。因此，比较同一患者接受口服抗精神病药和 LAI 治疗的镜像研究可能更能反映 LAI 的实际影响。
使用 MEDLINE/PubMed、Cochrane 图书馆、Web of Science、PsycINFO 和 CINAHL 进行了无语言限制的系统文献检索，检索时间截至 2012 年 5 月 31 日。检索词包括（1）抗精神病药和（2）精神分裂症及相关障碍和（3）储库、（长效）注射、微球、癸酸酯、棕榈酸酯、庚酸酯的同义词。
在 5483 篇确定的引文中有 607 篇全文进行了检查，其中 582 篇不符合入选标准。最终，来自 28 个国家的 25 项镜像研究符合纳入标准，这些研究共纳入了 5940 名精神分裂症患者，随访时间≥ 12 个月（≥ 6 个月分别接受口服抗精神病药和 LAI 治疗）。
主要结局为住院风险和住院次数。次要结局包括住院天数和住院时间。
LAI 在预防住院（16 项研究，N = 4066；风险比=0.43；95%CI，0.35-0.53；P <.001）和减少住院次数（15 项研究，6342 人年；率比=0.38；95%CI，0.28-0.51；P <.001）方面明显优于口服抗精神病药。次要结局和多个临床相关亚组和治疗组也观察到了这一明显优势。
在符合 LAI 临床应用条件的患者的镜像研究中，LAI 与口服抗精神病药相比，在预防住院方面具有明显优势。这与最近一项 RCT 的荟萃分析结果形成对比，后者显示 LAI 并无优势。鉴于镜像研究可能存在预期偏倚、自然病程和时间效应等偏倚，需要谨慎解释。然而，镜像研究中的人群更能反映临床实践中接受 LAI 的人群。
