Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
J Psychiatr Res. 2021 Jan;132:144-150. doi: 10.1016/j.jpsychires.2020.10.009. Epub 2020 Oct 16.
We investigated the association between discontinuation due to withdrawal of consent (DWC) in schizophrenia trials and the use of long-acting injectable antipsychotics (LAI-APs). In two categorical meta-analyses of randomized controlled trials, we compared DWC: individual and pooled LAI-APs vs. (1) placebo and (2) oral antipsychotics (OAPs). We also performed conducted a single-group meta-analysis to calculate the average DWC and a meta-regression analysis to examine the association between the results of the meta-analyses and factors related to study design, treatment, and patients. We identified 52 studies (total adult patients = 18,675, LAI-APs = 12,613, placebo = 2,083, and OAPs = 3,979; median study duration = 32 weeks). DWC was higher for LAI-aripiprazole than for the placebo [risk ratio (95% confidence interval) = 1.70 (1.23-2.39)]. Neither pooled nor individual LAI-APs differed from the placebo for fluphenazine, olanzapine, paliperidone, and risperidone or from the OAPs for aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol. The average DWC of each LAI-AP was as follows: LAI-aripiprazole = 10.98%, LAI-fluphenazine = 7.65%, LAI-flupenthixol = 3.33%, LAI-haloperidol = 6.71%, LAI-olanzapine = 10.50%, LAI-paliperidone = 10.38%, LAI-perphenazine = 7.06%, LAI-risperidone = 10.39%, LAI-zuclopenthixol = 4.45%, pooled LAI-APs = 9.88%, and placebo = 11.17%. Meta-regression analysis demonstrated that publication year (β = 0.02), percentage of males (β = 0.02), and mean age (β = 0.05) were associated with an average DWC for pooled LAI-APs. Study duration (β = -0.03), percentage of males (β = 0.08), and patient status (β = -0.85) were associated with an average DWC for LAI-aripiprazole. Presence of a placebo arm (β = 1.60) was associated with an average DWC for LAI-fluphenazine. LAI-AP use was unlikely to be associated with DWC. Although the LAI-aripiprazole had a higher DWC than did the placebo, its average DWC was similar to other those of LAI-APs.
我们调查了精神分裂症试验中因撤回同意而停药（DWC）与使用长效注射抗精神病药物（LAI-APs）之间的关系。在两项随机对照试验的分类荟萃分析中，我们比较了 DWC：单独和汇总的 LAI-APs 与（1）安慰剂和（2）口服抗精神病药（OAPs）。我们还进行了一项单组荟萃分析，以计算平均 DWC，并进行荟萃回归分析，以检查荟萃分析结果与与研究设计、治疗和患者相关的因素之间的关联。我们确定了 52 项研究（总成年患者=18675，LAI-APs=12613，安慰剂=2083，OAPs=3979；中位研究持续时间=32 周）。与安慰剂相比，LAI-阿立哌唑的 DWC 更高[风险比（95%置信区间）=1.70（1.23-2.39）]。与安慰剂相比，聚集体或个体 LAI-APs 在氟奋乃静、奥氮平、帕利哌酮和利培酮方面没有差异，在阿立哌唑、氟奋乃静、氟哌啶醇、奥氮平、帕利哌酮、利培酮和齐拉西酮方面与 OAPs 也没有差异。每个 LAI-AP 的平均 DWC 如下：LAI-阿立哌唑=10.98%，LAI-氟奋乃静=7.65%，LAI-氟哌啶醇=6.71%，LAI-奥氮平=10.50%，LAI-帕利哌酮=10.38%，LAI-奋乃静=10.39%，LAI-齐拉西酮=4.45%，聚集体 LAI-APs=9.88%，安慰剂=11.17%。荟萃回归分析表明，出版年份（β=0.02）、男性比例（β=0.02）和平均年龄（β=0.05）与聚集体 LAI-APs 的平均 DWC 相关。研究持续时间（β=-0.03）、男性比例（β=0.08）和患者状况（β=-0.85）与 LAI-阿立哌唑的平均 DWC 相关。安慰剂组的存在（β=1.60）与 LAI-氟奋乃静的平均 DWC 相关。LAI-AP 的使用不太可能与 DWC 相关。尽管 LAI-阿立哌唑的 DWC 高于安慰剂，但它的平均 DWC 与其他 LAI-APs 相似。
