Analysis Group, Inc, 111 Huntington Ave, 10th Fl, Boston, MA 02199, USA.
J Clin Psychiatry. 2013 Jun;74(6):568-75. doi: 10.4088/JCP.12r08167. Epub 2013 Apr 19.
Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs.
A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or all-cause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol.
Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons.
Age- and gender-adjusted risk ratios (RRs) (depot/oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs.
Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively.
The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.
精神分裂症治疗中，不依从是一个主要的挑战。长效（ depot ）抗精神病药物常被推荐用来解决依从性问题，但 depot 与口服抗精神病药物比较的有效性证据并不一致。我们假设这种不一致可能是由于研究设计的系统差异所致。本综述评估了研究设计对抗精神病制剂比较有效性的影响。在一般临床环境中，更好地理解不同研究设计中有效性差异的根本原因，有助于更好地利用不同的抗精神病制剂。
我们对 2000 年至 2011 年间的英语文献进行了 PubMed 文献综述，这些文献提供了 depot 和口服抗精神病药物治疗组在精神分裂症中复发、住院或全因停药的信息。选择这一时间范围是为了反映专注于新一代抗精神病药物的研究。检索要求至少包含以下三个类别中的每个类别的一个术语：（1）精神分裂症；（2）注射、注射剂、可注射、注射剂、注射、 depot 、长效；和（3）依匹哌唑、氟奋乃静、氟哌啶醇、帕利哌酮、利培酮、奥氮平、阿塞那平、氟戊噻醇、氟奋乃静癸酸酯、鲁拉西酮、氯普噻吨、氟司匹利醇、佐克拉酮、齐拉西酮。
两名独立审查员确定了 13 项相关研究，这些研究包括 19 项 depot-oral 比较的信息。
根据研究设计（随机对照试验 [RCT]、前瞻性观察和回顾性观察），计算了确定终点的年龄和性别调整后的风险比（RR）（ depot / oral ），并进行了汇总。采用随机效应荟萃分析估计了按研究设计汇总的 RR。计算了研究设计之间的平均转换因子，作为汇总 RR 的比值。
荟萃分析调整后的终点显示，在 RCT 中 depot 制剂没有明显优于口服制剂的优势，RR 为 0.89（P =.416）。相比之下，在其他研究设计中， depot 制剂具有显著优势（前瞻性 RR = 0.62[P <.001]；回顾性 RR = 0.56[P <.001]）。这意味着 RCT 与前瞻性和回顾性设计之间的转换因子分别为 1.43 和 1.59。
抗精神病制剂的比较有效性对研究设计敏感。 depot 制剂在非随机观察性研究中显示出显著优势，而在 RCT 中则没有观察到差异。估计的转换因子可能有助于跨研究进行比较。
