Background: Obsessive-compulsive disorder (OCD) is a common chronic mental disorder with a high disability rate. Serotonin reuptake inhibitors (SRIs), including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, such as clomipramine, are the most common choices for the pharmacological treatment of OCD. Optimizing their use is pivotal in guiding clinical practice of OCD. However, there are few studies on the optimal dose of SRIs and there is controversy about their dose–response relationship and optimal target dose. Therefore, the objective of this study was to summarize the relationship between the dose and effect of SRIs, as well as the optimal dose of SRIs for OCD, as to propose future research directions.

Methods: Medline, Embase, Biosis, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and CINAHL were searched for relevant publications, and the search was up to February 22, 2020. We used a one-stage, robust error meta-regression (REMR) model to deal with the correlated dose–response data for SRIs from different studies. Doses of SRIs were converted to fluoxetine equivalents when performing dose–response analysis. Review Manager Program Version 5.3 and STATA software package (version 15.1) were applied to analyze data. The study protocol was registered with PROSPERO (number CRD42020168344).

Results: Eleven studies involving 2,322 participants were included in final analysis. For SRIs, the dose–efficacy curve showed a gradual increase trend in the 0–40-mg dose range and then had a decreased trend in doses up to 100 mg fluoxetine equivalent. Dropouts due to adverse effects gradually increased throughout the inspected dose slope. The curve of dose of all-cause dropouts suggested no relationship between them. Sensitivity analysis proved that these results were robust.

Conclusion: The systematic review found that the optimal dose for efficacy was about 40mg fluoxetine equivalent. Tolerability decreased with increased doses, and there was no significant correlation between acceptability and doses of SRIs. Therefore, the optimal dose of SRIs needs to consider effectiveness and tolerability.

Systematic Review Registration: [PROSPERO], identifier [CRD42020168344].

背景：强迫症（OCD）是一种常见的慢性精神障碍，致残率很高。5-羟色胺再摄取抑制剂（SRIs），包括选择性5-羟色胺再摄取抑制剂（SSRIs）和三环类抗抑郁药，如氯米帕明，是强迫症药物治疗的最常见选择。优化它们的使用对于指导强迫症的临床实践至关重要。然而，关于SRIs最佳剂量的研究很少，其剂量反应关系和最佳靶剂量存在争议。因此，本研究的目的是总结SRIs的剂量与作用之间的关系，以及SRIs治疗强迫症的最佳剂量，以提出未来的研究方向。

方法：在 Medline、Embase、Biosis、PsycINFO、Cochrane Central Register of Controlled Trials (CENTRAL)、Web of Science 和 CINAHL 中检索相关出版物，检索截止至 2020 年 2 月 22 日。元回归（REMR）模型处理来自不同研究的 SRI 的相关剂量反应数据。在进行剂量反应分析时，SRIs 的剂量被转换为氟西汀当量。Review Manager Program 5.3 版和STATA 软件包（15.1 版）用于分析数据。研究方案已在 PROSPERO 注册（编号 CRD42020168344）。

结果：涉及 2,322 名参与者的 11 项研究被纳入最终分析。对于 SRI，剂量-疗效曲线在 0-40 毫克剂量范围内呈逐渐增加的趋势，然后在剂量高达 100 毫克氟西汀当量时呈下降趋势。在整个检查的剂量斜率中，由于不利影响导致的脱落逐渐增加。全因辍学的剂量曲线表明它们之间没有关系。敏感性分析证明这些结果是稳健的。

结论：系统评价发现，疗效的最佳剂量约为 40mg 氟西汀当量。耐受性随着剂量的增加而降低，并且在可接受性和 SRI 剂量之间没有显着相关性。因此，SRIs的最佳剂量需要考虑有效性和耐受性。

系统审核注册： [PROSPERO]，标识符 [CRD42020168344]。