Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Department of Methodology, Tilburg University, Tilburg, The Netherlands.
Psychopharmacology (Berl). 2024 Sep;241(9):1731-1755. doi: 10.1007/s00213-024-06645-2. Epub 2024 Jul 9.
Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood.
We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia).
We identified publications by searching Medline and Embase databases and assessed the risk of bias. A random effects meta-analysis was performed and moderator effects were analysed with Bayesian penalized meta-regression.
Our search yielded 105 elevated plus maze, 63 marble burying, 11 ultrasonic vocalization, and 7 stress-induced hyperthermia articles. Meta-analysis suggested that SSRIs reduce anxiety-like behaviour in the elevated plus maze, marble burying and ultrasonic vocalization test and that effects are moderated by pre-existing stress conditions (elevated plus maze) and dose dependency (marble burying) but not by duration of treatment or type of SSRI. The reporting quality was low, publication bias was likely, and heterogeneity was high.
SSRIs seem to reduce a broad range of unconditioned anxiety-associated behaviours. These results should be interpreted with caution due to a high risk of bias, likely occurrence of publication bias, substantial heterogeneity and limited moderator data availability. Our review demonstrates the importance of including bias assessments when interpreting meta-analysis results. We further recommend improving the reporting quality, the conduct of animal research, and the publication of all results regardless of significance.
选择性 5-羟色胺再摄取抑制剂（SSRIs）是治疗焦虑样障碍的首选药物。然而，SSRIs 影响焦虑的哪些方面尚未完全了解。
我们旨在系统地综述六种临床有效的 SSRIs 对非条件性焦虑的四个方面的影响：接近-回避行为（高架十字迷宫）、重复行为（埋珠）、痛苦行为（超声发声）和自主神经系统激活（应激诱导性发热）。
我们通过搜索 Medline 和 Embase 数据库确定了出版物，并评估了偏倚风险。进行了随机效应荟萃分析，并通过贝叶斯惩罚性元回归分析了调节效应。
我们的搜索结果得到了 105 篇高架十字迷宫、63 篇埋珠、11 篇超声发声和 7 篇应激诱导性发热的文章。荟萃分析表明，SSRIs 减少高架十字迷宫、埋珠和超声发声测试中的焦虑样行为，并且效应受到预先存在的应激条件（高架十字迷宫）和剂量依赖性（埋珠）的调节，但不受治疗持续时间或 SSRI 类型的调节。报告质量低，发表偏倚可能存在，异质性高。
SSRIs 似乎减少了广泛的非条件性焦虑相关行为。由于存在高度偏倚风险、发表偏倚的可能性、高度异质性和有限的调节数据可用性，这些结果应谨慎解释。我们的综述表明，在解释荟萃分析结果时，纳入偏差评估非常重要。我们进一步建议提高报告质量、进行动物研究，并无论结果是否具有统计学意义都要发表所有结果。
