Furmark Tomas, Wahlstedt Kurt, Faria Vanda
Department of Psychology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Front Psychol. 2025 May 12;16:1531725. doi: 10.3389/fpsyg.2025.1531725. eCollection 2025.
Selective serotonin reuptake inhibitors (SSRIs), widely used for anxiety and depression, are often criticized for their perceived similarity in efficacy to placebo treatments and the unclear connection between brain serotonin levels, on one hand, and the symptomatology of these disorders, on the other. In this perspective paper we discuss the complex mechanisms behind SSRI and placebo treatments in managing social anxiety disorder (SAD), focusing on both pharmacological and expectancy effects. Through a series of neuroimaging studies using positron emission tomography (PET), we investigated the neural, neurochemical and behavioral changes associated with SSRI and placebo responses in SAD patients. Results from one study revealed that both SSRI and placebo responders showed equal reductions in amygdala activity, a region central to fear processing, as well as comparable improvements in social anxiety symptoms. These findings suggest shared neural pathways between SSRIs and placebos, possibly related to response expectancies. In another study, we manipulated patient expectations using a deception design, showing that overt SSRI treatment yielded greater symptom reduction than covert administration. PET results further underscored the influence of expectation on dopamine signaling. Furthermore, PET data on serotonin transporters indicated that serotonin reuptake inhibition alone does not fully account for SSRIs' clinical efficacy, as serotonin transporter occupancy was not correlated with symptom improvement. In yet another study, combining SSRIs with cognitive-behavioral therapy (CBT) led to more robust and longer-lasting outcomes than placebo combined with CBT, with distinct effects on brain monoamine transporters. Overall, these findings emphasize the intricate interplay between pharmacology, brain mechanisms, and psychological expectations in the treatment of SAD.
选择性5-羟色胺再摄取抑制剂（SSRIs）被广泛用于治疗焦虑症和抑郁症，但其疗效常被认为与安慰剂治疗相似，且一方面脑内5-羟色胺水平与另一方面这些疾病的症状学之间的联系尚不明确，因此常受到批评。在这篇观点论文中，我们讨论了SSRIs和安慰剂治疗社交焦虑症（SAD）背后的复杂机制，重点关注药理学和预期效应。通过一系列使用正电子发射断层扫描（PET）的神经影像学研究，我们调查了与SAD患者中SSRIs和安慰剂反应相关的神经、神经化学和行为变化。一项研究的结果显示，SSRIs反应者和安慰剂反应者在杏仁核活动（恐惧处理的核心区域）方面均有同等程度的降低，社交焦虑症状也有类似程度的改善。这些发现表明SSRIs和安慰剂之间存在共同的神经通路，可能与反应预期有关。在另一项研究中，我们使用欺骗设计操纵患者的预期，结果表明公开给予SSRIs治疗比隐蔽给药能产生更大程度的症状减轻。PET结果进一步强调了预期对多巴胺信号传导的影响。此外，关于5-羟色胺转运体的PET数据表明，仅5-羟色胺再摄取抑制并不能完全解释SSRIs的临床疗效，因为5-羟色胺转运体占有率与症状改善无关。在另一项研究中，将SSRIs与认知行为疗法（CBT）相结合比将安慰剂与CBT相结合能产生更强效且更持久的效果，对脑单胺转运体有不同的影响。总体而言，这些发现强调了在SAD治疗中药理学、脑机制和心理预期之间的复杂相互作用。
