Scott Alexander examines the development and effectiveness of vilazodone and vortioxetine, two antidepressants designed to work faster and better than SSRIs, but which ultimately failed to live up to expectations. Longer summary

Scott Alexander discusses the development and effectiveness of two antidepressants, vilazodone and vortioxetine, which were designed to combine SSRI effects with 5-HT1A partial agonism. He explains the theoretical basis for their development, involving the role of presynaptic 5-HT1A autoreceptors in delaying SSRI effectiveness. The post then evaluates the clinical performance of these drugs, finding that despite their innovative design, they don't significantly outperform older antidepressants in efficacy, onset speed, or side effect profile. Scott expresses confusion about the theoretical underpinnings of these drugs and why pharmaceutical companies invested so heavily in their development. Shorter summary

Scott examines how the 5-HTTLPR gene was wrongly linked to depression for years, discussing the implications for psychiatric research and genetic testing products. Longer summary

This post discusses the history and eventual debunking of the 5-HTTLPR gene's supposed role in depression. Initially, numerous studies claimed to find links between 5-HTTLPR and various mental health conditions, interactions with stress, and even antidepressant efficacy. However, a recent large-scale study by Border et al. found no evidence for these claims, suggesting that hundreds of previous studies were likely false positives. The post explores the implications of this finding, including concerns about the reliability of psychiatric research, the tendency for studies to reinforce existing beliefs, and the questionable validity of pharmacogenomic testing products that rely on genes like 5-HTTLPR. Shorter summary