A review of David Foster Wallace's 'The Pale King', examining its themes, the author's style and personal struggles, and the reviewer's evolving perspective on Wallace's work and legacy.

The post challenges the notion that effect sizes below 0.50 for medications are clinically insignificant, using antidepressants as a case study and comparing them to other common drugs.

Scott Alexander presents a detailed guide on depression, covering its causes, symptoms, and various treatment options, including lifestyle changes, therapies, medications, and other interventions.

Scott Alexander investigates the optimal dosage of Lexapro, comparing it to other antidepressants and exploring the reasons behind its effectiveness at lower doses.

Scott Alexander critically examines a new theory on antidepressant mechanisms, expressing skepticism while acknowledging its potential significance if proven true.

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.

Scott examines the bidirectional relationship between depression and sense of smell, exploring potential mechanisms and treatment implications.

Scott Alexander analyzes the PANDA Study, a large real-world antidepressant trial, discussing its methodology, results, and implications for understanding antidepressant efficacy.

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

Scott Alexander revisits his stance on SSRIs, discussing new meta-analyses, broader trends in psychiatric medication efficacy, and potential explanations for the discrepancy between statistical and clinical observations.

Scott Alexander critically examines a major meta-analysis on antidepressant efficacy, noting potential biases and comparing its surprising drug rankings to his own previous analysis.

Scott Alexander examines the rise, fall, and alleged resurrection of the antidepressant NSI-189, expressing skepticism about its efficacy and the broader challenges in developing new antidepressants.

Scott reviews a theory about serotonin receptors that explains how they help cope with stress, and discusses its implications and limitations.

Scott Alexander examines the synapse hypothesis of depression, which links decreased synaptogenesis to various depression research findings, and raises questions for future investigation.

A Links post presenting various news items and articles, ranging from cultural curiosities like the multiocular O to scientific findings about brain sex differences and genetic research, along with commentary on current events and politics.

Scott Alexander critically examines pharmacogenomic testing for antidepressants, particularly the GeneSight test, expressing skepticism about its current effectiveness and validity.

Scott Alexander explores the complexities and inconsistencies of drug tolerance in psychiatry, highlighting how different drugs can produce varying tolerance effects across individuals.

Scott examines new research on ketamine's antidepressant effects and its implications for understanding depression and evaluating psychiatric literature.

Scott Alexander analyzes online drug ratings, finding patients prefer older antidepressants while doctors prefer newer ones, and explores potential explanations for this paradox.

Scott Alexander defends his stance on the 'chemical imbalance' theory of depression, arguing that Mad In America's critique actually supports his view of a more nuanced understanding in psychiatry.

Scott Alexander defends psychiatry's use of 'chemical imbalance' theory, arguing it was meant to emphasize depression's biological basis rather than claiming a simple serotonin deficiency.

Scott Alexander explains how psychiatric conditions like ADHD can be both over- and underdiagnosed simultaneously, due to statistical quirks in diagnosis and population prevalence.

Scott analyzes various criticisms of antidepressants, concluding they have modest but real benefits over placebo, with important considerations about side effects and efficacy.

Scott explores the fascinating etymology of 'placebo' from medieval funerals to medicine, then discusses the controversial placebo effect in depression treatment.

Scott Alexander offers a comprehensive guide for treating depression, covering professional help, lifestyle changes, and supplements, emphasizing the importance of persistence in finding effective treatments.