Scott Alexander explores Hallucinogen Persisting Perception Disorder (HPPD) and other conditions where drugs cause permanent effects, discussing potential mechanisms and their implications. Longer summary

Scott Alexander discusses Hallucinogen Persisting Perception Disorder (HPPD), a condition where some people experience permanent hallucinatory effects after using psychedelic drugs, particularly LSD. He explores the prevalence, potential mechanisms, and implications of this disorder. The post compares HPPD to other conditions with persistent effects like tardive dyskinesia, and examines various theories about how drugs could cause permanent changes in the brain. Scott considers two main hypotheses: the killing-off of specific neurons, and the idea of the brain as a chaotic system settling into new attractor states. He expresses a preference for the neuron death theory as it seems more understandable and less scary, but acknowledges the complexity and uncertainty surrounding these issues. Shorter summary

Scott explores the theory that clozapine's unique effectiveness in treating schizophrenia may be due to its combined action on dopamine and glutamate systems, potentially opening avenues for safer treatments. Longer summary

This post explores why clozapine is considered uniquely effective among antipsychotic drugs for treating schizophrenia. Scott discusses recent research suggesting clozapine's superiority may be due to its action on the glutamate system, specifically as an NMDA receptor agonist, in addition to its dopamine-blocking effects. He explains that adding NMDA modulators to other antipsychotics improves their efficacy, but not when added to clozapine, possibly because clozapine already has this effect. The post speculates that if this theory is correct, it could lead to safer treatments combining standard antipsychotics with NMDA agonists, avoiding clozapine's serious side effects. However, Scott notes that more research is needed to confirm this hypothesis and overcome regulatory hurdles. Shorter summary

Scott Alexander argues that the 33% rate of post-marketing safety events for FDA-approved drugs is not necessarily concerning and explains why post-marketing surveillance is a normal part of drug safety monitoring. Longer summary

Scott Alexander discusses a study showing that 33% of FDA-approved drugs in the past decade have faced post-marketing safety events. He argues that this doesn't necessarily mean the FDA is too lax, explaining that post-marketing surveillance is a normal and necessary part of drug safety monitoring. He points out that only 1.3% of drugs were actually withdrawn from the market, which he considers a good success rate. Scott explains why it's impossible to catch all potential side effects in pre-approval studies and gives examples of safety communications that range from important to seemingly trivial. He concludes that the 33% figure alone is meaningless without a broader cost-benefit analysis of FDA approval standards. Shorter summary

Scott Alexander criticizes websites that misleadingly suggest drug side effects by scraping FDA data, potentially causing patients to stop taking necessary medications. Longer summary

Scott Alexander criticizes websites like EHealthMe that automatically generate pages suggesting connections between drugs and side effects based on FDA data scraping. He argues these sites are misleading and potentially harmful, as they can cause patients to stop taking necessary medications due to unfounded fears of side effects. The post begins with a personal anecdote about a patient concerned about Xolair causing depression, then delves into how these websites operate and why their information is unreliable. Scott emphasizes the scummy nature of these practices and their potential to harm vulnerable individuals, concluding with a stark example of how such misinformation could lead to tragedy. Shorter summary

Scott examines how rare but severe drug side effects often lead to underprescription compared to drugs with common but less severe side effects, potentially resulting in suboptimal patient care. Longer summary

This post discusses the issue of rare but severe side effects in psychiatric medications versus common but less severe side effects. Scott uses two main examples: nefazodone vs SSRIs for depression, and modafinil vs Adderall for stimulants. He argues that drugs with rare but spectacular side effects (like nefazodone and modafinil) are often underprescribed compared to drugs with more common but less severe side effects (like SSRIs and Adderall). The post explores the reasons for this, including doctors' risk aversion, lawsuit concerns, and media coverage of rare side effects. Scott suggests that this pattern may lead to suboptimal treatment choices for patients. Shorter summary