Scott Alexander examines how compounding pharmacies are producing cheaper versions of GLP-1 agonist drugs, exploring the economics, safety, and future implications of this practice. Longer summary

Scott Alexander discusses the 'compounding loophole' that allows compounding pharmacies to produce cheaper versions of GLP-1 agonist drugs like semaglutide (Ozempic). He explains how these pharmacies operate, the cost differences, safety concerns, and potential future implications. The post covers the legal basis for this practice during drug shortages, the impact on drug manufacturers like Novo Nordisk, and speculates on what might happen when the shortage ends. Scott also touches on the broader implications for drug pricing and availability. Shorter summary

Scott Alexander examines the complexities of abolishing the FDA and proposes more practical alternatives to increase medical innovation while maintaining safeguards. Longer summary

Scott Alexander discusses the challenges of abolishing the FDA, a popular libertarian idea. He explores various issues that would arise, such as the fate of prescription medications, drug contamination inspections, and the potential for exploitation by unethical companies. The post then proposes two more practical alternatives to complete FDA abolition: legalizing artificial supplements and creating an 'experimental drug' category. These suggestions aim to increase medical innovation and access while maintaining some safeguards. Shorter summary

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. Longer summary

This post discusses the interpretation of effect sizes in medical studies, particularly for antidepressants. It challenges the common notion that effect sizes below 0.50 are clinically insignificant. The author presents a Danish study that simulates various hypothetical medications, showing that even drugs that cure or significantly improve depression in a large percentage of patients might not meet traditional effect size thresholds. The post explains why these thresholds might be unrealistic due to factors like the placebo effect, high standard deviations in placebo groups, and patient dropouts. It also compares antidepressant effect sizes to those of other widely accepted medications, concluding that many common drugs would be considered 'clinically insignificant' by strict effect size standards. The author suggests that claims about 'meaningless effect sizes' should be given less weight compared to other evidence, such as clinical experience. Shorter summary

Scott Alexander reviews comments on his posts about aducanumab and the FDA, acknowledging some mistakes while defending his overall critique of FDA conservatism. Longer summary

Scott Alexander reviews comments on his recent posts about aducanumab and the FDA. He acknowledges some mistakes in his original post, but defends his overall critique of the FDA as overly conservative. The comments cover various aspects of drug approval, including the aducanumab controversy, surrogate endpoints, the FDA's impact on small biotech companies, and comparisons to other regulatory systems. Scott reflects on how to improve his fact-checking process while still writing passionate pieces. Shorter summary

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 Alexander argues that pseudoaddiction is a real and important concept, despite being widely denounced as pharma propaganda in the context of the opioid crisis. Longer summary

Scott Alexander argues that pseudoaddiction - the concept that some drug-seeking behaviors are due to undertreated pain rather than addiction - is real and important, despite being widely denounced as pharma propaganda. He presents several case studies from his own practice where patients exhibited 'drug-seeking behavior' for legitimate medical reasons. Scott criticizes a key paper arguing against pseudoaddiction, suggesting its arguments are muddled and flawed. He theorizes that while the concept started well-intentioned, it was co-opted by pharma companies, leading to media exaggeration and expert silence. Scott concludes that the denial of pseudoaddiction represents a failure of epistemics amid moral panic about the opioid crisis. Shorter summary

Scott Alexander humorously describes his observations at the American Psychiatric Association meeting, highlighting pharmaceutical influence, social justice focus, and historical context of psychiatry. Longer summary

Scott Alexander attends the American Psychiatric Association meeting and shares his observations in a humorous photo-essay. He notes the overwhelming presence of pharmaceutical advertising, the conference's focus on social justice issues, the presence of Scientology protesters and CIA recruiters, and the abundance of new but seemingly unnecessary psychiatric drugs. He reflects on the historical context of psychiatry, including its past political biases and progress over time, while critiquing the current state of the field and its relationship with drug companies and social trends. Shorter summary

Scott Alexander analyzes how FDA regulations contribute to drug shortages and high prices, using buspirone and insulin as examples. Longer summary

Scott Alexander discusses two issues in the pharmaceutical industry: the buspirone shortage and high insulin prices. He argues that both problems stem from regulatory issues, particularly FDA policies that inadvertently encourage monopolies and make it difficult for generic manufacturers to enter the market. For buspirone, the Generic Drug User Fee Amendments (GDUFA) of 2012 and 2017 have created a fee structure that favors large-scale monopolies. For insulin, the complex nature of biologics and the FDA's stringent approval process for biosimilars make it extremely difficult and expensive to produce generic versions. Scott criticizes the tendency to blame these issues on the free market, arguing instead that poorly designed regulations are the root cause. Shorter summary

Scott Alexander critiques the FDA approval of esketamine for depression, discussing issues with drug development, efficacy, cost, and administration requirements. Longer summary

This post discusses the FDA's approval of esketamine for treatment-resistant depression, highlighting the issues with the pharmaceutical industry's approach to drug development and approval. Scott Alexander explains how companies often make minor changes to existing chemicals to patent them, as in the case of esketamine (a left-handed version of ketamine). He critiques the high cost of esketamine compared to regular ketamine and the FDA's stringent requirements for its administration. The post also questions the efficacy of esketamine based on clinical trials and discusses the inconvenience of the approved delivery method. Scott expresses disappointment that this approval may set a precedent for future psychedelic medicines, making them equally inconvenient and bureaucratic to access. Shorter summary

Scott Alexander examines and expresses skepticism about a theory that attributes high-dose melatonin supplements to patent avoidance, while reflecting on the challenges of evaluating such claims. Longer summary

Scott Alexander discusses a theory about why melatonin supplements are often sold in doses much higher than recommended. The theory, proposed by Dr. Richard Wurtman, suggests that supplement manufacturers used higher doses to avoid paying royalties on a patent for lower doses. Scott expresses skepticism about this explanation, citing reasons such as the unusualness of patenting only up to a certain dose and the fact that many supplements are sold in high doses. He also notes that some companies do sell melatonin at the recommended dose without legal issues. Scott reflects on the challenges of evaluating such claims, balancing expert knowledge against rational skepticism. An update clarifies that the patent likely influenced initial supplement production but has since expired, though high-dose traditions persist. Shorter summary

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. Longer summary

This post reviews a major meta-analysis by Cipriani et al on the efficacy of antidepressants. The study claims to definitively show antidepressants work, but Scott notes it doesn't actually refute previous critiques about their effectiveness. He examines potential biases and methodological issues in the study, particularly around industry funding of trials. Scott also discusses the study's ranking of different antidepressants, noting some matches with conventional wisdom but also some surprising results. He compares these rankings to his own previous analysis, finding major discrepancies, and concludes by urging some caution in interpreting the study's results despite its impressive scope. Shorter summary

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. Longer summary

Scott Alexander discusses the disappointing results of NSI-189, a promising new antidepressant, in FDA trials. He explains how the drug initially failed to outperform placebo on the primary endpoint, leading to a stock crash for Neuralstem. However, the company later released positive secondary endpoint results, causing their stock to rise again. Scott expresses skepticism about these new results, suggesting they may be due to statistical manipulation rather than true efficacy. He reflects on the challenges of developing new antidepressants and the tendency to get overly excited about new drugs, ending with a sardonic hope for another new antidepressant, SAGE-217. Shorter summary

Scott Alexander criticizes branded combination nootropics, explaining why they are often ineffective or harmful, and advises careful individual experimentation with single substances instead. Longer summary

Scott Alexander criticizes branded combination nootropics, arguing they are often poorly designed and potentially harmful. He begins by mocking the ridiculous names and exaggerated claims of many such products, then explains why even well-intentioned combinations are problematic. The post discusses how nootropics affect individuals differently, making one-size-fits-all approaches ineffective. Scott emphasizes the importance of careful individual experimentation with single substances, rather than relying on pre-made combinations. He also cautions against assuming synergistic effects between different nootropics, noting that even well-studied psychiatric drug combinations often fail to show benefits. The post concludes by advising readers to approach nootropics cautiously and individually, rather than relying on branded combinations. Shorter summary

Scott Alexander explores why recreational drugs like ketamine and MDMA have shown more promise in treating mental health conditions than intentionally developed pharmaceuticals, suggesting a new direction for drug research. Longer summary

Scott Alexander discusses the surprising effectiveness of ketamine and MDMA in treating depression and PTSD respectively, noting that these recreational drugs have shown more promise than intentionally developed pharmaceuticals. He speculates on why this might be, suggesting that drugs with strong effects on the brain, even if originally used recreationally, might be more likely to have significant therapeutic benefits. Scott proposes that pharmaceutical research might be more productive if it focused on chemicals with powerful psychoactive effects, rather than prioritizing minimal side effects. He acknowledges potential counterarguments, including the possibility that ketamine's antidepressant effects may come from a non-psychoactive metabolite. Shorter summary

Scott Alexander discusses potential Trump administration health-related appointments, focusing on FDA commissioner candidates Jim O'Neill and Balaji Srinivasan, and their potential to implement beneficial reforms. Longer summary

Scott Alexander discusses potential Trump administration picks for key health-related positions, particularly the FDA commissioner and NIH chief. He expresses excitement about the possibility of Jim O'Neill or Balaji Srinivasan being chosen for FDA commissioner, viewing them as principled libertarians who could implement beneficial reforms. Alexander outlines several policies these candidates might pursue, such as medical reciprocity with other countries and streamlining generic drug approvals. He also mentions John Ioannidis as a surprising potential pick for NIH chief, praising his work in improving medical research standards. The post concludes by noting that pharmaceutical industry stocks haven't moved much in response to these potential appointments. Shorter summary

Scott argues against Vox's proposal for drug price controls, citing studies that such policies would significantly reduce pharmaceutical innovation and potentially cost millions of life-years long-term. Longer summary

Scott Alexander responds to Sarah Kliff's Vox article about drug pricing, arguing that her proposal for price controls on brand-name drugs would significantly decrease pharmaceutical innovation. He cites multiple economic studies suggesting price controls reduce R&D and new drug development. Scott argues that while price controls might lower costs in the short-term, they could cost millions of life-years long-term by reducing new drug creation. He suggests focusing on increasing generic drug competition and reducing unnecessary prescriptions of expensive brand-name drugs with cheap generic alternatives as better solutions to high drug prices. Shorter summary

The post examines three major issues with generic medications: barriers to market entry, problematic FDA initiatives, and inconsistent pricing across pharmacies. Longer summary

This post discusses the problems with generic medications in the United States, focusing on three main issues. First, it explores why competitors don't easily emerge to challenge price gouging, using the example of Daraprim's price increase. The author suggests that FDA approval processes, including bioequivalence studies, create significant barriers to entry. Second, it critiques the FDA's Unapproved Drugs Initiative of 2006, which allowed companies to gain exclusive rights to public domain drugs by conducting studies, leading to price increases. Finally, it highlights the wide price disparities for generic drugs at different pharmacies, suggesting that comparison shopping can lead to significant savings. Shorter summary

Scott Alexander explores the nuanced ways pharmaceutical companies influence doctors, arguing that their tactics are more subtle and ethically complex than simple bribery. Longer summary

Scott Alexander discusses the complexities of pharmaceutical company influence on doctors, using personal anecdotes and hypothetical scenarios. He argues that pharma companies use subtle tactics beyond simple bribery, such as providing free lunches or drug samples, which can be difficult for even ethical doctors to resist. The post also touches on a community dinner sponsored by a pharmaceutical company, which highlighted tensions between different healthcare professionals. Scott emphasizes that pharmaceutical companies are 'sneaky' in their approach to influencing medical practitioners. Shorter summary

Scott Alexander examines overpriced medical products like Lovaza and Deplin, arguing they serve a purpose in the medical system, but criticizes exorbitant BRCA gene testing prices as harmful. Longer summary

Scott Alexander discusses two examples of overpriced medical products: Lovaza (fish oil) and Deplin (folate), which are essentially the same as much cheaper supplements. He argues that these products serve a purpose by making these substances 'Official' in the medical system, allowing doctors to prescribe them without fear of liability. The post then examines the case of BRCA gene testing, where a company charges exorbitant prices for a service that could be much cheaper. Scott criticizes this practice, contrasting it with the FDA's ban on 23andMe offering BRCA testing, suggesting potential conflicts of interest. Shorter summary

Scott Alexander presents a satirical list of fictional drugs banned by the FDA, each with an absurd reason for its prohibition. Longer summary

This post is a humorous fictional list of drugs banned by the FDA. Each drug is presented with a profile describing its intended use, followed by an absurd or ironic reason for its ban. The drugs cover a range of conditions from weight loss to erectile dysfunction, with each ban highlighting unexpected consequences or bizarre side effects. The post uses scientific terminology and real medical concepts to create a sense of plausibility, before subverting expectations with the ridiculous reasons for the bans. Shorter summary

Scott Alexander critiques the medical system's preference for expensive prescription sleep aids like Ramelteon over cheaper alternatives like melatonin, while sharing interesting facts about melatonin's uses. Longer summary

Scott Alexander discusses Ramelteon, a prescription sleep medication that mimics melatonin. He compares it to over-the-counter melatonin, highlighting the absurdity of the medical system that creates expensive prescription drugs when cheaper, effective alternatives exist. The post criticizes the pharmaceutical industry and medical practice for overlooking simple solutions like melatonin. Scott also shares interesting facts about melatonin, including its potential uses beyond sleep aid. Shorter summary