Hacker News Reader

You and the GP talking about entirely different things. You're talking about how investigators choose the initial dose for the clinical trials, he's talking about the dosage that is actually prescribed by doctors.

Hence the 'The dose we take is not a "BEST GUESS"' (emphasis mine). Unless you're a lab animal or a person in a clinical trial, the does you take is the end result of lots of money spent on first figuring out maximum safe dosages (Phase 1) to prescribing guidelines that doctors are taught (Phase 3).

Antidepressants are a unique group of drugs because the dosage is highly dependent on each person's unique brain chemistry and a huge part of a good psychiatrist's job is working with their patients to find the right dosage and combination. The problem is that many psychiatrists don't have the time (due to insurance billing practices) or the patience to do the work but any decent psychiatrist will tell you that recommended doses for antidepressants are just a safe starting point for most patients, not the dosage that they will eventually find most effective.

For the record, I have worked in the pharmaceutical industry on pre-clinical drug development and Phase 1-3 marketing applications and the GP's description is largely accurate whereas you seem to have a chip on your shoulder. I wouldn't trust a single book about the drug development process that wasn't heavily influenced by the pharmaceutical industry in one way or another just like I wouldn't trust anyone without semiconductor industry experience when talking about Intel's cutting edge fabrication processes.

> Antidepressants are a unique group of drugs because the dosage is highly dependent on each person's unique brain chemistry and a huge part of a good psychiatrist's job is working with their patients to find the right dosage and combination.

How does one accomplish this absent trial and error?

This fact undermines the entirety of your argument.

"Best guess" is exactly what they do.

You do know what "unique" means in this context, right? Hint: it means that antidepressants are the exception to my argument because psychopharmacology is so much more dependent on genetic/environmental factors than the rest of the pharmacological field that we cannot draw conclusions on the effectiveness of dosages pre-treatment without spending 100-1000x more time and money on the clinical trials than we do now.

Please take your clearly ignorant bias and anti-pharma prejudice somewhere else - you have no idea what you're talking about.

It is not a guess. It is statistics. Typically, the dose is either effective or partially effective and often on the smaller side as Phase 3 also looks at side effects.

>It's all a guess until the end, and even then we're often not sure. Look at anti-depressants. We still don't know how a lot of those work but prescribe them to millions of people regardless. How do you think they determined the dose when they don't know how the drug works?

We know how antidepressants work, the chemical reaction is well known and can be quantified at different doses. We just don't know why they work because we don't understand why/how the brain works.

Pedantic but important difference.

No, we don't know the antidepressive mechanism of antidepressants, therefore we don't know how they work. Understanding some neurochemical reactions and biological adaptations they cause is not enough. (We also don't have a complete understanding of depressive disorders, we don't really have very effective medication/therapy for many depressive people, etc.)

SSRIs, SSRIs, MAOIs and TCAs all have reasonably well understood pharmacology. As an extreme example, there are very detailed guidelines on how to prescribe venlafaxine, to whom, and who should supervise. You're free to dispute these claims but I think you need to produce more than a blanket dismissal, especially as the OP offers a seemingly reasonable source.