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Isn't it basically known at this point that insufficient pain medication is very likely to encourage addition? Specifically, if pain medication wears out before the next scheduled dose, so that the patient experiences significant pain and therefore is looking forward to their next does for relief from that pain... well, it seems obvious that that would be a perfect recipe to strengthen dependency on that drug. IIRC that was one of the main criticisms of Oxycontin, that it was claimed to have a longer efficacy period than it actually did, so too-long dosing periods were prescribed, resulting in this effect. (Not to mention all the unnecessary discomfort between doses itself.)

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I recently had a bad reaction to a (non-narcotic) prescribed drug, and it got me thinking about how we could improve use of pharmaceuticals.

1. We don't measure the patients metabolism of a drug at all. Individuals bodies process drugs differently and have different side effects. It seems that differences in reactions could be related to different metabolic pathways being used, resulting in more or less toxic byproducts. Could a urine or blood test a few hours after the first dose be an effective mechanism for screening for likelihood of side effects based on the metabolic byproducts detected? Could this test be effective at detecting these byproducts at dosages below what would cause side effects? Could this be incorporated into a "home drug test" style urine dip that patient could do themselves at home without returning to doc?

2. Dosage is too one-size-fits-all. AFAICT, the drug I was given is usually prescribed at the same dose to slightly-underweight me as they would a larger patient double my weight. For these fixed-dosage drugs, it seems like lower-weight patients will have higher risk of side effects and higher-weight patients will have higher risk of dosing at sub-therapeutic levels.

3. Drug half-life is assumed to be nearly constant across the population. Even more than dosage, many drugs have a constant X times per day, but only dosage is adjusted. For people with atypical metabolism of that drug, the effective duration could vary drastically. Patients with slow metabolisms could develop side effects at low dosages if taken over a long enough period.

I'd love to see pharma move towards a model where patients are started at a sub-therapeutic level to test for allergy, then have a urine test to screen for toxic metabolites, then pills are portioned in to small enough increments that the patient can gradually titrate up the dose: start at 1/100th a dose, if no problems go to 1/10, then 1/5, then 1/4, then 1/2, then 3/4, then full dose. If at any point the patient feels like its 'working' they pause dose increases. I really wonder if I had been on half the dosage or frequency if I would have had all of the therapeutic benefits without the gnarly side effects.

>I'd love to see pharma move towards a model where patients are started at a sub-therapeutic level to test for allergy, then have a urine test to screen for toxic metabolites, then pills are portioned in to small enough increments that the patient can gradually titrate up the dose: start at 1/100th a dose, if no problems go to 1/10, then 1/5, then 1/4, then 1/2, then 3/4, then full dose. If at any point the patient feels like its 'working' they pause dose increases.

How long would this take? It might work for some medications, but someone with horrible chronic pain might not want to wait.

A single Percocet can be nausea inducing for a good chunk of the population. I think ~20% of individuals may prefer half a pill to a full one, and if they can manage with a lower dose it makes discontinuation much easier.

Certainly less useful for acute conditions, but for chronic multi-week regimens I think this could be a useful way to mitigate risks.

"We don't measure the patients metabolism of a drug at all. Individuals bodies process drugs differently and have different side effects. It seems that differences in reactions could be related to different metabolic pathways being used, resulting in more or less toxic byproducts. Could a urine or blood test a few hours after the first dose be an effective mechanism for screening for likelihood of side effects based on the metabolic byproducts detected? Could this test be effective at detecting these byproducts at dosages below what would cause side effects? Could this be incorporated into a "home drug test" style urine dip that patient could do themselves at home without returning to doc?"

Strangely, just the other day I met someone in Cambridge (UK) who is moving forward with a startup solving this EXACT problem.

Let me know if you want me to connect.

Yep -- OxyContin has a timed-release coating and by preventing the "peaks and valleys" of opiate use, it was supposed to minimize addiction. This was a major selling point for doctors, which turned out be based on falsified data.

The thing is, I don't think any studies have actually validated that concept? If you say "it's basically known", I'm curious what evidence you have for that statement. Are there studies where people have been prescribed more opioids but been less addicted because they finally have "sufficient" medication?

I didn't say, "It's basically known." I said, "Isn't it basically known?" I'm just going from memory, probably of news articles. I would be interesting to know what follow-up research has been done as well.

Ah, my bad. I thought that was meant to be a rhetorical question.

No, I could have been more clear for sure. I can see how you read it that way.

Also fwiw my reply should have been "I would be interested to know," not "I would be interesting." Although maybe I would be more interesting too, if I could supply that information...

Anecdotal from a history of more than a few surgeries: I think the OxyContin is actually less addictive. A pain relieving dose of a non time release opioid will last about four hours. I’ve had pain bad enough that it prevents sleep. To get a good eight hours of sleep I would need to take a much higher dose, and that puts you pretty deep into euphoria. Some people will keep chasing that feeling.

With OxyContin I could take a normal dose before bed and sleep through the night.

Research on drug addiction points to socioeconomic and cultural factors predicting addiction, not consuming the drug.

See the work of Johann Hari. People become addicts because they’re unhappy with their lives and their environment, not because opioids are inherently addictive. Which shouldn’t be surprising to anyone who has experienced addiction.

I'm sure that's a factor, but it seems unlikely to me it's the only one. All else being equal, going through a repetitive cycle of pain/craving and relief throughout recovery seems likely to encourage addiction as well. Which of course isn't to say that everyone who experiences that will become addicted, or that those who do won't skew toward those who are facing other difficulties in life, but from what I've read it does have an effect. And it fits my common sense, not that one should rely on that in absence of real evidence.

My point is limiting access to opioids isn't effective at treating addiction. Yet that's how our society has chosen to respond to drug addiction across the board, from opioids to alcohol.

The war on drugs doesn't work. And we've had 50 years now to see that. It's sad that the extent of our national conversation about the opioid epidemic is a soap opera about the Sackler family. There will be no front page articles on HN about actually treating addiction.

Well, yes for opiates I believe that's largely true. But I will say that as somebody going through chronic pain and anxiety for the first time, I can definitely see how my meds for those respective conditions could lead to a dependency despite an otherwise good social/support network and job.

> People become addicts because they’re unhappy with their lives and their environment,

You know what's one thing that makes people very unhappy with their lives? Severe chronic pain. Aside from the pain, it also removes a great deal of agency and self-efficacy from their lives. They can't control the pain, the medical system is basically out of their control, and now there's a societal hysteria about opiates.

Beyond that, what you're describing it the difference between addiction and dependency. Any flesh and blood human will become dependent on opiates after a few weeks. It's why doctors have you taper off opiates and other meds that cause dependency.

Although even that distinction seems to be going by the wayside in the current hysteria.

> You know what's one thing that makes people very unhappy with their lives? Severe chronic pain.

That's my point. Having taken an opiate actually has little to do with whether they form an addiction. So we shouldn't be focused on restricting supply to treat and prevent addiction.

> Any flesh and blood human will become dependent on opiates after a few weeks.

Yes, if by dependency you're referring to withdrawal symptoms or tolerance. Opioid addiction however varies wildly depending on the demographic, despite all having consumed opioids. It's not the act of taking opioids that predicts whether someone becomes addicted. Research points to addiction not being caused by the drugs themselves. This isn't surprising when you consider that humans get addicted to such a wide variety of totally unrelated chemical combinations. When you think about it, isn't it a little suspicious that almost any chemical that can be consumed is potentially addictive? That strongly suggests that addiction is not about the drugs really, and research is finally corroborating this.

Having said that, now think about the fact that all food is drugs (chemicals that affect and manipulate your biology) and it becomes apparent that addiction is a much much bigger issue than one might assume when only thinking about things like Oxy and booze as drugs. If one qualifies harmful diet as drug addiction it turns out the majority of our society is suffering from addiction. But there's very little research going on in this area, despite diet probably being the most prevalent and harmful form of drug addiction. You can't unsee it. The similarity between someone talking about their struggles with poor diet ("but that cheeseburger/cheetos/soda/etc. is all I have, can't I have just one thing to look forward to?") and someone talking about alcoholism or smoking is almost indistinguishable.

> societal hysteria about opiates.

I don’t think hysteria is an accurate term here as the danger and massive negative impact of opiates is very real. It is not imagined.

I like the word hysteria but am careful in its use because historically it has been used to discount and ignore very real problems with large chunks of the population [0].

I think to help patients and to help people suffering from addition and at risk for addiction it’s important to understand the problem. If people dismiss the problem as imaginary or happening to “them” and not “us” it is much more difficult to not have tons of people die.

[0] https://en.wikipedia.org/wiki/Female_hysteria

This is very true. One needs to consider both physical addiction and psychological addiction.

If you give 100 people high doses of Oxycotin for a month, all 100 will exhibit withdrawal symptoms when the drug is stopped. However, 80 of those will probably suffer through it and not crave the drug after that, 17 will willingly continue to use the drug to avoid the withdrawal symptoms and 3 will (if possible) escalate the dose to the point they care about nothing else.

That's the psychological part of it.

And yes, I made those numbers up, but you get the point.

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