OxyContin's 12-hour problem (2016)
latimes.com
latimes.com
Article argues that OxyContin caused strong withdrawal symptoms when used as directed. Important, imo, because at a societal level we substantially blame addiction on "drug abuse" which is not always an adequate model.
While I agree that this model is not accurate, I'd also point out that just because you're taking a drug as directed doesn't mean you're not abusing it.
For whatever reason most people in the U.S. seem to have a wildly unjustifiable level of faith in western medicine, either way too much or way too little. Belief and disbelief in various forms of medicine have been successfully marketed as personal identities, which is easy to see from reading most HN comment threads on health issues.
I tend to think about drug misuse, rather than drug abuse, since not taking certain drugs can be just as irrational and damaging as taking too many drugs.
But basically I think people should use drugs as tools to maximize their utility based on their needs and values. And I think that drug misuse is anything that leads to significantly suboptimal utility that's clearly not justifiable by any sort of internally coherent reasoning.
Drug abuse seems straight forwardly defined as using a drug for purposes other than as prescribed. Not following the schedule or following it when it is unwise to shouldn't be considered abuse as long as you are still using it to manage pain. Of course that boils down to intent, which is hard to determine.
Yes. I put "abuse" in scare quotes, because I think it's definition should be better aligned with buisiness incentives, medical advice, and actual human behavior, especially if we put people in jail for it.
The crux of this article was that Purdue knew their dosing schedule was problematic but pursued it despite growing evidence it was reducing efficacy and increasing addiction. Then they hid behind their FDA certification as if that exempts them from acting on evidence that their shitty drug doesn't work right.
In general, no drug for acute _anything_ will last as long as the manufacturer advertises. They are incentivized to push an idealized dosing schedule, even when that makes the drug less effective for a significant number of patients. This is kind of a big deal when a drug causes severe physical withdrawal symptoms.
There are a multitude of reasons to explain how this happened but to quickly sum up an excellent book:
- Purdue created the whole "sell-direct-to-doctor" phenomena that is now the norm in the US medical profession
- One bad study that showed opiates for pain relief are NOT addictive and this study kept being cited by sales people
- Mexican drug dealers from a very tiny area in Mexico importing black tar heroin
- A prevailing idea in the US that people should never be in pain and managing it through lifestyle changes is not acceptable; a quick fix is needed
- economic depression in the Midwest and Appalachia regions
But really, read the book. It's eye opening and well written.
Good to know.
The data on how fast OC released its drug would have been available to the FDA, if not doctors.
Which is it? I honestly don't think the FDA is culpable in this. They're there to ensure that the manufacturer is meeting a minimum standard of proof, and if the manufacturer is falsifying that proof and ignoring clinical feedback then the manufacturer is solely responsible and needs to be held accountable. But to say that the FDA isn't doing its job here isn't particularly accurate, because they're doing their best to apply the law and ensure that the claims being made are accurate.
Like what if some of the requirements for new drugs are arbitrary (slowing approval) and the standard of proof for novel release mechanisms is too low?
Besides, "stepping back and letting pharma companies innovate" is not the same as not participating. The FDA can make drug development cheap by many means, and the required fiscalization or catching that kind of behavior is not done by increasing the weight of the approval process.
Watching how dependent my mom has become on this has been painful to watch.
Sadly this harmless opiate replacement is schedule 1 in seven states and counting.
As noted elsewhere, this isn't new content.
What's preventing a pill that releases a dose immediately and one after 6 hours? Or something like a diabetic pump that dispenses medication continuously? Surely such systems have the potential to be safer and more effective for patients?
Being plopped into a bath of hydrochloric acid makes this a little tricky, I am led to understand.
> Or something like a diabetic pump that dispenses medication continuously?
And this led me down a brief Google walk for what these are, and...huh, that's a really good question...
IV pain management often includes a button the patient can push (that releases a dose and sets a timer for the next dose). Or at least it used to, I don't know if it is still done.
"The system, which resembles a conventional tablet in appearance, comprises an osmotically active trilayer core surrounded by a semipermeable membrane with an immediate-release drug overcoat.
The trilayer core is composed of two drug layers containing the drug and excipients, and a push layer containing osmotically active components. There is a precision-laser drilled orifice on the drug-layer end of the tablet.
In an aqueous environment, such as the gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of methylphenidate. Water permeates through the membrane into the tablet core. As the osmotically active polymer excipients expand, methylphenidate is released through the orifice. The membrane controls the rate at which water enters the tablet core, which in turn controls drug delivery."
it doesnt rely on being mixed with something to delay its action or be pressed into a solid pill, in fact you can open up the capsules and eat the powder inside and there is no change in its effects (its also ineffective intranasally or as far as i am aware even if injected) its rate of release is difficult to change, its just how long the average body takes to strip the lysene away from the chemical.
Nothing. There are such pills for stuff like Adderall and Ritalin already, on the mass market.
Is it cultural?
What we don't have is the drug culture, people look for alternative ways to mitigate the pain.
A quick googling gave me this WHO paper:
https://www.hrw.org/sites/default/files/reports/hhr0511W.pdf
We found enormous unmet need for pain treatment. Fourteen countries reported no consumption of opioid pain medicines between 2006 and 2008, meaning that there are no medicines to treat moderate to severe pain available through legitimate medical channels in those countries.
These countries are concentrated in Sub-Saharan Africa, but are also found in Asia, the Middle East and North Africa, and Central America
You have nothing to back that up. In fact, all the evidence I've seen points towards the opposite: the places with the least opiate abuse are (1) not happy countries (2) with very strict laws. See Qatar, Saudi Arabia, Singapore, etc.
If money and greed on the supply side, and lack of happiness on the demand side is the true cause of this, surely those countries would be ravaged with an opiate epidemic. But they are not. The problem is much more nuanced than you make it out to be.
Obviously, ceteris paribus, less pain is much better than more pain, and there will probably always be acute and chronic pain for therapeutic innovation to tackle. There's no virtue in the experience of chronic pain. But the evidence strongly suggests that patients are worse off with casual access to powerful opiates, and that these products are packaged and sold irresponsibly.
No legitimate underlying medical phenomenon spurred the uptake in opiates.
50% of American adults suffer from chronic pain. If those levels don't qualify as an epidemic, what levels would?
I tried to avoid this pointless debate with a second paragraph to immunize my argument from the trope that arguments against opiates are arguments in favor of pain.
My point --- I think obviously --- is that no underlying medical pathology occurred to spur the uptake in consumer opiate products.
The uptake of opiates wasn't driven by any change in pathology, but it was partially driven by a change in how we think about pathology. The IOM report I linked to helped to popularize the idea of treating pain itself as a disease that should be treated, rather than as a symptom which shouldn't be treated until the underlying cause is known:
"Because pain often produces psychological and cognitive effects—anxiety, depression, and anger among them—interdisciplinary, biopsychosocial approaches are the most promising for treating patients with persistent pain. But for most patients (and clinicians), such care is a difficult-to-attain ideal, impeded by numerous structural barriers—institutional, educational, organizational, and reimbursement-related. [...] In addition, adequate pain treatment and follow-up may be thwarted by a mix of uncertain diagnosis and societal stigma consciously or unconsciously applied to people reporting pain, particularly when they do not respond readily to treatment. [...] Understanding chronic pain as a disease means that it requires direct treatment, rather than being sidelined while clinicians attempt to identify some underlying condition that may have caused it."
I'm definitely not arguing that opioids should be first line treatments for chronic pain, but I also agree with the IOM that they should be more accessible when needed.
Anecdotal evidence over six decades of life on Planet Earth suggests otherwise.
https://www.washingtonpost.com/news/to-your-health/wp/2015/0...
C.f. the IOM report on pain in America: https://www.nap.edu/catalog/13172/relieving-pain-in-america-...
Perhaps knowing that doctors would be vigilant against prescribing drugs with the potential for abuse, Purdue set out to distinguish OxyContin from rivals as soon as it dropped. The cornerstone of its marketing campaign was the drug's incredibly low risk of addiction, an enviable characteristic made possible by its patented time-release formula. Through an array of promotional materials, including literature, brochures, videotapes, and Web content, Purdue proudly asserted that the potential for addiction was very small, at one point stating it to be "less than 1 percent." (http://theweek.com/articles/541564/how-american-opiate-epide...)
Conversely, the country I live has a benzo problem. Hell, go into any doctor complaining you haven't been sleeping properly and he'll happily prescribe you clonazepam to help you with that. You have just been prescribed an addictive and strong psychoactive drug, just like that. He won't care if you have been working too much, or not eating or sleeping well, he will not care at all about possible factors that may be causing your current insomnia.
"take this and come back to reassess in 2 months", the doctor will say, and ofc, in 2 months you will come back saying this helped immensely, and from that there's a whole slew of problems that everyone knows: try to wane off it, insomnia comes back, sometimes worse. or maybe some new anxiety gets thrown in....
They want money, because if they wanted you to get well they you'd be treating the cause of your symptoms and not your symptoms :D
I know a handful of doctors as well as pain patients, but I'm curious to get more context outside of the small bubble I know.
That's the whole point - doctors have more work, so they can ask for more money and pharmaceutical companies make a killing. Doctors are not interested in curing their patients nowadays, they are interested in making money for pharma.
>Is it cultural?
That's actually a really common misconception on HN. The United States ranks 27th among countries which abuse opiates, [1] behind many first-world countries like the UK, Italy, Spain, Switzerland, Ireland, and Russia, to name a few.
What's the cause? A lot of HNers like to pin it on unemployment and low-wage, low-skill jobs. I think that's narrowing the field in the right direction, but it isn't quite right; I know many very happy people who just make ends meet. There's something more that no one has been able to pinpoint quite yet.
1. https://en.wikipedia.org/wiki/List_of_countries_by_prevalenc...
I further suspect that the availability of opiate-containing drugs over the counter in some countries accounts for some of the differences in those statistics (e.g. cocodamol in the UK).
Since this discussion is about synthetic opioids it's not a useful source.
Have a look here. The US has considerably higher use than each of the countries you list when we talk about prescription meds.
http://www.unodc.org/documents/data-and-analysis/WDR2011/Sta...
Say you have a messed up disk in your spine. Surgery is tens of thousands of dollars. Getting a prescription for opioids from a primary care physician is a bit cheaper.
You don't see doctors in europe routinely prescribing hard pain killers because they try to fix the problem instead.
Healthcare in america is set up in such a way that hospitals just bill whatever and then have the lawyers argue over whats reasonable. That kinda works when youre part of the medicare system and their lawyers represent your side, but when youre on your own, you're suddenly in hospital recovering from major surgery, facing bankruptcy and have to hire a lawyer to tell the hospital to suck it.
So you just take the painkillers and hope for the best.
There are situations where risks from surgery are potentially worse than the (yes, possibly misinformed) side effects of painkillers.
Is there any data on this? Anecdotally, I know a few people who are either living with pain or taking medication because surgery is too risky.
Its just that there are people who "should" have surgery who "can't" have it because money.
Another issue is that just because a doctor advises you to take opioids doesn't mean that you're not abusing them. Doctors tell you to do all kinds of things that are bad for you because they are the lesser evil. The prime example being chemotherapy.
The primary use-case of morphine-like substances is to treat acute pain. Taking any kind of opioid for prolonged periods of time leads to systemic adaptation and you end up an "addict".
Is there data on this? Probably. Depends on what you want data for. The fact that america is under-insured when it comes to healthcare is well-established fact.
I don't buy "people take opioids because their lives are lame" - because its bullshit. There are drugs that are way easier to acquire that provide a lot more "fun". You don't start on heroin and then switch to vicodin, either. A heroin addiction is treated with methadone.
If you want a really clean "feel awesome" high, you want a benzodiazepine like Lorazepam. I had a prescription for that once. Popping one of those pills, you smile from ear to ear within seconds and experience pure bliss. If you intentionally try to have negative thoughts, you just laugh harder because it feels so ridiculous. If you wanted to "trick" a doctor into prescribing those, faking the necessary symptoms is really simple.
The drug industry has a pretty good grasp on how to engineer drugs to do one specific thing really well without causing a bunch of secondary effects. Modern painkillers are good at dealing with pain, without turning people into loonies. But opioids are opioids and if you take them indefinitely, you mess with brain chemistry.
Who are THEN told that they just can't get drugs anymore because now they're just filthy addicts. That's actually impressive. For a glorious nation like the united states of america. Borderline malice.
And, it's culturally acceptable to be on medication so people take it for basically any inconvenience.
Sweating a little? Crank the AC. Small headache? take a pill. Bad day? Have a drink. Workout left muscles sore? Another pill. Sprained ankle? Obviously you need pain medication!
It's easy to see how there is a low threshold to abusing pain medication.
For people who've used opioid medication in the past year most of the developed world has a figure of around 1% or 2%. The US has over 5%.
There have been a few prosecutions of individual sales/marketing people for knowingly supplying pill mills, but it's just a cost of business expense for large pharma companies.
What the farma company did was exploit already existing predisposition of people to take painkillers. They were working on fertile ground.
I don't know - having large population of people that need constant painkillers in their day to day life is just strange. Abusing the people is despicable. But why did this population existed in the first place?
https://www.medpagetoday.com/publichealthpolicy/publichealth...
The patent for OxyContin was predicated on the claim that each dose lasted longer than older poducts. When that didn't work they raised the dose instead of shortening dosing intervals, which caused a reward/withdrawal cycle in patients.
Seems to me it comes down to competence and ethics of individual doctors, as well as to preferences and susceptability of individual patients, of course.
We are not experiencing quite the epidemic proportions of the US, presumably owing to a different structure of health services, and probably a higher general level of scepticism towards medical authority, but the mechanisms and the potential are clearly in place.
https://www.amazon.com/Dreamland-True-Americas-Opiate-Epidem...
My takeaway was that opiates were incorrectly classified as a non-addictive way to treat pain, so doctors started dolling them out far too liberally. Hospitals also started employing pain specialists who's sole job was to treat pain in patients. It's pretty easy to find people in any sort of "pain" if that's all you're looking for.
Can we please fix something to add dynamic compression to pain signals? log(x) will be a good idea past some pain level.
Sensible doctors do not believe drug company marketing.
I get large amounts of ad-junk from drug companies that ends up unread in the bin. I refuse to meet with drug company representatives. I smile politely at them if I bump into them in the corridor and suggest that they leave their ad-junk with my secretary. My staff then file their ad-junk in the trash bin.
On Friday, I had a drug company representative attempt to tell me ( he was hanging around my coffee area ) about the joys of Targin, a fixed-dose combination of oxycodone and naloxone. I gently shook him off, and directed him to my secretary.
Drug company representatives are usually decent human beings with lives and families. However they are poorly educated, poorly informed salesmen and women with sales targets to meet and product managers to keep happy. Even worse, they and the drug company have no accountability if a patient dies because of their recommendations. If avoidable death supervenes or if there are non-lethal complications or even just therapeutic failure, I am accountable.
Instead of relying on marketing, I rely on information from good, well performed randomised controlled studies published in reputable peer reviewed journals ( I like the NEJM ) and on meta-analyses of these. I view the results of these through a filter of scepticism, cynicism, pragmatism and a modicum of hope.
Many of my colleagues do likewise. I trust that you do the same in your respective vocations. Regrettably, there is a bell curve. I am sure that the drug companies find enough gullible prescribers out in the wild for their purposes.
Also, this should probably have a "[2016]" tag in the title.
I happen to have direct exposure to the medical industry at the practice level. I can tell you unequivocally that entire industry is compromised. Maybe you're a good doctor, and you have my best interests at heart, but you're in the minority, and your peers have ensured I won't be trusting you.