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Everybody Hurts: Still Panning for Gold Standard Evidence on Painkiller Addiction
November 01, 2013
Which came first? The addict or the addictive drug?
That’s the heart of the debate between journalists, researchers and clinicians over the extent of the country’s prescription painkiller problem and the remedies to address it. This month, I posted two parts to an interview with addiction expert Dr. Andrew Kolodny.
The debate taking place in news articles, op-eds and public forums moved to Twitter, and the fiercest critic of Kolodny’s view of painkiller addiction was writer Maia Szalavitz. So I asked them both (in a note hyper-abbreviated for Twitter): “Because you differ on claims of high addiction risk for patients without a history of addiction, why not cite one good study backing your point today?”
Szalavitz responded immediately with a link to a Cochrane review of opioid treatment studies published in 2010. I’m going to write about this review and then follow up with a look at some of Kolodny’s evidence in a later post.
At first glance, this review seemed pretty definitive. Even the title sounded all inclusive: “Long-term opioid management for chronic noncancer pain.” What’s stunning about this review, though, is how little it actually contains, and this is more of a commentary on the state of the science around painkiller addiction than it is on the Cochrane’s review process.
The review covers what the Cochrane researchers considered the best available science on opioids up to May 2009. The reviewers found 54 “relevant studies” by searching 11 databases and, of those, they found just 26 studies, including one with two treatment groups, that met the review’s criteria. The reviewers wrote, “Consistent with our inclusion criteria, these studies represent the administration of any opioid in any dose by any mode of administration for at least six months in the context of any prospective trial of any design.”
This in itself underscores the point made by Kolodny and others. They say that there aren’t enough studies examining the addiction risks of long-term use of opioids. Kolodny told me:
Nobody actually knows the exact rate of new onset addiction when opioids are prescribed long-term for chronic pain, so most experts provide a large range when estimating the risk. For example, the National Institute on Drug Abuse estimates the risk of addiction with long-term opioid treatment as ranging from 3% to 40%.
A look at the Cochrane evidence shows why.
First, what do the authors mean by “long-term”? They defined it as taking opioids for “at least six months.” That’s very standard for studies aimed at gaining FDA approval for any drug, but it’s not very long when trying to determine whether a drug turns people into addicts. Of the 26 studies, only four looked at the use of strong opioids over a period of more than one year and, of those, only one stretched even to the two-year mark.
For the sake of argument, let’s look at how many patients were examined over the one-year to two-year periods. Dr. Sanford Roth and colleagues in 2000 published a paper covering 133 patients. Dr. Laurie Allan and colleagues in 2005 published a paper covering 680 patients. That same year, Dr. Harris McIlwain and colleagues published a paper covering 153 patients. Finally, in 2007, Dr. Russell K. Portenoy and colleagues published a paper covering 233 patients.
That’s a grand total of 1,201 patients studied for one to two years.
And who funded these studies?
Both Roth’s study and Portenoy’s study were funded by Purdue Pharma, maker of OxyContin.
Allan’s study was funded by Janssen Pharmaceutica, maker of Duragesic.
McIlwain’s study was funded by Endo Pharmaceuticals, maker of Opana ER.
So, in sum, no studies reviewed by Cochrane looked at pain management for more than two years. No studies by themselves covered more than 1,000 patients. And no studies were independent from the manufacturers making the painkillers being studied.
In addition, none of these studies were structured to look at addiction itself. They were studies focused on whether the drugs were effective. Most of what we know about addiction to painkillers – and other drugs – comes from studies in animals, which is largely the result of how tricky it can be to set up a trial to determine whether a drug is addictive in humans. Institutional review boards don’t look kindly on studies where people are giving a drug in large doses that already is known to have damaging effects – like addiction – in mice.
With that in mind, what did the Cochrane review find in regard to addiction?
Concern that an individual with [chronic non-cancer pain] may develop dependence on the drug during long-term administration represents a potential barrier to treatment. However, the rate of observed signs of opioid addiction was extremely low in the body of evidence considered in this review (0.27%, conservatively). This rate would be 0.14% if no addictive behaviors occurred among the studies that did not mention addiction rates at all. Only three participants were reported as having potential abuse problems. These numbers do not support the contention that potential iatrogenic opioid addiction should limit therapy for well-selected and well-supervised patients.
But there’s a caveat here, too.
Cochrane looked closely at the studies and found that the studies themselves only included people with no prior history of addiction.
This goes to Szalavitz’s point that people without addiction histories are unlikely to get hooked on painkillers. As she said to me:
The reality is that most opioid addicts do not start in pain treatment, and most pain patients never get addicted. No one has produced any data that shows otherwise.
The lack of people with drug addiction problems in these studies also goes to Kolodny’s point that the evidence on addiction from painkillers is problematic. How can you understand how painkillers are going to affect a population if you’ve weeded out the part of the population with prior addictions? Cochrane writes:
Because most studies screened out potential participants with histories of substance abuse or addiction, the rates of addiction reported in these studies are only generalizable to patients without a history of addictive/abusive behaviors. This finding is consistent with that of another review article on opioid abuse and addiction that calculated an abuse/addiction rate of 0.19% in studies that prescreened chronic pain patients for long-term opioid use or addiction/abuse history, and 3.27% in all studies (Fishbain 2008).
This review does give the appearance of being the “gold standard,” as Szalavitz stated on Twitter. And it supports her claim that fewer than 1% of patients without addiction histories became addicted while using painkillers from one year to two years. What it does not do is present evidence independent of the pharmaceutical industry, nor does it show the truly long term health impacts – addiction or otherwise – from painkiller use.
As Cochrane noted:
Given the complexity of definitively diagnosing opioid addiction (see Ballantyne 2006) and in the interest of capturing the overall effect of opioid therapy on quality of life, we sought to analyze health-related quality-of-life outcomes in this review. However, findings on quality of life were inconclusive for all modes of administration.
If the drug doesn’t improve your quality of life, then why are you taking it?
Image by Ano Lobb @healthyrx via Flickr