A spike in narcotic deaths in Canada after shift in prescribing from short to long acting opioids

CMAJ reports:

From January 1991 to May 2007, the prescribing of opioid analgesics in Ontario increased by 29%, from 458 to 591 prescriptions per 1000 individuals annually (Figure 1). Codeine was the most frequently prescribed agent, although the number of prescriptions for the drug declined gradually during the study period. In contrast, the number of oxycodone prescriptions rose more than 850% during the same period, from 23 per 1000 individuals in 1991 to 197 per 1000 in 2007. The prescribing of hydromorphone, fentanyl and morphine also increased considerably over the same period,....

The prescribing change actually took place after 2000 when long acting oxycodone was introduced to the formulary.

We observed a substantial increase in overall opioid-related mortality following the addition of long-acting oxycodone tothe provincial drug formulary in January 2000. Between 1999 and 2004, the annual number of opioid-related deaths increased by 41% (p = 0.02), from 19.4 to 27.2 per million annually (Figure 2, top panel). The number of oxycodone-related deaths increased by 416% (p less than 0.01) during the same period, from 1.39 per million to 7.17 per million annually (Figure 2, bottom panel). The rise in opioid-related deaths was due in large part to inadvertent toxicity; there was no significant increase in the number of deaths from suicide involving opioids over the study period (Figure 3).

A little background. The beginning of this past decade marked a groundswell of activism for more aggressive pain management. It spread to the regulatory agencies (remember Joint Commission's roll out of pain management standards?), the courts, medical journals and even our CME courses. It was based almost entirely on opinion and dogma with very little science. Typical of the preaching of the day was this WJM editorial from 2001:

...there is a standard of care for pain management, a significant departure from which constitutes not merely malpractice but gross negligence. Even if professional boards might not hold their licensees to that standard, juries will. With the implementation of the new pain standards by the Joint Commission for the Accreditation of Healthcare Organizations, which recognize the right of patients to the appropriate assessment and management of their pain, public expectations will likely increase exponentially.

Public expectations did increase. So did the deaths, according to reports from all over, even in hospitalized patients:

The current emphasis on pain assessment as the fifth vital sign and the use of unscientific pain scales is causing serious injury and death from overmedication...

Overmedication with sedatives/narcotics, during the two periods, clearly contributed to deaths in 13 and 32 patients and probably contributed to deaths in 5 and 14 patients, respectively. This occurred in 17 and 43 patients, respectively, after blunt injury and in 1 and 3 patients, respectively, after penetrating injury. Two clinical scenarios predominated, ie, overmedication in preparation for an imaging study and overmedication after discharge from ICU to the floor. The sequel of hypotension and compromised airway requiring intubation initiated a cascade of negative events that led to death.

Purdue Pharma's illegal and non-evidence based promotion of Oxycontin, described in this NYT article from 2007, has some interesting parallels with what doctors were taught in CME courses and by Joint Commission leaders:

Federal officials said that internal Purdue Pharma documents showed that company officers recognized that, even before the drug was marketed, they would face stiff resistance from doctors concerned about the potential of a narcotic like OxyContin to be abused by patients.

As a result, prosecutors charged, the company effectively started a fraudulent and deceptive marketing campaign aimed at convincing doctors that OxyContin, because of its time-release formula, was less prone to abuse, and that it was less likely to cause addiction or to produce other narcotic side effects than competing drugs. In its plea agreement, the company acknowledged doing so.

It reminds me of some of the dogma they were shoving down doctors' throats at the time, including pain management talks at a couple of hospital medicine courses I attended. Our thought leaders told us that because short acting pain medications tended to be used “prn”, thus encouraging patients to repeatedly ask for more doses as analgesic effects wore off, they encouraged a form of “pseudoaddiction” which was really a symptom of inadequate pain control. Although this concern, as well as the concern about patients getting too much tylenol, had some merit, we were also told that addiction and abuse were rare when patients' pain control was adequate.

Industry promotion may have had a role but didn't explain most of the trend. In the U.S., alongside the spike in Oxycontin use was a spike in its generic, non-promoted but equally dangerous competitor methadone which, among narcotics, has been reported to be associated with the greatest number of deaths.