Meta-Analysis of Opioids for Chronic Noncancer Pain

This JAMA study showed what pain patients have always known, that the “use of opioids compared with placebo was associated with significantly less pain” and “significantly improved physical functioning”.

However, because the “magnitude of the association was small”, the anti-opioid zealots inspired a media circus trumpeting that pain relief from opioids was negligible. (Let’s see how they feel after they wake up from surgery without opioids.)

Below is the abstract of the study itself and then a clear and reasonable analysis of the results by Pat Anston, editor of Pain News Network.  

Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. | Substance Use and Addiction | JAMA | JAMA Network – December 18, 2018

Question: 
Is the use of opioids to treat chronic noncancer pain associated with greater benefits or harms compared with placebo and alternative analgesics?

Findings:
In this meta-analysis that included 96 randomized clinical trials and 26 169 patients with chronic noncancer pain, the use of opioids compared with placebo was associated with significantly less pain (−0.69 cm on a 10-cm scale) and significantly improved physical functioning (2.04 of 100 points), but the magnitude of the association was small. 

Meaning:
Opioids may provide benefit for chronic noncancer pain, but the magnitude is likely to be small.  

I’m sure many of us would consider any amount of relief significant.

Perhaps for mild pain like a strained muscle, the benefit of opioids might not be much more than that of specific drugs to treat the condition, like muscle-relaxants.

However, when suffering from multiple days of a headache that has me banging my head against the wall, non-opioid options do absolutely nothing, so even the slightest real relief is significant to me.

Continuing from the Abstract:

Conclusions and Relevance:

In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo.

Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

This study (often referred to as the “Busse study”) was hyped in the media as though it claimed that aspirin or acupuncture was as good as opioids for pain. The media portrayed it as though it had claimed opioid ineffective, which is absolutely did not.

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Pat Anson of the Pain News Network wrote the following article to clear up the confusion:

Study Finds Rx Opioids Provide Limited Pain Relief — Pain News Network – By Pat Anson – December 18, 2018

The study concluded that there *is* statistical significance to pain reduction, but the effect size in a *large population* is small. 

1. Prescription opioids relieve pain, improve physical functioning and help people with chronic pain sleep.
2. But the improvements are small and come with side effects such as vomiting.

Those are the findings from a new meta-analysis (a study of studies) published in the Journal of the American Medical Association (JAMA).

Researchers at McMaster University in Canada reviewed 96 clinical trials involving over 26,000 participants who received either prescription opioids or a placebo.

…lead author Jason Busse, DC, a researcher with the DeGroote Institute for Pain Research and Care at McMaster University.

“We found that, compared to a placebo,

• 12 per cent more patients treated with opioids will experience pain relief,
• 8 per cent more will notice an improvement in their physical functioning, and about
• 6 per cent more will find improvement in their sleep quality.”

One expert questioned the designs of the studies used in Busse’s analysis.

Because most participants received a relatively low dose of opioids, it’s not surprising such a small number experienced pain relief, according to Stephen Nadeau, MD, a research advisor for the Alliance for the Treatment of Intractable Pain (ATIP).      

“With few exceptions,

• doses of opioids achieved were low (median dose 45 MME),
• trials were short, and
• opioids were rapidly titrated,”

said Nadeau, a neurologist at the VA Medical Center in Gainesville, Florida.

Because the study designs in all but a handful of studies did not remotely emulate clinical practice, it cannot be inferred that the results of this analysis are applicable to management of the general population of patients requiring opioid management of moderate to severe chronic nonmalignant pain.”

This is a problem with most of the pain studies. It might be impossible to find a representative group of pain patients. They would all have to have

• similar pain
• from similar causes
• for similar time periods and
• have similar physiologic reactions to their pain.

None of the opioid studies reviewed by Busse and his colleagues lasted longer than six months and many were considered low-to-moderate quality evidence.

But the same thing could be said about virtually every pain reliever on the market.

There is no good quality evidence proving that acetaminophen, pregabalin, ibuprofen, gabapentin or any other non-opioid pain medication is safe or effective long-term.

But the only significant side effect the Busse study found was a 6% risk of vomiting.

The study drew no conclusions about opioids increasing the risk of addiction, overdose and death – although Busse says those risks should not be overlooked.

“Given their risks, modest benefits, and the comparable effectiveness of alternatives, our results support that opioids should not be first line therapy for chronic non-cancer pain,” said Busse, a chiropractor who was the lead author of Canada’s opioid prescribing guideline

But opioid critics were quick to focus on the Busse study as proof that opioids should rarely be prescribed for pain.

“The findings reported by Busse et al illustrate that most patients who are prescribed opioids for the treatment of chronic noncancer pain will not benefit from those drugs,” wrote Michael Ashburn, MD, and Lee Fleisher, MD, in a JAMA editorial

“Given the clear risk of serious harm, opioids should not be continued without clear evidence of a clinically important benefit.”

Well, of course!

No drug should be given without “clinically important benefit”, so this is not unique to opioids.