Diabetic peripheral neuropathic pain (DPNP) is a problem
that seems to afflict Canadians with unusual severity.
When Harris Poll conducted its Global Neuropathic Pain
Survey in nine countries, Canadians reported the worst
burden of symptoms, with 90% saying the pain was constant
and impacted every aspect of their lives.
Unfortunately, the condition is
also frequently mismanaged. That's why a group of neurologists
from the American Society of Pain Educators (ASPE) decided
to produce the first complete guidelines on the management
of neuropathic pain in diabetes. The new guidelines
appear in the current issue of the journal Mayo Clinic
Proceedings.
LONG
SUFFERING
Most patients eventually get treatment of some sort,
but they typically report having seen two or three doctors
before getting a correct diagnosis. Only one in four
Canadian sufferers say their current medication for
DPNP effectively relieves most or all of the pain. Many
say they've tried up to eight different drugs since
their diagnosis. Typically, patients with DPNP have
medication costs triple the norm for their age group.
These findings would come as no
great surprise to the guideline authors. "Until now,
diabetic peripheral neuropathic pain has been an under-diagnosed
and under-treated condition despite the growing public
health issue with obesity and diabetes mellitus," says
ASPE executive director Dr B Eliot Cole.
A disturbing survey published in
Clinical Diabetes last year revealed the extent
to which these patients are being under- or wrongly
treated. Prescribing data from 55,686 North American
patients suffering peripheral neuropathic pain showed
that nearly a quarter were receiving no pain management
treatment at all.
Of those getting some kind of treatment,
53% were on short-acting opioids, while fewer than 1%
were getting the safer and more effective long-acting
opioids. The second-most used treatment was non-steroidal
anti-inflammatory drugs, a class that has been shown
to be almost completely useless in the treatment of
DPNP.
The next most popular class was
benzodiazepines and selective serotonin reuptake inhibitors,
again drug classes for which no good evidence supports
their use in DPNP. The least popular categories of medicine
were the ones that have actually been shown to work
— tricyclic antidepressants and anticonvulsants.
In the whole sample, the number of patients receiving
one of these effective treatments was actually less
than the number whose pain was not being treated at
all.
NEW
GUIDELINES
These findings, needless to say, alarmed the specialists
at the ASPE, prompting them to meet for two days last
year and review the available evidence. The new guidelines
are the result of that meeting. "In the absence of guidelines,
physicians have relied on a combination of antidepressants,
anticonvulsants and various analgesics based on their
experience and comfort level," says Dr Cole diplomatically.
"Now they have a clear consensus on how to help alleviate
the pain of patients with DPNP."
The pain management specialists
concluded that four drugs should be considered first-line
treatments for DPNP: the anticonvulsant pregabalin;
the serotonin-norepinephrine reuptake inhibitor duloxetine;
the long-acting controlled release form of the opioid
oxycodone; and tricyclic antidepressants.
Pregabalin was approved in Canada
last September. It's fairly well tolerated, with no
known drug-drug interaction risk, and has been found
to bring significant pain reduction in DPNP, as well
as improvement in sleep quality, often a problem in
this population. Its main disadvantage is the need to
titrate dosage, and its strict thrice-daily regimen.
The humble and dirt-cheap tricyclic
performs surprisingly well in DPNP, particularly in
the many patients who suffer co-morbid depression. The
available evidence suggests that all tricyclics are
about equally effective, but amitriptyline is the most
studied. Various trials have shown numbers needed to
treat for significant pain reduction ranging from 1.3
to 3. Tricyclics' biggest disadvantage is that they
are less well tolerated than modern antidepressants.
Oxycodone poses well-known addiction
risks. As might be expected from an opioid, the drug
delivers very effective pain reduction at the price
of high rates of adverse events. Of the four first-line
recommendations, the most obvious place to start would
seem to be the SNRI antidepressant duloxetine. Approved
in the US for a wide range of conditions, it shot last
year to second place in the American drug sales top
ten. The ASPE's guidelines suggest that about half of
DPNP patients taking this drug will experience a 50%
or greater pain reduction, and the drug has far fewer
contraindications and adverse events than typical tricyclics.
There's just one problem: duloxetine is not yet approved
in Canada for any condition whatsoever.
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