Tuesday, July 3, 2012

Evidence Mounts: Methadone Risky in Chronic Pain

The opioid-treatment drug methadone is culprit in almost one in three prescription painkiller overdose deaths, even though it only accounts for a fraction of scripts for pain, CDC researchers said.

About 5,000 patients died from methadone overdose in 2009, about six times more than 10 years earlier, Thomas Frieden, MD, PhD, director of the CDC, and colleagues said in a Vital Signs report.

"Methadone is riskier than other prescription painkillers ... and we don't think it has a role in the treatment of acute pain," Frieden said during a call with reporters.

He emphasized that most of these accidental deaths are tied to the drug's use in chronic pain -- a condition for which there is little evidence of its benefit, he noted -- and are not associated with its indication for the treatment of substance abuse.

In 2009, methadone accounted for only 2% of all painkiller prescriptions in the U.S., though it makes up a greater proportion of painkiller scripts in some states than others, particularly the Pacific coastal states as well as Maine, Vermont, and New Hampshire.

Frieden said that proportion has risen over the years, as insurers have increasingly made it a top-tier drug for chronic pain given its low cost per pill.

"All of the evidence suggests that the increase in methadone-related deaths is related to the increased use of methadone to treat pain," he said.

He added that using methadone in this situation "is penny wise and pound foolish ... with higher societal costs in terms of death and other problems that can be avoided," he said, adding that there are other, safer opiates that can be used for pain.

Methadone can cause more respiratory depression and disruption of heart rhythm than these other opiates, he said.

And he cautioned that there's limited evidence for the effectiveness of opiates as a class in chronic pain that's not related to cancer, and the drugs have been related to a rising number of overdoses and deaths in recent years.

In 2009, for instance, there were 15,500 prescription painkiller overdose deaths in the U.S., and these drugs now account for more deaths than heroin and cocaine combined, Frieden said.
Government agencies have put forward many efforts to curb that tide, he said, noting that his agency has been working with states to create more effective prescription drug management programs (PDMPs), which are in place in 49 states.

They're of varying levels of quality, however, and agents have been working to make them more real-time and easier for doctors to access, Frieden said.

He added that recent campaigns by the FDA and the DEA appear to be having an impact on methadone overdose and deaths, as preliminary figures for 2009 have shown a slight decrease in methadone scripts.

"I think this shows that it's possible to make further decreases in the number of people who overdose or die from methadone," Frieden said.

Chronic pain can be predicted by pattern in brain, scientists find

Pain is a hard thing to measure, and also quite mysterious: Two people may experience very similar injuries and similar levels of initial pain, but where one may recover the other may go on to experience a crippling chronic condition.
Why does pain persist for some but not others?

Scientists at the Northwestern University Feinberg School of Medicine took an interesting look at this. Their work, just published in the journal Nature Neuroscience, tracked brain activity in 40 people with new back injuries and found a pattern of activity that could predict -- with 85% accuracy -- which patients were destined to develop chronic pain and which weren't.

Study subjects, all of whom had an episode of back pain that had lasted four to 16 weeks, were tracked for one year. Images of their brains were taken at the study start and then several more times over the year. After one year, they were divided into two groups: ones whose pain appeared to be resolving and those whose pain was persisting.

At the start, there wasn't much difference between the levels of pain reported by the two groups. However, the persistent-pain group did differ from the recovering group in terms of their emotional feelings about the pain.

And when senior author neuroscientist A. Vania Apakarian and colleagues looked at the brain patterns in these two groups, they found differences that had been there right from the start.
Two parts of the brain -- the nucleus accumbens and the medial prefrontal cortex -- were key in the pattern. The more connected these two regions were, the more likely a person in the study was to develop chronic pain later on, the authors found.

The nucleus accumbens "trains the whole rest of the brain as to values, judgments and motivations," Apakarian said in a phone interview. And the medial prefrontal cortex includes regions known to be involved in both acute and chronic pain.

The scientists speculate that strong connections between the nucleus accumbens and the medial prefrontal cortex might somehow teach the brain to develop chronic pain -- and that this process deserves more attention from researchers trying to develop better pain therapies. They note that most of the focus on chronic pain to date has been on damage in the peripheral nervous system and spinal cord that might set up nerves to send “I’m hurting” signals long past the time when an injury actually happened.

The scientists also found  -- as had others before them -- that people with chronic pain lost more gray matter in their brains over time compared with healthy controls and the people whose pain was getting better.

There are two ways in which the new findings could be useful, Apakarian says.
One is with prediction: "If you could tell a patient, 'Don't worry, your pain will go away in a few weeks,' that would be fantastic," he said.

And the people whose brain scans portend chronic problems?
Doctors could focus therapeutic efforts on them -- although, Apakarian said, treatments are not yet very good.

Which brings us to his second hope -- that the findings in his lab could help improve matters. Identifying the crucial brain regions offers clues to neurotransmitters that might be involved in setting up chronic pain, and therefore ways to potentially interfere with targeted medications.

Apakarian has received money from the National Institutes of Health to investigate potential drug therapies, first in animal studies.

WebMD and the National Institute of Neurological Disorders and Stroke offer additional resources on chronic pain management.