Buprenorphine for pain- recent studies

From an astute reader:
I copied and pasted this article. It’s been my impression that bupenorphine isn’t superior for chronic pain. I also read an article that three amputees with phantom pain got adequete relief from using buprenorphine suppositories. Is there a difference between using the under the tongue med in comparison to these other methods?

TRANSDERMAL BUPRENORPHINE EFFECTIVE FOR SEVERE CANCER PAIN Date updated: September 30, 2008 Content provided by Reuters NEW YORK (Reuters Health) – Transdermal buprenorphine appears to be effective and safe in a study of patients with severe cancer-related pain, European investigators report in the Journal of Pain and Symptom Management.
Dr. Philippe Poulain of Institut Gustave-Roussy in Villejuif, France, and colleagues compared transdermal buprenorphine 70 micrograms/hour with placebo in 289 opioid-tolerant patients with cancer pain requiring strong opioids in the dose range of 90-150 mg/day oral morphine equivalents.
The patients were enrolled in a 2-week run-in phase, during which time they converted to transdermal buprenorphine or a placebo patch. Rescue analgesia with buprenorphine sublingual tablets 0.2 mg was allowed as needed.
The researchers defined response as a mean pain intensity reduction of 5 points on a 10-point scale and a mean daily need for two or fewer buprenorphine sublingual tablets.
One hundred patients dropped out of the study during the run-in phase due to a lack of efficacy or because of adverse events, while 189 patients continued on to maintenance treatment. Thirty-one more patients dropped out at that time, most of whom were on placebo.

A response was seen in 74.5% of patients on transdermal buprenorphine and in 50% of patients on placebo.
“This result was supported by a lower daily pain intensity, lower intake of buprenorphine sublingual tablets and fewer dropouts in the transdermal buprenorphine group,” Dr. Poulain and colleagues write in the August issue of the Journal. “The incidence of adverse events was slightly higher for transdermal buprenorphine.”
Dr. Poulain’s group concludes that “transdermal buprenorphine 70 micrograms/hour is an efficacious and safe treatment for patients with severe cancer pain.” J Pain Symptom Manage 2008;36:117-125.
Thanks for the article Staci– To answer your question directly, once the buprenorphine is in a person’s body it works the same way regardless of how it got there.  I have been expecting a buprenorphine skin patch to come on the scene eventually;  it seems to me that a patch would be an ideal way to administer the drug for treatment of opiate dependence.  Implantables and long term injectable preparations are also on the horizon.
Opiate agonists have an advantage over partial agonists like buprenorphine in that the higher their dose, the higher their opiate effect.  Buprenorphine on the other hand has the ceiling effect– beyond a certain point increases in dose don’t cause greater analgesia.  BUT…  opiate agonists usually make people crazy over time– people taking them become tolerant to them and crave higher doses.  some people can maintain a constant dose but even in those cases the people become more and more obsessed with the medication and with their pain symptoms.
The pain takes on a psychological component over time;  it almost seems as if the mind is generating more pain so that the patient will take more opiates.  It becomes very difficult to treat the pain, as pain, addiction, tolerance, depression, and anxiety all become wrapped up together.

Buprenorphine offers some advantages in that it causes less craving for the drug.  The tolerance for buprenorphine also differs in that it is ‘fixed’ at a certain level;  this probably is related to the lack of cravings for the drug.

In the study above, the dose of buprenorphine was only 70 micrograms (0.07 mg) per hour.  At first blush this seems low, but given the long half life of buprenorphine (70 hours) the drug builds up over time.  Over 24 hours a person would get about 1.5 mg of drug, and again with the long half life the level would increase as days go by.  I would guess that the resulting plasma levels with long term use are in the same general ballpark as for patients taking 8-16 mg of the dissolving medication, as only a fraction of that medication gets absorbed by the oral mucosa.

One last comment– I have mentioned before that Suboxone is destroyed by the liver if swallowed by something called ‘first pass metabolism’.  Note that Staci mentions a study using suppositories;  that is a more effective way to give buprenorphine because the blood leaving the distal colon doesn’t go to the liver as the small intestine blood supply does, and so drugs absorbed from the colon are not subject to first pass metabolism.  Reminds me of a patient who was hard of hearing and a bit demented…  I gave him a prescription for suppositories but he was a bit confused about what to do with them.  I asked him later how they worked and he said ‘for all the good they did I should have shoved them up my ass!’

SD

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