Thursday, July 17, 2008
European Journal of Pain has a review of transdermal buprenorphine for pain. It's an interesting article and makes some dizzyingly impressive claims on behalf of the drug, which I note below.
Buprenorphine is a partial mu-opioid agonist and a kappa-opioid receptor antagonist. The article states that despite being a partial agonist no ceiling effect of analgesia has been observed in humans, and that it acts like a full mu agonist when used at 'analgesic doses.' On the other hand they present data that there is a ceiling effect to buprenorphine's respiratory depression effects (meaning that it's theoretically safer than other opioids regarding that toxicity; they note that dangerous respiratory depression is nearly unheard of with buprenorphine unless other CNS depressing drugs are being used). The article notes that buprenorphine not only does not induce mu-opioid receptor internalization (one of the mechanisms for opioid tolerance seen in other opioids) but that it actually increased cell surface density of mu-receptors, which may be an explanation for the impression that less analgesic tolerance is seen with buprenorphine than other opioids. It has an anti-hyperalgesic effect (as opposed to the hyperalgesic effects seen with other opioids). It has been demonstrated to have fewer side effects in head to head studies with morphine. It can be taken safely with other opioids with additive analgesic effects. In placebo controlled trials rates of nausea, dizziness, and tiredness were no worse with TD buprenorphine than with placebo. It's less constipating than morphine or fentanyl. At least one patch formulation can be cut to decrease the dose. It's had decent studies in both cancer and non-cancer pain. Theoretically people are less likely to have problems with psychologic dependence on it.
Whew. Reading this article leaves one with the feeling that TD buprenorphine is (in the parlance of my former residency program) liquid Jesus (i.e. good for just about pretty much anything - we would use it to describe drugs like aztreonam, etc.). Let's see: better analgesic with less side effects/tolerance/hyperalgesia which is nearly impossible to OD on? It seems almost too good to be true (there is no mention of who sponsored the article) and I sat here reading this saying to myself if all of this is true then why hasn't this revolutionized opioid pain management and why hasn't TD buprenorphine become the opioid of choice for chronic pain? It raises the skeptic bug in me, but perhaps this is simply because we're behind the times here in the US.
Transdermal buprenorphine is not available in the US (or Canada?), but sublingual buprenorphine is (it's approved for opioid maintence therapy in opioid dependent patients). I'm told that one can prescribe it for pain without a special license however I'm not entirely sure if that's true (this seems to contradict what I was told).
My questions are: 1) is anyone using this or seen sublingual buprenorphine used for pain in the US, 2) does anyone know if transdermal or sublingual buprenorphine are being evaluated for approval (for pain treatment) in the US?, and 3) are any of our European readers using this and if so is it good as this article tells us?