What Makes Buprenorphine Risky for Pain Patients

What Makes Buprenorphine Risky for Pain Patients — Pain News Network – October 17, 2017 – By Jane Babin, Guest Columnist

Buprenorphine is the darling of the addiction treatment industry, rapidly replacing methadone as the “medication assisted treatment” of choice for opioid use disorder (OUD) and addiction.

As a class III controlled substance, prescriptions for buprenorphine can be phoned or faxed in, and scripts can be refilled up to 5 times in 6 months without a new prescription.

Class II controlled substances, like hydrocodone, oxycodone and morphine, require a new prescription each month and can neither be refilled nor phoned in.  

some physicians and patients to turn to buprenorphine for chronic pain as class II opioids become increasingly harder to get.

Yet without training on buprenorphine’s unique pharmacology and its implications, physicians treating chronic pain may be unaware of the risks it presents. Let me explain why.

Buprenorphine’s Effect on Other Opioids

What distinguishes buprenorphine from other opioids is that it is only a partial MOR agonist (50%).

Thus the effects of buprenorphine — both pain relief and the undesirable side effects – don’t exceed half that of other, full agonist opioids.

This is important because buprenorphine cannot be substituted for high doses of opioids because it has only half the chemical/drug effect of “real” opioids.

Buprenorphine also has a ceiling of maximum effectiveness that reaches a plateau as the dosage is increased.

That ceiling is well below what can be obtained with morphine and other opioids, but the side effects can still lead to death in opioid-naïve patients.

Buprenorphine has a long plasma half life, binds very strongly to MOR, and remains bound for extended periods of time.

Its usefulness in treating OUD is believed to lie in these properties, because it activates MOR sufficiently to curb drug craving, but not enough to elicit the euphoric effects[nor the pain-relieving effects] that can lead to addiction. 

When an opioid that has higher analgesic potency, but lower MOR affinity, such as morphine or heroin, is also administered, buprenorphine wins the battle to bind and remains bound to MOR.

Basically, it sits in the mu-opioid-receptor so tightly that no other opioids can “kick it off”, and thereby blocks the action of all stronger opioids.

Buprenorphine is also a kappa opioid receptor antagonist, which is thought to further reduce euphoria and addictive reinforcement.

Increasingly, buprenorphine is being advocated for chronic pain patients.

With no more “proof” of efficacy for treating chronic pain than any other opioid, it has emerged as a less objectionable opioid because it appears safer in the eyes of addiction treatment specialists, such as Dr. Andrew Kolodny, who object to full MOR agonists for chronic pain.

This is barbaric: they suggest substituting a drug that is known to be only 1/2 as effective for the stronger pain-relieving opioids taken by pain patients.

Yet safety is in the eyes of the beholder.  Despite its decreased abuse potential, buprenorphine can still be abused and cause overdoses because the ceiling effect for respiratory depression does not apply universally, particularly to opioid-naïve patients and children.

So, it gives less pain relief but no less danger of overdose. Why do they want us to take it? Certainly not for our pain, but for the addiction they assume we all have.

Buprenorphine should not be used as the first opioid prescribed for chronic pain.

Because it cannot achieve the full analgesic effects that other opioids can, there is significant risk of buprenorphine leaving pain undertreated or even untreated.  

A chronic pain patient on long-term buprenorphine therapy who experiences acute or breakthrough pain may not be able to get relief by taking another opioid. E

Even more disturbing is the lack of pain control in patients who

• need surgery,
• have an acute injury from trauma or
• have an acute painful medical emergency.

Buprenorphine Injection

A once-a-month injection would be a significant advance for opioid administration because it would significantly reduce the risk of diversion.

Again, this isn’t a benefit for pain patients, it’s specifically targeted for people with addiction who need a rock-steady dose of the opioid all day and all night to stifle cravings and render any other opioid utterly ineffective.

This monthly injection would not allow for any variation in the amount of pain relief provided for a whole month. If your pain flares, you do not have the option to add breakthrough pain meds because all other opioids will be blocked by the buprenorphine – with only half the efficacy of other opioids.

To me, that’s terrifying.

For this reason alone, an opioid depot formulation for a chronic pain patient with monthly administration sounds very appealing. [???]

It sure doesn’t to me.

If your levels of pain vary significantly over 24 hours as mine do, you’d not only be undermedicated when the pain level is higher but overmedicated when the pain level is lower.

Such dosing would lead to increased tolerance, which many of us avoid by simply taking less medication on days that aren’t as painful.

It might eliminate the need for pain contracts, pill counts, urine drug testing, and other indignations chronic pain patients suffer every day.

Nevertheless, buprenorphine is not the right opioid for once-a-month dosing.

In a 2015 paper, lead author Dr. Yury Khelemsky described a horrifying case that illustrates the dangers inherent in daily buprenorphine use.  In this case, a patient with a history of drug addiction who was being treated successfully with Suboxone suffered a broken neck that required emergency surgery.

During the procedure, the anesthetized patient began to move in response to surgical stimulation, i.e., due to pain.  Despite increasing the amount of two anesthetics, Propofol and Reminfentanil, the patient continued to move. Only after receiving yet another drug (Ketamine) did the patient remain motionless during the delicate procedure.

Don’t let this happen to you!

Khelemsky noted that as little as 8 mg Suboxone (one third of the daily dose the patient was receiving), blocks the activity of hydrocodone for up to five days, and recommended discontinuing buprenorphine at least 72 hours prior to elective surgery.  

This is cold comfort to a patient requiring emergency surgery — which could be anyone.

An injectable depot formulation of buprenorphine would substantially increase the risk of severe and possibly untreatable pain in an emergency situation, since a depot, once injected, cannot simply be discontinued as a pill would be.  

Thank you, Ms. Babin for explaining this. Too many pain patients are told how great this is without making the risks clear.

Indeed, surgery may be needed to remove the depot and halt continued administration, while existing amounts of long-acting buprenorphine in plasma may necessitate higher, riskier doses of anesthetic to surgically treat the acute injury — all while risking inadequate pain treatment.

Inexplicably, the extensive prescribing information on a random sample of buprenorphine products contains no warnings to either patients or prescribers of the risk that pain relief from an acute medical condition, trauma or surgery may be inadequate, or that buprenorphine should be discontinued days or weeks before elective surgery.

It certainly seems like they are trying to hide this information. So many patients have no idea what they’ve gotten themselves into with this heavily promoted drug.

This seems to reflect the mindset of Kolodny and others in the addiction treatment industry, who always seem to minimize the significance of even the most severe pain encountered by an individual when compared to the perceived societal consequences of addiction.  

I was wondering when his name would come up; he’s been heavily invested in this drug for many years, so it’s little wonder that he wants everyone who is taking opioids to admit they’re addicted and switch over to his buprenorphine treatment. He has good ($$$) reason to be biased.

I wonder how many pain patients or addicts would choose such a long-acting opioid if they understood the possibility that their severe acute pain could not be controlled.

Jane Babin, PhD, is a molecular biologist and a biotechnology patent attorney in southern California.