Buprenorphine Overdose After Naltrexone Treatment

Naltrexone induces mu-receptor hypersensitivity.  Buprenorphine’s protective ‘ceiling effect’ may not prevent overdose in patients with this ‘reverse tolerance’.

A new patient described his recent history of respiratory failure several days into buprenorphine treatment.  He was told by his doctors that he experienced an allergic reaction to Suboxone. The rarity of buprenorphine or naloxone allergy led me to look deeper into his history, and my conclusion differs from what he was told by his last treatment team.

The patient, a man in his mid-50s, has a history of significant opioid use over the past 20 years.  He used a variety of opioid agonists over the past year, mostly prescription opioids, with an average daily dose greater than 200 mg of oxycodone per day.

Read more

Benzos and Buprenorphine

The high safety of buprenorphine, except when combined with a benzodiazepine, has been twisted in comments about the drug (and in the minds of regulators) to buprenorphine being uniquely dangerous when combined with benzodiazepines, which is not true.

I’ve heard more and more from insurers, regulators, and well-meaning agencies about the dangers of combining buprenorphine and benzodiazepines.   Some insurers protest paying for buprenorphine if patients are taking benzodiazepines.  Medicaid recently sent a letter that described a ‘severe risk’ of using benzodiazepines in patients on buprenorphine.  And the state drug database contains a graph for each patient of the morphine-equivalent narcotic dose over time, and shades the data in red if benzodiazepines are also prescribed.

Readers of my blog know I’m no big fan of benzodiazepines (read this for example).  But in an era of ‘fake news’, I’m even less of a fan of incorrect statements by doctors.   The drug database also ignores the ceiling effect of buprenorphine, and extrapolates the morphine equivalency of low doses of buprenorphine as if the dose response ‘curve’ was a straight line.  That ridiculous calculation leads the graph of opioid use to show buprenorphine patients as taking the equivalence of 900 mg of morphine per day.  The harm is minor I suppose by limitations on access to the database, but the error leads to misperceptions among doctors, and could potentially lead to mistakes in treatment decisions.

Read more

Does Suboxone Stop Working Over Time?

First Posted 12/31/2013

Buprenorphine is relatively unique among opioids in having a ‘ceiling’ to mu opioid effects.  There are other known molecules that act as partial agonists at mu opioid receptors, but buprenorphine is the most useful, at this point, because of other traits of the molecule– such as having few side effects from actions at non-mu receptors.

As most opioid users soon realize, opioid agonists increase tolerance over time to what appears to be an infinite degree.  The mechanisms of tolerance are complicated. I often describe tolerance as a process where receptors become less and less sensitive to opioids with stimulation, to the point where native opioids (endorphins and enkephalins) no longer activate opioid pathways.  Some of the change in sensitivity is caused by the binding of phosphate molecules to the intracellular portion of receptors, causing changes in conformation. Tolerance development is likely far more complicated, though, and includes other changes in synaptic transmission through different mechanisms.

Opioid Effect vs. Dose of Drug
Opioid Effect vs. Dose of Drug

Read more

A New Way to Stop Suboxone?

Originally Posted 10/27/2013

I usually have my wife/business partner review my posts and provide her opinion whether my arguments are sound.  For the record, she tells me that this post is technical and boring.  I disagree, but we aren’t planning to separate over the issue.  A valid criticism, I think, is that I’m doing a lot of guessing and wondering in this post.  This post is an example of the things I waste time wondering about.   I try to avoid writing things that are somewhat speculative, but I wanted to give it a shot for two reasons.  First, because there may actually be something to the idea I am about to describe.  But more important, I wish to point out some of the many ideas in the addiction world worth exploring…. And I hope that pharma continues to search for answers (i.e. spend money) in this area of medicine.

So I’ve been thinking more about ALKS 5461, the Alkermes pipeline medication that is a combination of buprenorphine and ALKS 33, which is a mu opioid antagonist also called Samidorphan with the structure shown at the left. ALKS 5461 is being developed by Alkermes for the treatment of major depression.  I don’t know much about the clinical actions of ALKS 33, (a proprietary molecule), except that it comes from a family of drugs that bind with high affinity and specificity to mu or other opioid receptors.  Samidorphan, a mu receptor antagonist, allows investigation of buprenorphine’s potential therapeutic effects at kappa and delta opioid receptors by blocking effects at the mu receptor.  Drugs with actions at other opioid receptors have be developed, and in some case patented.Until recently, theories about depression revolved around abnormalities in brain monoamine pathways or deficiencies of monoamine neurotransmitters.  Monoamines include serotonin, melatonin, and the catecholamines (noradrenaline, dopamine, and adrenaline). Most modern antidepressants act at serotonin or catecholamine receptors or reuptake sites. The new Alkermes medication ALKS 5461 is the first serious effort that I am aware of to treat depression from the opioid perspective.

Read more

Withdrawal from Suboxone or Buprenorphine

I received a question from a reader about withdrawal symptoms from stopping buprenorphine. My answer has relevance to opioid withdrawal in general, and to a common misconception about the duration of withdrawal symptoms.

The message:

Basically I quit Suboxone about 18 days ago. When I decided to quit I was taking about 8 to 12mgs per day. I got into taking Suboxone from trying to quit a Percocet habit that developed after a car wreck. I was stuck on Suboxone for near 3 years before I finally realized the person I thought I was really wasn’t the person I expected myself to become. So I decided I had enough and quitting Suboxone should be easier than quitting Percocet. I still laugh over that because I should have educated myself better before I landed myself where I am now. I am starting to feel marginally better but I have zero energy and my depression is off the charts. . . My question is because Suboxone has such a strong half-life being a partial instead of full agonist, how many more days weeks months do I have to suffer through before I can expect to return to normal? I am terrified of relapsing and have set a zero tolerance for myself. Hopefully I am strong enough and smart enough to stay away but is there anything extra I can do to help ease anxiety and the depression? Honestly I feel like I live in a personal hell no one gets or understands. I was just hoping u could give me some advice. Thanks for reading my message.

My answer:

Read more