What Did He Die Of?
A colleague asked a group of us Addiction Medicine specialists if we had any guesses of what killed a patient who died in his care. If reading a clinical description of a death or the thinking that doctors do after a death to improve care might bother you, stop reading. If not, read on.
The patient was in his late 20’s and had been treated for addiction involving opioids with medical withdrawal. Following the withdrawal, his treatment team implanted naltrexone, a long acting blocker of the opioid receptor meant to protect him from overdoses should he resume use of an opioid. He was described as stable on these monthly implants for 5 months after withdrawal and was found dead with no drug paraphernalia around him.
At autopsy, there were no physical findings except a white power in his mouth, which turned out to be clonidine, a medication used to counter the anxious activation of opioid withdrawal or stimulant intoxication. Post-mortem toxicology showed he had a high level of naltrexone, higher than usually seen in fact. He was negative for all opioids tested including fentanyl, sufentanyl and carfentanyl. He was positive for amphetamines.
The group gave a number of different theories. He had used amphetamine, overshot the mark, became nervous, took the clonidine to calm down which increased a specific electrical pause in his heart, that some amphetamines also increase, and this caused his heart to stop. Or he had taken a heretofore unknown opioid (probably a new, currently undetectable, even more powerful fentanyl analog) which displaced all the naltrexone, raising the level, and stopping his breathing. Or he had used cocaine long enough ago so that it wasn’t any longer in his system, but cocaine’s effect on the heart lasted long enough to interact with what he was taking to cause the sudden stoppage of his heart.
All good theories. Complex and speculative, but good theories non the less. But my mind didn’t go down this path. I didn’t think about what stopped his heart in the last moment. I didn’t think about what combination of substances could interact in what way to do what damage. I didn’t think about that, because I don’t see the point. It’s a wonderful academic exercise, but if we know, what will we change? Will we warn people not to use clonidine if they are going to use amphetamine? Will we warn people not to use any new opioids from China until everyone in their neighborhood has tried them and survived? At that point in the life of someone with addiction, when they are using what they need to use to feel normal, the parts of the brain that hear these kinds of warnings aren’t fully online. Why don’t we just go back to, “Just say, ‘No!’”? That worked so well.
Where my mind went was, “What was a “stable” person with addiction doing using amphetamine?” Why would he need to use a drug if he were stable? What did stable mean to his doctors? Not using opioids? That’s not stable to me. Stable means no symptoms, no craving, no need to use. So my mind went to this, “How is it his doctor thought he was stable when he really wasn’t?” The problem is that I run into this question a lot, and the problem isn’t the doctor. It’s us.
We, as a country, define this illness based on drugs. This guy had opioid addiction, so if he wasn’t using opioids he’s stable. But what if addiction is actually a brain disease that doesn’t care what drug you use. What if he had addiction because he didn’t release enough dopamine from his Ventral Tegmental Area to the Nucleus Accumbens (the brain’s reward center)? What if opioids increased this release, relieving his symptoms, and what if the naltrexone blocked not only external opioids but his own endorphins as well? What if naltrexone made taking opioids pointless but left him with the symptoms that led him to use opioids in the first place? Would it surprise you to know that alcohol also causes release of dopamine in the same way from the same receptor? Would it surprise you to know that amphetamines cause an increased release of dopamine a different way that naltrexone doesn’t block? Would it surprise you to know that cigarettes also increase dopamine release via a different receptor? While this may sound as speculative as the cardiac theories, it’s a story I hear every day, from patients with addiction. Addiction doesn’t care what drug you use to get dopamine tone back to normal, no matter how briefly, it just cares that you do.
So, what if this patient died because we don’t treat addiction, but only drug use? What if we killed him because we don’t care how he feels when he’s not using; we only want him not using, and not stealing hubcaps. What if we killed him because we don’t challenge a medical education system that embraces a paradigm where addiction is seen as a set of behaviors and not a brain illness? What if we killed him because we have congressmen and senators we allow to stay in office, who think that agonist substitution is just giving a person with one addiction another addiction, and who can’t stop practicing medicine without a license?
We don’t have problems in this country from addiction. We have addiction, but addiction doesn’t actually cause the problems. What causes the problems, many of the deaths, almost all the pain, is our lack of recognition of what addiction is. Addiction is a primary brain illness that can manifest with or without drugs and is rarely caused by drugs in a person without the illness.
So what did this patient die of? Untreated addiction, and our unwillingness to see it for what it really is. So, now what will you do about it? If you want to learn how to end addiction start here: https://www.youtube.com/watch?v=aYHtzR205Eg