Opiate painkillers: Can a balance be found?

Jerrold Winter: I’m a pharmacologist. I teach five hours of the principles of pharmacology to the first-year students. One of those hours I devote to tolerance, physical dependence and addiction. I try to get them to have an appreciation for the particular hazards that are out there for physicians, because of their easy access to the drugs and so forth. It became a little more personal recently. Six years ago I developed sciatica, and at that time, I was treated with hydrocodone, 15 mg a day divided into three doses. It worked wonderfully. Recently, I had a recurrence of it, and lo and behold, when I left my primary care physician’s office, not knowing what the prescription was, it had been cut by two-thirds. That prompted me to write a letter to The Buffalo News, which basically expressed my personal view that there is a tendency to believe that addiction is going to be prevented by denying patients who need the drugs.

Richard Blondell: When it comes to prescribing opioids for pain, like a lot of things, there’s an upside and a downside. Fire, for example, heats our homes and cooks our food, but if you have burns over 90 percent of your body, it’s not a good thing. So over the years, as a society, we’ve learned to use fire sort of correctly. It gets out of control from time to time, but whole cities don’t burn down anymore like they used to.

As a society, we need to have a framework to put around the use of things that are potent and powerful for relief of pain, without causing collateral damage. When I was in training, I never wrote [prescriptions] for narcotics. If I wrote for narcotics for more than 10 days, I would have gotten a call from the pharmacist, asking what I was doing. So we probably underprescribed at that time. And now it is clear we’re overprescribing. In 2012, physicians or other practitioners wrote 259 million prescriptions for opioids. That’s enough for every adult in the United States to have their own bottle of pills to last them a month. We don’t have that much pain.

So, to your point, it takes a wise and knowledgeable physician to know when these medications are appropriate and when they are not, and how much to give over what length of time to achieve the benefit that we want without creating so much collateral damage. We now have for the first time in decades, since the 30s or 40s, unintentional overdose deaths from drugs exceeding deaths from car accidents. The magnitude of the problem is unprecedented, and the origin of these pills is doctors’ prescriptions. We are not prescribing these wisely. Maybe there are some people undertreated for pain, but there are certainly a lot of people overtreated.

JW: I come from the undertreated for pain.

RB: So your course was about these potent medications that are powerful pain relievers, but also carry a risk to the individual and to society of debilitating addiction. You spend one hour teaching doctors about these potent medications.

JW: And they don’t remember much from the first year.

RB: The amount of curricular time that is devoted to this topic is clearly insufficient, because people leave medical school and residency training unprepared. They don’t fully appreciate how to diagnose the pain condition. They don’t understand how to prescribe these things correctly. They don’t know how to recognize addiction in its early phases. They don’t know how to talk to their patients about addiction. And they don’t know what to do and how to treat patients that have become addicted.

JW: I would go a little bit further and say that if you surveyed a representative group of physicians they would not be able to tell you the difference between physical dependence and addiction.

RB: That’s true. We’ve conducted those surveys. That’s absolutely true.

JW: And I think that’s really unfortunate. Do you have a spot in the curriculum?

RB: I teach a two-hour, 50-minute class on addiction. The whole thing. In the third year. Now that’s the formal curriculum. In the hidden curriculum, they get a lot of instruction.

JW: How?

RB: In the hospital wards, at the bedside, in the clinics, in the emergency, in the recovery room. They are taught now to prescribe these things liberally, because you don’t want to get patient’s complaints. You don’t want to get adverse evaluations. You don’t want to be called in the middle of the night, when the prescription runs out. They are taught that patients who become addicted do so because of willful misconduct, and that they often are not worthy of health care services. They come to medical school open-minded and they are taught prejudice and ignorance as they go through, in the hidden curriculum. So another important piece of this is not curricular time for the students, but curricular time for the faculty, the clinical faculty who are the teachers in the hidden curriculum. Whatever you could tell students in an hour could be undone in about three minutes in the emergency room. “Don’t listen to that guy. What does he know? Here’s what we really do.”

JW: This is what I would like physicians to be able to do: My wife and I fly frequently to New York City to see our kids, our grandchildren, and we go through TSA precheck. It speeds things up a little bit. I would like patients to have a precheck. I believe, and I believe I’m one of them, there are people who have chronic pain and get great relief from an opiate, who simply are not likely to become addicts. And yet every patient who walks into an office, some offices, is looked upon as a drug-seeker and a potential addict. And there are pill-seekers, doctor-shoppers who do that. But there are also people who are never going to become addicted. The New York Times had a lovely letter from a woman who said, “I’ve had chronic pain for decades and I take an opiate as needed and I’m simply not going to become an addict.” As you know better than I, addiction is a complicated business.

RB: How do you predict who’s going to become addicted and who is not?

JW: Well, I try to tell that to my personal physician. I tell him, “Look, I’ve got a schedule-one license. I’ve got every drug you want to think of sitting right there, and it’s been sitting there for 50 years. None of those have ever been used inappropriately.” So I believe there are ways to screen people for addictive possibilities.

RB: How’s that?

JW: “I’m depressed. I have some other form of mental aberration. I’m unemployed. I live in a neighborhood where you can walk down the street and buy the drugs. I have relatives who have had problems with alcoholism.” And so forth.

RB: Patients I see have few of those characteristics. They come from a good family, they have a job, they’re educated, they have money, they drive cars to my office, they haven’t had trouble with the law, but somehow they get prescribed into an addiction. All the time. The vast majority of my patients are not fundamentally different from anybody else. It’s an equal-opportunity, affirmative-action disease.

JW: I’m not sure I believe that.

RB: You’ll have to come to my office and see my patients. I’ll see 30 patients a day, and I’d say 25 of them fit into the white, middle-class, average American demographic.

JW: Where do they get their drugs?

RB: From doctors.

JW: That reminds me of something else. Do you believe what has been suggested by some that with the more stringent regulations with opiates, we’re going to drive some people into the illicit market?

RB: We already do that now.

JW: Well, we’re going to do more of it.

RB: I’m the medical director at a methadone maintenance clinic, and I have a lot of opportunity to talk to unemployed drug dealers. They tell me that before I-STOP [New York State’s electronic prescription monitoring program] went into effect, they knew that doctors were going to be cutting their patients off from their licit supply, and that these patient would need another source. So, ahead of I-STOP, they actually shipped in extra heroin and fentanyl to New York. They stockpiled it, because they were ready for the anticipated uptick in their market. They did this three years ago. Now, today, our political leaders are saying, “Oh, we didn’t see this coming.”

If we’re going to get our hands around this, we have to be smart. There were provisions in that I-STOP legislation for mandatory physician education that were never followed through on. It was fought by organized medicine and those provisions were stripped away from the original legislation. That’s why we got caught off-guard. The physician workforce was uneducated about what was going to happen. But the drug dealers knew. Now, in Erie County, we used to have maybe 20 overdose deaths a year. Last year we had over 250, and this year we’re on course to have one every day. And people are wringing their hands, going, “How did this happen?” Those of us in the business, we did try to educate our leaders, but the nature of politics is not proactive.

JW: Are you suggesting more stringent controls on prescriptions are doing more harm than good?

RB: It remains to be seen. It certainly has caused more problems in the short term, but in the long term, we have to get our hands around overprescribing. What we have done is shift a group of people from the licit market to the illicit market, because we weren’t prepared. We weren’t geared up for the collateral damage. We could have been. The drug dealers knew this was going to happen. Those of us who work in addiction knew this was going to happen.

JW: You and the drug dealers are smarter than the politicians, I think.

RB: Well, we’re smarter about this one thing, but politicians are much smarter about getting elected than I would ever be. This speaks to the nature of politics. If you’re a politician and you do something, you fight the hard fight, you take on organized medicine and the hospitals and the pharmaceutical companies, you cram this down everybody’s throats, against their will, and you prevent a problem, you can’t turn that into a campaign. If, on the other hand, you wait for a problem to happen, and then run around and look like you’re doing something, and have a lot of photo ops and press releases and press conferences, now it looks like you’re going to do something. When you run for reelection, you can say, “Look at all that I did.” The nature of politics rewards reactionary approaches to problems, not preventative.

JW: Let me raise another issue. There’s a term that I like called pharmacological Calvinism—the notion that if a drug makes you feel good, it’s bad. As you know, marijuana is on the march to become pretty freely available, and it makes people feel good, and somehow we decided that maybe locking people up for smoking pot is not such a good idea. In various countries in the world, Portugal is the main example,  drugs are available, they let people use them. Are we going to really be in trouble, should that come to pass?

RB: There’s an interesting study that was done, I forget exactly where, but it was off the coast of a small Central American country. Drug dealers were shipping cocaine from Miami or wherever to Columbia or wherever, and occasionally there would be a raid or something, and they would throw the cocaine overboard. The way the currents were, it would wash up on the shore of this particular area, so anthropologists studied the effects of what happens if you take this village and just dump cocaine on it, and compared that to villages that weren’t exposed to cocaine. As you might predict, the villages that were exposed to cocaine had a breakdown in their civil society and families, the ability to grow crops. There was starvation, kids were neglected and so forth. Not surprising. So, on a macro scale, if you take towns and you just dump narcotics there, there are going to be problems.

Another study was done by the state of Ohio. Turns out there were these pill mill clinics, pain clinics, set up along Interstate 75 in Florida—like, one on every interchange. So people from Ohio would drive down there and get a carload full of pills. They would go to multiple doctors, get multiple prescriptions, go to multiple pharmacies, fill them all, put them in the car and drive back to Ohio. The narcotics division for the state police in Ohio tracked this, and wherever there was an exit on I-75 in Ohio, they would begin to see problems related to opiates, opioid deaths, criminal behavior and so forth. They had a time-lapse map and it went from green, or few drug problems, to red, or maximum drug problems. Over time, you can see these little dots of red every interchange along I-75, and gradually, over time, all the red stuff spreads out.

JW: My fear is that we’re going to swing too far the other way now, and there are going to be countless people who benefit—I won’t say “need”—they benefit from these drugs. When their pain gets bad, they’ve got this opiate, which treats it, for many people miraculously, and we’re going to say to them, “We’re going to sacrifice you on the altar of stopping addiction.”

RB: It’s not an either-or question: Either we’re going to undertreat pain or we’re going to have more addicts. It’s that we’ve got to be smarter, and better, and use this tool more precisely, rather than just saying, “Write all you want,” or “Don’t write anything.” That’s not where the answer is.

JW: We can’t argue about that. That’s perfectly reasonable.

RB: I have a table I use. It’s broken into four quadrants. If there’s pain and addiction, you do A. If there’s addiction but no pain, you do B. If there’s pain but no addiction, you do C, and if there’s no pain or addiction you do D. It’s not a dichotomous decision here: overprescribe or underprescribe. It’s “prescribe smartly.” So look at your patient and see, now this is an oversimplification, but which quadrant does your patient fall into? And prescribe appropriately.

JW: This is where I come back to this notion of physical dependence versus addiction. I believe that you can be physically dependent and not be addicted.

RB: Absolutely true. No question.

AB: What is the difference?

JW: Physical dependence is a fundamental pharmacologic phenomenon. Anyone, exposed to a drug which induces physical dependence at a sufficient dose for a sufficient time, will become physically dependent, which is defined by an abstinence syndrome. That means that our brains have created these compensatory mechanisms. When the drug is removed, those compensatory mechanisms get loose, and for a depressant drug, they tend to be stimulatory in nature, so if I’m an alcoholic, and you cut off my booze, I may go into convulsions and so forth.

RB: Physical dependence is an observable phenomenon. It is objective. You can see it in humans and you can see it in laboratory animals. Addiction is more of a human phenomenon, and part of addiction is usually, not always, but usually the person who is addicted is physically dependent. But in addition to being physically dependent, an objective thing, aberrant social behaviors would characterize addiction. In that way, it is almost always a human phenomenon, because little rats don’t get out of their cages and start stealing car radios.

AB: So addiction is about behavior.

RB: It is evidenced by aberrant behaviors. People say, “Well, those are voluntary behaviors. It’s just a behavior problem.” To which I say, “What organ other than the brain produces behavior? Is it the kidney? Is it in the pancreas? No, it’s the brain.” So if you alter the function of the brain with drugs, particularly mood-altering drugs, you then get an alteration in behavior that becomes dependent upon chemico-electro activity there. So then there’s this whole notion of volition and what becomes voluntary and what isn’t voluntary. And now you start getting into the realm of metaphysics, and once you get there, there’s no escape. People can have these philosophical debates for a long time about how much is voluntary, what’s a behavioral flaw, but it’s very clear that the brain function has changed, and in some ways, permanently.

JW: There are arguments about that. I realize that the NIDA [National Institute on Drug Abuse] is totally on board with “addiction is a disease,” a chronic, relapsing disease. And you’ve got countless research grants out there trying to find out what happens to spinal dendrites and so forth. But I think that’s not quite established.

RB: Well, what other organ produces behavior?

JW: No, no, no, no. I argue that all behavior is brain. I’m on the extreme there. I don’t disagree with that, but the notion that we have permanently altered the brain by exposure to these drugs may not be true.

RB: Let’s take exposure to methamphetamine as an example. So we have little rats, and we have a rat that you don’t do anything to and a rat that you smack on the head with a little piston. You’ll see die-back of the dendrites in the prefrontal cortex of the rat that was whacked on the head with the piston. A similar pattern is seen in rats exposed to methamphetamine. You would conclude, then, that brain function’s been changed, in a physical manner, and that in turn changes their behavior.

JW: You may be overselling. It reminds me of fluoxetine, which has been around for a very long time. Animal studies said it was changing the pruning of synapses, but damned if they could show any adverse effect in humans in that regard. And somebody even went so far as to say, maybe it’s a good idea to prune those.

RB: It’s hard to say. You can’t expose humans to these drugs and then sacrifice them and do brain sections. So they’re tough studies to do.

JW: That’s why I prefer to say that addiction should be defined behaviorally. Are you craving and seeking a drug in the face of disincentives?

RB: Well, it has to be defined behaviorally because we don’t have the tools to define it biologically. HIV had to be defined by a cluster of clinical symptoms, because we didn’t have the antibody test. And then we had an antibody test, and we stopped using all that clinical scoring stuff. So before you have a gold standard diagnostic test, you’re going to use a behavioral checklist, but it’s imprecise. Just guesswork. And people have arguments about this. “Oh, they turned away from God” or “It’s brain disease.”

JW: I looked at the website for Malibu [a luxury rehab and treatment center]. For $80,000 a month, you can go get cured of addiction.

RB: They’re just treatment mills. A lot of this stuff doesn’t work, and we know it. Let’s look at the example of cervical cancer. In 1900 it was the number-one cancer killer in the United States. Röntgen discovered X-rays in 1895, the Curies isolated radium around 1900, surgeons developed ether and anesthesia and began to figure how to take the uterus out. So by the 1920s, we had all the treatment modalities we needed to treat late-stage cervical cancer. They didn’t work then, and they don’t work now.

Cervical cancer is now the number-ten killer in the country, but we didn’t get here because we put cancer treatment centers on every corner to treat late-stage cervical cancer. We got there because we recognized that there was a progression of this disease, and if we did Pap smears and cryosurgery and so forth, we could identify it early and stop it from progressing. Now we’ve got a vaccine that prevents people from getting infected by the virus that causes it.

We are never going to be able treat our way out of this epidemic. There’s no way. One, there’s not enough treatment on the planet. Two, it doesn’t work anyway, just like cancer treatment. The only way we’re going to beat this back is through prevention and early intervention.

JW: So you’re telling me that your treatment doesn’t work.

RB: Treatment doesn’t work. Behavioral treatment.

JW: Well then, shouldn’t you be out of the business and enforcing laws to prevent people from getting these drugs?

RB: We still have to take care of the people who are addicted as best we can. We don’t have good treatments. It doesn’t mean that nothing works for anybody, anytime. So I’ve got people on buprenorphine who are now functional. I have people on methadone who are staying out of trouble with the law, but they’re still doing all the rest of the stuff, buying and selling Xanax and stuff. They’re not stealing. They’re not shooting each other. It’s a harm reduction thing. There are people who become abstinent and live a normal life, in recovery, as they say. And the odd thing is, if I talk to those people who have been clean and sober for a number of years, who have returned to be productive citizens, and I ask them, “What do you think has been the biggest thing in your life that has helped this?” they say, “My relationship with God.” I’m a doctor. I don’t pretend to understand that, but I’ve heard this story over and over and over again from people who have cleaned up.

JW: In [The Buffalo News’] desire to cut down my little piece, where I said that the roots of addiction are multiple and often intertwined, I included in there the absence of love, meaningful work, some purpose in life.

RB: Here’s something I don’t understand. This is not just with addiction, but with a lot of diseases. There are people who are physically well, and are psychologically intact, but just don’t have something. For lack of a better way to describe it, they’re sick in their soul, whatever that is. You know, there’s mind, body, spirit. We really don’t understand the body, how DNA works, the ribosomes and all that kind of stuff. Even the physical stuff, we don’t know. We sure don’t know behavior and psychology. We’re just groping around in the dark with this stuff. But the spiritual stuff, we haven’t even begun to figure out what that is, or how that works, or how that influences humans. So you have to go to church for that now, and that doesn’t lend itself to the scientific method.

But taking care of people, taking care of patients, it’s more than just taking care of their bodies and their behavior. There are other things that happen there, which, I don’t know … Sometimes the compassion of the health care system toward patients who have been beat down with addiction, offering hope or a helping hand, is the missing ingredient in their treatment that affords some people the opportunity to turn their lives around. 

Jerrold: Here’s a pharmacological fact: Caffeine is not only a pleasurable stimulant, it can also induce physical dependence for which the withdrawal syndrome is headache. In any case, I’m not a coffee drinker.

Richard: Cream and sugar in the morning, black thereafter.