Next month I will be presenting a paper at the annual meeting of ASAM, the American Society of Addiction Medicine. The paper discusses a new method for treating chronic pain, using a combination of buprenorphine and opioid agonists. In my experience, the combination works very well, providing excellent analgesia and at the same time reducing—even eliminating– the euphoria from opioids.

Ten years ago, I would have really been onto something. Back then there were calls from all corners to improve the pain control for patients. The popular belief regarding pain control was that some unfortunate patients were being denied adequate doses of opioid medications. I remember our hospital administrators, in advance of the next JCAHO visit, worried about pain relief in patients who for one or another reason couldn’t describe or report their pain. Posters were put up in each patient room, showing simple drawings of facial expressions ranging from smiles to frowns, so that patients in pain could simply point at the face that exhibited their own level of misery.

What a difference a decade makes! Purdue Pharma, the manufacturer of Oxycontin, was fined over $600 million for claims that their medication was less addictive than other, immediate-release pain-killers. Thousands of young Americans have died from overdoses of pain medications, many that came from their parents’ medicine cabinets. Physician members of PROP, Physicians for Responsible Opioid Prescribing, have called out physicians at the University of Wisconsin School of Medicine and Public Health for having ties to Purdue while arguing against added regulations for potent narcotics.

I have tried to present both sides of the pain pill debate, without disclosing my OWN opinions on the issue—at least until today. And I must be at least somewhat ‘fair and balanced,’ because I’ve received angry messages from both sides—from people telling me I’m evil for not understanding their need for pain medications, and from people telling me I’m evil for not respecting the danger of the medications.

By the way… I have a policy of not printing messages that simply call me names, or that tell me how bad a doctor I must be for writing what I do. I love a good argument, so please feel free to comment on ANY points that I’m trying to make. But I don’t think that making efforts to lead a discussion warrants personal attacks—so please, stick to the issues!

Today, though, I would like to share a couple thoughts on the issue. The thoughts came after a discussion with one of my patients with chronic pain. I have been presenting one side, then the other side, and back again, trying to remain neutral… but from all that I’ve seen as a psychiatrist and as an anesthesiologist, some things cannot be denied.

1. Some people do have chronic pain that responds to opioids. Many doctors—including the doctors who are afraid of the DEA, or the doctors who don’t want to deal with the hard work of prescribing opioids, or the doctors who want a simple world where ‘pain pills are always bad’—don’t want to admit the truth of this statement. This is, with apologies to Al Gore, a very inconvenient truth.

I find it interesting that doctors who don’t want to prescribe pain pills act as if chronic pain does not exist– as if the suffering of people with painful disorders is less important in some way, if it lasts too long. Every prescriber is aware of the need to treat acute pain, but when it comes to chronic pain, the difficulties that arise with treatment (e.g. abuse, diversion, tolerance) lead some doctors to act as if something magical happens on the road from acute to chronic. The phenomenon is the exact opposite of the old saying, ‘to a man with a hammer, everything looks like a nail.’ In this case, ‘to doctors who don’t want to use hammers, there ARE NO NAILS.’ But in truth, there ARE nails; some patients have lots of them. And we doctors have a duty to hammer away at them… (OK, enough with the analogy already!).

2. Just because some people divert opioids does not mean that other people shouldn’t have necessary pain relief. Treating pain is about as fundamental as medicine can be. I do not understand the doctors who say ‘I do not treat pain—you’ll have to see someone else’—especially when there are no doctors available to fill that role. More and more ‘health systems’ are adopting this position, at least in my area. What gives?!

3. At the same time, there is no such thing as ‘complete pain control.’ Tolerance removes the power of narcotics, and chasing tolerance always ends badly. Patients with chronic pain must use ALL tools available, including non-narcotic techniques.

4. Being prescribed pain medications comes with certain responsibilities; the responsibility to use the medications appropriately, to communicate openly and truthfully with the prescriber, to avoid ‘doctor-shopping,’ etc. At some point, patients who refuse to honor these responsibilities will lose access to pain medications—at least to some extent. Is this humane or fair? I think so, as access to pain relief for these patients is balanced against the lives of those killed by illicit use of these medications.

I’m sure I could go on… but for now, this is enough food for thought. Besides, it’s almost time for dinner! Feel free to comment—but please, be nice!

A question was asked about the last post that warrants top billing:

“Buprenorphine acts similar to opioid agonists in lower doses, with the same addictive potential as oxycodone or heroin. In higher doses—doses above 8 mg or 8000 micrograms per day—the ‘ceiling effect’ eliminates interest and cravings for the drug.”

Ceiling Effect

I’m not sure I followed this. Can you explain more? What would you think about someone who is taking 1-2mg of Suboxone twice a day without a prescription, and says they want to stay on that dose once they find a prescriber? Are they better off on 8mg or more per day, or would it be ok for a prescriber to keep them at the lower dose? Is the answer the same if they hope to taper off the medication completely within a year (they don’t feel able to do this on their own right now, but hope to be able to when some life circumstances change). Thanks!

This gets a bit complicated, but I’ll do my best. A couple background issues; buprenorphine has a ‘ceiling’ to its effect, meaning that beyond a certain dose, increases in dose do not cause greater opioid effect. That is the mechanism for how buprenorphine blocks cravings.

If the blood level of buprenorphine is ABOVE that ceiling, the opioid receptors are maximally, 100% stimulated. If the person takes more buprenorphine, and the blood level increases, the opioid receptors don’t feel the increase, as they cannot be stimulated more than 100%. But more importantly: when the person takes less, and the blood level of buprenorphine goes DOWN, the receptors also sense nothing– as long as the level stays above the ‘ceiling’ level.

Read the above paragraph, and think on it until you grasp it– as it explains buprenorphine and Suboxone. If you understand that paragraph, you will know more about Suboxone than most doctors!

Below that ceiling level, the opioid effect from buprenorphine varies directly with dose—just as with oxycodone, hydrocodone, heroin, etc. Medications that have effects that increase with dose are called ‘agonists’. Buprenorphine is a ‘partial agonist;’ it acts like an agonist up to point, the ceiling effect, beyond which increases in blood level have no greater effect.

The level of this ‘ceiling’ varies from one person to the next, depending on efficiency of absorption (on average, only a third of a dose is absorbed from under the tongue), body size, liver function, differences in regional blood flow, and the presence of other medications that affect buprenorphine metabolism. In order for buprenorphine to have the unique, craving-blocking effects, the blood level of buprenorphine must stay above the ceiling level, for the reasons described above.

Lower levels (blood levels of buprenorphine below the ceiling level) still have SOME effects on cravings. Buprenorphine has a long half-life, an that alone reduces the desire to take more—especially if the medication is taken more than once per day– since the blood level drops very little between doses. For agonists or for buprenorphine below the ceiling level, drop in blood level equals drop in opioid effect, equals sense of things wearing off, equals cravings.

But the classic method for treating with Suboxone, as described in the certification course, is for it to be given at a high enough dose to stay above the ceiling level… and dosed only ONCE per day. If the blood level stays above the ceiling level, once-per-day dosing covers cravings completely. Yes, people still want to take more, especially initially, but that desire is not driven by chemical effects; the desire is instead based on psychological factors, like habit, or from being accustomed to feeling better after a dose, and getting a placebo ‘lift’ from taking a second dose.

A person can eliminate that second dose fairly easily, providing that the morning dose is high enough, i.e. usually 8-16 mg. To eliminate the second dose, the person should distract him/herself as soon as the thought about taking the second dose comes to mind. Immediately, do anything else—the dishes, call a friend, wrestle with the dogs… and the thought will pass. If the person does the distraction method for a few days, the need to take the second dose will go away—a psychological process called ‘extinguishment.’

Dosing every other day, and even every third day, has been studied; people cannot tell the difference, if the dose is raised enough to keep the blood level above the ‘ceiling’ (providing the person is given a placebo that tastes the same).

As for as the writer’s friend… I’m not a fan of any illicit use, but I am aware of the shortage of physicians. When the person has a physician, in my opinion the person should be prescribed a dose that allows for once per day dosing. Realize that buprenorphine wears off VERY slowly; it takes over three days for half of a dose to leave the body! So that ‘need’ to take more is almost always entirely learned or ‘conditioned.’ The medication does not wear off in that short period of time.

Even if the person has withdrawal symptoms, the sensations are almost surely imagined. How to tell? Use the distraction method, and note that a couple hours later, when the person remembers that the dose was skipped, note that the withdrawal went away. That doesn’t happen with ‘real’ withdrawal!

The sense of withdrawal that drives the second dose is simply a memory; a conditioned response that the body has that triggers the person to take more opioid. We become conditioned by drug use, just like the salivating dogs from science books! In the case of opioids, whenever we feel down, we think that an opioid will lift us up, as it has hundreds of times before. And even if what is taken is not a real opioid, the mind ‘feels’ a boost, just from expecting what has always happened in the past.

As for tapering, I look at many factors in order to recommend, or not recommend, stopping buprenorphine—things like age, presence/absence of using friends or contacts, physical health, mood, support network, personal motivation to stop buprenorphine, ability or lack thereof to dose once per day, consistently, number of relapses and personal ‘recovery’ plan, etc.

Realize that EVERYONE looks forward to a day when life circumstances will change for the better—but most of the time, life becomes more, not less challenging. Yes, it is nice to have a reliable job… but it is much more stressful being the sole breadwinner for a family with children, than working to pay for one’s self! Marriages settle down in some ways over time, but they also lose the intense infatuation that can gloss over personal differences.

As I have often written, it is VERY hard to stop opioids. It is a little easier to stop buprenorphine; I am convinced of that fact because I have seen opioid addicts taper off buprenorphine, but I know of no opioid addict who tapered off an agonist. But SOME people cannot taper of ANY opioids—including buprenorphine. I do not consider those people ‘addicted’ to buprenorphine, because they lack the constant obsession for opioids that is so destructive to the mind of an active addict. But they ARE physically dependent on buprenorphine— a fair trade, in my opinion, for a life of chaos, broken relationships, legal problems, and death.

I’ve received several complaints from patients and readers about one of the current buprenorphine formulations.  The primary complaint is that the tablet is ‘not ‘working as well as the other formulations;’ that it seems to wear off earlier, or that people feel compelled to take more than what is prescribed.

Buprenorphine 8 mg tabs

My understanding, admittedly based only on what people have told me, is that there are three current formulations of buprenorphine.  The brand form, Subutex, comes as a relatively-large, flat-oval tablet, white or off-white in color.  The Roxanne version is a round white tablet, with a diameter of about 0.5 inch.  The tablet people have complained about is from Teva, and is smaller;  about the size of a tic-tac.

In general, I think that generics are as good as brand name medications.  I have never come across a reliable instance, in my practice, of generics being less potent or less active.  I recognize that particularly for psychiatric medications, the placebo effect accounts for significant portions of the actions of medications—so if a person BELIEVES that generic fluoxetine is less likely to work, it IS less likely to work.  But take away the placebo issue, and a molecule of fluoxetine is a molecule of fluoxetine—regardless of where it comes from.

That said, I realize that the delivery of molecules can be affected by the design of capsules and tablets.  I remember a study, years ago, that showed that many of the vitamins sold in the US passed through the intestinal system without even dissolving, let alone getting into the bloodstream. If the active substance is encased inside insoluble resin, there is little to be gained from taking it.

The delivery issue is less of a concern with a medication that is delivered through the oral mucosa, as with buprenorphine.  There are several factors that affect absorption of buprenorphine;  the concentration of buprenorphine in saliva,  the amount of surface area that buprenorphine is allowed to pass through, and the time allowed for that passage to occur.  If the smaller tablet dissolves more slowly, molecules of buprenorphine may have less actual contact-time with oral mucosa, thereby reducing absorption.

On the other hand, I am well aware of the psychological reward that people describe from taking buprenorphine or buprenorphine-naloxone, even in the absence of any subjective sensation.  The fear of withdrawal is relieved by taking buprenorphine—making the dosing experience ‘rewarding.’  It may be that the smaller tablet provides less reward, as the small size engenders less confidence in those unfelt ‘effects.’

In any case, I invite readers to share their experiences, just in case those who have already written are truly onto something.  Please leave comments below—and thanks for sharing!

Today I met with representatives from Alkermes who were promoting Vivitrol, a long-acting mu opioid antagonist that is indicated for treatment of alcoholism and opioid dependence.

Naltrexone

I admit to some pre-existing bias against the medication.  I’m not certain, to be honest, whether that bias was based upon sound clinical reasoning, or whether it was based on personal, negative reactions to naltrexone in my past.  Or maybe, as a recovering opioid addict, I have negative feelings about anything that blocks mu receptors!

Vivitrol consists of naltrexone in a long-acting matrix that is injected into the gluteal muscle each month. The medication is expensive, costing about $1000 per dose (!)  That cost is usually covered by insurance, and like with Suboxone, Wisconsin Medicaid picks up the tab save for a $3 copay.  Alkermes, the company that makes Vivitrol, also has a number of discounts available to reduce or even eliminate any copays required by insurance companies.

I’ll leave the indication of Vivitrol for alcoholism for another post.  The indication for opioid dependence came more recently, and appears more obvious, given the actions of naltrexone at the mu opioid receptor.

In short, naltrexone blocks the site where opioids—drugs like oxycodone, heroin, and methadone—have the majority of their actions.  Blockade of that site prevents opioids from having any clinical effect.  There is some dose, of course, where an agonist would regain actions— an important feature in the case of surgery or injury.  But even in those high doses, the euphoric effects of addictive opioids would be muted.  People on Vivitrol, essentially, are prevented from getting high from opioids.

Back in my using days, I took naltrexone, thinking that doing so would help me get ‘clean.’  I didn’t wait long enough, however, and so I became very sick with precipitated w/d.  The makers of Vivitrol recommend waiting at least a week, after stopping opioids, before getting an injection of Vivitrol.  I suspect that a week is not long enough to prevent w/d, but I realize that it would be very difficult to expect patients to last longer, without using anything.  I would expect that any precipitated w/d could be reduced through use of comfort medications, at least for a day or two until the symptoms are mostly gone. This requirement, though, to be clean for a week or more is one of my problems with the medication.

As an aside, I was also prescribed naltrexone (oral tabs) at the end of my three months in residential treatment, and I took the medication for another three months.  I had no withdrawal or other side effects to naltrexone at that time.

Another issue was the concern that naltrexone has been connected to hepatic toxicity.  We discussed that issue today, including the studies that led to that connection—which are not compelling.  The discussion allayed most of my concerns about liver problems from Vivitrol.

Finally, I have always recommended buprenorphine over naltrexone because of the anti-craving effects of buprenorphine that result from the ‘ceiling effect’ of the medication.  I worried that naltrexone, by blocking the actions of endorphins, would actually increase cravings.  But that is not what the data shows.  In the studies with Vivitrol, cravings for opioids were dramatically reduced by the medication.  The mechanism of that effect is not entirely clear;  some of the anti-craving effect may be psychological, as addicts stop wanting something when they know there is no way to get it.  But there may be other complicated neurochemical effects at presynaptic opioid receptors that are not fully understood.

The bottom line is the result of treatment;  the very sick opioid addicts treated in the studies used by Vivitrol to gain FDA approval showed a profound reduction in opioid-positive urines, over a span of 6 months.

I suspect that I will continue to favor buprenorphine.  I do not buy into the ‘need’ some people describe to ‘get of buprenorphine as fast as possible.’  Buprenorphine is a very effective, safe, long-term treatment for inducing remission of opioid dependence.  But because of the cap, I am glad that another option is available to treat this potentially-fatal condition.  And I admit to perhaps being too quick to judge Vivitrol, which appears to be a safe alternative—particularly for people who have a lower opioid tolerance that do not want to push it higher, or for people who have been free of opioids for a week or two.

I would invite local people who are on my buprenorphine waiting list to consider Vivitrol as an option.

An Article by Mike Berens and Ken Armstrong, Seattle Times, discusses some of the problems with using methadone as a first-line treatment for pain:

When it comes to battling pain, Washington health officials have encouraged doctors to reach for methadone, a powerful and inexpensive prescription drug. For the past decade, the state has declared methadone to be as safe and effective as any other narcotic painkiller.

Methadone

But in a striking reversal that has gained momentum this week, doctors are receiving stark warnings that methadone is riskier and more dangerous — a drug of last resort — because it’s unpredictable and poses a heightened risk of accidental death.

“It’s a dangerous drug because it accumulates in the body and people die in their sleep,” Dr. Jane Ballantyne, a pain specialist at the University of Washington, said Friday. “It’s very tricky and difficult to use safely.”

Ballantyne and the university are helping spearhead a series of state-sponsored training programs to educate physicians, pharmacists and advanced nurse practitioners about the risks of pain drugs.

Earlier this week, while delivering a continuing medical education course for dozens of physicians and other medical professionals at the university, Ballantyne presented a slideshow in which she cautioned that methadone “should be considered a last option opioid, never a first line opioid.”

The state’s effort is a response to a Seattle Times series, “Methadone and the Politics of Pain.” The investigation, published in December, detailed that at least 2,173 people in Washington have died from accidental overdoses of the drug since 2003.

The Times found that year after year, a committee of state-appointed medical experts sanctioned methadone, empowering the state to designate it a “preferred drug” and steer people with state-subsidized health care — most notably, Medicaid patients — to the drug in order to save money.

The state has included only two drugs, methadone and morphine, on its preferred list of long-acting pain drugs.

During the committee’s meetings, officials from state agencies that have a financial stake in methadone’s selection consistently deflected concerns about the drug.

Methadone’s death toll has hit the hardest among low-income patients. Medicaid recipients account for about 8 percent of Washington’s adult population but 48 percent of methadone fatalities.

After the series, the state sent out an emergency public-health advisory that singled out the unique risks of methadone.

Medicaid officials faxed a health advisory to more than 1,000 pharmacists and drugstores about methadone, as well as about oxycodone, fentanyl and morphine. The state Department of Health mailed advisories to about 17,000 licensed health-care professionals.

The health advisory confirmed that Washington ranks among states with the highest rates of opioid-related deaths, exceeding the number of deaths each year involving motor vehicles.

Most painkillers, such as oxycodone, dissipate from the body within hours. Methadone can linger for days, pool into a toxic reservoir and depress breathing. With little warning, patients fall asleep and don’t wake up. Doctors call it the silent death.

Ballantyne noted that methadone is an indispensable drug and plays an important role in the treatment of many patients. However, due to the heightened risks, methadone should be prescribed only by those with extensive training and experience — and only after every other option has been exhausted.

Dr. Jeff Thompson, chief medical officer of the state’s Medicaid program, now readily agrees that methadone use carries unique risks and that it should not be the first choice if other drugs are equally suitable.

He said physicians are stepping up efforts to unravel the long-term impact on the body from prolonged use of prescription drugs now that Washington’s new pain-management law has gone into full force beginning this month.

The groundbreaking law requires practitioners to follow new standards for treatment and record-keeping. It also requires prescribers to consult with state-certified pain experts when narcotic dosages reach higher thresholds.

While the law’s goal is to lower doses and, if possible, wean patients from narcotic pain drugs, doctors are finding the task more difficult than hoped, Thompson said.

For instance, methadone patients can suffer prolonged withdrawal symptoms, like nausea and depression. With most pain drugs, withdrawal subsides within a week. Methadone’s grip can last for months, even years, he said.

State officials will review methadone’s role on the state’s preferred drug list during a meeting next month.

“I think we’re going back and relearning how to treat pain,” Thompson said.

A recent experience with a patient helped me realize some of the dramatic differences in the treatment of opioid dependence, in an era of buprenorphine.

I drug-test patients who are treated with buprenorphine or Suboxone.  The point of testing is not to catch someone messing up, but rather to determine when a person is in trouble.  It would be great if we could simply rely on the word of our patients, but once a person is using opioids, his/her own ability to know what is true falls apart. All of us who treat addiction have heard patients rationalize relapse as something they ‘had to do’ for one reason or another, for example.  The effects of active using on insight are why I like the use of ‘DENIAL’ as a mnemonic for ‘Don’t Even Notice I Am Lying.’

The effects of relapse on telling the truth are part of the profound impact of using on a person’s insight.  Insight disappears very quickly during active using, as the mind abandons the broad view and becomes focused on one goal. Before buprenorphine, drug testing was in some ways more, and other ways less important.  It was more important because after relapse, the person was immediately thrown back into the world of desperate scrambling, where risks for consequences are high.  On the other hand, testing was less important—or maybe necessary– because experienced addictionologists (and spouses) could see the effects of using, including the loss of insight, in the active addict’s eyes.

I was one of those people who experienced that rapid loss of insight after my relapse, back in 2000. For years I had attended AA and NA; hundreds if not thousands of meetings over seven years.  I remember comforting myself that ‘if I ever get off track, at least I now know where the door is to get back.’  I didn’t realize that at the instant one relapses, that door becomes nowhere to be found.

In retrospect, I don’t know if the door actually disappeared. I suspect that with the right attitude, that same door would have opened for me.  But the honesty and humility that I needed, in order to ask for help in finding and passing through the door, were suddenly replaced by the need for secrets—secrets about everything.  As soon as I relapsed, nobody could be trusted. Nobody would understand me.  I was on my own.

Contrast that with the experiences of patients on buprenorphine who relapse with opioid agonists. As I compare their experiences to mine, I realize that I am using the experiences of a couple people to make broad generalizations.  But I have seen a number of examples that support these generalizations, that have consistently followed the paths that I’m about to describe.

One patient—call him ‘Paul’—told me about his relapse before I even mentioned that I would be asking for a urine test.  In fact, he was eager to tell me about his experience, as if he looked forward to getting it off his conscience.  “I have to tell you that I really screwed up last week,” he said. When I asked him what happened, he said that a friend who he hadn’t seen for several months came through town and stopped by his house.  With little warning, his friend pulled out a bag of heroin and a couple clean needles, tossed them on the table, and said ‘let’s fire up.’

After shooting the heroin, Paul immediately felt disappointed in himself.  Unlike in the old days, he felt nothing from the heroin.  While his old friend nodded off next to him, Paul wondered what the heck happened—and immediately wanted to talk to me about the situation.

His desire to talk is an amazing thing—and worth noting.  Without buprenorphine, a person who relapses is not generally eager to speak to his/her sponsor, let alone counselor or physician.  In those cases, the mind reels from an avalanche of shame, and the need to keep secrets—even from one’s own awareness—becomes paramount.

There are many buprenorphine programs that would discharge a person for one relapse—and in such cases, I would not expect the same type of honesty from patients.  I don’t get the logic of those programs, and I become angry when I think about them.  As I’ve said before, if a person relapses, that person NEEDS help—not abandonment!  I believe that the proper approach to treating addiction can be found in almost all cases simply by considering opioid dependence to be another chronic illness.  And if someone with heart disease overexerts himself and comes in with chest pain, we don’t boot him from treatment!

Paul made an appointment to talk about his experience.  He explained how he felt when his old buddy contacted him, and we discussed ways to avoid meeting up with ‘old friends’ in the future.  He discussed the urge to escape when he saw the paraphernalia—to escape from life’s responsibilities—and we talked about how difficult it can be to simply tolerate life sometimes, and the powerful effects of triggers and cues.  Most interesting to me, as a psychodynamic psychiatrist, he talked about a complicated set of thoughts and feelings that came up when he saw the drugs—questions about who he was, about shame, about the heavy load that comes with doing the right thing, and about the pressure of not letting people down.  Those are all big issues, I said as I agreed with him.  How much easier, at least for a few moments, to just be ‘nothing’—to have no expectations about one’s self!

We talked about the challenge of being ‘someone’– of being proud of one’s self.  It feels good to do the right thing– but it may also feel bad.  Am I letting my old friends down, if I do better? I suggested that he might watch the old movie, Ordinary People, where a younger brother struggles after surviving an accident that claimed the life of his brother.

Before buprenorphine, people struggled with opioid dependence largely on their own.  Yes, we had twelve step groups—and still do—but twelve step groups place the responsibility to get one’s act together squarely on the back of the using addict.  Many people in AA or NA will say that “AA is a selfish program.”  It has to be.  When one relapses, one is left with his own distorted insight, accumulating consequences until, hopefully, he finds his way back to the pathway established by the simple program of the steps.

On buprenorphine, relapse doesn’t necessarily cause instant loss of insight.  I don’t mean to minimize relapse, as bad things can always happen.  For example, I have had patients stuck in a pattern of chronic relapse that was difficult to straighten out, even though there was little or no psychic effect from the drug being abused.  But from an optimistic standpoint, relapse on buprenorphine stimulates a deeper investigation into what is missing from the person’s life, and a renewed effort to gain what is missing.

This assumes, of course, that the person is not simply tossed from treatment for the relapse.  In that case, other people are left trying to figure out what happened—when the obituary appears a few months later.

A Reader Writes:

Message:

The State of XXXXXX prescription price list noted Target Pharmacy as the cheapest for Suboxone at $6.99/Suboxone pill, 8mg-2mg, qty. 30. So I started getting my prescriptions filled at Target.

Well, needless to say they raised their prices twice since then and I am now paying $8.158333/Suboxone pill, 8mg-2mg, qty. 30, Nov. 12, 2011.

My question: How can they be alowed to jack their prices up so fast and so high in a short period of time? What can I do? It’s like they pulled a bait and switch on me.

Please write back Dr. Junig

My Reply:

I sympathize with you.  The best thing you can do is have an educated and educatable doctor– someone who has enough humility to recognize when he/she is wrong, and adjust accordingly.  Somebody who recognizes that as physicians, we are constantly sorting through new data, responding clinically to phenomena according to science.  Most importantly, someone who recognizes that in medicine, as in all fields, people make assumptions about things with partial data, and sometimes later learn that their assumptions were wrong.

I realize that is difficult in the current era when people with addictions are considered ‘manipulative’ for simply raising appropriate questions.  The truth is also competing with the marketing and persuasion tactics by Reckitt-Benckiser– a company that has found a way to influence policy-makers in government and addiction societies.  I am generally a fan of corporate greed, as I believe that the marketplace is the best stage for ideas to rise or fall (mixing several metaphors, I know!)  But I am appalled by the extent of involvement of Reckitt-Benckiser, the British corporation that makes Suboxone, with physician societies– the groups that are supposed to be advocating for policies that save lives that are being lost to addiction.

The generic tablet of orally-dissolving  buprenorphine, 8 mg, is FDA-indicated for treating opioid dependence.  In Wisconsin, some pharmacies have it for as
low as $2.35 per tab;  the more expensive places sell it for $3.00.  It is CLINICALLY IDENTICAL to Suboxone;  the naloxone in Suboxone is not absorbed sublingually (actually, 3%-5% is absorbed, but does nothing clinically), and after being swallowed the naloxone is completely destroyed at the liver by first pass metabolism.

Suboxone is supposedly safer then generic buprenorphine because naloxone supposedly causes withdrawal if injected.  This is the only justification (initially put forth by the folks at Reckitt-Benckiser) for the need for Suboxone.  The justification is flimsy, since many people who would benefit from the lower price of buprenorphine have very little risk of injecting the medication.  But worse, the flimsy justification is a lie. People who have injected Suboxone intravenously (I have met and heard from many of them) report NO withdrawal from naloxone-containing Suboxone.  What’s more, people who wrote to me who have injected both buprenorphine and Suboxone, at different times based based on availability, have all reported the same thing– that the subjective experience from injecting either substance is identical.

I must point out here that there are MANY reasons to avoid injecting any substance– but particularly a substance made to be taken orally.  These compounds contain fillers that destroy the capillary beds of the lungs, where oxygen is absorbed– potentially leading to severe lung damage.  And infection is always a huge risk, when placing poorly-sterilized material directly into the bloodstream.  Please– don’t do it.

Back to taking buprenorphine properly… the high cost of Suboxone is an unfair burden for patients without insurance coverage, when a much cheaper, idential alternative is available.

I am going to remove your name and location, and put up your question on my blog;  you are then welcome to bring a copy of the post to your doctor. You can also tell him/her to read prior posts, where I explain all of this in greater detail.

For Doctors and Insurance Formulary Committees:

I implore you to look into the facts of this situation with an open mind.  I have a PhD in Neurochem, besides 10 years of experience as an anesthesiologist and training and experience in psychiatry.  Some insurers cover buprenorphine;  they are, of course, the smart ones.  Your company can save a great deal of money by simply allowing the generic equivalent to be covered.  States that mandate the use of Suboxone or Suboxone Film could save large sums of money for their taxpayers.  And doctors–  your cash-paying customers could really use the break, especially in this economy.  If you are concerned that a patient is injecting medication, I understand your hesitancy— even though, frankly, it is misplaced, given that BOTH Suboxone and buprenorphine can be injected.  If your patient pays cash, and never injected medication, do you REALLY think that person is going to start injecting buprenorphine– since doing so would not create any effects?  The ‘ceiling effect’ is in place for ANY route of administration, so a patient taking sublingual Suboxone, who injects buprenorphine, will feel… NOTHING.

Give your patient the gift of affordable treatment as a Christmas present.  You may be saving someone’s life.

JJ

As I give my last post more thought….  I wonder if there is ANY clinical difference between $uboxone at $7 per dose, vs. generic buprenorphine at $2.33 per dose?  Researchers out there– can anyone send me a reference?

Read my last post for details– but the essence is that naloxone is destroyed when Suboxone is taken properly (orally, sublingually), and has no action whatsoever– on that issue there is scientifc agreement (although there is a great deal of ignorance among prescribers about this fact).  The ONLY think naloxone does, is to supposedly serve as a deterrent to IV injection of buprenorphine.

Sounds good, but…  we know that people divert Suboxone intravenously, naloxone and all.  Buprenorphine binds opioid receptors very tightly- so tightly that the naloxone doesn’t effectively compete with buprenorphine.

The State of WI requires Medicaid patients to take expensive Suboxone Film, whereas in other cases they require prescribing the generic.  What is the argument for requiring the film?  RB would argue (now that the tablet has lost the luster of being on-patent) that the film is harder to ‘divert’– i.e. to inject.  But frankly, the intravenous diversion of buprenorphine is a tiny issue compared to things like heroin addiction and a budget crisis.  Most of the diversion of buprenorphine, either Suboxone or generic, is not injected, but rather taken orally to ward off withdrawal– and the film makes no difference in that case.

Insurers, likewise, are wasting millions of dollars (literally) by paying for Suboxone— sometimes exclusively(!)  Have the bean counters fallen asleep on this issue?

I have nothing personal against Reckitt-Benckiser, beyond the fact that they refuse to engage in conversation with me.  If the good Brits at RB have discovered a way to suck millions of dollars from the weakest members of society, more power to them.  But I am a big fan of intellectual honesty, particularly in regard to the science behind medical practice.  So if someone has evidence that $uboxone is clinically different than generic buprenorphine, whether used properly or injected, please send it my way.

This post is from a couple years ago;  I think it is important for people to have a basic understanding of how buprenorphine removes opioid cravings, so I’m republishing the post.

Note that naloxone has NOTHING to do with the effects of Suboxone.

In this video I explain why the ceiling effect is so important to the effects of buprenorphine for treating opiate dependence.

I have shared my thoughts about ‘Suboxone Film,’ a product that serves only one purpose:  to block generic competition from entering the Suboxone market.  Below I’ve copied a Bloomberg article that discusses the current nature of the buprenorphine/naloxone business, and the efforts by RB to prevent market penetration by generics– something that would lead to price reductions for healthcare consumers.

Unfortunately, the Bloomberg article overlooks the most significant threat to the profits of Reckitt-Benckiser.  This threat is mitigated only by the ignorance of many of the physicians who prescribe Suboxone.  The threat to profits consists of a simple fact that RB does not want anyone to realize:  that the generic equivalent of Suboxone is already available, in the form of orally-dissolving tablets of buprenorphine.

I encourage physicians who doubt my comments to do their own ‘due diligence’ and break out their old pharmacology textbooks.  I have a hard time understanding how people who graduated from accredited medical schools can get things as wrong as they do with this issue.  I sometimes present opinions, but not with this post.  The facts about buprenorphine and naloxone that I’m about to describe are described in any pharmacology textbook— e.g. Goodman and Gilman—and are not in dispute in any way.

Suboxone consists of buprenorphine plus naloxone.  Naloxone is an opioid antagonist that is added to reduce diversion of Suboxone in the form of intravenous injection of a dissolved tablet.  Naloxone is NOT ACTIVE when not injected.  The molecule is poorly absorbed through the oral mucosa because of the molecule’s size and poor lipid-solubility.  Instead, naloxone is swallowed, absorbed from the small intestine, and totally destroyed at the liver before reaching the systemic circulation through a process called ‘first pass metabolism.’

I suspect that some physicians confuse naloxone with the similarly-named substance naltrexone, an opioid antagonist (blocker) that IS orally active. There is NO naltrexone in Suboxone.

All of the beneficial aspects of Suboxone come from the partial agonist buprenorphine.  The ceiling effect of buprenorphine causes a reduction in cravings through a process that I’ve described in earlier posts.  Naloxone, on the other hand, does absolutely nothing to reduce cravings, to increase safety, to reduce euphoria, etc, provided that the medication is not injected.

The confusion surrounding buprenorphine essentially consists of intellectual laziness or intellectual dishonesty by the physicians who prescribe the medication and the pharmacists who dispense it.  I realize that not all doctors are cut out to be ‘physician scientists’ who understand pharmacology in great detail.  But I am particularly disappointed that the large organizations that supposedly oversee the science of addiction treatment have dropped the ball on this issue. I don’t know why groups like ASAM and SAMHSA don’t get it– whether the problem is ignorance, or whether there are mutually beneficial relationships between these organizations and RB that encourage the organizations to foster ignorance among
patients and doctors.  I don’t belong to the organizations primarily for this reason– and I blame ASAM and SAMHSA for the current status of addiction treatment as the ‘no science zone’ of modern medicine.

 A few examples of intellectual laziness: 

Example 1:  Physicians who prescribe Suboxone often say that one shouldn’t use buprenorphine ‘because it doesn’t have the opioid blocker and therefore….’ (add whatever here– it causes euphoria, it is addictive, it isn’t safe– any or all of these comments). The statement is partially correct. Generic buprenorphine does not have the opioid blocker naloxone— but naloxone is irrelevant to the actions of Suboxone!

There are TWO opioid blockers in Suboxone, but only one is clinically relevant—the one that is in both Suboxone and generic buprenorphine.  What is the relevant ‘opioid blocker’ that IS
in both Suboxone and generic buprenorphine?  Buprenorphine!   As a partial agonist, buprenorphine has antagonist properties that are responsible for ALL of the effective clinical properties of Suboxone.

Example 2:  Refusing to consider the cost of medication as a factor that determines access to treatment.  Some docs make ‘fear of diversion’ the only factor in determining what to prescribe.  Discussions with hundreds of opioid addicts over the years have convinced me that buprenorphine is rarely a drug of choice.  Rather, it is used by addicts who are sick and tired and want a break from using without withdrawal, or by addicts who have no money or access to agonists.  In such cases, buprenorphine or Suboxone are equally effective– and equally diverted.  When I ask addicts new to treatment about their injecting habits, I often ask whether they injected buprenorphine or Suboxone.  The typical response is either ‘can you do that?’ or ‘why would I do that, since heroin is cheaper?’

In my area, an 8 mg tab of buprenorphine costs as low as $2.33.  This low cost should be part of the equation for choice of medication, just as it is for other illnesses.  Does anyone doubt that there are some people kept from treatment by a price differential of 300%?!  Is it ethical to fear diversion so greatly that treatment is effectively withheld– for a condition with the fatality rate of opioid dependence?!   I’m sure readers know my answer, especially when there are effective ways to reduce diversion, such as close monitoring of prescribed doses, a ‘no replacement’ policy, and drug testing, among others.

Example 3:  There is some question whether the naloxone in Suboxone does anything to reduce diversion. Buprenorphine patients on my forum  who have injected Suboxone in the past have claimed that they did not experience withdrawal from either Suboxone or buprenorphine, consistent with what I would expect from combining a low-affinity antagonist with a high-affinity partial agonist.

Note: Injecting ANYTHING is in essence taking your life in your hands, and I strongly encourage anyone in such a position to seek treatment immediately.   Really—don’t do it.

Example 4:  Insurers generally refuse to cover generic buprenorphine (the generic form of the RB drug Subutex), even though it is much cheaper than Suboxone.  The one time they WILL cover Subutex or buprenorphine is for women who are pregnant or nursing.  The argument is that we shouldn’t expose the fetus/infant to one more drug (naloxone), since that drug isn’t necessary to the actions of Suboxone.  I agree with the argument, and wonder why it is extended only to the fetus?  Why does mom or dad have to be exposed to an extra substance(naloxone) that isn’t necessary to the actions of Suboxone?

I struggle to understand the insurance issue, as I would expect that someone at some major insurer would know enough about pharmacology to save money on Suboxone by favoring generic buprenorphine.

The ultimate of silliness is that the State of Wisconsin requires that people on Medicaid use only Suboxone FILM.  Getting Abilify for a patient is virtually impossible without first using a variety of older, cheaper medications… but the squishy arguments in favor of Suboxone Film push the med up the formulary chain past an alternative that sells at a fraction of the cost.  The film/Medicaid situation is doubly dubious, as we have the arguments for buprenorphine over Suboxone, and the even less-sound argument for Suboxone Film being favored over the tablet.

RB apparently convinced the state that for Medicaid patients, only the film was safe– and that the film should be required instead of the tablet form of Suboxone, placing future generics at a great disadvantage.  It is especially impressive that RB accomplished this feat after selling a million units of the tablets themselves!  I can picture the person making the point:  ‘the tablet is unsafe…. Starting NOW!’

I’m going to write all night if I don’t wrap this up.  To summarize, the Bloomberg article below describes why RB is winning the battle with generics, but the writers of the article, along with most doctors, miss the bigger issue– that misplaced fears, intellectual laziness, and misinformation have protected Suboxone sales from a much greater foe-– generic buprenorphine.  If doctors, states, and insurers ever get their acts together and prescribe according to science, brand name Suboxone profits will go down the toilet faster than the cleaning products made by RB.

The Bloomberg piece:

Reckitt Benckiser Kicks Heroin Tablet Habit With Film: Retail

By Clementine Fletcher

Reckitt Benckiser Group Plc may be kicking its heroin problem.

After losing U.S. patent protection in 2009 for its Suboxone tablet, designed to help heroin users quit, Reckitt Benckiser has said that the entrance of a generic competitor could erode pharmaceutical sales and profit by 80 percent (note by JJ:  What a shame?!  Consider the benefit of such a price reduction for addicts in need of treatment!).

Reckitt Benckiser, which gets most of its revenue from selling home and personal-care products like Lysol cleaners and Durex condoms, has faced calls to sell the business before a generic comes to market. Instead, the London-based company aims to divert the showdown by switching users to a film form of the drug — one whose last patent doesn’t run out until 2025 (note by JJ:  NOW do you see why they made the film?!)

To get people to make the switch, Reckitt Benckiser is thinking more like a consumer company than a pharmaceutical one. It’s drawing on a marketing technique first pioneered by Coca- Cola Co. more than 100 years ago: coupons. By offering up to $45 a month toward a user’s co-payment in the U.S., the company is making the film version, which looks like a Listerine Pocketpak, close to free. That offers patients who get part of the bill subsidized by health insurance little incentive to transfer to a generic pill once it appears on the market.

“They’ve done a good job of making a silk purse out of a not very compelling situation,” said Martin Deboo, an analyst at Investec Securities Ltd. in London.

Reckitt Benckiser’s shares have risen 55 percent in the last five years, outpacing Unilever and Procter & Gamble Co. Under Chief Executive Officer Bart Becht, who stepped down last month, the company more than doubled sales in a decade. The stock has dropped 3.7 percent this year, compared with Unilever’s 4.7 percent gain and P&G’s 1.2 percent gain.

Drugs Growth

The company is due to report third-quarter results tomorrow and will probably say revenue adjusted for purchases and asset sales rose 7 percent at the drugs division, analysts led by Andy Smith at MF Global in London estimate, compared with a 3.9 percent increase for the rest of the business. Profit likely rose 0.9 percent to 430 million pounds, they said.

The film version of Suboxone, introduced in September 2010, accounted for 41 percent of the drug’s U.S. sales by the end of the first half (note by JJ:  Thanks, Wisconsin Badgercare!). That surpassed the company’s own expectations, Becht said on an Aug. 30 conference call arranged by Sanford C. Bernstein. Becht was succeeded by Rakesh Kapoor, a company veteran.

Generic Delay

The film “has been a phenomenal success,” Becht said, according to a transcript of his remarks. “To make the business completely sustainable, we would like to have a share which is clearly much higher than where we are.” He added that the company aims to grow that share every month.

Right now, time is on his side. Teva Pharmaceuticals Industries Ltd., the world’s biggest maker of generics, began the year saying it might launch a Suboxone copy in 2011. Now the company has backed off, saying it no longer expects the product to win regulatory approval this year.

Biodelivery Sciences International Inc., another drugmaker going after Suboxone, said a study comparing its own version of the drug to a placebo failed to show a statistical difference in the treatment of chronic pain. A test in patients addicted to opioids, which include heroin and codeine, is scheduled to begin
later this year. Titan Pharmaceuticals Inc. on Aug. 31 said it’s preparing to seek approval of an upper-arm implant that would deliver buprenorphine, one of
the active ingredients in Suboxone, directly into the bloodstream (note by JJ:  the ONLY active ingredient in Suboxone!)

‘Massive Benefit’

“This delay has been a massive benefit,” said Andrew Wood, an analyst at Sanford C. Bernstein. “With every day that goes by, RB has an extra day to convert users.” Suboxone is either harder-than-expected to copy or generic-drug makers are having second thoughts about targeting addicts, according to Bernstein.

About 1 million people in the U.S. are addicted to heroin, the National Institute on Drug Abuse estimates. As many as 325,000 people use Suboxone to quit the drug or painkillers, says Pablo Zuanic, an analyst at Liberum Capital in London.

The medicine combines buprenorphine, a painkiller derived from the opium poppy that shares some of its properties, with naloxone, a chemical that blunts
withdrawal symptoms (note by JJ:  This is simply WRONG.  BLATANTLY WRONG.  Really–  an opioid antagonist BLUNTING withdrawal symptoms?  Shame on the writers!). The film sells for about $4.63 to $8.23 a dose at Walgreens stores, according to Liberum, depending on its strength and pack size. That means the strongest dose costs about $247 a month.  (note by JJ—a pharmacy near my practice sells generic buprenorphine dissolvable tabs, 8 mg, for $2.33 per tablet—a medication that works EXACTLY the same way IF NOT INJECTED INTRAVENOUSLY)

More than half of people on Suboxone use private insurance with co-pay, Zuanic says. Reckitt Benckiser offers $45 towards co-pay for the film, he said, meaning an insured patient who’d contribute $50 to the cost of the drug may end up spending $5.

‘Near Zero’

“The actual cash cost for some patients buying the film with private insurance could be near zero,” Zuanic said in a note to clients this month. (note by
JJ:  but we are all paying the cost in higher insurance premiums, and some insurers, notably Humana, have draconian policies that stop covering—forcing instant withdrawal- if a patient receives a prescription for a sleep medication such as Ambien, so many people are left paying cash).

Meantime, Suboxone is only becoming more important to Reckitt Benckiser. The drugs division, whose sales grew five times as quickly as the main business last year, accounted for almost 9 percent of sales and 24 percent of profit, up from 7.6 percent and 20 percent in 2009. Sales at the unit will probably rise 12 percent to 829 million pounds ($1.3 billion) this year, according Nomura International Plc estimates.

The maker of French’s mustard is even considering making an injectable Suboxone and developing new products for cocaine, alcohol and cannabis addicts.
The plan has met skepticism.

“We’re quite a long way from having any visibility on these products,” said Julian Hardwick, an analyst at Royal Bank of Scotland Group Plc in London. “Are they products that will work? Which will get approval?”

Prescription drugs are perceived as a bit of a misfit in the home of Vanish stain removers and Finish dishwasher tablets.

Misfit

“Reckitt Benckiser is basically a home and personal-care company with over-the-counter pharmaceuticals,” said Carl Short, an analyst at Standard & Poor’s in London. The drugs unit is “always going to be something that looks like it doesn’t fit with the rest.”

Reckitt Benckiser may look at selling the unit, which Becht himself has said is “not the No. 1 strategic part” of the company, once a generic form of Suboxone reaches pharmacy shelves, analysts said. (note by JJ:  i.e. after all of the profit has been wrung from suffering addicts).  But the company’s marketing savvy, coupled with delays in the launch of a generic, are giving Kapoor time to settle into his new job.

“This is a big job and he is coming in after someone’s done it for some considerable time and very well,” said Julian Chillingworth, who helps manage about 16 billion pounds in shares at Rathbone Brothers Plc, including Reckitt stock. “You wouldn’t want to come in as a CEO into a very successful business and start selling things off on the cheap.”

Not Time

Analyst valuations range from 2 billion pounds to 6.3 billion pounds, according to four estimates compiled by Bloomberg News. Estimates diverge because it’s hard to value the business without knowing how Suboxone sales will resist the generic challenge and whether the shift to film can counter some of that impact.

“Until you get generic competition for the tablet, I think it’s unlikely that prospective buyers would give you the full value for the business,” said Hardwick of RBS. “Now is not the time to sell.”

–With assistance from Naomi Kresge in Berlin. Editors: Celeste Perri, Marthe Fourcade.