Something New: Tianeptine

 

 

One of my doctor friends called me to ask if I’d seen any patients addicted to tianeptine. No, I had not. This was a new one for me, so I did some internet research for my readers.

Tianeptine is a medication used to treat depression, though some sources say it can be used for asthma and irritable bowel syndrome. Though structurally similar to tricyclic antidepressants, it exerts its action in a different way, via glutamate receptors. Other antidepressants are thought to work because they increase serotonin and norepinephrine levels, so tianeptine is novel in this sense.

Scientists know depression causes structural and functional changes in the brain, and some articles about tianeptine say this medication can reverse some of the stress-induced changes seen in depressed brains. We don’t fully understand all aspects of neurotransmitters and mood, and this medication shows us that serotonin and norepinephrine are not the only determiners of mood. [1, 2]

It’s an interesting medication, but not available in the U.S., Canada, or the United Kingdom. It is sold in Europe under the brand names Coaxil and Stablon. It appears to be more toxic to the liver than traditional antidepressants. And of course, if you Google tianeptine, you will see websites offering to sell it, with the fine of print of “not for human consumption,” with a wink and a nod, to protect the sellers, I assume. Mostly sites sell it in a powder form.

But what about this medication’s addictive potential? Why would people take it compulsively?

When I want to know how people are using various drugs, I go to several websites, including erowid, bluelight, and drugs-forum (www.erowid.org , www.bluelight.org , drugs-forum.com) On these sites, people record their experiences with various medications used for euphoria, and occasionally for other reasons too.

On these sites, people described a euphoria similar to opioids, though the described dose was usually far in excess of the recommended 12.5mg three times daily. One person took 500mg and described euphoria. Other people mixed it with other drugs, so it’s hard to know what effect the tianeptine had. Other people described a difficult withdrawal from tianeptine.

Kesa et. al., 2007, says tianeptine has some stimulating activity at the mu opioid receptors, thought it has a low affinity for those receptors. Apparently it takes high doses to produce euphoria, moderated through those opioid receptors.

In the Annals of Internal Medicine, 2003, Leterme et al describe five cases of tianeptine abuse. Withdrawal was said to be difficult, due mostly to anxiety.

Bence et al, Pediatrics, 2016, published a case study about a pregnant woman who was taking tianeptine, more than 650mg per day. Unexpectedly, her newborn had a withdrawal syndrome indistinguishable from opioid withdrawal, which was when her doctors discovered her tianeptine use. The baby was treated with morphine, and no mention is made of treatment for the mother until her next pregnancy, when she was admitted to a residential detox unit in her seventh month of pregnancy. Other than low birth weight, her second infant was delivered at full term with no withdrawal. Both children appear to have normal development.

From the collective experiences I read, it seems tianeptine is a weak opioid agonist, but at high doses gives an opioid effect. It sounds like people describe a typical opioid addiction after using these high doses daily for more than a few weeks. They described classic signs and symptoms of opioid withdrawal.

The doctor friend who first called me about this drug worked at an opioid treatment program. The tianeptine-consuming patient he was seeing wanted to be started on buprenorphine or methadone to treat tianeptine withdrawal. I told my friend I didn’t know enough about the drug to feel it was OK to try buprenorphine or methadone.

Since then I’ve done more research, and I suspect buprenorphine or methadone could help treat these patients, but I didn’t see any studies about their use for this addiction.

Particularly with methadone, if we prescribe it to people without a clear indication, they could later get nasty and angry about being started on methadone, a difficult drug to taper off of.

I’d like a need for a study of tianeptine-addicted patients, to see if using classic opioid use disorder treatment medications work for these patients.

Tianeptine could become the latest fad drug. Some drugs fade in and out of popularity, like the latest style of dress or music. I think this one could be a harmful fad, and we have no research about treatment.

1. Kasper et. al., “Neurobiological and clinical effects of the antidepressant tianeptine,” CNS Drugs, 2008;22(1);15-26.
2. McEwen et. al., “The neurobiological properties of Tianeptine (Stablon): From hypothesis to glutamatergic modulation,” Molecular Psychiatry 2010 March;15(3): 237-249.

Purdue Pharma Settles Kentucky Lawsuit

 

 

 

 

 

 
Since 2007, Kentucky has been litigating a case against Purdue Pharma, the manufacturer of OxyContin. Kentucky was the only state to opt out of a prior settlement offered by Purdue Pharma in 2007, preferring to litigate separately against the company, due to the devastation that state has endured from the opioid addiction epidemic.

Kentucky was offered $500,000 to settle with Purdue in 2007 lawsuit. Last month Purdue agreed to pay Kentucky $24 million to settle the case. This money is earmarked to pay for addiction treatment and prevention.

This does sound like a large sum of money, but it’s a drop in the sea of money Purdue has raked in from sales of OxyContin.

The turning point in the case may have been when Purdue Pharma lawyers were unable to get the case moved out of Pike County, Kentucky. Those lawyers probably knew county residents were likely to be bitter about the drug company’s antics, since the county’s overdose death rate is still extremely high.

In 2014, 51 people out of every 100,000 died from drug overdose, according to data on the state’s website (http://odcp.ky.gov/Pages/Overdose-Fatality-Report.aspx ) Of course, OxyContin is not the only reason for the overdose deaths, but citizens selected as jurors may have jumped at the chance to blame someone. Who better than a drug company? The company lawyers were facing the potential for an astronomically high judgement from jurors with the case heard in Pike County.

The drug company lawyers decided to play it safe, and settled for 24 million dollars. Purdue Pharma and its officials did not admit any guilt in this settlement.

This isn’t Purdue Pharma’s first legal loss. As you will recall from my July 8, 2015 blog post, Virginia won an award of $634 million from Purdue and from its top three executives after they pleaded guilty in May of 2007 to misleading the public about the drug’s safety. It was one of the largest awards against any drug company for illegal marketing…though Purdue made 2.8 billion dollars in sales from the time of its release in 1996 until 2001. How much the company made since 2001 is anyone’s guess but it has to be in the billions.

When I started working at my first opioid treatment program (OTP) in 2001, the only drug I heard about was OxyContin. The majority of the patients entering treatment used only Oxy’s, as they called them. Patients told me how easy it was to remove the time release coating, then crush the pills to snort or inject. All during this time, Purdue Pharma was touting their product as abuse-resistant.

Needless to say, their claims rang hollow in my ears, and the ears of other doctors treating addiction

Eventually, the U.S. General Accounting Office asked for a report about the promotion of OxyContin by Purdue Pharma. By 2002, prescriptions written for non-cancer pain accounted for 85% of the OxyContin sold, despite a lack of data regarding the safety for this practice. By 2003, primary care doctors, with little or no training in the treatment of chronic non-cancer pain, prescribed about half of all OxyContin prescriptions written in this country. By 2003, the FDA cited Purdue Pharma twice for using misleading information in its promotional advertisements to doctors. [1, 2] Purdue Pharma also trained its sales representatives to make deceptive statements during OxyContin’s marketing to doctors. [3]

Testifying before Congress in 2002, a Purdue Pharma representative said the company was working of re-formulating OxyContin, to make it harder to use intravenously. This representative claimed it would take several years to achieve this re-formulation. The re-formulated OxyContin was finally approved by the FDA in 2010, eight years later. Currently, this medication forms a viscous hydrogel if someone attempts to inject or snort the medication. It isn’t abuse-proof; probably no opioid will ever be so, but it is much more abuse-deterrent than the original.

Did Purdue Pharma drag their feet in this re-formulation? Experts like Paul Caplan, executive director for risk management for the drug company, said there were issues about the safety of incorporating naloxone into the pill to make it less desirable to intravenous addicts. He also pointed out that some delay in approval was due to the FDA.

For comparison, Sterling Pharmaceutical, when it became widely known patients were abusing their pain medication Talwin, re-formulated within a year, adding naloxone to the medication and reducing its desirability on the black market. Since this was in the 1980’s, I would assume there was less technology to help back then, compared to 2002.

I’ll let readers draw their own conclusions.

No one in the Sackler family, owners of Purdue Pharma, has been criminally charged with any crimes.

1. General Accounting Office OxyContin Abuse and Diversion report GAO-04-110, 2003.
2. 2. United States Senate. Congressional hearing of the Committee on Health, Education, Labor, and Pensions, on Examining the Effects of the Painkiller OxyContin, 107th Congress, Second Session, February, 2002.
3. 3. Washington Times, “Company Admits Painkiller Deceit,” May 11, 2007, accessed online at http://washingtontimes. com/news/2007/may/10/20070510-103237-4952r/prinnt/ on 12/18/2008.

Diversion of Prescribed Medications

 

 

 

I hope all my readers had a great holiday.

I followed my own advice about avoiding burnout and took eleven days off work. That’s the most days in a row that I’ve taken off for many years, and it was great. I went on a short but fun cruise of the Bahamas, during which I rested, spent time with family, read, ate great food, and tried to tan. (I know the sun is not a friend to the skin of pale people, but I just wanted a tiny bit of color. Instead, I think I bleached out to a lighter shade of pale.)

I also took a vacation from blog-writing, so I looked at previous blog entries I’ve written but never posted, to have something for my blog this week.

Toward the end of last year, I was intrigued by an article in my local newspaper. The newspaper published a story about the arrests of thirty or forty local residents on drug-related charges on the front page. In this article, a representative of the county’s Sherriff’s office narcotics unit said he estimated that ninety percent of people arrested for illegally selling prescription pain pills got them from doctors outside the county.

That seemed odd to me. My perception, shaped as it is by my work in the county’s only opioid addiction treatment program, has been just the opposite – that physicians in the area prescribe a great deal of the illegally sold controlled substance pills.

Indeed, I would be idealistic if I assumed that none of my own patients have ever sold their buprenorphine take home doses, despite my best efforts to prevent this.

Curious, I asked our state’s Injury and Violence Prevention branch of the NC Division of Public Health about how our county compares with other counties, in number of prescriptions written per capita. This last part is important, because more heavily populated counties have higher numbers of prescriptions, but only because there are more people living in the county.

One of the epidemiologists wrote me the next day, and said in 2014, there were 280 controlled substance prescriptions written for every 100 people living in my county. This compared with a state-wide rate of 201 controlled prescriptions per 100 people. He said that while our county was in the top 20 counties for number of controlled substances prescribed per capita, it was not number one in the state.

Since opioid treatment programs do not report any data to state prescription monitoring programs, none of my prescribing data would be captured in this information, with the exception of a dozen office-based buprenorphine patients I see in this county. Patients in office-based addiction practices do have their prescriptions reported to the state’s prescription monitoring website.

Anyway, back to my county’s prescribing rate…The prescribing rate quoted above is for all controlled substances, not only opioids. It includes opioid pain pills, benzodiazepines (Xanax, Valium, Klonopin), potentially addicting sleeping pills (zolpidem, or Ambien), and stimulants (amphetamines like Adderall, also Ritalin, Provigil, Nuvigil).

So the county has one of the highest prescribing rates of the state. That doesn’t necessarily mean any of the prescribed medications are diverted to the black market. However, past studies do show that higher prescribing rates are associated with higher diversion rates. But perhaps this county is different, as the sheriff’s office stated.

Furthermore, mere numbers can’t tell us if doctors are prescribing appropriately or not. Perhaps people living in my county have a higher-than-normal need for opioids, benzodiazepines, sleeping pills, and stimulants…

Food for thought, which I haven’t completely digested yet.

 

Safe Storage of Medication

Please please PLEASE, patients on opioid treatment programs, store your medication safely.

Of course, the vast majority of patients in opioid treatment programs, dosing with methadone or buprenorphine, store their medication safely and never have any medication storage issues.
The public never hears about these people, who calmly go about their daily lives as productive members of society.

But one incident of a pediatric overdose on medication prescribed for a patient in an opioid treatment program threatens the reputations of treatment programs and their patients. Each time a pediatric overdose occurs due to improper storage of medication, people who oppose opioid treatment programs get new ammunition to say patients should never be allowed any take home doses.

By the way, this information about safe storage of medication applies to opioids prescribed for pain and other controlled substances. Anyone prescribed any medication should store it safely.

So let’s review what should be done to keep medication safe and out of the hands of people for whom it isn’t prescribed, including children.
1. Store your medication in a lock box that is locked. It does no good to have a lock box if you leave the key in the lock. The key must be stored in another place. Otherwise, it’s just a box.
2. Unless you’ve been directed to split your dose, take your medication all at one time. The seal on the bottle is there for a reason. Once the seal is broken, all of the medication is meant to be taken at once. This gives less chance for part of your dose to be ingested by accident or on purpose by another person.
I know patients like to take a little bit of their dose at a time, multiple times during the day. That’s a pattern leftover from active addiction with short-acting opioids. Each time an addict takes something, it gives a feeling of benefit.
But the unique pharmacology of both methadone and buprenorphine means patients can take the entire dose once daily and feel the same as if they take multiple doses. In fact, with buprenorphine, some people in the early studies did OK with every other day dosing.
Some patients are fast metabolizers of methadone and have to have split dosing. We can determine who needs split dosing with careful dose titration and peak and trough blood levels when needed. Then the dose can be split precisely, in individual bottles.
3. Plan for the unexpected. People who don’t have children living in the home often get complacent about medication storage. But what about when friends or family visit? You may not remember to remove your medication bottles or unlocked box from plain site. It’s best to stay in the habit of storing your medication, in a locked box, out of sight and reach.
4. Children are driven by curiosity. If medication is stored where kids can get into it, overdose is more likely. Don’t underestimate a child’s capacity to get into things.
5. Be careful with your empty bottles. Patients are instructed to drink their methadone dose, and then put a little water in it to rinse any residual and drink that too. It’s possible a small amount of medication could still be in the bottle. That’s one reason we ask you to store empties in the lock box, too.
6. Don’t let your child be any part of your daily medication administration. Kids naturally like to imitate their parents. Take doses of all medications in private, out of their view. Of course, don’t let your kids play with or handle your empty bottles.
7. Your take home bottles should spend all their time in the lock box. That’s their home. That’s where they live. The only time they leave the lock box is for the few moments it takes to consume your day’s dose, and afterward the bottle goes right back in to the lockbox. It makes me nuts to see patients transporting empty bottles in their coat pockets and purses.
8. Don’t tell other people what medications you are on. Addicts in active addiction can do desperate things like break into your house and steal medication.
9. If your medication does get stolen, call the police right away. That way, if someone overdoses and dies from the medication dispensed to you, you have a record of doing all you can to report that it’s fallen into the wrong hands.
10. If the worse thing happens and a child or other person takes your medication, call 911 right away. You will lose take home medications, but it’s still the right thing to do. Remember that methadone and buprenorphine cause a peak effect anywhere from two to five hours later. Just because you don’t see any problems in the child for the first hour does NOT mean the child is safe. Don’t take any chances.
11. If you or a member of your household takes opioids either by prescription or illicitly, get a naloxone kit. Keep it in your house so that if an overdose happens, it can be reversed quickly. You can read more about naloxone kits on my blog post on April 27, 2013. You still need to call 911, because naloxone’s effects wear off much faster than methadone or buprenorphine.

Lastly, and it’s self-serving for me to say so, but store your take home doses safely for your doctor’s sake. That take home dose with my name on it is a vote of confidence that you will be careful about how you store your medication. It’s always a judgment call, and sometimes I get it wrong. I am affected when bad things happen with diverted or improperly stored take home doses that I’ve prescribed. Plus, I become more cautious when considering patients for take home doses. Medication-assisted patients complain about overly restrictive regulations around take home doses of medication, particularly methadone, but cases of pediatric overdose make those regulations necessary.

However, I try to remember that the vast majority of medication-assisted patients store their medication correctly and never have any incidents of accidental pediatric ingestion or any other misuse of medication. They’re responsible and careful. For every episode of carelessness leading to a pediatric overdose, hundreds of patients never have an episode with improper storage. It’s not fair to paint them with the same brush.

New Opioids

I’ve blogged about states that have passed new laws addressing the prescribing of opioids, but the manufacturers of prescription opioids medications also have made changes to help reduce the potential for medication misuse. Of course, opioids will never be misuse-proof, but at least it’s a little harder to misuse some of the newer ones.

Oxecta is a new immediate-release brand of the drug oxycodone. It’s formulated so that it breaks into chunks when crushed, instead of a powder. When it’s mixed with water, it forms a gel so that it can’t be injected. This pill contains sodium laurel sulfate, a substance that irritates the nose if snorted.

Lazanda is a new delivery form of a very potent opioid, fentanyl. This brand is designed to be used as a nasal spray, which I would expect to be very addictive. The preparation itself has no anti-abuse features, but in order to distribute, dispense, prescribe, or be prescribed this medication, parties have to sign an agreement and be enrolled with the drug company. This extra scrutiny is hoped to deter diversion by distributor, pharmacy, doctor, or patient. Physicians must take a training program specific for this brand, and be enrolled with the drug company as a prescriber, or pharmacies can’t dispense to the patient.

Patients also need to complete a patient-prescriber agreement. Many people (like me) think doctors aren’t likely to jump through these extra hoops to prescribe this particular brand, when other brands of the same medication are already on the market, though not in the form of nasal spray.

Remoxy, another brand of oxycodone, hasn’t yet been FDA approved. Supposedly, it’s resistant to injection or snorting, and also has been formulated to be resistant to alcohol extraction.

Drug companies are now required by the FDA to have plans to evaluate and mitigate the risks associated with the opioid drugs they manufacture, particularly if they make sustained release or long-acting opioid preparations. This cooperation by drug manufacturers is a necessary part of turning the tide of opioid addiction in this country.

Last year, Purdue Pharma re-formulated OxyContin, making it more difficult to crush to snort or inject.  I noticed a sudden drop-off in patients entering treatment for pain pill addiction who said OxyContin was their drug of choice. During the years 2002 through 2007, nearly all of the opioid addicts I admitted to treatment said OxyContin was their preferred drug. It became obvious that the re-formulation made a big difference.

Addicts can and will still abuse these medications orally to get high, but the new formulations really do reduce abuse by making pills less likely to be snorted or injected.

Doctors Are Poorly Trained About Addiction and Recovery

Addiction? What addiction?

Most medical schools and residency programs place little emphasis on educating future physicians about addiction. A survey conducted by the Center on Addiction and Substance Abuse at Columbia University (CASA) revealed that physicians are poorly trained to recognize and treat addictive disorders. (1)

CASA surveyed nine-hundred and seventy-nine U.S. physicians, from all age groups, practice settings, and specialties. Only nineteen percent of these physicians said they had been trained in medical school to identify diversion of prescribed drugs. Diversion means that the drug was not taken by the patient for whom it was prescribed. Almost forty percent had been trained to identify prescription drug abuse or addiction, but of those, most received only a few hours of training during four years of medical school. More shocking, only fifty-five percent of the surveyed doctors said they were taught how to prescribe controlled drugs. Of those, most had less than a few hours of training. This survey indicates that medical schools need to critically evaluate their teaching priorities.  

Distressingly, my own experience mirrors this study’s findings. My medical school, Ohio State University, did a better job than most. We had a classroom section about alcoholism, and were asked to go to an Alcoholics Anonymous meeting, to become familiar with how meetings work. But I don’t remember any instruction about how to prescribe controlled substances or how to identify drug diversion.

Is it possible that I’ve forgotten I had such a course? Well, yes. But if I can still remember the tediously boring Krebs cycle, then surely I would have remembered something juicier and more practical, like how to prescribe potentially addicting drugs. Similarly, less than half of the surveyed doctors recalled any training in medical school in the management of pain, and of those that did, most had less than a few hours of training.

Residency training programs did a little better. Of the surveyed doctors, thirty-nine percent received training on how to identify drug diversion, and sixty-one percent received training on identifying prescription drug addiction. Seventy percent of the doctors surveyed said they received instruction on how to prescribe controlled substances. (1)

This last finding is appalling, because it means that thirty percent of doctors received no training on how to prescribe controlled substances in their residency programs.  Could it be true that nearly a third of the doctors leaving residency – last stop for most doctors before being loosed upon the populace to practice medicine with little to no oversight – had no training on how to prescribe these potentially dangerous drugs? Sixty-two percent leaving residency had training on pain management. This means the remaining thirty-eight percent had no training on the treatment of pain.

Could it be that many of these physicians were in residencies or specialties that had no need to prescribe such drugs? No. The participating doctors were in family practice, internal medicine, OB/GYN, psychiatry, and orthopedic surgery. The study included physicians of all ages (fifty-three percent were under age fifty), all races (though a majority at seventy-five percent were white, three other races were represented), and all types of locations (thirty-seven percent urban, thirty percent suburban, with the remainder small towns or rural areas). This study reveals a hard truth: medical training programs in the U.S. are doing a poor job of teaching future doctors about two diseases that causes much disability and suffering: pain and addiction. (1)

 I remember how poorly we treated patients addicted to prescription medications when I was in my Internal Medicine residency program. By the time we identified a person as addicted to opioids or benzodiazepines, their disease was fairly well established. It didn’t take a genius to detect addiction. They were the patients with thick charts, in the emergency room frequently, loudly proclaiming their pain and demanding to be medicated. Overall, the residents were angry and disgusted with such people, and treated them with thinly veiled contempt. We regarded them more as criminals than patients. We mimicked the attitudes of our attending physicians. Sadly, I did no better than the rest of my group, and often made jokes at the expense of patients who were suffering in a way and to a degree I was unable to perceive. I had a tightly closed mind and made assumptions that these were bad people, wasting my time.

Heroin addicts were not well treated. I recall a discussion with our attending physician concerning an intravenous heroin user, re-admitted to the hospital. Six months earlier, he was hospitalized for treatment of endocarditis (infected heart valve). Ultimately his aortic heart valve was removed and replaced with a mechanical valve. He recovered and left the hospital, but returned several months later, with an infected mechanical valve, because he had continued to inject heroin. We discussed the ethics of refusing to replace the valve a second time, because we felt it was futile.

I didn’t know any better at the time. We could have started him on methadone in the hospital, stabilized his cravings, and then referred him to the methadone clinic when he left the hospital. Instead, I think we had a social worker ask him if he wanted to go away somewhere for treatment, he said no, and that was the end of that. Small wonder he continued to use heroin.

At a minimum, the attending physician should have known that addiction is a disease, not a moral failing, and that it is treatable. The attending physician should have known how to treat heroin addiction, and how to convey this information to the residents he taught. Instead, we were debating whether to treat a man whose care we had mismanaged. Fortunately, he did get a second heart valve and was able to leave the hospital. I have no further knowledge of his outcome.

 Despite having relatively little training in indentifying and treating prescription pill addiction, physicians tend to be overly confident in their abilities to detect such addictions. CASA found that eighty percent of the surveyed physicians felt they were qualified to identify both drug abuse and addiction. However, in a 1998 CASA study, Under the Rug: Substance Abuse and the Mature Woman, physicians were given a case history of a 68 year old woman, with symptoms of prescription drug addiction. Only one percent of the surveyed physicians presented substance abuse as a possible diagnosis.  In a similar study, when presented with a case history suggestive of an addictive disorder, only six percent of primary care physicians listed substance abuse as a possible diagnosis. (2)

Besides being poorly educated about treatments for patients with addiction, most doctors aren’t comfortable having frank discussions about a patient’s drug misuse or addiction. Most physicians fear they will provoke anger or shame in their patients. Physicians may feel disgust with addicted patients and find them unpleasant, demanding, or even frightening. Conversely, doctors can feel too embarrassed to ask seemingly “nice” people about addiction. In a CASA study titled, Missed Opportunity, forty-seven percent of physicians in primary care said it was difficult to discuss prescription drug addiction and abuse with their patients, for whom they had prescribed such drugs. (2).

From this data, it’s clear physicians are poorly educated about the disease of addiction at the level of medical school and residency. Even when they do diagnose addiction, are they aware of the treatment facilities in their area? Patients should be referred to treatment centers who can manage their addictions. If patients are addicted to opioids, medications like methadone and buprenorphine can be a tremendous help.

1. Missed Opportunity: A National Survey of Primary Care Physicians and Patients on Substance Abuse, Center on Addiction and Substance Abuse at Columbia University, April 2000. Also available online at http://www.casacolumbia.org

2. Under the Rug: Substance Abuse and the Mature Woman, Center on Addiction and

Substance Abuse at Columbia University, 1998. Available online at http://www.casacolumbia.org

Description of Methadone Patients

The following is an excerpt from Chapter 2 of my book, titled, “Pain Pill Addiction: Prescription for Hope.” In this chapter I’m describing the patients I saw at methadone clinics where I worked in the years 2001 through 2009.

 I was surprised how casually people shared controlled substances with one another. As a physician, it seems like a big deal to me if somebody takes a schedule II or schedule III controlled substance that wasn’t prescribed for them, but the addicts I interviewed swapped these pills with little apprehension or trepidation. Taking pain pills to get through the day’s work seemed to have become part of the culture in some areas. Sharing these pills with friends and family members who had pain was acceptable to people in these communities.

In the past, most of the public service announcements and other efforts to prevent and reduce drug use focused on street drugs. Many people seemed to think this meant marijuana, cocaine, methamphetamine, and heroin. The patients I saw didn’t consider prescription pills bought on the street as street drugs. They saw this as a completely different thing, and occasionally spoke derisively about addicts using “hard drugs.” Most addicts didn’t understand the power of the drugs they were taking.

 Some opioid addicts came for help as couples. One of them, through the closeness of romance, transmitted the addiction like an infectious disease to their partner. Most were boyfriend/girlfriend, but some were married. The non-addicted partner’s motives to begin using drugs seemed to be mixed. Some started using out of curiosity, but others started using drugs to please their partner. I was disturbed to see that some of the women accepted the inevitability of addiction for themselves as the cost of being in a relationship with an addicted boyfriend. Often, addicted couples socialized with other addicted couples, as if opioid addiction bound them like a common fondness for bowling or dancing. Addiction became a bizarre thread, woven through the fabric of social networks.

 We saw extended family networks in treatment for pain pill addiction at the methadone clinics. One addicted member of a family came for help, and after their life improved, the rest of the addicted family came for treatment too. It was common to have a husband and wife both in treatment, and perhaps two generations of family members, including aunts, uncles, and cousins. Many addicts who entered treatment saw people they knew from the addicted culture of their area, and sometimes old disputes would be reignite, requiring action from clinic staff. Sometimes ex-spouses and ex-lovers would have to be assigned different hours to dose at the clinic, to prevent conflict.

 When the non-profit methadone clinic where I worked began accepting Medicaid as payment for treatment, we immediately saw much sicker people. Over all, Medicaid patients have more mental and physical health issues. Co-existing mental health issues make addiction more difficult to treat, and these patients were at higher risk for adverse effects of methadone. However, data does show that these sicker patients can benefit the most from treatment.

 When I started to work for a for-profit clinic, I saw a slightly different patient population. I saw more middle class patients, with pink and white-collar jobs. Occasionally, we treated business professionals. The daily cost of methadone was actually a little cheaper at the for-profit clinic, at three hundred dollars per month, as compared to the non-profit clinic, at three hundred and thirty dollars per month. However, the for-profit clinic charged a seventy dollar one-time admission fee, to cover the costs of blood tests for hepatitis, liver and kidney function, blood electrolytes, and a screening test for syphilis. The non-profit clinic had no admission fee, but only did blood testing for syphilis. I believe the seventy dollars entry fee was enough to prevent admission of poorer patients, who had a difficult enough time paying eleven dollars for their first and all subsequent days.

The patients at the for-profit clinic seemed a little more stable. Maybe they hadn’t progressed as far into their disease of addiction, or maybe they had better social support for their recovery. This clinic didn’t accept Medicaid, which discouraged sicker patients with this type of health coverage. Both clinics were reaching opioid addicts; they just served slightly different populations of addicts. The non-profit clinic accepted sicker patients, which is noble, but it made for a more chaotic clinic setting. This was compounded by a management style that was, in a few of their eight clinics, more relaxed.

 For the seven years I worked for a non-profit opioid treatment center, I watched it expand from one main city clinic, and one satellite in a nearby small town, to eight separate clinic sites. The treatment center did this because they began to have large numbers of patients who drove long distances for treatment. This indicated a need for a clinic to be located in the areas where these patients lived. Most of this expansion occurred over the years 2002 through 2006.

 Three of these clinics were located in somewhat suburban areas, within a forty-five minute drive from the main clinic, located in a large Southern city. The other four clinics were in small towns drawing patients from mostly rural areas. One clinic was located in a small mountain town that was home to a modest-sized college. Nearly all of the heroin addicts I saw in the rural clinics were students at that college. But by 2008, we began to see more rural heroin addicts, who had switched from prescription pain pills to heroin, due to the rising costs of pills.

Within a few years, clinics near the foothills of the Blue Ridge Mountains of Western North Carolina were swamped with opioid addicts requesting admission to the methadone clinics. These clinics soon had many more patients than the urban clinic.

I saw racial dissimilarities at the clinic sites. In the city, we admitted a fair number of African Americans and other minorities to our program. Most of them weren’t using pain pills, but heroin. I don’t know why this was the case. Perhaps minorities didn’t have doctors as eager to prescribe opioids for their chronic pain conditions, or perhaps they didn’t go to doctors for their pain as frequently as whites. If they were addicted to pain pills, maybe distrust kept them from entering the methadone clinic. In the rural clinics, I could count the number of African-American patients on one hand. They were definitely underrepresented. The minorities we did treat responded to treatment just as well.

A recent study of physicians’ prescribing habits suggested a disturbing possibility for the racial differences I saw in opioid addiction. (1) This article showed statistically significant differences in the rate of opioid prescriptions for whites, compared to non-whites, in the emergency department setting. Despite an overall rise in rates of the prescription of opioid pain medication in the emergency department setting between 1993 and 2005, whites still received opioid prescriptions more frequently than did Black, Asian, or Hispanic races, for pain from the same medical conditions. In thirty-one percent of emergency room visits for painful conditions, whites received opioids, compared to only twenty-three percent of visits by Blacks, twenty-eight percent for Asians, and twenty-four percent for Hispanic patients. These patients were seen for the same painful medical condition. The prescribing differences were even more pronounced as the intensity of the pain increased, and were most pronounced for the conditions of back pain, headache, and abdominal pain. Blacks had the lowest rates of receiving opioid prescriptions of all races.

This study could have been influenced by other factors. For example, perhaps non-whites request opioid medications at a lower rate than whites. Even so, given the known disparities in health care for whites, versus non-whites in other areas of medicine, it would appear patient ethnicity influences physicians’ prescribing habits for opioids. The disparities and relative physician reluctance to prescribe opioids for minorities may reduce their risk of developing opioid addiction, though at the unacceptably high cost of under treatment of pain.

Interestingly, we had pockets of Asian patients in several clinics. We admitted one member of the Asian community into treatment, and after they improved, began to see other addicted members of their extended family arrive at the clinic for treatment. Usually the Asian patients either smoked opium or dissolved it in hot water to make a tea and drank it. When I tried to inquire how much they were using each day, in order to try to quantify their tolerance, the patient would put his or her thumb about a centimeter from the end of the little finger and essentially say, “this much.” Having no idea of the purity of their opium, this gave me no meaningful idea of their tolerance, so we started with cautiously low doses.

One middle aged patient from the Hmong tribe presented to the clinic and when I asked when and why he started opioid use, in broken English and with difficulty, he told me he had lost eight children during the Vietnam War, and was injured himself. After the pain from his injury had resolved, he still felt pain from the loss of his family and he decided to continue the use of opium to treat the pain of his heart, as he worded it. I thought about how similar his history was to the patients of the U.S. and how they often started using opioids and other drugs to dull the pain of significant loss and sorrow. I thought about how people of differing ethnicities are similar, when dealing with addiction, pain, and grief.

1. Pletcher M MD, MPH, Kertesz, MD, MS, et. al., “Trends in Opioid Prescribing by Race/Ethnicity for Patients Seeking Care in US Emergency Departments,” Journal of the American Medical Association, 2008 vol. 299 (1) pp 70-78.

The New OxyContin Formulation

Over the last three weeks, at least five of the opioid addicts I’ve admitted to treatment said they wanted help because they couldn’t abuse the new form of OxyContin.

 And I say: Hallelujah! It’s about time!!

 This new tablet, approved by the FDA in April of this year, appeared recently on the black markets of this area, replacing the older, more easily abused OxyContin. The new tablet is bioequivalent to the older tablet, meaning the same amount of oxycodone, the active ingredient, is available to the body when swallowed whole, as it’s meant to be. In other words, the same amount of pain reliever is given to the body. However, it’s more difficult to crush for the purpose of snorting or injecting, because it turns into a gummy ball.

Purdue Pharma, the drug company that makes OxyContin, admits this new formulation isn’t abuse-proof, but hopes it will be more resistant to abuse.

The patients I’ve talked to say the new tablet is a big disappointment. One patient, who usually chews her pill to get a faster high, said it was like trying to chew a jelly bean. Other patients said they could crush the tablet, but got a kind of gelatinous mess that was impossible to snort or inject.

 For pain relief, the opioid in OxyContin lasts much longer when it’s taken as directed and swallowed whole. Addicts prefer to crush and snort or inject because of the quick high they feel with this route of administration. But when used in this way, it leaves the body faster, and the addict usually needs to find more opioid within six to eight hours to avoid withdrawal.

Before I applaud Purdue Pharma for this change, my cynical mind asks a few questions: Why didn’t the company make this change earlier?

In 2002, a Purdue Pharma representative testified before congress, saying that the company was working on a re-formulation of OxyContin, to make it harder to use intravenously. This representative said they expected to have the re-formulated pill on the market within a few years. (1)  But it took eight more years.

Sterling, the drug company that makes Talwin, another opioid pain medication, was able to re-formulate their drug within a few years when they discovered it was being abused frequently. This was in the 1980s, when, presumably, medication technology wasn’t as advanced as today. Sterling added naloxone, an opioid blocker that’s inactive when taken by mouth, but puts an addict into withdrawal when it’s crushed and injected. It worked great. Talwin isn’t a commonly abused drug.

 I’m assuming that Purdue Pharma holds the patent for this new formulation that makes their tablet gummy when crushed. Purdue probably teaches its sales staff to market the new OxyContin as a safer option than older versions, perhaps available in cheaper generics. So did they wait to re-formulate until their patent was ready to expire? I don’t know, but time will tell.

At any rate, this drug is now just a little bit safer, for now. People with addictions are often clever and creative. I won’t be surprised if soon there’s a way to defeat this new technology.

Just think what addicted people could do, if they directed their talent and intelligence in ways that would help and not hurt them. There would be no stopping them.

1. United States Senate. Congressional hearing of the Committee on Health, Education, Labor, and Pensions, on Examining the Effects of the Painkiller OxyContin, 107^th Congress, Second Session, February, 2002.

Buprenorphine implants – study results

This week I read an article in the latest issue of the Journal of the American Medical Association describing the results of a randomized controlled trial comparing implantable buprenorphine compared to placebo. Buprenorphine implants are four (five for some patients) small cylinders, inserted just under the skin of the upper inner arm. They are each about an inch long, and release medication up to about six months.

Buprenorphine (brand names Suboxone or Subutex) works well for the treatment of opioid addiction, but only if the patient takes it every day. Like other doctors, I have some patients who occasionally stop taking buprenorphine, so they can use illicit opioids to get high. This problem is eliminated with buprenorphine implants, because the patient receives a steady level of buprenorphine for as long as the implants are in place.

The other problem with Suboxone tablets has been its diversion from patients to the black market. Granted, it’s the safest opioid on the streets, given the ceiling on its opioid effect, but diversion to the black market isn’t desirable to doctors or law enforcement. But the implants, for obvious reasons, can’t be diverted, or at least would be extremely difficult to divert.

In this trial of the buprenorphine implants, patients were randomized to receive either placebo implants or buprenorphine implants. The patients and study evaluators didn’t know who had placebo implants and who had the real thing.

The results surprised no one. The buprenorphine implants were much more effective than the placebo implants. Patients with buprenorphine implants were retained in treatment longer and used less illicit opioids, both at week 16 and week 24. After six months, the implants were removed. The implants were fairly safe, with main problems being related to pain, swelling, or infection at the implant site. In the buprenorphine group, most common side effects compared to placebo were headache and insomnia.

This study is hopeful, but of course the real question is how do buprenorphine implants compare to the sublingual (under the tongue) Suboxone tablets and film? More studies are on the way. But for patients I worry might stop their Suboxone to relapse now and again, and in patients I worry might sell their Suboxone, these implants will be a good option when they become available.