Suboxone Manufacturer Sued for Anticompetitive Practices

 

 

 

I read a brief news item online about the drug manufacturer getting sued, but I didn’t get detailed information until I read last week’s issue of Alcoholism and Drug Abuse Weekly (ADAW).

Here’s the scoop: the Attorneys General for thirty-six states are suing Reckitt-Benckiser (RB, now called Indivior), because the company attempted to block generics from entering the market after RB’s patent for sublingual buprenorphine products expired.

Reckitt-Benckiser manufactured Suboxone and Subutex, which were the initial buprenorphine products that came to market in 2002, after the DATA 2000 law was passed.

As a reminder, before DATA 2000 was passed, it was illegal to treat opioid use disorder in an office setting with an opioid prescription. Doctors have gone to jail for this. Before DATA 2000, opioid treatment programs (OTP) were the only setting where prescribing (methadone was the only approved medication) for opioid addiction was permitted, and these OTPs have always been strictly regulated by multiple governmental agencies.

The FDA has approved only one medication, buprenorphine, to be used under DATA 2000, and only the sublingual form was approved. Then earlier this year, a second form of buprenorphine was approved to treat opioid addiction: the six-month, sustained release implantable rods impregnated with buprenorphine, known as Probuphine.

Buprenorphine taken by other routes of administration aren’t covered by DATA 2000, and therefore can’t be used to treat opioid addiction. These forms include the name brands Butrans patch, Belbucca oral film, and IV/IM buprenorphine used for pain control.

Reckitt-Benckiser’s patent for sublingual buprenorphine tablets was set to expire around 2008. Years before that, RB worked on finding a different delivery system, and the film version of Suboxone came out in mid-2010. This new form had its own patent, so that RB was the only company that could manufacture and sell that form of their medication.

However, since their sublingual tablet had come off patient, other drug companies could make generics, which would bring down the price to consumers of this life-saving medication.

But the Attorneys General allege RB tried to block the release of the generic tablets. RB told their drug salespeople to tell doctors that children were dying from ingesting buprenorphine tablets, and that the risk of prescribing this form of treatment was too great. They said the safest way to treat patients was with the film, which comes individually wrapped in a foil packet. And remember, only RB manufactured this film.

On May 12, 2012, I blogged about Reckitt-Benckiser’s attempt to persuade me to prescribe only the film. In that blog post, I describe how the drug representative told me that sublingual tablets were now suddenly too dangerous to prescribe, due to pediatric overdoses. She also told me it was much better for patients to be prescribed the film, since people addicted to pills could be triggered by tablets.

Her credibility took a big hit that day, because she’d promoted the hell out of her company’s tablet form of Suboxone and Subutex to me for years. I called her out on the inconsistency and disingenuousness of her statements, promulgated by her company, and I blogged about it.

At her next visit, she told me she was “disappointed that I chose such a public forum to describe our conversation.”

It was the first time someone chastised me for something I wrote on my blog, and I was elated. I felt like a real journalist!

She hasn’t visited my office since, and I haven’t missed her. She’s a nice lady, which is the only reason I put up with her in the first place. Right or wrong, I‘ve always found drug reps to be tedious.

I harbor no illusions about what drug reps do. Their job is to sell their product. When I worked in primary care, I was lied to on a regular basis by drug reps. For example, when the drug rep for a company that sold Prempro told me that estrogen replacement therapy reduced the risk of breast cancer. I remember being shocked into silence as I frowned at him, wondering if he thought I was really, really stupid.

Back to the point of this blog. So in 2012, R-B tried to prevent the generic from coming onto the market by saying the pediatric overdose problem was so bad that only the films (still under patent with R-B) should be prescribed

The lawsuit alleges consumers had to pay higher prices due to RB’s efforts to block generic tablets. These states want Indivior, formerly Reckitt-Benckiser, to pay back billions of dollars of profit obtained through unfair practices.

The lawsuit alleges the company manufactured claims of pediatric safety as a way to manipulate doctors into switching their patients over to the film, instead of continuing to prescribe the tablet form of the medication, which would have generic versions coming onto the market soon.

The drug company, as well as the company that developed the film technology, both say they did nothing wrong, and that their product has saved countless lives.

So…what is the price difference for different forms of buprenorphine? I did some current comparisons for my area on www.goodrx.com, recording the lowest price on the site for people with no insurance. Here are the results:

Generic buprenorphine: dose of 16mg per day, #60 tabs: $133

Generic combination product, buprenorphine/naloxone, dose of 16mg per day, #60 tabs: $243

Name brand Suboxone Film, same dose of 16mg per day, #60 films: $455

Name brand Zubsolv, dose of 5.7mg, two per day, #60 tabs: $455

Name brand Bunavail buccal film, 4.2mg, two per day (highest recommended maintenance dose) #60 films: $455

I’m sure readers find it remarkable, as I do, that all three of the name brand forms are the same price. It’s also interesting that the cheapest form, generic buprenorphine monoproduct, is only 28% of what the name brands all cost.

Here’s something more fascinating – BlueCross/Blue Shield of NC requires prior authorization for every one of their covered patients who are prescribed buprenorphine. For years, this insurance company will ONLY authorize payment for the name brand Suboxone in film form. They refuse to pay for the cheaper generic, either mono or combination forms.

I don’t know why BC/BS decided to only cover the name brand Suboxone films.

I could understand if they wouldn’t pay for the monoproduct, due to concerns that it’s more desirable on the black market, and the insurance company may not want to contribute to this problem. But why do they object to the generic combo product? Perhaps they worked out a special, cheaper deal, or perhaps they were swayed by drug manufacturer patter.

It’s hard for me to see that Reckitt-Benckiser/Indivior did anything different than what other drug companies do routinely. Of course their drug salespeople exaggerated the danger of pediatric exposure to buprenorphine tablets in an effort to influence doctors to prescribe only the films. But their claims were so weak and transparent that it would be a gullible doctor indeed who fell for the company line.

And since when do doctors accept what a drug company salesperson tells them at face value? I’m not saying outright lying by drug company representatives should ever be OK, but…it happens.

The drug companies make big bucks, but they counter by saying they spend so much money in research and development of new drugs, and if it weren’t for their work, we wouldn’t have all these new medications that we have that are extending peoples’ lives.

That’s somewhat of a legitimate point, but at what point do we say the drug companies are making adequate profits or excessive profits? And at what point does an exaggeration about a medication become a lie?

 

The Facts About Methadone

methadone

The treatment of opioid addiction (heroin or prescription pain pills) with methadone still has an unwarranted stigma attached to it.  I wanted to devote at least one blog entry to a summary of the most well-known studies that support this evidence-based treatment. When people speak against methadone, they usually say they don’t “believe” in it, without being able to give any scientific basis for their stance. 

Well, this is why I do “believe” in it. It’s not opinion. It’s science.

 Amato L, Davoli, et. al., An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment 2005; 28 (4):321-329. In this overview of meta-analyses and other reviews, they conclude that methadone maintenance is more effective in the treatment of opioid addiction than methadone detoxification, buprenorphine, or no treatment. Higher doses of methadone are more effective than low or medium doses. 

Bale et. al., 1980; 37(2):179-193. “Therapeutic Communities vs Methadone Maintenance” Archives of General Psychiatry Opioid-addicted veterans who presented to the hospital for treatment were assigned to either inpatient detoxification alone, admission to a therapeutic community, or to methadone maintenance. One year later, patients assigned to therapeutic communities or methadone maintenance did significantly better than patients whose only treatment was detoxification. Patients in these two groups were significantly more likely to be employed, less likely to be in jail, and less likely to be using heroin, than the patients who got only detox admission. Patients in the therapeutic communities needed to stay at least seven weeks to obtain benefit equal to patients assigned to methadone maintenance. 

Ball JC, Ross A., The Effectiveness of Methadone Maintenance Treatment. New York, NY: Springer-Verlag Inc., 1991. This landmark study observed six hundred and thirty-three male patients enrolled in six methadone maintenance programs. Patients reduced their use of illicit opioids 71% from pre-admission levels, with the best results (no heroin use) seen in patients on doses higher than 70 milligrams. Longer duration of treatment with methadone showed the greatest reductions in heroin use. Of patients who left methadone maintenance treatment, 82% relapsed back to intravenous heroin use within one year. This study also found a dramatic drop in criminal activity for addicts in methadone treatment. Within one year, the number of days involved in criminal activity dropped an average of 91% for addicts maintained on methadone. This study showed that methadone clinics vary a great deal in their effectiveness. The most effective clinics had adequate dosing, well-trained and experienced staff with little turnover, combined medical, counseling and administrative services, and a close and consistent relationship between patients and staff.

 Caplehorn JRM, Bell J. Methadone dosage and retention of patients in maintenance treatment. The Medical Journal of Australia 1991;154:195-199. Authors of this study concluded that higher doses of methadone (80 milligrams per day and above) were significantly more likely to retain patients in treatment.

 Caplehorn JR, Dalton MS, et. al., Methadone maintenance and addicts’ risk of fatal heroin overdose. Substance Use and Misuse, 1996 Jan, 31(2):177-196. In this study of heroin addicts, the addicts in methadone treatment were one-quarter as likely to die by heroin overdose or suicide. This study followed two hundred and ninety-six methadone heroin addicts for more than fifteen years. 

Cheser G, Lemon J, Gomel M, Murphy G; Are the driving-related skills of clients in a methadone program affected by methadone? National Drug and Alcohol Research Centre, University of New South Wales, 30 Goodhope St., Paddington NSW 2010, Australia. This study compared results of skill performance tests and concluded that methadone clients aren’t impaired in their ability to perform complex tasks.

 Clausen T, Waal H, Thoresen M, Gossop M; Mortality among opiate users: opioid maintenance therapy, age and causes of death. Addiction 2009; 104(8) 1356-62. This study looked at the causes of death for opioid addicts admitted to opioid maintenance therapy in Norway from 1997-2003. The authors found high rates of overdose deaths both prior to admission and after leaving treatment. Older patients retained in treatment died from medical reasons, other than overdose.

 Condelli, Dunteman, 1993: examined data from TOPS, the Treatment Outcome Prospective Study, assessed patients entering treatment programs from 1979 – 1981 and found data on improvement similar to DARP; longer duration of treatment in methadone maintenance shows lower use of illicit opioids. 

Dole VP, Nyswander ME, Kreek, MJ, Narcotic Blockade. Archives of Internal Medicine, 1966; 118:304-309. Consisted of thirty-two patients, with half randomized to methadone and the other half to a no-treatment waiting list. The methadone group had much higher rates of abstention from heroin, much lower rates of incarceration, and higher rates of employment.

 Faggiano F, Vigna-Taglianti F, Versino E, Lemma P, Cochrane Database Review, 2003 (3) Art. No. 002208. This review article was based on a literature review of randomized controlled trials and controlled prospective studies that evaluated the efficacy of methadone at different doses. The authors concluded that methadone doses of 60 – 100mg per day were more effective than lower doses at prevention of illicit heroin and cocaine use during treatment.

 Goldstein A, Herrera J, Heroin addicts and methadone treatment in Albuquerque: a year follow-up. Drug and Alcohol Dependence 1995 Dec; 40 (2): p. 139-150. A group of heroin addicts were followed over twenty years. One-third died within that time, and of the survivors, 48% were on a methadone maintenance program. The author concluded that heroin addiction is a chronic disease with a high fatality rate, and methadone maintenance offered a significant benefit.

 Gordon NB, Appel PW., Functional potential of the methadone-maintained person. Alcohol, Drugs and Driving 1995; 11:1: p. 31-37. This is a literature review of studies examining performance and reaction time of patients maintained on methadone, and confirms that these patients don’t differ from age-matched controls in driving ability and functional capacity.

 Gowing L, Farrell M, Bornemann R, Sullivan LE, Ali R., Substitution treatment of injecting opioid users for prevention of HIV infection. The Cochrane Database of Systematic Reviews, 2008, Issue 2, Ar. No. CD004145. Authors reviewed twenty eight studies, concluded that they show patients on methadone maintenance have significant reductions in behaviors that place them at risk for HIV infection.

 Gronbladh L, Ohlund LS, Gunne LM, Mortality in heroin addiction: Impact of methadone treatment, Acta Psychiatrica Scandinavica Volume 82 (3) p. 223-227. Treatment of heroin addicts with methadone maintenance resulted in a significant drop in mortality, compared to untreated heroin addicts. Untreated addicts had a death rate 63 times expected for their age and gender; heroin addicts maintained on methadone had a death rate of 8 times expected, and most of that mortality was from diseases acquired prior to treatment with methadone. 

Gunne and Gronbladh, 1981: The Swedish Methadone Maintenance Program: A Controlled Study, Drug and Alcohol Dependence, 1981; 7: p. 249 – 256. This study conducted a randomized controlled trial on inpatient opioid addicts to methadone maintenance with intensive vocational rehabilitation counseling, or a control group that were referred to drug-free treatment.  Over 20 years, this study consistently showed significantly higher rates of subjects free from illicit opioids, higher rates of employment, and lower mortality in the group maintained on methadone than the control group.

 Hartel D, Selwyn PA, Schoenbaum EE, Methadone maintenance treatment and reduced risk of AIDS and AIDS-specific mortality in intravenous drug users. Abstract number 8546, Fourth Annual Conference on AIDS, Stockholm, Sweden, June 1988. This was a study of 2400 opioid addicts followed over fifteen years. Opioid addicts maintained on methadone at a dose of greater than 60mg showed longer retention in treatment, less use of heroin and other drugs, and lower rates of HIV infection. 

Hubbard RL, Marsden ME, et.al., Drug Abuse Treatment: A National Study of Effectiveness. Chapel Hill: University of North Carolina Press, 1989. Shows decreased use of illicit drugs (other than opioids) while in methadone treatment, and increased again after discharge.

 Kosten TR, Rounsaville BJ, and Kleber HD. Multidimensionality and prediction of treatment outcome in opioid addicts: a 2.5-year follow-up. Comprehensive Psychiatry 1987;28:3-13. Addicts followed over two and a half years showed that methadone maintenance resulted in significant improvements in medical, legal, social, and employment problems.

 Lenne MG, Dietze P, Rumbold GR, et.al. The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol on simulated driving. Drug Alcohol Dependence 2003; 72(3):271-278. This study found driving reaction times of patients on methadone and buprenorphine don’t differ significantly from non-medicated drivers; however, adding even a small amount of alcohol (.05%) did cause impairment.

 Marsch LA. The efficacy of methadone maintenance in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis Addiction 1998; 93: pp. 515-532. This meta-analysis of studies of methadone concludes that methadone treatment reduces crime, reduces heroin use, and improves treatment retention.

 Mattick RP, Breen C, Kimber J, et. al.,Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane Database of Systematic Reviews,  2003; (2): CD002209. This is a meta-analysis of studies of methadone treatment. The authors concluded that treatment of opioid dependence with methadone maintenance is significantly more effective than non-pharmacologic therapies. Patients on methadone maintenance are more likely to be retained in treatment and less likely to be using heroin. This study did not find a reduction in crime between the two groups. 

Metzger DS, Woody GE, McLellan AT, et. al. Human immunodeficiency virus seroconversion amoung intravenous drug users in- and out- of- treatment: an 18-month prospective follow up. Journal of Acquired Immune Deficiency Syndrome 1993;6:1049-1056. Patients not enrolled in methadone maintenance treatment converted to HIV positivity at a rate of 22%, versus a rate of 3.5% of patients in methadone maintenance treatment.

 Powers KI, Anglin MD. Cumulative versus stabilizing effects of methadone maintenance. Evaluation Review 1993: Heroin addicts admitted to methadone maintenance programs showed a reduction in illicit drug use, arrests, and criminal behavior, including drug dealing. They showed increases in employment. Addicts who relapsed showed fewer improvements in these areas. 

Scherbaum N, Specka M, et.al., Does maintenance treatment reduce the mortality rate of opioid addicts? Fortschr Neurol Psychiatr, 2002, 70(9):455-461. Opioid addicts in continuous treatment with methadone had a much lower mortality rate (1.6% per year) than opioid addicts who left treatment (8.1% per year).

 Sees KL, Delucchi KL, et.al. “Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence” Journal of the American Medical Association, 2000, 283:1303-1310. Compared the outcomes of opioid addicted patients randomized to methadone maintenance or to180-day detoxification using methadone, with extra psychosocial counseling. Results showed better outcomes in patients on maintenance. Patients on methadone maintenance showed greater retention in treatment and less heroin use than the patients on the 180 day taper. There were no differences between the groups in family functioning or employment, but maintenance patients had lower severity legal problems than the patients on taper.

 Sells SB, Simpson DD (eds). The Effectiveness of Drug Abuse Treatment. Cambridge, MA: Ballinger, 1976: This was an analysis of information from DARP, the Drug Abuse Reporting Program, which followed patients entering three types of treatment from 1969 to 1972 and showed that methadone maintenance was effective at reducing illicit drug use and criminal activity. This study also demonstrated that addicts showed more improvement the longer they were in treatment. 

Strain EC, Bigelow GE, Liesbon IA, et. al. Moderate- vs high –dose methadone in the treatment of opioid dependence. A randomized trial. Journal of the American Medical Association 1999; 281: pp. 1000-1005. This study showed that methadone maintenance reduced illicit opioid use, and more of a reduction was seen with the addition of psychosocial counseling. Methadone doses of 80mg to 100mg were more effective than doses of 50mg at reducing illicit opioid use and improving treatment retention. 

Stine, Kosten; Medscape Psychiatric and Mental Health eJournal: article reminds us that though it’s clear that better outcomes for methadone patients are seen with higher doses (more than 80mg), many opioid treatment programs still underdose their patients.

 Zanis D, Woody G; One-year mortality rates following methadone treatment discharge. Drug and Alcohol Dependence, 1998: vol.52 (3) 257-260. Five hundred and seven patients in a methadone maintenance program were followed for one year. In that time, 110 patients were discharged and were not in treatment anywhere. Of these patients, 8.2% were dead, mostly from heroin overdose. Of the patients retained in treatment, only 1% died. The authors conclude that even if patients enrolled in methadone maintenance treatment have a less-than-desired response to treatment, given the high death rate for heroin addicts not in treatment, these addicts should not be kicked out of the methadone clinic.

 Do these studies mean that methadone works for every opioid addict? I don’t think so. Every medication has side effects and dangers. Methadone is no different. For a variety of reasons, methadone may not work for some addicts.  But this treatment has helped many addicts. At the very least, it can keep them alive until a better treatment comes along.

Great New Book to Recommend!

by Rebecca Janes, LMHC, LADC

So there I was, cruising Amazon.com, looking for new books about opioid addiction and treatment, when I saw an intriguing title: Methadone: The Bad Boy of Drug Treatment.

I ordered it, and just finished it.

I fully recommend this book for anyone interested in learning more about methadone treatment. It’s written by Rebecca Janes, LMHC, LADC. The book’s cover says she has around fifteen years’ experience working in methadone treatment centers. She’s obviously knowledgeable about the studies supporting treatment of opioid addiction, and she’s able to summarize this knowledge succinctly. She explains complicated ideas in simple ways that make sense.

 It’s a small book, at 120 pages, and doesn’t have many references, but it covers most essential areas. The price is $12.95, and it’s published by Outskirts Press. As I said, you can buy it on Amazon, where it’s also available as a Kindle edition for only $2.99.

 The first chapter is dedicated to correcting mistaken impressions the general public has about methadone treatment, and Chapter Two corrects myths addicts often tell each other. Chapter Three describes what does not work in treatment, and Chapter Four tells what does work. Chapter Five tackles more controversial aspects, such as appropriate treatment of pain and anxiety for patients maintained on methadone.

 Patients on methadone will find this an ideal book to give to important people in their lives who nag them about getting off methadone. It’s great for parents and other relatives. It would be ideal to give to doctors with negative or judgmental attitudes, since it’s a quick read, and doctors aren’t likely to want to spend much time reading about a treatment they don’t believe in. It would be a great book to recommend to probation officers and social workers who don’t have much knowledge about methadone and its use. 

The only criticisms I have of the book are its few references, and it doesn’t cover buprenorphine at all. But then, if you want more in-depth information about opioid addiction, methadone, and buprenorphine, complete with references, you should buy my book: Pain Pill Addiction: Prescription for Hope. You can get it for $13.95 on EBay, shipping included. Or have I mentioned this before?

The Pain Management Movement

 In the late 1990’s, organizations like the American Pain Society and the American Academy of Pain Management declared that doctors in the U.S. were doing a lousy job of treating pain, and were under-prescribing opioid pain medications, due to a misguided fear of causing addiction. As a result, there was a national push to treat pain more aggressively. Some states even passed pain initiatives, mandating treatment for pain. Lawsuits were brought against doctors who didn’t adequately treat pain. The Joint Commission on the Accreditation of Healthcare Organizations (JACHO), the organization that inspects hospitals to assess their quality of care, made the patient’s level of pain the “fifth vital sign,” after body temperature, blood pressure, heart rate, and respiratory rate. Pain management specialists encouraged more liberal prescribing of pain medication. These experts told their primary care colleagues that the chance of developing addiction from opioids prescribed for pain was about one percent.

With these limited facts, the pain management movement was off and running. Many pain management specialists, some of whom were paid speakers for the drug companies that manufactured powerful opioid pain medications, spoke at seminars about the relative safety of opioids, used long term for chronic pain. Pain management specialists taught these views to small town family practice and general medicine doctors, who were relatively inexperienced in the treatment of either pain or addiction.

The problem was…the specialists were wrong.

These specialists, in their well-intentioned enthusiasm to relieve suffering, used flawed data when reciting the risk for addiction. The one percent figure came from a study looking at patients treated in the hospital for acute pain, which is quite different from treating outpatients with chronic non cancer pain. (1) In other words, they compared apples to oranges.

To many addiction specialists, an addiction risk of only one percent seemed improbable, since the general population has an addiction risk estimated from six to twelve percent. Surely, being prescribed pain pills would not lessen the risk for addiction. Yet the one percent figure was often cited by many pain management professionals, as well as by the representatives of the drug companies selling strong opioids. 

Some pain management specialists even took a scolding tone when they spoke of some primary care physicians’ reluctance to prescribe strong opioids. They often muddied the waters, and grouped patients with cancer pain, acute pain, and chronic non-cancer pain together, and spoke of them as one group. This can feel insulting to doctors who, though reluctant to prescribe opioids endlessly for a patient with chronic non cancer pain, are adamant about treating end-of-life cancer pain aggressively with opioids. No compassionate physician limits opioids for patients with cancer pain or with acute, short term pain. However, chronic non-cancer pain is different, with different outcomes than acute pain or cancer pain.

 We didn’t learn from history, or we would have learned that when many people have access to opioids, many will develop addiction.  We are scientifically more advanced than one hundred years ago, but we still have the same reward pathway in the brain. The human organism hasn’t changed physiologically. The present epidemic of opioid addiction is reminiscent of the early part of the twentieth century, just after the Bayer drug company released heroin, which for a short period of time was sold without a prescription, before physicians recognized that over prescription of opioids caused iatrogenic addiction.

 Few pain patients intended to become addicted. Some addicted people blame their doctors for causing their opioid addiction, but most doctors were conscientiously trying to treat the pain reported by their patient, and the pain management experts had told these doctors the risk of addiction was so low they didn’t have to worry about it.

Certainly many patients made bad choices to misuse their medications, either from curiosity or peer influence, pushing them farther over the line into addiction. Patients need to recognize their own contribution to their addiction. But with opioid addiction, as the disease progresses, the addict loses the power of choice that he once had. If the addict is fortunate enough to have a moment of clarity, before the disease progresses too far, he may be able to stop on his own, without treatment.

 By their very nature, opioids produce pleasure. Any time doctors prescribe something that causes pleasure, we should expect addiction to occur. Some people, for whatever reason, feel more pleasure than others when they take opioids, and seem to be at higher risk for addiction. As discussed in previous chapters, genetics, environment, and individual factors all influence this risk.

Opioids treat pain – both physical and emotional. Many of the neuronal pathways in the brain for sensing and experiencing pain are the same for both physical and psychological pain. For example, the brain pathways activated when you drop a hammer on your toe are much the same as when you have to tell your spouse you spent the rent money while gambling. Opioids make both types of pain better. Chronic pain patients with psychological illnesses are at increased risk for inappropriate use of their pain medications.

 In a recent study, the rate of developing true opioid addiction in patients taking opioids for chronic pain was found to be increased fourfold over the risk of non-medicated people. (2) Instead of a one percent incidence, as estimated by pain medicine specialists in the past, it now appears eighteen to forty-five percent of patients maintained long-term on opioids develop true addiction, not mere physical dependency. (3) If this information had been available in the late 1990’s, doctors may have taken more precautions when they prescribed strong opioids for chronic pain.

 Researchers have identified the risk factors for addiction among patients who take opioids long-term (more than three months) for chronic pain. Studies now show that a personal past history of addiction is the strongest predictor of future problems with addiction, as would be expected.  A patient with a family history of addiction is also at increased risk for addiction, as are patients with psychiatric illness of any kind, and younger patients. (4)

However, at the height of the pain control movement, there were no good studies of the addiction risk when opioids were used for more than three months. The little information that did exist was misused, resulting in an incredible underestimation of the risk of addiction in patients with chronic pain, who were treated with opioid medications for more than three months.

 With the momentum of the movement for better control of pain, both acute and chronic, the number of prescriptions for opioid pain pills increased dramatically. In the years from 1997 through 2006, prescription sales of hydrocodone increased 244%, while oxycodone increased 732% during that same time period. Prescription sales for methadone increased a staggering 1177%. (5)

It’s not just patients who are at risk for abuse and addiction. The increased amount of opioids being prescribed meant there was more opioid available to be diverted to the black market. When an addicting drug is made more available, it will be misused more often.

1. Porter and Jick, New England Journal of Medicine, 302 (2) (Jan. 10, 1980) p. 123.
2. Michael F. Fleming, Stacey L. Balousek, Cynthia L. Klessig, et al. “Substance Use Disorders in a Primary Care Sample Receiving Daily Opioid Therapy,” Journal of Pain, 207; Vol. 8, issue 7: 573-582.
3. 7. Steven Passik M.D., Journal of Pain and Symptom Management, Vol. 21 No. 5, (May 2001), pp.359 – 360.
4. Chou, R, Fanciullo, G, Fine, P, et. al., “Opioid Treatment Guidelines: Clinical guidelines for the use of Chronic Opioid Therapy in chronic, non-cancer pain.” The Journal of Pain, 2009, Vol. 10, No. 2. pp. 113-130

5. Andrea Trescott, MD, Stanford Helm, MD, el. al., “Opioids in the Management of Chronic Non-cancer Pain: An Update of American Society of the Interventional Pain Physicians’ Guidelines,” Pain Physician 2008: Opioids Special Issue: 11:S5 – S 62.

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.

Bibliotherapy: More Addiction Memoirs

If I Die Before I Wake, by Barbara Rogers

Anyone struggling with addiction to drugs including alcohol can get something out of this book. The author describes what her addiction was like, what happened to get her into recovery, and what it’s like now. And she went further than that. She described the trials she faced while in recovery, and how she applied the spiritual principles of the twelve steps as she went through these trials. This book is like going to a really good speaker meeting. It will resonate with both newcomers and old-timers in recovery. I will be recommending it to my patients.

Pill Head, by Joshua Lyons

I was envious as I read the book, because he did such a great job of writing an interesting, engaging book, while also educating the reader with (mostly) accurate facts about the disease of opioid addiction. It’s more interesting than my own book, Pain Pill Addiction, though I have more science in mine. Anyway, the author shows the dividedness of many addicts. He wants to be in recovery, and hates the negative consequences that are occurring as a result of his addiction, but he still wants to use pain pills. I don’t think people newly in recovery should read it because it may trigger cravings in the places he describes drug euphoria. His story isn’t one of hope, and I wish he’d waited until he was further into recovery to write the book.

 

Loaded, by Jill Talbot

            Ugh. I didn’t like this book. It was false advertising, for one thing. It was more about her unhappy love life than it was about her alcohol addiction. For the first two-thirds of the book, she laments about how dating married men made her lonely. Duh. Then toward the end she does talk of some sticky situations due to alcohol, and describes her fellow patients at a drug rehab. But then she is vague about her relapse back to drinking, and if she was able to do controlled drinking, or if she went back to her former state.

Wired: the life and Fast Times of Jim Belushi, by Bob Woodward

            It could have been cut in half and been a much better book. The renowned author put in a great many details of the days and nights during the years leading up to the star’s death from drug overdose, and it felt like too much after a few chapters. We get it. He was a wild and crazy guy. He did outrageous things and was tremendously talented and deeply flawed. Maybe knowing the ending made it sad from the start. Another big talent obliterated by addiction.

Broken, by William Cope Myers

            He’s the son of the famous journalist William Myers, and now a spokesman for Hazelden recovery center in Minnesota. This memoir is one of the better ones. He does a good job of describing the guilt that comes after a drug binge, and about his family’s disappointment in him. With a famous father, the press of expectations was an added stress that may have pushed his addiction further.

Go Ask Alice, by Anonymous

I came across a paperback copy in a bargain bin at a thrift store, and bought it to re-read. I read it as a teen, and at that time suspected it was written by an adult to scare kids away from drugs. I wondered if I’d think differently reading it as an adult. I didn’t. I certainly didn’t sound like it was written by a fifteen year old. It’s a fair book, but probably fictional.

Can’t Find My Way Home, by Martin Torgoff

I’ll re-read this one. It’s a comprehensive history of drug addiction in the U.S. from 1945 until 2000. Focused on the various political movements and popular trends of different years, it puts drug use into cultural context. It also gives some specifics behind some famous drug users and drug legalization proponents. It was fascinating. At the end, the author unexpectedly described his own recovery. Anyone wanting to read more about the 1960’s and 70’s drug culture should read this book.

“The End of My Addiction,” by Dr. Oliver Amiesen

            I only got this book because a few patients mentioned it. I pre-judged this book, thinking the author must be a pompous doctor, hater of Alcoholics Anonymous, who wrote a lame book on a half-baked theory about addiction treatment, just for his self-glorification. I was completely wrong. The author writes about his own addiction with self-awareness and humility. He doesn’t claim to have all the answers, but presents a credible treatment that may benefit alcoholics. He started himself on high-dose baclofen, a muscle relaxant that’s been around for years. It quenched his thirst for alcohol. He presents a good enough argument to justify a large randomized controlled trial to test the theory that high-dose baclofen suppresses alcohol cravings. The book is well-written and interesting. Dr. Amiesen describes his own travails with addiction in some detail.

The MOTHER trial – New Information about Buprenorphine and Methadone in Pregnancy

 The long-awaited MOTHER trial is done, and the data just published. (1) MOTHER (Maternal Opioid Treatment: Human Experimental Research) was one of the first studies to follow pregnant opioid-addicts during pregnancy and up to 28 days after they delivered their babies.

 The purpose of the study was to compare the use of buprenorphine during pregnancy with the use of methadone. For the past forty years, methadone has been the treatment of choice for opioid-addicted pregnant women. This is because it prevents withdrawal in the mother and fetus. With short-acting, illicit opioids like heroin or OxyContin without the time release coating, the mother and baby get high peaks of opioid followed by periods of withdrawal.

 Healthy adults get very sick while in withdrawal, but they usually don’t die. However, the developing fetus can die during opioid withdrawal, and miscarriage or preterm labor are more likely to occur. Methadone, since it’s a long-acting opioid, can keep both mother and baby out of withdrawal for twenty-four hours, when properly dosed. Compared with opioid-addicted mothers left untreated, or treated with non-opioid means, methadone-maintained mothers have fewer complications, better prenatal care, and higher birth weight babies.

 Now for the bad part: about half of the infants born to moms maintained on methadone have opioid withdrawal symptoms. No one wants to see a newborn having symptoms of opioid withdrawal. And yet, it’s still better than the alternatives.

 But now, it appears that the use of buprenorphine during pregnancy gives as much benefit as methadone, but less severe withdrawal in the newborns. The percentage of babies with opioid withdrawal was similar in the methadone and buprenorphine groups, but the severity and duration of the babies’ withdrawal were markedly less.

 If a woman addicted to heroin or pain medications discovers she’s pregnant, her best choice is to get into treatment with buprenorphine. But if that’s not available, methadone is still better than other alternatives.

 1. “Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure,” by Hendree Jones, Karol Kaltenbach, et. al., New England Journal of Medicine, December 9, 2010, 363;24: pages 2320-2331.

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.

Naltrexone to Treat Opioid Addiction

Opioid antagonists (blockers)

Opioid antagonists are drugs that firmly attach to the opioid receptors, but don’t activate these receptors. Antagonists prevent other opioids from reaching and activating the receptors. They also remove opioids from the receptors, so if antagonists are given to an actively using opioid addict, the addict will become sick with immediate withdrawal. This is called “precipitated withdrawal” because it was caused, or precipitated, by a medication.

Naltrexone is the most common oral opioid blocker that is used. It’s taken orally, in pill form. It’s started after an opioid addict has completed opioid withdrawal. It can be a difficult medication to start. Because it is a blocker, it may also block endorphins, our own naturally made opioids. Some patients complain of headache, muscle aches, and fatigue while taking naltrexone. Many times these unpleasant symptoms will subside with more time on the medication. The medication can be started at a half dose for the first week or so, then increased to the full dose, for better tolerability.

Naltrexone has been used in this country mainly for relapse prevention, particularly for addicted professionals. Many professionals such as doctors and pharmacists, who have been treated for opioid addiction, are started on naltrexone when they return to work. These professionals may need to work around opioids, and if they relapse while taking naltrexone, the illicit opioids will have no effect. The antagonist thus serves as extra insurance against a relapse. Many licensing boards for impaired professionals insist they take naltrexone as a condition of being allowed to return to work in their career fields.

Naltrexone works well – but only if the patient takes it every day. If the addict “forgets” to take her dose for one or two days, it is then possible for her to get high from ingested opioids. Because of this, the medication is also available in an implantable form. Pellets containing naltrexone are placed just under the skin and the medication is released into the body over three months. With this method, compliance is ensured, unless the addict wants to dig the pellets out to be rid of the blocking drug.

Naloxone is the intravenous form of an opioid antagonist, better known by its brand name Narcan. It’s injected to rapidly reverse the effects of opioids. Emergency workers often carry Narcan with them to use if they encounter a person who has overdosed with opioids. This medication can be life-saving, but it also puts the opioid addict into immediate withdrawal.

Sometimes people get confused, and think that this drug will alleviate opioid cravings. It doesn’t. Sadly, those cravings are still present, but opioid blockers can be an added bit of insurance against an opioid relapse.