Probuphine Update

Sorry it’s been some time since my last post; I broke my leg, had to have surgery, and only recently got out of the hospital. How’d I break my leg, you ask? Ah, I had a little trouble sticking the landing of that double axel…ok that’s not true…I broke it walking the dog.

And here is an update regarding the latest on Probuphine…

Probuphine, a new implantable form of buprenorphine, was not approved by the FDA, despite a recent recommendation by the FDA’s advisory committee to approve this new form of buprenorphine. This drug is better known under the brand name of the sublingual form, Suboxone.

According to last week’s Alcoholism and Drug Abuse Weekly, Titan Pharmaceuticals, maker of Probuphine, was told by the FDA they needed more information to show that Probuphine provided adequate opioid blockade , and they needed to show the effects of a higher dose of Probuphine. According to studies, the present formulation of Probuphine gave a lower buprenorphine blood level than compared to the sublingual form dosed at 16mg per day. The FDA asked for testing of the training that’s planned to be given to physicians who implant and remove the Probuphine cylinders.

I was quoted in the article; as I stated in an earlier blog entry, I think the present formulation of Probuphine under-dosed patients in Titan’s study. I think it should be re-formulated so that more medication is released per cylinder. Patients switching from sublingual could have their Probuphine dose varied according to how many cylinders are implanted. I also criticized the complicated procedure for both implantation and explantation. Doctors with Suboxone waivers can store the cylinders in their offices, but we’d have to assure security of the substance and keep records for the DEA. We would also have to be present with the surgeon during implantation and explantation, which is not financially practical for me, at least. Some Suboxone doctors may decide they want to learn to do the implants themselves.

I see a possible area for use of Probuphine in incarcerated opioid addicts. Prison systems say they don’t want to try to dose inmates with a controlled substance, because of diversion fears. With Probuphine, there’s less risk of diversion, and inmates’ opioid addictions could be treated with Probuphine implantation every six months. This may not give ideal blood levels, but it’s far better than letting a person with opioid addiction endure opioid withdrawal while incarcerated, which does nothing to help the underlying disorder. These people would still need psychosocial addiction treatment, though.

Moving On…

As a few of you have noticed, I am not posting all of your comments at this point. I gave the anti-12-step folks more than enough space to voice their opinions, but when a few of you felt you needed to be insulting and derogatory, I deleted comments. If you want to bash 12-step meetings, opioid treatment programs, or medication-assisted treatment in general, there are plenty of other sites/blogs you can go to for that.

I want my site to be about solutions, working together, positive ideas, and not an endless bitch session.

Correction: Johnson City, Tennessee, OTP Certificate of Need Accepted, not Approved

My bad. I misread news about the certificate of need submitted to the state of Tennessee for an opioid treatment program in Johnson City. The certificate of need has been accepted, meaning it is complete. It has not been approved, as I said in my previous blog entry.

Sorry folks. I got excited. but let’s hope for that good news for real, soon.

Probuphine: the Injectable Suboxone

Last week, the FDA’s advisory committee voted to approve Titan Pharmaceutical’s Probuphine. This is an implantable form of buprenorphine, a drug more commonly known under the brand names of the sublingual forms Suboxone and Subutex.

Probuphine is a slender rod, as pictured above, containing buprenorphine that is released into the body over time. Probuphine is meant to be inserted a few days after the patient has stabilized on sublingual buprenorphine. Four of the Probuphine rods are inserted under the skin of the inner upper arm in a fan formation, just like birth control implants such as Norplant. Four rods contain 320mg of buprenorphine, released over six months.

Probuphine has been touted as the answer to this country’s problem with Suboxone and Subutex drug diversion. Even though studies show most people who buy Suboxone off the black market use it to stay out of withdrawal and not to get high, many officials are appalled at how the medication, intended to treat opioid addiction, seems to be a new favorite street drug. But implantable Probuphine, for obvious reasons, is highly unlikely to be diverted to anyone besides the patient for whom it was intended. With this implantable form of the medication, pediatric exposures would be practically non-existent.

Safety data of the implants appears acceptable. Even minor surgical procedures can cause infection and bleeding, and these were the main problems with insertion. A fair number of patients also had irritation over the implants, possible from the medication.

But how effective is Probuphine? For me, the study results are underwhelming. It did outperform placebo in double-blind randomized controlled trials, but not as well as I expected. In Titan’s two studies, 40% and 60% of patients given active Probuphine also required supplemental sublingual buprenorphine. If patients continued to require extra sublingual buprenorphine, a fifth Probuphine rod was inserted.

Even worse, 35% of the Probuphine patients did not complete the twenty-four week study, and only 8% of Probuphine patients had 80% or more of their urine drug screens negative for illicit opioids. So the Probuphine did outperform placebo, but not robustly. Only a few of the Probuphine patients were negative for opioids at the end of the study.

The surprisingly low blood levels of buprenorphine produced by Probuphine may have caused these disappointing results. Researchers found that blood levels from four rods of Probuphine gave only 31% of the blood levels of patients dosing with 16mg of sublingual buprenorphine. Many of the patients may have been under-dosed. To get the same blood level, I’m assuming it would take 12 implants, too many to be practical.

The FDA Advisory Committee also mentioned other concerns. Obviously, the doctors implanting the medication need to be trained to do so. In the past, sub dermal implants like Norplant were inserted by doctors with training in surgical procedures, like OB/GYN doctors. With buprenorphine, around 21% of patients are treated by psychiatrists, with little training in surgery. The other doctors treating addiction with buprenorphine tend to be like me – minimal experience with surgical procedures. Titan Pharmaceutical has a plan for teaching doctors how to do this procedure, but is it enough to make us proficient?

Do I want to learn to do this procedure, or would I prefer referring patients to a general surgeon? Would the local surgeons be interested in doing these implants? Who follows the patients afterward?

I have no doubt I could learn how to do the implants if I wanted to. But that’s the question…do I want to? I’ve done minor surgical procedures during my years in primary care, like suturing lacerations, incising and draining pustules and abscesses and the like. But I don’t really enjoy doing that kind of thing. I’m slow at it, tend to be nervous, and I don’t like pus. I’m an accomplished quilt maker and I can handle a needle & thread, but memories of surgery rotations during medical school haunt me.

My surgical rotations weren’t the disaster that my OB rotation was, but that’s not much of a horse race. Actually, I did fine in my OB/GYN rotations as long as I didn’t watch any babies being born, but that was kind of hard to avoid. And I got “Honors” in my two-week rotation in Cardiothoracic Surgery, but not because I was brilliant. I was an idiot savant when it came to holding retractors, largely because I was too scared of the surgeons to move a millimeter. These were prototypic 1980’s cardiothoracic surgeons; they threw things and swore, and called the nurses “honey.” They liked me because they didn’t have to keep telling me to hold still and pull on the retractors. I could stand like a statue, for hours, literally scared stiff.

My other surgery rotations were not much better; I did my general surgery rotation at an urban trauma center in a big Ohio city. On my first day, my resident commanded me to record the history of the trauma victims arriving in the Emergency Department. So I would sidle up to a fresh trauma patient, blood spraying, body parts partially amputated, clear my throat to ask, “Um, can you tell me what happened?” The answers were usually short and colorful. Eventually I learned to ask the EMS workers, and confirm with the patients after they were out of surgery.

I didn’t enjoy that month. I saw young people die in quick and brutal ways, forcing my 24-year old self to realize that I wasn’t immortal. I’ve been a careful driver ever since, and always, always, ALWAYS wear my seatbelt.

So do I want to risk re-activation of my medical school post-traumatic stress disorder?

Titan Pharmaceutical’s answer to the FDA’s demand for a Risk Evaluation and Management Strategy (REMS) for Probuphine includes plans for a closed distribution system. This means that the drug company will only ship Probuphine directly to providers who have been trained to implant the cylinders, and are approved to prescribe buprenorphine. This means I would have to store medication in my office. I’d need a system of accounting for controlled substance medication. I wouldn’t be too hard to implement in my small office, but it’s another bit of work for me, and I don’t like the idea of having controlled substances on the premises.

I assume I would have to buy the implants, and then ask my patient to pay me for the implants, the surgical procedure, and my time and expertise. That’s a big financial risk for a bare-bones operation such as mine. I can only have one hundred buprenorphine patients at any one time, so I keep my overhead very low in order to survive financially. This expense does not fit into my business plan.

If I find a surgeon to implant the Probuphine, there are even more barriers to the process. The REMS says not only would I have to store Probuphine until the implantation procedure, but I also have to be present for the implantation procedure, and also for explantation six months later, when the rods are taken out.

Are you kidding me?? This is not practical in my world. And is the patient going to pay for the time of not one doctor, but two? Would health insurance pay for both doctors’ time? I know the answer to that.

I’ve saved the big question for last: how do you get patients with Probuphine implants to keep counseling appointments? Yes, some patients, hungry for recovery, will go to great lengths to get counseling. And others won’t go at all. With our present system, the prescription for sublingual buprenorphine is the leverage used for counseling. Many doctors won’t continue to prescribe unless the patient goes for counseling. But after a patient gets a Probuphine implant, she can decide she doesn’t need counseling doesn’t want counseling, and what’s the doctor going to do about it? Surely not go dig the implant out of her arm.

Probuphine is a great idea, and may work for some patients. But in the real world, I see problems: limited efficacy, muddled plan for implantation and explantation, financial and reimbursement issues, and no way to leverage patients into counseling. This idea needs more work.

Obstetricians Behaving Badly

Dealing with uninformed obstetricians is getting old. Overall, about four percent of opioid addicts are pregnant, according to past data. At one of the opioid treatment programs where I’m medical director, the percentage is a bit higher at five or six percent, but it seems like many more.

Maybe it seems like more because of the unpleasantness I encounter when I contact these patients’ obstetricians, to coordinate care with them. Aside from a few pleasant exceptions, I dread calling these OB’s.

For example, today I saw a pregnant patient who entered treatment about a month ago. She’s not far along, and saw her obstetrician for the first time last week. She was admitted to our program with a starting dose of 2mg of buprenorphine, and we have raised her dose to 4mg for better control of her withdrawal symptoms. This patient told me that her OB doctor said if she had stayed at 2mg, he could deliver her baby, but since she had increased all of the way up to 4mg, he had to refer her to a high-risk OB.

By now, I’ve learned that my patients usually are not exaggerating when they tell me about what their obstetricians say about treatment with buprenorphine and methadone.

Sure enough, I called this doc and he said, “I was willing to deliver her baby if she stayed at 2mg, but since YOU increased her dose to 4mg, I don’t feel comfortable delivering her at this hospital. She’s going to have to see a high risk OB.”

If he’s not comfortable, it’s good he’s going to refer her, because we want experienced people caring for our patients. So of course I didn’t argue with him, but I couldn’t resist one long, breathless run-on sentence: “The data shows that maternal dose doesn’t correlate with the risk of neonatal abstinence syndrome and shows best outcomes for mom and baby are seen with adequate doses in the mother and I have several recent review articles to send you if you don’t mind” (deep inhalation) [the below references are the ones I send to all OB’s who agree to read more information].

“Sure, send it, whatever.”

I hope he will read these references, but I kind of doubt it.

Then there was my patient who delivered a beautiful baby at a teaching hospital at a fair-sized city in my state. She was scolded for not being on methadone, but rather buprenorphine. She was told her baby would not have had bad withdrawal if she had been maintained on methadone. Her baby only had to stay in the hospital for an extra four days, so I don’t think there was much withdrawal anyway. Of course, latest trial (the MOTHER study, [3]) shows less withdrawal in babies born to moms on buprenorphine compared to methadone, but that trial has only been published for a little over two years. Guess it takes time for this information to reach doctors and nurses at that teaching hospital, ironically located in the same state as the main author of the study. It was published in a kind of obscure journal, the New England Journal of Medicine. Who reads that??

Then there’s the hospital that discharges moms maintained on methadone or buprenorphine and their infants within 24 hours. The moms say they are told that if the baby doesn’t have withdrawal by 24 hours, then all is well. This isn’t true, of course, due to the very long action of methadone and buprenorphine. Neonatal withdrawal can be delayed as long as six days, maybe even more. During their pregnancy, I talk to all pregnant patients about what to watch for in their babies after delivery. These moms watch their babies carefully, and often take them to the pediatrician several days after delivery for evaluation, just to be safe. But no one at the hospital where they delivered tells them to do this.

I’m becoming disappointed and appalled at how little the OB’s in my part of the country know about opioid addiction in pregnancy. I’m tiring of trying to gently educate these obstetricians who hold strong opinions that are contrary to current science.

I don’t say what I’d like to say to them, which is something along the lines of, “How can you be so uninformed about this issue, given the present epidemic of opioid addiction in our country? Of course many addicts will be women of child-bearing years. Addiction is now the number-one cause of accidental death in this country. You will see many patients with this problem, and should know how to treat this medical issue, based on what your colleagues have discovered from clinical trials. It’s pitiful and ironic that an addiction medicine doctor like me, who nearly fainted while witnessing my first delivery of a baby in medical school, has to teach you what you should already know. Get off your ass, learn a little something about this issue, and stop giving me such a hard time when I call you to coordinate care for these women!”

There. I’ve said it. I feel better.

1. Opioid Abuse, Dependence, and Addiction in Pregnancy, Committee Opinion, Committee on Health Care for Underserved Women and the American Society of Addiction Medicine, Number 524, May, 2012 http://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Health%20Care%20for%20Underserved%20Women/co524.pdf?dmc=1&ts=20130323T1036473227
2. Helmbrecht et al, “Management of Addiction Disorders in Pregnancy, Journal of Addiction Medicine, 2008 Mar; 2(1) pp1-16.
3. Jones, H.E., et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. New England Journal of Medicine 363(24):2320–2331, 2010. Full Text

Some Difficulties of Using Buprenorphine at the Opioid Treatment Program

As I’ve described in recent blog entries, buprenorphine, better known as the brand names Suboxone and Subutex, is now being offered at some opioid treatment programs as an alternative to methadone for the treatment of opioid addiction.

Buprenorphine is much safer than methadone, and works well for many patients. Since it’s a partial opioid instead of a full opioid, most patients find it’s easier to taper off of than methadone. However, some patients have a difficult time tapering off of it, too. It’s not a perfect medication, but is another tool we can use.

When medication is prescribed at an opioid treatment program (OTP), federal and state regulations decree the OTP must observe each patient take his or her dose of medication daily, until the patient meets criteria for take home doses. With methadone, the patient quickly swallows the dose, speaks to the nurse to prove it’s been swallowed, and is done with the dosing process.

But with buprenorphine, particularly with the generic, each patient needs ten or fifteen minutes to dissolve their dose. This means a longer process for the patient, and a longer time of observation by staff, to make sure no diversion occurs. The staff of the OTP need to make sure all of the buprenorphine has been dissolved and no dose remains before the patient leaves. In both of the programs where I work, buprenorphine patients sit in an area reserved for them while medication dissolves. This area has to be closely monitored by a counselor or nurse. Thus, buprenorphine dosing is a little more labor-intensive, and takes some extra space in the clinic that’s not needed for a methadone-only clinic.

I’ve been surprised and disappointed at how many patients try to divert part of their dose. Some try to slip it from their mouth to a pocket or tissue, so we’ve had to ask all patients not to touch their face with hands or tissue while dissolving. Several patients tried to slide a partially dissolved dose into their bra. When we see a patient clearly attempt to divert medication, we crush the tablets and the patient places this powder under the tongue to dissolve, rather than dispense whole tablets. We can be sure there will be no diversion doing this, but I can’t find any data that says the absorption and blood levels will be unaffected. Still, it seems a better option than switching to methadone or asking the patient to leave treatment.

Diverted doses are often intended for sale on the black market. If a patient has sold or attempted to sell a dose, that patient can’t get any take home medications at all, and can’t dose at all unless we can be sure they are taking all of their dose without diversion.

However, some patients who are caught trying to put part of their dose in a pocket say they want to save part of their medication for self-use later in the day. This does make sense, in a way. While using illicit drugs, most addicts use short-acting opioids that require administration of the drug three or more times during the day to ward off withdrawal. Addicts become accustomed to taking a drug when they feel any physical or emotional discomfort. That tendency doesn’t go away quickly in some patients, even when they are on medication like buprenorphine that only needs to be taken once daily to prevent withdrawal. That compulsion to take something remains for a period of time as part of the addiction, and has to be addressed with counseling. For some addicts just starting treatment, it’s scary to think they will have nothing to take later in the day.

Once I treated an addict who was addicted to pills containing barbiturate, acetaminophen, and caffeine. She took fifteen or twenty pills per day. She went into a medical detox, then an intensive outpatient program, and remained abstinent from all drugs. However, she compulsively took acetaminophen, particularly during times of stress. She chewed them, despite their bitter taste, because that’s how she used her drug of choice. She said the bitter taste of acetaminophen somehow calmed her when she felt bad. This behavior persisted for the better part of a year, and she had difficulty trying to stay under the maximum recommended dose of acetaminophen, despite knowing it could cause liver damage.

Clearly, she wasn’t getting a high from acetaminophen. But she was used to taking something multiple times during the day, to make her feel better. Also, since the drug of abuse, a barbiturate, had been paired with acetaminophen’s taste for so long, I think it’s possible her brain still released the same sort a pleasure chemicals as it did when she used the addicting drug.

We can’t allow patients to take part of their dose at home during the start of treatment, though I’m sure many of my office-based patients take their medication in divided doses. Buprenorphine works better for pain in divided doses, but if the patient only has addiction, and no pain, I prefer the dose be taken all at one time. That means my patient only has to think about taking medication once per day.

If Suboxone film could be affordable enough to use for dosing at opioid treatment programs, it would solve most of these issues. The film dissolves quickly, so once it’s placed into the mouth, it would be difficult to spit out for later use or for sale. Patients wouldn’t have to wait long for their dose to dissolve.

If they were smart, the Reckitt-Benckiser pharmaceutical company, manufacturer of Suboxone and Subutex films, would offer special much-reduced pricing to opioid treatment centers, perhaps matching the generic or even lower than the generic. The company could regain a market share lost to the generic monoproduct, and garner some good will in the process. As an added advantage, their concern about pediatric overdoses could be further allayed. Daily dosing of patients new to recovery at opioid treatment programs would keep the film out of the homes of small children, further reducing pediatric risk. Perhaps only after the patients make progress in their recovery would they be allowed to take the film home as take out doses.

News Outlets Behaving Badly: Appalling Article by Bloomberg

I don’t know if any of my readers caught that awful article on bloomberg.com, criticizing methadone clinics and their patients. I’m not going to post a link to it because it doesn’t deserve a link. But I did write to the editor, the writer of the story, and a comment to their post:

I read this disjointed and error-ridden article with sadness. I wish you could spend a day with me, talking to the patients I treat with methadone for their opioid addiction. You’d hear how, for many patients, methadone has been a life-saver. Most of my patients are ordinary people who became addicted before they knew what was happening. A very small number are criminals, and those few get media attention, propagating the myth that all methadone patients are irresponsible criminals. This just isn’t true. My patients are housewives, blue collar workers, secretaries, and schoolteachers. Anyone can become addicted.

Patients tell me how getting into recovery with the help of methadone has allowed them to keep their families together and allowed them to become productive members of society again. And my personal experience overlays the science: we now have 40-plus years of research on methadone that shows it reduces overdose death risk, reduces suicide rates, increases employment, dramatically reduces criminality, and improves overall mental and physical health. But don’t take my word for it; go to this NIDA website and see the research for yourself: http://international.drugabuse.gov You will discover that the treatment of opioid addiction with methadone is one of the most evidence-based treatments in all of medicine. And yet the stigma continues, due to ignorance and prejudice.

Is methadone the right treatment for every opioid addict? Of course not. No medication is right for everyone. Some addicts are too sick for methadone, and others not sick enough. Are there bad methadone clinics? Sadly, yes. But don’t overgeneralize and smear the reputations of good opioid treatment programs by the actions of the bad ones.

I am the medical director at a very well-run program, and proud of it. Not once in the year I’ve worked for them have I been pressured by administrators to “keep numbers up.” I have never been pressured to compromise my medical judgment in order to maximize company profits. In the past I haven’t been as fortunate, and quit programs that I felt put patients at unreasonable risk in order to cut costs, so I do think it’s an issue that needs attention.

Methadone overdose deaths are of enormous concern to everyone. But both the CDC and SAMHSA have published reports of investigations done on methadone overdose deaths. Both organizations concluded that opioid treatment programs did not contribute to the rise in methadone overdose deaths. The increase in deaths from methadone was seen with methadone diverted from pain clinics. Since these reports, the 40mg tablet has been taken off the market for pain, and doctors discouraged from using methadone for the treatment of chronic non-cancer pain. Since these measures were put in place, methadone death rates have started to drop just a bit.

You quote local law enforcement people who likely don’t even know there’s a difference between methadone and methamphetamine. And the officer who thinks methadone patients are induced to rob banks…who is more likely to rob a bank, and addict with a $50 to $200 per day drug habit, or a patient paying $12 per day for methadone and counseling. That’s too ridiculous for words.

Buprenorphine at the Opioid Treatment Program: Wave of the Future

Figuring out how to provide quality treatment at a reasonable cost is one of the most difficult snags of incorporating buprenorphine into an opioid treatment program

Buprenorphine is much more expensive than methadone. With methadone in the opioid treatment program, the money patients pay each day isn’t really for the methadone, which is pennies per dose, but for the personnel of the clinic: counselors, nurses, doctors, and support staff. With buprenorphine, those costs are still present, plus the increased cost of the medication.

There’s no generic for the brand name product Suboxone. Suboxone, now only available in film form, is a combination product containing the active ingredient, buprenorphine, plus naloxone, and opioid blocker that’s only active when injected. This combo product is preferred by doctors because it is less subject to diversion and misuse.

If you read my blog, you know plenty of addicts have written comments meant to cast doubt on that last statement. They say they can still inject Suboxone. I have no reason to doubt that, and I know no medication containing an opioid is diversion- or misuse-proof. But research shows the combo product isn’t as likely to be injected and has a lower street value, compared to the monoproduct containing only buprenorphine. The monoproduct is the equivalent of the name brand Subutex.

The retail pharmacy cost of Suboxone, based on what my uninsured office-based patients tell me, costs anywhere from $7 to $12 for an 8mg film. With a maximum dose of 24mg, that means the cost could be as high as $720 just for medication. Opioid treatment programs could get a better deal from Reckitt-Benckiser, manufacturer of Suboxone, if they buy wholesale and in bulk, but the cost is still significant. At a small opioid treatment program that I helped to start, the company wasn’t able/willing to drop their prices enough to make it affordable for patients who are mostly self-pay.

So we considered the generic form, the buprenorphine monoproduct. It is significantly cheaper than the name brand, though still much more expensive than methadone. I prescribe it for some of my extremely stable self-pay patients I treat in my office practice, and they tell me they spend around $3 to $4 per 8mg generic tablet. One patient found it for $2 per tablet at a Sam’s club pharmacy (I didn’t even know they had a pharmacy).

I had to consider the safety of the monoproduct, given the information that it’s at least somewhat more subject to abuse that name-brand Suboxone. But what was the other option? Methadone? There’s no contest. I decided, in consultation with some of my colleagues, that generic buprenorphine was so much safer than methadone that it outweighed the risk of misuse. Plus, opioid treatment programs can use diversion control methods like more frequent pill counts/bottle recalls with patients on the generic monoproduct.

At both my clinics, patients on buprenorphine pay more than patients on methadone, if they need more than one eight milligram tablet. For a patient who requires twenty-four milligrams, the cost is more than with methadone, but still attainable for many patients. I’m hoping that the generic cost will continue to drop, so we can make this option even more affordable in the future.

The profit margin is, I suspect, slimmer for opioid treatment program owners of programs that offer buprenorphine. This might make it unattractive for some for-profit businesses that own treatment programs. These may continue to be traditional methadone-only programs, and there’s nothing wrong with that. Methadone, appropriately prescribed, has been saving lives for decades.

But it’s great to have options. I’m proud and pleased that both of the for-profit companies I work for, one locally owned and one a large national company, are determined to provide buprenorphine as an option for patients at their programs. It’s the wave of the future.

My experience is with programs that do not accept Medicaid as payment. I don’t know how buprenorphine could fit into an opioid treatment program that does accept Medicaid. There’s no doubt it would get more patients into treatment, and since Medicaid patients tend to be much sicker, they could potentially benefit more than self-pay patients. It will all depend, I suspect, on re-imbursement rates. Medicaid demands a higher level of paperwork and documentation for payment, so I assume personnel costs would be higher. I hope the programs that accept Medicaid will be able to offer buprenorphine, since it is a safer and better medication for some opioid-addicted patients.

Buprenorphine at Opioid Treatment Programs

In this column and columns to follow, I’d like to describe in broad terms how we’ve implemented buprenorphine into the opioid treatment programs where I work, the benefits we’ve seen, and also some of the unexpected challenges we’ve had.

I’m fortunate to be the medical director at two opioid treatment programs that offer buprenorphine (active ingredient in the name brand products Suboxone & Subutex) in addition to methadone. I consider this to be the state of the art for opioid treatment programs, formerly called methadone clinics. Now, we can offer buprenorphine first-line, and save methadone for patients who don’t respond well to buprenorphine, and who need a stronger medication.

Don’t get me wrong – I prescribe methadone, and know that it’s a potentially life-saving medication when used appropriately. We have decades of evidence to show that it reduces death and disability in opioid addicts, reduces crime, increases employment, and reduces the risk of HIV. But addiction medicine, like in all other fields of medicine, needs to change with the science. We shouldn’t remain stuck in old ways of thinking. Buprenorphine is a partial opioid, with a ceiling effect, and for that reason is safer than methadone, which is a full opioid. There’s nothing wrong with methadone – but buprenorphine may be a better medication for many patients.

At one of my clinics, approximately half of our three hundred and sixty or so patients dose daily with buprenorphine, and the other half with methadone. I didn’t create this program. Another doctor created the program, and then after a few years sold it to a large mental health care company. I was lucky enough to get hired during the transition, and I’ve had a great time since starting to work there. At my other program, we have a significant minority of our patients dosing on buprenorphine. I’ve been with this program since its inception, and have helped develop techniques for use of buprenorphine from the start.

First of all, a distinction must be made between buprenorphine when prescribed in an office-based program, and buprenorphine prescribed and dispensed in an opioid treatment program. These two settings have different regulations.

An office-based program, frequently termed an OBOT, exists when a doctor who possesses the special “X” DEA number sees patient in an office setting, and writes prescriptions for buprenorphine for patients. The patient pays his doctor for each visit, or his insurance company pays. The patient takes the prescriptions to his pharmacy, and pays with whatever means he has – insurance or self-pay.

A doctor in this office-based setting must take a special course and apply for the special “X” DEA number. He can only have up to thirty patients the first year. After that, the doctor can petition to have up to one-hundred patients for whom he’s prescribing at any one time. In this state, the doctor also has to register with the state’s department of health and human services. That doctor’s office is subject to inspection by the DEA at any time (see my positive experience with this in my blog of December 16th, 2012).
The doctor has to have the ability to refer for counseling, though in our state it’s necessary to have some sort of written agreement with the person or facility who will provide the counseling.

Beyond these recommendations, the physician has wide latitude to alter treatment to fit the patient’s needs. This flexibility is the big advantage that office-based programs have over opioid treatment programs. Some patients may need to be seen every week. Some stable patients, in recovery for years, may need to be seen once every two months. The physician has the freedom to decide frequency of visits, of drug screens, and also the duration of treatment, though ideally with the collaboration and input of the patient.

Doctors working in opioid treatment programs have different regulations. Opioid treatment programs are heavily regulated by state and federal laws, and are inspected by the DEA, the state’s department of health and human services, and each state’s methadone authority, which now also encompasses buprenorphine, when prescribed in OTPs. Buprenorphine patients must follow all of the same regulations as methadone patients. There are a prescribed number of urine drug screens that must be obtained, and half of these must be observed. Bottle recalls to check for medication diversion must be done just like with methadone patients. The federal government recently dropped the requirement of time in treatment criteria for take homes for patients on buprenorphine, but that won’t apply in states with stricter state regulations, like mine. (See my blog of 1/20/13).

However, at an opioid treatment program, the doctor isn’t required to have an “X” number to prescribe buprenorphine rather than methadone. And there are no limits on the number of patients dosing with buprenorphine, so long as the buprenorphine is dispensed under the OTP’s DEA number and not the physician’s “X” number. This is how I’m able to prescribe buprenorphine at OTPs, while still maintaining my office based practice, so long as the latter number stays less than one hundred.

At the OTP, counseling requirements are already built into the system, and don’t differ for patients on buprenorphine compared to those on methadone.

This is confusing stuff, not only for the patients but also for clinic staff and even doctors. I’ve seen patients who were in an office-based program become confused and resentful about the different requirements when they had to switch to an opioid treatment program for buprenorphine. Hopefully I’ve helped illuminate why the regulations are different even though the medication is the same.

In the next blog I’ll talk about some of the specific challenges of using buprenorphine in the OTP setting.

Federal Regulations Revised for Opioid Treatment Patients on Buprenorphine

Illustration of relative strength of methadone compared to buprenorphine

[Please note: this post applies only to patients getting buprenorphine from opioid treatment programs and not to patients in office-based settings, where the doctor gives the patient a prescription to take to the pharmacy.]

As of January 7th of this year, the federal regulations regarding take home doses of buprenorphine (active ingredient in Subutex and Suboxone) in opioid treatment programs were relaxed. Instead of having to follow the same take home guidelines as patients on methadone, buprenorphine patients enrolled opioid treatment programs no longer have to meet the time in treatment requirements. This means a patient on buprenorphine who is doing well can get take home doses much earlier, at least in some states. These patients still must meet the other criteria, like no illicit drug use, stable home environment where medication can be stored safely, freedom from criminal activity, engagement in counseling, and the like.

To illustrate, if a new buprenorphine patient is doing very well, she can get some take home doses as early as a few weeks, instead of having to wait until ninety days of treatment, as is the regulation for methadone patients. The opioid treatment programs have discretion deciding how many take homes can be granted, and how soon. Theoretically, this patient could get up to 27 take home doses relatively early in treatment.

Only the federal regulations were revised. States like mine, North Carolina, have state regulations regarding take home doses for buprenorphine opioid treatment program patients, and programs still must still follow these state laws. Opioid treatment programs are governed by both federal and state regulations, and if they are different, the most restrictive regulations take precedence. North Carolina still has a time in treatment requirement, until/unless lawmakers change this to match the new federal regulations. So in my state, nothing changes because of the new federal ruling.

I have mixed feelings about the new federal ruling. It would be nice to have the freedom to grant take homes with less effort. However, I don’t see our state’s present regulations as a problem, since we have always had the ability to ask the state for exceptions to the time in treatment requirements for buprenorphine patients, and permission is nearly always granted by our state methadone authority. For example, if I have a buprenorphine patient who has been in treatment only a month, but who is doing exceptionally well in all areas, I can electronically submit a request asking for permission to give this patient four take home doses per week, and the state’s methadone authority usually approves it within 24 hours. This is because buprenorphine is so much safer than methadone, and less likely to kill someone who misuses it.

I like our present system, since it forces me and the treatment center staff to discuss all aspects of the patient’s progress before we submit a take home request. With the relaxed regulations, I worry some programs may make rushed decisions about early take homes, since the time in treatment criteria have been dropped. Our present system means a little more work for staff, but it also means we pay more attention to patient progress.

I can imagine a worst-case scenario where unconcerned clinics could grant twenty-seven take homes to a patient new to treatment. I can picture unscrupulous clinics using that as a marketing tool to lure addicts to their clinics, though it may not be in the addict’s best interest.

On the other hand, some people argue that doctors already give office-based patients monthly prescriptions. They do, but hopefully not until these patients are doing well and engaged in counseling. Until then, most are seen weekly or bi-weekly. Also, office-based treatment was originally meant for more stable patients: no or minimal other illicit drug use, stable home and work life, no or minimal mental health issues.

When issuing the new federal ruling, SAMHSA (Substance Abuse and Mental Health Services Administration) mentioned that in the past, people feared that increased take home for buprenorphine will mean more illicit intravenous use of the product. However, the five thousand patients already on buprenorphine in opioid treatment programs and already getting take homes don’t appear to be using buprenorphine intravenously.

Also importantly, SAMHSA re-iterates that in the opioid treatment program setting, physicians aren’t limited to only thirty or one hundred patients, as office based practices are. However, some states may require limits on the number of buprenorphine patients. Opioid treatment programs still need to adhere to the recommended drug testing, counseling, and other services described by the federal government.