Treatment Implications for Intravenous Buprenorphine Use

 

 

During the admission of new patients for opioid use disorder treatment, I ask about prior use of all drugs. I include the medications we use for treatment. I’ve done this since I started working at opioid treatment programs (OTPs) fifteen years ago.

Over the last few years, more patients say they’ve used illicit buprenorphine in the past. At first, I saw patients who were using it sublingually (under the tongue), as recommended, though still illicitly. Most of them wanted to see if this medication would work for them before they committed to the time and expense of entering a treatment program.

Over the past six months, I’m seeing more and more new patients who say they’re using buprenorphine intravenously. This past month, I’d estimate that a fourth of the patients who use buprenorphine illicitly are injecting it. Only a few said they snort buprenorphine.

This presents a big wrinkle to the treatment process.

I see why people use intravenous buprenorphine. It has low sublingual bioavailability, at around thirty percent. That means injecting two or three milligrams gives the same blood level as eight milligrams sublingually. In the short term, people injecting buprenorphine feel like it saves them money. In the long term, I’m certain it will cost more than they can imagine.

Buprenorphine tablets and films were not designed to be injected. Pills and films have fillers in them, and they aren’t sterile. Heating a mixture prior to injection will kill off some of the bacteria, so that’s a harm reduction practice. Using a filter can remove some of the particulate matter, also reducing the potential for harm. However, heat and filters can’t remove all the risk of injecting.

People on the internet insist the bioavailability of snorted buprenorphine is higher than sublingual use, but I doubt that. Either way, you bypass the liver because it crosses to the bloodstream via the veins of the nose or tongue. Plus, alkaline environments increase absorption and bioavailability for this drug, and the mouth is more alkaline than the nose.

Of course there is another reason people with opioid use disorder inject or snort their medication. Their brains associate the act of injecting or snorting with pleasure and euphoria, and can become addicted to the process and feeling of both means of ingestion.

Due to the ceiling on buprenorphine’s opioid effect, it is… arguably… one of the safest opioids a person could inject. But intravenous use is never safe.

Here’s only a partial list of complications from intravenous drug use:

1. Overdose resulting in death, brain damage from low oxygen, stroke or heart attack from prolonged low oxygen
2. Pulmonary edema (lungs fill with fluid)
3. Skin abscesses and cellulitis
4. Endocarditis (infection of heart valve that is life-threatening)
5. Deep vein thrombosis (blood clot)
6. Septic thrombophlebitis (infected blood clot)
7. Contracting infections: HIV, Hep C or B
8. Bacterial infections and abscesses in weird places like the spine, brain, joints, spleen, muscles, or eye
9. Necrotizing fasciitis – rapid, “flesh- eating” infection, also botulism
10. Pneumonia
11. Septic emboli – when infected clots break off and go to the lungs, brain from infected heart valves
12. Fungal blood/eye infections – (seen frequently when pills mixed with saliva are injected)

I have seen patients with every one of these complications. Most of them were in the distant past, when I was an Internal Medicine resident during the late 1980’s, but not all of them. Over the past six months, I’ve seen two patients with spinal abscesses from injecting drugs, though not necessarily buprenorphine.

The last time I posted about intravenous use of buprenorphine (November 2015), Dr. Wartenberg M.D. (pioneer in the addiction treatment field) wrote about the mitochondrial disease, which has caused liver failure, in European IV buprenorphine drug users. This disorder is specific to buprenorphine

So what are the treatment implications for a new patient who has injected buprenorphine?

First of all, these patients aren’t appropriate for office-based practices, even if the physician plans to prescribe the combination product with buprenorphine/naloxone. Clearly there are some patients who inject combination products and monoproducts. Granted, it’s less common, but it still occurs. There’s usually not enough oversight available at office-based practices to treat more complicated patients. I think they should be referred to opioid treatment programs, where they can be offered treatment with methadone.

What if the patient refuses methadone for some reason, or their risk with methadone is at too high from a medical view? Should patients with a history of injecting buprenorphine ever be treated with buprenorphine?

I think they can be – with great caution and daily dosing, on-site at the opioid treatment program.

At our OTP, we ask all buprenorphine patients to sit in a designated area while their dose dissolves. It usually takes around ten minutes, and they are watched by program personnel. Before they leave, each buprenorphine patient shows one of the staff their mouth, to show the medication is completely dissolved. It does feel a little “police-y” but we had a high incidence of diversion until we started this close observation.

If a patient tries to spit out their medication, they meet with me. I’m rarely willing to continue to prescribe buprenorphine if it appears they are trying to divert their medication. I meet with the patient and we discuss the option of methadone. If they refuse methadone, we try to refer them to another form of treatment.

If a patient with a history of injecting buprenorphine wants treatment with buprenorphine, I tell him I’m willing to give it a try, but that he can’t expect take home doses for a very long time, after months of observed dosing and stability. So far, this approach seems to be working. These patients are getting counseling, and haven’t attempted to divert their medication, so far as we can see. I’ve checked these patients for track marks, which in all cases appear to be healing, with no new marks.

When/if to grant these patients take homes remains a huge question. I don’t want to unduly burden a patient by insisting he must come every day forever, but I also don’t want to give the patient take home doses that could lead to a relapse back to intravenous use.

Injecting Buprenorphine (Suboxone, Subutex)

I know why addicts inject buprenorphine (Subutex): they think it saves them money. Over the long run, however, I doubt that’s true, given the hidden costs of addiction.

Buprenorphine has a relatively low bioavailability, at around 30%, when taken sublingually (under the tongue). This means only 30% of the total dose reaches the blood stream. If the pH of the mouth is lowered, bioavailability is reduced even further. This is why we recommend patients on buprenorphine avoid eating or drinking anything acidic for about twenty minutes prior to taking their dose.

By definition, when a drug in injected, it has 100% bioavailability. Therefore, some people inject their prescribed buprenorphine in order to get the desired blood level with a lower dose of buprenorphine. If they are prescribed 8mg per day, perhaps they use 4mg intravenously and sell the rest of their dose, or stockpile it.

People who misuse buprenorphine in this way may be blinded by their addiction to the multiple dangers of injecting drugs.

Anytime humans inject drugs into their bodies that weren’t meant to be injected, problems will occur. All sorts of medical complications can arise, which can cause exorbitant medical bills for drug users…and tax payers.

Skin: These pills weren’t meant to be injected, so they are not sterile. Buprenorphine does come in a sterile ampule to be used intravenously in healthcare settings, but I doubt that form would be found on the street for sale. The sublingual pills and film have bacteria in them, and we all have bacteria on our skin. Inevitably, some bacteria “go along for the ride” when pill matter is injected. This can cause skin and soft tissue infection of varying severity. Patients who inject can get anything from a mild cellulitis, which is an infection of the skin and soft tissues underneath, to life-threatening sepsis, which is a blood infection from bacteria. Many patients get abscesses, which are localized pockets of pus which must be drained in order to resolve.

The worst skin infection is called necrotizing fasciitis, which is a rapidly progressive infection that kills tissue. It’s also known as “flesh eating” bacteria. Often, surgeons have to remove whole infected areas of this dead tissue in order to save the patient’s life.

Scars and track marks are probably the most common skin manifestation of intravenous drug use. These can be minimized by also using a new needle, and not re-using needles.

As an aside, please don’t try to treat your own skin infections by yourself. I’ve seen horrible complications when patients try to drain abscesses on their own. And that leftover antibiotic you have on the shelf at home may not be a good choice to treat skin infections, particularly not the newer resistant bacteria.

Cardiovascular system: The tablets aren’t pure buprenorphine. The manufacturer’s website lists corn starch as another main ingredient. I don’t know for sure what that does to veins, but I know I use it in the kitchen to thicken a concoction if it’s too liquid. I imagine it does the same thing to blood in the veins. Even if the addict uses something to filter what he is injecting, some particles can still get through to the veins. Risks can be minimized by using a micron filter.

Again, bacteria can cause problems in the cardiovascular system. Sepsis, an overwhelming blood infection, can lead to endocarditis. This is a serious and life-threatening infection of heart valves. If the infection destroys a heart valve, heart surgery with valve replacement may be necessary.

Thrombophlebitis is a condition where the veins become clotting and possibly infected, usually at the injection site but sometimes further “downstream” in the vein. If this occurs in the deep veins pieces can break off and go to the lungs, causing pulmonary emboli.

If a drug is accidently injected into an artery instead of a vein, catastrophic complications can occur, including loss of limb below the level of injection. The artery becomes damaged which causes inflammation and clotting. The patient usually feels intense pain and burning immediately after injecting. Some sources suggest this can be treated with elevation of the limb and blood thinners, so go to your local emergency room if this happens to you.

Pulmonary: Corn starch and other particles like talc can cause clots and inflammation, creating structures called granulomata. As more granulomata are created, oxygen exchange in the lungs becomes more difficult, causing low oxygen levels in the patient.

Pulmonary emboli are clots from the venous blood system that break off and travel to the pulmonary arteries. When these clots are large enough, they can kill rapidly. The patient may have sharp chest pain, feel short of breath, and have a fast heart rate with low blood pressure. Blood can’t travel through the lungs to get oxygen, and the patient dies from lack of oxygenated blood. Even small clots can cause serious problems, particularly if they are also infected with bacteria.

This list isn’t complete – many other medical problems occur with intravenous drug use. Of course the most common may be transmission of the Hepatitis C or B viruses if needle/syringes/injection works are shared, as well as HIV. There are weird things like endophthalmitis, and infection of the internal eye, and other medical problems too numerous to list.

Opioid addicts using intravenously can get addicted to the process of injection. The brain repeatedly associates the ritual of injection with a rush of pleasure, and so the whole act of injecting can be difficult to stop. I’ve had patients on methadone and buprenorphine who continue to inject saline with no drugs just to feel the rush from using a needle. This can be overcome with time and counseling, but some patients have enormous difficulty with this.

So if you are reading this and considering injecting your buprenorphine in order to save money, please don’t do it. You will likely end up paying much more in the long run, and I don’t necessarily mean in a financial sense.

Opioid Addicts in Indiana Contract HIV

The New York Times ran an article 5/5/15 about a small town in rural Indiana that is facing a relative epidemic of new cases of HIV.

Austin, Indiana, a town of only 4200, has more than 140 people just diagnosed with HIV. The town is struggling to understand what to do about this epidemic, since the area has had a low HIV rate in the past.

The new cases of HIV were intravenous opioid addicts, and Opana was specifically mentioned by the opioid addicts in the article.

As in many small towns, needle exchange has been met with resistance from citizens who feel giving free needles to addicts only serves to encourage them to use more drugs.

Fortunately, the Indiana governor has authorized a needle exchange program for the area where addicts were sometimes using the same needle as many as three hundred times. Unfortunately, the needle exchange is not being run according to best practices. People must sign up for the service. Obviously, many opioid addicts who could benefit from free new needles are hesitant to register with anyone, due to the shame and stigma associated with addiction in this country.

To add to the difficulty, local police still arrest any addict found with needles, unless they are enrolled with the needle exchange. In other words, if one addict signs up for needle exchange and distributes these new needles to other drug users, those users could still get arrested if the police find their needles. Police say they are doing this to force addicts to register with the needle exchange.

We already know, from decades of studies, that actions like these by the police erode trust in the whole needle exchange program. Studies show needle exchange works best when people aren’t asked to register, and are allowed to procure free needles for other people who won’t come to a needle exchange. These type programs are very effective at halting the spread of HIV

The article only tangentially mentions treatment; it says some intravenous drug users have gone to a residential treatment center about 30 miles away, and others remain on a waiting list.

Sadly, no mention is made of medication-assisted treatment of opioid addiction with buprenorphine and methadone.

I did my own research: residents of Austin can drive to an opioid addiction treatment center less than a half hour away, in Charlestown, Indiana Also, there are at least two OTPs in Louisville,, only a few minutes farther, in Kentucky.

I hope someone is telling all the opioid addicts about this option. We know that after an opioid-addicted person enters medication-assisted treatment, the risk of contracting HIV drops at least three-fold. Thankfully HIV can now be treated, and is more like a chronic disease than the death sentence it was twenty-five years ago, but wouldn’t it be better to prevent HIV in the first place?

I fear Austin, Indiana is a harbinger of things to come in other small towns in our nation. Let’s stop with the politics, and get patients into medication-assisted treatment. Let’s do unrestricted needle exchange, and let’s hand out naloxone kits!

Is Heroin the New Opana?

From CDC data released 3/15

The Center for Disease Control and Prevention (CDC) released new data last month showing a rapid rise in heroin overdose deaths. While total overdose deaths from opioids remained level for the past few years, deaths involving heroin escalated sharply.

The rate has tripled since 2010, and nearly quadrupled since 2000. Males have a four times higher rate than females with the highest rate seen in white males aged 18 to 44. All areas of the country had increased heroin overdose death rates, but the highest were seen in the Midwest, with the Northeast right behind them. The South, for a change, had the lowest rate of heroin deaths, after the West.

Those of us treating patients at OTPs knew heroin was moving into areas where pain pills once dominated, but I had no idea deaths had tripled in three years. That is appalling even to me, and I see appalling things all of the time. I can’t stress enough how bad this is.

Why is this happening? I’ve read and heard various opinions:

 Some people speculate that since marijuana became legal, that crop is less profitable to Mexican farmers, who switched to growing opium poppies. This is just a theory, though the timing supports the premise. I don’t know how it can be proved, short of taking surveys of Mexican farmers, which seems problematic and unlikely to happen.

 As we implemented measures to reduce the availability of prescription opioids, the price increased. Heroin is now cheaper than pain pills in many areas, and heroin’s purity has increased. Many addicts who can’t afford pain pills switch to heroin to prevent withdrawal. NIDA (National Institute for Drug Addiction) estimates one in fifteen people who use prescription opioids for non-medical reasons will try heroin at some point in their addiction.

Maybe that’s why the South still has the lowest heroin overdose death rates: we still have plenty of prescription opioid pain pills on the black market.

 With the increased purity, heroin can be snorted instead of injected. Many people start using heroin by snorting, feeling that’s safer than injection. It probably is safer, but addiction being what it is, many of these people end up injecting heroin at some point.

 Heroin has become more socially acceptable. In the past, heroin was considered a hard-core drug that was used by inner city minorities. Now that rural and suburban young adults are using heroin, it may have lost some of its reputation as a hazardous drug.

Most experts in the field agree that much of the increase in heroin use is an unintended consequence of decreasing the amount of illicit prescription opioids on the street. But we are doing the right thing by making prescription opioids less available. Physicians are less likely to overprescribe and that’s essential to the health of our nation.

Now it’s critical that we provide all opioid addicts with quick access to effective treatment, no matter where they live.

The face of heroin addiction has changed. It is no longer only inner-city minorities who are using and dying from heroin; now Midwestern young men from the suburbs and rural areas are the most likely to be using and dying from heroin.

In the past, when drug addiction was seen as a problem of the poor and down-trodden (in other words, inner-city minorities), the general public didn’t get too excited. But when addiction affected people in the middle classes, there was a public outcry. The Harrison Act of 1914 was passed due to public demand for stronger drug laws.

I think the same thing will happen now. Suburban parents will organize and demand solutions from elected officials for this wave of heroin addiction. Indeed, I think that’s already started to happen.

Let’s make sure a big part of the solution is effective treatment.

Let’s make treatment as easy to get as heroin.

Case Study of an Opioid-addicted Patient: New England Journal of Medicine

A doctor friend of mine sent me an article from the New England Journal of Medicine from November 13. 2014. I subscribe to the NEJM, but somehow overlooked this article, so I’m happy he brought it to my attention. My friend reads my blog and knows I have lamented how I was taught in my Internal Medicine residency to treat endocarditis (potentially life-threatening infection of a heart valve), but not the underlying cause, which was addiction (read in my blog post of December 7, 2014).

The journal article he sent me is a case study of a young woman with endocarditis from intravenous drug use. The case study begins in the usual way, describing her history and physical findings. Nothing was uncommon here: the patient told them she was a drug user, and she had track marks, fever, and a heart murmur. The history and physical findings screamed, “Endocarditis! “ A chest x-ray and then chest CT scan showed multiple septic emboli, commonly seen with endocarditis, sealing the diagnosis.

But this case wasn’t only about the diagnosis and standard treatment with antibiotics. To my delight, the first sentence describing the case management was “Methadone was administered orally.”

Huzzah!

But as it turned out, the patient was only put on a methadone taper while hospitalized. She was started on a protracted course of antibiotics and sent to an extended-care facility, where she quickly relapsed. This relapse illustrated the second point of the article: medication-assisted therapy must be continued to be effective.

As the case discussion points out, “As with other medications for chronic diseases, the benefits, at least in the short term, last only while the patient is taking the medication.” In other words, her relapse was predictable, and not due to failure on the part of the patient. The relapse happened because of failure to continue the medication by the doctor.

A little later in the case study I read these wonderful sentences: “Although making a diagnosis of endocarditis is a crucial first step (emphasis mine), understanding the root cause of the endocarditis is a key feature in the diagnosis and management of this patient’s illness. Endocarditis is only a symptom of her primary illness, which is an opioid-use disorder.”

I loved this case presentation for two reasons: it emphasized treating the entire patient, including the underlying disease of addiction, and it pointed out that short-term medication with methadone or buprenorphine doesn’t work, just like temporary treatments for other chronic diseases don’t cure anything.

This patient developed endocarditis again after her relapse, and needed a second hospitalization. This time, she left the hospital on buprenorphine maintenance. She relapsed again after two months, had a third episode of endocarditis, this time due to a fungus, and required a third hospitalization.

After that treatment was over, she was maintained on buprenorphine. At the end of the article, the authors reported that the patient had over a year of abstinence from drug addiction, was taking buprenorphine, and going to AA and NA regularly.

In the discussion of appropriate treatment of both the endocarditis and the opioid addiction, I read this delightful sentence::The opioid agonists methadone and buprenorphine are among the most effective treatments for opioid-use disorder.”

Can I get an “Amen!”?

The same paragraph goes on to describe the benefits seen with MAT, which include decreased opioid use and drug-related hospitalizations, and improved health, quality of life, and social functioning. This article also clearly states MAT will reduce the risk of opioid overdose and death. Many references are cited at the end of the article for non-believers in MAT.

This article also included recommendations about educating patients about overdose risk, and providing them with naloxone.

At the end of the article, the patient who was the subject of this case study discussed her perspectives regarding her treatment. She related how each time in the past, she was treated for whatever medical problem she had, and then sent on her way, with little effort to treat her addiction. She says she’s grateful for the second episode of endocarditis, because she met the doctor who treated the addiction and gave her hope that she had a treatable disease. Prior to that, she doubted she could stop her active addiction, because she saw herself as a bad person, not as a sick person.

This article ends with this patient’s words: “To be honest, I never thought I would be standing here, clean for over a year. I thought that I was going to die.” That effectually describes the hopelessness of patients in active addiction.

I hope such endorsement of medication-assisted treatment of opioid addiction by the prestigious New England Journal of Medicine will help convince more doctors of the legitimacy of MAT.

During my training in the 1980’s, I didn’t learn how to treat the underlying cause of the endocarditis. I am delighted and encouraged to find the New England Journal of Medicine has published an article that does just that. This article clearly and overtly states the importance of treating the real problem, not just symptoms of the problem. Today’s doctors have a valuable opportunity to change the lives of many of their future patients.

Medication-assisted Treatment of Opioid Addiction Reduces Incidence of Hep C

We already know that medication-assisted treatment of opioid addiction reduces the incidence of HIV. Indeed, people in active opioid addiction contract HIV six times more often than patients on medication-assisted treatment (Metzger et al, 1993). But previous studies haven’t shown clear reduction in the transmission of Hep C.

Until now.

This new study does show a reduction in the incidence of Hepatitis C in opioid addicts who enter medication assisted treatment.

This prospective observational study by Tsai et al of 552 opioid addicts was done in San Francisco from 2000 to 2013. All subjects tested negative for Hep C in order to enter the study, and all were under thirty years old. These addicts enrolled in various forms of treatment: opioid agonist detoxification with methadone or buprenorphine, opioid agonist maintenance treatment with either methadone or buprenorphine, or non-opioid agonist forms of treatment. Some of the group elected not to get any form of treatment. Follow up testing for Hep C was done quarterly.

One-hundred and seventy-one study subjects tested positive for Hep C as the study progressed, giving an incidence rate of 25% per 100 patient-years. However, the study subjects who entered opioid agonist maintenance treatment were significantly less likely to become Hep C positive as compared to the addicts who got non-opioid agonist treatment or opioid agonist detox treatment. Addicts who enrolled in opioid-agonist maintenance treatment had a 60% reduction in the incidence of Hep C compared to the other study groups, which was statistically significant.

The patients on opioid agonist maintenance therapy had an incidence of 8.6 new cases of Hep C during 100 person-years of the study, while the group of subjects who entered non- opioid agonist forms of treatment, which included 12-step recovery and other abstinence-based forms of treatment, had an incidence of 17.8 over 100 person-years. People who didn’t get any treatment had an incidence of 28.2 per 100 person-years, while opioid addicts who underwent detox only had the highest Hep C conversion rate of 41% per 100 person-years.

As alarming and confusing as this last bit was, the data didn’t reach statistical significance, so we shouldn’t draw any conclusions about that bit.

Other studies have suggested a lower rate of Hep C transmission in opioid addicts who enter medication-assisted treatment, but none showed this as definitely as did this study.

Several things stood out to me as I read the study – first, these were young people. The average age was 23, and the study purposely excluded addicts over age 30. Maybe younger age means less time of exposure to Hep C. Older populations may already have Hep C.

This study looked at opioid addicts who sound like they are sicker than addicts I admit to treatment. For example, a whopping 69% were homeless. Do the homeless re-use needles at a higher rate? I don’t know, but perhaps homeless people have fewer resources to get clean needles, and could be at higher risk for Hep C than the rural inhabitants I treat.

The most common drug of use was heroin, used by 60% of the study population. While heroin has just started to invade my rural area, most of my new patients use opioid pain pills. It seems possible that intravenous heroin users have progressed further into addiction than pain pill users.

Even if the subjects in this study aren’t exactly the same as patients I see, this is good evidence that medication-assisted treatment reduces the risk of Hep C. It’s not the best reason for entering MAT; not dying from an opioid overdose is the best reason. But still, reducing the risk of Hep C is a good thing.

Buprenorphine and the Liver

When buprenorphine was approved for office-based treatment of opioid addiction in the U.S, doctors worried about possible liver toxicity. We’d seen case reports of acute liver necrosis (death of liver tissue) in patients with Hepatitis C who injected buprenorphine illicitly. So was this damage due to the drug itself, from intravenous use of the sublingual product, or from buprenorphine interaction with Hepatitis C? Until we had more information, experts recommended checking liver function tests before starting buprenorphine and periodically during treatment to monitor for liver damage.

Fortunately, further studies show no liver damage in patients prescribed buprenorphine.

In 2012, Saxon et al followed over 700 patients on buprenorphine or methadone over 24 weeks, and checked their liver function tests periodically, looking for elevations that would indicate liver inflammation or damage. Neither patients on methadone or patients on buprenorphine had significant increase in their liver function test levels, leading the study’s authors to conclude that neither methadone or buprenorphine cause liver damage. Patients with Hep C who were in this study did have elevated liver enzymes, but did not get worse over the twenty-four months while taking either medication.

In the November/December, 2014, issue of American Journal on Addictions, a new study by Soyka et. al. found the same thing. This study looked at 181 patients on buprenorphine/naloxone and followed their liver enzymes for over a year. Thirty-six percent of these patients had Hepatitis C, a group who may be at increased risk for liver damage due to drugs and medications. Liver tests were done at baseline, then at 12 and 24 weeks, and at the end of the first year at 52 weeks. One to two percent of these patients showed mild elevation of liver tests but none had evidence of drug induced liver injury.

This latest study adds to the medical literature that shows buprenorphine isn’t damaging to the liver, even in patients with Hepatitis C, in patients who take the medication as intended. (For obvious reasons, no one would ever do a study asking patients to inject the sublingual form of buprenorphine, since the medication isn’t sterile and the study would put test subjects at risk for all sorts of complications.)

So do we still need to check liver function tests for patients on buprenorphine? Most of the published guidelines about how to prescribe buprenorphine in an office setting still recommend checking liver function tests, but this data from Saxon study and the Soyka study seem to indicate this isn’t a particularly helpful thing to do.

About half of my buprenorphine patients have no insurance. After reading these studies, I’ve decided not to ask my patients to get routine liver function tests. I still think they need screening for Hepatitis C. Some doctors would say liver function tests can suggest Hep C if they are elevated, but since it’s possible to have Hep C and normal liver function tests, I think their money would be better spent on Hep C testing. Patients who test positive would then need to get further testing, which would likely include liver function tests, as well as confirmatory testing for Hep C.

Let’s use new information to spend health care dollars wisely.

Finding a Better Way to Treat Addiction

In my previous blog, I mentioned a great new resource that CASA has published about the condition of addiction treatment in this country. The book, “Addiction Treatment: Closing the Gap between Science and Practice,” is available for free as a download at http://casacolumbia.org

I’ve been reading this document in detail, finding facts that support what I see in the real world of treatment. In the U.S., our approach toward funding of addiction treatment is exactly backwards. We spend a relatively small amount on prevention and treatment of the actual disease of addiction, but billions on the constellation of medical issues caused by addiction.

Most addiction-related medical expenses are paid for from public funds. In fact, over ten percent of all federal, state, and local government dollars are spent on risky substance use and addiction problems. Sadly, over 95% of this money is spent on the consequences of drug use and abuse. Only 2% is spent on treatment or prevention.

Untreated addiction costs mightily. People with untreated addiction incur more health care costs than nearly any other group. An estimated one third of all costs from inpatient medical treatment are related to substance abuse and addiction. Untreated addicts (I include alcohol addicts with drug addicts) go to the hospital more often, are admitted for longer than people without addiction, and require more expensive heath care than hospitalized non-addicts. The complications these people suffer could be from underlying poor physical health and lack of regular preventive healthcare, but most of the cost is incurred treating the medical problems directly caused by addiction and risky substance use.

That data is consistent with my experiences when I worked in primary care. I always felt like I was slapping Band-Aids on gaping wounds when I treated people with alcohol or other drug addictions. I never felt like I was treating the real problem, and I wasn’t, as this report so eloquently indicates. My practice had a handful of “frequent fliers” who came to the ER several times per month with the same addition- related illnesses, over and over. I admitted one patient to the hospital at least twenty times over four years for the treatment of alcoholic gastritis. Each hospital visit lasted four or five days until he was well enough to go home and drink again. Another patient was admitted about every two months after he got pancreatitis from another bout of binge drinking. This went on for years.

This was in the early 1990’s, in my former life as a doctor of Internal Medicine. I didn’t know what to do with these people. They frustrated me. Maybe I told these patients to go to Alcoholics Anonymous, and probably I asked the social worker to arrange inpatient treatment if possible. But I didn’t have the knowledge or tools to really help these people, and instead only did what I was trained to do: treat the medical problems caused by addiction.

In my Internal Medicine residency, I admitted many patients to the hospital for endocarditis (infected heart valve) contracted from IV heroin use. Each time, this required six month of intravenous antibiotics. Back then we kept such patients in the hospital the whole time. You can imagine the cost of a six week hospital stay, not that these addicts had any money to pay. Just a fraction of that amount could have paid for treatment at a methadone clinic, the most effective way to treat heroin addiction, and prevent dozens of medical problems. But I never referred them to the methadone clinic available in that city. I didn’t know anything about methadone or the medical-assisted treatment of opioid addiction, and apparently my attending physicians, responsible for my training, didn’t know about it either. It was a shame, because in those years, the late 1980’s, we were making new diagnoses of HIV almost daily among IV drug users. Since then, a study showed a patient using IV heroin drops his risk of contracting HIV by more than threefold if he enrolls in a methadone clinic.

Family members of people with untreated addiction have higher health costs, too. Families of people with addiction have 30% higher health care costs than families with no addicted member. I presume that’s from the stress of living and dealing with a loved one in active addiction. Often family members are so caught up in trying to control the chaos caused by active addiction that they don’t take time for routine health visits.

The costs of untreated addiction aren’t only financial. Addiction and risky drug use are the leading causes of preventable deaths in the U.S. Around 2.9 million people died in 2009, and well over a half million of these deaths were attributable to tobacco, alcohol, and other drugs. Overdose deaths alone have increased five-fold since 1990.

We know addiction is a chronic disease, yet we spend far less on it than other chronic diseases.

For example, the CASA report says that in the U.S., around 26 million people have diabetes, and we spend nearly 44 billion dollars per year to treat these patients. Similarly, just over 19 million have cancer, and we spend over 87 billion for treatment of that disease. In the U.S., 27 million people have heart disease, and we spend 107 billion dollars on treatment.

But when it comes to addiction, we spend only 28 billion to treat the estimated 40.3 million people with addiction, including nicotine. Most of the money we do spend is paid by public insurance. For other chronic diseases, about 56% of medical expenses are covered by private payers, meaning private insurance or self-pay. But for addiction treatment, only 21% of expenses are paid from private insurance or self-pay. This suggests that private insurance companies aren’t adequately covering the expense of addiction treatment. Indeed, patients being treated with private insurance for addiction are three to six times less likely to get specialty addiction treatment than those with public insurance such as Medicaid or Medicare.

In the U.S., we don’t treat addiction as the public health problem that it is. Some people still don’t believe it’s an illness but rather a moral failing. Doctors aren’t educated about addiction is medical school or residencies, and we often have an attitude of therapeutic nihilism, feeling that addiction treatment doesn’t work and it’s hopeless to try.

Families and medical professionals often expect addiction to behave like an acute illness. We may mistakenly think addiction should be resolved with a single treatment episode. If that episode fails, it means treatment is worthless. Families want to put their addicted loved one into a 28-day treatment program and expect them to be fixed forever when they get out. They’re disappointed and angry if their loved one relapses.

This reminds me of an elderly man I treated for high blood pressure many years ago. I gave him a month’s prescription of blood pressure medication, and when he came back, his blood pressure was good. I was pleased, and I wanted to keep him on the medication. He was angry. He said he was going to find another doctor. He thought the one prescription should have cured his high blood pressure so that he would never have to take pills again, and was disappointed with my treatment.

If we keep our same attitude toward addiction treatment, we are doomed to be as disappointed as my patient with high blood pressure. Addiction behaves like a chronic disease, with period of remission and episodes of relapse.

We have a lot of work to do. As this CASA publication shows, we have to change public attitudes with scientific information and do a much better job of training physicians and other health care providers. We should pay for evidence-based, high-quality addiction treatment, rather than spend billions on the medical problems caused by addiction as we are now doing.

Hepatitis C: Now Curable

New medication combinations are giving Hep C cure rates of up to 75% with genotype 1, traditionally the toughest to treat. This is exciting news for the estimated 3.4 million people in the U.S. infected with the Hep C virus.

My last blog entry contained some general information about Hepatitis C viral infection, and the proper steps to take after a patient has screening tests that’s positive. If the second test, called a qualitative test, shows positive for the presence of the Hep C virus, what’s next?

In the past, many people didn’t get any further follow up testing done to see if they needed treatment, because cure rates were low, medication expensive, and the medication makes many people ill. Only about15% of people with hepatitis C go on to have cirrhosis, but the sheer number of people infected in the U.S. means there will be many people diagnosed with cirrhosis.

Now that much higher cure rates are being achieved, patients with Hep C infection need to get themselves to a liver specialist. Since cure rates are much improved, if treatment is needed, it may be time to get on with it.

To see if treatment is needed, most specialists still want to do a liver biopsy to determine the amount of damage, if any, that the Hep C virus is doing to the patients. The liver biopsy is relatively simple, with a complication rate of less than half of one percent even for patients with liver damage.

This liver tissue sample is studied under the microscope and given a Metavir score. This score, ranging from 0 to 4, tells us how much damage there has been to the liver.  A “0” score shows no damage at all, a very good thing. A score of 1 means there’s a small amount of fibrosis, or scarring, and so on until the score of 4 which means cirrhosis with much scarring is seen.

Most hepatologists (liver specialists) have not been treating patients with a Metavir score of 0 through 2, and most do recommend treatment for patients with a score of 3 or 4, since these higher scores mean there is ongoing liver damage. If the patient is already in end-stage liver disease, he may be unable to tolerate the treatment. In such a case, the hepatologist may not recommend treatment even for a patient with a Metavir score of 4.

In the past, treatment consisted of interferon and ribavirin, two agents that worked on the patient’s immune system. This treatment gave response rates of around 40 to 50%, at least with Hep C genotype 1. Genotypes 2 and 3, seen less commonly in the U.S., are easier to treat and had higher response rates.

Now there are two directly-acting agents that can be used with interferon and ribavirin: boceprevir and telaprevir. They are both protease inhibitors, and act directly on the virus, instead of on the patient’s immune system. This triple therapy is, at present, only indicated for the treatment of patients with genotype 1.

In a recent Phase II trial, telaprevir, combined with ribavirin and interferon and taken for 24 weeks, gave sustained viral response rates of 75%. This was in the group of patients who had never been treated. In patients who had been previously been treated for Hep C with just interferon and ribavirin, an new course of treatment with all three medications resulted in sustained responses in 88% of patients.

This is big news. These results are the best seen to date in the treatment of Hep C.

Some specialists still argue whether a sustained response means the same thing as a cure, but we now have long-term studies on patients who respond to interferon-based treatments. A recent study of 344 patients showed that when studied more than three years after successful treatment, the virus remained undetectable in 98.3% of these patients. Even more exciting, regression of cirrhosis was seen in 64% of these patients. This means that not only did these patients still have no detectable Hep C virus, the liver scarring improved.

This combination of three medications that work in different ways probably works better because the Hep C virus tends to change and mutate in small ways, and can become resistant if only one type of anti-viral medication is used.

Now for the bad news: both of these medications do have significant side effects. Treatment with just interferon and ribavirin is hard enough, but addition of either of these new medications makes treatment even more difficult. For example, telaprevir must be taken with large amounts of fat for better absorption, and can cause rectal pain and burning if it’s not well-absorbed. Many patients have lowered counts of red and white blood cells as well as low platelets. Some people can get a potentially fatal rash.

Even in view of the added difficulty, the markedly improved response rates, which appear to be cure rates, may make it worthwhile to consider treatment. In the future, specialists predict drug regimens that don’t have to include interferon. Soon there may be specific direct-acting agents for all of the genotypes of Hep C, with cure rates predicted to be as high as 90%. Courses of medications are expected to become ever shorter with fewer side effects.

Because we have better treatments, and because the Center for Disease Control and Prevention is recommended expanded testing for Hep C to include all baby boomers, it’s likely we’ll uncover many more cases of active Hep C.

My only worry is that diagnosing patients won’t help anyone unless it’s linked to coverage for further testing and treatment.

Patients at my clinics who screen positive for Hep C can’t even afford the confirmatory testing that they need to see if they have an active infection, if they have no insurance. Their local Health Department isn’t set up to do this kind of testing. Local doctors can’t afford to give this free care. There are some low-cost community clinics, but they don’t seem to be set up to afford the expensive testing needed for these patients. And what if they do have the virus? How can they pay to see the liver specialist and get the biopsy? Who pays for the very expensive treatment if they have no insurance?

When I worked at an opioid treatment program near a teaching hospital, it was possible to get an appointment for that patient in the resident physicians’ general medicine clinic, where they could get further testing and be referred for specialty care if needed. It’s a much bigger challenge for patients who live where there are few low-cost options for medical for the uninsured.

Because of the exciting new developments in the treatment of Hep C, there are many ongoing clinical trials. For patients with no insurance, enrolling in a clinical trial may be a way to get some medication for free, though you probably wouldn’t be able to pick which treatment regimen you get.

If you have Hep C, and are fortunate enough to afford it, it’s definitely worth consulting – or re-consulting – with a liver specialist to see what your best options are.

Though the new hepatitis medications do have some serious drug interactions, they aren’t a problem with either methadone or buprenorphine.

Cotton Fever

An addict still using heroin recently asked me what “cotton fever” was, and how he could tell if he was sick with it.

 Cotton fever is caused by bacteria commonly found on cotton plants, initially named Enterobacter agglomerans, later changed to Pantoea agglomerans. Most intravenous drug addicts filter heroin through cotton filters, to remove particles that could clog both their injection needle and their veins. Sometimes fibers of cotton break off from the filter, carrying the bacteria with it. These bacteria in the bloodstream cause fever and chills, but in a healthy person, this usually resolves on its own. It’s rare to see it cause serious infection. However, doctors still recommend addicts with cotton fever seek medical care and receive appropriate antibiotics. (1)

At least one study isolated an endotoxin produced by this bacteria, so it’s possible that the fever is actually caused by this toxin, released from the bacteria, and not from an actual infection.

 Enterobacter species, while found in feces of both animals and humans, are also found in the plant world. Usually, these bacteria aren’t a particularly vicious, which is why they rarely cause sepsis (overwhelming infection) unless the individual has an impaired ability to fight infection. In the 1970’s, some medical products (blood, IV fluids) were found to be infected with this species, and caused significant infections, but this was probably due to a large amount of the bacteria infused into patients.

 Cotton filters become more fragile with use, so addicts using new filters probably have a lower risk of cotton fever. After cotton filters are used, they remain moist and can become colonized with all sorts of bacteria, especially if they are kept warm, as happens when they are stored in a pocket, close to the body. This bacteria can cause infection when injected. Cotton filters can transmit hepatitis C and possibly other infections, if they are shared with other drug users. (2)

 Filters also retain some of the injected drug, making them of some value in the world of intravenous addicts. It’s considered a gesture of generosity to offer another addict your “cottons” because the addict will get some small amount of the drug. (3)

 Even in view of all of the above, it’s still better to use a filter than to use unfiltered heroin. A new cotton cigarette filter has been shown to remove up to 80% of particulates in heroin, and reduces the risk of thrombosis of the vein from particles. Other makeshift filters are made from clothing, cotton balls, and even tissue paper.

 Syringe filters are manufactured for medical and laboratory use. They can be designed to filter particles down to 5 micrometers. Besides being more expensive and difficult to obtain, studies show these filters retain more of the drug than other makeshift filters, making them less desirable to some addicts. (2)

 Cotton fever itself usually isn’t fatal. The biggest challenge is knowing if the addict has cotton fever or something worse, like sepsis. Sepsis is an infection of the blood stream, and even heart valves can become infected, causing serious and life-threatening problems. 

I asked a former IV drug addict about his experience with cotton fever.

 Me: What does cotton fever feel like?

 Former Addict: You get a fever that kind of feels like withdrawal. You know there’s something bad wrong, and you don’t know what to do about it. I’ve laid on the floor and thought I was going to die. A lot of times people get it when they’re rinsing, and that means they’re coming down anyway. When the dope got short and I was rinsing cottons, that’s when I got it.

 Me: How long does it last?

 FA: It seems like it lasts a long time, but the intensity is bad maybe an hour or two. You shake, you sweat; it feels just like the flu.

 Me: Ever go to the hospital with cotton fever?

 FA: No, no! (said emphatically) I was usually wanted by the police. Only time I went to the hospital is with severe trauma.

Me: I don’t understand what you mean by rinsing.

 FA: Rinsing’s when you squeeze that last little bit of drug out of the cotton [filter]. You rinse the spoon and cotton with a little water. I would save all my cottons. That was my rathole for when the dope ran out. I would actually load the cottons into the barrel of a syringe then draw water in to the barrel of syringe, then squeeze until they were bone dry. I squirted that on to a spoon, and used a new cotton to draw that into a syringe.

 Me: Why do you use cotton filters? Do you use it with every drug you injected?

 FA: I used cotton to strain any dirt that may be in the product, that might get up in the syringe. I didn’t want no dirt. Didn’t have to be cotton. [If you don’t use a filter, you] shoot a bunch of trash up in yourself, and get trash fever.

 I used an itty bitty cotton. Some people would use a quarter of cigarette butt. That was wasteful to me. It got too saturated, could hold too much residue, or dope.

 I didn’t have to use cotton with quarter gram morphine or Dilaudid. Not enough trash to stop it up. If there’s trash in the syringe, I used a cotton.

 Thankfully, this person has been in recovery from addiction for more than thirteen years. When I asked him how he was able to stop, he said Narcotics Anonymous meetings.

 Recovery is the best way to avoid cotton fever. You never have to go through that again.

1. Rollinton, F; Feeney, C; Chirurgi, V; Enterobacter agglomerans-Associated Cotton Fever,  Annals of Internal Medicine 1993; 153(20): 2381-2382.
2. Pates, R; McBride, A; Arnold, K; Injecting Illicit Drugs, (Oxford, UK, Blackwell Publishing, 2005) pp. 41-43.
3. 3.       Bourgois, Phillippe; Schonberg, Jeff; Righteous Dopefiend,(Berkeley, California, University of California Press, 2009) pp8-9, 83-84.