Archive for the ‘Methadone dosing’ Category

Drug Interactions with Methadone

aaaapilsfighting

Recently, medical directors of opioid treatment programs in my state pondered how to handle the risk of medication interactions with methadone. In my area of the country, chart reviews of patients who died while taking methadone revealed many decedents were taking other medications with known interactions with methadone. Obviously, we want to prevent these deaths, and need to protect against drug interactions.

To predict a possible drug interaction, the OTP doctor must know all of the other medications that the patient is taking, both prescription and non-prescription. I assume all doctors at opioid treatment programs ask the patients what medications they are prescribed on the first day, along with what they take over the counter. That’s a good start, but often it’s not sufficient.

On that first day, patients aren’t feeling well. They are in opioid withdrawal and they yearn to feel better. They may forget about some medication or assume it’s not important to mention. They may forget about over-the-counter medications. Sometimes patients deliberately keep silent about medications if they’re worried they won’t be allowed to continue them. Most commonly this happens with benzodiazepines, but doctors can detect prescriptions for these controlled substances, since they are listed on our state’s prescription monitoring program.

Benzodiazepines are the most common drug found in patients who have died while prescribed methadone.

At my opioid treatment programs, we keep lists of our patients’ medications in their charts.
We tell patients to please tell us right away if they are prescribed any medications after they enter our program, so we are alerted to possible drug interactions. Patients are instructed to tell the nurses, since they see nurses most often, and the nurses then tell me. It’s OK for patients to tell counselors, but counselors aren’t medically trained so they must pass the information on the nurses and doctors.

Keeping an up to date list of each patient’s medications is challenging, but do-able with a good system in place. However, the list isn’t worth much unless the doctor is made aware of all prescribed medications, so each opioid treatment program’s system must include a way to provide the doctor with all this information.

At my programs, I sign a form giving my approval (or disapproval) of all medications that are prescribed for the patient, and I write orders if any further action needs to be taken, like asking the patient about any withdrawal symptoms or sedation. But this might happen a few days after the medication is started, so nurses also send me texts with notice of any new medication. This is the best method for me, since I can quickly text back with any orders for enhanced patient monitoring. One program sends emails which I can receive on my smart phone, read immediately, and send my response.

Opioid treatment program physicians need to know which medications can interact with methadone. This list can be long, and varies somewhat depending on the source of information.

Methadone interacts with other drugs in several ways; since it’s metabolized by specific enzymes in the liver, called the cytochrome P450 system, other drugs affect this system can affect the patient’s blood level of methadone. Sometimes other medications can induce, or speed up, methadone’s metabolism, which can drop the patient’s methadone blood level. Other medications inhibit methadone’s metabolism, causing the methadone blood level to rise. In the first situation, a previously stable patient may start to feel withdrawal. In the second situation, the patient may become sedated from methadone and even be at risk for a fatal overdose.

Other medications, mostly sedatives, act on the same centers in the central nervous system as methadone to produce even more sedation. These actions can be synergistic. Synergy between two medications means that the effect of two drugs is greater than you would expect. To put it another way, instead of one plus one equals two, suddenly one plus one equals three or even four. You get more effect than you bargain for.

Then there’s the whole QT interval prolongation that can be caused by methadone. Many other commonly used medications also prolong the QT interval, so that when they are prescribed with methadone, patients are theoretically placed at increased risk of a potentially fatal heart arrhythmia. Relatively common drugs like citalopram (Celexa), erythromycin, and cipro can cause QT interval prolongation.

How can a doctor know about the ways drugs interact with methadone? Most of the main drugs, like sedatives, methadone inducers and inhibitors, we know off the top of our heads, but technology gives us many ways to augment our brain power. Doctors can reference one of the three or four free smart phone apps. These are particularly helpful with the QT interval prolongers, since that list is very long and frequently changing.

Now for the hardest part: what should a doctor to do when a patient gets a medication that can interact with methadone? I’ve scoured the internet, and there are no easy answers. The Addiction Treatment Forum, has published some general guidelines that seem prudent: http://www.atforum.com/pdf/Drug_Interactions.pdf

As the AT Forum points out, just because an interaction may occur doesn’t mean it will occur. Certainly we should notify the patient of possible drug interactions and ask them to report any sedation or withdrawal while they are taking the new medication so that we can adjust the methadone dose accordingly. If the new medication is only prescribed for a week or two, the patient may not need a dose adjustment.

We may recommend getting an EKG if the new medication is known to prolong the QT interval. It’s nice if that can be done at the opioid treatment program, but OTPs may not be doing regular screening, especially after the Cochrane report of 2013 called routine EKG screening of methadone patients into question. (See my blog post of 9/19/13)

Should an EKG be done? Who should do it? What should we do if the QT interval is prolonged? If the second medication is essential to treat a serious ailment, should the patient’s methadone dose be reduced? Should that patient switch to buprenorphine? Is the risk of partially treated opioid addiction potentially more harmful to the patient than the other serious ailment for which the patient is being treated?

I don’t know the answers and I can’t find anyone else who can give me solid answers about what to do in cases where my patients are prescribed other medications that interact with methadone. For now, I am taking what I feel are prudent precautions, and trying hard not to over-react and pull a patient off methadone, since I know for sure methadone is live-saving. It’s important to remember that just because an interaction is possible doesn’t mean it will happen.

If another doctor prescribes a medication short-term that may interact with methadone, I want the patient to be informed of a possible reaction. I may, with the patient’s permission, call the doctor to ask them if it can be changed to a safer medication, or I may ask the nurses to check with the patient about sedation or withdrawal each day when they come in to dose. Sometimes I’ve asked patients on higher take home levels to come to the OTP more often for closer monitoring until we see the full effects of a new medication, then return them to their usual take home status.

Patients need to tell us when they stop medications, too. I had one patient who was on phenytoin (Dilantin) for the treatment of seizures. Since this medication induces methadone metabolism and drops the serum methadone level, I had increased the patient’s dose of methadone to keep him out of withdrawal. But then, deciding he no longer needed to take phenytoin, he suddenly stopped it and became sedated. Thankfully he reported his sedation to the nurses and we quickly figured out what had happened. His dose had to be lowered quite a bit to prevent overdose, since off phenytoin, his blood level of methadone apparently rose abruptly.

At one of the OTPs where I work, I can easily get an EKG to monitor the QT interval. At the other, I have to ask the other doctor to check and EKG. Particularly with psychiatric medications, this creates difficulties, since psychiatrists usually don’t do EKGs in their offices. The patient has to be referred to a third facility if I feel an EKG is essential. This can become expensive to a patient without insurance, so it’s better if the doctor prescribes a medication that doesn’t affect the QT interval, if possible.

As time goes on, I think we’ll get more information about medication interactions with methadone, and I’d like to see more specific guidelines about how to handle potential

Advertisements

Inspired at AATOD

aaaaaaatod

I just got back from the AATOD (American Association for the Treatment of Opioid Dependence) conference, and I feel inspired, enthusiastic, and relaxed.

Several days before I left for the conference, I talked to a pregnant patient at one of the opioid treatment programs where I work. This patient, dosing on methadone, said her obstetrician insisted she taper down on her dose during pregnancy. When she told me that, my shoulders slumped with fatigue and disappointment. This was a doctor I’ve called on the phone a few times, and met in person once. We’ve talked collegially, and I physically, personally handed her a copy of ACOG/ASAM (American College of Obstetrics and Gynecology, American Society of Addiction Medicine) position paper on the treatment of opioid-addicted pregnant patients.

Needless to say, that document does NOT advise taper of methadone during pregnancy. When I talked to this obstetrician, I’d explained why we usually need to increase the dose during pregnancy. Yet now she’s telling a patient to lower her dose. This is not best practices.

I felt tired, and hopeless about improving physician education in my area. Do these doctors have Teflon brains, and all the information I’ve been trying to provide keeps sliding off their cortexes, into the ozone somewhere?

Yesterday at the AATOD conference, I heard a lecture by one of the main authors of the MOTHER (Maternal Opioid Treatment: Human Experimental Research) trial, Dr. Karol Kaltenbach. I’ve posted blogs about this trial (see Dec 16, 2010, March 23, 2013), which randomized opioid-addicted pregnant women to treatment with either methadone or buprenorphine. The goal was to compare outcomes of the babies born to moms maintained on methadone versus buprenorphine.

Dr. Kaltenbach opened her lecture by making an excellent point: use of legal drugs such as alcohol and tobacco during pregnancy are viewed as public health problems, even though they cause as much or more harm to the fetus as illicit drugs. Yet the general public demonizes moms who use illegal drugs. Pregnant women who use illegal drugs are faced with harsh moral judgments, and punitive responses.

Alcohol, a legal drug, causes harm to 40,000 kids per year, and is the leading preventable cause of developmental disabilities. Consistently, research shows physical and behavioral effects in the children born to moms who drink alcohol. Even though researchers have stated that there’s no safe amount of alcohol during pregnancy, according to the 2011 NSDUH (National Survey of Drug Use and Health), 9% of pregnant women said they were current drinkers, 2.6 said they were binge drinking, and .4% were heavy drinkers.

Pregnant smokers of tobacco are more likely than non-smokers to have a variety of complications, including spontaneous abortions, placenta previa and placental abruption, retardation of fetal growth, low birth weight babies, and preterm labor and birth. After delivery, the risk of SIDS (Sudden Infant Death Syndrome) is six times higher than for babies of non-smoking moms. Their babies are more likely to have ADHD, inattention disorders, ear and respiratory infections.

Yet newspapers now publish sensational articles about “addicted babies” born to mothers with opioid addiction, while ignoring the more common and more harmful effects of alcohol and tobacco. Remember the “crack baby” scare of the 1990’s, which was a media creation with no backing by science?

From the MOTHER study we learned that babies born to moms on buprenorphine have about the same risk of withdrawal, called neonatal abstinence syndrome (NAS), as babies born to moms on methadone. In both groups, fifty percent of the babies had NAS severe enough to need medication to treat opioid withdrawal. The babies were scored on the Finnegan scale, which grades the babies on many signs of withdrawal to indicate when treatment is needed. (By the way, at the AATOD conference I sat near Loretta Finnegan, creator of the Finnegan scale and internationally recognized for her many contributions to the field of alcohol and drug abuse!)

So in both groups, about half of the babies needed medication for withdrawal symptoms. However, the babies with NAS born to the moms on buprenorphine required 89% less medication (morphine solution) and spent 43% less time in the hospital as compared to the babies with NAS born to moms maintained on methadone. The babies born to moms on buprenorphine also spent 58% less time being medicated to treat their NAS.

That’s a significant benefit.

This study was very important for many reasons, but after these results, buprenorphine is slowly becoming the standard of care for pregnant opioid-addicted moms, if it’s available. True, there was a higher drop out of the moms on buprenorphine, but it was not statistically significant, and the moms didn’t leave treatment; they dropped out of the study for whatever reason.

Now for the exciting part: a supplemental study of these children is being completed. This data hasn’t yet been published, but Dr. Kaltenbach says it will show that kids of moms on methadone and buprenorphine were compared and assessed at three months, six months, twelve, twenty-four, and thirty-six months. A standardized scoring system for infant development called the Bayley Scale was used to study these children, and the groups were compared to scores for normal children.

Dr. Kaltenbach says there are no differences between the babies born to methadone versus buprenorphine, and better yet – both groups showed scores in the normal ranges on this scale. The scale measured things like language and motor skills, cognitive abilities, and conceptual and social skills.

The kids are alright!

This data is going to be a huge comfort to worried moms, dosing on methadone or buprenorphine.

And I got inspired at the AATOD conference. I heard one speaker tell the audience “you do it until they get it. You tell them over and over and over again. Whatever it takes.” And I thought to myself, this is correct. I can’t give up on the obstetricians in my area. Maybe they don’t agree with me, but I am not out on a limb with what I’m saying. It’s backed up with fifty years of studies and science. I am listening and reading information from the experts in the field. I need to be persistent, and keep repeating the data, mailing the data…skywriting the data…whatever.

It’s refreshing to be around people who understand opioid addiction and its treatment. It’s encouraging to hear how workers in the opioid addiction field are finding new ways to help our patients and advocate for them.

I’m going to call this OB – again –and re-inform her – nicely – about what’s found in that position paper, co-authored by doctors from her own specialty. I’m also going to suggest she direct some of her concern towards her patients who use the legal drugs of alcohol and tobacco, since they cause significant harm to infants.

And yes, I know most of the patients enrolled in OTPs also smoke, and I am going to help them with that, too…if they want it.

1. http://www.asam.org/docs/publicy-policy-statements/1-opioids-in-pregnancy—joint-acog-4-12.pdf?sfvrsn=2

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

Guest Dosing at Opioid Treatment Programs

aaaaaaguest

Patients of opioid treatment programs have to dose daily on their medication, unless they meet criteria for take home doses. For buprenorphine (formerly known as Suboxone or Subutex) regulations have loosened in many states, so that take home doses are granted much earlier. (The federal regulations have completely dropped the time in treatment requirement for take home doses of buprenorphine.) But for methadone, patients have to dose at the facility each day for at least the first ninety days, and after that, if doing well, they can get up to three take homes per week for the next ninety days, then up to four per week after a half of a year, and so on.

What happens if the patient needs to go out of town?

There are three options: leave treatment, the worst option, because of the increased risk of death for patients who leave treatment; special take home doses, often risky if the patient isn’t able to take them as prescribed; and guest dosing.

Guest dosing means a patient of one treatment program can be dosed at another program if that patient travels to another area. All opioid treatment programs send their patients for guest dosing and allow guest dosing for patients of other facilities. It should be a smooth and simple process, under ideal circumstances.

But sometimes circumstances get complicated.

Most difficult are the last-minute guest dosing requests. These tend to come at particularly stressful times for the patient, because often a patient’s family member is sick, or just passed away. The patient needs to be with his family.

Setting up guest dosing at the last minute is more difficult for the referring clinic, the accepting clinic, and the patient. Most clinics ask for 24-48 hours advance notice for guest dosing, but some situation don’t allow that much time. We do the best we can, try to explain circumstances to the receiving clinic, and usually are able to work out something.

Guest dosing requires good communication between clinics. Usually the home clinic needs to fax a form with the patient’s picture, their dose, and any take home doses to be dispensed. Most receiving clinics like to see at least the last three drug screen results. Some receiving clinics ask for a doctor’s signature to assure the physician is aware of the guest dosing request. Then when the guest dosing patient arrives at the receiving program, the nurse calls to verbally confirm all of the info on the guest dosing request.

Some opioid treatment programs charge steep guest dosing fees, affecting the patients’ ability to pay for guest dosing. Some clinics charge a one-time fee to set up guest dosing, and after that pays the same as any other patient dosing at that clinic. Some programs charge elevated fees every day the patient guest-doses.

As the medical director, I am consulted any time one of our patients wants to guest dose at another clinic, and any time a patient from another clinic wants to guest dose. We have general guidelines for guest dosing, but often have to consider other factors.

For example, at both of the treatment centers where I work, we prefer not to guest dose patients during induction. Induction is the riskiest time of treatment, and usually lasts at least thirty days. But each request must be considered and the risk/benefit analyzed. What about if a patient admitted three weeks ago finds out a close relative is dying, and wants to be with them? I might agree with guest dosing such a patient, if she is doing well, isn’t actively using benzodiazepines or alcohol, and won’t be gone for many days.

Some clinics won’t allow guest dosing for any patient with positive drug screens. Generally I would agree with that, but for me it depends on what the drug is, and why the patient needs to go out of town, and for how long. For example, if a patient is stable on his dose, but is still smoking marijuana with every drug screen positive for THC, I’d still support guest dosing if this patient needs to work out of town. I’m not OK with continued illicit marijuana use, but the problems caused by missing a work opportunity may be greater than problems caused by marijuana use. If that same patient were using benzodiazepines or alcohol, I probably wouldn’t agree with guest dosing, due to the much higher risk of methadone when combined with these drugs. If the marijuana-smoking patient wanted to guest dose out of town in order to attend a friend’s bachelor party…I’d be hesitant, as I’ve heard rumors that these events tend to involve heavy drinking of alcohol. I’d have to talk to the patient.

Guest dosing in patients on buprenorphine is usually out of the question, since so few programs are using buprenorphine. One of the programs where I work is owned by CRC Health, and they are the only large opioid treatment program operator (that I know of) offering buprenorphine at all of their clinics. If a buprenorphine patient is lucky enough to be traveling near one of CRC’s clinics, guest dosing can be arranged easily.

But since buprenorphine is such a safer medication than methadone, usually we can get permission for take home doses, if the patient doesn’t already qualify for them. Even though federal regulations dropped the time-in-treatment requirements for take homes in buprenorphine patients, my state still requires time in treatment, unless we ask for an exception, which is usually granted.

The whole goal of treatment is to help drug addicts regain their ability to live a normal life. Opioid treatment programs should make every effort to remove obstacles to travel during treatment, while still following state and federal regulations. And of course, the freedom to travel and guest dose must be balanced with patient safety. Ideally, the decisions regarding guest dosing should be made by the physician, who is informed by the input of the treatment team, so that the best possible decisions can be made.

How to Switch from Methadone to Buprenorphine (Suboxone)

Change Can Be Good

Change Can Be Good

I’ve helped about thirty or forty people switch from methadone to buprenorphine. Some were patients at my office, where I do office-based treatment with buprenorphine (formerly known as Suboxone or Subutex), and some have been patients at one of the two opioid treatment programs where I work.

Most of the time, the transition goes smoothly; however, around fifteen percent of the time, the patient doesn’t feel right on buprenorphine and goes back to methadone. I haven’t found a way to predict who will do poorly with buprenorphine.

Most of these patients had been in treatment for months or years, and were trying to taper their methadone dose. These patients heard that since buprenorphine is a partial opioid, it’s easier to taper off of than methadone. For the most part, that seems to be true, but everyone’s different.

Some patients switched because they wanted a medication that wasn’t as “heavy” as methadone. Most patients say they feel lighter, or less medicated, or more normal, on buprenorphine as compared to methadone.

Buprenorphine seems to have fewer medication interactions. For patients with complicated medical problems on many medications, it’s a better choice. It’s also a better choice for patients who have prolonged QT interval syndrome (condition of the heart) from methadone.

Also, restrictions on take home doses for buprenorphine when it is prescribed at opioid treatment programs aren’t as strict as rules for methadone, because buprenorphine is much safer than methadone. Patients switch to buprenorphine to get take homes more quickly, particularly helpful if they live a great distance from their treatment program.

In January of 2013, the federal government dropped the time in treatment requirement for take home doses for buprenorphine. With methadone, a patient has to be doing well with negative urine drug screens for a minimum of ninety days before getting extra take home doses. According to the new federal law, buprenorphine patients can get take homes regardless of time in treatment, so long as they meet all the other seven requirements for take homes. (These are: negative drug screen including alcohol, no ongoing criminal activity, regular clinic attendance, absence of serious behavioral problems at the clinic, stability of home environment, assurance that take-home doses can be stored safely, and rehabilitative benefits to the patient outweigh risk of diversion).

Some states have more restrictive regulations than federal law. In that case, the opioid treatment program has to follow the more restrictive of the two laws. In my state of North Carolina, time in treatment regulations still apply. However, I can petition the state opioid treatment authority for early and extra take home doses for patients who are doing well, and those requests are nearly always granted.

Some patients switch to buprenorphine at the opioid treatment program to prepare for transition to an office-based buprenorphine program. Office-based treatment is better for patients who have made progress on their recovery, and need less oversight with dosing of their medication. It’s an excellent step for stable patients.

Buprenorphine is a partial opioid and methadone is a full opioid. And buprenorphine has a higher affinity for opioid receptors. This means that it sticks like glue to the receptors, and if there’s methadone on the patient’s opioid receptors, buprenorphine will toss it off, throwing the patient into withdrawal. That’s a simplistic explanation, but you get my drift. This is why patients on methadone have to be in at least moderate withdrawal before taking the first dose of buprenorphine. Otherwise, the patient will be miserable, in withdrawal, with little to be done to ease the situation.

I ask patients to taper to about 30 or 40 milligrams of methadone per day prior to making the switch. I recommend tapering by about 5mg per week, or more slowly if needed. If I’m in the opioid treatment program on Mondays, I ask the patient to take her last dose of methadone on Friday, and then skip Saturday and Sunday. I see her first thing on Monday and evaluate the degree of withdrawal. By then, this patient has gone without methadone for seventy-two hours, and should be in at least moderate withdrawal. We check vitals signs (blood pressure, heart rate, etc.) and check a COWS (clinical opioid withdrawal scale) score. I talk with the patient and do a quick exam. If she’s in enough withdrawal, we start buprenorphine, usually at 4mg. If possible, we have the patient stay for an hour or return in an hour so we can see how she’s feeling. Sometimes we give a second dose on that first day.

Here are some issues I’ve seen in patients making the switch from methadone to buprenorphine:
-Coming down too fast on the methadone dose. Don’t zoom from 115mg to 40mg in a week or two and expect the transition to buprenorphine to go well. It probably won’t. I tell patients that if you’re going to expend time, money, and energy in making the switch, do it the right way, and optimize your chance for success.
-Not planning ahead for the increased cost of buprenorphine. In most clinics, buprenorphine costs more than methadone. If it’s not financially feasible over the long term, it’s best to stay on methadone.
-Expecting to take buprenorphine for a few weeks and then taper off with no withdrawal. Most people do not have this experience. Even the taper off buprenorphine can take months and be difficult. Besides, getting off opioids is one thing; staying off is another. I tell patients not to taper off buprenorphine unless they are ready. Have they spent the time getting counseling against relapse? Have they changed friends, and put distance between them and people still using drugs? Do they work around people using drugs? Do they have a chronic pain condition that will require opioids intermittently? If so, what’s the plan to avoid relapse?
– If buprenorphine lasts longer than methadone, don’t be tempted to miss days without telling your counselor what is going on. Some patients on buprenorphine are able to dose three times per week, so talk to your doctor about setting this up instead of missing days on your own.
-DO NOT attempt to divert medication. At one treatment center, we’ve detected many patients trying to “save” part of their dose for later use. I think most are telling the truth, but some are probably selling their medication. I can’t tell who is selling and who is saving doses for later. If we have a problem with patients selling their medication in the community, our treatment program can get a bad reputation in the community and even get closed down. So we have to act on any attempt to divert medication, and at times may even have to dismiss a patient from treatment, which I hate to do. So don’t divert medication.
-Don’t feel bad if buprenorphine doesn’t work for you. No medication works for everyone. If methadone did work, go back to it. Methadone has been around for forty years and has a proven track record.

I’m happy to work for two opioid treatment programs who offer both buprenorphine and methadone. It’s a little more difficult to offer buprenorphine, and the profit margin is likely much slimmer than treatment with methadone, but it’s the state of the art treatment. I fear some methadone clinics are going to get left behind with their “methadone only” mindset. Methadone will always be needed, but now we need to have other choices readily available for patients seeking treatment. Soon, I think we will see opioid treatment centers also offer naltrexone/ naloxone, medications that can prevent opioid relapse in patients who have completed withdrawal from opioids.

Methadone Dosing: Use the Evidence

methadone

methadone

The most successful opioid treatment programs and the most successful patients in those programs use evidence-based dosing of methadone. Many studies over the last 40 years show patients do better on adequate doses of methadone. They have better outcomes when they’re on enough methadone to block physical withdrawal signs and symptoms than when they’re on insufficient doses.

In the past, methadone clinics often had dose caps. Some clinics told their patients they didn’t need any more than 60 or 70mg of methadone per day. But over the last 40 years, we have multiple studies showing poorer outcomes at clinics with these low dose caps, as opposed to individualized dose determination. Numerous studies show higher drop-out rates in patients on doses less than 60mg, as well as more illicit opioid use and higher rates of HIV infection, as compared to patients on 100mg or more. For most patients, the blocking effect is seen in the neighborhood of 80 to 120mg of methadone per day. (In Tennessee, there are still dose caps. In that state, doctors have to get approval from a non-physician at the state’s Department of Mental Health to take a patient’s dose above 120mg.)

Patients vary widely the way they metabolize methadone. A patient with slow methadone metabolism may do best on 30mg of methadone per day, and a fast metabolizer may need much more than 120mg per day. This rate of methadone metabolism is probably determined by our genetics. When patients ask me how much methadone they should be taking, my answer is, “Enough.” I’m not advocating taking doses higher than they need to be, but if the patient looks like they’re in withdrawal, and they feel like they’re in withdrawal, it’s best to take the dose up. We want to use the lowest effective dose.
There are still misguided opioid treatment programs that try to keep methadone doses low. Sometimes clinic staff can send shaming verbal or nonverbal messages, and imply patients who ask for an increase in their dose are somehow trying to get one over on the clinic. Staff shouldn’t shame patients who ask for a dose increase; staff should defer decisions about methadone dosing to their medical personnel.

Sometimes patients don’t want to increase their dose of methadone because they have mixed feelings about their treatment. If they feel guilty about being in a methadone program, they may want to keep their dose low. Sometimes family members, with the best of intentions, will demand the patient stay on a low dose, not understanding that their loved one is less likely to do well on an inadequate dose.

Frequently I see patients who are feeling bad, not sleeping, and achy all over in the mornings, and dosing at 40mg. I ask them if we can increase their dose, and they say something like, “No, I promised myself I wouldn’t go higher than 40mg.” Too often, patients don’t increase their dose for fear that coming off methadone will be harder to do at higher doses. This may be partly true. It may not be harder to come off of, but it take longer to taper off a higher dose. But the patient won’t do as well while they’re in treatment, so what’s the point?

Some patients prefer low doses because they want to have just enough methadone per day to keep them out of terrible opioid withdrawal, but not so much to block the euphoria they get from using an illicit opioid later in the day.
I tell patients that methadone is a little like chemotherapy. For chemo to work, you have to take a big enough dose to do the job. It’s the same way with methadone. It’s not a perfect analogy but patients get what I’m saying.

Let’s turn to the other side of dosing. I’ve seen some clinics with many patients on what I would consider very high methadone dosing. It’s hard to criticize, because I do think there are some patients who need doses higher than 250mg, particularly if they’re on certain medications, or are pregnant. But that’s rare, and at some clinics, many patients seem to be on these big doses. Since these patients have their dose increased slowly, they build a tolerance to the methadone, so such patients aren’t sedated. There’s no long-term damage to the body with very high dose methadone, but higher doses can cause some problems.

It may be hard for a patient on a very high dose to transfer to another clinic. Some methadone clinic medical directors are hesitant to accept a patient in transfer if they’re on 200-plus milligrams of methadone, unless there’s evidence that this dose is required. For example, I was looking over the records of a patient on 290mg, in preparation for transfer. This man was on no other medications and otherwise healthy. When I saw the peak and trough data, I was puzzled, because they were both high, and this was done at 200mg of methadone. So why was the patient taken to 290 milligrams? I know peak and trough levels aren’t the only factor to be considered when determining the right methadone dose, but there was scant information about why the doctor decided to raise the dose, or even if the patient had even seen the doctor recently. I wasn’t particularly concerned the patient would be sedated, because the dose had been raised slowly, over months. But I was concerned that the patient was on more methadone than he needed, especially since many of the patients at this clinic were on doses of more than 200mg per day.

Some studies have shown higher doses of methadone affect the way electrical impulses are transmitted through the heart. In some studies, higher methadone doses are more likely to produce prolongation of the QT interval than lower doses. (2) This QT prolongation does put patients at risk for a potentially fatal heart rhythm problem. The medical literature at present suggests that periodic EKG screening of patients on doses above 100mg is probably a good idea, but there’s still disagreement on this issue.

There is another factor to be considered. This may offend some readers, but we need to acknowledge the nature of addiction. It’s a disease who tells its sufferers, “More is better!” I think it’s important to acknowledge this point, and discuss it openly, but not in a shaming way. This psychological part of addiction doesn’t always go away within the first few weeks.
My approach to a patient on a relatively high dose, who desires an increase in methadone, is to meet with the patient, preferable prior to dosing. Sometimes I like to meet the patient two hours post-dose if I’m worried about sedation. I ask about withdrawal symptoms and check for pupil size and reaction, and other signs. I check the last drug screen. If the patient doesn’t describe withdrawal symptoms, and I don’t see objective signs of withdrawal, I’ll ask the patient how they expect to feel on an ideal dose of methadone, and if it’s possible their addiction is driving the desire to increase. I’m surprised that most patients aren’t offended, but welcome the opportunity to talk openly. Some patients say they honestly can’t tell if they are in withdrawal, or if their addiction tells them they are in withdrawal. My job is to help decide which it is.

Some patients feel “high” for the first few days after a dose increase, but tolerance builds quickly to this feeling. Some patients mistakenly believe they should always get that high after dosing. If the addiction is driving the patient’s way of thinking, the dose may never be “enough.” When I explain this to patients, most understand.

1. http://international.drugabuse.gov/sites/default/files/pdf/methadoneresearchwebguide.pdf
2. Krantz, Lewkowlez, Hays, et.al., “Torsade de Pointes Associated with Very-High Dose Methadone, Annals of Internal Medicine, Sept. 17, 2002, Vol 137(6) pp 501-505.

Closing Down a Methadone Clinic

 

I read the front page article in last week’s Alcoholism and Drug Abuse Weekly with mixed emotions. http://www.alcoholismdrugabuseweekly.com/

The state of Minnesota revoked the license of the only methadone treatment program in the city of Duluth and ordered it to shut down. This order was suspended until the outcome of an appeal by the owners on the clinic, Colonial Management Group.

I felt angry and chagrined.  I support methadone treatment programs, both because they conduct one of the most evidence-based treatment interventions in all of medicine, and because that’s the type of setting where I work. I’ve seen the life changing benefits many patients get from methadone treatment. Closing this clinic would deprive opioid addicts of an effective treatment for their addiction in the city of Duluth, and existing patients would be essentially abandoned.

But bad clinics harm the reputations of good clinics. The list of charges against the clinic is appalling, and if true, couldn’t be ignored. I’d hope that instead of closing the clinic, some other option could be found. CSAT’s Nic Reuter, interviewed for the ADAW piece, said that in extreme cases, a team of professionals could be requested from CSAT, to come to this program and make changes, help turn things around.

I’m also suspicious. A Duluth newspaper had run a weeklong series of articles critical of for-profit methadone clinics just before the order to close was issued. Is this a bad clinic or the victim of a witch hunt? Were the inspectors pressured to find flaws, or were the flaws chronic and egregious?

I’ve worked for one non-profit program with several different clinic sites, and I’ve worked for four for-profit sites. If I graded overall quality of care, I’d rank the non-profit program fourth.  Just because a program is non-profit doesn’t mean it’s well-run, and for-profit clinics often are extremely well-run. From my personal experience, the bias against for-profit programs isn’t justified.

Colonial owns fifty-eight clinics in seventeen states, according to the ADAW article. I’ve never worked at a Colonial clinic, but I do know they’ve had problems in other states.

At one Colonial program near me, I heard from several of their former patients that their clinic once ran short of methadone. According to these two sources, the clinic reduced everyone’s dose until they could procure more methadone. I would die of embarrassment if I worked for a clinic that did such a thing. I would much rather guest dose everyone at a nearby clinic so that the patients didn’t de-stabilize. Guest-dosing would likely cost both clinic and patients extra money, though.

The Colonial programs in my area also allow methadone patients to have prescriptions for benzodiazepines, because I’ve had a few patients transfer for that reason. In my medical opinion, this is prohibitively risky for most patients, though may be appropriate for a limited few.

I’m more suspicious than the average person because I’ve worked at a well-run clinic that was the victim of an apparent witch hunt. I believe the pair of inspectors from the state’s Division of Health Service Regulation arrived with an agenda…to uncover nefarious doings at the methadone clinic. Their routine would have been comedic, if the outcome hadn’t been so awful.

Prior to this encounter, I’ve had positive experiences with the state’s methadone clinic inspectors. They were educated and competent, and often able to suggest ways to do things better and more efficiently, based on what they’ve seen at other clinics. Before I encountered this pair, I viewed inspectors not as adversaries but as potential information resources.

These two were different. They caused one problem after another at the clinic they were inspecting. I wasn’t there, but heard second hand that they interrogated nurses and counselors in an aggressive and demeaning manner. I believe these accounts, because they did the same with me.

After several days spent inspecting and disrupting the clinic, they wanted to talk to me because I was the medical director at that time. First of all, they were an hour and a half late for our appointment, which did not endear me to them. When they finally appeared, their dress and demeanor didn’t inspire confidence that a fair evaluation was about to be done. One of them was openly hostile to methadone maintenance treatment and the other didn’t say anything…but she wore an outfit that could be fittingly accessorized by a lamppost and a public defender, if you get my drift.

The spokeswoman of the two was a nurse – she kept reminding me of that for some reason – who would ask questions along the lines of, “Have you stopped endangering patients yet?” A yes or no answer wasn’t possible. Plus, at first, part of my mind was distracted, marveling at the silent partner’s outfit. I was wondering if I could ever get away with wearing an ensemble like that to work. Probably not, since we couldn’t even wear open-toed shoes…plus, was I a little too long in the tooth to be able to pull it off?….Maybe if I had tattoos like her…

“Why do you let patients keep going up on their dose?” Her aggressive tone snapped me back to attention. “Wouldn’t you agree few people need more than 70mg?” I tried to educate her that best results were seen when patients were at blocking doses, and that 70mg wasn’t a blocking dose for many people. She stared at me over the top of her reading glasses for a long moment. Then she sighed deeply and slowly shook her head side to side as she wrote something on her papers.

Then she said I was providing substandard care by not doing EKGs on patients. This was in 2007, and ironically enough I’d just returned the week before from an ASAM conference where we talked in detail about whether EKGs should be done and under what circumstances. I told her there was no clear consensus yet, but that may become the standard of care. She argued, said no, I was wrong, that was the standard of care now.

She asked why patients with positive drug screens were allowed to remain in treatment. My eyelid started to twitch about them, because it was clear she knew nothing about methadone maintenance treatment, but held a strong bias against it. I told her many patients have positive drug screens, and we see best results by keeping them engaged in treatment. If they’re still using opioids, we actually need to increase their dose, as I described before. And she argued with me about that.

I asked if she’d ever inspected methadone clinic before ours. She said no, but that she was a seasoned state inspector. Hoping to educate her, I asked her if she was familiar with TIP 43, SAMHSA’s published guideline to methadone treatment of opioid addiction. She said no. I jumped up and ratted around in several counselors’ offices, finally finding a copy that wasn’t too dog eared. I gave it to her, hoping she would read it. If she’d read it before trying to inspect a methadone clinic, she’d have known how to do her job better.

The next day, I wrote a complaint letter to her supervisor at the state, describing her objectionable behavior and lack of knowledge. I heard nothing more until a few months later, when a disjointed and rambling report, authored by the nurse inspector, accused my clinic of numerous misdeeds. We were charged with two major level one violations and charged thousands of dollars in fines for substandard care.

Her report was so jumbled that I couldn’t tell specifically what the violations were, but they seemed to focus on a patient in methadone maintenance who had surgery and received post-operative pain pills. Her report said this could have caused a fatality and was substandard care. (So much for my hope that she would read TIP 43!). This patient had actually received great care. Release of information was passed both ways, to and from her methadone clinic. She didn’t relapse on her post-op prescriptions, and had no problems. But this inspector thought she ought not to have been allowed to take opioids post-operatively.

This report was released to local media, and an article based on her report landed on the front page of the city paper. The real facts – that this woman didn’t have the education to be able to know if a clinic was well-run or not – weren’t known to the writer at the paper. Our clinic, coincidently a non-profit, took the case to court. Possibly to avoid a public hearing, the state dropped the level one charges and the fines. The clinic was left with several misdemeanor violations, easily cleared up. Everyone seemed happy but I still object to the misplaced power this woman had. I had looked forward to a public hearing so that flaws of the present system could be exposed and fixed. This inspector had caused harm to our clinic’s reputation.

This year, five years later after that episode, I heard this same inspector, still employed by the state, gave a very negative report of another clinic. The regional director of that clinic described it as an unfair hatchet job, and I have no doubt that’s true. I don’t understand why the state allows such a person to represent them in the field.

So in summary, the Duluth Colonial program may be a bad clinic that should be overhauled and possibly managed by a special team if other treatment options can’t be located for the patients. Or it may have received unfair assessment by someone with a political axe to grind.  Things are not always what they appear to be in the world of medication-assisted treatment.

Methadone Dosing in Opioid Treatment Programs: Use the Evidence

The most successful opioid treatment programs and the most successful patients in those programs use evidence-based dosing of methadone. Many studies over the last 40 years show patients do better on adequate doses of methadone. They have better outcomes when they’re on enough methadone to block physical withdrawal signs and symptoms than when they’re on insufficient doses.

In the past, methadone clinics often had dose caps. Some clinics told their patients they didn’t need any more than 60 or 70mg of methadone per day.  But over the last 40 years, we have multiple studies showing poorer outcomes at clinics with these low dose caps, as opposed to individualized dose determination. Numerous studies show higher drop-out rates in patients on doses less than 60mg, as well as more illicit opioid use and higher rates of HIV infection, as compared to patients on 100mg or more. For most patients, the blocking effect is seen in the neighborhood of 80 to 120mg of methadone per day.

However, there’s a great deal of difference between how patients metabolize methadone. A patient with slow methadone metabolism may do best on 30mg of methadone per day, and a fast metabolizer may need much more than 120mg per day. This rate of methadone metabolism is probably determined by our genetics. When patients ask me how much methadone they should be taking, my answer is, “Enough.” I’m not advocating taking doses higher than they need to be, but if the patient looks like they’re in withdrawal, and they feel like they’re in withdrawal, it’s best to take the dose up. We want to use the lowest effective dose.                                                                                                                                 

There are still misguided opioid treatment programs that try to keep methadone doses low. Sometimes clinic staff can send shaming verbal or nonverbal messages, and imply patients who ask for an increase in their dose are somehow trying to get one over on the clinic. Staff shouldn’t shame patients who ask for a dose increase; staff should defer decisions about methadone dosing to their medical personnel.

Sometimes patients don’t want to increase their dose of methadone because they have mixed feelings about their treatment. If they feel guilty about being in a methadone program, they may want to keep their dose low. Sometimes family members, with the best of intentions, will demand the patient stay on a low dose, not understanding that their loved one is less likely to do well on an inadequate dose.

Frequently I see patients who are feeling bad, not sleeping, and achy all over in the mornings, and dosing at 40mg. I ask them if we can increase their dose, and they say something like, “No, I promised myself I wouldn’t go higher than 40mg.” Too often, patients don’t increase their dose for fear that coming off methadone will be harder to do at higher doses. This is partly true. It may not be harder to come off of, but it does take longer to taper off a higher dose. But the patient won’t do as well while they’re in treatment, so what’s the point?

Some patients prefer low doses because they want to have just enough methadone per day to keep them out of terrible opioid withdrawal, but not so much to block the euphoria they get from using an illicit opioid later in the day.

I tell patients that methadone is a little like chemotherapy. For chemo to work, you have to take a big enough dose to do the job. It’s the same way with methadone. It’s not a perfect analogy but patients get what I’m saying.

Let’s turn to the other side of dosing. I’ve seen some clinics with many patients on what I would consider very high methadone dosing. It’s hard to criticize, because I do think there are some patients who need doses higher than 250mg, particularly if they’re on certain medications, or are pregnant. But that’s rare, and at some clinics, many patients seem to be on these big doses. Since these patients have their dose increased slowly, they build a tolerance to the methadone, so such patients aren’t sedated. There’s no long-term damage to the body with very high dose methadone, but higher doses can cause some problems.

It may be hard for a patient on a very high dose to transfer to another clinic. Some methadone clinic medical directors are hesitant to accept a patient in transfer if they’re on 200-plus milligrams of methadone, unless there’s evidence that this dose is required. For example, I was looking over the records of a patient on 290mg, in preparation for transfer. This man was on no other medications and otherwise healthy. When I saw the peak and trough data, I was puzzled, because they were both high, and this was done at 200mg of methadone. So why was the patient taken to 290 milligrams? I know peak and trough levels aren’t the only factor to be considered when determining the right methadone dose, but there was scant information about why the doctor decided to raise the dose, or even if the patient had even seen the doctor recently. I wasn’t particularly concerned the patient would be sedated, because the dose had been raised slowly, over months. But I was concerned that the patient was on more methadone than he needed, especially since many of the patients at this clinic were on doses of more than 200mg per day.

Some studies have shown higher doses of methadone affect the way electrical impulses are transmitted through the heart. In some studies, higher methadone doses are more likely to produce prolongation of the QT interval than lower doses. (2) This QT prolongation does put patients at risk for a potentially fatal heart rhythm problem. The medical literature at present suggests that periodic EKG screening of patients on doses above 100mg is probably a good idea, but there’s still disagreement on this issue.

There is another factor to be considered. This may offend some readers, but we need to acknowledge the nature of addiction. It’s a disease who tells its sufferers, “More is better!”  I think it’s important to acknowledge this point, and discuss it openly, but not in a shaming way. This psychological part of addiction doesn’t always go away within the first few weeks.

My approach to a patient on a relatively high dose, who desires an increase in methadone, is to meet with the patient, preferable prior to dosing. Sometimes I like to meet the patient two hours post-dose if I’m worried about sedation. I ask about withdrawal symptoms and check for pupil size and reaction, and other signs. I check the last drug screen. If the patient doesn’t describe withdrawal symptoms, and I don’t see objective signs of withdrawal, I’ll ask the patient how they expect to feel on an ideal dose of methadone, and if it’s possible their addiction is driving the desire to increase. I’m surprised that most patients aren’t offended, but welcome the opportunity to talk openly. Some patients say they honestly can’t tell if they are in withdrawal, or if their addiction tells them they are in withdrawal. My job is to help decide which it is.

Some patients feel “high” for the first few days after a dose increase, but tolerance builds quickly to this feeling. Some patients mistakenly believe they should always get that high after dosing. If the addiction is driving the patient’s way of thinking, the dose may never be “enough.” When I explain this to patients, most understand.

I could be wrong, but I have an impression that very high doses are seen more frequently in patients enrolled in large, for-profit methadone clinic chains, with numerous facilities scattered across the country. I wonder if the doctors working there talk often with their patients, examine them, and talk about their symptoms and expectations.

I’d like to hear feedback from patients at opioid treatment centers. What do you think? Are clinic doctors too reluctant to order dose increases? Or too quick to increase doses, without talking to the patient?

 

  1. http://international.drugabuse.gov/sites/default/files/pdf/methadoneresearchwebguide.pdf

      2. Krantz, Lewkowlez, Hays, et.al., “Torsade de Pointes Associated with Very-High Dose Methadone, Annals of Internal Medicine, Sept. 17, 2002, Vol 137(6) pp 501-505.