Archive for the ‘American Society of Addiction Medicine’ Category

Drug Interactions with Methadone

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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

A Really Good Book – For Free

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If you haven’t read CASA’s (Center on Addiction and Substance Abuse, at Columbia University) masterpiece publication from June, 2012, titled “Addiction Medicine: Closing the Gap between Science and Practice,” you should do so. This publication can be downloaded for free, and has essential information about addiction and its treatment. http://www.casacolumbia.org/addiction-research/reports/addiction-medicine

Casa also has other free and informative publications about other issues, like how to reduce the risk of addiction in teens (“The Importance of Family Dinners” series), the cost and impact of untreated addiction on society (“Shoveling Up”), substance abuse and the U.S. prison population (“Behind Bars” series), and the availability of drugs on the internet ( “You’ve got Drugs” series). All of these contain useful and thought-provoking data.

“Addiction Medicine: Closing the Gap between Science and Practice” outlines all aspects of what is wrong with addiction treatment in the U.S., along with recommendations about how we can fix this broken system. When it was published in June of 2012, I thought it would be would be widely read and discussed. However, I’ve only heard it mentioned once, and that was at an ASAM meeting. I wish popular press, so eager to write sensationalistic pieces about addiction, would write more fact-based information.

Every politician should read it. Every parent should read it. Physicians and treatment center personnel should read it. Anyone who is concerned about the extent of addiction and its poor treatment in the U.S. should read it.

CASA describes their key findings of the drawbacks of the U.S. system – or non-system – of addiction treatment. This nation is doing many things wrong, to the detriment of people afflicted with addiction, their families and their communities. Our mistakes are based on ignorance, misperceptions, and prejudice. All of these impede our ability to help our people with addiction. The CASA report describes these factors and how they have contributed to our present situation.
Our nation hasn’t waged a war on drugs, but rather on people who use drugs.

The CASA report describes how public opinion about addiction isn’t based on science. Science proves addiction is a brain disease, yet this fact is still debated. We know that continued use of addicting substances alters the structure and function of the brain, affecting judgment and behavior about the continued use of drugs even when bad consequences occur. We know that half of the risk for developing addiction is determined by genetic makeup. Yet surveys show that about a third of U.S. citizens still feel addiction is due to lack of willpower and self-control. Why are public attitudes so disconnected from science?

Addiction is a complicated diagnosis, existing as it does at the end of the continuum from occasional drug use to regular use to compulsive use. People often compare a drug user with a drug addict. They say that since the drug user was able to stop when he wanted that the drug addict should be able to stop when he wanted. This compares apples to oranges. If someone can comfortably stop using drugs when given a good enough reason to do so, this person isn’t an addict. They may be a drug abuser, a problem user, and at high risk for addiction, but they haven’t crossed the line into uncontrollable use.

The CASA report pointed out that most addiction treatment and prevention isn’t done by physicians and health professionals. Most addiction treatment is provided by counselors who, for the most part, aren’t required to have any medical training. Only six states require a bachelor’s degree to become an addiction counselor, and only one (Alabama, go figure) requires a master’s degree.

Even when physicians are involved in the treatment of addiction, most of us have very little, if any, training in medical school or residencies about addiction prevention or treatment. Ironically, most of our training focuses on treating the consequences of addiction.

In medical school and residency, I spent countless hours learning about the proper treatment of cirrhosis, gastritis, anemia, pancreatitis, dementia, and peripheral neuropathy from alcohol addiction. I had little if any training about how to treat alcohol addiction, and none about how to prevent it.

We know brief interventions by physicians during office visits can reduce problem drinking and are an effective way to prevent problems before they occur. Yet few physicians are trained to do this brief intervention. Even if they are trained, primary care physicians and physician extenders are being asked to do more and more at each visit with patients, and asked to do it with less and less time. Primary care providers may not be adequately paid for screening and brief intervention for problem drinking and drugging, and valuable opportunities are lost. Yet that same patient may consume hundreds of thousands of healthcare dollars during only one hospital admission for medical consequences of problem alcohol use.

When I practiced in primary care, I often thought about how I never got to the root of the problem. I would – literally – give patients with serious addiction strikingly absurd advice. “Please stop injecting heroin. You got that heart valve infection from injecting heroin and you need to quit.” I could see it was ineffective, but I didn’t know any better way at the time. I assumed if there was a better way to treat addiction, I’d have learned about it in my training.

Wrong. The doctors who trained me couldn’t teach what they didn’t know themselves.

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.

I didn’t learn about the evidence-based treatment of opioid addiction until I agreed to work at a methadone clinic for a few days, covering for a friend of mine when he wanted to go on vacation. I was amazed to learn about decades of evidence showing the benefits of such treatment.

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.

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, and that includes 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. Hopefully we will see a change since the parity law was passed. (which told insurance companies they had to cover mental health and substance addiction to the same degree they cover other health problems)

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, not knowing any better, 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.

Check out this landmark publication at CASA’s website: http://www.casacolumbia.org

Information from the ASAM Conference: the CDC

At the recent ASAM conference, Dr. Ileana Arias, Deputy Director for the Centers for Disease Control and Prevention, spoke at a plenary session, explaining the public health impact of our epidemic of prescription drug abuse and addiction. She did a great job explaining how bad the problem of opioid addiction has become in the U.S. She also had some great slides. The above slide shows how by 2008, poisonings overtook motor vehicle accidents as the number one cause of death in the U.S. Overwhelmingly, the poisonings were drugs, and the vast majority of these drug overdose deaths involved opioids. Dr. Arias explained the ice berg phenomenon, where for each person who dies from opioid overdose death, an estimated 118 are estimated to meet the diagnosis for opioid abuse and dependency. She presented information showing that the amount of prescription opioids sold quadrupled between 1999 and 2010.

Dr. Arias spoke at our conference to encourage us and to let us know the CDC was committed to help solve our nation’s prescription opioid addiction problem.

She outlined some of the measures the CDC is taking to help prevent opioid addiction and overdose deaths.  She explained the new lock-in programs now being used by some insurance companies, where the patient can have only one doctor and one pharmacy to prescribe and fill medications. The CDC is advocating for all states to have prescription monitoring programs, and for those state programs to be linked, so that a doctor can access medications filled in other states.

Dr. Arias mentioned the progress being made in Florida, where pill mills are being shut down. Unfortunately, some pill mills have moved to other states like Georgia, Texas, Louisiana, Ohio, and – my favorote state to criticize – Tennessee.

She also spoke of the success of medication take-back days, where people drop off old medication for appropriate disposal so that it doesn’t fall into the wrong hands, and she described many other actions the CDC has started.

This was all great information, familiar to those of us treating opioid addiction over the past five to ten years. I’m grateful the CDC has joined the effort to quelch this problem. Their resources and experience can help a great deal. I just wish all doctors in the country could hear her message.

The addiction medicine doctors had a chance to make comments and further suggestions to the CDC through Dr. Arias, and I was pleased to see how carefully she listened.

One of the suggestions I liked the best addressed the expense of maintaining state prescriptoin monitoring programs. Apparently these can cost around a million dollars a year to administer. One doctor said why not have the pharmaceutical companies that make and sell controlled substances pay or help pay for the monitoring programs? These companies are the main entities that have benefitted from the sales and diversion of their products; why not ask them to bear at least some of the cost for detecting the problems they cause? Genius, though it would be hard to mandate the pharmaceutical companies to do this.

One doctor suggested that law enforcement personnel be educated about the types of treatment available to opioid addicts, so they can stop being barriers toward effective treatments, namely medication-assisted treatments using buprenorphine and methadone.

Another doctor suggested the CDC promote the naloxone programs that provide kits to reverse fatal opioid overdoses. Why not help fund these projects and/or help create more? The Harm Reduction Coalition estimates there are around 155 naloxone programs in the U.S. Some are government-funded and some are privately funded, but around 10,000 fatal opioid overdoses have been reversed. Like Project Lazarus in North Carolina, many of these programs started at a grass roots level because citizens got involved.

Another doctor made the extremely common sense suggestion that the best way to allow more patients into suboxone treatment would be to allow doctors to treat more than one hundred patients at a time. At present, suboxone doctors are allowed to have no more than thirty patients on buprenorphine in their first year prescribing, and no more than one hundred after the first year. This would cost next to nothing for the government to implement, and expand treament dramatically.

One of our past ASAM presidents endorsed mandatory physician education as a requirement for maintaining medical license.

One person compared the prescription opioid addiction to HIV infection in past years, and commended the CDC on its past efforts to reduce the stigma associated with having HIV. This person asked the CDC to make public service announcements to help reduce the stigma of addiction, and encourge people to get treatment.

Another doctor asked the CDC to produce public service announcements telling people to lock up their medications, to prevent medication diversion to a teen or other person for whom it was not prescribed. This doctor also said that patients need to know that not all pain conditions require prescription opioids. He recommended telling the general public the true risks of opioid addiction, which have been downplayed. In the past, pain medicine experts underestimated the incidence of addiction in patients prescribe opioids for chronic pain for more than three months.

The CDC representative, Dr. Arias, confirmed that the CDC already has plans to make PSAs about pain pills and pain pill addiction, much like their present (and very successful) anti-smoking television PSAs.

All great information, and now let’s get the word out to all physicians, and the public too.

Medications in the Military

While I was at the ASAM meeting in Atlanta last month, I heard an interesting presentation by Diana Jeffery, PhD, from the Department of Defense. She described the results of an assessment of controlled substance medications prescribed to U.S. military personnel on active duty in 2010.

To put her information into context, the military’s Health Related Behavior Survey, done every three to five years, showed a near-tripling of self-reported prescription medication misuse, going from 4% in 2004 to 11% in 2011. This health survey asks anonymous questions of randomly selected military personnel, regarding drug and alcohol use, as well as questions about tobacco use and some gender-specific topics.

In the newer 2010 survey, information was gathered on schedule II, III, and IV controlled substances prescribed to about 1.4 million U.S. active duty military personnel during 2010. The study’s interesting results show that during 2010, approximately 26.4% of these military personnel were prescribed an opioid, which compares to 11% of the civilian population. Central nervous system depressants were prescribed to 11% of military personnel, while only 3.4% of civilians were prescribed these sedatives. And for stimulant medications, only 1.1 % of military were prescribed these, while 1.7% of civilians were prescribed stimulants.

When further examining the information about prescribed opioids, 90% of the military personnel received between 1 to 5 prescriptions for opioids during 2010, and 6% of personnel has from 6 to 10 prescriptions, and 2% received more than 15 prescriptions during 2010.

In further analysis of opioid prescriptions, personnel over age 45 were more likely to be prescribed opioids, and those in the Army and Air Force were twice as likely to be prescribed opioids as personnel in the Navy, marines and Coast Guard. (The latter arms of service tend to have younger personnel than the Army and Air Force.)

Around 32% of active military personnel had a prescription for any controlled substance during 2010, which compares to around 14% for the U.S. civilian population.

Around 8% of military personnel were prescribed controlled substances for more than 90 days, and those with prescriptions were more likely to have been injured, have mental illness, substance abuse or dependence, be male, and be married.

For me, this information raises more questions than it answers. Are military personnel overmedicated? After all, they should be much healthier than civilians, since many illnesses exclude people from military service. But on the other hand, this survey was done on people actively serving in the armed forces. Many of the personnel receiving opioids were wounded in battle, whether in 2010 or earlier. With more advanced treatments available in this war compared to those twenty years ago, soldiers with more severe injuries are able to survive their injuries, and need treatment for the pain of those injuries. For many injuries, that pain doesn’t go away after a few weeks.

And what about the central nervous system sedatives? Are soldiers in active combat impaired by these medications? From this data we can’t tell if military personnel are taking sedatives once every couple of weeks to help them sleep, or if are they taking three doses every day while in active service. That would make a huge difference, because one pattern of use wouldn’t cause impairment, while multiple daily dosing can impair.

The Army branch of the military has already initiated measures to help reduce the risk of addiction. For example, known risk factors for the development of addiction are noted by Army physicians: past treatment for anxiety or depression, past personal history of drug or alcohol abuse or addiction, increased stress, or family history of addiction. Then the patient can be given more information about his or her personal level of risk when prescribed potentially addictive medications. The Army has also been more closely monitoring the use of scheduled prescription medication, to identify a problem with medication misuse early.

As in civilian life, the risks and benefits of potentially addicting medications have to be carefully considered to avoid over or under reaction to the information gleaned from the military’s studies. Many more studies are on the way to further illuminate the incidence and risks of addiction in military personnel.