Archive for the ‘methadone’ Category

Methadone Overdose Deaths: First Two Weeks

Methadone

 

Methadone is a tricky drug to start, due to the narrow margin between therapeutic dose and fatal dose. Making it more difficult, people vary a great deal in the rate at which they metabolize methadone.  Some people have a methadone half -life as short as 15 hours, while others have half- lives as long as 60hours. The average is 22 hours. So even for people with a high tolerance to other opioids, increasing methadone too quickly can be deadly.

Methadone’s long half-life makes it good for a maintenance medication, since after stabilization, there’s not much fluctuation in the blood levels. However, the long half-life makes it more difficult to adjust the dose. The change I make in a patient’s dose today may not be fully experienced by the patient for five or more days.

The tolerance to the anti-pain effect of methadone builds faster than the tolerance to respiratory suppression, adding to the danger. When methadone is used inappropriately, patients may take more methadone to relieve pain, but by the time the pain is gone, they could easily have taken a methadone overdose.

All of this explains why the first two weeks of methadone maintenance treatment are the most dangerous. According to some studies, death rates for patients starting methadone at opioid treatment programs are actually higher during the first two weeks than when using illicit opioids. (1, 2)

Even so, it’s a risk worth taking, given the proven life-saving benefits of methadone (and buprenorphine) maintenance

Patient overdose during the first two weeks is a serious concern for doctors working at opioid treatment programs. We must do all we can to keep patients safe. It’s a fine line; if we start at too low of a dose or go up too slowly, we risk having our patients drop out of treatment. And if we increase the dose too quickly, it increases the risk of overdose…

The American Society of Addiction Medicine (ASAM) recently updated their methadone induction guidelines. In past years, doctors working at opioid treatment programs (OTPs) tended to start patients at 30-40mg and increase the dose rather quickly. Now, the expert ASAM panel recommends a starting dose of 10-30mg. If that dose isn’t sufficient to suppress withdrawal, a second dose can be given after three hours, so long as the total dose is not greater than 40mg. The expert panel recommends increasing the dose no more quickly than every five days, and no more than five milligrams at a time.

Some patients are more susceptible to overdose, and physicians should consider lower methadone starting doses for these people:

-Age over 60

-Using sedating drugs like benzodiazepines

-Regularly consume alcohol

-Are on prescription medications which can interact with methadone

-Medically fragile patients, for example patients with coronary artery disease, morbid obesity, -chronic obstructive pulmonary disease (COPD), or sleep apnea

-Have risk factors for prolonged QT interval, such as a recent heart attack, personal history of heart rhythm problems, or family history of heart disease

-Patients who have been abstinent from opioids for five or more days (e.g. recent incarceration, recent detoxification or hospitalization). These patients lose some of their tolerance and might be more prone to overdose with any opioid.

 

Interestingly, the degree of withdrawal that the patient has when entering treatment does not correlate with the dose of methadone they will need to get rid of withdrawal symptoms. In other words, one person in terrible withdrawal may need a smaller dose than another person with milder withdrawal. The degree of withdrawal that a patient feels is only partly due to opioid tolerance. Genetic makeup may be the reason why some people have more severe withdrawal than other people.

While I always ask my new patients how much opioid they have been using per day, that alone doesn’t determine methadone starting doses. There’s incomplete cross-tolerance between other opioids and methadone, meaning we can’t use the table of equianalgesic doses.

Last week I found an interesting article describing a large study of Canadian methadone patients, which will contribute even more to what we already know about risk during the first two weeks of methadone. This study showed which patient characteristics are associated with overdose death.

The study was done in Canada from 1994 until 2010, and covered over 43,000 patients enrolled in an opioid treatment program in those years. The study looked at all overdose deaths in this patient population and found 175 deaths deemed to be from opioids. These cases were matched with patients who entered treatment around the same time as the patient who died, creating a nested case-control study.

This study found, as expected, a higher degree of risk in the first few weeks on treatment. In this study, patients in the first two weeks of treatment were 16 times more likely to die in the first two weeks of treatment than any other time in treatment.

Psychotropic drugs were associated with a two-fold risk of overdose death overall, with antipsychotics associated with a 2.3-fold risk and benzodiazepines a 1.6-fold increased risk. Antidepressants were not associated with increased risk of overdose death. Alcohol use disorder diagnosis was also associated with a two-fold increase risk of overdose death.

Even more interesting, heart disease was associated with over five times increased risk of overdose death, and serious lung disorders (sleep apnea, COPD) were associated with a 1.7 times increase in overdose death.

This is a powerful study because it was so large.

This is information I can use. I’ve been stressing about patients whom I thought were at increased risk – those who use alcohol and benzodiazepines, and those with severe lung disease. While these patients are at higher risk, from this study it appears patients on anti-psychotics are at even higher risk. And I need to do a better job of getting patients to see primary care doctors, to screen for heart disease, which gave the highest risk of all.

As time goes on, I think we’ll get more information about which patients are at higher risk. Those patients need a higher degree of interaction with treatment center staff, and better coordination of care with mental health providers and primary care doctors. I know I plan to implement a system at the OTP where I work to make sure I see patients more often if they have the risk factors described.

Obviously any patient death is a terrible thing. Of course it’s worst for the family, but it also affects the treatment team. I feel badly for the families of those 175 patients in the Canadian study who died, but they gave us information that can hopefully help us provide better care for future patients.

 

  1. Caplehorn et al, “Mortality Associated with New South Wales Methadone Programs in 1994: Lives Lost and Saved,” Medical Journal of Australia, 1999 Feb 1;170(3):104-109
  2. Cousins et al, “Risks of drug-related mortality during periods of transition in methadone maintenance treatment: A cohort study,” Journal of Substance Abuse Treatment, October 2011, Vol 41(3); pp252-260.
  3. Leece et al, “Predictors of opioid-related death during methadone therapy,” Journal of Substance Abuse Treatment, Oct 2015,

Who Should NOT Be in Medication-Assisted Therapy with either Methadone or Buprenorphine?

addiction cartoon

I spend much time and effort explaining how medication-assisted treatment for opioid addiction works for many addicts. It occurred to me that I should explain who isn’t a good candidate for such treatment.

I enthusiastically support medication-assisted treatment (MAT) of opioid addiction, but no treatment works for everyone. MAT doesn’t work for every opioid addict. Here are some reasons a patient may not be suitable for MAT:

1. The patient isn’t addicted to opioids. That seems obvious, but occasionally I encounter an addict who wants to be started on methadone even though he’s not addicted to opioids. Rarely, an addict using cocaine, benzodiazepines or other drugs will come to the OTP after they have heard how well it worked for other (opioid) addicts. After I explain that buprenorphine (Suboxone) and methadone only work on opioid addiction, some of these patients have become angry.

One patient accused me of discriminating against her because of the type of drug she used. I said yes, but only because methadone doesn’t treat cocaine addiction. (I tried to refer her for more appropriate treatment.)

2. The patient takes opioids for pain, but has never developed the disease of addiction.
Such a patient may be physically dependent, but lacks the hallmark indicators of addiction, such as misuse of medication, obsession and compulsion regarding opioids.

Opioid treatment programs, (OTPs) have stringent regulations put on them by both federal and state government, because OTPs are designed to treat patients with addiction. These patients have lost the ability to control their intake of opioids, so the OTP regulates a maintenance dose of either methadone or buprenorphine to keep the patient out of withdrawal and able to function normally.

If a patient has only pain and no addiction, there’s no reason to enroll in an opioid treatment program, because patients without addiction are still able to take opioid medication as prescribed. Pain medication can be prescribed by any doctor with a DEA license.

Opioid treatment programs aren’t intended to treat chronic pain, but if a patient with both addiction and chronic pain finds methadone also helps with pain, it’s a nice benefit. Many of these patients do find they have less pain once they’re out of the miserable cycle of intoxication and withdrawal. So less pain is a happy side effect of addiction treatment.

3. The opioid addict presenting for treatment has been physically dependent for less than one year.
Methadone is difficult to get off of, and federal and state regulations say it cannot be prescribed for opioid addicts with less than one year of addiction (daily use or near daily use). This is a somewhat arbitrary cut off, and the OTP physician can ask for an exception to this regulation if needed. Even if the OTP wants to treat the patient with buprenorphine (Suboxone), which is usually much easier to taper off of than methadone, permission must be sought from state and federal authorities before enrolling a patient who has used opioids less than one year.

If buprenorphine is prescribed in the office setting, the prescribing physician can use her best judgment about who is appropriate for treatment, without needing government approval.

4. The opioid addict has the ability to go to a prolonged inpatient residential treatment program for his addiction.
This is controversial, because some doctors think medication-assisted treatment should be given to everyone because of its success rate compared to abstinence-only treatments.

But who gets the best of medical treatment in our country? Possibly it is medical professionals like doctors and dentists, airline pilots, politicians, and celebrities. They usually get the gold standard of treatment for whatever disease ails them.

If such people have opioid addiction, they are treated with inpatient medical detox, using buprenorphine to ease withdrawal, followed immediately with prolonged inpatient residential drug addiction treatment. I know doctors and dentists who spent six to nine months in treatment. After treatment, they must sign monitoring contracts with their licensing boards in able to go back to work. These contracts usually involve a mandated number of group sessions per week and random drug testing. With this kind of support and accountability, these medical professionals have excellent outcomes. Studies show that more than 80% are still off all drugs and alcohol at five years after entering treatment.

If only everyone could get that kind of treatment!

If this kind of treatment is available to the addict…take advantage of it. But most opioid addicts can’t access this kind of treatment, with post-treatment accountability. Insurance companies might pay for a one-week stay in detox, which won’t help. Even if the addict gets a few weeks of inpatient treatment, it’s usually not enough. What I’m talking about is months of quality inpatient treatment.

5. An opioid addict who is also physically addicted to alcohol, benzodiazepines or other sedatives. These drugs can be deadly when mixed with methadone or buprenorphine. I prefer such patients enter a medical detox unit to get off these sedatives prior to entering treatment in an OTP.

Of course this is a complex issue, and there may be times when starting methadone or buprenorphine can be done, perhaps keeping the patient at a relatively low dose, while the patient undergoes a gradual taper from benzos. The OTP physician should be free to use her best judgment about how to treat these complex and high-risk patients.

6. The opioid addict also has acute, severe mental illness. An actively suicidal patient is too sick for an outpatient opioid treatment program. So is an acutely psychotic patient who is having hallucinations and delusions. These patients often can’t to understand what is real and what isn’t. Ideally these patients need inpatient treatment at a facility that will treat both mental illness and addiction. Sadly, it’s getting ever harder to find such facilities for patients who need them.

7. A patient has behavior that interferes with treatment.
OTPs have an obligation to all their patients to maintain a safe and orderly treatment environment. Patients who start physical fights, threaten staff or other patients, or sell drugs shouldn’t be kept in treatment. I know that sounds harsh, but OTPs have a hard enough time maintaining good standing in their communities without having to face accusations about illegal behavior on premises.

Patients need to be emotionally stable enough to conduct themselves in a non-threatening manner to be able to remain in treatment. Some patients, after being counseled about acceptable behavior, are able to comply with requests for behavioral changes. Some patients have erratic behavior due to mental illness, and shouldn’t be blamed, but their behavior still may be too disruptive for the OTP setting.

8. The patient has serious co-existing physical health problems.
Actually, I can’t think of any physical health problem that would make the treatment of opioid addiction with methadone riskier to the patient than untreated opioid addiction. We know for sure that untreated opioid addiction produces high risk of death and disability.

Issues like severe lung disease and specific heart rhythm problems do increase the risk of medication-assisted treatment, especially with methadone. I try to contact the patient’s other doctors and consult with them before the patient goes above a low dose of methadone.

Ideally, I’d like to talk to the other doctors on the day of admission, before methadone is started, but that can’t always be done. With the time pressures doctors are under, it’s getting ever harder to claim some of their time for a patient consultation.

Some of these patients could be started on buprenorphine instead of methadone, which is safer with these health conditions, and has fewer medication interactions.

9. The patient has transportation difficulties.
Some patients can’t get a ride to their treatment program every day, which interferes with delivery of quality treatment. With buprenorphine, federal requirements for daily dosing were lifted, but states still have varying regulations. With methadone, the patient must come for treatment daily. During the first two weeks of stabilization, it’s important for medical personnel to be able to evaluate the patient every day, to assess the effects of dose increases.

10. A patient who enters treatment expecting to be completely drug free in the near future.
I try to make sure patients entering treatment with methadone or buprenorphine understand that I am not switching them from illicit opioids to these medications because tapering off of them is easier. Particularly with methadone, it is not. But both methadone and buprenorphine are so long-acting, they can be dosed once per day, giving the patient a steady level of opioids. This allows the addict to function normally, without withdrawal or impairment, once the dose has stabilized.

Both medications give the opioid addict time to regain physical and mental health. Once on a stable dose, the recovering addict can make changes in his life, with the help of counselors and other OTP workers. The addict can get back to work, stop a life of crime, form better relationships with his family and himself, and recover a better quality of life.

Will that addict ever do well off methadone? There’s no way to be sure about this. Some patients can taper off methadone, as long as they address all of their issues prior to the taper, and if they bring the dose down slowly enough that they don’t feel intolerable withdrawal. Some, perhaps most, recovering addicts find they will do better if they stay on methadone.

All this is to say that the goal of entering an opioid treatment program isn’t necessarily to
get off the treatment medication.

So if a patient seeks to enter methadone treatment but also expresses a desire to be off buprenorphine or methadone within weeks to months, I tell them their expectations aren’t realistic. These medications don’t work like that. If the patient wants to get off all medications quickly, they need referral to an inpatient program. This way, patients can’t later say they were mislead, and they feel like they have liquid handcuffs, chained forever to methadone, with its many regulations for treatment.

News From the World of Addiction Medicine Research

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The latest issue of the Journal of Addiction Medicine, Vol. 7 (2) March/April 2013 had several interesting articles relating to opioid addiction and its treatment. Here’s my quick summary and thoughts on one of them, “Promethazine Misuse among Methadone Maintenance Patients and Community-Based Injection Drug Users,” by Brad Shapiro et al, pp. 96-1001.

This study attempted to get an idea of the prevalence of promethazine (better known under its brand name Phenergan) use in opioid addicts both in and out of treatment.

I was interested in this article because I’ve had methadone patients misuse promethazine. Most of these patients say that Phenergan gives them sedation with methadone, but most say it’s not a true euphoria, so I’m puzzled as to why they mix the two. Since promethazine can be sedating in many people, obviously I worry about overdose deaths when it’s mixed with methadone.

The authors of this study tested for promethazine in the patients enrolled in a county hospital methadone clinic in San Francisco. Twenty-six percent were positive for promethazine and only 15% had a prescription for this medication. Also, promethazine use was associated with benzodiazepine use.

The authors then recruited two hundred intravenous drug users, and discovered that only 139 were opioid addicts. Of those 139 addicts, seventeen percent reported promethazine use in the past month. However, of the addicts who had been on methadone in the past, twenty-four percent reported promethazine use in the past month.

What does this study tell us? The authors’ conclusion was that promethazine needs to be investigated further as a drug of abuse in opioid addicts.

Well, yeah.

My clinical experience gave me some thoughts about the study. For one thing, pregnant addicts were excluded. But in my experience, pregnant patients are the ones most likely to be prescribed Phenergan because of morning sickness during pregnancy. And this study doesn’t tell us much about the overdose risk when methadone and Phenergan are combined. Early in their article, they do provide some data: In Kentucky, over 14% of decedents from methadone toxicity overdose deaths also had promethazine present in their system. In Seattle, 2.5% of fatal overdoses had promethazine present.

Promethazine, along with many other medications, prolongs the QT interval just like methadone does. I haven’t seen any studies of methadone patients comparing QT intervals before and after promethazine, which may be helpful to further assess risk.

Important Factors for Successful Opioid Treatment Centers: Staff Experience

As discussed in my last blog entry, some opioid treatment centers (previously called methadone clinics) are better than others. Last time I blogged about the importance of communication between staff members. This blog is about the importance of hiring experienced, competent staff.

For an opioid treatment center, the worst counselor to hire is one who doesn’t believe in methadone. This should go without saying, but sometimes clinics hire people who are conflicted about methadone (or Suboxone), and either verbally or non-verbally communicate their uncertainty or negative attitudes about methadone. The effects on patients can be devastating. Fortunately most of these employees don’t remain at opioid treatment programs, either because they must be terminated for the welfare of patients, or because they quit on their own.

Some patients say they’d rather have a counselor who has personal experience with addiction and recovery, because he understands addiction at a deep level. Such a counselor can be valuable, but it’s not enough. A counselor also needs knowledge of counseling techniques and the skill to apply them appropriately. If recovery from addiction is the only attribute of your counselor, why pay for treatment? You can get the same thing for free at any 12-step meeting.

The factor most correlated with patient success in counseling is the relationship with their counselor. A warm and accepting, non-judgmental attitude is most successful. In short, compassion is important. While it’s true that another recovering addict can understand the pain of still-suffering addicts, non-addicts can be just as compassionate, and may have fewer preconceptions about what recovery must be.

The Substance Abuse and Mental Health Services Administration, often called SAMHSA (SAM-sah) for short, produces many publications to serve as guidelines for substance abuse and mental health treatment facilities. They’ve published “Technical Assistance Publication Series, Number 21: Addiction Counseling Competencies.” This document outlines all the necessary skills and knowledge that an addictions counselor should have to work in any drug addiction treatment program.

Counselors must understand addiction. They need to have education about drugs of abuse and how they affect the body and how withdrawal from various drugs affects the body. Counselors should know about all forms of drug addiction treatment, and know which treatment is most appropriate for their client. They should be able to apply helping strategies to best meet the needs of their clients.

Counselors need to be professionals, and conduct themselves in a capable and courteous way. One of my peeves is to hear clinic personnel refer to a urine drug screen positive for drugs as a “dirty” screen. Language matters. Counselors need to have a certain level of self-awareness with good boundaries. This prevents them from being too involved with their clients, or too distant from their clients. They need to follow the profession’s ethical standards. They need to be aware of the need for continued education and be open-minded to new information. This is a rapidly changing field, and counselors shouldn’t continue to work with dated knowledge from the 1980’s.

Once a clinic gets good counselors, they need to keep them. Patients get discouraged when they’re assigned a new counselor every few months. At one clinic where I worked several years ago, a patient told me he’d had six counselors over fifteen months. That’s not OK. Patients get tired of discussing their issues with one person and form a counseling relationship, only to have to start anew a few months later. Staff turnover discourages patients.

Of course, some turnover can’t be avoided in our mobile society, where people switch jobs frequently. But clinic owners need to try to keep good counselors (and nurses and doctors) and retain them to benefit the patients. Clinic owners should be willing to pay staff well, and provide adequate benefits.

Opioid treatment programs need to hire good nurses and doctors, too, with experience and training treating patients with addiction. Doctors should be certified in Addiction Medicine either through the American Board of Addiction Medicine, or through the American Academy of Addiction Psychiatry. And they need to go to continuing education meetings to stay current, since the field of Addiction Medicine changes so rapidly with new research and results.

When I started work at my first methadone clinic, I didn’t know much more than to start the dose low and increase slowly. In retrospect, I should have had more training. If a new doctor has no prior experience working in opioid treatment programs, I’d favor a training course similar to the  course available for doctors who want to prescribe Suboxone.

I love my present opioid treatment program, Stepping Stone of Boone. We’re a new clinic, and relatively small at around 130 patients. We opened in April of 2010, and have had no staff turnover. That’s right – none. All the staff that pioneered the clinic is still there, and all of the new people hired over the last 18 months have stayed. That’s a sign of a good clinic.

It’s a fun place to work because each of us loves what we do, and we believe in what we do. We enjoy not only our patients but also the other staff members. We feel like we are helping people.

My next blog entry will be about the importance of evidence-based dosing of methadone.

Qualities of Good Opioid Treatment Programs

Not all opioid treatment programs are created equal, meaning some are better than others. Over the years, studies have shown which clinic factors are associated with better patient outcomes. Over the next week or so, my blog postings will elaborate on each of the following factors:

  • Good communication between medical, counseling, and administration portions of the clinic
  • Experienced staff with adequate training and low turn-over
  • Low patient to counselor ratios
  • Program follows evidence-based guidelines for dosing
  • Opioid treatment program provide more care than just methadone treatment (also provide primary care, vocational rehabilitation, etc)

Today I’ll blog about communication between staff members. Communication is a good quality in any business, allowing it to run more smoothly. But it’s even more important in healthcare, where patients’ lives and well-being are affected.

In opioid treatment programs, communication happens in many ways, but case staffing is the most formal and efficient. Case staffing is when multiple members of the treatment team gather in one place, usually at a set time, to discuss what’s going on with patients. The treatment team usually includes all of the counselors, the nurses, the doctor, and the program manager. Besides communicating information about patients, case staffing also helps generate creative solutions to problems, and checks for negative emotions among staff. This can also be a forum where concerns about clinic protocols can be raised by staff.

At the program where I work, once or twice per week, after we finish seeing the day’s patients, the nurses, the counselors, nurses, program director and program manager sit in our lobby and discuss patients. First we talk about the new admissions. I tell the staff of any medical concerns I found on my intake assessment. For example, if a patient was found to have an enlarged liver on my exam, I ask the counselor to follow up with the patient later in the week to make sure the patient makes an appointment with his primary care doctor. The counselors raise concerns about new patients. Perhaps one of the counselors noticed symptoms of depression and we decide I should check that patient again the next week, when opioid withdrawal isn’t as severe.

Then we discuss established patients, and try to problem-solve. For example, maybe a patient needs to travel out of town for work, and there’s no opioid treatment program nearby where he can guest dose. We talk about the patient’s progress and whether it’s appropriate to ask the state methadone authority for extra take-home doses. We have some leeway to decide about Sunday and holiday take home doses, and discuss who is ready for these take homes.

Counselors may ask about how to approach ongoing drug use. The approach is different for different types of drugs. If a patient has had repeated relapses to opioids, maybe the methadone dose needs to be increased. If benzos are a problem, we must discuss if it’s safe to continue to dose that patient with methadone. For marijuana and cocaine, more intense counseling is indicated, and we discuss the best approaches.

Case staffing also helps us watch each other for negative attitudes. Patients with addiction sometimes behave badly. In active addiction, some addicts have had to lie and deceive to survive, and these tendencies don’t disappear overnight. The whole staff of an opioid treatment program needs to watch each other for negative or pessimistic attitudes developing toward patients.

For example, recently I was in a case staffing where we were talking about the repeated relapses of a patient. I made a comment which was more negative than the situation warranted, and this patient’s counselor appropriately challenged my comment. I’m no different than any other human and can take a skeptical view of a patient when it’s not reasonable. This counselor made me re-consider my opinion, and she was right to do so.

We talk about clinic policies that may need to be changed. For example, when patients can’t pay for treatment, how long do I have to taper their methadone dose? I’ve worked in clinics where if you didn’t have money for that day’s dose, you didn’t get a dose. They had no policy in place to allow a taper. I’ve worked in clinics where the dose was tapered over 4 days. At my present clinic, the dose is tapered over ten days. That’s still too short, and I’d prefer to keep everybody in treatment for free, but that’s not possible. The program would fold. I’ve had the unpleasant experience of working for a methadone program that closed because it ran out of money to operate. So it’s important to include the clinic administrators in some aspects of case staffing.

The best part of case staffing is talking about patient successes. Counselors talk about patients who are participating in counseling, who’ve had negative drug screens, and qualify for take home levels. Unless any staff member has concerns, I sign a form to make it official. We talk about patients who have recently gone through difficult situations without using drugs. We even have an unofficial “patient of the week,” a term for the patient who has worked hard on recovery and had a recent success. Sometimes it’s a patient who got a job promotion. Sometimes it’s a patient who has started going to 12-step meetings. Sometimes it’s a patient who has a negative drug screen for marijuana because he’s stopped smoking pot for the first time in his entire adult life.

Talking about this good stuff is so important for staff. We get to feel like we are at least some small part of the positive changes happening in the lives of our patients. Fortunately, there’s much to celebrate at every case staffing. As I’ve said before, I never saw the kind of positive changes when I worked in primary care that I see working in addiction medicine.

 

Dosing Methadone for Pain versus Addiction

Using methadone for pain is different from using methadone for addiction.

It’s illegal in the United States for a doctor to prescribe methadone for the purposes of treating addiction, unless she is working at an appropriately licensed Opioid Treatment Center. Some doctors don’t know this, and have had grumpy DEA agents pay them a visit. However, it is legal for a doctor to prescribe methadone for pain, as long as she has an appropriate DEA license.

Methadone is prescribed differently when treating pain than when treating addiction. This is because each dose of methadone has an analgesic (anti-pain) effect of about six hours. However, methadone’s opioid blocking effect lasts for twenty-four hours or more. This is why methadone for pain should be dosed multiple times per day, but methadone for addiction can be given once per day.

The dose of methadone often varies, too, depending on the disease being treated. Doses of methadone 10 to 20mg, dosed three to four times per day, are adequate to treat pain for many patients. When treating addiction, studies have shown that patients do better when the doses are high enough to block other opioids. Usually, this occurs at doses 80 – 120mg per day, given as one dose. The patient doesn’t become sleepy or sedated at this dose because the dose is raised gradually, allowing time for tolerance to build to the sedating effect.

Some patients prefer to stay at a low methadone dose, so they can still feel intoxication from illicit opioids like heroin or oxycodone. For example, one patient told me he liked keeping his dose around 60mg, which was high enough to stave off the worst of his withdrawal symptoms. But it was also low enough to allow him to feel high from an injection of heroin in the evenings. He resisted going up on his dose as recommended by his treatment team.

Doctors have to be very careful prescribing methadone for pain. The very characteristic of the drug that makes it effective to treat addiction, its long duration of action, also makes it dangerous to prescribe. Too many patients, experimenting with methadone for the purpose of getting high, die of a drug overdose. Tolerance to the euphoric effect of methadone develops more quickly than the tolerance to the sedative effects. People consume a fatal dose before feeling high.

Over the last decade, the incidence of overdose deaths from methadone rose sharply. Most of these deaths were from people taking methadone pills, dispensed from local pharmacies, and prescribed by doctors who were treating patients for pain. Along the way, many milligrams were diverted to the black market, with disastrous results. Some methadone was diverted from opioid treatment centers, but appears to be a fraction of the total.

Given the overdose potential of methadone, it should be used cautiously when prescribed by physicians for pain. Soon, doctors may be required to take a training course before they can prescribe the long-acting opioids. This training will educate doctors on how to recognize if a patient is developing the complication of addiction, and to identify evidence of drug diversion.

Tramadol, AKA Ultram, Ultracet

I just returned from the American Society of Addiction Medicine’s spring conference, held in Washington, D.C. I go to at least one of their meetings every year, to stay current with the latest research and developments in Addiction Medicine. It was impossible to attend all of the sessions, since four or five meetings are often conducted at the same time. This makes it the intellectual equivalent of a three ring circus. I think I learned some new stuff, and will share some of this in my blog over the coming weeks.

The first day, I went to a day-long course called “Pain and Addiction: Common Threads.” I think this is the fourth time I’ve attended that particular seminar over the last eight years. I hear something new every year.

 It’s striking how much this meeting has changed. The first year I went was 2005. At that time, pain medicine specialists still debated with the addiction medicine specialists about the risk of addiction in patients who were prescribed opioids long-term for chronic non-cancer pain. By 2010, I didn’t hear any debates about the risk of addiction. I heard lectures about how to manage chronic pain without opioids, and about the risk of hyperalgesia in patients on long-term opioids. Hyperalgesia is an increased sensitivity to pain, sometimes seen in patients prescribed opioids for months or years. The human body accommodates to the presence of these prescribed opioids, which adjusts the pain threshold, making a patient on opioids paradoxically more sensitive to pain.

This year, the Pain and Addiction conference had lectures on several interesting topics, but one that captured my interest was about the not-so-safe “safe” medications. Included were carisoprodol (Soma), zolpidem (Ambien), butalbital (found in Fioricet and Fiorinal), and tramadol (Ultram). These are all medications that many doctors think are safe for addicts, but really aren’t all that safe.

I’ve seen many patients develop problems with tramadol, so the rest of this blog is about this medication.

Tramadol is a messy drug. It’s a pain reliever that has actions on several types of brain receptors: the mu opioid, serotonin, norepinephrine, NMDA, and other receptors. Because it stimulates the mu opioid receptors, it can cause feelings of pleasure as well as pain relief. Tramadol is far less active at the mu opioid receptors than its metabolite, and it takes time for the tramadol to be metabolized in the liver to its first metabolite. Because of this delay, some experts thought it wouldn’t appeal to addicts, who prefer an immediate high. Overall this is probably true, and tramadol has a much lower rate of addiction than other opioids, but it still causes addiction in some patients.

Some of tramadol’s pain relieving properties may also be produced by its actions on serotonin and norepinephrine receptors, since tramadol’s pain relieving capability is only partially reversed by a pure opioid antagonist like naloxone.

When this medication was first released, it wasn’t a controlled substance. That is, the DEA didn’t control it strictly like medications that can cause addiction. Now, it’s a Schedule IV drug, thought to have benefit but also some risk of addiction, though lower than that of hydrocodone, for example.

Tramadol is usually dosed in 50mg pills, one or two every six hours, giving the maximum dose of 400mg per day. Recreational use of this medication (to get high) is dangerous, since it causes seizures at doses higher than 400mg. In susceptible patients, it can even cause seizures at lower prescribed doses.

I’ve seen patients in tramadol withdrawal who were so sick it frightened me. This drug can produce a severe withdrawal. When it’s stopped suddenly, patients have opioid withdrawal symptoms like sweating, nausea, diarrhea, high blood pressure and heart rate, and severe muscle and joint pains. The sickest patient I’ve ever seen in opioid withdrawal had been using only tramadol, in doses of around 600mg per day. She had fever to 103 degrees, and dehydration from the diarrhea and vomiting. That patient needed hospitalization.

Besides the opioid-withdrawal symptoms, some of these patients also have withdrawal symptoms similar to those seen when certain serotonin-affecting antidepressants, like Paxil and Celexa, are stopped suddenly. They can have fairly severe anxiety, depression, mood swings, and restlessness. Many times they have weird sensory experiences, often called “brain zaps,” or the sensation of electric shocks throughout the body. They can have seizures during this withdrawal.

If the patient had only physical dependency and no addiction, the dose of tramadol can usually be tapered slowly over a few weeks to months, as an outpatient. But if the patient has not only physical dependency but also the disease of addiction, the obsession and craving for the medication will usually prevent a successful outpatient taper, unless a dependable non-addict holds the pill bottle, and dispenses it as prescribed.

Traditional treatment for tramadol addiction starts with detoxification. As above, that can rarely be done as an outpatient, so medical inpatient detoxification admissions for five to seven days can be helpful. However, since tramadol acts so much like an opioid, patients ready to leave detox probably need to go on to an inpatient residential treatment center for at least thirty days.  Intensive outpatient treatment probably isn’t enough support for these addicts. But that’s only my opinion, since I haven’t found any studies describing success rates with tramadol addicts.

Opioid maintenance medications like methadone and buprenorphine do stop the opioid-type withdrawal symptoms from tramadol, and patients probably benefit from medication-assisted therapy just like any other opioid addicts. Using these medications, they can be successfully treated as outpatients. However, as above, I can’t find any long-term studies of tramadol addicts on replacement medications. One of the addictionologists with whom I work doesn’t think it’s wise to put an addict who is addicted only to tramadol on methadone, given the lack of data. However, usually these addicts are using other opioids too, and physically addicted to them as well as tramadol.

Often, methadone patients at the opioid treatment centers where I work are given tramadol by their primary care doctors who think it’s a low risk medication for opioid addicts. It probably is lower in its risk for abuse, but it can cause withdrawal in patients on stable, blocking doses of methadone. (1)

Tramadol is a synthetic, pared-down version of codeine. Interestingly, a structurally similar medication, tapentadol, has just been released, and is now being sold under the brand name Nucynta. That medication is a schedule II drug, presumably because of a higher abuse potential than we’ve seen with tramadol. Tapentadol stimulates opioid mu receptors, and also acts as a norepinephrine re-uptake inhibitor, like some antidepressants. It will be interesting to follow abuse and addiction patterns with this medication.

The bottom line is this: if you are in recovery from addiction (alcohol or drugs) this medication should be used with caution. Let your doctor know that you’re in recovery from addiction. If you must take a potentially addicting medication, talk to your sponsor and your support network. Go to extra meetings. Let a dependable non-addict hold the pill bottle and dispense as prescribed. If you have to take the medication for more than a few weeks, have your doctor taper your dose instead of stopping suddenly.

I’ll have upcoming blog entries concerning Soma, Ambien, and Fioricet.

  1. Leavitt, MA, PhD, “Methadone-Drug Interactions,” Pain Treatment Topics, Addiction Treatment Forum, January 2006