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Dr. Column 3/97-9/97 / 10/97-3/98 / 4/98-10/98 / 11/98-7/99 / 8/99 - 7/00 / 8/00 -
High Dose Methadone Associated with Less Crime in
Released Prisoners - July 2000, Vol V. No. VII
Dependency Briefing
Dose Levels - June 2000, Vol V, No. VI
Pregnancy
Perplexed - Urinalysis - May 2000, Vol
V, No. V
Menopause
Methadone Deaths (article summary) - Dr. Andrew
Byrne - April 2000, Vol V, No. IV
Editor's Note
Test Negative for Benzos - Does Methadone Mask Other Meds? - March 2000, Vol V, No. III
Taking Extra Methadone & Proper Dosing // Methadone & Depression - Feb. 2000, Vol. V, No. II
Methadone--False Negatives and False Positives - January 2000, Vol V, No. I
Federal Regulations on Dosing over 100 or 120 mg
- December 1999, Vol IV, No. XII
Also: LAAM Dosing - Dr. Hopper
Do the Federal Regulations Discourage or Prohibit
Dosing over 100 or 120 mg? - November 1999, Vol IV, No. XI
Also: LAAM Dosing
Should You Tell Your Dentist You Are Taking Methadone? - September 1999, Vol IV, No. IX
Different Formulations of Methadone-
August 1999, Vol. IV, No. VIII
Dear Doctor:
Many patients have varying side effects and/or "feel" different formulations of methadone differently (e.g.: clear liquid methadone, cherry methadose, wafers, etc.); some patients say one kind will "hold" longer than another, or one is "better" than another. What is your opinion/experience with this? Does your clinic offer patients a choice as to what formulations the prefer? - Donna B.
Dear Donna:
We offer the orange Disket ®, white 5 and 10 mg. Tablets, clear liquid and OrLAAM [Note: OrLAAM is not methadone, it is another medication, with somewhat similar properties to methadone, used for maintenance therapy]. We have tried flavored liquids, but the patients did not like them. I do not obsess about why patients prefer one thing or another. We just try to make treatment as desirable as possible.
Marc Shinderman, M.D.
Center for Addictive Problems (CAP)
Chicago, Illinois
=============
Dear Donna:
There are always some patients who cannot tolerate certain formulations so alternatives should be available. Just as children sometimes need a 'spoonful of sugar', so adults also need to have a preparation which is tolerable. All formulations of methadone that I have heard of taste disgusting. Some people are driven to vomit just from the smell! We offer an alternative to the usual gluggy syrup as a pure solution without sugar, preservatives, alcohol, coloring or flavoring. About 10% of our patients cannot tolerate the usual solution and about half of these are happy with the pure solution (methadone powder dissolves easily in water). Tablets are not permitted by most State laws and are not feasible for doses over about 50mg anyway. Our average is now 90mg and maximum 400mg.
The more formulations we offer, the greater the patient acceptability and the higher the retention rates will be. Some side effects are due to the formulation while others may be due to the methadone itself. Hence in a perfect world we need to offer LAAM, buprenorphine, long acting morphine or other drugs for difficult cases. Some would even add prescribed heroin to the list as happens now in Switzerland.
I hope this information is useful.
--Dr. Andrew Byrne
General Practitioner, Drug and Alcohol, NSW, Australia
Be aware that regulations may differ State to State. For example, the following is written in Michigan's state regs:
I'd like to know if you think it's absolutely necessary to tell
a dentist or oral surgeon that a patient is on methadone. In my experience
over the years, I find the doctor AND dentists are super reluctant to give
me any kind of pain medication once I've told them I'm a methadone patient.
I plan on going to a new dentist, and I don't see any reason to tell this
lady about the methadone, do you? -MG
Dear MG:
The FDA consent to treatment specifies that you inform health care providers of your being on methadone/LAAM. Ultimately, the responsibility and timing for notifying the provider rests with you. I think notification is critically important if you are going to receive any medications or prescriptions from this provider. If you are asked to list your medications, you are protecting yourself from potential injury by letting the provider know about your methadone/LAAM treatment.
- John Hopper, M.D.
University Psychiatric Center
================
Dear MG:
In a perfect world you would always tell your dentist that you took methadone. I can understand some not doing so in the current climate of prejudice against dependent patients, some of whom have never used heroin in their lives, but are dependent on other opioids. The emergency ward is another place where a methadone history can cause a change in attitude of ignorant staff.
If there is any chance of the dentist or doctor giving "systemic" drugs (e.g. tablets or injections but not "local" anesthetics) then you should certainly reveal your other medications, including methadone. Certain pain killers contain partial opioid antagonists—pentazocine is an example—and these will cause immediate severe withdrawals in patients on methadone.
So you have to make another balanced decision, as elsewhere in
life. Do you risk the potential problems knowing that there may also
be adverse consequences in revealing that you are on methadone?
I hope this information is helpful.
Dr. Andrew Byrne,
General Practitioner, Drugs and Alcohol,
New South Wales, Australia
Do the Federal Regulations discourage or prohibit doses over 100 mg or 120 mg? Also, wouldn't a dose in excess of 200 mg just make the patient intoxicated? -B.P.
Dear B.P.:
The Federal Regulations do NOT discourage or prohibit doses over 100 or 120 mg.
The fact that the physician has to write in the chart "this patient requires a dose exceeding 100 mg" does not seem to be a significant obstacle. The fact that a letter of "exception" has to be written which justifies take-home privileges in such cases is not an overwhelming administrative burden either. I think that the feds get too much blame for this aspect of poor treatment.
Another particular is that they state that a very wide range of doses is associated with significant benefits in MMT, and that, surely, is a truth that resonates with all of our experience. I don't think they know how wide the range really is. We have one patient over 2000 (two thousand) mg currently, and "yes" it's hard to believe, and "no" she is NOT intoxicated.
Marc Shinderman, M.D.
(CAP, Chicago, Illinois)
======================================><>
In the proposed rules, the Secretary states that LAAM specific regulations may be dropped--in particular, the prohibition on LAAM take-homes [as currently, giving LAAM take-homes is prohibited].
I am curious as to how this might impact the dosing schedule for LAAM patients. As I understand it, the current dosing schedule for LAAM patients is Monday - Wednesday - Friday (a higher dose on Friday or sometimes a methadone take-home dose for Sunday). How might the dosing schedule vary if the prohibition on LAAM take-homes is lifted? Wouldn't it be better for a LAAM patient to dose every 48 hours? (i.e.: the patient would dose on: Monday-Wednesday-Friday and then the next week, Sunday-Tuesday-Thursday-Saturday, and so on...) -Curious
Dear Curious:
LAAM dosing, if left to patient take-homes, would become, for better or worse, all the possibilities that you mention and more (patients, people, do the darndest things). Now, patients take it as infrequently as twice a week.
LAAM has proven to be a very low value medication. It is
complicated, has many side effects in induction, is impossible to computerize
administration, is costly, and no one stays with it if they can get methadone
pick ups, except about one percent of the patient population in a pay clinic
(mine), where there is real choice.
Dr. Byrne's answer to Dear Curious:
The weekend dosing arrangements for LAAM patients have always worried me. If it is fine and satisfactory to miss two days on weekends, then why not the same in the week? For example: doses on Tuesday, Friday and then the following Monday? According to reports I have heard, for most patients the 72-hour gap is unsatisfactory and even a dose supplement for the weekend is not sufficient to prevent some withdrawal symptoms developing. If doctors used such schedules on other patients with medical illness they would be severely criticized for not acting in the patients' interests. It would be very unusual to do this for Prozac, Valium, penicillin or migraine medication. The practice is clearly being done for the convenience of the clinic and not of the patient. There is no evidence that LAAM as a dispensed drug is more harmful than methadone [Editor's note: methadone does no organic damage to the patient], and it is very likely that as a longer acting drug, it has less scope for illicit use. I believe that it should be given EVERY second day if this abolishes withdrawals and EVERY third day in any patients who find this suitable - presumably those with slower metabolisms and/or lower tolerance.
We know from good research (Rhoades) that when there are fewer visits to the clinic, there is an improved retention rate of those in treatment. A flexible approach to dispensed doses and transfers clearly also improves the acceptability of maintenance treatment. There is little dispute amongst experts in the field that there should be maximum supervision for new and unstable patients but less so as patients document their progress. There is still some uncertainty about whether this should be twice weekly or even less often. Isolated reports have shown certain selected stable patients can attend second or even fourth weeks with few, if any, problems (Senay; Novick).
Research shows that outcomes are significantly better in those who have some control over their doses (Goldstein et al. - ref. methadone) and in those on higher rather than lower daily doses (Strain - ref. LAAM).
Dr. Byrne was also asked whether LAAM treatment is available in
Australia—his answer follows:
No, there is no alternative to methadone in our country at present.
Various drugs have been used in trials, including a large interstate study
of buprenorphine, another long-acting opioid agonist absorbed under the
tongue. These trials usually employ parallel regulations to methadone
maintenance.
There are slightly different regulations in different states and, unfortunately, methadone is still not available at all in one remote area called the Northern Territory. Regulations can always be over-ridden by established, appropriate medical practice if approved by health authorities. I have never known them to reject a reasonable proposal based on sound principles and patient needs.
We know that methadone does not suit everyone. It is hoped that over the next year or two both buprenorphine and LAAM will be introduced into clinical practice in Australia so that family doctors, hospitals, clinics, psychiatrists and prison doctors will be able to offer these alternatives to methadone.
Dr. Andrew Byrne,
General Practitioner, Drugs and Alcohol,
New South Wales, Australia
Last month, the Doctor Column had a question regarding LAAM dosing schedules. In addition to the doctors whose answers appeared last month, Dr. John Hopper also sent us an answer to this question. Below is his answer, along with the original question.
Dear Doctor:
In the proposed rules, the Secretary states that LAAM-specific regulations may be dropped--in particular, the prohibition on LAAM take-homes.
I am curious as to how this might impact the dosing schedule for LAAM patients; as I understand it, the current dosing schedule for LAAM patients is Monday - Wednesday - Friday [a higher dose] and/or (sometimes/if possible) a methadone take-home dose for Sunday. How might the dosing schedule vary if the prohibition on LAAM take-homes is lifted? Wouldn't it be better for a LAAM patient to dose every 48 hours? (i.e.: the patient would dose on: Monday-Wednesday-Friday and then the next week Sunday-Tuesday-Thursday-Saturday, and so on...) Is it possible that some LAAM patients will need/would do better on "split dosing" schedules? (i.e.: Dosing every day [24 hours] instead of every 48-72 hours).
Dear Curious:
Most patients do very well with three times a week dosing [as described above]. Some patients cannot tolerate a 72-hour dosing interval [i.e.: the interval between the Friday and Monday dose], and the ability to have a take-home to maintain 48-hour intervals would be very helpful. I imagine most people would want to continue three days a week with one 72-hour dose out of every three doses. In fact, some are able to dose as little as twice a week with LAAM; I would like to see more patients try this if they have the option and currently are dosing more than three times a week.
Some patients might not be able to tolerate the same dose [for] 48 hours. [Among these patients] it may be possible for some to tolerate daily dosing with LAAM, but this would need to be well researched before put into clinical practice. Someone who quickly breaks down medications (aka: "rapid metabolizers") may or may not do well on LAAM (everyone is different). Because LAAM is a very long-acting medication, it is possible to have "too much" medication in your system if it is taken everyday.
- John Hopper, M.D.
University Psychiatric Center
========================================
Do the federal regulations discourage or prohibit doses over 100 or 120 mg? Also, wouldn't a dose in excess of 200 mg just make the patient intoxicated? B.P.
Dear B.P.:
The federal regulations do NOT discourage or prohibit doses over 100 or 120 mg. [*See applicable excerpts from the federal regulations below this reply.]
The fact that the physician has to write in the chart "this patient
requires a dose exceeding 100 mg" does not seem to be a significant obstacle.
The fact that a letter of "exception" has to be written, which justifies
take-home privileges in such cases, is not an overwhelming administrative
burden either. I think that the feds get too much blame for this
aspect of poor treatment.
Another particular is that they state that a very wide range of doses
is associated with significant benefits in MMT and that, surely, is a truth
that resonates with all of our experience. I don't think they know how
wide the range really is. We have one patient over 2000 (two thousand)
mg currently, and "yes, it's hard to believe," and "no, he is NOT intoxicated."
Marc Shinderman, M.D.
(CAP, Chicago, Illinois)
*What is written in the FDA (Federal) regulations is as follows:
'291.505, (6) Dosage of Methadone..., (I) Dosage and responsibility
for administration:
8 The administering licensed physician shall ensure that a daily
dose greater than 100 milligrams is justified in the patient's record.
As '291.505(v) states below, a patient on a dose over 100 mg may also be permitted to receive take-homes; typically, the FDA is willing to give approval once the patient is believed to be "stabilized" (e.g.: on the same dose for a period of time and free of illicit drug use, withdrawal symptoms, cravings, signs of improper dosage, etc.).
(v) Take-home requirements...
(D) "Each patient whose daily dose is above 100 milligrams is required to be under observation ingesting the drug at least 6 days per week irrespective of the length of time in treatment, unless the program has received prior approval from the Food and Drug Administration with the concurrence of the State authority."
Editor's Note: Although there are states that place limits on methadone dosages, never assume that dose caps are required by government regulations. Unfortunately, dose caps are still fairly common and are usually the result of clinic policy, not government regulations. The same caveat applies to restrictions on take-homes for patients on doses above 100-120 mg. Some states do place additional restrictions on take-homes for patients on certain doses, but often, methadone clinics may make their own restrictions for various reasons (i.e.: the clinic doesn't want to bother with getting FDA approval).
As has been mentioned in past issues of Methadone Today, the *TIP/TAP series of government publications, published by CSAT (Center for Substance Abuse Treatment), may be purchased free of charge. These publications contain federal guidelines regarding opiate maintenance treatment. Such publications are excellent for looking up specific questions regarding what the federal regulations require, as well as proper treatment practices. For example:
Do the regulations require monitored urine screenings? The answer is
"no." How should a "fast metabolizer" of methadone be treated?
Some of the TIP/TAP publications also contain contact information for state
regulators (Note that some publications may have outdated contact information
(if possible, use the most recently printed publication to look up state
regulator contact information). These individuals should be able
to send you a copy of the regulations or refer you to someone who can.
*CSAT's TIP/TAP publications may be ordered by contacting the National
Clearinghouse for Alcohol and Drug Information (NCADI), (800) 729-6686.
We are required to have a UA at least once a month at my clinic. In addition to methadone, I take Xanax t.i.d. for severe anxiety/panic attacks and Sinequan at bedtime for depression. I've been faithfully taking these meds as prescribed for many years and have never abused them. Every 2-6 months a UA will test negative for benzos! This also occurred while I was being treated at an abstinence-based facility which used a different lab, so that isn't the problem.
My doctor, counselor, myself, and other clinic staff are baffled by this and have no idea why it keeps occurring. I've been told that benzos stay in your system for 2-3 weeks*. I had two tests done one day (one by the State of Michigan for my PO and one by the clinic); one tested positive and the other negative, despite the fact that they were done less than an hour apart, and there was no change in circumstances. Although my counselor and doctor believe I'm taking the meds, my PO could make an issue of it, and I could be in big trouble since I'm court ordered to take these meds as prescribed. Do you have any idea what could be causing this? Could the methadone be masking the other meds? -Concerned
[*According to Dr. Shinderman, this is not true—no benzos are detectable for three weeks. Most benzos are probably not detectable for more than a week, but this shouldn't be an issue for medication taken on a daily basis.]
Dear Concerned:
A "negative" urine does occasionally occur in the setting where someone is taking a medication as prescribed. This is unusual, but no test is perfect and with hundreds and hundreds of tests being done, some "positive" urine tests will show up with no drug in the system.
What are the possible causes of a test showing up with no drug when someone is taking their medication. As you implied, error by the lab or the collecting site can occur. The urine could be labeled incorrectly, and the results are for another person. This should never happen in a setting where there is "chain of custody" (such as employment testing). This requires extra monitoring and cost and is generally not used in treatment settings. "Lab" error could occur by improper testing. In critical tests (such as criminal investigation), a sample will be tested by two different labs or tests or technicians. Occasionally, the results will be different, and we won't know which is right.
Can the person be metabolizing the drug so fast it doesn't show up in the urine? This is possible and would depend on how much of the drug is "stored" in the body, such as in fat or the liver. This is probably very, very rare in treatment settings for drugs that are given every day. This is probably not the case for you.
Different labs will have different "cut offs" for what they consider a positive test. If someone has a relatively low amount of drug in their urine, one lab may consider it "negative". Labs are most interested in not calling a urine "positive" by mistake (because of the employment implications), so a "false positive" is much less common than a "false negative". In other words, a lab is more likely to miss a urine that has a little drug in it (false negative) than call a urine "positive" when there is no drug in it (false positive).
In summary, testing the wrong urine, improper testing procedure, and variations in the lower limits of the test results can all result in an incorrect result. In your particular case, if the results are negative more than a couple of times a year, you might want to pay attention to see if there is a pattern to this (which lab; when did you take your last medication dose; what time of day were you tested). I'd be interested to know if your State of Michigan sample was positive or negative.
Although only careful testing could tell us the answer for what happened with you, I hope this provides some additional insight.
- John A. Hopper, M.D.
University Psychiatric Center
Editor's Note: In answer to another of Josh's questions, Dr. Byrne writes, "no, methadone does not mask the appearance of other drugs in urine tests." A related question, addressed by Dr. Shinderman, is whether methadone would increase (e.g.: speed up) the metabolism of Xanax [and therefore, decrease the period of time it is detectable in the patient's urine]. Dr. Shinderman explains that methadone would not increase the metabolism of Xanax, and "should, theoretically, increase the half life of Xanax." In other words, methadone should actually decrease the metabolism of Xanax, perhaps increasing the period of time Xanax is detectable in the patient's urine.
Basically, Dr. Shinderman and Dr. Byrne share Dr. Hopper's opinion, that a lab testing error is the most likely cause of your "false negative" test results.
In the final analysis, mistakes happen, and if a false test result
is used against you (i.e., you are charged with a parole violation, your
take-home "privileges" are terminated, etc.), you should demand a confirmation
test (e.g., a test of your original urine sample using a more accurate
drug test, ideally a "gas chromatography" test) or a retest [providing
another urine sample].
Dear Doctor:
If someone were at their correct dosage would they still feel the desire to drink a Sunday take home right after being dosed on Saturday? I only did it once, but I'm worried about it if/when I start getting take-homes on a regular basis.
-Josh
Dear Josh:
The temptation to consume additional methadone must occur to all patients taking this drug. However, a confidence in the prescriber, the dose, and oneself should reduce this to no more than a passing thought most of the time.
There are always two risks in taking extra methadone - firstly, although this is a relatively safe drug, toxicity and deaths have occurred from excessive doses, especially when taken with pills and/or alcohol. Secondly, if ones doses are taken ahead of time, there will be a period spent without medicine down the track. This may further increase cravings, perhaps tempting the use of other illicit drugs, pills or alcohol.
Methadone patients should be entitled to dose levels that are adequate. Most clinics have a couple of patients on very low doses and equally they should have some on very high doses (upwards of 150 mg daily). This is due to the variability of the 'half life' metabolism of methadone that has been known for many years (between 8 and 80 hours in the extremes). Some doctors used to believe that all patients should be increased in doses gradually to "blockade" levels of around 120 mg daily, but this is now known to be potentially dangerous and unnecessary. However, the principle is sound as long as the "blockade" dose is arrived at individually and where the patient was not faring well on lower doses.
Most patients I know cope fine with take-home doses from early in treatment (after the first month or two). They realize that these are the means to keep feeling well and 'normal'. Such doses also allow the liberty to go about one's business without needing to go to the clinic every single day.
If there is a continuing temptation to take extra or to inject the liquid, then the dose, mental state, and other matters should be discussed with the prescriber. Depression is another common reason for these thoughts, and this in turn is sometimes due to inadequate doses—so a methadone blood level may also aid in clarifying the issue.
Dr. Andrew Byrne
General Practitioner, Drug and Alcohol
New South Wales, Australia
=============================
Dear Josh:
Patients do not drink their next day's take home dose unless they are under dosed in all but an insignificant percentage of cases. All substance abuse in methadone maintenance treatment, including early ingestion of take home medication, should be considered an indication of under dosage or an attempt to deal with opioid side effects before any other more complicated theories of pathology are employed to explain this behavior. Double dosing occurs rarely in the stabilized patient and only as a response to destabilizing factors, such as severe emotional or physical pain and relapse.
We believe that our patients report this to us if it happens. CAP patients know that we will treat their complaints seriously. They know what it feels like to be stable. If they find themselves sipping on the next day's medication or double dosing, they know there is something wrong. We attempt to find the cause of the instability and, while sometimes more structure may be needed, address the situation in our medical model, non-punitive manner.
Marc Shinderman, M.D.
Center for Addictive Problems (CAP)
Chicago, Illinois
===========================
Dear Doctor:
Have you ever heard of methadone causing depression? I have
heard accounts of methadone acting as an "anti-depressant" in maintenance
patients but not anything about methadone actually causing depression.
Dear Patient:
In patients who are candidates for addiction--that is, the compulsive pursuit of opiates after exposure to them, I have seldom seen depressive effects attributable to methadone treatment. However, 40-50 percent of people do not even like opiates very much. For example, most (pain) patients do not take enough medication even if they have access due to the disagreeable side effects of opiates. Most of the time, they would rather have some pain than a full load of opiates.
Opiates decrease dopamine, which is one of the neurotransmitters that is involved in depression, sense of well-being and elation, along with serotonin, endorphins, and others. It is certainly possible that suppression of dopamine could account for some folks being depressed while taking opiates.
For some reason, it is "well known" among physicians that opiates "cause" depression. I have my doubts about the degree to which this occurs, and I have not seen real data to support this, but you can be certain that it is part of the consensual wisdom imparted in medical training. There is much more written on the anti-depressant properties of opiates, as you already know.
Such depression does really affect a small percentage of vulnerable individuals, in my experience. It happens in some patients who select themselves out of methadone treatment, for example. There are a few for whom methadone is quite depressing, although they do function well on heroin or hydrocodone. I believe that such people are among those opting for heroin treatment in Switzerland, which is quite restrictive compared to what they would get with methadone treatment.
Marc Shinderman, M.D.
Dear Dr. Hopper:
We are required to have a UA at least once a month at my clinic. In addition to methadone, I take Xanax t.i.d. for severe anxiety/panic attacks and Sinequan at bedtime for depression. I've been faithfully taking these meds as prescribed for many years and have never abused them. Every 2-6 months a UA will test negative for benzos! This also occurred while I was being treated at an abstinence-based facility which used a different lab, so that isn't the problem.
My doctor, counselor, myself, and other clinic staff are baffled by this and have no idea why it keeps occurring. I've been told that benzos stay in your system for 2-3 weeks*. I had two tests done one day (one by the State of Michigan for my PO and one by the clinic); one tested positive and the other negative, despite the fact that they were done less than an hour apart, and there was no change in circumstances. Although my counselor and doctor believe I'm taking the meds, my PO could make an issue of it, and I could be in big trouble since I'm court ordered to take these meds as prescribed. Do you have any idea what could be causing this? Could the methadone be masking the other meds? -Concerned
[*According to Dr. Shinderman, this is not true—no benzos are detectable for three weeks. Most benzos are probably not detectable for more than a week, but this shouldn't be an issue for medication taken on a daily basis.]
Dear Concerned:
A "negative" urine does occasionally occur in the setting where someone is taking a medication as prescribed. This is unusual, but no test is perfect and with hundreds and hundreds of tests being done, some "positive" urine tests will show up with no drug in the system.
What are the possible causes of a test showing up with no drug when someone is taking their medication. As you implied, error by the lab or the collecting site can occur. The urine could be labeled incorrectly, and the results are for another person. This should never happen in a setting where there is "chain of custody" (such as employment testing). This requires extra monitoring and cost and is generally not used in treatment settings. "Lab" error could occur by improper testing. In critical tests (such as criminal investigation), a sample will be tested by two different labs or tests or technicians. Occasionally, the results will be different, and we won't know which is right.
Can the person be metabolizing the drug so fast it doesn't show up in the urine? This is possible and would depend on how much of the drug is "stored" in the body, such as in fat or the liver. This is probably very, very rare in treatment settings for drugs that are given every day. This is probably not the case for you.
Different labs will have different "cut offs" for what they consider a positive test. If someone has a relatively low amount of drug in their urine, one lab may consider it "negative". Labs are most interested in not calling a urine "positive" by mistake (because of the employment implications), so a "false positive" is much less common than a "false negative". In other words, a lab is more likely to miss a urine that has a little drug in it (false negative) than call a urine "positive" when there is no drug in it (false positive).
In summary, testing the wrong urine, improper testing procedure, and variations in the lower limits of the test results can all result in an incorrect result. In your particular case, if the results are negative more than a couple of times a year, you might want to pay attention to see if there is a pattern to this (which lab; when did you take your last medication dose; what time of day were you tested). I'd be interested to know if your State of Michigan sample was positive or negative.
Although only careful testing could tell us the answer for what happened with you, I hope this provides some additional insight.
- John A. Hopper, M.D.
University Psychiatric Center
Editor's Note: In answer to another of Josh's questions, Dr. Byrne writes, "no, methadone does not mask the appearance of other drugs in urine tests." A related question, addressed by Dr. Shinderman, is whether methadone would increase (e.g.: speed up) the metabolism of Xanax [and therefore, decrease the period of time it is detectable in the patient's urine]. Dr. Shinderman explains that methadone would not increase the metabolism of Xanax, and "should, theoretically, increase the half life of Xanax." In other words, methadone should actually decrease the metabolism of Xanax, perhaps increasing the period of time Xanax is detectable in the patient's urine.
Basically, Dr. Shinderman and Dr. Byrne share Dr. Hopper's opinion, that a lab testing error is the most likely cause of your "false negative" test results.
In the final analysis, mistakes happen, and if a false test result is used against you (i.e., you are charged with a parole violation, your take-home "privileges" are terminated, etc.), you should demand a confirmation test (e.g., a test of your original urine sample using a more accurate drug test, ideally a "gas chromatography" test) or a retest [providing another urine sample].
Sunjic S, Zador D. Methadone syrup-related deaths in New South Wales, Australia, 1990-95. Drug and Alcohol Rev (1999) 18:409-415
This study identified all NSW coronial files over 5½ years in which methadone was involved, whether or not it was causally implicated by the findings. Of approximately 1300 opioid overdose deaths, 242 involved methadone, 134 being from the syrup which is used in methadone maintenance treatment (MMT). Methadone tablets, which are used for pain management, were implicated in 52 cases, and the methadone was of uncertain or mixed origin in 67 cases.
These authors carefully analyzed the 134 'certain' methadone syrup related deaths (MSRD) in relation to treatment status at the time of death. Those on registered treatment at the time of death (54%) were compared with those who were not in treatment [if we add in the 'uncertain' 67 cases, this makes 202 total and *if* the same proportion were in treatment - 54% - then this would leave 109 deaths of MMT patients in which methadone syrup was a possible factor. This is very close to Zador and Sunjic's figure of 105 overdoses reported in January 'Addiction' journal report covering the same period.]
A very worrying proportion (13% and 9%) of cases had been released
from prison in the month prior to death, demonstrating what a high-risk
period this is [see Seaman 1998]. It would be instructive to know
how many had already been on MMT on release.
It appeared that one-third of the non-treatment group had previously
been registered for MMT but two-thirds had never had MMT in the state.
There were three HIV positive cases among the 134.
The researchers confirmed the almost self-evident finding that most of the methadone in the treatment cases was from their own prescribed doses (96%) while most of that taken by the non-MMT cases was diverted from others and obtained on the black market (68% with 31% 'uncertain').
A much higher proportion of those out of treatment had injected
the methadone syrup. Around 80% died in the home environment.
In around 85% of cases in each group, two drugs in addition to
methadone were detected at autopsy. Tranquilizers, morphine and alcohol
accounted for most while only about 10% were apparently due to methadone
alone.
After close examination of clinical records, only six cases of the 72 MMT cases were thought to be due to inappropriate clinical practices. This included dosing errors, excessive take-away doses or faulty assessment. Most of these received treatment which was outside official treatment guidelines.
The authors' final conclusion states: "Almost half of [the syrup deaths] occurred in drug users not in MMT. . . [who were single, unemployed male known drug users]. . . similar to cases in MMT. If we include the 25% of cases where [the] form of methadone involved was unknown. . . the total proportion of diversion-related deaths may be as high as 63%. In some of these cases, methadone may have been merely another drug of abuse for a group of injecting drug users who represent a high risk group and for whom safe use messages need to be appropriately and sensitively targeted. However, for other cases, illicit methadone may have been used to medicate symptoms of withdrawal, which may indicate a high unmet demand for MMT."
Of these two possibilities, the former is probably exceptional, as methadone is rarely used as a recreational drug. This latter is supported by the documented and continuing shortage of treatment places in Sydney and elsewhere. Numerous patients entering treatment state that they had purchased 'street' methadone in favour of using heroin. Both of these groups should receive targeted preventive education as recommended by the authors.
Editor's Note: This study refutes AMTA's claim that the practice of methadone treatment by "undertrained physicians" has resulted in a significant number of "methadone related deaths" in Australia. This leaves us with little choice but to conclude that AMTA has either not done its homework or has drawn such conclusions to satisfy an ulterior motive to pressure regulators to adopt overly-restrictive requirements regarding medical maintenance treatment in order to protect the economic interests of methadone clinics.
Either way, AMTA's conclusion that private physicians providing opiate maintenance treatment must be heavily regulated and tied to "narcotic treatment programs" [methadone clinics], as well as their advocacy of overly restrictive medical maintenance regulations* are contrary to the experience in countries where methadone treatment is already safely and successfully provided by physicians in private practice. Clearly, such office-based treatment with proper training of physicians can be safe and effective—especially with stable patients—without strict regulations or control by narcotic treatment programs.
See an analysis of their recommendations "A
Critique of AMTA's Medical Maintenance Recommendations"
There's a clinic in New York I used to be on that when you give a urine, the guy holds the cup for you. This just started over there but it's quite humiliating to say the least. For some reason, instead of getting better, it gets worse at some of these clinics. They also went from being open six days a week [closed Sunday] to seven days. Why are they doing this all of a sudden? The only reason I can think of is that they're doing it due to the dramatic increase in the number of urine samples testing positive for illicit drugs since they changed labs.
-A Perplexed Patient
Dear Perplexed:
It is amazing what ignorant people will do to make MMT oppressive.
When it is clear from what we and other experts have demonstrated, that
drug abuse can be totally eliminated with good treatment (adequate and
individualized dosing), it is tragic that emphasis on humiliating staff
and patients with this kind of urinalysis is seen to be relevant at all.
They could double the average dose in the clinic for three dollars a week
per patient to get better clinical results.
Cynically, I believe that this clinic gets more money for doing things
in the way that you describe, and the frequency of positive urines has
nothing to do with it. Why they should believe that the second lab
is any more accurate than the first one is not clear to me. I just
hate to admit that people in our field are so stupid and prefer to characterize
them as greedy, I suppose. The truth is, they are probably ignorant
and mean-spirited, and the money has nothing to do with it.
It is only necessary to look at the average dose to predict the percentage
of positive urines in a clinic anyway. If the average dose
is 80 mg, the positives will be around 30 percent, 100 mg around 10 percent
and 150 mg, probably one percent, in our experience. If you add cocaine
to the mix, you can add a few percentage points to each category, but that
too diminishes at some dose level.
The emphasis should be on treatment, not upon discouraging the development
of a therapeutic alliance.
Marc Shinderman, M.D.
Center for Addictive Problems
Chicago, Illinois
Can you tell me if you've heard of any female methadone patients who
are going through menopause finding that their usual dose no longer holds
them? I've been on the same dose for several years (95 mg), and it
always used to hold me. Now that I've entered menopause (according
to my gynecologist), I've started experiencing withdrawals several hours
before it's time to dose. Another problem is that the maximum dose
my clinic gives out is 100 mg, so I don't know what to do. -Mary
Dear Mary:
There are many changes in the body during menopause, and it is not surprising that methadone requirements may change over this time. I am not aware of any factors unique to methadone dose levels during menopause, but clearly if there is any instability, emotional or physical, then the requirements may go up. Equally, if the hormonal changes can be treated, then the problems may subside with time.
There should be no arbitrary maximum dose level for any medical prescription, whether this be insulin or methadone. State or Federal "regulations" or guidelines do not take precedence over a doctor's clinical judgment in prescribing for their patient. The dose should be according to the patient's needs.
If you are on 95 mg daily, and there are signs and symptoms of withdrawal, then a dose increase should be consideredCprobably to 100 or 105 mg. If there are concerns of toxicity, then "trough" blood levels can give guidance. Doses of up to 180 mg per day have been used in the US for over 30 years, and they appear to be safe. Even higher doses have been used occasionally under close supervision with documented benefits.
So if your clinic has an arbitrary maximum, they may be guilty of malpractice. There are consistent reports of good quality methadone treatment having average doses of around 80 mg, meaning that many patients take more than that. The new U.K. dependency guidelines state that an effective dose of methadone is usually in the range 50 mg to 120 mg but that some patients need more than this.
So, ask your doctor for more methadone, and if they are not comfortable
with this request, then ask for a blood level. If this is in the
low range, then a dose increase would not be harmful and may well prevent
a disaster.
I hope this information helps you with your current problems.
Dr. Andrew Byrne
General Practitioner, Drug and alcohol
Redfern, New South Wales, Australia
The dose levels of methadone are just as important as for any other drug. As with insulin, cortisone or penicillin, the consequences of incorrect doses can be very serious. But the "science" is not quite as simple when the effects cannot be easily measured. Anti-depressants and analgesics have a strong psychological and emotional component to their actions and thus may be more difficult to optimize.
A few 'rules' might be starting points, knowing that there are sometimes exceptions. For a given person with an established opioid dependence, there will be a particular methadone dose level which will abolish cravings and have a maximal positive effect without intoxication. This may be as low as 30 mg or as high as 300 mg or more in rare cases. This level will depend upon the metabolism of the drug and the person's individual 'sensitivity' or 'tolerance' to it.
Doses well below this particular individual level may be adequate for long periods if other matters are stable. However, in the event of stress, the original dose will often be required again for periods of time. Indeed, if the patient has resumed using other opioids such as heroin, then a return to the original dose (not necessarily straight away) is nearly always required in my experience. Such events may be emotional such as bereavement, divorce or job loss. Equally, dental surgery, physical injury or migraine may be the trigger for higher dose requirements.
Once stable, it is essential that a certain period of time elapses before dose reductions are attempted. The trigger must be sufficiently remote which may be weeks, but often it will be a number of months further off.
While doctors now know plenty about medicating patients, what
we lack is knowledge about dose reductions and withdrawals. It can
be said that those who attempt reductions that are very rapid or steep
are unlikely to succeed than those who use more graduated declines.
If it is done for financial or other "external" reasons, it is even less
likely to result in long-term abstinence.
The signs of impending success at abstinence may be very obvious.
These usually involve a degree of stability regarding emotional, financial
and employment matters and a genuinely expressed desire to become drug-free.
Such people need encouragement [not nagging--Ed. Note] to embark on reductions
as a positive and active process. This should be done at a pace that
can be reviewed along the way rather than setting arbitrary goals that
may not be achievable.
Editor's Note: It should be added that withdrawing, even using ideal methods under optimum conditions, is associated with a high relapse rate (80-90%). Extremely motivated patients who have other factors in their favor may have slightly higher success rates, but still over 3/4 will relapse when withdrawing. And, of these "successes", a percentage will abuse other drugs or alcohol. Needless to say, a relapse carries possible risks such as incarceration, contraction of HIV, HCV, or overdose. In addition, some patients find that they simply cannot function or feel "normal" without a maintenance dose of opiates--quite possibly because of a physiological imbalance--a dysfunctional opiate receptor ligand system and insufficient endorphin production.
The choice of whether to withdraw--at any given time--should always be the patient's. Patients should be properly educated about the risks of withdrawing so that they can make an informed decision.
================
*The following is reprinted From Chapter 5 of "Physicians' Guide:
Opioid Agonist Medical Maintenance Treatment [Draft]," written by the Medical
Maintenance Consensus Panel convened by CSAT
Methadone maintenance treatment is associated with healthy outcomes for both mother and infant. Methadone is not teratogenic to the fetus, and there is no evidence that it causes developmental problems. Patients can breast feed their infants. Withdrawal from methadone or reduction of dosage during pregnancy is hazardous to the fetus and may destabilize the mother; consequently, these should never be done without the advice of an expert in the field. The patient should be reminded that the safest place for the baby to be withdrawn is outside the womb in the hospital nursery under direct medical care.
During the later stages of pregnancy, methadone doses may need to be adjusted. The greater plasma volume and other aspects of pregnancy can result in a reduced or more rapid fall of methadone level in the blood. As a result, the pregnant woman's maintenance dosage may be insufficient to prevent cravings or withdrawal. These changes in plasma levels may require that the dose be increased and/or that the single daily dose of methadone be split and taken twice a day to achieve a more even blood level throughout the 24-hour period.
The medical maintenance physician, the obstetrician, and the pediatrician should consult the following protocols and guidelines for managing pregnancy and encouraging breast feeding in opioid-maintained women, as well as managing withdrawal syndrome in the neonatal nursery:
Chapter 9 in CSAT's Treatment Improvement Protocol (TIP) No.
1, State Methadone Treatment Guidelines (CSAT 1993c)
CSAT's TIP No. 2, Pregnant, Substance-Using Women (CSAT 1993b)
CSAT's TIP No. 5, Improving Treatment for Drug-Exposed Infants (CSAT 1993a).
TIPS No. 2 and No. 5 can be searched online through the National Library of Medicine's HSTA website; this site can be accessed from www.samhsa.gov/csat/csat.htm. [CSAT's TIP and TAP publications can also be ordered by calling 1-800-SAY-NOTO].
Editor's Note: In the last ten years, clinical experience has resulted in a modification of medical guidelines for pregnancy and breast feeding. At one time, it was recommended that pregnant methadone patients be maintained on the lowest possible dosage, as little information existed regarding the impact of methadone on infants exposed to methadone in utero. For similar reasons, breast feeding by methadone-maintained mothers was discouraged--particularly for mothers on doses over 100 mg.
For this reason, we felt that reprinting this section of the Physicians' Guide is important--even though these subjects have been addressed in past issues of Methadone Today. This addresses the issues in a clear and accurate manner, as well as providing a list of publications where other information may be sought.
Sadly, there are still methadone clinic doctors and hospitals that operate on the principle that "the lower the dosage the better" for pregnant methadone patients. As noted above, such dose reductions are hazardous to the fetus; however, lowering the pregnant methadone patient's dose may also precipitate a relapse to illicit opiate or other drug use. If a relapse should occur, the patient runs the risk of contracting HIV or Hepatitis C or of overdose; similarly, the fetus could also contract these diseases or suffer damage or developmental deficits. Medical personnel need to be properly educated on this issue, as such "low dose" policies are potentially very dangerous for pregnant methadone patients and especially their fetuses.
Finally, pregnant methadone maintained patients should be assured
that newborn infants can be withdrawn safely with minimal discomfort; as
a matter of fact, many babies born to methadone maintained mothers do not
experience any withdrawal symptoms. By the same token, breast feeding
while on methadone is safe [unless for some other reason, breast feeding
is contraindicated--like HIV positive status]. Please contact Methadone
Today if you have any questions regarding these issues.
This large New York City prison study finds substantial and significant benefits in re-offense rates of prisoners who chose 'high dose' (median 70mg daily) versus low dose (30mg) [most authorities outside the US now consider 'high dose' methadone as greater than 100mg daily].
The study examined the two methadone groups (1400 high dose, 1800 low dose), as well as controls in whom methadone had never been prescribed (10,000), and those who were detoxified in prison (7000). The median times to reincarceration were 187 days in the low dose group and 253 days for the high dose group. The calculated percentage reduction in recidivism was 14% on a log scale. The 'control' groups were not comparable as they appeared to represent less serious offenders with far shorter sentences.
These authors plead for a collaboration between the medical and legal professions as occurred in the tuberculosis epidemic of the 1950s. In this they say that all methadone patients who come to the attention of the authorities should have a blood test performed and dose level adjusted to enable a 'blocking' level of 200ng/ml [Editor's Note: this is not a blocking level--it is a barely adequate trough serum level]. Even when doses are adequate, such treatment, they say, is often terminated once in the community because of a lack of funding, amongst other reasons, denying the patients and community the known benefits associated with continued treatment.
These authors describe a simple and highly significant finding but derive two important conclusions about dependency management. One is support for the known effectiveness of methadone treatment in reducing criminal behaviour. The other inescapable observation is that when this treatment is inadequate, the effects are correspondingly muted.
Their support for mandatory blood methadone testing in those showing
signs of withdrawal may not be justified in all cases. Usually a
good history and physical examination can accurately determine the patient's
requirements. But, as in the case of anticonvulsants, digoxin and
certain other drugs, where clinical doubt exists, blood estimations can
be invaluable.
]
The authors express disappointment in the relatively small percentage benefit shown in the 'high dose' group [No wonder--see Editor's Note], but this could presumably be improved by further raising average doses in line with clinical requirements. There are numerous reports of clinics with *mean* doses over 90mg daily (from Germany, Switzerland, Israel and elsewhere) and isolated cases of patients requiring from 200mg to 400mg daily before reaching clinical stability (US, UK).
It should be noted that methadone in prisons is only an established
modality in a very few jurisdictions including New South Wales, Holland,
Hong Kong and parts of metropolitan New York (Riker's Island). The
evidence is now overwhelming that all prisoners who qualify for methadone
treatment out of jail should also be offered it when in custody.
The consequences of not doing so are tragic and costly both for those directly
involved and for the communities to which the prisoners return. Reported
moves to this end in Britain, Victoria, Queensland and elsewhere are to
be commended.
Earlier this month, the Journal of the American Medical Association carried a major feature on methadone maintenance treatment (MMT). Two interesting studies and a major editorial probably constitute the most prominent airing that methadone treatment has had in the mainstream medical press for quite some time.
Rounsaville and Kosten make some intriguing statements in supporting office-based methadone prescribing for heroin addiction. They assume that 1) American clinic MMT is of a high quality and that 2) this will necessarily be compromised by allowing physician treatment in the community. This would seem to be contrary to a number of reviews of quality of care in US clinics (eg. D'Aunno &Vaughn) and shows a lack of confidence in the abilities of American physicians to embrace this modality. Much U.S. treatment is currently inadequate, intrusive and expensive. Where doctors are directly in control of patients' treatment, it is likely that improvements according to research and therapeutics will occur, as in every other medical sphere from psychiatry to orthopedics.
Most, however, would agree with Rounsaville and Kosten that the low
access rates of methadone availability to American addicts (about 14%)
needs to be raised and, further, that office-based treatment is the only
feasible way this can be done. So why wait?
The report by Weinrich and Stuart et al from Scotland shows that it
is not only feasible and acceptable to introduce MMT into general medical
practice, with supervised dosing at community pharmacies, but it also has
dramatic and measurable benefits for patients and community generally.
Uptake rates were excellent and overdose deaths dropped.
Doctors Sees, Delucchi and co-workers have shown (perhaps for the 100th time) that methadone maintenance treatment works better than compulsory detoxification. Their claim to novelty in this report was that they allowed substantial doses, at least initially (up to 100mg daily in both groups), a 6 month gradual dose reduction, and intensive psychosocial supports. Even so, the median stay for patients on the 180-day reduction course was 174 days, despite intensive non-drug treatments being available for up to 16 months (488 days). The randomized methadone maintenance group had a median retention of 439 days. There was also less heroin use and less drug-related HIV-risk behavior in the MMT group.
With such persuasive evidence, it is to be hoped that this will be the last ethical trial in which subjects are given forced reductions in preference to maintenance treatment, which is known to be superior. Owing to waiting lists in most American cities, these patients may not have had access to agonist treatment outside of the trial setting.
Interestingly, it is stated "Editorials represent the opinions of the authors and THE JOURNAL and not those of the American Medical Association." I have heard from other sources that methadone treatment 'is not embraced by the American Medical Association' (AMA), which would be intriguing if it is true. Doctors do not usually have the luxury of 'embracing' treatments except as guided by scientific knowledge on the particular subject. (Editor's Note: The AMA's official stance on methadone treatment is quite favorable, so we are not sure why this was inserted at the end of their journal article.)
References:
Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H, Banys P, Hall SM. Methadone Maintenance vs 180-Day Psychosocially Enriched Detoxification for Treatment of Opioid Dependence: A Randomized Controlled Trial. JAMA (2000) 283: 1303-1310. http://jama.ama-assn.org/issues/v283n10/full/joc91501.html#13
Weinrich M, Stuart M. Provision of methadone treatment in
primary care medical practices: review of the Scottish experience
and implications for US policy. JAMA (2000) 283: 1343-1348
http://jama.ama-assn.org/issues/v283n10/full/jpp90021.html.
Rounsaville BJ, Kosten TR. Treatment for Opioid Dependence:
Quality and Access. JAMA (2000) 283: 1343-1348. http://jama.ama-assn.org/issues/v283n10/full/jed1337.html.