If you have any questions you need answered by the doctors about methadone, here is the place to send them. However, please read this first, or your question may not be answered.

Methadone & Organ Donation - November 2001, Vol VI, No. XI

Adding Water to Methadone - October 2001, Vol VI, No. X

Benzodiazepines Banned by Some Clinics - September 2001, Vol VI, No. IX

Pregnancy, Methadone, Anesthesia - August 2001, Vol VI, No. VIII

Research into Buprenorphine-Naloxone Combo Raise Questions of Safety, Ethics - July 2001, Vol VI, No. VII

Naltrexone Dangers - June 2001, Vol VI, No. VI
    LAAM Warning - An Update

Warning: Do Not Take St. John's Wort While on Prescribed Medications - March 2001, Vol. VI, No. II

Methadone and Mortality:  Higher Doses (over 75 mg) More "Protective - February 2001, Vol. VI, No. 1
        Methadone and Prilosec
           Methadone, Tegretol & Seizures

Methadone Toxicity - November 2000, Vol. V. No. 11

OrLAAM Complications - October 2000, Vol. V, No. 10

Report Tracks Patients of Ultra Rapid Opiate Detoxification (UROD)  September 2000, Vol V, No. 9

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Albanese AP, Gevirtz C, Oppenheim B, Field JM, Abels I, Eustace JC.  Outcome and Six Month Follow Up of Patients After Ultra Rapid Opiate Detoxification (UROD).  (2000) Journal of Addictive Diseases, 19(2):11-28.

 This report describes the six-month progress of 120 American patients given antagonist induced opiate detoxification under anaesthetic.  Patients were addicted to heroin (57%), methadone (28%) or other analgesics (15%).  78% were male and mean age was about 36 years (18 - 55).

 Three patients had the procedure performed twice during the six-month study period.  All patients successfully completed the detoxification procedures and were discharged on naltrexone after a mean hospital stay of two days at one site (New York) and four days at the other (Miami).

 "Morbid events" were described for 14 of the 120 patients.  These included eight with severe vomiting requiring return to the hospital.  Three needed intravenous rehydration while five were treated as out-patients.  One developed a bigeminal cardiac arrhythmia during the anaesthetic.  One went into delirium tremens while emerging from the procedure, and another had a suicide attempt on day three.  One patient developed severe asthenia which only resolved when the naltrexone was withdrawn.  One patient had a psychotic episode following the procedure which required intravenous treatment with haloperidol.  There were said to be no long-term sequelae from the procedure.

 Data on opioid use was obtained from about 111 of the 120 patients with 61 (55%) remaining "relapse-free" at follow-up.  This was defined as (1) reported abstinence from opioids [70%] OR (2) a single self-reported "lapse" but no development of dependence and thus a return to oral naltrexone without repeat procedure [30%].  For 10 of the 18 who "lapsed" this occurred in the 8 weeks post-procedure.  For 5 of the 18, the timing of the lapse was unknown.  No demographic differences could be determined between the individuals who relapsed when compared statistically with those who did not.  Hence we deduce that about 45% of the 111 traced study patients not only "lapsed" but also developed a dependency on opioids in the 6-month follow-up period, or "relapsed".

 The most serious aspect of this study is the absence of information on about ten patients.  While some of them are likely to be doing well, others may have returned to compulsive drug use, and others still may be deceased.  A simple search of State death records in the areas where these procedures took place has not been reported.  This is an essential part of a complete study, especially in the knowledge that other reports have shown overdoses and deaths in those prescribed naltrexone (Miotto and Ling 1997).  There is also now a reported mortality associated with the rapid detox procedure, although this appears to be very low.
 Rabinowitz's report from Israel in 1997 found 57% still on naltrexone at 12 to 18 months after the ultra-rapid detox procedure.  Thus it is helpful to finally read another description of a group of self-selected private patients who have undergone this accelerated detoxification procedure.  From a causation/scientific standpoint, these reports are of limited value, having no randomisation (sic) nor true control groups.  But it is useful to have observational studies, especially when they are consistent with anecdotal experience and with each other.  They also tell us (and would-be patients) some of the benefits and limitations of such procedures.

 The authors may reveal some of their personal preferences by stating in conclusion: "Many patients are able avoid the social, legal and infectious complications of opiate addiction by using long-term agonist therapy (methadone/LAAM).  Many others, however, do not want to commit to a lifetime of narcotic dependence." [.. and therefore choose detoxification in one of its many forms].   " [F]or individuals who historically leave detoxification programs, due to inability to tolerate prolonged discomfort, and for those who have not been able to succeed with traditional tapered programs due to physical or psychological distress, the Ultra Rapid Opiate Detoxification procedure appears to provide a particularly viable treatment option."

 While it would appear that these procedures are here to stay in some form or another, it should be noted that naltrexone is not approved for use in accelerating detoxification from opiates.  In fact, the manufacturers specifically advise against its use in those with a current opioid dependency.  In addition, the use of naltrexone as a relapse prevention measure has not withstood scientific scrutiny despite many studies.  Apart for its supervised use in custodial cases, its effect has never been adequately documented, and placebo controlled trials have been negative.

 This current study and coronial reports dispel the myth that there is a magic bullet or that rapid detox is pain-free, harmless and simple.  There was a reported complication rate of 12%, and there is a small mortality associated with the procedure.  While it certainly appears to benefit some well-motivated folk, it is expensive, somewhat invasive and unproven as an effective modality in the long or medium term.  The very least we can expect is that patients who seek this treatment are made aware of the risks and benefits of the procedure and that they receive a clear, unbiased presentation of the alternatives.

 Editor's Note: Among the shortcomings of this study is the fact that it only tracks patients for six months following the procedure.  Given the nature of the disease of opiate addiction, it is likely that some of the patients who remained abstinent during the first six months following the procedure will eventually relapse.  While it might not be fair to regard the treatment as a failure if the patient relapses after a year or two of abstinence, it is certainly an issue when UROD practitioners routinely tout the treatment as a one-time, permanent "cure" (e.g.: when UROD doctors attempt to persuade prospective patients to undergo the treatment--which costs thousands of dollars--they probably will not tell the patient that they may eventually need to undergo the treatment again).  Besides, UROD practitioners often downplay the cost of the treatment by comparing the cost of one UROD procedure to years of maintenance or other treatment.  This is making the assumption that once a patient has undergone UROD, he will never require it again, a false assumption if the majority of patients will eventually relapse.

 Despite the study's shortcomings, it reveals some of the shortcomings of UROD and paves the way for further research into this procedure.  Up until now, prospective patients only had the claims of UROD practitioners, who stand to profit from the procedure, to go by.  Independent research will allow prospective patients to make a more informed choice regarding this treatment.
 
 

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Dear Dr. Byrne:

 The last time my husband and I went into the clinic, we were told that we have to have a mandatory EKG test.  It was something about the drug company is insisting on it, or they will remove us from OrLAAM and put us on methadone right away.  Are you aware of any new issues that have come out recently concerning OrLAAM?

 -Two happy LAAM folk [but now a little insecure]
 

Dear "Folk":

 Yes, there has been a bit of a scare about a rare heart conduction defect being aggravated by LAAM after a report from a doctor in Chicago.  It is mostly in patients on a very high dose and might apply to methadone as well.  The doses of methadone for most of those involved are over 200mg daily and thus do not apply to most people.  The defect is called "long Q-T syndrome" and is rather unusual.

 What you have been told is typical of modern American 'defensive' medical practice.  It is hard to know if this is to help the patient or the doctor but is worth considering.  Tire and motor car companies do the same things for the same reasons.

 From the point of view of overall risks, the most important thing is that you are well and not using other drugs.  If you have had a cardiograph in recent times, then this should be noted in your clinic file.  After the age of 40, in smokers or those with a family history of heart disease, a baseline cardiograph is a good idea anyway.  If your clinic doctor (methadone must be prescribed by a doctor) is interested in your welfare, then the clinic would do a blood pressure check, weight, cholesterol, hepatitis screen and vaccination, periodic skin checks amongst other things.  Chest X-ray and EKG are 'optional extras', usually in those at some risk of chest complaints.

 You should have the option of discussing these things, and the threat that you might have to transfer to methadone precipitously is highly irregular and premature in my opinion.  In fact, changing drugs might entail more personal and health risks than continuing on LAAM, regardless of any cardiograph trace.

 I have always pointed out that LAAM is a relative newcomer compared with methadone and should only be used where methadone has proven unsatisfactory.  We know from Rhoades study* that it is perfectly possible, indeed desirable, to treat many methadone patients with twice weekly attendance and 5 dispensed doses.  There were fewer drop-outs and less high-risk behavior in such patients when compared to those only given weekend "privileges" (another misnomer).

 Thank you for raising this important issue.

Dr. Andrew Byrne
General Practitioner, Drug and alcohol
Redfern, New South Wales, Australia
 
 

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Dear Dr. Byrne:

What are the symptoms of methadone toxicity?  I have been on medication for chronic pain (fibromylasia) and many other medical problems (at one point I had a Duragesic patch, but I am now on methadone).  I have been falling asleep a lot and I sweat terribly.  I am afraid that I may be on too high of a dose.  I am taking 50 mg in the morning and 50 mg at night.  I went up to that dose about two or three weeks ago, because [at the time] I felt like I was going through withdrawal.

I have a liver disorder and [presumably for that reason] medications seem to work different for me.  I am also taking ½ of a 5 mg Valium twice a day because of anxiety and panic disorders.

I am concerned that my sleep problems will begin to disrupt my life; I have been working for over a year and plan to go to school, but every time I sit down I start to fall asleep and I cannot sleep at night.

Can you help me?  I don't want to detox because methadone is the only medication that helps me.  - Polly
 

Dear Polly,

The symptoms of methadone toxicity are sedation and skin scratching in the 2-6 hours after taking the medication.  There may also be sweating, but this can also come from withdrawal.  There is nearly always constipation and tiny pupils all day long.

The problems you are describing with sleep disturbance and fatigue may be due to the benzodiazepine tranquilizers (i.e., Valium-type drugs).  Such drugs are best avoided in methadone patients, but they should not be stopped too suddenly either.  I have found that methadone is often a good treatment for panic attacks on its own, but [only when used] in sufficient doses.

You may be better to see your doctor about cutting down the Valium.  Even at low doses it can adversely affect sleep, balance, memory and other things.  And you may also feel a lot better on a slightly lower dose of methadone, too.

Detoxing [from methadone] is not really advisable when you are unstable with unresolved symptoms.  After at least a month's stability regarding other matters, it may well be appropriate to cut down but it should be from one drug alone by then and gradually.  Detoxing from two drugs is almost impossible outside of an in-patient setting.

Dr. Andrew Byrne
General Practitioner, Drug and alcohol
Redfern, New South Wales, Australia
 

Editor's Note: On this issue of benzodiazepines, Dr. Marc Shinderman has noted that there are cases where their use is appropriate in methadone patients - thus, a blanket prohibition on such medications [by clinics] is a bad idea.  However, Dr. Byrne makes an excellent point - if an increase in methadone dosage is all that's necessary to control panic or anxiety attacks, this strategy should be used in lieu of taking benzodiazepines.
 
 

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This study of 500 subjects over 5 years reveals an apparent protective effect from methadone treatment.  Reductions in overdose mortality by a factor of 3 are demonstrated in those on doses of up to 50mg while greater and more sustained reductions occurred in those taking over 50mg, approaching a 10-fold reduction on over 75mg when compared with addicts not in treatment.  While the findings do not prove causation, other studies' outcomes and the principle of cross-tolerance are consistent with a "chemical protection" from methadone.

[Another report from New York* describes death rates among discharged methadone patients as more than twice that of patients who continued in treatment prior to the HIV epidemic.  The death rate from 'heroin-related causes' in discharged patients was 51 times the rate among continuing patients!]

The Dutch researchers have examined the effects of "low threshold" treatment which may be in some ways comparable with "liberal" office-based community treatment.  Given that a dependent person is registered for treatment, its quality may be good or bad, and the patient's compliance may vary.  It is clear from research that optimal treatment retains more addicts in treatment and lowers the incidence of many of the adverse consequences of drug use and the associated behavioural disturbances.

It is known that several factors lower retention rates:  inadequate doses; restricted take-home doses; a lack of psychosocial supports; increased prices without safety-net; a lack of input from the patient into their treatment decisions.  Along with more drop-outs, these factors increase mortality and may cause higher risk behaviour regarding viral disease transmission.

It is no longer justifiable to treat most patients in the methadone dose range of 30 to 60mg daily.  Therapeutic guidelines generally agree that most patients need from 60 to 120mg with only a minority needing more or less than this level for reasons of varied metabolism and/or tolerance.  Most good treatment services have a small proportion of patients taking less than 40mg and more than 150mg daily.  A recent report from Israel described a mean clinic dose of 104mg daily with excellent outcomes# (up to 80% annual retention).

*Appel PW, Joseph H, Richman BL.  Causes and Rates of Death Among Methadone Maintenance Patients Before and After the Onset of the HIV/AIDS Epidemic.  Mount Sinai Journal of Medicine (2000) 67;5/6:444-451.
#Adelson MO, Hayward R, Bodner G, Bleich A, Gelkopf M, Kreek MJ.  Replication of an Effective Opiate Addiction Pharmacotherapeutic Treatment Model: Minimal Need for Modification in a Different Country.  (2000) J Maintenance in the Addictions 1(4)5-13.
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Dear Doctor,

I take Prilosec for stomach problems - Would Prilosec or other such medications have an effect on methadone metabolism or absorption?  If it could have such an effect, would it matter when I take the Prilosec (i.e., before dosing)?

I am also interested in whether fiber supplements, antacids (i.e.,  Tums), or anti-gas medications could have an effect on methadone absorption or metabolism if taken soon before taking one's methadone dose.  (I mention fiber supplements, because I have read cautions stating that fiber supplements can interfere with the absorption of certain drugs.)  -LM

Dear L.M.,

Drug interactions with methadone are common and very important questions.  No one person, book, or even computer program can keep track of every possible interaction.  Fortunately, the relation between Prilosec (omeprazole) and methadone has been studied. There is no problem taking both medications.

 The issue of fiber and antacid is a little more complicated. There are many types of fiber supplements and antacids.  In general, there shouldn't be an interaction between the two. Having said that, I would probably separate methadone dosing from these other products by at least an hour.

 I use a computer program called "Drug Therapy Monitoring System" to check for interactions.  I suggest that when you get any new prescription or supplement, you ask your pharmacist if these medications interact with methadone.  You may be a little reluctant to tell your pharmacist that you are on methadone, but it is in your best interest for them to know. Your pharmacist should look up interactions on the computer or in a book.

John A. Hopper, M.D.
University Psychiatric Center
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Dear Doctor,

Are methadone and methadone HCl the same thing?  And If they are, can methadone cause seizures like methadone HCl?  If so and you are taking Tegretol, should you be "iffy" about higher doses?  -Tony

Dear Tony,

Methadone and methadone HCL (hydrochloride) are the same medication.  Although there are few absolutes in medicine, methadone, by itself, should not cause seizures.  Even very high doses of methadone should not cause seizures.  Some opiate medications, such as meperidine (Demerol) and propoxyphene (Darvocet), can cause seizures in high doses.

Tegretol (carbamazepine) is a medication used for treatment of seizures.  Tegretol is a very good treatment for seizures, but it does interact with several other medications, so it is good that you asked about it.  A person taking Tegretol should not require additional Tegretol while on methadone.  However Tegretol increases metabolism (breakdown) of methadone.  Many patients taking methadone who are started on Tegretol will require an small increase in their methadone dose as a result.

John A. Hopper, M.D.
University Psychiatric Center
 
 

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St. John's Wort reduces levels of methadone, other opiates, benzodiazepines, anticonvulsants, anti-rejection drugs, anti-depressants, anti-virals and a host of other medications.

At my clinic (CAP), we have known one patient who had a cardiac arrest after taking St. John's Wort for a week.  It probably lowered levels of her anti-epileptic medication (clonazepam) and methadone, leading to a seizure.  Treatment for the seizure involved a new medication (to her) which led to arrhythmia and required cardioversion (the electric shock "paddles").  Since then she has continued on her prescribed medications (methadone, etc.), but without the herbal "remedies" and has not had another such episode.

If you want your methadone, benzodiazepines or host of other medications to do what they have to, AVOID this CYP 450 enzyme-inducing agent, St. John's Wort.

Editor's Note:  We believe that there is a place for "herbal" or alternative remedies.  However, some manufacturers of herbal products have misled the public into believing that herbals are completely safe under all circumstances.  Advertisements sometimes state that the herbal is "all natural", implying that by definition "natural" equals safe.  But this is in fact, not the case; for instance, plants are natural, yet a surprising number of them are very poisonous.  This is why humane societies warn about the dangers of pets eating common house plants.

In truth, most herbal products on the market are safe if used as directed by someone who is not taking any prescribed medications and does not have a serious, chronic illness (i.e.,  HIV or diabetes).  However, those of us who are taking prescribed medications must use caution with herbal remedies.

St. John's Wort is not the only such remedy that interacts with medications.  For example, valerian root may amplify the effects of certain medications, such as phenobarbital.  Individuals with certain chronic illnesses must be even more careful:  HCV (Hepatitis C) patients have to always be wary of whether a product will stress the liver; products or drugs like ibuprofen (Advil) that normally pose little risk of liver damage, may stress the liver in an individual with HCV or compromised liver function.

Most importantly, never count on the government or product manufacturers to protect you or warn you of potential dangers.  The federal government's failure to regulate herbal products (with a few exceptions) has sent the wrong message to the public.  Herbal products have escaped serious regulation, not because they are safer than "drugs" but as the result of a loophole.  Herbal products are technically regarded as "nutritional supplements"; in other words, they are regulated as foods.  To put it another way, methadone patients should know better than anyone that the degree and severity of U.S. government regulations often has little relation to the potential for harm posed by a medication [or herbal product].

The sensible approach to herbal products is to educate yourself about a product you are considering using, and always consult a physician.  For that matter, if you intend to use an herbal product to treat a specific illness or condition, research whether another drug or herbal remedy would be safer and/or more effective than the one you are about to take.  You may be surprised to discover that a prescription medication is safer for you to take than the herbal remedy.  This is precisely the case for individuals on prescribed medications like methadone or anti-epileptics who are looking for a remedy for depression--prescription anti-depressants are much safer for such individuals than St. John's Wort [the herbal remedy]).

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Dear Doctor,

I am a Christian Surgeon running my own private, 25-bed surgical hospital; besides that we are also running a drug abuse centre (sic) for all kinds of addicts.  We keep the addicts for three months in the centre.  So far, we have treated 127 patients but most of them relapse--75 patients relapsed when they went home.  Kindly guide us and advise on how we can stop this relapse.  Any advice from your side will be highly appreciated.
 -Dr. JP
 

Dear Dr. JP,

 What I would suggest to you is that neither being Christian, a physician or a surgeon is useful or relevant to the task which you now confront.  Worse, if you imagine that those elements prepare you to treat addicts, I can assure you that you are not only mistaken, but arrogant.  There is no preparation  of any value for addiction in medical school.  Surgery is experimental in this regard, and Christianity per se has little to do with it.

 What is necessary is that you treat addiction as a disease and that you have some idea what it is medically.  Do you realize how ridiculous your question would be if the patients were hypertensives or diabetics or arthritics?  These are chronic diseases, as are most addictions.

 Effective medical treatments for addiction are few, but they do exist.  Behavioral treatments for addiction are about as good as they are for diabetes--some Type 2 cases will get better with diet and exercise, most will relapse and some will spontaneously resolve.  Effective medication, along with behavioral treatment, is the key.  Many people believe that some sort of spiritual void exists in addicts that group meetings or divine revelation of religious nature will help.  That is true for a minority and is not, in my opinion, the proper role for a doctor to play, though referral to such processes is.

 If you educate yourself or find an expert on addiction and get your hands on medications, combined with structure and behavior treatments that work, you will be on the right road.  There is a wealth of information available on the World Wide Web (Internet) at the samhsa.gov site, at the NIDA site (www.nida.gov), at the American Society on Addiction Medicine site (www.asam.org), even at my site (www.capqualitycare.com) and DONT/Methadone Today's (see bottom of page 4).  Do some homework and get back to us.

 What is it you are doing to your patients now that you imagine should alter the course of these chronic relapsing disorders?  What kind of "addictions" are you treating?

Marc A. Shinderman, M.D.
Center for Addictive Problems

Editor's Note:  Although we consider it a positive that Dr. JP is asking for advice, we nonetheless find it discouraging that he is running a treatment facility when he appears to know little about addiction treatment.  Unfortunately and tragically, too often facilities are run by staff who know little or nothing about addiction--especially methadone maintenance.
 
 

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A recent study found that opiate addicts treated with naltrexone were twice as likely to die as untreated opiate addicts.  Methadone Today has printed several patient stories documenting bad experiences with UROD (rapid detox), where patients are given naltrexone and other antagonists while under anesthesia; the accounts suggest that UROD is inhumane and ineffective.  This study confirms that UROD and the aftercare provided (after the treatment, patients are given naltrexone pills to take or are implanted with a pellet that continuously feeds naltrexone into the patient’s system for a period of weeks) also may be unsafe.  Prior to this study, there had been reports of deaths immediately following UROD but little research into the mortality rates of UROD patients in the weeks and months following the procedure.

Opiate addicts should carefully consider the risks before undergoing UROD.  There are safer and more humane methods of withdrawing from opiates; however, it should be stressed that neither UROD nor any other detox method is as effective as opiate maintenance treatment.  Finally, do not rely on UROD practitioners to inform you of the facts and risks about the procedure--this study demonstrates that there is a very real risk to any treatment utilizing naltrexone.

The following comments were made by Marc Shinderman, M.D. of our Medical Advisory Board and are in regard to the aforementioned study:

I am well aware of the apparently excellent results some practitioners have using naltrexone for opioid dependence.  I do use it sparingly with stabilized, high-functioning patients.  In light of this new information, however, I plan to use it even less.  My numbers of patients are so small, compared with the sample cited in the article, that I can only consider myself and my patients “lucky,” statistically.  This is often the case with drugs which are found to have unacceptable death risks.  In the post marketing period when wholesale use occurs, longer-term follow up is available, and the structure and patient selection in pre-marketing trials no longer apply.

Any medication whose use is linked to almost doubling twice the death rate seen in untreated heroin addiction and 7.5 times the rate seen in methadone maintenance treatment should be severely restricted, if not banned, in the treatment of opioid addiction.  Instead, we see its use offered to anyone and, even worse, misrepresented by some as being preferable to traditional withdrawal methods and treatment: opioid tapered withdrawal and methadone maintenance.  ASAM has cautiously endorsed its use, and some of its members are vociferous advocates of naltrexone administration to opioid addicts.

Having always been dubious of UROD and naltrexone-based treatment of opioid addiction since the beginning, I welcome this study and repeat my admonition to addiction professionals, patients and their families.  In consideration of the excessive and unacceptable death rate associated with naltrexone used in any phase of opioid withdrawal or treatment in opioid addiction, such procedures should be further studied and not marketed until this glaring defect can be repaired.

Prior to this, we had only Ling’s article and many anecdotes of “prejudiced” practitioners like myself, who learned of deaths and overdoses of naltrexone-treated patients which never found their way into the long-term evaluations done by UROD practitioners or others using naltrexone to treat opioid dependence.

These risks were certainly not made prominent by most centers offering UROD in the US, either in solicitation or education of patients, in the majority of instances known to me.  I am sure there are exceptions.  So, what?  Better informed consent may not be sufficient to counterbalance the risks herein above described.

Addiction medicine professionals should discourage naltrexone use for opioid addicts and focus on making agonist maintenance options more numerous and accessible as well as the use of safer medical withdrawal procedures (when they are justified or inevitable) the standard of care.  While I am hopeful that there might be a place for this medication under some set of circumstances, only further research can elucidate exactly how naltrexone can be used safely.

I hope to revisit this with the members of relevant committees at the next ASAM meeting.

Editor’s Note: When speaking of naltrexone, Dr. Shinderman refers to the use of naltrexone both as a medication given to patients who have already withdrawn from methadone or other opiates and in UROD (so-called “rapid detox”) treatments.  Thus, when he refers to the small number of patients to whom he has given naltrexone, these patients had already withdrawn from methadone and were not given naltrexone for “rapid detox” purposes (Dr. Shinderman does not perform UROD and even before this information came out was highly suspect of UROD treatments).

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Obviously, the U.S. is not part of the European Union, so this will not change the legal/regulatory status of LAAM in the U.S.  But physicians, individuals on LAAM, and individuals contemplating LAAM therapy (opiate addicts or methadone maintenance patients who may switch to LAAM for various reasons) should take notice of the EMEA’s recommendation.  Clearly, there is a real danger associated with LAAM.  At minimum, LAAM should not be chosen over methadone for frivolous reasons.

Thanks to the new federal regulations and the accreditation standards that are coming with them, methadone dose caps should soon be a thing of the past and adequate dosing of patients will hopefully become the rule at U.S. clinics rather than the exception.  Some patients who switched to LAAM from methadone either requested LAAM or were pushed by clinic staff to try LAAM as a consequence of inadequate methadone dosing (i.e., a patient was on the maximum dosage permitted by the clinic [the dose cap] but still experienced withdrawal symptoms, opiate cravings, etc., so s/he switched to LAAM in hopes that it would more effectively control withdrawal symptoms and opiate cravings).  However, had these individuals received an adequate methadone dose, most of them would have been happy to remain on methadone and therefore not be at risk of LAAM-induced cardiac arrhythmias.

In any case, the risk associated with LAAM means that treatment with LAAM should NOT be used as a substitute for poor methadone treatment.  Try an adequate methadone dose first.
 
 

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*Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine.  Harris DS,
Jones RT, Welm S, Upton RA, Lin E, Mendelson J.  (2000), Drug and Alcohol Dependence 61:85-94.

This exhaustive and informative trial paper* on the co-administration of naloxone and buprenorphine tells us that a ten-minute IV infusion of the combination did not cause withdrawals in the subject patients, who were heroin addicts stabilised (sic) temporarily on buprenorphine maintenance 8 mg.

If I have understood correctly, this work has not supported the combination as being more or less “abusable” than simple buprenorphine on its own in such subjects.  It has demonstrated that the naloxone is partially absorbed with 10% bioavailability and at least one objective physiological change (pupil size) in the subjects given it “blind” with their buprenorphine.  The combination did, however, abolish cravings in the same way as the pure drug.
We know that if heroin addicts use buprenorphine (even without naloxone) they are likely to experience withdrawal symptoms on occasion and sometimes these will be very severe, due to the antagonist properties of the drug.  Regarding buprenorphine maintained patients, the authors state: “IV buprenorphine and naloxone produced subjective effects similar to those of SL [sublingual] buprenorphine and did not precipitate opiate withdrawal.”
It appears that some of the trial subjects may have had to return to street drug use after being released from this two-week trial.  There are only limited chances of receiving agonist treatment in some areas and this is a major ethical dilemma for such research in America.

In my own practice in Sydney, I have prescribed buprenorphine (alone) for five heroin dependent patients, all of whom had failed at many previous treatments, including methadone.  The results have been extremely positive and the patients are all most grateful for this innovation.  They all stabilised (sic) on low doses and ceased other opioid use.  It reminds me of the initial patients I had on methadone more than 15 years ago.

My own feeling is that the addition of naloxone is questionable and derives from motivations unrelated to ethical medical practice but as part of a law enforcement and “big-stick” approach.  There are unknown dangers of adding naloxone, so these must be balanced against KNOWN, and not just theoretical, benefits.  We do not know whether the combination is likely to solve “diversion” problems.  The theory seems to assume patients are inherently dishonest, and this could add to the pre-existing stigma of addiction.  Also, the “punishment” strategy is known to generally be ineffective in this field.  Where buprenorphine is supervised like methadone (as in the new Australian proposals), such arguments are only academic since dispensed doses would be exceptional.  Good U.S. research also indicates that most diverted methadone is taken by addicts who would be assessed as appropriate for treatment, meaning that improving access and treatment quality could eliminate it, and it may even have a beneficial aspect if it encouraged some into treatment.

We should not support the use of new interventions unless they are proven to be both safe and effective.  Would we put live yeast into penicillin capsules to dissuade people from injecting it?  I am not aware of any long-term research on naloxone... and naltrexone studies have not been without their problems.  The jury is still out on this one, and the combination is still not proven safe to my mind, nor is it necessarily “effective”, not just for the immediate patient, but in the senses hoped for by its proponents.

Editor’s Note: As we have reported in past issues of Methadone Today, buprenorphine is an opiate agonist-antagonist (e.g.: it has both agonist and antagonist properties) that is already being used to treat opiate addiction in certain countries, such as France, and has been used for this purpose in the U.S. on a trial basis (FDA approval of the buprenorphine-naloxone combination for the treatment of opiate addiction is expected soon).  Unlike the current situation in Australia, buprenorphine will be prescribed/dispensed for unsupervised use in the U.S.; opiate addicts will be able to obtain treatment at a doctor’s office.  The provider will not have to be accredited as is required of providers using methadone or LAAM to treat opiate addiction, under the current federal regulations.

Naloxone is an opiate antagonist, similar to naltrexone (used to reverse opiate overdoses, prescribed to former opiate addicts to block the effect of opiates should they relapse/use opiates, and administered in “rapid detox” procedures to precipitate withdrawal--see “Naltrexone Dangers” on page 2 of Methadone Today’s June 2001 issue).  Naloxone is being added to buprenorphine, supposedly, to deter individuals from injecting it in an effort to “get high”.  Theoretically, if the combination were injected, the user would not feel any intoxication from it and, if opiate dependent, the naloxone may actually precipitate withdrawal.

For treatment of opiate addiction, buprenorphine is not swallowed but taken sublingually [held and absorbed under the tongue].  Proponents of the combination argue that naloxone will not induce withdrawal or decrease the effectiveness of the buprenorphine if the combination is taken sublingually.
As Dr. Byrne points out, this study appears to contradict the original premise behind the combination--when used IV, the naloxone did not appear to block the effects of the buprenorphine.  This calls into question whether the addition of naloxone has any effect on the potential for abuse.  Thus, it is shocking that such a drug is being added when it has not even been demonstrated that it is effective at reducing the probability of abuse.  It is not good enough that the drug is demonstrated to be safe (and many, like Dr. Byrne, are not even convinced of naloxone’s safety), but it must actually work as well.

Furthermore, Dr. Byrne is correct to question the entire purpose of adding naloxone.  The term “effective” does not mean anything unless we know the purpose or goal (what is adding naloxone supposed to accomplish?).  We fail to see how adding naloxone to reduce diversion and abuse of the medication benefits patients.  It is unethical to force patients to ingest a drug that is not medically necessary or helpful just to help make the job of law enforcement easier.  If this is such a good idea, why not just prescribe opiate antagonists to every American simply to reduce the probability of opiate abuse?  Thus, we are suspect of the addition of any drug that serves no medically justifiable purpose.

On the other hand, we must point out that policymakers might not permit buprenorphine to be prescribed at all for the treatment of opiate addiction if it were not combined with a drug like naloxone to supposedly reduce the risk of diversion and abuse.  At the least, the U.S. Congress may not have allowed private physicians to prescribe buprenorphine (without being an accredited opiate treatment provider) in an unsupervised manner had naloxone not been added.  Still, we are not convinced of its safety or if adding it is even ethical.
 
 

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Dear Doctor,

I am a nurse educator in Georgia--my hospital delivers 160-190 babies a month.

We opened a NICU in January 2001.  We have a patient who is going to deliver in July on methadone--I would like to know the best way to handle her pain in labor.  Her lawyer and doctor have contacted us regarding her low pain threshold.  I would like some info regarding pain control.  I am planning to have a meeting with her doctor and maybe an anesthesiologist regarding this.  But I also need to educate my nursing staff.  Thank you in advance for your help.  -Lisa
 

Dear Lisa,

There is no formula for treatment and you have not given enough specific information to make an educated guess.

I can say that it is not uncommon that methadone patients need 50% more analgesia [e.g., pain medication] and that on a more frequent schedule, with drugs like morphine; but the main thing is to be attentive to the problem and respond appropriately to the patient's complaints.  A patient on 30 mg of methadone and stable is not the same with regard to analgesia as a patient on 150 mg; the former will be much like any other patient who is opiate naive.

Marc A. Shinderman, M.D.
Center for Addictive Problems

Editor’s Note: We commend Nurse Lisa for taking the step of educating herself by researching the issue rather than drawing her own conclusions based on myths and misinformation.  If every medical professional operated in this manner, mistreatment of methadone patients by medical professionals would be far less common.

Unfortunately, many medical professionals simply assume that the patient’s usual methadone dose provides plenty of pain relief--and certainly they would not believe that a methadone maintenance patient requires MORE pain medication than the opiate naive patient [due to cross tolerance to opiates].  Add to this mistaken belief, the fear that the patient will become addicted to the pain medication (since methadone maintenance patients WERE opiate addicts) and the stereotypical view that opiate addicts will always exaggerate pain to obtain more medication than they really need, and one can clearly see why so many medical professionals seriously undermedicate patients.

In response to the aforementioned concern about methadone maintenance patients becoming addicted to opioid pain medication, we should note that once a patient is stablized on a given dose, the methadone has a “blockade” effect.  A maintenance dose actually blocks the intoxicating effects of opioids.  To what degree depends upon the level of the maintenance dose.  Patients on blockade doses will feel virtually no intoxicating effects from pain medication at the level that would be prescribed for pain relief.  But the intoxicating effects of pain medication will be somewhat muted even in maintenance patients on lower doses of methadone.
 
 

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Dear Doctor,

Many U.S. methadone clinics “ban” benzodiazepines (i.e., Valium, Xanax); that is, any use of benzodiazepines [which is determined by drug testing] is treated as illicit drug use--even if the patient was legitimately prescribed a benzodiazepine by a physician.  Do you agree with this policy?  Also, is the prescription of benzodiazepines ever justified in methadone patients?  -Wayne
 

Dear Wayne,
 

The issue of benzodiazepines is almost the same as alcohol.  Sometimes such use could be classified as “discretionary” or even “recreational” but on other occasions it is very clearly “therapeutic”, such as for epilepsy or panic attack treatments.  I know some patients who say a certain amount of alcohol is, for them, therapeutic, and nobody would consider a “couple of drinks” after a day’s work necessarily dangerous.

Benzodiazepines have a great deal in common with alcohol, and we should never reject a patient from methadone treatment for drinking excessively or for taking tranquillizers.  However, such behaviour (sic) should flag the need for close assessments and added services to be offered, knowing of the increased risks involved.  The very issue of a patient having two doctors should not arise since before putting a patient onto methadone, a good specialist clinic would normally seek a referral from the patient’s usual doctor and send a report of progress so treatment is coordinated.  Unfortunately, owing to the nature of some clinics, this does not always happen and patients’ treatment can become a confusing “hodge-podge” of arbitrary and ill-conceived decisions.

It is simply illogical to base important decisions relating to opiate addiction treatment on the patient’s use of benzos or alcohol.  They are in treatment by definition for opiate dependency, and other intercurrent problems need to be treated individually and sensitively.  Cannabis [marijuana] is the most obvious, where apart from simply education on the dangers, such as with fatty foods, there is little point in any medical intervention in most cases for patients on methadone maintenance treatment.

My feeling is that all people are better of without benzodiazepines if they can cope with reductions.  Most can reduce to zero as long as they are receiving adequate doses of methadone, which abolish cravings for 24 hours.  For a small proportion, perhaps 10%, repeated attempts at reductions have resulted either in relapse to uncontrolled drug and alcohol use or the occurrence of unacceptable anxiety/panic symptoms.  These patients should be given access to small doses of supervised diazepam in most cases, which should be given along with their methadone, with dispensed doses for take-home days.  Some patients can regain control of their tranquillizer use, but others will need continuing supervision up to three times weekly.

Dr. Andrew Byrne
General Practitioner, Drug and Alcohol
New South Wales, Australia
 

Editor’s Note: We respect Dr. Byrne’s belief that ideally, treatment should be coordinated.  However, such coordination rarely exists in the U.S. between substance abuse treatment and other medical treatments.  In the case of treatment of certain mental illnesses, some methadone clinics (either the physician who makes dosage/treatment decisions or an in-house psychiatrist) will actually provide such treatment--including the prescription of medications (i.e., anti-depressants for clinical depression or benzodiazepines for anxiety).  But the majority of methadone clinics do not have in-house psychiatrists and will not provide treatment for mental illness beyond the “counseling” provided to  patients.  Although these clinic counselors may be able to help with some psychiatric problems, many methadone clinic counselors are not psychologists or psychiatrists and are, therefore, not qualified to treat mental illnesses. . . and, of course, cannot prescribe medications.

In our experience, many methadone clinic physicians have no interest whatsoever in providing treatment for mental illness or anything else aside from drug addiction.  These physicians may refer patients to outside doctors but will not take any kind of role in such treatment.  At many clinics, patients cannot even see a doctor unless they have a specific issue directly related to drug addiction/methadone treatment.  We bring this up, not as a criticism of clinic physicians, but to point out the way it is.  We do not necessarily expect methadone clinics to provide treatment for mental illnesses and other medical conditions, but if they are not going to provide such treatment, they ought to respect medical treatments provided to patients by outside doctors.  Thus, a universal ban on certain medications by methadone clinics is unreasonable.  If an outside doctor prescribes a medication, the clinic should accept that it is medically necessary.

Another interesting issue Dr. Byrne raises is how methadone clinics should handle certain non-medical drug use--at least in cases where the patient is not addicted to the drugs being used.  Many methadone clinics do not concern themselves with alcohol use if there is no evidence that the patient is addicted to alcohol, as long as s/he is not actually under the influence of alcohol when attending the clinic.  In part, this is for practical reasons--breath and blood tests generally only detect alcohol while the individual is under the influence.  Clinic staff may also be unwilling to address moderate alcohol use, since alcohol is a legal drug.  Except in a handful of states, treatment providers are not required to test for marijuana.  Still, many methadone clinics do regularly test for it.  We question whether they should be testing for marijuana, at least in cases where there is no evidence of marijuana addiction.  Methadone clinics have been known to basically drive patients out of treatment for marijuana use.  We cannot agree with such tactics when the consequences of cessation of methadone maintenance treatment are far worse than any possible harm resulting from marijuana use.

One final observation is that the patient should seek a second and maybe even a third opinion on the best course of treatment for a panic or other anxiety disorder--or any other mental illness--where benzodiazepines are being prescribed.  Given that treatment is often improperly coordinated, multiple medical opinions are important in order to get proper medical treatment.

We would like to say that all physicians are well-informed regarding methadone maintenance treatment and potential drug interactions, but this is not the case.  As Dr. Byrne states above, increasing the dose of methadone may eliminate the need for benzodiazepines or at least reduce the required dose of benzos.

Methadone increases the effects of benzos, and benzos increase the effects of methadone.  Therefore, dose determinations can be quite complex.  For example, a methadone patient who stops taking benzodiazepines will need a methadone dose increase just to prevent the onset of opiate withdrawal symptoms.

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Dear Doctor,

My methadone clinic adds tap water to take-home doses (they use Methadose, which is a liquid [and not wafers/diskettes that must have water or juice added to them]), supposedly to deter diversion.
I want to know what happens to our methadone that’s been sitting in stagnant tap water in a sealed bottle for two weeks (or more)*.   Water that may be chlorinated or have fluoride in it.  Do those chemicals affect that methadone?  And what kind of germs can grow in tap water that’s left to sit around for such a long period of time?  What if the containers aren’t sterile?  -Terri

Dear Terri,

We [CAP] are changing to dry medication for greater than 6 day take-home supplies.

The label on Methadose recommends addition of liquid, which we think is ridiculous, but have been doing so, per adding Tang, for years.  There have been instances of doses going bad in this scenario, even exploding.  The truth is that this is rare, but, if avoidable, dilution should be abandoned as a practice.

Marc Shinderman, M.D.
Center for Addictive Problems (CAP), Chicago, Illinois

*Editor’s Note:  This question is all the more relevant now, because the new federal regulations allow for extended take-homes (14-30 day supplies).  Unlike the former federal regulations, the current regulations allow “dry” medication to be used (tablets or pills may be provided to patients without adding water or juice).  We feel that there are other advantages to dry medication, and that dry medication should at least be an option for most patients.

The rationale some clinics give for diluting take-home doses is that it makes diversion of doses more difficult, but we are skeptical of this claim.  Diluting take-home doses only adds inconvenience to the vast majority of patients who are not diverting their doses.  The dispensing of doses in liquid form is done for the same reason, which we also believe does nothing to stop diversion [which is uncommon anyway] and, if anything, may make accidental overdose by children more likely [though accidental overdose of methadone is already rare].

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Can a methadone patient's organs be used for transplantation?  In other words, is there anything about methadone maintenance  that would cause a problem with using the organs of a methadone patient?
 

Dear Prospective Donor,

There is nothing [regarding methadone maintenance treatment] that would prevent donation of organs.  HIV and HCV [Hepatitis C] are issues (organs taken from an individual who has/had HIV or HCV may not be useable in transplantation), but that is not an issue of methadone maintenance treatment per se.

Marc Shinderman, M.D.
Center for Addictive Problems (CAP)
Chicago, Illinois

Editor’s Note: It is possible that discrimination exists regarding the use  of a methadone patient’s organs, though we have not heard of any such cases.  This is not an issue that comes up much, since the perspective organ donor is often deceased.

Many methadone maintenance patients have other health issues that may make use of at least certain organs problematic.  As Dr. Shinderman mentioned, HIV and HCV are certainly relevant issues--and some experts estimate that 90% of methadone maintenance patients have hepatitis C.  In addition, abuse of certain drugs, including cocaine, tobacco, and alcohol, can damage various organs.  But being a methadone patient should not disqualify one from being an organ donor, especially considering the shortage of available organs for transplantation.
 

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