Pain Management" Enough" Is Not  EnoughPeak & TroughTreatment Of Pain Chronic Pain & Opioids
Methadone Forum
Rate Your Program
"What's Your Story?"
The Director's View
Talk Back
Addiction Science
An Addict's View
Bits and Pieces
Drug Tests
Erosion Of Rights
Federal Regulations
 Frequent Questions
Georgia Opiate Clinics
Georgia Regulations
Hepatitis HCV
   Internet  Resources
 Legal Issues
Methadone Talk
Methadone and Pain
Methadone Interactions
Methadone Maintenance
Myths Of Methadone
News And Views
  Opiate Drug Treatment
Rights of Patients
Video Library
For Women Only


CSAT Guidelines V11. A (1.)   General Dosage Principles

1.  The dose of methadone maintenance medication is individually determined on the
     basis of good clinical judgement after review by a physician or other professional
     practitioner with prescribing privileges who is knowledgeable about, and experienced       in addiction medicine including methadone therapy.

The signs and symptoms associated with full withdrawal and acute opioid overdose are well known.  The changes associated with overmedicating and undermedicating are less dramatic and often subjective in nature. 

The mildly to moderately overmedicated patient may show constriction of the pupils.   Nodding may occur as well as some scratching of the face, especially the nose.  Sedation may not be at all apparent, and, in some cases, the patients feel mildly stimulated.  Nausea may be a complaint, particularly in the newer patients.  At a fixed dose, these effects tend to pass as tolerance is developed. 

When overmedication is suspected or detected, a reduction in the dose is indicated along with careful explanation to the patient, except in cases using "blind dosing" techniques. 

The minimally or very mildly overmedicated patient may pose a greater problem.  During the time the patient experiences effects of a dose slightly in excess  of the established tolerance threshold, there is a definite but mild sense of well being.  Energy and motivation levels are increased ao that the individual may want to clean house or wax the car, for example.  What is important is that the individual not attribute this feeling to the drug, as was the case during the "high" or nodding phase. 

The addict may associate this state with being "normal;"  hence the term "addict's abnormal normality."  The state is experienced after a euphorigenic dose of heroin or methadone.  It lasts much longer with methadone. 

As the effect wears off, the exaggerated sense of well-being, motivation, and energy are no longer present.   This state is in reality the addict or patient's  "normal" state, which can be described as a full awareness of one's internal and external environment.  This  individual , who is just now feeling normal, is convinced that he or she is starting to " get sick."

As further tolerance develops, the abnormal normality is no longer experienced, and the patient complains that the dose is no longer holding and that an increase in methadone dose is neededIf a dose increase is granted, there is a brief return to this condition that the patient thinks is normal.  The return is brief in that it depends on a dose increase in excess of the established threshold -----  which will further raise the tolerance threshold to the new dose level. When that happens, the patient is back again wanting more methadone.  

It is important for the physician and other staff to be aware of this phenomenon.  By  carefully explaining it to the patient with reference to the patient's own experience with heroin, patients can learn to recognize the problem anf facilitate stabilization.   

The underdosed patient is easy to detect if the pupils are dilated and yawning, sniffles, lacrimation, and chills are noted The undermedicated patient relates the presence of anxiety, insomnia, drug hunger, and drug-seeking behavior.  Hence, it is not possible  to rely on purely objective means as a basis for a dose increase.

There are various reasons other than the dosage amount that could hinder you from receiving the full benefit of your dosage.  I covered some of the reasons in "Methadone Interactions" but we will look at them again. 

A variety of complaints may introduce the case for more methadone, for example, "I wake up sick; I have a strong urge to fix; I am fixing."  There are a number of reasons why the patient who was stable may be having problems in relation to dose.

Perhaps the most frequent cause is the ingestion of other substances,  especially alcohol.  Any drug that stimulates the liver's microsomal enzyme-oxidizing may accelerate the metabolism of methadone.  Barbiturates and other sedative-hynotics may produce this effect.   

Specific drugs known to accelerate methadone metabolism, and at times, to produce the " Abstinence Syndrome", include rifampin (Tong et al. 1981), phenytoin (Dilantin®) (Kreek 1978).  A. J. Saxon (1989) suggested that valproic acid, unlike other anticonvulsants, has no effect on methadone metabolism.  Although this opinion was based on only two cases, consideration of valproic acid would be justified when the clinician faces a choice between sezures or abstinence.  

Inadvertent administration of opioid agonist/antagonist drugs can also precipitate  "Abstinence Syndrome" by an entirely different mechanism.

Environmental changes and other stresses can cause the patient to perceive that the dose is not adequate and to experience increased drug cravingEvents that increase the availability of drugs, such as another addict moving in at a home or a " connection" opening nearby, can intensify craving.  Dose increases may be quite appropriate in such cases, although efforts should focus on resolving the offending situation, than relying on more methadone.  Conversely, diminished availability of drugs, as may occur in prison or jail, may diminish drug craving. 

In the absence of medication or enviromental contributions and polysubstance abuse in an apparently destabilized methadone treatment patient, plasma level determinations should be considered.  This ratio is important for the clinician  who is interpreting methadone plasma levels.  At present 150ng/ml is generally accepted as the lowest level that will maintain steady-state effect. (Dole, 1998). 

The optimum 24-hour mean plasma level may be more in the 400ng/ml range (Goldstein pers. com. 1991; Kreek1973; Tennant 1987; Wolff et al.)  Loimer and colleagues (1991) suggest that  "methadone plasma concentrations of 400ng/ml  are necessary to suppress any further opiate action and to provide stabilized maintenance."  The optimum dose is the level at which there is adequate methadone to provide constant availability to the opiate receptors.  

Excretion of methadone via the kidneys is pH dependent.  Studies have shown that by alyering the pH from very acid to very alkaline, the half-life of methadone may vary from less than 18 hours to greater than 40 hours. (Nilsson  et al.1982)  

State Methadone Treatment Guidelines Tip 1 (Chapter 5) Principles Of Methadone Dose Determination   

Traditionally, healthcare practitioners seek to prescribe the lowest dose of medication "to get the job done," believing this will help reduce unwanted side effects   However, in the case of methadone, inadequately low doses often have been prescribed for more philosophical, moral, or psychological reasons than for sound pharmacological  and clinical ones. These misguided practices stem from stigmitization of methadone as "evil" and a belief that patients should be administered the lowest  possible and then discontinue methadone as soon as possible.  It also was falsely believed that it would be easier to eventually withdraw patients from lower rather than high doses. 

However, there is no evidence of lower doses being truly adequate for the vast majority of the patients.  Just how large a dose is "enough" depends on individual patient needs.

Letter regarding dose increase written by J. Thomas Payte, M.D. on the advantages of patients receiving an adequate dose.

Below is a copy of Dr. Payte's letter.  If you are having any difficulty in obtaining an increase ---- I would suggest printing a copy of the letter and politely asking your physician if he would read it and give you his opinion.  Maybe since it was written by one of their peers and an expert in the field of methadone, they might be interested in reading the letter and who knows --they may have a change of heart.   

J. Thomas Payte, MD, CMA                                                                                     
Corporate Medical Director
Colonial Management Group, LP
14050 Town Loop Blvd. Suite 204
Orlando, FL  32837

September 12, 2003

Bad Patients or Bad Treatment???

To Colonial Management Staff at all levels, interested patients and significant others,and anyone interested in quality patient care with favorable treatment outcomes:

Recently I was in communication with a methadone patient and his father involved in a struggle with a methadone program trying to get an adequate individualized dose of methadone.  The last report I had suggested that resolution was still pending. 

Having dealt with many patient-program conflicts, as patient advocate and program physician, I have learned to avoid judgments without input from all perspectives.  This correspondence is not an attack on any specific program, rather a condemnation of the practice of denying dose increases despite strong clinical indications that the current dose is not achieving optimal results for the desired period of time. This is a response to a chronic and recurring situation that affords a teaching opportunity. The situation I describe is not at all a rare occurrence.

I like to think that in the 40 years since I treated my first young couple addicted to heroin, that I have learned a few things.   Occasionally I learn a valuable lesson that is not found in journals, policies, procedures, or guidelines. The purpose of this letter is to share that experience and it’s simple lesson.

In 1985 we were in the midst of a low-dose hysteria that was running through programs like the Sobig virus is running through computers today.  I was not immune to this phenomenon and was trying to lower my maximum doses for take-home to 80 mg.  At this point I can’t imagine why I wanted to do that, other than most programs were involved in the same pointless effort without a shred of scientific or clinical evidence to support such bizarre behavior.

In the midst of the frustration of patients complaining and doing poorly, I read an article in one of the addiction journals by Forrest Tennant and colleagues. What they did was to compare a group of really good, well-behaved patients with a group of very poor performers guilty of non-compliance, positive urines, and a host of sins committed against the methadone establishment.

Both groups were on 80 mg methadone daily.  The simple test was to measure trough blood levels 24 hours after an observed dose.

The average methadone levels for the good guys was over 400 ng/ml, while the bad guys averaged about ¼ of that, with mean trough levels of about 100ng/ml.   In a rare moment of clarity it came to me…Just maybe, the poor performers are not bad patients but are getting bad treatment!

At that point I abandoned the pursuit of the lowest possible dose and adopted individualized adequate dosing, with occasional use of methadone serum levels to detect aberrant metabolism.

Lesson number 2 occurred in the late 80’s when I admitted a patient who had been administratively discharged from another program. 

He had been considered non-compliant, had positive urines, and was thought to be lacking in motivation.   During his admission process I noted that, according to his history, he had never been stable on methadone and his drug use was most likely a form of self-medication, rather than recreational.

His initial time in our program was dedicated to adjusting his dose to a level that would control craving and prevent withdrawal. This number turned out to be considerably higher than the maximum dose allowed in his former treatment program.

The outcome?  Within a few weeks there was a complete turn-around with negative urines and improvement in all domains of the ASI (Addiction Severity Index).  He became a model patient and quickly earned full take-home privileges.

Since that time I have had this experience reinforced many times with minor variations.

When forced to deal with a ‘difficult’ patient, the first order of business is to insure that the patient is receiving an adequate individualized dose.

Adequacy of dose is based on 2 factors:

How Much? The amount of medication
How Often? Frequency of dosing; the interdose interval such as: Every 24, 12, 8 hours.

In the simplest of terms an “adequate dose” is defined as that amount of methadone needed to suppress drug craving/hunger and prevent the onset of withdrawal for a time in excess of the dosing interval (usually 24 hours).

While doses in the 80 to 120 mg range are effective for a majority of patients, the actual range of individual adequate doses ranges from as little as 10 mg daily to, in rare cases, up to 500 mg, or more.

It is not my intention to imply that all methadone patient problems are dose related.   I do strongly suggest that, as a first step, assurance that the dose is adequate will often correct the problem, and at a minimum, improve the    chances of success of other strategies and interventions that will follow.

Before we label a patient as a “bad patient” we need to be certain that the problem is not “bad treatment.”

If you want to know if a patient is on an “adequate dose” simply ask how they are feeling, at various times of day in relation to the methadone dose (4, 12, and 24 hours after dosing).

Having asked, then listen. The very first thing that Dr. Marie Nyswander taught was to "always listen to your patient, and you will never go wrong."  You have to be able to listen and to ask the questions to get you the answers and information  to be able to make decisions to ensure that we are providing quality treatment.

Serum methadone levels will NOT provide this information (adequacy of dose).

I do hope you will consider the contents of this correspondence with an open mind.  What is suggested here is really a simple step, which in many cases may be the only step in resolving the problem of a difficult patient.

Don’t be a Low-Dose program, don’t be a High-Dose program, be an Adequate Dose program.

Respectfully submitted in the interest of the best possible treatment for those we serve.

Tom Payte, MD

Note from The Director:  If anyone copied Dr. Payte's address before--I apologize but it was not correct. The above address attached with the letter has the correct address..  Please click on the link below to access more of Dr. Payte's work at his website.

Click Here

 There should be no cap on your methadone dose.  If you need a
 legitimate increase -------- and are having problems?  Call us? 


Guidelines For Interpretation Of Serum Methadone Levels

 Numerous questions are received about the intrepretation and utility   of  serum blood levels of methadone.
The following are the current guidelines  -  used for intrepretation of serum methadone levels.  
These are intended only as a guide and are not to be taken too literally or to replace sound judgement.               

Numerous questions are received about the interpretation and utility of serum blood levels of methadone.  The following are the current guidelines used for interpretation of serum methadone levels.  These are intended only as a guide and are not to be taken too literally or to replace sound judgment.

General Principles:

"Steady-state" effects of a methadone depend on adequate amounts of the drug available to receptor sites at all times.  Adequacy of dose is a clinical determination based on the degree to which drug craving is eliminated and withdrawal prevented.

Adequate methadone levels are considered to something above a minimum of 150ng/ml - 200ng/ml is a more acceptable minimum (trough level, 24hour level).  Trough levels alone are of little clinical utility and do not define adequacy, inadequacy, or excessive methadone dose.

Effective cross- tolerance (blockade) is believed  to require levels of 400ng/ml and above, at all times with a peak/trough (P/T) ratio of 2 or less.  Not all patients need blockade levels and effective blockade has been reported at levels less than 400ng/ml.

Peak levels, drawn at 3 (2-4) hours, should be no more than twice the trough level but up to 2.5 is probably ok.  The ratio is obtained by dividing the peak by the trough (P/T ratio).  Ideal is less than 2, 2.5 is on the "fast" side, 3.0 or more clearly indicates rapid metabolism and split dose should be considered if supported by clinical presentation.

The optimum trough level is probably 400ng/ml and higher.  Loiner has shown that levels should be at 400 or greater  at all times for best outcomes.  150-200ng/ml is considered a minimum.

Dose Increase

Ø  Clinical picture suggests dose not adequate, subjective symptoms.

Ø  24 hour level less than 400ng/ml with P/T ratio of < 2.5.  Higher trough levels  do not contraindicate a dose increase in the presence of clinical indications of inadequate dose.

To Justify Maintaining A Dose

Ø  Clinical picture stable (regardless of blood levels and ratios)

Ø  24 hour level at 150-1000ng/ml +/- and P/T ratio of < 2.5

Dose Reduction

Ø  Clinical picture supports excessive dose levels

Ø  Blood levels not relevant if signs and symptoms of overmedication is present

Split Dose

Ø  Clinical picture of being OK at 3-12 hours but "sick" before the 24 hours

Ø  P/T ratio >2.5

Split Dose With Increase

Ø  Not holding for 24 hours

Ø  P/T ratio > 2.5 and trough level  < 200ng/ml

Split Dose With Decrease

Ø  "loaded" during peak hours, normal, then "sick " before 24

Split Dose Induction

Ø  Day one of split, patient should receive 80% -100% of regular dose as observed dose in clinic.  50% of total dose (after split, if different) is provided to take 12 hours later.

Ø  Day  two: 50% of total every 12 (10-14) hours

Ø  Patient on 100mg receives 100mg on the morning of day one and 50mg  "to go" to take about 12 hours later.  On day two will get 50mg q 12 hours.

Note:  Patients who are already having problems with dose do not do well getting half their usual dose at the beginning of a split dose routine.


With over ten years clinical experience with methadone levels we have found clinical indications to be more than adequate for proper and adequate dose determinations.  Methadone levels may be useful to confirm clinical impressions in some cases but Serum Methadone Levels  per se are of limited value in dose determination.

The primary value of serum methadone levels is to measure the rate of change over a dosing interval to document indication for split dosing if there are reservations regarding the clinical presentation alone.

Article was written by J. Thomas Payte M.D.

Methadone Maintenance Treatment Patients in Pain Need Higher Methadone Doses Researchers at an Israeli Methadone Maintenance Treatment Clinic known for providing adequate methadone doses studied the special needs of patients experiencing chronic pain..

During a 4-month period,.patients participated in a questionnaire survey on pain duration and severity methadone dosages and urine test results for drug abuse during the month before and at the time of the survey were recorded. Chronic pain was defined as lasting for 6 or more months.

More than half (55%) of the 170 patients experienced chronic pain and, as expected, they had a significantly higher proportion of chronic illness (75%) compared with non-pain patients (45%). Among the chronic pain patients, 53% experienced mild to moderate pain and 47% had severe or very severe pain.

The duration of pain was significantly associated with pain severity and it also significantly influenced methadone dose requirements (see Table). Beyond the first year, patients with chronic pain needed increasingly higher daily methadone doses to remain stable in Methadone Maintenance Treatment.


Duration Average Methadone Dose (mg/d) Approximate Dose Range


>10 years 180 120–240
1-10 years 160 105–215
<1 year 135 60–205
No pain 150 95–200

All numbers rounded; range = mean ± 1
standard deviation.

The authors concluded that, although methadone was not prescribed for pain treatment in these patients but rather for opioid addiction    -------------------------
Methadone Maintenance Treatment patients with prolonged pain required significantly higher methadone doses ------------  compared with patients having shorter pain duration or no chronic pain.

Source: Peles E, Schreiber S, Gordon J, Adelson M.  Significantly higher methadone dose for Methadone Maintenance Treatment  patients with chronic pain. Pain. 2005;113(3):340-346

Modified: 2 July 2005