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Methadone-maintained patients occasionally require medical, surgical and dental procedures that are provided or performed away from the methadone maintenance program.  When conditions are procedures cause pain, serious errors in patient management commonly occur.  As a result, pain is either not treated or seriously undertreated. 

The practitioner often believes that a patient taking 80mg daily could not possibly need anything else for pain.  Is this true or false?


This  is  absolutely  incorrect!  It  should  be  cyrstal clear that  the methadone-maintained patient is fully tolerant of the maintenance dose of methadone and thus  experiences  no  analgesic  effect  from  the  narcotic at  the  stable dose!

Another common clinical error is based on the belief that any exposure to opioid agonist analgesics will somehow aggravate the addictive disorder.  There is some basis for this belief, in that relapse to illicit opioid self-administration has occured when former heroin addicts, in remission or recovery, have been given narcotics..  In the authors' experience, these  situations most often occur when the prescribing practioner is unaware of the history of opioid dependence and the patient takes an active role in seeking narcotics, justified by the temporary pain condition. 

In 1980, Kantor and coworkers compared a group of methadone maintenance patients who were exposed to significant amounts of narcotic analgesics in the course of hospital treatment with a group of methadone maintenance patients with no such exposure. The patients were followed for a mean of twenty months, with the narcotic-exposed group showing no differences to controls. 

The inadequate treatment of pain in methadone-maintained patients commonly leads to disruptive behavior by abgry and frightened patients and discharge against medical advice, often to the detriment of the patient's health. (Zweben and Payte)

The principles of managing acute severe pain in the methadone-maintained patient are quite simple: 

* Do not interrupt daily methadone maintenance.

* The patient's dose should not be changed, whether by oral or intramuscular routes, although it may be divided:  50 percent of usual before and 50 percent after surgery, intramuscular administered. .          

* Discuss pain management with the patientand give assurances that he or she will be provided adequate relief. 

* When nonnarcotic analgesia is not effective, short-acting opioid agonist drugs should be used in frequent and more higher doses against the background of continued methadone maintenance.

* Do not use agonist/antagonist drugs such as pentazocine (Talwin®), butorphanol tartrate (Stadol®), nalbuphine hydrochloride (Nubain®) and buprenorphine (Buprenex®).  These agents may precitate AS in the methadone - maintained patient.

*Change to nonnarcotic agents as soon as practical.

*Avoid-prescribing for self-administration.

Patients  may  request  a  temporary  increase  in  methadose dose during an episode  of  pain. This  practice  is  not  uncommon.    However,  increasing  the methadone dose may afford only approximately six hours of  analgesia. Short-acting opioid  analgesics  are appropriate and effective in methadone maintenance treatment  patients if used properly.   Because of the established cross-tolerance, the short-acting opioid agonist agents may require  larger- than - usual - doses   and more frequent administration.  Attending physicians may need both firm guidance and reassurance from experienced addiction medicine professionals because  the  attending  physicians  are  not  accustomed to using   such  large narcotic doses.  Still others, may become judgemental, angry, and punitive  and  with-hold medication.  Many unpleasant situations and much unneccessary suffering can be avoided by discussing pain management plans  with both  patient  and  physician before surgery whenever possible.  


Chronic pain, by itself, is among the most difficult clinical problems seen in the medical practice.  Primary chronic opioid dependence (as opposed to iatrogenic drug-dependence secondary to the chronic pain disorder) seen in combination with chronic pain is especially problematic.

A referral to a professionally Comprehensive Pain Center is usually appropriate. The methadone-maintained chronic pain patient is a suitable canditate for most techniques employed in such centers, such as neuroblative procedures, biofeed-back,  acupuncture,  psychotherapy,  behavioral management, and other proce-dures.   A  common  problem  in  such  referrals  is the insistence of the expert on pain management  to  withdraw the patient from methadone. This is rarely a appropriate  and will often result in a failure of both the treatment of addiction and the pain disorder .To be effective   the   pain  management  expert  and  the  addictionologist  should  coordinate treatment in an extended team approach.

The  chronic  pain patient seen in methadone mangement treatment programs have  often  failed  at  one  or  more  pain  clinic treatments, have had multiple useless surgical procedures, are suffering from serious chronic depression, and have escalated drug use significantly. 

Many  of  these  dual- diagnosis  patients  have  a level  of  chronic  pain,  with episodes of more acute severe pain.   Surprizing as it may seem, the authors have experience  suggesting that at least some chronoc pain patients benefit from long-term adequate-dose  methadone  maintenance  with  episodic  use of   short-acting   opioid analgesics  during  episodes  of   acute  pain.  Careful  supervision  and  monitoring is essential.   Medications  are  not provided  to be  on  hand  in the  event  pain   occurs.   However, provisions must be made to promptly respond to  the  episodes  of acute pain.

As in the management of acute pain , when opioids are used, both the dosage and  frequency  of administration  should  be  increased  in  order  to  provide adequate relief.  

For many such patients, there are no really satisfactory answers and treatment   is    reduced  to  a   process  of  containment  and   damage control.    Support, reassurance,   and compassion are the most essential features in managing the patient  with  chronic  pain.

Reference:  Principles of Methadone Dose Determination Chapter 5 pp.59-61      
State Methadone Treatment Guidelines  J. Thomas Payte M.D. Elizabeth T. Khuri M.D.



OPIOID AGONIST THERAPY is an accepted treatment for opioid addiction, with documented efficacy.  Methadone Maintenance Treatment of Addiction is  the most common form of Opioid Agonist Therapy, is approved by all major medical and professional organizations concerned with addiction treatment.

Approximately 179,000 persons (1) in the United States are currently enrolled in methadone treatment. The federal government advocates expanded availability of the modality. Although some individuals require opioid treatment of addiction on a time-limited basis, others require treatment on a long-term basis and may, during the course of treatment, present with medical disorders associated with acute   or  chronic  pain.     Although  the  problem of pain management during methadone  maintenance  has  received   little  systematic   attention, pain  is a common   problem  in   this   population  and  likely  to become more  so as  the population ages and a larger number  of  medically  ill  patients  are enrolled in programs.

Undertreatment of pain, which is a recognized problem in all populations, occurs with relatively greater frequency in those with histories of chemical dependency, including patients enrolled in Mathedone Maintenance Treatment (2). The barriers to effective pain treatment are multiple and complex. Its undertreatment may be related to deficiencies in clinician practice, including the failure to assess pain and co-morbid disorders adequately, and to inadequacies in their knowledge and skills.  Additionally, persistent pain may be ascribed to patient-related problems, such as inadequate insurance or reimbursement for analgesic therapies.

In populations with chemical dependency, analgesic therapy using opioid drugs requires a high level of knowledge and skill on the part of responsible clinicians. In the case of methadone maintained patients, effective analgesic therapy requires careful attention to both clinical and pharmacologic principles. Misinformation about the pharmacology of opioids, including methadone, may contribute to inadequate pain management. Misinformation about opioid tolerance is also common.

Physicians may also believe erroneously that methadone taken for maintenance  is sufficient to provide adequate analgesia. In addition,there are widespread concerns regarding possible legal sanctions related to physicians’ use of state-mandated prescription forms for opioids.

When an "Methadone Maintenance Treatment Patient is in pain," aberrant drug-related  behaviors may occur, and may raise concerns about relapse. A detailed assessment often indicates that desperation arising from the unrelieved pain is more likely to be the cause. In  the context  of a medical problem such as pain, simple labeling of aberrant behaviors as abusive “drug seeking” is inappropriate.  Without a careful assessment by a concerned and knowledgeable clinician, behaviors can be misinterpreted.

Cycles of clinician concern and patient distress my be difficult to interput.  The process requires the ability to perform a sophisticated assessment of  both  pain  and  drug  use, and the ability to respond to unrelieved pain with appropriate interventions. Professionals working  with  addicted  individuals  need to become aware of  their own possible biases, which may detract from  their  care of these  patients.  Examples  of  common  biases include (3):

"They  are morally culpable for their addiction.   It's their fault.”

Pain is ‘payback’ for their own vices and for  getting high.”

They are deceitful and always manipulating  to get drugs to get high.”

All of these issues can become particularly daunting when the pain and clinical context suggest role for long-term  opioid  analgesic therapy in  patients receiving methadone maintenance. To  address these issues, this article  briefly reviews the   principles of opioid agonist therapy of addiction and  the principles of pain  management for methadone-maintained patients.



Basic Pharmacology

Methadone is a synthetic opioid with a long and variable half-life (between 12 and 100 hours.4). Although it can be administered intravenously or intramuscularly to treat pain, its utility as a maintenance medication in the treatment of opioid ad-diction is based on its long half-life and ready, reliable absorption when used as an oral medication. The slow onset of methadone taken orally does not produce a sudden “rush,” and produces no euphoric effects in most patients (5). As a treat-ment for opioid addiction, it is effective in blocking craving and withdrawal for 24 – 36 hours..

For decades, methadone has also been used as an analgesic, and interest in the drug as a treatment or pain has been increasing because of recent evidence that the commercially available racemic mixture includes an isomer that does not bind to opioid receptors, but is an antagonist at the n-methyl-D-aspartate (NMDA) receptor. By blocking this receptor, this d-isomer could potentially yield analgesia by a mechanism that potentiates that produced by binding of the l-isomer to the opioid receptor. Moreover, NMDA-receptor antagonism reverses opioid tolerance, and this effect may explain the unexpectedly high analgesic potency of methadone when it is administered to patients who are receiving another mu agonist drug. 

The analgesic effects of methadone typically last 4 – 8 hours after a dose. Although some patients are able to achieve stable analgesia with dosing every 12 hours, most patients require analgesic doses every 6 – 8 hours, and some can avoid end-of-dose failure only by dosing every 4 hours.

Single-dose, controlled analgesic studies indicate that methadone is slightly more potent, on a milligram per milligram basis, than morphine sulfate. (6). These studies have limited relevance to chronic administration, during which the combination of kinetic factors (a slow and gradual increase of plasma concentration because of the long half-life) and dynamic factors (increased potency presumably because of the NMDA receptor antagonism of the d-isomer) produce an unexpectedly high potency, gradual accrual of effects over days to a week or more, and variability in response based on the existing therapy. As a result of these factors, current guidelines indicate that the use of methadone for pain should be initiated at a dose that is 75 – 90% lower than the    calculated equianalgesic dose. This initial dose is usually co-administered with a short-acting opioid rescue” medication. Close monitoring during dose titration is needed until sufficient time has passed at a stable dosing level to ensure that the plasma concen-tration has plateaued. This steady-state plateau, which requires 4 – 5 half-lives to
achieve, can in the case of methadone require days to weeks.


Tolerance is the loss of drug effect over time, induced by persistent exposure to the drug (7). Alternatively, tolerance can be defined as the need to increase the dose to maintain the initial effects of the drug. Tolerance may develop to any opioid effect, and tolerance to different effects typically occurs at varied rates (8, 9). Tolerance to some adverse effects of a drug, such as respiratory depression and nausea, is clinically favorable and typically occurs within days to weeks. Tolerance to the respiratory depressant effects allows stepwise dose escalation to occur in a manner that is safe and can optimize analgesic outcomes (9). As a consequence of this phenomenon, some patients can be gradually titrated to very high doses of methadone — equivalent to many grams of morphine per day — in an effort to attain pain relief.

In contrast to tolerance to adverse effects, analgesic tolerance can be a clinical problem. Fortunately, however, extensive clinical experience has documented that the doses required to maintain analgesia typically stabilize in the absence of progressive disease. Although dose escalation may be needed periodically to sustain analgesia, tolerance is seldom a problem in the clinical setting. The corollary to this observation is equally relevant: when a need to increase the dose does materialize, the clinician should search for worsening disease,rather than assume that analgesic tolerance has ocurred.


Physical dependence is an expected form of physiologic adaptation which occurs as a result of regular drug exposure and is reflected in the development of an abstinence, or withdrawal, syndrome when there is abrupt cessation of the drug, administration of an antagonist, or rapid decrease in dose (10). Physical depen-dence is not addiction, and much of the misunderstanding about the risk of addiction occurs because these terms are often mistakenly used as synonyms. Although physical dependence must be assumed to exist after a few days of opioid administration, it is, like the phenomenon of tolerance, neither necessary nor sufficient to yield an addictive disorder. Physical dependence that occurs in the course of therapeutic opioid use does not indicate addiction and should never be labeled in this manner.


Opioid addiction is a neurobiologically based disorder, with social and psycho-logic influences, characterized by a pattern of maladaptive behaviors, including: loss of control over use, craving and unwarranted preoccupation with nonthera-peutic use due to craving, and continued use of the drug despite harm resulting from use.  Physical dependency and tolerance may or may not be present in addiction. Opioid addiction occurs as a result of neurobiologic changes within the limbic reward systems, changes that are induced in biologically vulnerable individuals through repeated use of rewarding drugs. The induced neurobiologic changes are protracted and appear to drive persistent drug craving.  Addiction is associated with down-regulation of the hypothalamus-pituitary adrenal axis (11). Drugs with rapid onset of action are believed to pose the greatest risk for develop-ment of addiction in vulnerable individuals (11).


RATIONALE

Opioid agonist therapy of addiction is based on the understanding that stable and continuous occupation of opioid receptors in the limbic system and other brain centers associated with addiction blocks opioid craving without causing euphoria or significant cognitive changes or sedation.  This permits the user to focus on life activities unrelated to obtaining and using drugs, resulting in gradual return to normal function and a productive lifestyle.

Methadone has a relatively slow onset of action and a long half-life. With daily use of consistent doses, relatively stable blood levels of the drug are achieved. Methadone causes less stimulation of limbic reward centers than shorter-acting opioids, has a relatively low abuse potential, and, at relatively high stable blood levels, it blocks the
“high” obtained from use of short-acting opioids. These attributes make methadone particularly effective as therapeutic opioid agonist agent.  Recently, other agents, including buprenorphine and levomethadyl acetate (LAAM), have
been introduced as therapeutic agents. They appear to have good safety and efficacy profiles as therapeutic
opioid agents in addiction treatment, and it is likely that their use in clinical practice will
increase over time.


Methadone maintenance treatment for addiction normalizes the impairments associated with opioid addiction (2, 11). Methadone treatment has been documented to reduce the use of illicit opioids and to reduce morbidity and mortality  among heroin addicts. Patients stabilized on methadone are able to take advantage of educational,
vocational and employment opportunities, Increases in social stability and productive behavior have been documented in numerous studies over the past three decades (12). Outcomes of methadone maintenance treatment for addiction are improved when combined  with counseling, social support, and educational or vocational opportunities (12).


Under federal law, methadone may be prescribed for maintenance therapy of addiction in ambulatory patients only by physicians who have a special license to prescribe opioid therapy of addiction and who are affiliated with a licensed opioid treatment program. However, any physician with a standard, unrestricted  Drug Enforcement Administration (DEA) license may prescribe maintenance methadone to a patient who is hospitalized for a cause unrelated to addiction.  That is, if a patient is admitted for an acute medical illness such as pancreatitis or renal lithi-asis, or for a surgical procedure,any treating physician may, and should, prescribe for the patient’s maintenance methadone while the patient is hospitalized.  It is imperative that maintenance methadone be continued during hospitalization in order to avoid withdrawal and potential complications in medical, surgical and pain treatment.

The guiding principles for prescribing medications to Methadone  Maintained Treatment Patients include:

Avoid medications with antagonistic properties, such
as naltrexone and agonist/antagonist opioids such
 pentazocine.     
 Morphine or other opioids should be administered to
 control pain.  The dosage may have to be increased
because of tolerance induced by methadone. 
 A fixed schedule of administration is preferable to    
 a variable schedule.   


Methadone has been used as an effective analgesic agent for decades. New infor-mation about NMDA receptor antagonist actions, combined with its relatively low cost, has generated increasing interest for use in pain management. The use of methadone as a treatment for addiction has complicated efforts to appropriately position the drug  for analgesic therapy. For example,some physicians erroneously believe that a special
license is required to prescribe methadone as an analgesic agent. This concern is particularly strong when the patient is receiving Methadone Maintenance Treatment and
the use of methadone is being used for pain. 
Physicians must be reassured that a specialized license to provide opioid therapy is required only when methadone is administered for the treatment of addiction, even if the patient is also receiving the drug as part of Methadone Maintenance Treatment.  Methadone may be prescribed for the treatment of pain in any patient,including a patient on methadone maintenance therapy of addiction, without a specialized license other than a standard DEA license. Careful documentation is required if methadone is selected as an analgesic, especially in "Methadone Maintenance Treatment Patients.."

Because of methadone’s use on a once-a-day basis for the treatment of addiction, many physicians assume that methadone can be used once daily for pain.  A very large clinical experience refutes this. Most patients will require a dose interval of 6 – 8 hours to maintain analgesic effects.

Although it is most often used orally both for maintenance therapy and as an anal-gesic, methadone may be used parenterally when the oral route is unavailable. Although methadone may be too irritating for continuous subcutaneous infusion, it can be administered by parenteral bolus injection or infusion, like any other opioid
administered for pain.

Finally, some physicians believe that methadone has a unique profile of analgesic
actions and side effects, although this has not
been clearly documented from studies of longterm therapy for pain. There is very large intra-individual variability in the response to opioids, and a single patient may experience different patterns of analgesic responses and side effects to each of the pure mu agonist opioids. When
methadone and other drugs are compared at equianalgesic doses, there is no evidence for systematic differences between them; however, an individual patient may or may not find a switch to
methadone to be a favorable intervention.



Patients receiving Methadone Maintenance Treatment for addiction often receive sub-optimal, or even negligible, treatment of acute pain while hospitalized. A series of approximately one hundred reports indicates the following common errors in management:

***Methadone doses were lowered in the hospital, and as a result,patients experienced withdrawal symptoms.

***.Pain medication was denied because the clinician believed that the patient's chronic
maintenance methadone dose s would provide adequate analgesia.

***Patients for whom analgesics were prescribed were usually inadequately dosed because clinicians feared that medication in addition to the patient's prescribed methadone would cause repiratory depression.

***Patients were told to withdraw from methadone prior to surgery or other procedures because of the incorrect belief that methadone may interfere with the procedures and/or
impair their general health.

***During hospitalization, patient's maintenance dose was increased in an attempt to achieve analgesia. Patients were then released from the hospital on excessively high doses of methadone.

***Patients reported that opioid antagonists were inappropriately administered, inducing severe withdrawal.

***Because of the stigma associated with Methadone Maintenance Treatment, many methadone patients had negative experiences with health profesionals when their status as patients became known (12, 13).  As a result, some methadone patients admitted to an emergency room or a hospital concealed their status from staff, with occasional dire
consequences (e.g.administration od pentazocine or other agonist/antagonist drugs
which can precipitate withdrawal) (14).
   



There is widespread consensus that opioid therapy is the mainstay approach for the treatment of moderate-to-severe acute pain, and moderate to- severe chronic pain associated with cancer or AIDS. As noted previously, undertreatment is common despite this consensus, and chemically dependent patients are more likely to be undertreated than those without this history. Although a history of addiction and Methadone Maintenance Treatment for addiction may yield challenges during opioid therapy for pain, there is clinical agreement that opioid drugs should still be considered the major approach in these settings.

The role of long-term opioid therapy for noncancer-related pain is evolving rapidly. There are now consensus statements from major professional societies, including the American Society of Addiction Medicine, that acknowledge the
appropriateness of this treatment for selected patients. Although the use of this therapy for those with a history of chemical dependency has barely been studied, it is clear from a clinical perspective that, when opioids are required to relieve significant and persistent chronic pain in this population, they must be utilized with appropriate care and structure to avoid complications of use.

Careful assessment must be done when opioid therapy of chronic pain is contemplated for individuals with addictions, in order to clarify the state of the addictive disorder (active, at risk orrecovering); to determine the presence or absence of co-morbid psychopathology; to assess the degree to which unrelieved pain may be driving aberrant drug-related behaviors; and to establish a means to structure treatment in a way that would reduce the risk of inappropriate use. The active abuser may be very different from the patient in Methadone Maintenance Treat-ment or in stable drug-free recovery, and the decision to consider long-term opioid therapy for chronic pain in these patients presumably carries very different degrees of risk.

When deciding whether to consider long-term opioid therapy for chronic pain in patients with a history of chemical dependency, the clinician should also recog-nize the difficulties that the patient may experience because of anxiety about
relapse, abandonment by friends, or challenges from addiction treatment
pro-grams
. In all cases, the treatment requires a detailed assessment, including an open discussion with the patient,concerning all risks and benefits.


Many patients who are receiving Methadone Maintenance Treatment for addiction recognize that pain is often inappropriately managed in patients on Methadone Maintenance Treatment, and this may cause significant anxiety among those confronting injury, illness or surgeryPatients often fear ineffectively treated pain, loss of effective maintenance therapy, and the emergence of acute withdrawal, as well as the possibility of disrespectful treatment by health-care personnel. Anxiety related to these fears may in turn result in behaviors that become challenging to clinicians. Reas-suring the patient that pain management is a high priority, including the patient in deci-sion making, and adhering to good basic principles of pain management are critical to providing effective pain treatment.

Methadone Maintenance Treatment Patients may also experience anxiety about using opioid medications for pain.  Some believe they should their pain because of
concern that taking an opioid analgesic constitutes a relapse and will lead to readdiction (15).
  These patients and their families and physicians often need reassurance and encouragement to accept the analgesic treatment. It is sometimes helpful to point out that medication prescribed for acute pain are most often time limited and that relief of pain is essential for a quick and healthy recovery.

Many former illicit drug users fear losing control over medications and thus refuse any analgesia. Methadone patients receiving a blockade dose can be reassured that their daily dose of methadone will generally block any euphoric effects of the analgesic medications and that analgesics will only produce relief of pain.  Methadone patients on lower doses can similarly be advised of a partial blockade and assured that in all proba-bility they will feel very little euphoria, if any at all, from pain medication. If  patients persist in declining medication, their request for no pain medication should be
respected and non-medication approaches to pain control implemented whenever possible. However, in some patients, pain may eventually overcome this fear, and a request for pain medication may be made.

Some methadone patients fear that use of analgesic opioids will result in the need to increase their maintenance dose of methadone. It has been documented, however, that use of opioids for analgesia does not result in increased dose requirement for maintenance therapy once acute pain is resolved (16). With treatment, methadone patients will most likely continue with their usual maintenance treatment.


In order for pain management to be effective, patients who require maintenance therapy of addiction must be on an effective dose of methadone for their addiction treatment.  Patients receiving subtherapeutic doses, who are experiencing early symptoms of withdrawal or craving, will be much more difficult, or impossible, to treat for pain.  It may be difficult for patients on subtherapeutic doses to distinguish between the pain from surgical procedures and the pain from withdrawal syndrome. Opioid blockade may reduce the risk of euphorigenic effects and provide relative protection against re-addiction and relapse associated with the therapeutic use of an opioid analgesic.


Although supporting data are inconclusive, there is suggestive evidence that methadone maintained patients may be more sensitive to noxious stimuli — i.e., experience a relatively high level of pain following a noxious eventthan non-maintained individuals.  A study by Compton et al. (17), which examined pain, pain thresholds and pain tolerance in the presence of experimentally induced cold-pressor pain in humans, demonstrated that stable doses of methadone used as maintenance therapy appear to provide no analgesic effect and that methadone maintenance patients overall have lowered pain thresholds (increased pain sensitivity) and less pain tolerance than non-maintained individuals.

This research affirms that the usual dose of methadone used chronically for opioid therapy of addiction does not relieve pain and that individuals/receiving Metha-done Maintenance Treatment for addiction may require more aggressive pain management because of a predisposition to pain. If opioid analgesia is selected for the Methadone Maintenance Treatment Patient, relatively high doses may be needed, both to overcome whatever level of analgesic tolerance the Methadone Maintenance   Treatmnet has produced and to address the predisposition to pain (17).


Studies suggest that 30 – 80% of substance abusers suffer from co-existing psychiatric illness (14). (Anxiety, panic disorder, and the range of mood disorders (depressive and bipolar) which have a high prevalence in the addiction populations
may all be associated with bodily discomfort,pain itself, or distorted somatic perception (14).
Psychiatric evaluation and effective treatment can be crucial to relieving the pain syndromes in many of these people.


DISCUSSION AND DOCUMENTATION OF BENEFITS, RISKS, AND STRUCTURE OF THERAPY

Unless there is compelling evidence suggesting otherwise, all patients presenting with complaints of pain, including those with addictive disorders, should be evaluated and treated for their presenting pain complaint. Most often, individuals seeking opioids for non-medical uses will declare themselves eventually, through a pattern of aberrant behaviors.

If opioid therapy is selected as an intervention for pain in the patient with addictive disease, it is important to establish a clear understanding with the patient. Appropriate discussion and documentation of the potential risks and benefits of therapy, as well as the structural guidelines of treatment,  should be made. If therapy takes place in the ambulatory setting and is expected to continue for a prolonged period of time, it may be helpful to detail this understanding in the medical record and have it signed by both treatment provider and patient. This is often referred to as a “contract,” agreement, or covenant (18). A number of structural supports may facilitate effective pain therapy
in patients with addictive disorders and should be noted in any agreement between patient and provider. These are discussed below.


In.the ambulatory setting, it is best for the patient to have one physician prescribe all the analgesics and, preferably, all controlled medications. This provides continu-ity of care, eliminates overlap of medications, reduces the risk of drug interactions, and is reassuring to both the patient and the clinicians. In this arrangement, the physician
prescribing analgesic medications should inform other doctors who are prescribing for the patient, including the methadone prescriber, primary care physicians and any consultants who see the patient on a regular basis.


For those patients in Methadone Maintenance Treatment for addiction,it is essential that their team of counselors, nurses and others participate in the evaluation and treatment planning process. The treatment staff must know what medications the patient is prescribed in order to observe for effects and side effects,  be aware of potential drug interactions, and support the individual in his or her recovery.

Some Methadone Maintenance Patients who are receiving opioids for chronic pain choose to drop out of their formal Methadone MaintenanceTreatment Program.  Although using the opioid for pain may continue to block craving, the physician prescrib-ing the drug for pain must carefully document that the intention of therapy is analgesic and not addiction management.  A decision to leave the Methadone Management Treat-ment program should be carefully discussed with the patient and members of the treatment team. It may be convenient, but such a decision may eliminate an important source of support for the patient.


When possible, it is best for the patient to obtain all precriptions from one phar-macy.  This facilitates tracking of medications. The patient should be asked to consent to ongoing contacts between the prescriber and the pharmacist.  When a patient has difficulty controlling the use of medications, he or she should be given medications in small quantities, at frequent intervals.  Some patients require daily dispensing from their pharmacy. This is often impractical, and sometimes a trusted other may dispense medications to a patient.


It is often helpful to ask patients to bring their medications to each clinic visit so that care providers can observe whether the patient is using medications as prescribed.  If concerns arise regarding whether or not a patient is using the prescribed medications, urine screens may be helpful for documentation. However, the clinician
must be aware of the usual ranges
that the particular laboratory utilizes when specific tests are requested, and what the reporting cutoff limits are for particular drugs; there is great variability among laboratories. 

In rare instances, if a patient appears highly tolerant to medications and requires very high doses, use of the medication can be confirmed by asking the patient to take the prescribed dose while under observation. An opioid antagonist should be available in case the patient has been diverting medications and demonstrates no tolerance to the sedative or respiratory effects of the opioid. In patients on blocking doses of opioids, such side effects are not expected, but caution is appropriate nonetheless.


On occasion, clinicians who are prescribing long-term opioid therapy to a patient with a history of chemical dependency are asked to replace a prescription that is reported as lost or stolen.  From the start, there should be a clear agreement about how such circumstances will be managed, and this should be documented in the agreement. It is helpful to advise patients that they are responsible for keeping the prescriptions and medications safe. One way to handle the problem of lost or stolen medication is to request that all losses or thefts be reported to the police. The police report will have to be presented and placed in the patient’s record before any replace-ment medication can be prescribed. Some clinicians follow a practice of replacing only a single reported loss or theft and advising the patient that he or she will have to accom-modate to any subsequent loss or, if the occurrence is frequent, therapy may be discontinued.


CONTINUATION OF MAINTENANCE METHADONE AT UNCHANGED DOSE

A patient on Methadone Maintenance Treatment who presents with pain should be continued on his or her usual dose of methadone for maintenance. This should usually be given orally in one daily dose.  However, if the dose cannot be verified, it is safest to give the reported daily dose in three to four divided doses at appropriate intervals and observe the patient’s response, to assure that a potentially dangerous
dose is not given. If the daily dose cannot be confirmed and if the oral route is unavailable, one-half the usual daily oral, in divided doses, should be given parenterally. Continuing treatment thereafter should be based on the patient’s response.


Opioid analgesics should be titrated according  to reported pain, as with all patients reporting pain. Use of pain scales such as a numeric pain scale (0 – 10) or a visual analogue is recommended in order to evaluate both pain and responses to pain treatment. Because of relative tolerance to opioids and possibly lowered pain thresholds, Methadone Maintenance Treatment  patients often will require higher-than-standard analgesic doses given at more frequent intervals. This must be established
with clinical observations. (17)


Although methadone is an effective analgesic, it is generally preferred to select an alternative mu agonist opioid such as morphine, hydromorphone or oxycodone, to provide analgesia in methadone-maintained patients. This allows clear distinction between treatment of addiction and treatment of pain, and lessens possible confusion
over clinical issues of pain and addiction. In addition, because of its relatively slow onset of action and long half-life, methadone may be difficult to titrate rapidly enough to meet acute pain needs.

In some cases, however, methadone will be the preferred analgesic (this usually relates to cost). If the patients remains in Methadone Maintenance Treatment, the treatment must include visits to the Methadone Maintenance Treatment Program to receive a single daily dose for addiction, and visits to the physician who treats the pain, for a prescription that will be filled by a regular pharmacy; the latter will provide analgesic methadone, to be administered several times per day on a fixed schedule. This approach is not pharmacologically necessary, of course, but is required by regulation
if the methadone is still being used to treat the addiction. There are anecdotal reports of former  Methadone Maintenance Treatment Patients who receive prescriptions for analgesic methadone.

Long-acting opioids, such as controlled release oral morphine, oxycodone, or hydromorphone (soon to become commercially available) or controlled-release transdermal fentanyl, provide consistent pain relief for continuous pain,while short-acting opioids are more rapidly effective for addressing intermittent, incident or breakthrough pain.


A fixed schedule is preferable to a variable “prn” schedule. For an inpatient, this avoids the request for opioids, which may be interpreted by some staff as patho-logic drug-seeking behavior, rather than the seeking of pain relief. For ambulatory
patients, it avoids the situation where the individual with an addictive disorder has to make a decision as to whether or not to take a potentially rewarding or reinforcing drug based on subjective pain level, a situation which may cause confusion, distress or, possibly, an escalating pattern of pain and medication use.

If only intermittent analgesia on an irregular basis is required, it is helpful, when possible, to link doses with activity or time, rather than increased pain alone, in order to avoid the potentially reinforcing effects of opioids on pain perception. In the case of the ambulatory Methadone Maintenance Treatment Patient requiring additional opioids for analgesia, therefore, treatment may consist of a single methadone dose per day as addiction therapy, plus a fixed schedule of the opioid as used for pain.

It is important to be aware that individuals on methadone maintenance therapy of addiction and those using opioids chronically for analgesic purposes will often require relatively short intervals, due to tolerance.  Opioids should be titrated to reported effect while observing for improvement in pain and function versus signs of overuse, abuse or addiction. Ambulatory patients should be given medications in quantities that both they and their providers are confident that they can control.

When planning long-term opioid therapy in the ambulatory setting, it is often useful to begin with a small prescription, such as a seven-day supply. Before increasing the dose independently, the patient should be given instructions to contact the prescribing physician if the medication is not effective. The frequency of future prescription refills
should be determined by effective dose, adherence of the patient, and the nature of the illness.


Patient-controlled analgesia (PCA) may be used with Methadone  Maintenance Treatment Patients who are believed to be in secure addiction recovery.   A continuous background  infusion may be used with the PCA component, if indicated. PCA allows patients to titrate their own analgesic needs without frequent medication requests to health-care staff. These requests, in an individual with addictive disease,
are often perceived as drug-seeking behaviors.  Doses should be titrated to effective reported analgesia, while observing for side effects such as intoxication or persistent sedation, which may occur with overuse. Caution is indicated if a patient is not securely in recovery, may be at risk for relapse, and/or has visitors who are  actively abusing     opioids, since PCA makes IV forms for opioid
reasonably available to tamperers.    


A patient using methadone or other mu agonist opioids on a regular basis must avoid the use of opioids with agonist-antagonist properties,such as butorphanol (Stadolgs®), pentazocine (Talwin®), nalbuphine (Nubain®), and dezocine (Dalgan®) activity at non-mu opioid receptors, but act as antagonists at the mu receptor, thus reversing the actions of methadone or other therapeutic mu agonist opioids. Therefore, they may precipitate an acute withdrawal syndrome in patients using mu agonist medications such as methadone (16).


Because individuals on Methadone Maintenance Treatment may be relatively tole-rant to the effects of opioids, thus requiring high-dose therapy, meperidine and
propoxyphene should not be used when prolonged or high-dose analgesia is anticipated. 
Normeperidine, a metabolite of meperidine, and norpropoxyphene, are potentially neurotoxic agents that may accumulate in such circumstances, causing tremors, agitation and even seizures in some cases. Meperidine is also very short acting, is poorly absorbed after oral administration, and provides only transient analgesia. It has few indications in the treatment of pain.


Non-opioid pain treatment approaches may provide effective analgesia for patients with pain, in many settings, either alone or as a complement to opioid therapy. Non-opioid medications with analgesic activity include nonsteroidal antiinflammatory
drugs (NSAIDs), tricyclic antidepressants,anticonvulsants, corticosteroids, and local anesthetics, among others.  Antidepressants and anticonvulsants may be especially helpful in treating neuropathic pain, which may be less responsive to opioids than is nociceptive pain.  Non-opioid pharmacologic treatments should be dosed in the standard amounts used for analgesia in nonmethadone-maintained patients, since individuals
on Methadone Maintenance Treatment are not expected to have tolerance to the effects or side effects of these medications.  Only the opioid analgesic may need to be used in higher doses for the methadone patient, unless the patient has developed tolerance to nonopioid substances.  For example, a Methadone Maintenance Treatment Patient with concurrent alcoholism also may have developed tolerance to sedative-hypnotics. Another approach is that offered by anesthesiologists, such as nerve blocks and intraspinal infusion.

There are are numerous non-medication approaches to pain treatment, beyond the scope of this paper, which may be helpful in individuals on Methadone Maintenance Treatment. These include psychological (e.g., cognitive,behavioral and other therapies) and physical modalities (e.g., physical therapy, analgesic modalities such as cold or heat, and neurostimulatory modalities such as transcutaneous electrical nerve stimu-
lation, acupuncture and dorsal column stimulation).  Attention to nutrition and weight (loss or gain) may also have a role in pain treatment.


Treatment of the pregnant woman demands special physiologic considerations according to trimester, and attention given to the well-being of the fetus. It is generally agreed that the pregnant patient should receive as high a maintenance dose
of methadone as is necessary to achieve blockade, so that she will cease using illicit opioid. The physiologic changes of pregnancy including slowed gastrointestinal absorption, expanded fluid load, and increased glomerular filtration, all indicate
a possible need to increase the amount of
methadone for maintenance, especially in the
third trimester. As with other patients on Methadone Maintenance Treatment may be necessary to use higher analgesic doses opioids to treat pain; opioids utilized to provide
analgesia should be titrated to effect.


The special needs of patients who have a history of illicit drug use and are infected with HIV are of critical relevance when considering pain management.  It has been well documented that pain associated with HIV-related disease is routinely under-treated (2). The World Health Organization and U.S. Agency for Health Care Policy recommend that a cancer pain model of pain treatment be utilized in managing pain in patients with HIV-related illness. The complexity of the issues in treating these patients requires that the first step in their management be a comprehensive assessment. Careful attention to addiction recovery and to principles of pain management in Metha-done Maintenance Treatment Patients, as discussed above, is requisite to providing effective pain management for HIV- infected patients on Methadone Maintenance Treatment.


Patients with active drug addiction who present with acute or chronic pain due to injury, to the pillness or surgery present special challenges to the pain treatment provider.   It has been documented that periods of acute illness often represent opportunities for meaningful intervention in addictive disease, as patients are often confronted with their vulnerability to illness and, sometimes, specifically to the harmful sequelae of their disease.  Attempts to engage the patient in addiction treatment should therefore be aggressive at these times.

Clinicians not knowledgeable in addiction treatment should seek professional expertise when treating patients who are active drug users.

Pain management for all patients with addiction requires relatively tight controls, monitoring and documentation, while at the same time meeting the individual’s analgesic needs through appropriate titration of medications and use of other modalities.  A smooth course of analgesic therapy is often facilitated when addicted patients are reassured that the staff is aware of their addictive disorder and that every effort will be made to treat their pain; their addiction will not be an obstacle, if they are willing to work with the team.  Opioid-addicted individuals should be assured that they will be given enough methadone to prevent ithdrawal and craving while they are hospitalized.  The relative tolerance to the analgesic effects of opioids in opioid abusers must be considered when titrating medica-tions . The use of a written contract that is kept in the medical record, defining the regimen and explicitly stating the responsibilities of both the patient and the physician, may be especially helpful in treating these patients.


The methadone-maintained patient experiences as much pain in association with illness, injury, and surgery as do other individuals.   Methadone used chronically for maintenance does not treat acute or chronic pain. Therefore, the methadone patient needs adequate analgesic medications prescribed to relieve pain.

Methadone-maintained patients who have pain often require relatively large doses of opioids at relatively short intervals to control their pain, since they have some level of tolerance to opioid medications.  At a blockade dose of approximately 80 120 mg/day, the methadone-maintained patient has relatively high tolerance to the respiratory depressant effects of opioids, and will not experience drug craving or euphoric effects in association with short-acting opioids prescribed for relief of pain.

Clinicians should therefore not feel apprehensive about the relatively large doses of analgesics often required to treat pain in methadone patients, but should ob-serve patients carefully and adjust analgesic doses according to reported relief and observed effects. Methadone will not interfere with analgesic responses to opioids, although dose requirements may be higher than in non-maintained patients.

The simplest approach to the treatment of acute pain in the methadone patient is to prescribe adequate doses of an alternative mu opioid, while maintaining the maintenance dose of methadone.  The type and dosing pattern of the opioid used
should be determined with consideration of the type, intensity, and temporal pat-tern of
the patient’s pain.   When an opioid is used for chronic pain, successful therapy is predicated on a careful assessment of the pain, a detailed history of chemical dependency, and an awareness of co-morbid physical and psychosocial factors. Treatment requires a knowledgeable and committed physician who will
administer the opioid in doses required to attain analgesia, while monitoring the
patient for other critical outcomes, including function, drug-related behaviors, and side effects.  A team approach is often helpful.

Patients should generally not be withdrawn from opioid medications while they are experiencing acute pain. If it is necessary to change the maintenance dose of methadone for any reason, this should be done in consultation with the patient and the clinician who is treating the patient for his or her drug dependence. If basic principles of pain management are followed, analgesic management of the methadone patient should be as effective and safe as for any other patient treated for acute or chronic pain.

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Modified:  July 8, 2005  Edited by: Deborah Shrira

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