Printer Friendly
The Free Library
22,710,190 articles and books

Opioids for chronic nonterminal pain.



Abstract: This article first reviews the evidence for and against chronic opioid opioid /opi·oid/ (o´pe-oid)
1. any synthetic narcotic that has opiate-like activities but is not derived from opium.

2. any of a group of naturally occurring peptides, e.g.
 therapy. Evidence supporting the opioid responsiveness of chronic pain, including neuropathic pain, includes multiple randomized ran·dom·ize  
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment.
 trials conducted over months (up to 8 months). Observational studies observational studies,
n.pl an investigational method involving description of the associations be-tween interventions and outcomes. Outcomes research and practice audits are examples of this investigational method.
 are conducted for longer, and many also support opioid analgesic analgesic (ăn'əljē`zĭk), any of a diverse group of drugs used to relieve pain. Analgesic drugs include the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, and synthetic drugs  efficacy. Concerns have arisen about loss of efficacy with prolonged use, possibly related to tolerance or opioid-induced hyperalgesia Opioid-induced hyperalgesia[1] or opioid-induced abnormal pain sensitivity[2] is a phenomenon associated with the long term use of opioids such as morphine, hydrocodone, oxycodone, and methadone. . Mechanisms of tolerance and opioid-induced hyperalgesia are explored. Evidence on other important outcomes such as improvement in function and quality of life is mixed, and is less convincing than evidence supporting analgesic efficacy. It is clear from current evidence that many patients abandon chronic opioid therapy because of the unacceptability of side effects Side effects

Effects of a proposed project on other parts of the firm.
. There are also concerns about toxicity, especially when opioids are used in high doses for prolonged periods, related to hormonal and immune function Immune function
The state in which the body recognizes foreign materials and is able to neutralize them before they can do any harm.

Mentioned in: Herbalism, Traditional Chinese, Stress Reduction
.

The issue of addiction during opioid treatment of chronic pain is also explored. Addiction issues present many complex questions that have not been satisfactorily answered. Opioid treatment of pain has been, and remains, severely hampered because of actual and legal constraints related to addiction risk. Pain advocacy has focused on placing addiction risk into context so that addiction fears do not compromise effective treatment of pain. On the other hand, denying addiction risk during opioid treatment of chronic pain has not been helpful in terms of providing physicians with the tools needed for safe chronic opioid therapy. Here, a structured goal-directed approach to chronic opioid treatment is suggested; this aims to select and monitor patients carefully, and wean wean (wen) to discontinue breast feeding and substitute other feeding habits.

wean
v.
1. To deprive permanently of breast milk and begin to nourish with other food.

2.
 therapy if treatment goals are not reached.

Chronic opioid therapy for pain has not been a universal success since it was re-established during the last two decades of the twentieth century. It is now realized that the therapy is not as effective or as free from addiction risk as was once thought. Knowing this, many ethical dilemmas arise, especially in relation to patients' right to treatment competing with physicians' need to offer the treatment selectively. In the future, we must learn how to select patients for this therapy who are likely to achieve improvement in pain, function and quality of life without interference from addiction.

Efforts will also be made in the laboratory to identify opioids with lower abuse potential.

Key Words: pain, chronic disease, opioids, drug tolerance drug tolerance Psychiatry Repeated use of some substance or drug, often narcotics, so that ever larger doses are required to produce the same physiologic and/or psychologic effect obtained previously by a smaller dose. , addiction, neuroendocrine neuroendocrine /neu·ro·en·do·crine/ (-en´do-krin) pertaining to neural and endocrine influence, and particularly to the interaction between the nervous and endocrine systems.

neu·ro·en·do·crine
adj.
 effects

**********

Changes arising during the twentieth century profoundly altered the way opioids were used for the treatment of pain. These included the introduction in the first decade of drug regulations attempting to control the proliferation of addictive drugs; the subsequent difficulties of convincing patients and physicians that opioids could be used for the treatment of pain without fear of censure; the scientific breakthroughs of the early 1970s confirming the existence of endogenous opioid systems and their role in analgesia analgesia /an·al·ge·sia/ (an?al-je´ze-ah)
1. absence of sensibility to pain.

2. the relief of pain without loss of consciousness.
 and addiction (1,2); the realization that pain is a destructive disease process that should be treated; the acceptance that opioids are indispensable for the treatment of acute and terminal cancer pain; and finally, during the last two decades of the century, the extension of opioid treatment to patients with chronic, nonterminal pain.* Physicians must now accept that it is not considered legal, ethical or good medical practice to withhold opioids from patients whose lives could be improved with treatment. Yet chronic opioid management is not suitable for every patient; there are considerable risks involved, and the treatment is not universally effective. This article presents current evidence on the benefits and risks of long-term opioid therapy, suggests a structured approach to chronic opioid management for pain, and discusses some of the issues surrounding opioid treatment of chronic pain that make achieving a balance and satisfying the needs of patients a veritable challenge.

Evaluating Chronic Opioid Therapy

Analgesic Efficacy

Adding to concerns about addiction during opioid treatment of chronic pain, there has been a traditionally held view that chronic pain states such as neuropathic pain are not sensitive to opioids. Yet clinical observation suggests that chronic pain states are, in fact, relieved by opioid treatment. It was this uncertainty about the opioid sensitivity of chronic pain that prompted several investigators to conduct randomized controlled trials A randomized controlled trial (RCT) is a scientific procedure most commonly used in testing medicines or medical procedures. RCTs are considered the most reliable form of scientific evidence because it eliminates all forms of spurious causality.  (RCTs) assessing the analgesic efficacy of opioids for chronic pain states such as the arthritides and neuropathic pain. In some trials, a single IV treatment was used, (3-5) in others, oral treatment was used over longer periods of up to 32 weeks. Table 1 summarizes the controlled trials of oral treatment. (6-23) In both types of trials, chronic pain conditions are seen to be sensitive to opioids. In fact, opioids provide superior analgesic efficacy when compared both to placebo and to established treatments (usually nonsteroidal anti-inflammatory drugs Nonsteroidal Anti-Inflammatory Drugs Definition

Nonsteroidal anti-inflammatory drugs are medicines that relieve pain, swelling, stiffness, and inflammation.
) for a number of chronic pain conditions. In the case of neuropathic pain specifically, the dose-response curve dose-response curve A graphic representation of the effects that varous doses of an agent–eg, ionizing radiation or a chemotherapeutic agent, have on a given parameter–eg, cell viability, mutation frequency, DNA damage, tumor growth or metastasis or  is shifted to the right (a higher dose is needed), but the opioid sensitivity of neuropathic pain states is confirmed. (12,16,19-21,23)

While the short-term efficacy of opioids for treating several chronic pain conditions now seems certain, the information from controlled trials is limited by their being conducted only for short periods. This limitation occurs largely because of the impracticability Substantial difficulty or inconvenience in following a particular course of action, but not such insurmountability or hopelessness as to make performance impossible.  of conducting controlled trials over prolonged periods. The question of whether analgesic efficacy and other benefits of chronic opioid therapy can be maintained over years rather than months remains unanswered. Long-term analgesic efficacy is much more difficult to assess, not least because the factors that influence analgesic effect over time are complex. These factors include the development of tolerance, and the development of opioid-induced hyperalgesia and psychological factors such as changes in the placebo component. Reports in the literature comprise case and case series reports, surveys (24-35) and open-label follow-up studies in association with some RCTs. (5,15-17,23,36,37)

These report treatment durations of up to 6 years. The general finding is that patients attain satisfactory analgesia using moderate nonescalating doses (up to 195 mg morphine equivalence per day), often accompanied by an improvement in function, and minimal risk of addiction. It must be remembered, though, that these studies are anecdotal, comprising reports written by experts who likely carried out the treatment with unusual care. This inherent bias is particularly relevant to chronic opioid therapy, which requires considerable dedication, patience and caution to be successful. (25)

A slightly different picture emerges from recently published open-label follow-up studies, which suggests that the failure rate of chronic opioid therapy may be higher than was previously thought. The authors of a 2004 meta-analysis of chronic opioid therapy systematically assessed available follow-up studies and found a 56% drop-out rate. (36) Although these reviewers were unable to distinguish drop out due to inadequate analgesia from drop out due to unacceptable side effects, the high dropout (1) On magnetic media, a bit that has lost its strength due to a surface defect or recording malfunction. If the bit is in an audio or video file, it might be detected by the error correction circuitry and either corrected or not, but if not, it is often not noticed by the human  rate does seem at odds with the high success rates reported in observational studies. Further study is needed to determine how many, and particularly which, patients respond well to long-term opioid therapy in terms of analgesic efficacy.

As more patients are treated with opioids, (38,39) more patients present to physicians with severe pain despite opioid treatment--sometimes despite high-dose opioid treatment. (40,41) Reports of difficulty controlling acute pain when it arises in opioid-treated or opioid-using patients, also suggest that something is interfering with analgesic efficacy. (42) Several authors have reported that weaning weaning,
n the period of transition from breast feeding to eating solid foods.


weaning

the act of separating the young from the dam that it has been sucking, or receiving a milk diet provided by the dam or from artificial sources.
 some patients off opioids results in an improved sense of well being and no change in pain--sometimes pain may even improve. (43,44) It seems that in these patients at least, there is virtually no analgesic effect, since treatment discontinuation dis·con·tin·u·a·tion  
n.
A cessation; a discontinuance.

Noun 1. discontinuation - the act of discontinuing or breaking off; an interruption (temporary or permanent)
discontinuance
 results in no change in pain. Why should pain improve or remain the same upon discontinuing opioid treatment? Here, advances in basic science have helped us understand mechanisms that could account for analgesic failure. Opioid-induced hyperalgesia, for example, is now understood to coexist with opioid analgesia, with analgesia being predominant in most circumstances. N-methyl-Daspartate (NMDA NMDA

N-methyl-D-asparate
) receptor mechanisms are seen to be involved in the development of hyperalgesia hyperalgesia /hy·per·al·ge·sia/ (-al-je´ze-ah) abnormally increased pain sense.hyperalge´sic

hy·per·al·ge·sia
n.
Extreme sensitivity to pain.
, whether induced by opioid treatment or associated with neuropathic pain. The NMDA receptor NMDA receptor
n.
A brain receptor activated by the amino acid glutamate, which when excessively stimulated may cause cognitive defects in Alzheimer's disease.
 is also involved in the development of pharmacological opioid tolerance. (40,45) Repeated administration of opioids results not only in the development of tolerance (a desensitization desensitization
 or hyposensitization

Treatment to eliminate allergic reactions (see allergy) by injecting increasing strengths of purified extracts of the substance that causes the reaction.
 process), but also leads to a pro-nociceptive process (sensitization sensitization /sen·si·ti·za·tion/ (sen?si-ti-za´shun)
1. administration of an antigen to induce a primary immune response.

2. exposure to allergen that results in the development of hypersensitivity.
): thus pharmacological tolerance and induced hyperalgesia are seen to coexist, just as analgesia and hyperalgesia coexist. (40) The clinical quandary is obvious--increasing doses could improve or worsen pain. A great deal of uncertainty remains about whether opioid dose, length of treatment or drug choice influences the development of hyperalgesia; and the exact clinical circumstances in which opioid-induced hyperalgesia interferes is also uncertain. Nevertheless, it has become clear that open-ended dose escalation often fails to sustain analgesic efficacy, and the premise that tolerance can always be overcome by dose escalation is now questioned. (24) It is also clear that good analgesic efficacy is not always sustained over time, and that there are clinical situations in which pain and well being can be improved by weaning rather than continuing opioid treatment.

Function and Quality of Life

Many medical practitioners believe that improvements in function and quality of life are needed for long-term opioid treatment to be deemed a success, although a few believe that good pain relief, regardless of other markers of successful treatment, is enough to justify continued opioid treatment. Despite the importance of this debate, the literature provides surprisingly little evidence on nonanalgesia-related outcomes. Some randomized trials combine assessments of pain relief with assessment of function, but the focus of these assessments tends to vary with the primary interest of the investigators. (7,10,13,15,15) While some investigators demonstrate improvements in limited measures of function, others find no difference (Table 1). Observational trials contribute little in the way of assessment of function. Although some report improvement in broad measures such as ability to perform activities of daily living and return to work, others do not comment. Few opioid trials measure quality of life, which is again surprising given the importance of this factor and the fact that there are several validated measurement instruments available.

Several studies have looked specifically at cognitive function cognitive function Neurology Any mental process that involves symbolic operations–eg, perception, memory, creation of imagery, and thinking; CFs encompasses awareness and capacity for judgment , including the ability to drive and operate machinery while on opioids. This question is obviously critical in terms of whether opioid-treated patients should be encouraged to return to work, to normal daily activities and in particular, to driving. These studies find that cognitive function, manual dexterity and reaction times are maintained at normal levels provided a stable dose of opioid is used. (46-49) This may not be true when dosing is irregular or escalates. (46)

Side Effects and Complications

Opioid side effects are well known and include respiratory depression, nausea, sedation Sedation Definition

Sedation is the act of calming by administration of a sedative. A sedative is a medication that commonly induces the nervous system to calm.
Purpose

The process of sedation has two primary intentions.
, euphoria or dysphoria dysphoria /dys·pho·ria/ (-for´e-ah) [Gr.] disquiet; restlessness; malaise.dysphoret´icdysphor´ic

gender dysphoria
, constipation and itching itching
 or pruritus

Stimulation of nerve endings in the skin, usually incited by histamine, that evokes a desire to scratch. It is often transient and easily relieved. Pathological itching with skin changes usually signals dermatologic disease.
. With chronic use, most side effects subside, since tolerance seems greater to side effects than to analgesic effects. Constipation is an exception, and there appears to be no tolerance to the direct slowing effects of opioids on the bowel, so that constipation remains a high risk and usually requires treatment. Although common side effects (except constipation), usually subside during chronic treatment, they can sometimes interfere to the extent that patients abandon the therapy. (36) Respiratory depression is rarely seen during chronic opioid therapy, but since this is a potentially lethal side effect, one should remain vigilant. The situation in which it most likely arises during chronic opioid pain treatment is when the dose is rapidly escalated, dosing errors occur, or when drugs with unpredictable pharmacokinetics such as methadone methadone (mĕth`ədōn', –dŏn'), synthetic narcotic similar in effect to morphine. Synthesized in Germany, it came into clinical use after World War II. It is sometimes used as an analgesic and to suppress the cough reflex.  are used. (Methadone's complexities are described under "Structured Opioid Therapy"). Other complications of opioid use are more insidious, tend to be associated with long-term rather than short-term use, and are complex and poorly understood. These include hormonal and immune effects, and addiction.

Hormonal and Immune Effects

Long-term opioid use results in clinically relevant suppression of both hypothalamopituitary-adrenal and -gonadal axes, with suppression in luteinizing hormone lu·te·in·iz·ing hormone
n.
Abbr. LH A hormone produced by the anterior lobe of the pituitary gland that stimulates ovulation and the development of the corpus luteum in the female and the production of testosterone by the interstitial
, follicle-stimulating hormone follicle-stimulating hormone (FSH): see gonadotropic hormone. , testosterone, estrogen and cortisol cortisol (kôr`tĭsôl') or hydrocortisone, steroid hormone that in humans is the major circulating hormone of the cortex, or outer layer, of the adrenal gland. . (50-52) These effects have been demonstrated in addicts, past addicts treated with methadone maintenance Methadone maintenance is a way of stabilizing someone who is addicted to heroin or has severe pain problems that are resistant to other drugs.

Methadone Maintenance Treatment
 (50) and more recently, in opioid-treated chronic pain patients. (51) The effects are most prominent in patients treated with intrathecal intrathecal /in·tra·the·cal/ (-the´k'l) within a sheath; through the theca of the spinal cord into the subarachnoid space.
Intrathecal 
 opioids. (53-55) The gonadal gonadal

pertaining to or arising from a gonad. See also testicular, ovarian.


gonadal cords
cords formed by epithelial cells which migrate from the mesonephric tubules in the embryo to the gonadal ridge and establish the indifferent
 effects can result in male and female infertility and in decreased libido libido (lĭbē`dō, –bī`–) [Lat.,=lust], psychoanalytic term used by Sigmund Freud to identify instinctive energy with the sex instinct. , drive and aggression. Clinically, testosterone deficiency is the most frequently manifest of the deficiencies, and male patients can benefit from testosterone replacement. (54,56) Although the suppressive sup·pres·sive  
adj.
Tending or serving to suppress.

Adj. 1. suppressive - tending to suppress; "the government used suppressive measures to control the protest"
 effect of opioids on the endocrine system endocrine system (ĕn`dəkrĭn), body control system composed of a group of glands that maintain a stable internal environment by producing chemical regulatory substances called hormones.  seems clear, determining the exact contribution to health of these effects is not straightforward. Most chronic pain patients present with complex medical and psychosocial histories, and many have underlying neuroendocrine derangements, either because of coexisting medical illness, or because of the effects of their treatment. Thus, even knowing the likely direct effects of opioids on endocrine function, their exact clinical relevance in an individual patient is not clear.

Opioid drugs may affect immunity through their neuroendocrine effects, or through direct effects on the immune system immune system

Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders.
. Preclinical research has shown that opioids alter the development, differentiation and function of immune cells, and opioid receptors Opioid receptors
Receptors located in the brain and various organs that bind opiates or opioid substances.

Mentioned in: Methadone

opioid receptors,
n.pl any of the several receptors to which opiates bind.
 have been demonstrated on immune cells. (57,58) Evidence of immune modulation in humans is limited, but opioids have been shown to exacerbate immunosuppression immunosuppression

Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects.
 in HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States.  patients, which suggests that prolonged opioid use may affect the immune system, at least in immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer).  persons. (59) There are no studies of immune function in patients receiving long-term opioid therapy for chronic pain, but the direct evidence that opioids impair immune function in susceptible individuals is concerning. Pain itself can suppress immune function, so patients receiving prolonged opioid therapy without good pain relief are probably the most vulnerable.

Addiction

There is no doubt that the association of opioid use with addiction produces many conflicts with regard to opioid treatment of pain. When it became necessary to introduce drug regulations because the availability, use and abuse of opioids and other addictive drugs had reached unacceptable levels, this compounded the problem, adding a host of legal considerations to the existing moral and ethical dilemmas inherent in balancing humane care with protection from addiction. After the introduction of regulations, it took many years to reestablish opioid treatment as necessary and proper for the control of acute and terminal cancer pain. In fact, as opioid use was reestablished for these indications, it became clear that problematic addiction virtually never arose during the treatment of severe, acute and cancer pain. (25,60) But long-term outpatient opioid treatment is likely to be associated with higher risk. Indeed, despite the somewhat optimistic picture painted by early reports such as the seminal report by Portenoy and Foley estimating addiction risk during chronic opioid treatment at approximately 5%, (25) higher estimates of up to 19% (this being the upper limit of addiction rates found in a systematic review by Fishbain et al), (61) are now accepted by the medical community. There is a problem, however, with all estimates of addiction risk, and that is that iatrogenic iatrogenic /iat·ro·gen·ic/ (i-a´tro-jen´ik) resulting from the activity of physicians; said of any adverse condition in a patient resulting from treatment by a physician or surgeon.  opioid addiction (addiction arising during opioid treatment of pain), is poorly defined and understood, despite years of effort to clarify its terminology and processes. (62,63) It seems that iatrogenic opioid addiction is simply what the reporting person says it is, and that the vast range of published estimates of risk reflects the lack of an agreed definition. Portenoy and Foley understood at the outset that problematic addiction is unlikely to arise when treatment is provided in a controlled, careful and supportive setting. As they said: "It must be recognized ... that the efficacy of this therapy and its successful management may relate as much to the quality of the personal relationship between physician and patient as to the characteristics of the patient, drug, or dosing regime." (25) As is the case with opioid maintenance for opioid addiction, (64-66) a careful structured maintenance regimen is the best course for preventing the emergence of problematic opioid-seeking behaviors. It follows that observed addiction rates are likely to be higher when practice deviates from the careful controlled approach recommended in published guidelines. (24,67,68)

Summary of Evidence Supporting Long-term Opioid Use

Many years of clinical use of opioids for pain made it clear that opioids are strong and effective analgesics Analgesics Definition

Analgesics are medicines that relieve pain.
Purpose

Analgesics are those drugs that mainly provide pain relief.
. Randomized trials confirm the sensitivity of several common chronic pain conditions to opioids, and demonstrate that a short course of treatment (up to 32 wk) using moderate doses (up to 180 mg morphine or equivalent) is effective.

With regard to sustained analgesic efficacy, many authors report (in case reports and case series) prolonged and satisfactory analgesia for up to 6 years using moderate doses of opioid (up to 195 mg morphine or equivalent). On the other hand, some investigators report that failed patients improve when taken off opioids. The suggestion that analgesic efficacy can always be maintained, and tolerance reliably overcome by continued dose escalation must therefore be questioned. With regard to broader outcomes such as function (ability to work and perform normal daily activity) and quality of life, which are considered the most important outcomes of chronic opioid therapy by many clinicians, evidence is limited.

Data on side effects suggest that common side effects such as sedation and nausea usually resolve during chronic treatment, but a significant minority of patients will abandon opioid therapy because of side effects. More insidious liabilities include hormonal and immune effects and addiction. With regard to the hormonal effects, which are known to arise in addicts and chronic pain patients, an important question is whether the effects, independent of other more direct opioid effects, contribute to the general poor psychological and physical health of opioid-treated patients. On the question of addiction and its prevalence during the treatment of pain with opioids, the literature is uncertain. While extremes of addiction and freedom from addiction may seem clear, it remains hard to determine whether the patients who fall between the extremes are addicted or not. There are no satisfactory definitions of iatrogenic opioid addiction, and the lack of an accepted incidence stems from this lack of agreed definition. The published rate lies between 5% in some practice settings and 19% in others, but as stated earlier, these figures can only be interpreted as reflecting addiction as defined by the person reporting--not by a generally agreed definition.

Structured Opioid Therapy

Given the uncertainty that exists about the extent to which iatrogenic opioid addiction arises, and which patients will be affected, the concept of "universal precautions universal precautions,
n.pl 1. approaches to infection control designed to prevent transmission of bloodborne diseases, such as AIDS and hepatitis B in health care settings.
" applied to chronic opioid therapy has recently arisen. (67) This approach suggests that since current understanding precludes making reliable assessments of which patients are at risk of developing problematic addiction, or indeed, which patients have already developed precursor tendencies toward addiction, the treatment should be applied in a uniformly careful and structured manner. The following describes one such approach.

When a patient first presents with debilitating de·bil·i·tat·ing
adj.
Causing a loss of strength or energy.


Debilitating
Weakening, or reducing the strength of.

Mentioned in: Stress Reduction
 pain, early aggressive treatment using a rehabilitative approach that aims to restore function and reduce reliance on medications is often the best approach. Opioids can and should be used as needed as needed prn. See prn order.  to facilitate this approach, preferably for a short time only. If this fails, and the physician and patient decide on a long-term commitment to opioid treatment, then the treatment should be goal-directed, and carefully controlled. This means selecting patients with the best chance of benefiting, continuously monitoring for the achievement of preset goals and onset of problematic behavior, and maintaining the lowest effective dose to maintain analgesia and minimize complications. The principles of structured long-term opioid therapy are set out in Table 2.

Selecting patients who are suitable for chronic opioid therapy remains one of the greatest challenges surrounding the therapy, and there is little hard information to guide this selection. Although there are well-established addiction comorbidities including depression, anxiety disorder anxiety disorder
n.
Any of various psychiatric disorders in which anxiety is either the primary disturbance or is the result of confronting a feared situation or object.
, personality disorder personality disorder

Mental disorder that is marked by deeply ingrained and lasting patterns of inflexible, maladaptive, or antisocial behaviour to the degree that an individual's social or occupational functioning is impaired.
, history of physical or psychological trauma Psychological trauma is a type of damage to the psyche that occurs as a result of a traumatic event. When that trauma leads to Post Traumatic Stress Disorder, damage can be measured in physical changes inside the brain and to brain chemistry, which affect the person's  and history of substance abuse, it is unclear whether patients in controlled and consistent treatment programs are at risk of developing problematic addiction. Present evidence suggests that "at risk" patients do well in controlled programs, and should not be denied opioid treatment of pain solely on the basis of existing addiction comorbidities. (69-71)

The commitment to long-term opioid therapy is a serious one, and should be considered such by both patients and physicians. Often, opioid therapy has already been started, but this does not obviate ob·vi·ate  
tr.v. ob·vi·at·ed, ob·vi·at·ing, ob·vi·ates
To anticipate and dispose of effectively; render unnecessary. See Synonyms at prevent.
 the need for careful review of the implications of long-term treatment once the long-term treatment phase is entered. The pain diagnosis should be clearly established and documented. Both parties should be satisfied that all other treatment options have been explored and do not provide adequate relief. Physicians should carefully describe the complications and risks of long-term opioid therapy, explain the monitoring policies of the clinic or practice, and allow patients to express their anxieties. It may be helpful to have an explicit record of the patient's understanding of the liabilities of long-term treatment and the clinic's policies for monitoring, and this could be in the form of a signed written agreement or consent. It is also helpful, at this stage, to establish and document the goals of treatment.

After an initial titration titration (tītrā`shən), gradual addition of an acidic solution to a basic solution or vice versa (see acids and bases); titrations are used to determine the concentration of acids or bases in solution.  to an effective dose, patients should ideally be maintained on a stable dose. In fact, the ability to maintain a stable dose is often an indication of successful treatment. For several reasons, including less likelihood of developing euphoria and therefore addiction, less disruption of normal activity, and less likelihood of focusing on medication throughout the day, long-acting opioid preparations administered round the clock are usually chosen when treating long-term pain. The exact choice of opioid is less important, and for a detailed description of opioid drugs, the reader is referred to the standard texts. It is worth describing some of the problems that arise during treatment with methadone. Since methadone has an intrinsically long half-life, it can be used as a long-acting preparation. It does not need pharmacological manipulation to extend its activity, therefore it is cheap. It has often been recommended as a substitute for long-acting morphine and oxycodone oxycodone /oxy·co·done/ (-ko´don) an opioid analgesic derived from morphine; used in the form of the hydrochloride and terephthalate salts.

ox·y·co·done
n.
 preparations, partly on the basis of price, and partly because of the problems that occurred when OxyContin Ox·y·con·tin

A trademark for the drug oxycodone.


oxycodone hydrochloride

ETH-Oxydose, OxyContin, OxyFast, Oxy-IR, Oxynorm (UK), Roxicodone, Supeudol (CA)

Pharmacologic class: Opioid agonist
 became a popular drug of abuse. However, methadone's metabolism, though prolonged, is variable and idiosyncratic id·i·o·syn·cra·sy  
n. pl. id·i·o·syn·cra·sies
1. A structural or behavioral characteristic peculiar to an individual or group.

2. A physiological or temperamental peculiarity.

3.
. This means that the degree to which the drug accumulates varies from patient to patient. Deaths due to respiratory depression have occurred because of this unpredictability. Moreover, there can be serious interactions, notably with antibiotics and antifungals, as well as rare but dangerous prolongation of the QTc interval on the electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. . (72)

During the stable phase of treatment, it is mandatory (by law in most states) to provide prescriptions on a monthly basis, and advisable to conduct comprehensive follow-up on a regular basis, assessing pain, the effect of pain on well-being, the achievement of treatment goals, level of function, and quality of life. The patients' appearance in the clinic on a monthly basis provides an opportunity to observe aberrant aberrant /ab·er·rant/ (ah-ber´ant) (ab´ur-ant) wandering or deviating from the usual or normal course.

ab·er·rant
adj.
1.
 behaviors. Extra visits, requests for interim prescriptions and frequent telephone calls to the clinic are considered warning signs for addiction, although it is often impossible to determine whether these type of "nuisance" behaviors reflect desperation with uncontrolled pain uncontrolled pain Neurology Pain that doesn't respond to medications at doses that usually provide appropriate analgesia , fear of withdrawal associated with physical dependence, or a chaotic lifestyle, rather than addiction. Toxicology screening can be a helpful adjunct to monitoring for problematic opioid use, including for addiction and diversion. Some practitioners believe that all opioid-treated patients should be subjected to random urine screening. In support of this view, in one pain clinic, 43% of opioid-treated chronic nonterminal pain (CNTP CNTP Condições Normais de Temperatura e Pressão
CNTP Common Network Time Protocol
) patients were judged "problematic," and of these, 49% were identified using toxicology screening, not behavioral parameters. (73) In some practice settings, however, routine or random testing (programming, testing) random testing - A black-box testing approach in which software is tested by choosing an arbitrary subset of all possible input values. Random testing helps to avoid the problem of only testing what you know will work.  would seem unnecessary.

Sometimes an increase in dose will be needed, but careful consideration should be given before each dose escalation. Tolerance to the analgesic effects of opioids can develop over time, but the more common experience is that tolerance levels out, and most patients can be maintained at a stable dose. Thus, if an increase in dose is needed, it should always alert the physician to the possibility that there are other reasons for the need for an increased dose. There may be a change in the patient's pain or underlying disease, which should be sought and treated if necessary. The need for a higher dose may also be a manifestation of psychological need or addiction, which should also be identified and treated if necessary. At high doses, apparent tolerance may be a sign of opioid-induced hyperalgesia, which will be made worse by dose escalation.

Nevertheless, it is always reasonable to try a controlled dose escalation and see if this improves the pain and overall status of the patient. The aim of each dose escalation is to reach a new, stable dose. For severe pain, it may be helpful to admit the patient to the hospital to help with diagnosis and rapid titration.

The use of very high doses of opioids is rarely helpful. It is hard to say exactly what dose should be considered a high dose, and the issue of whether there is a clinical dose ceiling is much debated. The traditional teaching is that an opioid dose can be increased in a limitless fashion, and that dose increases are capable of overcoming pain. However, there are several clinical situations in which continued dose escalation does not seem to help, and patients complain of severe pain despite high-dose opioid therapy. For example, now that we see very long survival in cancer patients, we also see cancer pain that gets out of control, and dose increases that do not seem to help. This observation, together with the basic science observation that there are multiple splice variants of endogenous opioid receptors resulting in much cross-sensitivity between various opioids, was the genesis of the clinical practice of opioid rotation. (41,74) A switch to a different opioid can provide equal or better analgesia at half or less of the equivalent dose of the first opioid, and opioid rotation is a reasonable way to control dose escalation. Purely on the basis that the highest daily dose of opioid used in existing trials is 180 mg morphine or morphine equivalent, this dose is suggested as the point one should begin to consider dose reduction or opioid rotation. That is not to say that some patients do not do well on higher daily doses, but rather, that clinical experience suggests that the majority of patients do better if the daily dose is maintained below this level. One should also consider that some liabilities, including neurotoxicity neurotoxicity /neu·ro·tox·ic·i·ty/ (noor?o-tok-sis´it-e) the quality of exerting a destructive or poisonous effect upon nerve tissue. , hyperalgesia, hormonal and immune effects and problematic behavior predominate when high doses are used.

To decide whether to maintain or terminate opioid treatment, one must establish criteria for success and failure. These criteria tend to be subjective, and highly dependent on the treating physician's viewpoint. Pain relief that improves well being, progress toward achieving treatment goals, improved function, and improved quality of life, are all reasonable criteria for success and continuing therapy. Criteria for failure might include failure to reach any of the criteria for success, or deterioration in the cooperative relationship between physician and patient.

If the treatment fails, as determined by agreed criteria, it should be weaned wean  
tr.v. weaned, wean·ing, weans
1. To accustom (the young of a mammal) to take nourishment other than by suckling.

2.
 and discontinued. It is important to wean cautiously to avoid unpleasant withdrawal, the experience of which can make it hard for the patient to give up the medication a second time. Weaning can usually be accomplished over 10 days, but the exact weaning schedule will depend on dose, drug and duration of treatment. If there is addiction, discontinuation may not be the appropriate course of action, but specialized treatment by a psychiatric or addictionist may be needed. Many patients, especially those who are not doing well on opioids, report an improvement in well being, and possibly also in pain, after an opioid wean. If necessary, opioid treatment can be restarted after a period of abstinence. Opioid weaning is not always straightforward, and it is often helpful to undergo the wean in a rehabilitation setting.

Success

Pain relief that improves well being, progress toward achieving treatment goals, improved function, and improved quality of life.

Failure

Failure to reach any of the criteria for success, or deterioration in the cooperative relationship between physician and patient.

Ethical Dilemmas

Rapid changes in medical science, technology and funding during the past century have had a profound effect on the role of physicians in society and their relationship with patients. Physicians are provided with tools that can alter life itself, so patients are no longer content to put medical decisions solely in the hands of physicians. The Hippocratic tradition of benevolent paternalism paternalism (p·terˑ·n , protecting patients through an ethical code Noun 1. ethical code - a system of principles governing morality and acceptable conduct
ethic

system of rules, system - a complex of methods or rules governing behavior; "they have to operate under a system they oppose"; "that language has a complex system
 "producing good for the patient and protecting that patient from harm," (75) has been replaced by a guidance-cooperation model where the physician steers the patient, but the patient is the primary decision maker. Increasingly, moral and ethical decisions are removed from the confines of individual physician-patient relationships, and move into the realm of public morality Public morality refers to moral and ethical standards enforced in a society, by law or police work or social pressure, and applied to public life, to the content of the media, and to conduct in public places. . As part of this trend, medical practice is directed more by guidelines, laws and mandates, and less by the dictates of individual physicians. Patients' right to direct their own treatment is expressed in the Patients Bill of Rights, (76) and their right to pain and opioid treatment expressed in "intractable pain intractable pain Refractory pain Pain medicine Persistent pain which does not respond to at least 3 dosease of parenteral analgesics given over a 12-24 hr period; pain that does not respond to appropriate doses of opioid analgesics. " statutes. (77) Physicians are encouraged to provide pain and opioid treatment by Federal Agencies, (78) State Medical Boards (68) and credentialing bodies. (79) But they are also constrained by legal barriers that tend to inhibit prescribing, and that compound the moral and ethical dilemmas that are inherent in the provision of opioids because of their indispensable role in pain management pitched against their tendency to produce addiction. Against a background of conflicting directives, physicians face real patients, all presenting with a cry for relief, all complex, and many whose decisionmaking capacity is compromised by the pervasive effect of pain or the drugs used to treat pain. The challenge of balancing the needs and rights of patients, and the safety of patients and community is enormous.

Future Directions

Early, when opioid treatment was extended to patients with chronic pain, and the medical community was buoyed by the success of opioid therapy for acute and cancer pain and the negligible addiction rates associated with these, there was a great deal of confidence that the tenets of opioid treatment for acute and cancer pain would apply equally to chronic pain. Moreover, it was no longer acceptable to deny this treatment to those in need, who now had an indisputable right to be treated. Opioid prescribing for chronic pain increased exponentially during the last two decades of the twentieth century, (80) but so also did prescription drug prescription drug Prescription medication Pharmacology An FDA-approved drug which must, by federal law or regulation, be dispensed only pursuant to a prescription–eg, finished dose form and active ingredients subject to the provisos of the Federal Food, Drug,  abuse (81,82) and the medical community's concern over addiction during opioid treatment of chronic pain. It was realized that the pendulum had swung too far and indeed, opioid prescribing and prescription drug abuse have leveled off since the year 2000. Despite the cost, the lessons learned from this experience have been invaluable. It is now understood that opioid efficacy can diminish over time, and that open-ended dose escalation does not always overcome apparent tolerance. It has become clear how little is understood about the complex relationship between pain, analgesia and addiction, and this has prompted the adoption of structured management protocols that aim to minimize addiction. Concerns about efficacy and addiction have prompted an urgent search to discover more about the basic mechanisms of opioid analgesia, tolerance, dependence and addiction. Insidious opioid complications, such as hormonal suppression, that potentially worsen pain's disability, have emerged as a valid additional reason for keeping doses within a moderate range. But perhaps the greatest lesson is that it does not help to deny the addiction risk, or to fragment pain and addiction care. Remembering that opioid maintenance treatment for opioid addiction has shown remarkable success in keeping addiction under control and allowing afflicted af·flict  
tr.v. af·flict·ed, af·flict·ing, af·flicts
To inflict grievous physical or mental suffering on.



[Middle English afflighten, from afflight,
 individuals to lead near normal lives, (64-66,83) careful structured opioid treatment of pain is the best way known to protect opioid-treated pain patients from becoming addicted. The surest way to hurt them (and society) is to abandon them when they deviate from the constructive relationship envisaged by the treating practitioner, only to trail from physician to physician to obtain the drug they need, or worse still, seek illicit supplies. There is still a lot to be learned about basic opioid mechanisms, and about how to predict success and avoid disaster. Several groups are in the process of developing tools to help identify and predict risk, and these efforts are likely to help physicians who are currently torn between their duty to patients, the community and the law, with little guidance to help them. (84-88) In the meantime Adv. 1. in the meantime - during the intervening time; "meanwhile I will not think about the problem"; "meantime he was attentive to his other interests"; "in the meantime the police were notified"
meantime, meanwhile
, existing evidence strongly suggests that the best way to help patients needing opioid treatment for chronic pain is to provide the treatment in a cautious, selective and supportive manner.

References

1. Pert CB, Snyder SH. Opiate receptor opiate receptor
n.
Any of various cell membrane receptors that can bind with morphine and other opiates; concentrations of such receptors are especially high in regions of the brain having pain-related functions.
 binding of agonists and antagonists affected differentially by sodium. Mol Pharmacol 1974;10:868-879.

2. Hughes I, Smith TW, Kosterlitz HW, et al. Identification of two related pentapeptides from the brain with potent opiate opiate /opi·ate/ (o´pe-it)
1. any drug derived from opium.

2. hypnotic (2).


o·pi·ate
n.
1.
 agonist agonist /ag·o·nist/ (ag´ah-nist)
1. one involved in a struggle or competition.

2. agonistic muscle.

3.
 activity. Nature (London) 1975;258:577-579.

3. Max MB, Schufer SC, Culnane MS, et al. Association of pain relief with drug side-effects in postherpetic neuralgia Postherpetic neuralgia (PHN)
Persistent pain that occurs as a complication of a herpes zoster infection. Although the pain can be treated, the response is variable.
: a single dose study of clonidine clonidine /clo·ni·dine/ (klo´ni-den) a centrally acting antihypertensive agent, used as the hydrochloride salt; also used in the prophylaxis of migraine and the treatment of dysmenorrhea, menopausal symptoms, opioid withdrawal, and , codeine codeine (kō`dēn), alkaloid found in opium. It is a narcotic whose effects, though less potent, resemble those of morphine. An effective cough suppressant, it is mainly used in cough medicines. Like other narcotics, codeine is addictive. , ibuprofen ibuprofen (ī`byprō'fən), nonsteroidal anti-inflammatory drug (NSAID) that reduces pain, fever, and inflammation.  and placebo. Clin Pharmacol Ther 1988;43:363-371.

4. Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine lidocaine /li·do·caine/ (li´do-kan) an anesthetic with sedative, analgesic, and cardiac depressant properties, applied topically in the form of the base or hydrochloride salt as a local anesthetic; also used in the latter form as a  and morphine reduce the pain of postherpetic neuralgia. Neurology 1991;41:1024-1028.

5. Dellemijn PL, Vanneste JA. Randomised Adj. 1. randomised - set up or distributed in a deliberately random way
randomized

irregular - contrary to rule or accepted order or general practice; "irregular hiring practices"
 double-blind active-placebo-controlled crossover trial of intravenous fentanyl fentanyl /fen·ta·nyl/ (fen´tah-nil) an opioid analgesic; the citrate salt is used as an adjunct to anesthesia, in the induction and maintenance of anesthesia, in combination with droperidol (or similar agent) as a neuroleptanalgesic, and  in neuropathic pain. Lancet 1997;349:753-758.

6. Kjaersgaard-Andersen P, Nafei A, Skov O, et al. Codeine plus paracetamol paracetamol

see acetaminophen.


acetaminophen, paracetamol

an analgesic and antipyretic drug in dogs. It is contraindicated for cats because of serious side-effects which include intravascular hemolysis, methemoglobinemia and hepatic necrosis.
 versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis osteoarthritis
 or osteoarthrosis or degenerative joint disease

Most common joint disorder, afflicting over 80% of those who reach age 70. It does not involve excessive inflammation and may have no symptoms, especially at first.
 of the hip. A randomised, double-blind, multi-centre study. Pain 1990;43:309-318.

7. Moran C. MS continous tablets and pain control in severe rheumatoid arthritis rheumatoid arthritis

Chronic, progressive autoimmune disease causing connective-tissue inflammation, mostly in synovial joints. It can occur at any age, is more common in women, and has an unpredictable course.
. Br J Clin Res 1991;2:1-12.

8. Arkinstall W, Sandler A, Groghnour B, et al. Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized placebo-controlled clinical trial. Pain 1995;62:168-178.

9. Moulin moulin (mlăN`): see pothole.  DE, Iezzi A, Amireh R, et al. Randomized trial of oral morphine for chronic non-cancer pain. Lancet 1996;347:143-7.

10. Jamison RN, Raymond SA, Slawsby EA, et al. Opioid therapy for chronic noncancer back pain: a randomized prospective study. A randomized prospective study. Spine 1998;23:2591-2600.

11. Sheather-Reid RB, Cohen cohen
 or kohen

(Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male.
 ML. Efficacy of analgesics in chronic pain: a series of N-of-1 studies. J Pain Symptom Manage 1998;15:244-252.

12. Watson CPN CPN Communist Party of Nepal
CPN Commercial Property News
CPN Civic Practices Network
CPN Calling Party Number
CPN Community Psychiatric Nurse (UK)
CPN Cisco Powered Network
CPN Connaitre et Proteger la Nature
, Babul ba·bul  
n.
A tropical African tree (Acacia nilotica) that yields a gum similar to gum arabic and has a bark used in tanning.



[Persian b
 N. Efficacy of oxycodone in neuropathic pain. A randomized trial in postherpetic neuralgia. Neurology 1998;50:1837-41.

13. Caldwell JR, Hale ME, Boyd RE, et al. Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen acetaminophen (əsēt'əmĭn`əfĭn), an analgesic and fever-reducing medicine similar in effect to aspirin. It is an active ingredient in many over-the-counter medicines, including Tylenol and Midol.  added to nonsteroidal non·ste·roi·dal or non·ster·oid
adj.
Not being or containing a steroid.

n.
A drug or other substance not containing a steroid.
 antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. J Rheumatology rheumatology /rheu·ma·tol·o·gy/ (-tol´ah-je) the branch of medicine dealing with rheumatic disorders, their causes, pathology, diagnosis, treatment, etc.

rheu·ma·tol·o·gy
n.
 1999;26:862-869.

14. Peloso PM, Bellamy N, Bensen W, et al. Double blind randomized placebo-control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee. J Rheumatol 2000;27:764-771.

15. Roth SH, Fleischmann RM, Burch FX, et al. Around-the-clock, con-trolled-release oxycodone therapy for osteoarthritis-related pain. Arch Intern Med 2000;160:853-860.

16. Huse E, Larbig W, Flor H, et al. The effect of opioids on phantom limb pain phantom limb pain
n.
Pain or discomfort felt by an amputee in the area of the missing limb.


phantom limb pain,
n
 and cortical reorganization. Pain 2001;90:47-55.

17. Caldwell JR, Rapoport RJ, Davis JC, et al. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Manage 2002;23:278-291.

18. Maier C, Hildebrandt J, Klinger R, et al. Morphine responsiveness, efficacy and tolerability in patients with chronic non-tumor associated pain--results of a double-blind placebo-controlled trial (MONTAS). Pain 2002;97:223-233.

19. Raja SN, Haythornthwaite JA, Pappagallo M, et al. A placebo-controlled trial comparing the analgesic and cognitive effects of opioids and tricyclic antidepressants Antidepressants, Tricyclic Definition

Tricyclic antidepressants are medicines that relieve mental depression.
Purpose

Since their discovery in the 1950s, tricyclic antidepressants have been used to treat mental depression.
 in postherpetic neuralgia. Neurology 2002;59:1015-1021.

20. Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy Diabetic Neuropathy Definition

Diabetic neuropathy is a nerve disorder caused by diabetes mellitus. Diabetic neuropathy may be diffuse, affecting several parts of the body, or focal, affecting a specific nerve and part of the body.
: a randomized controlled trial. Neurology 2003;60:927-934.

21. Morley JS, Bridson J, Nash TP, et al. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med 2003;17:576-587.

22. Rowbotham MD, Twilling L, Davies PS, et al. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med 2003;348:1223-1232.

23. Watson CPN, Moulin D, Watt-Watson J, et al. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003;105:71-78.

24. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003;349:1943-1953.

25. Portenoy RK, Foley KM. Chronic use of opioid analgesics Analgesics, Opioid Definition

Opioid analgesics, also known as narcotic analgesics, are pain relievers that act on the central nervous system. Like all narcotics, they may become habit-forming if used over long periods.
 in non-malignant pain: report of 38 cases. Pain 1986;25:171-186.

26. Urban BJ, France RD, Steinberger EK, et al. Long-term use of narcotic/antidepressant medication in the management of phantom limb pain. Pain 1986;24:191-196.

27. Tennant FS, Robinson D, Sagherian AS, et al. Chronic opioid treatment of intractable non-malignant pain. NIDA NIDA National Institute on Drug Abuse
NIDA National Institute of Dramatic Arts (Australia)
NIDA Northern Ireland Development Agency (UK)
NIDA Northern Ireland Dairy Association
 Res Manag 1988;81:174-180.

28. Bouckoms AJ, Masand P, Murray GB, et al. Chronic nonmalignant pain treatment with long term analgesics. Ann Clin Psychiatry 1992;4:185-192.

29. Zenz M, Strumpf M, Tryba M. Long-term opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 1992;7:69-77.

30. Pappagallo M, Raja SN, Haythornthwaite JA, et al. Oral opioids in the management of postherpetic neuralgia: a prospective survey. Analgesia 1994;1:51-55.

31. Gardner-Nix JS. Oral methadone for managing chronic nonmalignant pain. J Pain Symptom Manage 1996;11:321-328.

32. Lorenz J, Beck H, Bromm B. Cognitive performance, mood and experimental pain before and during morphine-induced analgesia in patients with chronic non-malignant pain. Pain 1997;73:369-375.

33. Simpson Jr. RK, Edmondson EA, Constant CF, et al. Transdermal fentanyl for chronic low back pain. J Pain Symptom Manage 1997;14:218-224.

34. Ytterberg SR, Mahowald ML, Woods SR. Codeine and oxycodone use in patients with chronic rheumatic disease Rheumatic disease
A type of disease involving inflammation of muscles, joints, and other tissues.

Mentioned in: Temporal Arteritis
 pain. Arthritis Rheum rheum (rldbomacm) any watery or catarrhal discharge.

rheum
n.
A watery or thin mucous discharge from the eyes or nose.



rheum

any watery or catarrhal discharge.
 1998;41:1603-1612.

35. Altier N, Dion D, Boulanger A, et al. Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study. Burns 2001;27:771-775.

36. Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004;112:372-380.

37. Attal NA, Guirimand R, Brasseur L, et al. Effects of IV morphine in central pain. A randomized placebo-controlled study. Neurology 2002;58:554-563.

38. Gilson AM, Ryan KM, Joranson DE, et al. A reassessment of trends in the medical use and abuse of opioid analgesics and implications for diversion control. J Pain Symptom Manage 2004;28:176-188.

39. U.S. Drug Enforcement Administration The Drug Enforcement Administration (DEA) was established in 1973 by President richard m. nixon as part of the Justice Department, thus uniting a number of federal drug agencies that had often worked at cross-purposes. . Automation of Reports and Consolidated Orders System (ARCOS); Retail Drug Summary Report. Available at: http://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/index.html. Accessed October 12, 2006.

40. Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain 2002;100:213-217.

41. Mercadante S. Opioid rotation for cancer pain. Cancer 1999;86:1856-1866.

42. Mitra S, Sinatra RS. Perioperative perioperative /peri·op·er·a·tive/ (-op´er-ah-tiv) pertaining to the period extending from the time of hospitalization for surgery to the time of discharge.

per·i·op·er·a·tive
adj.
 management of acute pain in the opioid-dependent patient. Anesthesiology anesthesiology (ăn'ĭsthē'zēŏl`əjē), branch of medicine concerned primarily with procedures for rendering patients insensitive to pain, and for supporting life systems under the strains of anesthesia and surgery.  2004;101:212-227.

43. Schofferman J. Long-term use of opioid analgesics for the treatment of chronic pain of nonmalignant origin. J Pain Symptom Manage 1993;8:279-288.

44. Harden RN. Chronic opioid therapy: another reappraisal. APS Bulletin 2002;12: vol 1.

45. Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and opiate tolerance: a current view of their possible interactions. Pain 1995;62:259-274.

46. Bruera E, MacMillan K, Hanson J, et al. The cognitive effects of the administration of narcotic narcotic, any of a number of substances that have a depressant effect on the nervous system. The chief narcotic drugs are opium, its constituents morphine and codeine, and the morphine derivative heroin.

See also drug addiction and drug abuse.
 analgesic in patients with cancer pain. Pain 1989;39:13-16.

47. Vainio A, Ollila J, Matikainen E, et al. Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 1995;346:667-670.

48. Galski T, Willimas JB, Ehle HT. Effects of opioids on driving ability. J Pain Symptom Manage 2000;19:200-208.

49. Haythornthwaite JA, Menefee LA, Quatrano-Piacentini AL, et al. Outcome of chronic opioid therapy for non-cancer pain. J Pain Symptom Manage 1998;15:185-194.

50. Mendelson JH, Meyer RE, Ellingboe J, et al. Effects of heroin and methadone on plasma cortisol and testosterone. J Pharmacol Exp Ther 1975;195:296-302.

51. Daniell HW. Hypogonadism Hypogonadism Definition

Hypogonadism is the condition more prevalent in males in which the production of sex hormones and germ cells are inadequate.
 in men consuming sustained-action oral opioids. J Pain 2002a;3:377-384.

52. Lee C, Ludwig S, Duerksen D. Low serum cortisol associated with opioid use: Case report and review of the literature. Endocrinologist 2002;12:5-8.

53. Paice JA, Penn RD, Shott S shott  
n.
Variant of chott.



shott or chott  

A shallow lake or marsh with brackish or saline water, especially in northern Africa.
. Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage 1996;11:71-80.

54. Finch PM, Roberts LJ, Price L, et al. Hypogonadism in patients treated with intrathecal morphine. Clin J Pain 2000;16:251-254.

55. Abs R, Verhelst J, Maeyaert J, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clinic Endocrinol Metab 2000;85:2215-2222.

56. Daniell HW. Narcotic-induced hypogonadism during therapy for heroin addiction. J Addict Dis 2002;21:47-53.

57. Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386.

58. Risdahl JM, Khanna KV, Peterson PK, et al. Opiates Opiates
Analgesic, pain killing drugs, such as heroin and morphine that depress the central nervous system.

Mentioned in: Withdrawal Syndromes
 and infection. J Neuroimmunol 1998;83:4-18.

59. Peterson PK, Sharp BM, Gekker G, et al. Morphine promotes the growth of HIV-1 in human peripheral blood peripheral blood Cardiology Blood circulating in the system/body  mononuclear mononuclear /mono·nu·cle·ar/ (-noo´kle-er)
1. having but one nucleus.

2. a cell having a single nucleus, especially a monocyte of the blood or tissues.


mon·o·nu·cle·ar
adj.
 cell cocultures. AIDS 1990;4:869-873.

60. Porter J, Jick H. Addiction rare in patients treated with narcotics narcotics n. 1) techinically, drugs which dull the senses. 2) a popular generic term for drugs which cannot be legally possessed, sold, or transported except for medicinal uses for which a physician or dentist's prescription is required.  (letter). N Engl J Med 1980;302

61. Fishbain DA, Rosomoff HL, Rosomoff RS. Drug abuse, dependence and addiction in chronic pain patients. Clin J Pain 1992;8:77-85.

62. Savage S, Covington ED, Heit HA, et al. Definitions related to the use of opioids for the treatment of pain. A consensus document from the American Academy The American Academy in Berlin is a non-partisan academic institution in Berlin. It was founded in September 1994 by a group of prominent Americans and Germans, among them Richard Holbrooke, Henry Kissinger, Richard von Weizsäcker, Fritz Stern and Otto Graf Lambsdorff and opened in  of Pain Medicine, the American Pain Society and the American Society of Addiction Medicine The American Society of Addiction Medicine is a professional organization for physicians who specialize in the treatment of addiction. It is based in Chevy Chase, Maryland.  2001.

63. Savage SR, Joranson DE, Covington EC, et al. Definitions related to the medical use of opioids: evolution towards universal agreement. J Pain Symptom Manage 2003;26:655-667.

64. Dole VP, Nyswander M, Kreek MJ. Narcotic blockade narcotic blockade
n.
The use of drugs to inhibit the effects of narcotic substances.
. Arch Intern Med 1966;188:304-309.

65. Dole VP, What we have learned from three decades of methadone treatment. Drug Alcohol Rev 1994;13:3-4.

66. Brecher EM. How well does methadone maintenance work? In: The Consumers Union Report on Licit and Illicit Drugs. Schaffer Library of Drug Policy. Available at: http://www.druglibrary.org/schaffer/Library/studies/cu/cumenu.htm. Accessed October 12, 2006.

67. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med 2005;6:107-112.

68. West JE, Aronoff G, Dahl JL, et al. Model guidelines for the use of controlled substances for the treatment of pain. A policy document of the Federation of State Medical Boards Federation of State Medical Boards,
n.pr an association comprising the medical boards of the United States, the District of Columbia, the Virgin Islands, Guam, Puerto Rico, and 13 state boards associated with osteopathic medicine.
 of the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area.  Inc [Abstract]. Euless, Federation of State Medical Boards of the United States Inc, 1998.

69. Weaver MF, Schnoll SH. Opioid treatment of chronic pain in patients with addiction. J Pain Palliat Care Pharmacother 2002;16:5-26.

70. Collins ED, Streltzer J. Should opioid analgesics be used in the management of chronic pain in opiate addicts? Am J Addict 2003;12:93-100.

71. Newman RG. Analgesia and opiate addicts. Am J Addict 2004;13:494.

72. Fishman SM, Wilsey B, Mahajan Mahajan is an Indian surname, found among the Vaishya castes (business communities). In India surname Mahajan is used by two communities: - one residing in North of India(mainly on the Amritsar to Jammu belt) and another belonging to North Maharashtra.  G, et al. Methadone reincarnated: novel clinical applications with related concerns. Pain Med 2002;3:339-348.

73. Katz NP, Sherburne S, Beach M, et al. Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth Analg 2003;97:1097-1102.

74. Pasternak GW. The pharmacology of mu analgesics: from patients to genes. Neuroscientist 2001;7:220-231.

75. Veach RM. The Theory of Medical Ethics medical ethics The moral construct focused on the medical issues of individual Pts and medical practitioners. See Baby Doe, Brouphy, Conran, Jefferson, Kevorkian, Quinlan, Roe v Wade, Webster decision. . New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
, Basic Books, 1981, p 23.

76. Advisory Commission on Consumer Protection and Quality in the Health Care Industry. Patients' Rights The legal interests of persons who submit to medical treatment.

For many years, common medical practice meant that physicians made decisions for their patients. This paternalistic view has gradually been supplanted by one promoting patient autonomy, whereby patients and
 and Responsibilities http://www.consumer.gov/qualityhealth/rights/htm. Accessed October 12, 2006.

77. Joranson DE, Gilson AM. State intractable pain policy: current status. APS Bulletin 1997;7:7-9.

78. Acute Pain Management: Operative or Medical Procedures and Trauma. Clinical Practice Guideline. AHCPR AHCPR,
n.pr See Agency for Healthcare Research and Quality.
 Pub. No. 92-0032. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS
 1992.

79. Joint Commission on Accreditation of Healthcare Organizations Joint Commission on Accreditation of Healthcare Organizations,
n.pr the United States body that accredits healthcare organizations.

Joint Commission on Accreditation of Healthcare Organizations (JCAHO/TJC),
n.
. Pain management standards. Effective January 1, 2001. Available at: http://www.jcrinc.com/subscribers/perspectives.asp?durki=3243&site=10&return=2897. Accessed October 12, 2006.

80. National Institute of Drug Abuse (NIDA). Info Facts: Prescription Pain and Other Medications 1999. Available at: http://nida.nih.gov/Infofacts/PainMed.html.

81. DHHS DHHS Department of Health & Human Services (US government)
DHHS Dana Hills High School (Dana Point, California)
DHHS Deaf and Hard of Hearing Services
DHHS Deaf and Hard of Hearing Services
, SAMHSA SAMHSA Substance Abuse and Mental Health Services Administration : National Household Survey on Drug Abuse Main Findings. Series H-11. 1998.

82. DHHS, SAMHSA: National Survey on Drug Use and Health www.oas.samha.gov. 2003.

83. Chambers CD, Babst DV, Warner A. Characteristics predicting long-term retention in Methadone Maintenance Programs. Proceedings, Third Methadone Conference, 1970.

84. Chabal C, Erjavec MK, Jacobson L, et al. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence and predictors. Clin J Pain 1997;13:150-155.

85. Compton P, Darakjian J, Miotto K. Screening for addiction in patients with chronic pain with "problematic" substance use: evaluation of a pilot assessment tool. J Pain Symptom Manage 1998;16:355-363.

86. Passik SD, Kirsh KL, Whitcomb L, et al. A new tool to assess and document pain outcomes in chronic pain patients receiving opioid ther-apy. Clin Ther 2004;26:552-561.

87. Adams LL, Gatchel RJ, Robinson RC, et al. Development of a self-report screening instrument for assessing potential opioid medication misuse in chronic pain patients. J Pain Symptom Manage 2004;27:440-459.

88. Butler SF, Budman SH, Fernandez K, et al. Validation of a screener and opioid assessment measure for patients with chronic pain. Pain 2004;112:65-75.
Begin challenging your own assumptions. Your assumptions are your
windows on the world. Scrub them off every once in awhile, or the light
won't come in.
--Alan Alda


Jane C. Ballantyne, MD, FRCA FRCA Fast Response Cache Accelerator
FRCA Farming and Rural Conservation Agency
FRCA Fellow of the Royal College of Anaesthetists (UK)
FRCA Free Reformed Churches of Australia
FRCA Fire Retardant Chemicals Association
 

From the Division of Pain Medicine, Massachusetts General Hospital Massachusetts General Hospital Health care The major teaching hospital for Harvard Medical School, widely regarded as one of the best health care centers in the world  Department of Anesthesia and Critical Care and the Department of Anesthesia, Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , Boston, MA.

Reprint requests to Jane C. Ballantyne, MD, FRCA, Chief, Massachusetts General Hospital Pain Center, 15 Parkman Street, WACC WACC

See: Weighted average cost of capital
 333, Boston, MA 02114. Email: jballantyne@partners.org

Accepted March 23, 2006.

*The term nonterminal is used so that it includes cancer patients with long survival who suffer chronic pain.

RELATED ARTICLE: Key Points

* Opioid treatment was extended to patients with long-term (chronic) pain after it had been firmly established as safe and effective for acute and cancer pain.

* Two decades of experience with this therapy have taught that there are reasons for caution related to loss of efficacy over time, toxicity and higher than expected addiction risks.

* Most authorities agree that improved quality of life--regardless of whether this occurs in the presence of addiction--is a satisfactory outcome of chronic opioid therapy for pain.

* A cautious and selective treatment approach is recommended.

* Future efforts will be focused on developing screening tools to help identify patients at risk before and during treatment.
Table 1. Controlled studies: Summary of results

Reference              Study type      Type of pain

Kjaersgaard-           RCT             Osteoarthritis of the hip, in
  Andersen 90 (6)                        elderly patients
Moran 91 (7)           RCT, crossover  Rheumatoid arthritis
Arkinstall 95 (8)      RCT             Musculoskeletal in most patients
Moulin 96 (9)          RCT, crossover  Musculoskeletal or soft tissue
Jamison 98 (10)        RCT             Back pain
Sheather-Reid 98 (11)  RCT, crossover  Cervicobrachial syndrome,
                                         fibromyalgia
Watson 98 (12)         RCT, crossover  Postherpetic neuralgia
Caldwell 99 (13)       RCT             Osteoarthritis
Peloso 00 (14)         RCT             Osteoarthritis, hip and knee
Roth 00 (15)           RCT             Osteoarthritis
Huse 01 (16)           RCT, crossover  Phantom limb pain
Caldwell 02 (17)       RCT             Osteoarthritis
Maier 02 (18)          RCT, crossover  Mixed
Raja 02 (19)           RCT, crossover  Postherpetic neuralgia
Gimbel 03 (20)         RCT             Diabetic neuropathy
Morley 03 (21)         RCT, crossover  Mixed neuropathic
Rowbotham 03 (22)      RCT             Peripheral and central
                                         neuropathic pain
Watson 03 (23)         RCT, crossover  Diabetic neuropathy

Reference              n/N          Drug

Kjaersgaard-           83/75        Codeine with acetaminophen vs.
  Andersen 90 (6)                     acetaminophen
Moran 91 (7)           20           CR morphine vs. placebo
Arkinstall 95 (8)      46           CR codeine vs. placebo
Moulin 96 (9)          46           CR morphine vs. active placebo
                                      (benztropine)
Jamison 98 (10)        24/12        Oxycodone or CR morphine plus
                                      oxycodone vs. naproxen
Sheather-Reid 98 (11)   6           Codeine vs. ibuprofen or placebo
Watson 98 (12)         38           CR oxycodone vs. placebo
Caldwell 99 (13)       71/36        CR oxycodone or oxycodone with
                                      acetaminophen vs. placebo
Peloso 00 (14)         31/35        CR codeine vs. placebo
Roth 00 (15)           44/(44)/45   CR oxycodone, high dose (or low
                                      dose) vs. placebo
Huse 01 (16)           12/12        CR morphine vs. placebo
Caldwell 02 (17)       73/73/76/73  CR morphine (24 hr) or CR
                                      morphine (12 hr) vs. placebo
Maier 02 (18)          49           CR morphine vs. placebo
Raja 02 (19)           76/44        CR morphine or methadone vs. placebo
                                      (or tricyclic antidepressant)
Gimbel 03 (20)         63/52        CR oxycodone vs. placebo
Morley 03 (21)         11/(18)      Methadone high dose (or low dose)
                                      vs. placebo
Rowbotham 03 (22)      43/38        High-dose levorphanol vs. low-dose
                                      levorphanol
Watson 03 (23)         35/36        CR oxycodone vs. active placebo
                                      (benztropine)

                                                        Pain    Level of
Reference              Daily dose (mg)     Follow up    relief  function

Kjaersgaard-           180                 4 weeks      +
  Andersen 90 (6)
Moran 91 (7)           up to 120           10 weeks     +       0
Arkinstall 95 (8)      200-400             1 week       +       +
Moulin 96 (9)          up to 120           11 weeks     +       0
Jamison 98 (10)        up to 130           16-32 weeks  +       +
                         (morphine
                         equivalent)
Sheather-Reid 98 (11)  120                 12 weeks     0       0
Watson 98 (12)         28-62               8 weeks      +       +
Caldwell 99 (13)       up to 60            8 weeks      +       +
Peloso 00 (14)         up to 400           4 weeks      +       +
Roth 00 (15)           up to 40            14 weeks     + (0)   + (0)
Huse 01 (16)           70-160 (300 in one  4 weeks      +       0
                         patient)
Caldwell 02 (17)       30                  4 weeks      +       0
Maier 02 (18)          up to 180           2 weeks      +       +
Raja 02 (19)           15-225 morphine,    8-24 weeks   + (0)   0
                         40-140 methadone
Gimbel 03 (20)         20-120              6 weeks      +       +
Morley 03 (21)         20 (10)             20 days      + (0)
Rowbotham 03 (22)      up to 11.8          8 weeks      +       0
                         (approximately
                         60 morphine
                         equivalent)
Watson 03 (23)         10-40               4 weeks      +       +

Where two numbers are given, the first is the number of patients in the
experimental group and the second is the number in the control group.
Parentheses link treatment with outcome when more than two treatment
groups are included in the study.
RCT, randomized controlled trials; CR, controlled release (study drugs
not labeled CR were immediate-release preparations); +, statistically
significant positive difference; 0. no statistically significant
difference.
Table is also used in ASA Refresher Courses, Ballantyne JC "Opioid
therapy: is it appropriate in patients with non-cancer pain? An
evidence-based look at the issue" to be published in Anesthesiology Vol.
34, 2006.

Table 2. Principles of chronic opioid therapy

* First try aggressive rehabilitative approach that may utilize opioids,
  but aims to restore function and reduce reliance on medications
* Consider longer term treatment a serious undertaking that will require
  the commitment of both physician and patient
* Ensure that other treatment options have been maximized
* Consider opioid therapy as an adjunct; sole opioid therapy is rarely
  successful
* Use goal-directed therapy; set limits and goals and agree to these
* Use of a written agreement, contract or consent is helpful for setting
  out terms of treatment, terms for discontinuing treatment, and a clear
  statement of likely benefits and risks
* Unless pain is occasional, base regimen on long-acting opioids, and
  avoid breakthrough medication
* Ensure careful and regular follow up
* Monitoring of opioid use is helpful using pharmacy databases,
  pill-counting or urine toxicology
* Be prepared to wean and discontinue if treatment goals are not met
* Maintain good documentation
COPYRIGHT 2006 Southern Medical Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2006, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

 Reader Opinion

Title:

Comment:



 

Article Details
Printer friendly Cite/link Email Feedback
Author:Ballantyne, Jane C.
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Nov 1, 2006
Words:8605
Previous Article:CME questions: irritable bowel syndrome: a practical review.
Next Article:An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures.
Topics:



Related Articles
No relief in sight.
Selected Guidelines [*].
Chronic pain: we're undertreating the elderly: having read many accounts of undertreatment, this consultant pharmacist mounted his own study. Here's...
Incidence of constipation associated with long-acting opioid therapy: a comparative study.
Disappearing docs: DEA painkiller flip-flop.
Origins of ache: immune proteins may yield chronic-pain clues.
Oxycodone accumulation in a hemodialysis patient.

Terms of use | Copyright © 2014 Farlex, Inc. | Feedback | For webmasters