Opioids

The text to follow was published by Professor Harald Breivik, February, 10, 2007 at the meeting of the Norwegian Pain Association.

I do not necessarily support the statements and recommendations being made.

As professor in anesthesiology and leader of the pain clinic at `Rikshospitalet` Breivik is Norway`s leading Autocrat when it comes to Pain Treatment. For this reason, the text below is rather lengthy and detailed. Some of the new `guidelines` are significantly different from what is common in general practice today. I will therefore summarize some of what is new first.

Somadril, Aporex, Paralgin Forte, Kodein, Nobligan, Tramadol, Pethidine, Ketorax, Temgesic, Oxynorm, Ketogan, Paralgin minor and Morphine should not be used in the treatment of chronic pain.

Widespread chronic pains without an exact diagnosis should not be treated with opioids or, of course, any of the substances listed above. The same restriction applies to chronic headaches.

When opioids are prescribed, only slow release formulations should be considered.

The patient`s regular doctor should always be involved in the decision regarding possible prescriptions of opioids. The patient shall be informed about how the drugs work and their side effects, both orally and in writing.

On to Breiviks Text:

Use of opioids in patients with long lasting pain-conditions where there is a normal life expectancy.

Introduction:

Long term use of opioids is indicated in treatment of severe pains in patients with cancer. The same is applicable for bothersome pain conditions in other types of serious primary disease where there is a short life expectancy. Clinical experience and limited documentation from controlled studies show that in selected cases it may also be correct to use opioids in long term pain conditions that are not related to cancer, or serious primary disease. Opioids used in treatment of such pain conditions should however be used conservatively, and after a thorough comparison of the effect on the pain, the patient's quality of life, and adverse effects.

Treatment should be continuously evaluated and adjusted as needed. When significant side effects appear and advantageous effects abate, in spite of adjustment of dose and type of opioid used, and the addition of adjuncts has been attempted; then the opioid treatment should be gradually abandoned.

Incorrect use of opioids.

Patients with sustained chronic pain who get rapid and short half-life opioid analgesics (which is intended for acute pain, for instance Paralgin Forte/Pinex Forte, and Aporex,) will experience only short-term pain relief followed by acute abstinence-reinforcement of pain and suffering once the effect abates. The patient will then increase his intake and use these acute pain drugs incorrectly. The Patient will want and desire larger and more frequent doses. This is perceived as "dependence and emerging abuse." This is iatrogenic induced incorrect use.

Patients who are treated with depot-opioids (tablets or patches) will also develop tolerance

and have after a while an increased dosage need. They will also experience pain breakthrough and acute abstinence toward the end of the period that a given dose is effective (diminishing efficacy.) The patient will then request an increase in dosage. If this is misinterpreted as the beginning of "addiction and abuse", the patients trust is eroded quickly and the patient enters a situation where the medicines are used incorrectly.

Primary Message:

The goal is all who need it shall receive as good pain treatment as possible, while side effects and incorrect use are kept at a minimum, and abuse of opioids is avoided.

Opioid analgesics should only be attempted in selected patients when other available interventions do not lead to results, and should only be part of a holistic treatment plan.

Moderate doses of opioids (both weak and strong) can function adequately as long term treatment in some patients, in other patients such treatment may lead to significant problems. An agreed upon, limited, trial period can help determine this. A well informed patient must be significantly co-responsible for monitoring positive and adverse effects, and for control and storage of prescriptions and medicines.

In controlled studies, (a few weeks duration) the effect of opioids in the treatment of long-term pain has been documented to being moderate (in average a 30% reduction in pain intensity.) Nerve damage (Neuropathic) Pain requires larger doses.

Controlled long term studies are missing. Open studies show that over half of participants terminate opioid treatment in the course of one to two years because of adverse effects. Most frequently opioid induced digestive dysfunction overshadows the positive effects, or the pain and quality of life effect of the opioids is insufficient. Some terminate treatment because the underlying pain has improved.

Decrease in analgesia can be attributed to the development of tolerance which requires adjustment of dosage. No maximum dose can be stated, but empirically, adverse effects and control problems when the dose escalates over the equivalent of 200 to 400 milligrams of morphine per twenty-four hour period. This may be due to tolerance development with the development of opioid-induced hyperalgesi. Some patients have receptors that are not highly sensitive to opioid treatment. Long term, high dose opioid treatment in both sexes has negative effects on endocrine functions such as testosterone production and reduced libido (the latter in both sexes). Immune system function, upper and lower gastro-intestinal function (constipation and nausea, etc.), mood (depression and anhedoni with may last long beyond the termination of opiate treatment.)

About 10% of patients are subjected to incorrect use of opioid analgesics; a few develop a (definition- see fact sheet) substance abuse problem requiring professional intervention. (This will require resources and treatment from substance abuse specialists.)

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Abuse (substance abuse) as defined in the DSM IV

One or more of the criteria below must be met, repeated or sustained in a single 12 month

period.

Repeated use of a medicine that leads to an individual fails in fulfilling his obligations in school, work, or at home. (For instance the individual is tired and lacks concentration at work, poor performance, low attendance.) (Nevertheless, this could be the result of the pain condition and completely legal use of opiate analgesia.)

Repeated use of medicines in such a manner as to place the individual in situation exposing the risk for physical injury (operating a motor-vehicle or heavy machinery.)

Repeated contact with the legal system (For crimes such as forgery of prescriptions, the acquisition or sale of controlled substances.)

Continued, abnormal, use in spite of ongoing or returning problems (in the physical, psychological, or social sphere.)

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Advice on the selection of patients, initiation, follow-up, and termination of long term opiate treatment.

So called "weak" opioid analgesics (in Norway: codein, tramadol, dextroproproxyphene) have the same type of action (somewhat weaker) and side effects as the strong opioid analgetics. Therefore the same guidelines should be followed for long term treatment with all opioids.

The pain condition including psychosocial aspects should be thoroughly explored and well known

by the doctor responsible for a patient's treatment.

Before a trial with opioids is initiated to evaluate positive and negative effects the following should have been evaluated:

More casual treatment with less risk-laden alternatives should have been attempted without satisfactory relief from pain or improvement in function.

The patient’s quality of life, physical, psychosocial function should be strongly reduced by the pain condition.

Not all pain with associated conditions is relieved by opioids. A trial period with individualized opiaoid treatment four to twelve weeks in duration will be able to tell if treatment with opiates may have positive effects on the patient’s pain-condition, ability to function, or quality of life. Only good follow-up can determine if the positive effects endure. The follow-up must be highly frequent during the next four to eight months.  Following this, yearly, two to four assessments by the patient's primary doctor and a yearly assessment by a pain specialist should follow.

The primary doctor in charge of the patient's treatment and the patient should always participate in the assessment and decision on initiation and follow up of a trial period with opioid treatment. Further they should participate in the decision if this trial period should be extended. Assessment of positive and adverse effected shall be continuous. Long term opioid treatment should not be life-long

One should be particularly restrictive in younger patients, those less than 50 to 60 years old. However, the patient's ability to have insight, responsibility, and the whole situation plays a very important role as well. These patients must be assessed extra thoroughly regarding rehabilitation attempts and other possible modalities of treatment before long term treatment with opioids is commenced. The physician must be aware of the risk of leading the patient into an opiate misuse situation with short acting "weaker" opioids of the type such as tramadol, dextropropoxyphene, codeine while other treatment options are evaluated.

Patients with significant, complex psychosocial problems should always receive assessment by a pain team with offers of treatment such as cognitive behavioral therapy.

Patients with unclear, generalized chronic pain conditions should not be treated with opiates.

Chronic headache should not be treated with opioids.

The threshold for opioid treatment in the elderly is lower than what it is for younger patients; nevertheless this former patient group is more exposed to side effects. Opioids at part of treatment in elderly patients with a clear pain problem of long-lasting character, (for instance, arthroses, osteoporotic fractures, posherpetic neuralgia, and painful diabetic neuropathy), can usually be initiated and followed up in full by a general practitioner.

The patient should be informed of positive as well as adverse effects of long term opioid treatment. This should be done both orally and in writing to ensure that the patient fully understands and receives adequate information. That this was done should be documented on the patient's chart.

Treatment goals should be discussed with the patient, and the patient should be in agreement that theses must be achieved and maintained for the opiate treatment to be initiated and continue through a longer period of time.

Such treatment goals should be:

One for clinically significant pain relief, at least 30% on the numeric scale from 1 to 10

A certain physical improvement in function. What is here clinically significant, desirable is agreed upon the patient.

A certain improvement in social functioning. Again what is clinically significant is agreed upon with the patient.

A certain improvement in global functioning, well being, and quality of life. Specific goals are again agreed upon with the patient.

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Under surveillance of treatment goals, the following must also be assessed and agreed upon with the patient:

Adverse effects, specifically opioid induced gastrointestinal dysfunction, must be tolerable (slow ventricle-emptying, nausea, reflux, dyspepsia, and severe constipation.) Constipation must be prevented or managed with daily additions of fibre and stool softeners such as sorbitol. Secretion and peristaltic laxatives such as biscodyl or senna will most often be necessary once to twice per week. In exceptional cases, stronger osmotic agents are needed such as makrogel and contact laxatives such as sodiumpicosulphate.

The patient must communicate to the doctor if desirable effects are diminishing, or adverse effects are on the rise such that the treatment may be adjusted.

Of dosage adjustment agreed upon in advance to a certain level, or adverse effects appear that overshadow pain relief, the opioid treatment should be terminated gradually.  If the opioid treatment has lasted for some weeks or months, the pain may be perceived more bothersome in such a reduction period. The patient may experience this as bothersome that the patient desires a return to the opioid treatment, in spite of, its marginal effect and bothersome adverse effects.

If the patient continues treatment, one should now agree upon control and assessment intervals at a very minimum every six months. Opioid treatment should not be seen as a life-long treatment, but be subject to reconsideration at each assessment.

If the patient shows signs or symptoms of incorrect opioid use, the treatment must be thoroughly assessed, perhaps terminated or be subject to dosage adjustment. If continued treatment is indicated, frequent assessments must be done of positive and adverse effects. If trust, between the doctor and patient has become a problem, portioned dispensing from a certain pharmacy may offer a solution.

In the case of serious misuse-problems, safe limits and controlled dispensing must be ensured.

Use of benzodiazepines and carisoprodol has no place in pain treatment.

Tricyclic antidepressants, SSRI's, gabapentin, or pregabalin may give a synergistic effect when administered with opioids and could improve the quality of sleep a patient with a pain problem receives.

There is least risk for problem use of an opioid with opioid administration is in such a manner that the patient get a slow, lasting dose, with slow reduction in effect. Opioids in depot (slow release) formulations may function in this manner. Patients who are receiving treatment with such drugs must not be given rapid and short duration opioids in addition.

Injections must not be used because of great danger for misuse and other complications.

Other short rapid and short lasting forms of administration should also, in general be avoided. Exceptions can be made in the case of patients who have activity induced, short-lasting, pain attacks.

For patients on around the clock treatment, the treatment plan, should contain room for variations according to pain intensity. (Breakthrough Pain). These should not be treated with rapid and short lasting opioids, but with opioids that cover the pain time span (such as twelve hour depot tablets.)

Patients who are not on round the clock opioid treatment, and have intermittent strong pains, that are exacerbated by everyday activities, can be treated with opioids that cover the time span the pain is provoked. (For instance, in the case of nightly pains due to arthritic conditions.)

The risk of misuse of opioids must be thoroughly evaluated before the treatment starts and at least once a year during continuing treatment.

To avoid incorrect opioid use one must show special vigilance in acute and sub-acute pains that last longer than what should be expected. At follow-up, issuing of prescriptions the patient's pain situation and opioid treatment must be assessed thoroughly.

If in spite of precautions, misuse of opioids does occur, adequate treatment for this must be initiated without delay. To help the patient and the treating physician, experts in pain should be contacted. Some pain clinics have experience in treating such patients, possibly in conjunction with substance abuse clinics. Methadone in adequate doses can help both patients with their pain and ease control or misuse of other opioid analgetics. (Rhodin A et al EJP 2006; 10:271-8.)

Methadone may have an analgetic effect in conjunction with other opioid analgetica, and reduces the abuse reinforcing effects of opioids and discomfort of abstinence.

The patient's regular physician, or his substitute, has the responsibility for there being a treatment plan with substantive treatment goals. Further, the onus is on him that this treatment plan should be followed up in close conjunction with the patient and other health care professionals involved in the care a patient.

In patients with long term opioid treatment who receive acute pains due to injury, surgery, or acute medical illness (for instance an acute myocardial infarction), it is absolutely necessary to administer higher doses of opioids than what is the normal practice in patients who do not regularly use opioids. Individual titration to pain relieving dose, (often a high dose), is always necessary.

The operation of a motor vehicle is not necessarily excluded if a patient is treated with opiaoid analgesics in a regular dose through longer periods of time. It is up to the patient and doctor, who have a shared responsibility, to determine if the patient is capable of operating a motor vehicle in a responsible and safe manner. The patient has the responsibility to never drive when he feels under the influence, is tired, or feeling out of the ordinary. If the patient uses sedatives, anxiety relieving medicines, or sleep aids in addition to an opioid, operation of a motor vehicle is not advisable. (Breivik H:Acta Anaest Scand 2006;50:651).

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Drug dependence according to the DSM IV

Three or more criteria must be fulfilled within the same twelve month period:

Tolerance: need for a larger dose to achieve the same effect, or significantly reduced effect at the current dose.

Abstinence: Symptoms in case of reduced or interrupted supply of the substance.

Loss of Control:  intake of larger amounts or over longer periods of time than what was agreed upon. This accompanied by a lasting desire or failed attempts to reduce or control intake.

Drug seeking behavior: a large part of a patient's life is dominated by needs such as acquiring, consuming, and recovering; following use of a substance/dose.

Important social activities (socially, work-related, and free-time activities) are abandoned or significantly reduced due to the medicine/substance.

Continued misuse in spite of knowledge that it has caused or exacerbated physical or mental ailments of a lasting or recurring nature.

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