What is opioid therapy for chronic pain
Opioids for non-tumor pain
Opioids are used increasingly around the world. Above all, non-tumor-related pain is the main indication. In the now thoroughly revised S3 guideline "Long-term use of opioids for chronic non-tumor-related pain" (LONTS), indications and long-term prescriptions were particularly examined. In the case of neuropathic pain (especially diabetic polyneuropathy) and osteoarthritis pain, there is a proven efficacy, for all other indications the data are either insufficient or opioids are not recommended, e.g. B. in chronic headaches and functional disorders (e.g. fibromyalgia, irritable bowel syndrome). It is important for all opioid applications that they are not the only therapy, but that they should be embedded in activating therapies (physiotherapy, psychotherapy). After thorough clarification, regular reviews of the effectiveness and indication are essential.
Opioids are used increasingly worldwide. Non-cancer-related pain is the main indication. In the thoroughly revised S3 guideline "Long-term use of opioids for chronic non-cancer-related pain" (LONTS) indications and long-term prescription were particularly investigated. Opioids are effective in neuropathic pain (especially diabetic polyneuropathy) and pain due to osteoarthritis. For all other indications, there is insufficient data available or opioids are not recommended, e.g. in chronic headache and functional disorders (such as fibromyalgia, irritable bowel syndrome). It is important for all opioid applications that they are not prescribed as the only treatment, but that prescription should be embedded in activating therapies (physiotherapy, psychotherapy). After informed consent, regular monitoring of the effectiveness and indication is essential.
Almost 8% of the population in Germany suffer from chronic, non-tumor-related pain, which significantly affects them. The proportion of opioid prescriptions for non-tumor pain in Germany shows that these are very often treated with opioids (BARMER GEK Arzneimittelreport 2012):
This is 77%. Internationally, the long-term use of opioids is very controversial (1). In particular, the safety of these drugs is currently the subject of controversy in the USA. The recently published guideline on the long-term use of opioids for non-tumor-related pain provides a differentiated analysis of the current study situation (2-4).
As part of the creation of this guideline, possible therapy indications were defined, but comparisons between the individual preparations or with other therapies for special indications were also analyzed. Three time categories were defined in the studies: short-term use (4–12 weeks), medium-term use (13–25 weeks) and long-term therapy over 25 weeks. If the study situation permitted, there was a separate analysis.
With regard to the indications, there are again three categories: 1. Diseases for which an opioid therapy is effective based on the study situation, 2. Diseases for which the study situation is inconsistent, but opioid therapy can be offered as an attempt, and 3. Diagnoses for which one Therapy does not make sense due to the study situation. Overall, the recommendation for all indications is to prescribe opioids for a defined period of time and not alone, but only together with therapies in which the patients themselves actively participate (physical training, relaxation training, etc.) (Table 1).
1. Effectiveness and possible use of opioids
There are two chronic pain syndromes for which opioid therapy can be offered for a period of four to twelve weeks: diabetic polyneuropathy and chronic osteoarthritis pain. Likewise, opioids can be used to treat others neuropathic pain, such as post-zoster neuralgia, phantom pain, pain after spinal cord injury, radiculopathies and other polyneuropathies. There is currently no evidence that antidepressants or anticonvulsants should be used primarily here. The most recent meta-analysis on the treatment of neuropathic pain, on the other hand, has classified opioids as a third-line therapy (5). The gradation in the choice of medication for neuropathic pain is viewed as controversial, however. In the individual patient, comorbidities or potential side effects (e.g. weight gain) may speak for the use of one or the other substance class.
Opioids can also help chronic osteoarthritis pain offered for four to twelve weeks (6). This “can-do” recommendation also applies to chronic back pain (7). However, if the desired pain relief and / or improvement in function does not occur, drugs containing opioids should be discontinued. The National Care Guideline for Low Back Pain recommends multimodal programs for chronic pain. At rheumatoid arthritis Limited opioid therapy may be offered for six weeks. The standard here is more like NSAIDs. The administration of opioids in rheumatoid arthritis should be exceptional and limited in time.
2. Possible use of opioids: individual therapy attempts
In patients with the following diseases, there is insufficient data on opioid therapy to make a recommendation for opioids; Therefore, opioids can be used as an individual therapy attempt over four to twelve weeks and, if successful, also over a longer period: These include chronic bone pain in osteoporosis (vertebral body fractures), chronic post-operative pain, chronic ischemic pain of the extremities, chronic soft tissue pain for pressure ulcers or contractures and that complex regional pain syndrome. The practical information (see below) must be observed in particular.
3. Indications not recommended
In patients with primary headache (Tension headaches and migraines) should not be used due to the high potential for dependence and the increased chronification of headaches under opioid-containing analgesics in the sense of a drug-induced headache. Patients should also use Pain in functional disorders (Irritable bowel syndrome, fibromyalgia, chronic pelvic pain) are not treated with opioids. Only tramadol - presumably via the inhibition of the absorption of noradrenaline and serotonin - can be considered for four to twelve weeks in fibromyalgia syndrome. Unfortunately, patients with high psychosocial proportions of pain symptoms report high pain intensities and suffering, which can lead the doctor to prescribe opioids as the “strongest” painkillers. This requires high medical skill and good patient management in order to treat these patients sensibly - and without opioids.
The third group is in patients with chronic pain as a symptom of mental disorders Opioids not indicated. These include depression, anxiety disorders, post-traumatic stress disorder, and a persistent somatoform pain disorder. The differentiation of these pains can often only be recognized through specialist exploration and / or follow-up observation. Opioids should not be used for treatment, particularly in the case of severe affective disorders or suicidality.
In the case of chronic pancreatitis and chronic inflammatory bowel disease, opioids should not be offered for more than four weeks, because there is good evidence that this therapy is not effective or associated with relevant side effects.
How should opioids be used in practice for non-tumor pain? Special features of the prescription and education
If a patient can in principle be offered opioids, the advantages and disadvantages as well as alternatives (see below) should be explained with him / her in the sense of a participatory decision. There are corresponding information sheets for the following information:
Prerequisites for the opioid prescription are a thorough medical history including the clinical status, the assessment of the functional level, a psychosocial anamnesis and a screening for current and / or previous mental disorders.
Documented oral and / or written explanations, including aspects relevant to traffic and workplaces, are just as important.
Opioids should never be the only treatment for non-tumor pain, but should be embedded in (preferably independent) physical, physiotherapeutic and psychotherapeutic therapy components including a change in lifestyle. At the beginning of treatment should individual realistic therapy goals be set, such as B. 30% reduction in pain and / or improvement in functionality (walking distance, ability to work, etc.). When providing information, it is important to think about precise intake regulations, “only one prescribing doctor”, safe storage and disposal and the consequences of non-compliance. The regular review of the indication should also be agreed.
disadvantage Long-term opioid therapy in younger people is mainly a loss of libido, emotional disorders, limitations in cognitive performance and responsiveness (job / ability to drive) and physical dependence. In elderly patients, the risk of falling and confusion are important disadvantages. It is precisely because of these disadvantages that centrally active substances such as hypnotics or tranquilizers should be discontinued beforehand. At the beginning of therapy, temporary nausea and vomiting may occur, which can be treated antiemetically for two to four weeks. Constipation usually remains a long-term side effect, so specific prophylaxis is necessary in the long term. Serious side effects, in particular, depend on the dose (8).
In the practice In the case of non-tumor pain, no reliever medication with non-sustained-release opioids should be prescribed, but only delayed-release medication should be used, as these have a lower risk of falling or developing addiction. This also includes tramadol or tilidine drops. Fentanyl nasal sprays are only approved for cancer pain. The choice of opioid also depends on secondary diseases such as liver or kidney failure. If more than 120 mg opioid equivalent per day is necessary, tolerance development and / or misuse should be considered. In elderly patients, opioids should be started with a dose reduction of 25-50%. Long-term opioid therapy in children is reserved for specialists.
For the Termination of opioid therapy there are various reasons. Of course, opioids should be gradually withdrawn again if the therapy goals are within the scope of Therapy monitoring cannot be achieved. An evaluation of signs of misuse or abuse is also necessary on a regular basis. Such signs include psychological changes, a lack of adherence to therapy with both opioids and other activating therapies, cravings for short-acting opioids, psychotropic effects, resistance to changes in therapy, although negative effects are evident.
A dose reduction or a drug break after six months is also recommended for all other patients. In addition to the spontaneous improvement in symptoms, the physiotherapeutic / physically activating measures carried out in parallel or the psychotherapeutic procedures could also make opioid therapy superfluous. The reduction or withdrawal can lead to withdrawal symptoms; Supportive drug and psychotherapeutic / physiotherapeutic treatments may be necessary.
Are Opioids Indicated for Chronic Neuropathic Pain?
Opioids have been shown to be effective in treating neuropathic pain (9). Most studies so far have been carried out on diabetic polyneuropathy and post-zoster neuralgia, even if the latter disease only has a prevalence of 0.07%. There are no data on all other neuropathic pain syndromes (radiculopathy, multiple sclerosis, etc.) and mixed forms. With a mean study duration of six weeks in the analysis by Sommer et al. (9) In the pooled data from twelve randomized clinical trials, opioids were more pain-relieving than placebo, but had more side effects. Above all, it is unclear whether this also leads to better physical functioning. Unfortunately, there are not enough studies that directly compare opioids with antidepressants or anticonvulsants. It is therefore difficult to distinguish between first-line and second-line therapy. A multifactorial evaluation that carefully weighs the benefits and risks makes more sense as long as there are no new studies. In neuropathic pain, too, there is no evidence that a particular opioid is superior to another. In the overall analysis, oxycodone, morphine, tramadol and tapentadol were considered.
Are there differences between the different opioids?
According to analyzes by the health insurance company Barmer GEK, transdermally administered opioids are primarily prescribed in Germany. However, it is unclear whether the effectiveness, tolerability and safety of the opioids differ at all in direct comparisons over four weeks. In a systematic review of this question, the pooled data analysis of an opioid from a sponsor compared with a standard opioid showed no difference in pain reduction, functional improvement, serious adverse events and mortality (10). Transdermal systems did not differ from oral administration in terms of effectiveness, tolerability and safety. The choice of opioid is likely to be related to comorbidities or patient and doctor preferences, but should also include costs.
Are Opioids Better Than Non-Opioids for Non-Cancer Pain?
To answer this question, nine studies were evaluated that compared opioids, depending on the indication, with NSAIDs, flupirtine, antidepressants or antiarrhythmics (11). In terms of pain reduction, functionality, tolerability and safety, opioids were not superior to non-opioids. In this respect there is (so far) no evidence of non-tumor pain requiring opioids. In the treatment of osteoarthritis, NSAIDs were superior to opioids in terms of functionality and tolerability for a short time (4–12 weeks).
In clinical practice, comorbidities that contain a contraindication, specific side effects for the individual patient, previous response to certain analgesics and preferences of the patient must also be taken into account. Overall, the study situation should be significantly improved with regard to certain clinical pictures.
Under what conditions is long-term therapy useful?
Long-term use of opioids over twelve weeks has hardly been investigated in clinical studies, if at all. This is in blatant contradiction to the supply situation in Germany and internationally. In a recently published analysis, eleven open-label follow-up studies in patients with low back pain or osteoarthritis pain as well as neuropathic pain were included (3; 6; 12). Only a few patients continued opioid therapy for six months in these long-term studies, but then had a good effect at the same dose. Therefore, only clear responders should be treated with opioids for more than three months. Furthermore, patients should be carefully monitored (see above) and doses of more than 120 mg opioid equivalent should be avoided.
conclusion for practice
- Retarded opioids can be indicated for non-tumor pain.
- Retarded opioids do not exist alone, but only in combination with an accompanying therapy that requires the active cooperation of the patient.
- Therapy goals are adequate pain relief and / or functional improvement.
- There is no evidence that one controlled-release opioid is superior to another or that one dosage form is superior to the other.
- Non-delayed opioids are not indicated for non-tumor pain.
Conflicts of Interest
The author denies a conflict of interest.
1 Katz JA, Swerdloff MA, Brass S D et al .: Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology 2015; 84: 1503-1505.
2 Hauser W, Bernardy K, Maier C: Long-term therapy with opioids for chronic non-tumor-related pain: Systematic overview and meta-analysis of the effectiveness, tolerability and safety in open follow-up studies over at least 26 weeks. Pain 2015; 29: 96-108.
3 Hauser W, Bock F, Engeser P et al .: Recommendations of the updated guideline LONTS: Long-term use of opioids for chronic non-tumor-related pain. Pain 2015; 29: 109-130.
4 Houses W, Klose P, Welsch P et al .: Method report of the updated guideline "Long-term use of opioids for non-tumor-related pain - LONTS". Pain 2015; 29: 8-34.
5 Finnerup NB, Attal N, Haroutounian S et al .: Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162-173.
6 Schaefert R, Welsch P, Klose P et al .: Opioids for chronic osteoarthritis pain Systematic overview and meta-analysis of the efficacy, tolerability and safety in randomized, placebo-controlled studies over at least 4 weeks. Pain 2015; 29: 47-59.
7 Deyo RA, Von Korff M, Duhrkoop D: Opioids for low back pain. BMJ 2015; 350: g6380.
8 Chou R, Turner JA, Devine EB: The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015; 162: 276-286.
9 Sommer C, Welsch P, Klose P: Opioids for chronic neuropathic pain: systematic review and meta-analysis of efficacy, tolerability and safety in randomized, placebo-controlled studies over at least 4 weeks. Pain 2015; 29: 35-46.
10 Lauche R, Klose P, Radbruch L et al .: Opioids for chronic non-tumor pain - are there differences? Systematic overview and meta-analysis of the efficacy, tolerability and safety in randomized direct comparisons of opioids over at least 4 weeks. Pain 2015; 29: 73-84.
11 Welsch P, Sommer C, Schiltenwolf M, Hauser W: Opioids for chronic non-tumor-related pain - are they superior to non-opioid analgesics? Systematic overview and meta-analysis of the efficacy, tolerability and safety in randomized direct comparisons of opioids and non-opioid analgesics over at least 4 weeks. Pain 2015; 29: 85-95.
12 Petzke F, Welsch P, Klose P et al .: Opioids for chronic low back pain: Systematic overview and meta-analysis of efficacy, tolerability and safety in randomized, placebo-controlled studies over at least 4 weeks. Pain 2015; 29: 60-72.
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