Even though clinical pain studies in humans are biased by many confounders they are still considered the gold standard, and the examples we have used in the more basic sections are mainly included to support the bridge from basic science to the clinical situation. Although the data are supported by abundant animal experiments, we have mainly restricted the literature to human studies. The aim of the current review is to highlight differences between opioids from a pharmacological, experimental and clinical point of view. reporting of data spanning from basic research to clinical trials that looks into differences between opioids and the inter-individual response to treatment with these drugs. It is therefore the responsibility of the scientific community to question these data and move towards more evidence based practice, e.g. Hence, reported data have often been of poor quality and may have been biased for marketing purposes. This is likely to be due to solid marketing from the pharmaceutical industry rather than due to scientific knowledge. Opioid prescriptions have increased dramatically over the past 20 years and some opioids have become very popular. The same trend has been seen, for example, in depression which shares many pathogenic mechanisms with pain, where the effect of treatment is markedly increased if the whole spectrum of available drugs is used. In this light it is of major concern that some national recommendations appear to neglect the fact that inter-individual variability in pharmacodynamics and pharmacokinetics results in some patients responding more favourably to one opioid than to another. Hence, both the National Cancer Institute, the American Pain Society, the British Pain Society and The European Association for Palliative Care recommend that several opioids should be available for the clinicians to ensure an optimal and individualized treatment approach. Furthermore, pharmacological, experimental and clinical data support that there are major differences between opioids, and that, for example, switching from one opioid to another results in improvement of symptoms or less side-effects in more than 50% of patients. On the other hand, clinical experience and case reports suggest that on an individual patient level, some patients respond to certain opioids but are intolerant to others. Accordingly, there has been pressure from regulatory authorities to restrict opioid use to the cheapest drugs. Hence, one can speculate that selection of opioids is driven by local traditions in medical practice rather than rational pharmacotherapy. This is illustrated in Table 1 using data from ‘The International Narcotics Control Board’. In fact major variability between consumption of different opioids between countries is seen, even though they share borders and their populations are thought to have the same genetic and cultural background. In head to head comparisons, most studies have failed to show relevant differences between drugs on a population level. Randomized studies provide little evidence that, at equi-analgesic doses, commonly used opioids differ markedly in their side effects. Although opioids have many side effects and their use has been associated with dependence, increasing misuse and mortality, no other strong analgesics can substitute for these drugs. Pain is the most common reason for individuals seeking medical care in the Western World and opioids are increasingly used to treat different types of pain. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs.
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