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6 THE VICIOUS CIRCLE IN PHARMACOLOGICAL TREATMENT OF SEVERE CHRONIC PAIN uation. An increased awareness among the medical community of how these factors are linked is necessary if effective treatment is to be achieved. Pain relief and tolerability One of the major challenges in the pharmacological treatment of severe chronic pain is to achieve a balance between sufficient pain Professor Joseph Pergolizzi Struggles but stays Drops out - Opioid rotation Low Quality of Life Inefficient Pain Management = higher costs in healthcare system Side effectsInsufficient analgesia Pharmacological treatment Adequate analgesia Analgesic tolerance Still sufficient treatment Dose reduction Dose increase Insufficient analgesia Reason: Low tolerability? Interaction? Polymedication? Reason: Wrong substance? / - dose? Neuropathic pain component? Others? insufficient efficacy acceptable tolerability sufficient efficacy unacceptable tolerability relief (analgesia) and medication tolerability. Insufficient analgesia leads to dose increases in order to achieve satisfactory pain relief. Since classical opioids demonstrate dose-dependent efficacy this results in effective analgesia, but at the same time it increases the risk of side effects. When tolerability then becomes unacceptable or the side effects uncontrollable, physicians or even patients by themselves may reduce the analgesic dose again with the unintentional consequence that analgesic efficacy decreases. This can in turn prompt another increase in the analgesic dose leading to a cyclical pattern of treatment or the so-called Vicious Circle. As a result of the Vicious Circle, patient compliance (i.e. adhering to the recommendations with regard to timing, dosage and frequency of administration) is often poor and the level of patients discontinuing treatment may be high. Non-compliance Evidence of poor patient satisfac- tion and treatment adherence exists among patients with chronic pain. Reviews of clinical trials show that 20 – 30% of patients who receive opioids for chronic non-cancer pain stopped their treatment due to ad- verse events or lack of efficacy in short to mid term treatment (Moore and McQuay, 20051; Kalso, 20042). In reality this level may be much higher, and many patients drop out of opioid therapy in the beginning of the treatment because side effects are experienced and the optimal analgesic effect is not fully achieved. One of the main reasons why the treatment of severe chronic pain re- mains insufficient is the problem caused by the side effects of the drugs used. This is especially true for strong opioids where side ef- fects often limit the effective anal- gesic dosage that can be achieved. Side effects, lack of efficacy and the development of analgesic tolerance can all lead to treatment discontin-