Opioid tolerance and dependence: an inevitable consequence of chronic treatment?

Although opioids provide effective analgesia, largely unsubstantiated concerns about opioid-induced tolerance, physical dependence and addiction have limited their appropriate use. As a consequence, many patients receive inadequate treatment for both malignant and non-malignant pain. However, it has been shown that analgesic tolerance develops less frequently during chronic opioid administration in a clinical context than in animal experiments, and that instituting an appropriate dosing regimen can minimise withdrawal symptoms. Early studies had suggested that addiction might result from chronic opioid therapy, though more recent data indicate a low risk in patients with no history of drug abuse. New treatment regimens may also reduce the risk of tolerance, physical dependence and addiction. Long-acting preparations, such as transdermal fentanyl and possibly some forms of other slow release opioids, which maintain constant opioid concentrations in the plasma, minimise the occurrence of the 'between-dose' symptoms such as withdrawal and opioid-induced euphoria. This review discusses the development of tolerance, physical dependence and addiction during opioid therapy, and the influence of these factors on the choice of treatment.