Such data are difficult to obtain in traditional clinical studies, but are readily available in pharmacoepidemiologic database studies. The study showed that intermittent farnesyltransferase exposure to opioids is a common phenomenon, a finding that has been described previously [18], and that in subjects with intermittent exposure, the dose of opioids remains stable over time. This group potentially includes subjects Inhibitors,research,lifescience,medical with subacute pain, pain exacerbations and chronic pain. The initial

median daily oral morphine equivalent dose was approximately 50 mg. Such doses aligned with those reported in studies performed in chronic pain clinics [19] and in the general population [18]. In the latter study, Von Korff et al described Inhibitors,research,lifescience,medical opioid use in noncancer patients in 2 US health plans. In subjects with no cancer diagnosis and continuous exposure to opioids, the 95th percentile dose rose early, but the mean, 25th, 50th, and 75th percentile doses remained stable for the first 2 years of use then increased. However, over the full eight year course of the study the median dose of 45 mg increased to 130 mg and the 95th percentile dose increased from 142 mg to 210 mg. Seven percent of subjects with no cancer diagnosis received at some point in time Inhibitors,research,lifescience,medical high doses of opioids. The results of the present study are similar to the study by Bercovitch et al in patients receiving palliative care for terminal

illnesses. These authors found that only a small percentage of subjects (approximately 9%) required doses of morphine equivalent to 300 mg or more [16]. The study by Sullivan et al, although not directly assessing the variation Inhibitors,research,lifescience,medical of opioid dose over time, corroborates our findings [2]. In that study, opioid use was characterized in commercially insured and publicly insured populations over a 6-year period. The study found that the cumulative yearly opioid dose increase was due to increases in the number of days supplied rather than the dose per day supplied [2]. The very large number of subjects exposed to Inhibitors,research,lifescience,medical opioids intermittently

permits us to characterize with confidence the dose of opioids over time. On the other hand, only a small number Tryptophan synthase of subjects were continuously exposed to opioids for more than 4 years. Therefore, extrapolating the findings of the study beyond this time period is not recommended. Dose escalation is considered one of the major factors that could curtail the effectiveness of opioids [1,10]. The findings of this study show that dose escalation among commercially insured patients who are prescribed opioids continuously occurred in seven percent of subjects. For most subjects with continuous exposure, dose escalation was seen only after the first 2 years of use. A study in a different population, subjects with back injuries at risk for long term disability continuously exposed to opioids for a year, found a more rapid dose escalation –thirty nine percent of subjects moved to a higher dose category at the last quarter of follow up [20].