P. C. Borchgrevink

Assessment of pain

UNLABELLED Valid and reliable assessment of pain is essential for both clinical trials and effective pain management. The nature of pain makes objective measurement impossible. Acute pain can be reliably assessed, both at rest (important for comfort) and during movement (important for function and risk of postoperative complications), with one-dimensional tools such as numeric rating scales or visual analogue scales. Both these are more powerful in detecting changes in pain intensity than a verbal categorical rating scale. In acute pain trials, assessment of baseline pain must ensure sufficient pain intensity for the trial to detect meaningful treatment effects. Chronic pain assessment and its impact on physical, emotional, and social functions require multidimensional qualitative tools and health-related quality of life instruments. Several disease- and patient-specific functional scales are useful, such as the Western Ontario and MacMaster Universities for osteoarthritis, and several neuropathic pain screening tools. The Initiative on METHODS Measurement, and Pain Assessment in Clinical Trials recommendations for outcome measurements of chronic pain trials are also useful for routine assessment. Cancer pain assessment is complicated by a number of other bodily and mental symptoms such as fatigue and depression, all affecting quality of life. It is noteworthy that quality of life reported by chronic pain patients can be as much affected as that of terminal cancer patients. Any assessment of pain must take into account other factors, such as cognitive impairment or dementia, and assessment tools validated in the specific patient groups being studied.

Clinical pharmacology of methadone for pain.

Background: This topical review addresses methadones pharmacology, its application in malignant and non‐malignant pain conditions, practical issues related to methadone for the treatment of pain and its influence on QTc time.

Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses.

Aim: Defined daily dose (DDD) is the most common measurement unit used in drug consumption studies. The DDD for opioids may not reflect their relative clinical potencies. The aim of this study was to explore whether opioid consumption data may be interpreted differently when adding oral morphine equivalent (OMEQ) dose as a measurement unit compared with using DDD. Methods: The equianalgesic ratio of each opioid relative to morphine was tabulated. Data on opioid consumption expressed in DDD were converted to OMEQs using the equianalgesic ratios. The opioid consumption was compared in three different study settings: clinical data from an opioid switching study, trends within one country and a comparison between countries. Results: Using DDD, the opioid consumption in Norway between 2004–2008 increased of 6.7%, while the increase was 23.6% using OMEQ. While DDD/1000 inhabitants/day showed that Sweden had the highest consumption of opioids among the Nordic countries, OMEQ/1000 inhabitants/day showed that Denmark had the highest consumption. In the switching study DDD indicated a reduction in analgesic dosing and OMEQ an increase when switching from WHO step II to III. Conclusion: OMEQ reflects clinical dosing better than DDD, and can give additional insight into opioid consumption when combined with DDD. Using OMEQ can also lead to different conclusions in opioid consumption studies compared with using DDD alone.

Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: A prospective survey in 300 adult cancer patients

Background:  In order to make treatment decisions physicians should have knowledge about the relations between patient characteristics and drug disposition. Dose, route of administration, gender, age and renal function are reported to influence the serum concentrations of morphine, morphine‐6‐glucurnide (M6G) and morphine‐3‐glucuronide (M3G) during chronic treatment of cancer pain. These factors, however, are not evaluated in studies with a sample size sufficient to explore predictive factors.

Prescription pattern of codeine for non‐malignant pain: a pharmacoepidemiological study from the Norwegian Prescription Database

Background: Opioid prescription for pain relief is increasing. Codeine is the dominating opioid in several European countries, with Norway being among the highest codeine users.

Concomitant medication among persistent opioid users with chronic non-malignant pain

Recent guidelines for opioid treatment of chronic non‐malignant pain discourage co‐medication with benzodiazepines and benzodiazepine‐related hypnotics, whereas co‐medication with non‐opioid analgesics and co‐analgesics may offer a beneficial opioid sparing effect, and is recommended. The aim of this study was to describe 1‐year periodic prevalence of co‐medication with benzodiazepines, benzodiazepine‐related hypnotics, non‐opioid analgesics, co‐analgesics and antidepressants in persistent opioid users with chronic non‐malignant pain.

Differential patterns of opioid use : Defining persistent opioid use in a prescription database.

The aim of this study was to develop definitions to identify persons with clinically different patterns of persistent opioid use based on data from prescription databases.

Long- or short-acting opioids for chronic non-malignant pain? A qualitative systematic review

In selected patients with chronic non‐malignant pain, chronic opioid therapy is indicated. Published guidelines recommend long‐acting over short‐acting opioids in these patients. The aim of this systematic review was to investigate whether long‐acting opioids in chronic non‐malignant pain are superior to short‐acting opioids in pain relief, physical function, sleep quality, quality of life or adverse events. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for relevant trials up to July 2012. Reference lists of included trials and relevant reviews were in addition searched by hand. Of the 1168 identified publications, 6 randomised trials evaluating efficacy and safety filled the criteria for inclusion. None of them found a significantly better pain relief, significantly less consumption of rescue analgesia, improved quality of sleep or improved physical function from long‐acting opioids. None of the trials investigated quality of life. None of the trials investigated adverse events properly nor addiction, tolerance or hyperalgesia. Three trials in healthy volunteers with a recreational drug use, found no difference in abuse potential between long‐ and short‐acting opioids. While long term, comparative data are lacking, there is fair evidence from short‐term trials that long‐acting opioids provide equal pain relief compared with short‐acting opioids. Contrary to several guidelines, there is no evidence supporting long‐acting opioids superiority to short‐acting ones in improving functional outcomes, reducing side effects or addiction.

A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain

Summary Long‐acting dihydrocodeine does not provide better pain relief, less depression, better quality of life, or better sleep quality than short‐acting dihydrocodeine in chronic pain patients. ABSTRACT Guidelines for opioid treatment of chronic non‐malignant pain recommend long‐acting over short‐acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double‐blind, double‐dummy, 8‐week comparison of long‐acting dihydrocodeine tablets (DHC‐Continus) with short‐acting dihydrocodeine tablets in 60 patients with chronic non‐malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine‐paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11‐point numerical rating scale in a 7‐day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health‐related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long‐acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long‐acting opioids.

Patients with problematic opioid use can be weaned from codeine without pain escalation

Background: Brief treatments for chronic non‐malignant pain patients with problematic opioid use are warranted. The aims of the present study were to investigate (1) whether it is possible to withdraw codeine use in such patients with a brief cognitive‐behavioural therapy (CBT), (2) whether this could be done without pain escalation and reduction in quality of life and (3) to explore the effects of codeine reduction on neurocognitive functioning.