Olav Fredheim

Increasing use of opioids from 2004 to 2007 – Pharmacoepidemiological data from a complete national prescription database in Norway

Background: A high opioid consumption for cancer related and acute pain may indicate adequate pain treatment. Analysis of a national, compulsory and complete database of all dispensed prescription drugs in Norway (NorPD) may reveal important epidemiological data on prescription pattern of opioids. This study investigated the prevalence of opioid dispensions in 2004–2007 and explored patterns of use.

Chronic non-malignant pain patients report as poor health-related quality of life as palliative cancer patients

Background: Patients with chronic non‐malignant pain (CNMP) conditions are known to report reduced health‐related quality of life (HRQoL). The objective of this exploratory study was to compare HRQoL between patients admitted to a multidisciplinary pain centre, palliative cancer (PC) patients and national norms.

Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study

Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospective study. Primary outcomes were patient preference for opioid and pain control while physical, cognitive and role functioning were secondary outcomes. The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period. During switching and a one-week dose titration period, patients were given additional methadone if required. During dose titration one patient experienced sedation requiring naloxone. Four patients were switched back to morphine due to poor pain control, drowsiness or sweating. Seven patients preferred long-term (>nine months) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved. This study brings novel information on the long-term consequences for pain control, health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain.

Chronic pain and use of opioids: a population-based pharmacoepidemiological study from the Norwegian prescription database and the Nord-Trøndelag health study.

Summary Three quarters of patients using opioids persistently reported strong or very strong pain despite of the medication. ABSTRACT In previous studies on prescription patterns of opioids, accurate data on pain are missing, and previous epidemiological studies of pain lack accurate data on opioid use. The present linkage study, which investigates the relationship between pain and opioid use, is based on accurate individual data from the complete national Norwegian prescription database and the Nord‐Trøndelag health study 3, which includes about 46,000 people. Baseline data were collected in 2006 to 2008, and the cohort was followed up for 3 years. Of 14,477 people who reported chronic nonmalignant pain, 85% did not use opioids at all, 3% used opioids persistently, and 12% used opioids occasionally. Even in the group reporting severe or very severe chronic pain, the number not using opioids (2680) was far higher than the number who used opioids persistently (304). However, three quarters of people using opioids persistently reported strong or very strong pain in spite of the medication. Risk factors for the people with chronic pain who were not persistent opioid users at baseline to use opioids persistently 3 years later were occasional use of opioids, prescription of >100 defined daily doses per year of benzodiazepines, physical inactivity, reports of strong pain intensity, and prescription of drugs from 8 or more Anatomical Therapeutic Chemical groups. The study showed that most people having chronic nonmalignant pain are not using opioids, even if the pain is strong or very strong. However, the vast majority of patients with persistent opioid use report strong or very strong pain in spite of opioid treatment.

To what extent does a cohort of new users of weak opioids develop persistent or probable problematic opioid use

&NA; When opioid therapy is initiated for a new pain condition, it may be unknown whether the pain will persist beyond the time of tissue healing. The aim of this study was to determine the prevalence of prescription patterns indicating persistent and/or problematic opioid use in a cohort of opioid‐naive patients starting therapy with weak opioids. Data were drawn from the nationwide Norwegian Prescription Database. The study population was all new users of opioids receiving prescriptions of a weak opioid in 2005 for nonmalignant pain. This cohort was followed until December 2008. In order to be classified as having probable problematic opioid use, patients had to meet all of the following criteria: received opioids at least once every year from 2005 to 2008 and in 2008; (1) were dispensed more than 365 defined daily doses (DDDs) of opioids; (2) received opioid prescriptions from more than 3 doctors; and (3) were dispensed more than 100 DDDs of benzodiazepines. There were 245,006 persons who were new users of weak opioids in 2005 (216,902 codeine, 26,326 tramadol, 1778 dextropropoxyphene). There were 17,252 (7% of new users) who received a prescription for opioids at least once each of the 3 following years. Of these subjects, 686 patients were dispensed more than 365 DDDs of opioids in 2008 and are probably persistent users. There were 191 subjects who met our criteria for probable problematic opioid use. In a cohort of new opioid users who started treatment with weak opioids, only 0.3% and 0.08% developed prescription patterns indicating persistent opioid use and problematic opioid use, respectively. A national Norwegian cohort of new users of weak opioids was followed from 2005 until 2009; only 0.08% developed problematic opioid use.

A pharmacoepidemiological cohort study of subjects starting strong opioids for nonmalignant pain: A study from the Norwegian Prescription Database

Summary In a complete national cohort of persons starting opioids for chronic nonmalignant pain, only 24% of the cohort received opioids 5 years later. Abstract Clinical studies of short duration have demonstrated that strong opioids improve pain control in selected patients with chronic nonmalignant pain. However, high discontinuation rates and dose escalation during long‐term treatment have been indicated. The aim of the present study was to determine discontinuation rates, dose escalation, and patterns of co‐medication with benzodiazepines. The Norwegian Prescription Database provides complete national data at an individual level on dispensed drugs. A complete national cohort of new users of strong opioids was followed up for 5 years after initiation of therapy with strong opioids. Of the 17,248 persons who were new users of strong opioids in 2005, 7229 were dispensed a second prescription within 70 days and were assumed to be intended long‐term users. A total of 1233 persons in the study cohort were still on opioid therapy 5 years later. This equals 24% of the study cohort who were still alive. Of the participants, 21% decreased their annual opioid dose by 25% or more, whereas 21% kept a stable dose (±24%) and 34% more than doubled their opioid dose from the first to the fifth year. High annual doses of opioids were associated with high annual doses of benzodiazepines at the end of follow‐up. It is an issue of major concern that large dose escalation is common during long‐term treatment, and that that high doses of opioids are associated with high doses of benzodiazepines. These findings make it necessary to question whether the appropriate patient population receives long‐term opioid treatment.

Long term methadone for chronic pain: A pilot study of pharmacokinetic aspects

Methadone is used as an alternative opioid when first line opioids fail to provide adequate pain control. Highly variable morphine:methadone dose ratios make switching challenging and little is known about the pharmacokinetics of long lasting methadone treatment for pain. Twelve patients treated with morphine for chronic non‐malignant pain were switched to methadone. Seven of these patients continued with methadone throughout the nine months study period and only minor dose adjustments were performed. Serum concentrations of morphine, methadone and their metabolites were measured at baseline, day one and two, after dose titration and one week, five weeks, three months and nine months after the end of dose titration. Serum concentrations of methadone and its metabolite EDDP did not change significantly from the end of dose titration and during the nine months (repeated measures ANOVA: p = 0.88 and p = 0.06). Very low correlation between dose ratios and serum concentration ratios between morphine and methadone was observed. Large interindividual differences in serum concentrations and metabolism were observed. Our findings contradict that autoinduction of methadone metabolism takes place during long term treatment and supports that a 3‐day opioid switch from morphine to methadone followed by a one week titration seems pharmacologically sound.

Prevalence of use of non-prescription analgesics in the Norwegian HUNT3 population: Impact of gender, age, exercise and prescription of opioids

BackgroundThere are concerns about potential increasing use of over-the-counter (OTC) analgesics. The aims of this study were to examine 1) the prevalence of self-reported use of OTC analgesics; 2) the prevalence of combining prescription analgesics drugs with OTC analgesics and 3) whether lifestyle factors such as physical activity were associated with prevalence of daily OTC analgesic use.MethodsQuestionnaire data from the Nord–Trøndelag health study (HUNT3, 2006–08), which includes data from 40,000 adult respondents. The questionnaire included questions on use of OTC analgesics, socioeconomic conditions, health related behaviour, symptoms and diseases. Data were linked to individual data from the Norwegian Prescription Database. A logistic regression was used to investigate the association between different factors and daily use of paracetamol and/or non-steroid anti-inflammatory drugs (NSAIDs) in patients with and without chronic pain.ResultsThe prevalence of using OTC analgesics at least once per week in the last month was 47%. Prevalence of paracetamol use was almost 40%, compared to 19% and 8% for NSAIDs and acetylsalicylic acid (ASA), respectively. While the use of NSAIDs decreased and the use of ASA increased with age, paracetamol consumption was unaffected by age. Overall more women used OTC analgesics. About 3-5% of subjects using OTC analgesics appeared to combine these with the same analgesic on prescription. Among subjects reporting chronic pain the prevalence of OTC analgesic use was almost twice as high as among subjects without chronic pain. Subjects with little physical activity had 1.5-4 times greater risk of daily use of OTC compared to physically active subjects.ConclusionsUse of OTC analgesics is prevalent, related to chronic pain, female gender and physical inactivity.

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.

Behandling av postoperativ smerte i sykehus

BACKGROUND Relief of post-operative pain has a bearing on the patients well-being, mobilisation and time confined to bed. The article discusses indications, contraindications and the efficacy of the various treatment modalities. MATERIAL AND METHOD We have examined review articles, meta-analyses and randomised controlled trials, identified through literature searches in PubMed. RESULTS The use of several medicines and techniques (multimodal pain treatment) is necessary to achieve a good balance between pain relief, side effects and risk. Systemic administration of paracetamol, NSAIDs, opioids and glucocorticoids is effective for post-operative pain. The same applies to epidural analgesia, peripheral nerve blocks and local anaesthetic wound infiltration. Subanaesthetic doses of ketamine have an opioid-sparing effect, but the optimal dosing regimen is uncertain. Gabapentinoids have an effect on post-operative pain, but the effect appears to vary depending on the type of operation and analgesic regimen. The effect of one analgesic will depend on which other drugs are used in multimodal pain treatment. Epidural analgesia, peripheral nerve blocks or extensive local infiltration analgesia is often necessary to relieve movement-related pain. INTERPRETATION Many treatment modalities are effective for post-operative pain. It is crucial that the treatment is well organised and that it includes routines for systematic pain assessment, efficacy and side effects of the pain management.