The main findings of this study are that approximately 2 % of the population receives pain-relieving drugs on reimbursable prescriptions because of chronic non-malignant pain and that 0.14 % of the population is given opioids under this scheme. These are low percentages in view of the fact that 24 – 30 % of the Norwegian population reports to have chronic pain (1) – (3) and that over 1 % of the population uses opioids continuously on a long-term basis for other indications than palliative treatment (7).
A large percentage of those prescribed opioids on reimbursable prescriptions have received both short and long-acting opioid formulations and/or benzodiazepines. This is contrary to national guidelines (5, 6). More patients received pain relievers with reimbursement due to non-malignant pain in 2010 than in 2009, but the patterns appear to be stable. The increase may be due to increased awareness of the scheme and to the fact that there was a limited capacity for specialist assessments regarding opioids when that particular reimbursement right was introduced.
This study shows that in 2009/2010 less than 10 % of all those reporting chronic pain received reimbursement for analgesics under the new regulation. This is a significantly lower percentage than was assumed to use analgesics continuously, based on previous studies. In a telephone interview study conducted in Norway as well as a number of other countries, 52 % of those with chronic pain reported that they «currently used prescribed analgesics» (1). A slightly older Norwegian study showed that 43 % of the portion of the population who reported chronic pain used analgesics (3). In an American telephone interview study, 4.9 % of the general population reported having used opioids on at least five days a week for the previous four weeks (14).
While data on how many people use non-opioid analgesics and co-analgesics on a long-term basis is very uncertain, more reliable data has recently become available on how many use opioids continuously. Data from the National Prescription Database has shown that in excess of 1 % of the population receive opioids on a long-term basis because of other indications than palliative treatment (7).
The number receiving reimbursable opioids for chronic non-malignant pain amounts to 0.14 % of the population in our sample. The interpretation of this difference is either that the overwhelming majority of patients who receive opioids for chronic non-malignant pain are not receiving the refund to which they are entitled, or that a high number of patients receive opioids long-term without fulfilling the conditions for reimbursement of the costs of opioids. The former explanation would imply that many patients have an unreasonable and unnecessary financial burden in addition to their pain disorder; the latter would imply a significant social problem with many patients using opioids on a long-term basis without a good medical indication for this. Since we do not have access to clinical data on patients in the National Prescription Database, it is impossible to decide, based on the data in this study, which explanation is the correct one. There is, however, reason to assume that there are few good indications for long-term treatment with opioids where the treatment does not meet the requirements for reimbursement with reimbursement code -71. Individual doctors should therefore carefully assess whether such patients should either receive opioids under the drug reimbursement scheme, or whether opioid treatment should be discontinued. For patients at the end of life there are other drug reimbursement schemes and prescribing of this type was not included in this study. The number of patients receiving reimbursable opioids for palliative treatment was previously 12 000 – 13 000 per year (9).
Non-opioid analgesics must be the first line of treatment for chronic non-malignant pain. This is reflected in this study, with approximately one third of patients who are reimbursed for analgesics receiving paracetamol and one third being reimbursed for NSAIDs. Paracetamol is relatively safe for long-term use, while long-term use of NSAIDs can give rise to side-effects which in some circumstances may be serious, e.g. gastrointestinal bleeding in the elderly and in patients with heart, lung or kidney disease. In this study we found that many had paracetamol and non-steroid anti-inflammatory drugs reimbursed in addition to opioids. This can give an opioid-saving effect but must be carefully weighed against the risk of side-effects of NSAIDs.
The pattern of prescribing also reflects that amitryptiline is a first-line drug for neuropathic pain. A higher percentage of reimbursements for gabapentin compared to pregabalin is presumably due to the requirement that the cheaper drug, gabapentin, must be tried first, while reimbursement for pregabalin is available only on application from individual patients. The number receiving amitryptiline, gabapentin or pregabalin without being given opioids is considerably higher than the number receiving both opioids and one of these drugs. This indicates that opioids are used as supplementary treatment only in a relatively small percentage of patients with neuropathic pain.
For duloxetine and pregabalin, changes to the reimbursement rules may have influenced the pattern of prescribing between 2009 and 2010. In those cases where reimbursement is linked to specific diagnoses, it is possible to speculate whether there is a tendency to make diagnoses that qualify for reimbursement. Patients who receive medium or higher dosages of weak opioids should, according to the guidelines, be switched to a depot formulation of a strong, long-acting opioid. Worthy of mention in this connection is that persons using high doses of tramadol or combining tramadol with certain other medicines have a risk of developing serotonin syndrome.
The increased incidence of dispensing of opioids with increasing age is commensurate with the increased prevalence of painful conditions in the elderly (1, 2). Opioids can have a good effect in the elderly while side-effects such as a tendency to fall and reduced cognitive function mean that the effect and the side-effects must be evaluated carefully.
Of those who receive opioids on reimbursable prescription, four times as many primarily receive long-acting opioids as the number receiving short-acting ones. This indicates that there is a general attempt to follow the guidelines on this point. Nevertheless it is worrying and clearly contrary to the guidelines that there are > 30 % who co-medicate with benzodiazepines and > 50 % who co-medicate with other opioids outside of the reimbursement scheme.
Approximately 10 % of the general population receive opioids in the course of a year, mainly in small quantities (9) and presumably because of acute pain. One would expect that acute conditions would also occur in those using opioids on a regular basis, with an indication for short-term increase in the opioid dosage. However, the very high percentage of patients receiving opioids both with and without reimbursement in the course of a year indicates that many who are reimbursed for long-acting opioids use a short-acting drug in addition, without this being attributable to an acute injury or similar circumstance. This type of use is warned against in the guidelines, and may indicate established problematic opioid use or a risk of developing such. The prevalence of co-medication with other potentially addictive drugs is especially high in the group being reimbursed for large quantities of both short and long-acting opioids, and it can be assumed that both the incidence and risk of developing problematic opioid use is therefore higher here than among the other patients in the study population.
The strength of studies based on the National Prescription Database is that the data material includes all prescriptions dispensed in Norway in the study period and that data is available at the individual level that is not based on self-reporting. The weakness of these types of studies is that it is impossible to know when or whether the medication is used by the recipient. Another disadvantage is that there is no access either to individual data on the use of medication in hospitals or nursing homes. There is therefore an underestimation of both the use and dosage of medications, especially for the elderly and chronically ill.
A weakness of this study is the lack of knowledge of whether those who have received different opioids and opioid formulations in the course of the study period use the different drugs concomitantly, whether they have had a change in their treatment or whether they switch between treatments. The sequence in which the prescriptions are dispensed does not necessarily reflect the sequence in which the medications are used.
Opioids were defined according to ATC code N02A, ATC code N07BC02 (methadone) and ATC code R05DA04 (codeine). The opioids were classified into long-acting and short-acting according to their route of administration. Long-acting opioids were defined as depot tablets, depot capsules, depot plasters and all routes of administration for methadone (tablets and oral solution). Short-acting opioids were defined as tablets, capsules, sublingual tablets, suppositories, transmucosal fentanyl, injection forms, oral solution and nasal spray.
Benzodiazepines were defined according to ATC codes N05BA (anxiolytics), N05CD (hypnotics and sedatives) and N03AE01 (clonazepam). Benzodiazepine-type sleep medications were defined according to ATC code N05CF (benzodiazepine-related medicines). Other pain-relieving medications with reimbursement code -71 which were investigated in this study were gabapentin, pregabalin, carbamazepine, amitryptiline, duloxetine, levomepromazine, paracetamol and NSAIDs. The latter was defined according to ATC code M01A.