Prevalence and associated factors of the use of opioids in the treatment of chronic non-cancer pain. Perspective of the general Spanish population and the experience of patients.

Aims The general aim of this thesis was to study the situation of opioid treatments for chronic noncancer pain (CNCP). The specific aims were: first, to determine and synthesize the prevalence of the therapeutic use of opioids in patients with CNCP, and to analyze the factors associated with their use through a systematic review of the literature and a meta-analysis; second, to investigate the evolution of opioid-related mortality and potential years of life lost in the general population in Spain from 2008 to 2017 and to compare the results by gender and age with the United States; third, to describe the current perspective of the Spanish population toward opioid use in the treatment of pain and to identify groups of individuals based on their point of view on these drugs; and finally, to explore the experiences of patients with chronic non-malignant low back pain in Spain undergoing long-term treatment (>3 months) with opioids. Methods In the first study of the thesis, a systematic review of the current literature and meta-analysis were performed using two databases (PubMed and SCOPUS). For this purpose, original crosssectional studies published in English or Spanish between 2009 and 2019 with the main objective of determining the prevalence of opioid use in CNCP patients were included. Search terms and search strategies were adapted to each database. The articles included in the meta-analysis were stratified according to the source of the sample, the type of pain, and the duration of the opioid treatment. The second paper of the thesis is a descriptive study using retrospective annual data from 2008 to 2017 in the general population of Spain and the United States. Information on the population and opioid-related deaths stratified by age and sex was obtained from the Spanish National Statistics Institute and from the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death Database, according to the ICD-10 codes. Years of life lost, crude and standardized mortality rates were calculated and compared with the results in US. The third article included in the thesis is a cross-sectional study carried out on a nationwide representative sample of 1,299 Spanish adults. Data and information about beliefs, knowledge, fears, opinions and, attitudes towards the use of opioids were collected via a computer assisted telephone interview (CATI). A descriptive analysis of the variables studied and a cluster analysis were performed to identify groups of people based on these parameters. In addition, a 18 ABSTRACT. 18 multinomial logistic regression model was developed to analyze the variables related to the clusters. Finally, in the last part of the thesis, a qualitative study was performed using semi-structured interviews. Recruitment and data collection were conducted from April to October 2018. Fifteen participants were recruited from the Pain Clinic in Hospital Puerta del Mar. Inclusion criteria for the study were: adults suffering from chronic non-malignant low back pain and receiving longterm treatment (>3 months) with opioids. We conducted interviews until very similar experiences were described in the last interviews as in the previous ones. A constructionist perspective was adopted. The interviews were analyzed by the qualitative content method described by Graneheim and Lundman, and developed categories and themes discussed in the light biomedicalization theoretical framework. Results In the first article, we identified that of the 1062 potential articles found in the systematic review, 23 studies fulfilled the inclusion criteria. In the general population, the prevalence of long-term (>3 months) opioid use was 2.3% (95%CI:1.5%-3.6%), the prevalence of short-term opioid use was 7.3% (95%CI:4.3%-11.9%), and 5.8% among people with chronic low back pain (95% CI:0.5% - 45.5%). The prevalence of opioid use among patients from the health records or medical surveys was 41% (95%CI:23.3%-61.3%). Finally, in patients with musculoskeletal pain, the prevalence was 20.5% (95%CI:12.9%-30.9%) and 24.5% among patients with fibromyalgia (95%CI:22.9%-26.2%). A higher prevalence of opioid use was observed among the following groups: men; younger people; patients receiving prescriptions of different types of drugs; smokers and patients without insurance or with non-commercial insurance. In addition, nonwhite and Asian patients were less likely to receive opioids than non-Hispanic white patients. The results of the second study showed that the crude rate of opioid-related deaths per 10^5 inhabitants has changed from 1.68 in 2008 to 2.25 in 2017 in Spain, with around 30,000 years of life lost per year. The most affected groups were middle-aged men and women over 65, and the main cause of death was accidental poisoning. The standardized rates per 10^5 inhabitants across the years were between 1.19 and 1.62 in Spain and between 11.17 and 20.68 in the US population. 19 ABSTRACT. 19 In the analysis of the beliefs, fears, opinions and attitude towards opioids analyzed in the third article in the general Spanish population, three groups of subjects were identified: a group with a positive point of view (N=448) composed of people >65 years who would accept a treatment if prescribed and were less fearful of these drugs; a group with a moderate point of view (N=337) formed of younger subjects with university education, and who were better informed about opioids, afraid of these drugs (OR=2.67), and more frequently associated them with drowsiness (OR=2.58), nausea (OR=3.04), and tolerance (OR=2.16); a third group with a negative point of view (N=468), with a lower educational level who would more often reject treatment with opioids, and were more afraid of them (OR=3.95), considering that they may not be able to stop the treatment (OR=3.04) and that the opioids may produce tolerance (OR=3.03). Finally, in the analysis of the experiences of people with chronic pain (CP) taking opioids, described in the fourth article, we developed one overarching theme - living with opioids: dependence and autonomy while seeking relief - which crosscut three categories: 1) The long pathway to opioids due to the invisibility of pain, 2) Opioids: from blind date to a long-term relationship and 3) What opioids cannot fix. The results show that the long and difficult process to obtain effective treatment was a fundamental part of the struggle to cope with pain, involving long-term relationships with the health system. The two first categories refer to the journey participants made to get a diagnosis and treatment with opioids, and their experiences during this long and difficult process, which was quite unique for each person. The third category describes the circumstances and situations experienced by the patients before and after the painful episode started, and how these influenced the whole process. Conclusions The results obtained in the different studies lead to the following conclusions: - The prevalence of opioid use in patients with CNCP varies depending on the duration of treatment and the population analyzed, with higher prevalence in clinical studies based on health registries and occasional users. Age, race, and the access to the health service delivery system and its characteristics are the factors most related to the use of opioids. - Regarding opioid-related mortality, an opioid overuse crisis does not seem a likely scenario in Spain. However, it is a social problem that requires special health surveillance, particularly in middle-aged men and women over 65. 20 ABSTRACT. 20 - The different perspectives of patients regarding the use of opioids to treat pain should be taken into consideration by physicians when designing strategies to inform patients about the treatment of pain with opioids. This should promote their correct use, and prevent their misuse in particular. - The experiences of patients should be considered to a greater extent by healthcare professionals when giving information about opioids and setting treatment goals. Greater consideration of the social determinants of health that affect chronic pain experiences might lead to more effective solutions to chronic pain