Chronic pain affects around 20% of the general population and can therefore be considered a public health problem. Apart from the issue of pain itself, chronic pain often has far-reaching consequences on an individual’s physical and mental well-being, functioning, and quality of life (QoL). Opioids are narcotic drugs with potent analgesic properties, and these drugs have in modern medical practice become widely used in acute, cancer-related, and chronic non-cancer pain (CNCP) conditions. However, guidelines generally advise against the use of opioids for CNCP because of lack of efficacy regarding improvements in pain intensity, physical functioning, and QoL for patients with CNCP. Furthermore, serious adverse effects may be associated with opioid treatment for both individuals and society, as evidenced by the opioid epidemic in the United States. The overarching aim of this doctoral thesis was to contribute knowledge on how physicians in clinical practice can prescribe opioids in a safer manner.

The problem of pain, opioids, the opioid-treated patient, and the prescriber, are first introduced and detailed. Thereafter, each study is thoroughly described. Paper I and II used quantitative methodology, and Paper III used qualitative methodology. More specifically, Paper I was a cross-sectional, registry-based study on patients referred to specialized pain care at the Pain and Rehabilitation Clinic in Linköping in 2015. Medication data were self-reported and matched with patient-reported outcome measures (PROMs) that were extracted from the Swedish Quality Registry for Pain Rehabilitation. 441 patients had complete medication data and PROMs; 30% used opioids daily and 13% used opioids “as needed”. Daily opioid treatment did not correlate with better PROMs when compared to patients without opioid treatment. Despite some methodological limitations, this study added important prevalence data regarding opioid use in chronic pain patients in Sweden and added to the growing body of knowledge which challenges the notion that opioids lead to improved pain, physical function, or QoL for patients with CNCP.

In Paper II, 25 men and 12 women with head-neck cancer who received adjuvant radiotherapy (RT) were followed for 12 months. When RT-induced mucositis began to subside, opioid tapering was started, and blood samples were drawn at five time points. In men, after opioid tapering began, testosterone and dehydroepiandrosterone sulfate levels increased quickly during the first month and remained relatively constant thereafter. Significant changes in levels of follicle-stimulating hormone (FSH) and prolactin were also seen. In postmenopausal women (n = 10), levels of FSH and luteinizing hormone changed significantly during the study period. Two premenopausal women were presented as case reports which indicated that opioid-induced changes on estradiol were reversed after tapering began. This study indicated that previously known opioid-induced effects on endocrine measures, e.g., opioid-induced hypogonadism, were reversible after opioid tapering was started.

In Paper III, 20 board-certified pain specialists were interviewed digitally, and interviews were transcribed verbatim. Manifest inductive content analysis was used to analyze interviews, and the experiences of pain specialists were summarized in two main categories: Navigating the doctor-patient relationship and Challenges and opportunities when prescribing opioids. The former included communication, conflicts, managing expectations, and the emotional and ethical aspects of opioid prescribing which pain specialists had experienced. The latter included handling complexity and heterogeneity, organizational aspects, and the doctor’s due diligence which was needed when prescribing opioids. This study identified important prescriber needs and opportunities for system-level improvements, such as the issue of sufficient time when prescribing, which would likely support responsible and safer opioid prescribing in health care.

Papers I–III are then synthesized in the thesis discussion, and leaning heavily on the results found in Paper III, the 4T-model (time, team, trust, adjust) is suggested as a simple, theoretical framework to support safe and responsible opioid practices in health care. The 4T-model is presented as a pyramid of basic needs, where each level builds upon each other. It is applicable not only to the individual prescriber but also to the health care systems in which prescribers work. The 4T-model offers the prescriber a flexible approach to assess the potential benefits and risks a patient may experience and be exposed to due to their opioid treatment, respectively. The 4T-model may also support health care systems in identifying which level of the pyramid may be lacking, allowing issues related to opioid prescribing to be addressed, thereby supporting safer opioid prescribing.

In conclusion, Papers I–III indicated that on group-level, opioid efficacy for treating CNCP was lacking, that there were potential benefits to tapering opioids, and that the risks and benefits associated with opioid prescribing required complex assessments to be made by prescribers which may strain the doctor-patient relationship, and that simple system-level changes would likely lead to improved prescribing practices. All in all, this doctoral thesis provides quantitative and qualitative insights into the practice of prescribing opioids in clinical practice, with emphasis on opioid prescribing in a chronic non-cancer pain setting.