Long-Term Opioid Therapy in Chronic Non-Cancer Pain: Risks and Benefits

The Time Line Follow-Back (TLFB) Structured interview, calendar format, using 4 week intervals starting with the most recent complete week, week 1, working backward one week at a time recording days of use for each opioid.

Self report. The Brief Pain Inventory. Pain severity is measured with 4 items where worst, least, average, and current pain during the past week are scored. Each scale ranges from 0-10, where 0 = 'no pain' and 10 = 'pain as bad as can be'.

Pain interference is measured with 7 items measuring how pain have interfered with the respondent's general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life during the last 24 ours. Each scale ranges from 0-10, where 0 = 'Does not interfere' and 10 = 'Interferes completely'.

Higher scores indicate more pain severity and pain interference.

Self report. The EuroQoL - Five dimension (EQ-5D-5L). The five dimensions are: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each with five levels of functioning: "1=no problems," "2=slight problems," "3=moderate problems," "4=severe problems," and "5=unable to"/ "extreme problems" for all dimensions that describe unique health states.The health states can be converted into index scores derived from population-based studies, that ranges from states worse than dead (<0) to 1 (full health), anchoring dead at 0.The EQ-5D questionnaire also includes a visual analog scale where perceived health status is rated with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).

Self report: Patient Health Questionnaire - 9 (PHQ-9), Swedish version. 9 items ranging from 0 ='not at all', to 3 ='almost every day'. 1 item ranging from 0 ='no difficulties, to 3 = 'extreme difficulties'. The first 9 items are summed to a sum score ranging from 0 to 27, where: 0-4 = no signs of depression, 5-9 = mild depression, 10-14 = moderate depression, 15-19 = moderately severe depression, 20-27 = severe depression. Item 10 is reported as a single item where high scores indicate high interference with daily function.

Self report: Generalised Anxiety Disorder (GAD-7). 7 items ranging from 0 ='not at all', to 3 ='almost every day'. 1 item ranging from 0 ='no difficulties, to 3 = 'extreme difficulties'. 1 item ranging from 0 ='not at all, to 3 = 'very disturbing'. The first 7 items are summed to a sum score ranging from 0 to 21, where: 0-4 = no signs of anxiety, 5-9 = mild GAD, 10-14 = moderate GAD, 15-21 = severe GAD. Item 8 is reported as a single item where higher score means higher interference.

Self-report: The insomnia severity index (ISI) The ISI comprises 7 items that assess current (i.e., preceding 2 weeks) sleep problems. The first three items evaluate the severity of sleep onset, sleep maintenance, and early morning awakening problems. Subsequent items assess current sleep problem, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and amount of worry due to the current sleep problem. Items are rated on a five-point Likert scale ('0' representing none or not at all and '4' representing very much). Total scores range from 0 to 28, with higher combined scores indicating worse insomnia severity.

The Pain Self-Efficacy Questionnaire 2 (PSEQ-2), comprises 2 items that asses the participants beliefs about their ability to accomplish activities despite their pain: 'I can do some form of work, despite the pain. ("work" includes housework,paid and unpaid work)', and 'I can live a normal lifestyle, despite the pain'. Items are rated on a seven-point Likert scale ('0' not confident at all '6' Completelt confident). Total scores range from 0 to 12, with higher combined scores indicating stronger self-efficacy beliefs.

Self report: Injustice Experience Questionnaire (IEQ), Swedish version. IEQ measure the degree of experienced injustice following an injury. Respondents are asked to indicate on a five-point scale, ranging from 0 ='never, to 4 ='all the time'. The total score is calculated by adding the scores of each item. A total score is computed by summing the scores to all 12 items, ranging from 0-48 where higher scores indicate higher experience of injustice.

Self report, The Tampa Scale of Kinesiophobia-11 (TSK-11), Swedish version. 11 items ranging from 1 to 4 where 1 = 'does not agree at all', 4 = 'totally agree'. A total score is calculated ranging from 11 to 44 where higher scores indicate higher fear of movement/kinesiophobia.

Self report, self-administered form. The Pain Catastrophizing Scale (PCS) - Swedish version. 13 items, ranging from 0 to 4 where 0 = 'not at all', 4 = 'all the time'. A total score is calculated ranging from 0 to 52 where higher scores indicate higher catastrophizing.

Self-report. The Lifestyle questionnaire by the Swedish National Board of Health. Assesses physical activity and sedentary (duration in minutes and intensity), tobacco use (any use, tobacco cessation= stopped using> 6 month ago or stopped< than 6 months, and amount), diet (eating vegetables, fruit/berries, fish or shellfish, and candy/cookies; twice/day, once/day, couple of times/week, once/week, couple of times/month or less. Breakfast; every day, almost every day, few days/week, one/week or less) and alcohol use (any use, occasions/week and amount).

Self report: Alcohol Use Disorder Identification Test (AUDIT) Swedish version, a 10-item measure of past-year harmful and hazardous alcohol use. The AUDIT addresses three conceptual domains: alcohol consumption (three items), alcohol-related problems (four items), and adverse psychological reactions (three items). The first 8 items are scored on a 5-point scale ranging from 0 to 4, and the last two are scored on a 3-point scale with values 0, 2, and 4. The total score ranges from 0-40 with cut-off values of 8 and 6 points for men and women respectively indicate hazardous alcohol use and a score of ≥19, indicates alcohol-related problems including dependence.

Self report. The Drug Use Disorder Identification test (DUDIT) Swedish version,an 11-item screening instrument developed to identify non-alcohol drug use patterns and drug-related problems. The first nine items are scored on a 5-point scale ranging from 0 to 4, and the last two are scored on a 3-point scale with values 0, 2, and 4. Thus, scores range from 0-44 with higher scores indicating a more severe drug problem, with cut-off values of 4 and 2 points for men and women respectively indicate hazardous drug use.

International classification of disease (ICD-11).

Self report. Swedish universities scale of personality (SSP), an instrument developed to measure personality traits intended to be markers for various neurobiological processes related to vulnerability to mental illness. It consists of 91 items that generates 13 different scales. For all items the respondent fill in one of four possible answer alter; not true at all, does not match particularly well, agree somewhat, exactly right. Each of the 13 scales represent relevant personality aspects and are as follow; Somatic trait anxiety (STA), Psychic trait anxiety (PsTA), Stress susceptibility (SS), Lack of assertiveness (LA), Detachment (D), Embitterment (E), Mistrust (M), Physical trait aggression (PhTA), Verbal trait aggression (VTA), Adventure seeking (AS), Impulsiveness (I), Social desirability (SD), and Trait irritability (TI). SSP has also been factor-analysed into three major dimensions, Neuroticism, Aggressiveness and Extraversion.

Self report. ADHD Self-Report Scale (ASRS v.1.1) includes 18 items of recent DSM-IV Criterion A symptoms of adult ADHD. Respondents are asked how often a symptom has occurred over the past 6 months on a scale ranging from 0 to 4 (never, rarely, sometimes, often and very often).

Self-report. the Life Events Checklist (LEC) consists of 16 items inquiring about the experience of 16 different potentially traumatic events (PTE) known to result in PTSD or other posttraumatic difficulties. For each PTE, respondents rate their experience of that event on a 5-point nominal scale (1 = happened to me, 2 = witnessed it, 3 = learned about it, 4 = not sure, and 5 = does not apply).

Physical functional test. 10 meters test of walking

Physical functional test.The Mini Balance Evaluation Systems Test (mini-BESTest) consist of 14 item measuring dynamic balance. Each item is scored on a 3-category ordinal scale from 0 (unable or requiring help to perform) to 2 (normal) with a total score from 0 to 28.

Structured interview: Modified version of the Swedish Mini International Neuropsychiatric Interview, Part J (Substance use). The M.I.N.I (J) assesses eight categories of substances, including both prescribed medications and illicit substances: opioids (heroin and opium as a separate category), stimulants, cocaine, hallucinogens, inhalants, marijuana, and benzodiazepines. The substance use disorder section was modified to assess current as well as life-time drug use, and medical as well as non-medical use. Response format yes/no.

Substance use disorder defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Mild substance use disorder = 2-3 symptoms Moderate substance use disorder= 4-5 symptoms Severe substance use disorder = 6 or more symptoms

Biomarkers will be explored by use of the OLINK (name of brand) panel which enables analysis of 92 inflammation-related protein biomarkers.

Self report. Patient global impression of change (PGIC). The measure reflects participant's beliefs about the efficacy of treatment. The patient rates overall improvement on a 7-point scale where 3 = 'very much improved', 2 = 'much improved', 1 = 'minimally improved', 0 = 'no change', -1 = 'minimally worse', -2 = 'much worse', and -3 ='very much worse'.

Self report. Patient global impression of change (PGIC). The measure reflects participant's beliefs about the efficacy of treatment. The patient rates overall improvement on a 7-point scale where 3 = 'very much improved', 2 = 'much improved', 1 = 'minimally improved', 0 = 'no change', -1 = 'minimally worse', -2 = 'much worse', and -3 ='very much worse'.

Self report. Patient global impression of change (PGIC). The measure reflects participant's beliefs about the efficacy of treatment. The patient rates overall improvement on a 7-point scale where 3 = 'very much improved', 2 = 'much improved', 1 = 'minimally improved', 0 = 'no change', -1 = 'minimally worse', -2 = 'much worse', and -3 ='very much worse'.

Self report. Patient global impression of change (PGIC). The measure reflects participant's beliefs about the efficacy of treatment. The patient rates overall improvement on a 7-point scale where 3 = 'very much improved', 2 = 'much improved', 1 = 'minimally improved', 0 = 'no change', -1 = 'minimally worse', -2 = 'much worse', and -3 ='very much worse'.

Self report. Patient global impression of change (PGIC). The measure reflects participant's beliefs about the efficacy of treatment. The patient rates overall improvement on a 7-point scale where 3 = 'very much improved', 2 = 'much improved', 1 = 'minimally improved', 0 = 'no change', -1 = 'minimally worse', -2 = 'much worse', and -3 ='very much worse'.