Tapering off long-term opioid therapy in chronic non-cancer pain patients: A randomized clinical trial.

BACKGROUND: The indications for initiating long-term opioid treatment (L-TOT) for chronic non-cancer pain (CNCP) are often unclear and associated with problematic use. This study aimed at evaluating the efficacy of stabilizing opioid therapy followed by a sequential opioid tapering off program in CNCP patients. METHODS: A randomized clinical trial with a medications stabilization period (Phase 1) was followed by an opioid tapering off program (Phase 2). In Phase 2, patients were randomized to Control Group (stable treatment) or Taper off Group (sequential opioid dose reduction) and assessed at baseline, after stabilization and up to 6 months. Primary outcomes: measures of cognitive function; secondary outcomes: pain, sleep, rest, quality of life, depression, anxiety, opioid misuse and opioid withdrawal symptoms. RESULTS: In all, 274 patients were screened; 75 were included, out of which 40 dropped out before Phase 2. Those who succeeded Phase 1 (n = 35) had weak/moderate improvements of psychomotor function (p = 0.020), sleeping hours (p = 0.031), opioid withdrawal symptoms (p = 0.019), measures of quality of life (p ≤ 0.043) and opioid misuse scores (p = 0.003). In Phase 2, patients in Taper off Group (n = 15) experienced stable pain intensity and felt significantly more rested at third assessment than the Control Group (n = 20). CONCLUSIONS: The opioid tapering off program was not successful due to the vast number of dropouts. Phase 1 was associated with weak to moderate improvements on psychomotor function, sleeping, opioid withdrawal symptoms, quality of life and reduced risk of opioid misuse. In the intervention group of Phase 2, pain intensity was stable and patients felt more rested. SIGNIFICANCE: This trial showed that sequential tapering off L-TOT in CNCP patients may be an unfeasible approach. However, improvements after opioid treatment stabilization were achieved and stable pain intensity in those tapered off may encourage the development of more refined programs.

Long-term opioid therapy in Denmark: A disappointing journey.

BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.

Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain.

BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried out at a multidisciplinary Danish pain centre. All patients aged 18 or more in treatment at the pain centre on the 1st of September 2013 were invited to participate in the study. RESULTS: A total of 98 patients (65%) participated in the study. The prevalence of current smokers was twice as high as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher doses than never smokers and former smokers not using nicotine. CONCLUSIONS: The study supports previous evidence that smoking is associated with chronic pain. Our data suggest that information about use of nicotine substitution in chronic non-malignant patients are relevant both in a clinical setting, but also in future studies of the association between smoking habits, pain and opioid use.

Chronic non-cancer pain and the epidemic prescription of opioids in the Danish population: trends from 2000 to 2013.

BACKGROUND: Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non-cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD-related drugs in the Danish population. METHODS: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals ≥16 years (response rates: 51-63%). Respondents completed a self-administered questionnaire, which included the analyzed items on identification of chronic pain (≥6 months). RESULTS: From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD-related drugs has decreased from 2010 to 2013, but still one-third of long-term opioid users were co-medicated.

Validation of the Danish-language chronic pain acceptance questionnaire.

BACKGROUND: The Chronic Pain Acceptance Questionnaire (CPAQ, 20 items) measures patients' acceptance of chronic pain. This questionnaire has demonstrated good psychometric qualities and versions have been validated in several different languages. This study describes the validation of the Danish version of the CPAQ. METHODS: A total of 114 patients with chronic pain completed the questionnaire as well as other measures of pain, anxiety, depression, coping, and health-related quality of life. RESULTS: Internal consistency was satisfactory and the factorial analysis yielded a two-factor solution, confirming the original structure of the questionnaire. CONCLUSION: The psychometric properties of the Danish version of the 20-item CPAQ were satisfactory, showing that the Danish version of CPAQ is valid and reliable.

Symptoms and side effects in chronic non-cancer pain patients: clinical implications and development of new assessment tools.

OBJECTIVE: To improve a 41-item screening tool evaluated in our previous study by making it more simple and convenient to patients and at the same time maintain the level of information and the sensitivity. METHODS: In a prospective, two-period questionnaire study, patients suffering from chronic pain of non-cancer origin for more than 6 months, were asked to fill in two questionnaires: QSSE-41 or QSSE-33 and SF-36. The first part of the study (QSSE-41) included an age- and sex-matched control group. RESULTS: A total of 67 patients were included in QSSE-41 and 60 patients in QSSE-33. In QSSE-41, the mean number of symptoms reported by the patient group (12.3) was significantly higher than those reported by the controls (6.8) (P < 0.001). Out of the total number of symptoms, 40.3% were reported to be side effects caused by analgesics, and out of those 61.3% were reported as acceptable and 38.7% as unacceptable side effects. In the QSSE-33, the mean number of symptoms reported by the patient group was 13.6. Out of the total number of symptoms, 46.3% were reported to be side effects caused by analgesics, and out of those 56.4% were reported as acceptable and 43.6% as unacceptable side effects. CONCLUSIONS: This new and shorter screening tool QSSE-33 may substitute the original QSSE-41 and in clinical use, contribute substantially to a more comprehensive and detailed understanding of symptoms/side effects and may consequently lead to improved therapies.

Chronic pain and the development of a symptom checklist: a pilot study.

BACKGROUND: There is currently no instrument to systematically assess the range of symptoms/problems and their bothersomeness in patients with chronic non-cancer pain (CNPN). Systematic assessment and prioritizing may target treatments and improve outcomes. METHODS: The authors developed a checklist of symptoms and problems, the Copenhagen Symptom Checklist (CSC), presented clinically by patients. Fifty-three items representing biological, psychological and social areas were selected. Symptom/problem severity was rated on a 5-point scale anchored at 0 = 'not at all' and 4 = 'severe'. Patients ranked the five most bothersome symptoms/problems and could add five open-ended items. Patients completed the CSC after the first visit at the multidisciplinary pain centre. RESULTS: One hundred and twelve consecutive patients completed the CSC. Eighty-nine percent scored pain as rather severe or very severe (score = 3 plus score = 4), followed by reduction in physical activity (67%), fatigue (66%) and sleep disturbance (53%). Pain and fatigue, but not reduction in physical activity, were given highest priority. Cognitive problems were important to a third of the patients. Depressive symptoms, cognitive problems and worry explained 17.5% of the total variance. Patients filled in the CSC without important loss of information, but a minority prioritized more than three areas or used the free text alternative. CONCLUSIONS: Patients prioritized pain and fatigue as the most burdensome symptoms, but reduction in physical activity and sleep problems were also highly ranked. Patients were positive to the idea of symptom reporting; however, the 53-item number in this version of CSC is larger than may be necessary.

Cognitive function in patients with chronic pain treated with opioids: characteristics and associated factors.

BACKGROUND: The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids. METHODS: In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied. RESULTS: Patients scored poorly in the Trail Making Test-B (mean = 107.6 s, SD = 61.0, cut-off = 91 s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5 h of sleep the night before assessment (P < 0.05). CONCLUSIONS: Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions.

Validation and usefulness of the Danish version of the Pain Medication Questionnaire in opioid-treated chronic pain patients.

BACKGROUND: Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful. METHODS: The Pain Medication Questionnaire (PMQ) was translated into Danish by a 'forward' and 'backward' translation procedure. Patients with chronic non-cancer pain and cancer pain treated at a tertiary pain center were screened for addiction using Portenoy's criteria and invited to answer the Danish version of the PMQ. RESULTS: Two hundred nine patients participated in the study. PMQ was able to discriminate between addicted and non-addicted patients. Patients with high PMQ scores indicating a risk of addiction drank more alcohol, smoked more tobacco, used higher doses of morphine, had a higher anxiety and depression score, and had poorer mental health. Using a cut-off score of 22, the PMQ had a sensitivity of 82%, but the specificity at this cut-point was 56%, indicating a risk of false positive cases. Convergent and discriminant validity were confirmed by correlation with opioid doses, alcohol and tobacco use, anxiety and depression scores, and inverse correlation with mental health and social role. Test-retest showed a very strong correlation. Cronbach's alpha for internal consistency was 0.61. Ten components were found to have eigenvalues above 1.0, confirming the multidimensional structure of the questionnaire. CONCLUSIONS: The PMQ may assist physicians in addiction risk assessment and stratification when treating chronic pain patients with opioids. PMQ is not a diagnostic tool and should only be used as an indicator for possible addiction problems.

Symptoms and side effects in chronic non-cancer pain: patient report vs. systematic assessment.

BACKGROUND: relieving distressing symptoms and managing the side effects of analgesics are essential in order to improve quality of life and functional capacity in chronic non-cancer pain patients. A quick, reliable and valid tool for assessing symptoms and side effects is needed in order to optimize treatment. We aimed to investigate the symptoms reported by chronic non-cancer pain patients after open-ended questioning vs. a systematic assessment using a list of symptoms, and to assess whether the patients could distinguish between the symptoms and the side effects induced by analgesics. METHODS: patients treated with either opioids and/or adjuvant analgesics were asked to report their symptoms spontaneously, followed by a 41-item investigator-developed symptom checklist. A control group also filled in the checklist. RESULTS: a total of 62 patients and 64 controls participated in the study. The numbers of symptoms reported by the patients (9.9 ± 5.9) were significantly higher than those reported by the controls (3.2 ± 3.9) (P<0.001). In the patient group, the number of spontaneously reported symptoms (1.3 ± 1.4) was significantly lower than the symptoms reported when using the symptom checklist (9.9 ± 5.9) (P<0.001). The six most frequently symptoms reported by the patients were: (1) Fatigue; (2) Memory deficits; (3) Dry mouth; (4) Concentration deficits; (5) Sweating; and (6) Weight gain. Out of the six most frequently reported symptoms, the share of side effects due to analgesics was: (1) Dry mouth (42%); (2) Sweating (34%); (3) Weight gain (29%); (4) Memory deficits (24%); (5) Fatigue (19%); and (6) Concentration deficits (19%). CONCLUSION: the number of symptoms reported using systematic assessment was eightfold higher than those reported voluntarily. Fatigue, cognitive dysfunction, dry mouth, sweating and weight gain were the most frequently reported. The patients reported the side effects of their analgesics to contribute substantially to the reported symptoms.

Breakthrough pain in opioid-treated chronic non-malignant pain patients referred to a multidisciplinary pain centre: a preliminary study.

BACKGROUND: Breakthrough pain (BTP) has not formerly been discussed as such in chronic non-malignant pain patients referred to pain centres and clinics. The purpose of the study was to investigate the prevalence, characteristics and mechanisms of BTP in opioid-treated chronic non-malignant pain patients referred to a pain centre and to assess the short-term effects of pain treatment. METHODS: Patients were assessed at referral (T(0)) and after a treatment period of 3 months (T(3)) using the visual analogue scale (VAS) of the brief pain inventory (BPI) within somatic nociceptive, neuropathic and/or visceral pain conditions, the mini mental state examination (MMSE) and the hospital anxiety and depression scale (HADS). The main treatment intervention from T(0) to T(3) was to convert short-acting oral opioids to long-acting oral opioids and to discontinue on demand and parenteral use of opioids. RESULTS: Thirty-three patients were assessed at T(0) and 27 at T(3). The prevalence of BTP declined significantly from T(0) (90%) to T(3) (70.4%). Worst, least, average and current pain intensities as well as duration of BTP were significantly reduced from T(0) to T(3.) The majority of BTPs were exacerbation of background pain assumed to be of the same pain mechanisms. High average pain intensity (BPI) was significantly associated with high scores for both anxiety and depression (HADS). CONCLUSION: BTP in chronic non-malignant pain patients seems to be surprisingly frequent and severe. Stabilizing the opioid regimen seems to reduce pain intensity in general as well as the intensity and duration of BTP. Average pain intensity was associated with anxiety and depression.

Patients' evaluation of shape, size and colour of solid dosage forms.

AIM: The aim of the study was to investigate the swallow ability and the patient preferences of tablets and capsules with different sizes, shapes, surfaces and colours. METHOD: Patients were asked to swallow tablets with different surface and size, while tablets with different shape and colour were visually assessed. They were asked to indicate their preferences. RESULTS: Gelatine capsules were found easier to swallow than tablets and coated tablets were found easier than uncoated normal tablets. The preferred colour was white both for tables and capsules, and the most disliked colours were purple tablets and brown capsules. The preferred shape was strongly arched circular for small tablets, oval for medium sized and big tablets. The difficulty to swallow tablets increased with increasing size. CONCLUSION: According to the results of this study, the ideal tablet is small and white, strongly arched circular and coated. If the amount of drug requires a bigger tablet, the preferred fomat is oblong or oval with a coating. In general capsules were preferred over tablets.

[Sociodemographic predictors of therapeutic results in patients with chronic, non-malignant pain]. / Sociodemografiske praediktorer for behandlingsresultat hos patienter med kroniske, ikke-maligne smertetilstande.

INTRODUCTION: Chronic pain is in its nature multidimensional and is most successfully treated by a multidisciplinary approach. Some patients do not benefit from treatment, and psychological and socio-economic factors may play a major role. The present study investigated the ability of sociodemographic variables to predict the short-term effect of multidisciplinary treatment in patients with chronic pain who where referred consecutively to a Danish multidisciplinary pain centre. METHOD: Pain scores (VAS) and health-related quality of life (HRQL) were assessed. On entry and three and six months later HRQL was evaluated by medical outcome short form (SF-36) and the psychological general well-being scale (PGWB). Sociodemographic variables were: age, gender, educational level, civil status employment status, and disability pension (DP) status. RESULTS: Of the sociodemographic variables evaluated, only the DP status seemed to be a significant outcome predictor. Patients applying for a DP do not improve. Patients receiving a DP and those who do not achieved moderate improvements, but these were significantly larger. The same pattern was seen for changes in psychological well-being and social functioning. The DP status predicted improvement in pain and social functioning. DISCUSSION: The present study indicates that the multidimensional problems experienced by patients applying for a DP are dominated by sociodemographic factors. Focus on the solution of these socio-economic problems is important, if patients with chronic pain are to benefit from multidisciplinary pain treatment.

[Utilization of health care system by patients with chronic pain who apply for disability pensions. A registry study]. / Forbrug af sundhedssystemet hos kroniske smertepatienter der søger førtidspension. En registerundersøgelse.

INTRODUCTION: Patients with chronic pain may be awarded a disability pension if their working capacity is reduced as a result of an illness. Patients with chronic pain very often consult several specialists in order to obtain proof of their illness. The aim of this study was to investigate how an application for disability pension affected the utilization of health care services by patients with chronic pain. METHOD: Patients with chronic pain who applied for a disability pension in 1989 and 1990 were entered. The study period was divided into three: the year preceding the submission of the application for a disability pension, the time from submission of the application to the making of the decision, and the year following the decision of the health authorities. The patients were divided into four subgroups according to whether the disability pension was awarded or rejected, and whether the patients accepted or appealed the decision. The total costs of care in the primary sector were calculated on the number of and charges for visits to GPs and the total costs of hospital care were calculated on the number of bed days, visits to outpatients clinics, operations, and investigations. RESULTS: Patients with chronic pain had a significantly lower health care utilisation after the case has been closed. Those who did not get a disability pension and those who were not satisfied with the level of the disability pension, continued their utilisation of health care after the decision. The mean health care used by patients who appealed the level of the disability pension was three times higher than that used by patients who accepted the level of the disability pension. CONCLUSION: The study indicates that lack of or insufficient economic compensation from the social system in patients with chronic pain may contribute to inexpedient behaviour leading to increased costs to the health care sector.

[Diagnosis and treatment of postoperative nerve damage. Chronic neuropathic pain]. / Diagnose og behandling af perifere nerveskader efter operationer. Kroniske neuropatiske smerter.

Neuropathic pain is caused by lesions in the peripheral and/or central nervous system. Patients with pain due to nerve damage after operations are often misinterpreted and met with suspicion of malingering. Neuropathic pain typically presents with a characteristic set of sensory disorders independent of the cause. The sensory dysfunction may manifest itself as hypo- and/or hyperesthesia to one or more modalities, increased pain to painful stimuli (hyperalgesia) and/or pain to non-painful stimuli (allodynia). Conventional analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs and opioids are often ineffective. Instead, antidepressants and anticonvulsants may be tried. The pain condition is unknown to most physicians. This may result in mistreated patients having undergone several unnecessary and ineffective investigations and treatments.

[Knowledge about amd attitude to postoperative pain therapy of health personnel. A questionnaire survey]. / Sundhedspersonalets viden om og holdning til postoperativ smertebehandling. En spørgeskemaundersøgelse.

From research results published over the last years it appears that many surgical patients are still undertreated for their postoperative pain. The study was performed in order to reveal the attitudes and knowledge of physicians and nurses towards postoperative pain therapy. Questionnaires were sent to physicians and nurses at the surgical and anaesthesiological wards at the hospital. The study revealed that the real purpose of postoperative pain management, to ensure early mobilization and nutrition of the patients, did not receive proper attention. Too many of the house staff accepted that the patients should have moderate or severe pain, especially the younger physicians. The house staff is still concerned about the risk of inducing dependency when using opioids. The knowledge of the analgesics used in the ward is not sufficient and inappropriate methods of administration of opioids are still used. Educational intervention to improve the staff's knowledge about pain management in postoperative care is strongly needed.

[Abuse--of hospital services too]. / Misbrug--også af hospitalsvaesenet.

A 75 year-old man with a well known opioid abuse is described. Within the last 10 years the patient had 161 acute admissions to hospital--in total 942 in-hospital days. The diagnoses were either angina pectoris, low back pain or migraine. With time, the patient had become very skilled in mimicking these three diseases, knowing all subjective and objective signs even better than most of his doctors. In connection with all admissions he received the opioids he wanted. Nevertheless, he was astonished that it was so easy to fool the doctors. It is recommended that the patients' own doctor should be the coordinator and the only person responsible for prescription of opioids to these patients. In case of admissions to hospital, this should only be possible to a few selected departments who know the patient.

Effect of oral calcium on noninvasive indices of bone formation and bone mass in hemodialysis patients: a randomized double-blind placebo-controlled study.

The purpose of this study was to evaluate the effect of high-dose oral calcium on biochemical indices of bone formation, bone bisphosphonate clearance (BBC) and bone mineral content (BMC) of the distal forearm in patients undergoing hemodialysis. Eighteen patients agreed to participate and were randomized in a double-blind manner to receive either 2 g elemental calcium/day (n = 9) or placebo (n = 9) for 6 months. Previous treatment with aluminum-containing phosphate binders was continued unchanged throughout the study. In the placebo group, serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and 10.2%, respectively, while BBC changed significantly by 49.5% (p < 0.05). In the calcium group the opposite was observed with small decreases in alakline phosphatase and osteocalcin by 8.2 and 11.0%, respectively, and no change in BBC. BMC decreased by 5.0% in the placebo group, but increased by 5.2% in the calcium group, resulting in a difference of 10.2% (p < 0.05). The present study demonstrates that high-dose oral calcium tends to reduce bone turnover and seems able to prevent bone loss in hemodialyzed patients.