Impaired neuropsychological performance in chronic nonmalignant pain patients receiving long-term oral opioid therapy

The study investigated neuropsychological performance in chronic nonmalignant pain patients receiving long-term oral opioid therapy. Forty patients treated solely with regular and stable doses of an oral opioid were compared with 40 healthy volunteers. The patients received daily opioid doses of 15-300 mg of oral morphine (median: 60 mg) or equianalgesic doses of other opioids. The neuropsychological tests consisted of continuous reaction time (CRT), which measured vigilance/attention; finger tapping test (FTT), which measured psychomotor speed; and paced auditory serial addition task (PASAT), which measured working memory. Three months after the study had been carried out, 14 of the controls were retested in order to determine the reliability of the three tests. The patients performed statistically significantly poorer than the controls in all the tests. Significantly positive correlations were found between the PASAT and pain visual analogue scales (VAS). In the retesting of 14 controls, it was found that the tests showed high reliability. Vigilance/attention, psychomotor speed, and working memory were significantly impaired in chronic nonmalignant pain patients. The present study cannot determine which factors influenced the test results, but pain itself seemed to have an arousal effect on working memory.     

Epidural opioid therapy for chronic nonmalignant pain: Critique of current experience

The current use of epidural catheter techniques for nonmalignant pain follow directly from its successful use of treating intractable malignant pain states. Long-term studies are confirming the safety of epidural infusions of morphine and local anesthetics. Limitations of this technique related to technical catheter considerations, neuropathic pain states, and cost considerations are being reevaluated as more information is developed. Epidural infusions in nonmalignant pain may prove their value in prolonged treatments for conditions that may resolve in time. They are also being utilized increasingly as screening tools prior to implanting permanent infusion pump systems.     

Intraspinal opioid therapy for chronic nonmalignant pain: Current practice and clinical guidelines

The multidimensional nature of chronic nonmalignant pain lends itself to numerous treatment options, which vary in cost and invasiveness. Based on the principle that use invasive and less costly interventions for pain treatment should be attempted first, a continuum of interventions for chronic pain states is presented. Although intraspinal opioid therapy is a relatively invasive and costly modality for pain treatment, it has a rational place in the treatment continuum for some chronic nonmalignant pain patients. A through review of the literature, supplemented by clinical experience, provides a foundation for the development of management guidelines.     

Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain

This open-label, multicenter study assessed the efficacy and tolerability of conversion to once-daily OROS hydromorphone from previous opioid agonist therapy in patients with chronic cancer pain. Patients were stabilized on their previous therapy before conversion at a 5:1 ratio of morphine sulfate to hydromorphone hydrochloride. The OROS hydromorphone dose was titrated over 3 - 21 days to achieve effective analgesia and was maintained for up to 14 days. Efficacy was assessed using the Brief Pain Inventory (BPI). Adverse events and vital signs were monitored. Dose stabilization was achieved in 119 of the 127 (94%) patients who received the study medication; in 77%, stabilization was achieved with no titration steps. Mean BPI pain intensity ratings and BPI pain interference scores decreased significantly after OROS hydromorphone treatment compared with pretreatment values. Mean pain-relief level remained stable after conversion and throughout treatment with OROS hydromorphone. Adverse events were as expected for cancer patients receiving opioid agonists. There were no clinically significant changes in vital signs.     

Predictors of self-rated health in patients with chronic nonmalignant pain.

Self-rated health (SRH) is an important outcome measure that has been found to accurately predict mortality, morbidity, function, and psychologic well-being. Chronic nonmalignant pain presents with a pattern that includes low levels of power and high levels of pain, depression, and disability. Differences in SRH may be related to variations within this pattern. The purpose of this analysis was to identify determinants of SRH and test their ability to predict SRH in patients with chronic nonmalignant pain. SRH was measured by response to a single three-option age-comparative question. The Power as Knowing Participation in Change Tool, McGill Pain Questionnaire Short Form, Center for Epidemiological Studies Depression Scale, and Pain Disability Index were used to measure independent variables. Multivariate analysis of variance revealed significant differences (p = .001) between SRH categories on the combined dependent variable. Analysis of variance conducted as a follow-up identified significant differences for power (p < .001) and depression (p = .003), but not for pain or pain-related disability; and discriminant analysis found that power and depression correctly classified patients with 75% accuracy. Findings suggest pain interventions designed to improve mood and provide opportunities for knowing participation may have a greater impact on overall health than those that target only pain and disability.     

Clinician beliefs about opioid use and barriers in chronic nonmalignant pain

A survey of the medical directors of multidisciplinary pain clinics and multidisciplinary pain centers listed in the American Pain Society Pain Facilities Directory was conducted to define those pain specialists' beliefs about the role of opioid analgesia in 14 types of chronic nonmalignant pain. Respondents also reported their perceptions of barriers to their prescribing opioids for chronic nonmalignant pain and what they perceived as barriers to opioid prescribing for chronic nonmalignant pain by other, non-pain specialist clinicians in their communities. The respondents are characterized by demographics, disciplines, specialties, and time in practice. The percentage of time that a pharmacist was available in the pain programs also is reported. There is increasing acceptance of opioids for most of the listed types of chronic nonmalignant pain, but the acceptance varies by types of pain syndromes. Opioids were most consistently accepted for sickle cell disease pain and least commonly endorsed for headaches, myofascial pain, and fibromyalgia. Factors that may influence clinicians' perceptions about opioids are discussed.     

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients

Background

The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients.

Methods

Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents.

Results

Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001).

Conclusions

Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT.

Significance

This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.     

Literacy demands and formatting characteristics of opioid contracts in chronic nonmalignant pain management.

Chronic nonmalignant pain affects a significant number of adults, with many requiring opioid medications to manage their symptoms. Although the content of typical opioid contracts (OCs) has been explored, no studies have examined the literacy demands and formatting characteristics of OCs currently used throughout the United States. We evaluated 162 English-language OCs submitted to us by current American Pain Society members residing in the United States. OCs were evaluated for reading grade level and formatting characteristics. The mean readability of OCs was at grade level 13.8 +/- 1.3 (range = 10-17), whereas the average text point size was 11.0 +/- 1.4 (range = 6-16). Active voice was used exclusively in almost half of OCs (n = 79, 48.8%). Most OCs contained not only sophisticated medical language but multisyllable, nonmedical terms and vocabulary not used in typical everyday conversation. Overall, most OCs reviewed presented information at much too high a reading grade level, and with formatting characteristics that probably would make these documents difficult for the average patient to fully comprehend. PERSPECTIVE: This study indicates that there is a mismatch between the reading demands of most OCs and the actual health literacy skills of American adults. Accordingly, those developing OCs should be cognizant of the actual literacy abilities of their patient population and design and evaluate OCs accordingly.     

Intravenous opioid testing in patients with chronic non-cancer pain.

The clinical use of an intravenous opioid testing can help to predict whether opioids will be beneficial. The determination of individual opioid responsiveness justifies subsequent long-term opioid treatment and is generally recommended. An overview over current testing procedures is given with particular regard to choice of opioid, maximum dose, determination of endpoints and duration of testing and recovery. Remifentanil testing is a new approch and is studied in a randomized placebo-controlled cross-over study in 24 patients suffering from severe non-cancer pain. An ascending infusion of remifentanil and placebo respectively was titrated against endpoints. The testing allowed a disctinction between 11 opioid-responders and 13 non-responders. Complete recovery after end of infusion was rapid with a reach of baseline conditions after 25 min in all patients. Thus the complete remifentanil testing procedure required at utmost 1 h. In conclusion, remifentanil testing offers a more rapid procedure allowing the routine use in an ambulatory setting.     

Multicultural influences on pain medication attitudes and beliefs in patients with nonmalignant chronic pain syndromes.

The objective was to develop an integrated review of quantitative and qualitative research regarding the influence of patients' beliefs and attitudes toward pain medication prescribed for the treatment of nonmalignant chronic pain on use of the pain medication. Studies involving patients at least 18 years old with nonmalignant chronic pain were included. Studies of patients with acquired immune deficiency syndrome, cancer, and acute pain were excluded. Medline, CINAHL, PsychInfo, and Cochrane databases from 1985 to 2005 were searched. Reference lists were screened for relevant articles. Abstracts were screened for compliance with the study criteria, and the articles were obtained for those that met criteria. By using a systematic process, each article was subjected to repeated review and data abstracted to the collection sheets. Evidence tables were created to assist with data review. High levels of concern positively correlate with nonadherence, preconceived ideas about when the drug should start working can cause the patient to discontinue it before it begins to work, and patients may perceive that if medication is taken on a regular basis to control pain it may not be effective in the future if the pain increases. Research also showed that if patients perceived the benefits of taking the pain medication to be high, they were willing to risk the side effects.     

Opioids for chronic nonmalignant pain. Choosing suitable candidates for long-term therapy

Opioid maintenance analgesia for chronic nonmalignant pain can be successful in selected cases, but it is not a panacea for all pain, and management of patients using opioids can be an arduous process. A consistent and principle-based approach is recommended. Passion and chauvinism exist on both sides of the controversy and should be discouraged.     

Psychological correlates of opioid use in patients with chronic nonmalignant pain: a preliminary test of the downhill spiral hypothesis

There is still controversy surrounding the use of opioid medication for patients with chronic nonmalignant pain. Schofferman has argued that long-term opioid use leads to a "downhill spiral" associated with loss of functional capacity and a corresponding increase in depressed mood. The present study was a retrospective comparison of opioid users vs. non-users to determine whether: (a) users have higher levels of disability, medical visitation, depression, and pain; (b) the behavioral problems associated with opioid use persist after controlling for the influence of other medication; (c) opioid use is in fact a predictor of illness behavior; and (d) higher levels of opioid consumption are associated with higher levels of disability and depression. A consecutive series of 243 patients with nonmalignant pain about to enroll at a tertiary clinic were retrospectively assigned to either an Opioid User (n = 87) or Non-User (n = 156) group. Compared to Non-Users, Opioid Users were more likely to be physically disabled ( P <0.05) and depressed ( P<0.05), as well as more likely to report pain at higher levels (P<0.001) and in more locations ( P<0.05). Despite the appearance of a downhill spiral, we were unable to demonstrate an association between opioid use and any measure of illness behavior after controlling for benzodiazepine use (with the possible exception of domestic disability). Instead, we found that benzodiazepine use was significantly associated with activity level ( P<0.05), medical visitation ( P<0.01), domestic disability ( P<0.01), depression ( P <0.01), and to a lesser degree, disability days (P<0.1). Using somatization as a reference variable, we found that opioid use failed to explain a comparable amount of variance in illness behavior. Finally, there was no evidence that higher levels of opioid use were associated with higher levels of disability or depression.     

Long-term opioid analgesic therapy for severe refractory lumbar spine pain.

OBJECTIVES: To determine the effect of opioid analgesics on pain and function in patients with severe, refractory low back pain and to see if any benefits were sustained long term. DESIGN: Longitudinal evaluation was conducted in two stages. Stage I was an opioid trial, and stage II was long-term treatment. Treated patients were compared with dropouts and trial failures. OUTCOME MEASURES: Pain was measured by the Numerical Rating Scale (NRS) and function was measured by the Oswestry Low Back Disability Score (OSW). Outcomes were evaluated by patient questionnaire and therefore not subject to investigator bias. SETTING: Private office practice. METHODS: Patients were treated for 6-12 weeks with a long-acting or sustained-release opioid. Those who improved significantly were treated long term. The treatment group was compared with dropouts and failures. RESULTS: Thirty-three patients underwent opioid trial. Treatment was discontinued because of intolerable side effects in 5 patients. In the remaining 28, mean NRS improved from 8.6 to 5.9 (p < 0.001), and mean OSW improved from 64 to 54 (p < 0.001). There were 21 patients treated long term (mean, 32 months). NRS improved from 8.45 to 4.90 (p < 0.001), and OSW improved from 64 to 50 (p < 0.001). Two patients returned to work. The changes in pain and function in the treatment group were significantly better than the comparison group. There was no drug diversion, addictive behavior, or organ toxicity. Doses remained stable. CONCLUSION: Long-term opioid analgesic therapy is reasonable treatment for some well-selected patients with refractory low back pain who have failed all other forms of care.     

Problems and concerns of patients receiving chronic opioid therapy for chronic non-cancer pain

The value of chronic opioid therapy (COT) for chronic non-cancer pain (CNCP) patients is determined by a balance of poorly understood benefits and harms. Traditionally, this balance has been framed as the potential for improved pain control versus risks of iatrogenic addiction, drug diversion, and aberrant drug-related behaviors. These potential harms are typically defined from the providers’ perspective. This paper seeks to clarify difficulties with the long-term use of opioids for CNCP from the patients’ perspective. We used the Prescribed Opioids Difficulties Scale (PODS) to assess current problems and concerns attributed to opioid use by 1144 adults receiving COT. Subjects were grouped into low (56.9%), medium (25.6%) and high (17.5%) PODS scorers. Among patients with high PODS scores, 64% were clinically depressed and 78% experienced high levels of pain-related interference with activities, compared to 28% depressed and 60% with high interference with activities among those with low PODS scores. High levels of opioid-related problems and concerns were not explained by differences in pain intensity or persistence. Patients with medium to high PODS scores were often concerned about their ability to control their use of opioid medications, but prior substance abuse diagnoses and receiving excess days supply of opioids were much less common in these patients than depression and pain-related interference with activities. These results suggest two types of potential harm from COT attributed by CNCP patients to opioids: psychosocial problems that are distinct from poor pain control and opioid control concerns that are distinct from opioid misuse or addiction.     

Transdermal fentanyl in patients with chronic, nonmalignant pain: a case study series.

Four cases of patients with chronic, nonmalignant pain who received transdermal fentanyl are presented. These indicate that some patients may benefit from such treatment but also serve to emphasize the importance of careful patient selection and assessment.     

Treatment of nonmalignant chronic pain

Nonmalignant, chronic pain is associated with physical, emotional and financial disability. Recent animal studies have shown that remodeling within the central nervous system causes the physical pathogenesis of chronic pain. This central neural plasticity results in persistent pain after correction of pathology, hyperalgesia, allodynia, and the spread of pain to areas other than those involved with the initial pathology. Patient evaluation and management focus on pain symptoms, functional disabilities, contributory comorbid illnesses, and medication use or overuse. Treatment of chronic pain involves a comprehensive approach using medication and functional rehabilitation. Functional rehabilitation includes patient education, the identification and management of contributing illnesses, the determination of reachable treatment goals and regular reassessment.