Brandly Cole

What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? a structured evidence-based review

DESIGN This is a structured evidence-based review of all available studies on the development of abuse/addiction and aberrant drug-related behaviors (ADRBs) in chronic pain patients (CPPs) with nonmalignant pain on exposure to chronic opioid analgesic therapy (COAT). OBJECTIVES To determine what percentage of CPPs develop abuse/addiction and/or ADRBs on COAT exposure. METHOD Computer and manual literature searches yielded 79 references that addressed this area of study. Twelve of the studies were excluded from detailed review based on exclusion criteria important to this area. Sixty-seven studies were reviewed in detail and sorted according to whether they reported percentages of CPPs developing abuse/addiction or developing ADRBs, or percentages diagnosed with alcohol/illicit drug use as determined by urine toxicology. Study characteristics were abstracted into tabular form, and each report was characterized according to the type of study it represented based on the Agency for Health Care Policy and Research Guidelines. Each study was independently evaluated by two raters according to 12 quality criteria and a quality score calculated. Studies were not utilized in the calculations unless their quality score (utilizing both raters) was greater than 65%. Within each of the above study groupings, the total number of CPPs exposed to opioids on COAT treatment was calculated. Similarly, the total number of CPPs in each grouping demonstrating abuse/addiction, ADRBs, or alcohol/illicit drug use was also calculated. Finally, a percentage for each of these behaviors was calculated in each grouping, utilizing the total number of CPPs exposed to opioids in each grouping. RESULTS All 67 reports had quality scores greater than 65%. For the abuse/addiction grouping there were 24 studies with 2,507 CPPs exposed for a calculated abuse/addiction rate of 3.27%. Within this grouping for those studies that had preselected CPPs for COAT exposure for no previous or current history of abuse/addiction, the percentage of abuse/addiction was calculated at 0.19%. For the ADRB grouping, there were 17 studies with 2,466 CPPs exposed and a calculated ADRB rate of 11.5%. Within this grouping for preselected CPPs (as above), the percentage of ADRBs was calculated at 0.59%. In the urine toxicology grouping, there were five studies (15,442 CPPs exposed). Here, 20.4% of the CPPs had no prescribed opioid in urine and/or a nonprescribed opioid in urine. For five studies (1,965 CPPs exposed), illicit drugs were found in 14.5%. CONCLUSION The results of this evidence-based structured review indicate that COAT exposure will lead to abuse/addiction in a small percentage of CPPs, but a larger percentage will demonstrate ADRBs and illicit drug use. These percentages appear to be much less if CPPs are preselected for the absence of a current or past history of alcohol/illicit drug use or abuse/addiction.

Do Opioids Induce Hyperalgesia in Humans? An Evidence-Based Structured Review

UNLABELLED DESIGN/OBJECTIVES: Consistent rodent evidence indicates that opioid exposure will decrease the rodents pain threshold (ptr). This is termed opioids-induced hyperalgesia (OIH). Currently, the consistency of the evidence for the occurrence of OIH in humans is unclear. This is a structured evidence-based review for all levels of evidence (all studies and case reports) on OIH in humans in order to determine the consistency of this evidence. METHODS Computer and manual literature searches yielded 504 OIH references (human and animal). Of these, 48 remained after application of inclusion/exclusion criteria. These references addressed 10 hypotheses that the OIH literature has utilized to test for the possibility of OIH in humans. These are the following: opioid addicts maintained on opioids will have decreased ptr and/or tolerance; detoxifying opioid addicts from opioids will increase their ptr and/or tolerance; stopping, decreasing, or rotating to a different opioid or detoxifying from an opioid will improve pain and/or allodynia; chronic pain patients(CPPs) placed on opioids will develop decreased ptr and/or tolerance; CPPs on opioids will have decreased ptr and/or tolerance vs CPPs not on opioids; opioid infusion in normal volunteers or CPPs will decrease ptr and/or tolerance; former opioid addicts exposed to opioids will demonstrate a decrease in ptr and/or tolerance; opioid infusion in normal volunteers will increase secondary hyperalgesia as measured by allodynia or hyperalgesia; perioperative opioids will increase postoperative pain and/or opioid requirements; and placement on opioids postsurgery leads to progressive increased intake (acute tolerance). Each report was characterized by the type of study it represented according to the Agency for Health Care Policy and Research (AHCPR) guidelines and independently rated by two raters according to 14 quality criteria with a quality score calculated. For studies under each hypothesis, an average quality score and the percentage of studies supporting the hypothesis was calculated. Finally, for studies under each hypothesis, utilizing AHCPR criteria, a consistency rating was derived based on the percentage score of studies supporting the hypothesis. RESULTS Two studies had quality scores below 65% and were not utilized. Overall, the strongest evidence (consistent, A) came from opioid infusion studies in normal volunteers as measured by secondary hyperalgesia. This evidence was supported by inconsistent evidence (C) from: studies addressing opioid infusions in normal volunteers or CPPs for decreasing ptr and/or tolerance; and studies addressing increases in postop opioid requirements or pain if peri-opioids were utilized. For the other seven hypotheses, there were too few studies to draw a conclusion or the evidence for the hypothesis were case reports or the results of the studies within the hypothesis were not interpretable. CONCLUSIONS There is not sufficient evidence to support or refute the existence of OIH in humans except in the case of normal volunteers receiving opioid infusions. Prospective CPP clinical studies measuring ptrs and tolerances pre- and post-opioid placement with CPP non-opioid control groups are required.

Is chronic pain associated with somatization/hypochondriasis? An evidence-based structured review.

Study Design:  This is an evidence‐based structured review.

What is the evidence for chronic pain being etiologically associated with the DSM-IV category of sleep disorder due to a general medical condition? A structured evidence-based review.

DESIGN This is a structured evidence-based review of all available studies on the relationship between chronic pain and sleep problems as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) category of sleep disorder due to a general medical condition. OBJECTIVES To determine whether chronic pain is etiologically associated with this sleep category. METHODS Computer and manual literature searches yielded 146 references that addressed this area of study. One hundred and five studies were excluded from detailed review based on exclusion criteria detailed by this category of sleep disorders. Forty-one studies were reviewed in detail and sorted according to six natural groupings: multivariate analysis, prospective studies, path analysis, correlation between pain and sleep problems, univariate analysis using comparison groups, and do nonsedating drugs with analgesic properties improve sleep? Study characteristics were abstracted into tabular form and each report was characterized by the type of study it represented according to the Agency for Health Care Policy and Research (AHCPR) guidelines. Each study was independently evaluated by two raters according to 12 quality criteria and an independent quality score was calculated. Studies were not utilized in the calculations unless their quality score (utilizing both raters) was greater than 60%. For each of the above groupings, an average quality score was calculated and a calculation performed as to the percentage of studies that supported the hypothesis that pain is etiologically related to the above DSM-IV category of sleep disorders. Finally, the strength and consistency of the evidence for this hypothesis was rated according to the AHCPR guidelines. RESULTS Of the 41 reports, all had quality scores greater than 60%. In all the above groupings except for multivariate analysis, 100% of the studies supported this hypothesis. In the multivariate analysis grouping, 77.2% of the studies supported this hypothesis. The strength and consistency of this evidence was rated at A (highest possible) for all study groupings except multivariate (B rating) and path analysis where there were too few studies to generate a conclusion. For all the studies combined, 89.7% of the studies supported this hypothesis. This evidence was rated as A: consistent, multiple studies. CONCLUSIONS The results of this evidence-based structured review indicate that for the pain-sleep studies defined by the DSM-IV category of sleep disorder due to a general medical condition,chronic pain may be etiologically related to that sleep problem. However, these results do not preclude this relationship from being bidirectional.

International Headache Society headache diagnostic patterns in pain facility patients

Objective: Previous studies have indicated that many patients with chronic pain (PWCP) referred to pain facilities for the treatment of neck and/or low back pain complain of associated headaches. The purpose of this study was to characterize the nature of these headaches according to International Headache Society (IHS) headache diagnostic criteria. Design: In preparation for this study, a questionnaire that reflected IHS headache diagnostic criteria was developed. All consecutive patients admitted to our pain facility complaining of headache completed this questionnaire and received a physical and neurologic examination focused on key aspects of headache. A headache interview was also conducted, using the questionnaire as a question guide. All questionnaires were entered in a computerized database, and IHS diagnoses were arrived at for each patient. As many IHS diagnoses as possible were assigned to each PWCP as long as IHS criteria were fulfilled. In addition, a frequency distribution for headache precipitants and neck-associated symptoms was developed and evaluated by discriminant analysis to determine the diagnostic value of these factors in relation to each IHS diagnostic group. Setting: Pain facility (multidisciplinary pain center). Patients: Consecutive PWCP. Results: Of 1,466 PWCP, 154 (10.5%) were identified as suffering from severe headache interfering with function. Of these, 55.8% indicated that their headaches were related to an injury for which they were seeking treatment and 83.7% had neck pain. Migraine headache represented the most common diagnostic group (90.3%), with cervicogenic headache representing the second most common (33.8%). Of the total group, 44.2% had more than one headache diagnosis, that is, there was overlap. Cervicogenic headache patients had the greatest percentage of overlap (94.2%), with migraine patients being second (68.3%). The most frequent headache precipitant was mental stress, followed by neck position and activity/exercise. The migraine and cervicogenic headache groups had a statistically significant greater number of neck-associated symptoms when compared with the remaining patients. Of the total headache group, 74.6% complained that they had a tender point at the back of their neck. Cervicogenic, migraine, and tension PWCP had the greatest frequency of head or neck tender points. The discriminant analysis for neck-associated symptoms yielded the following symptoms as the most common predictors of headache across IHS diagnostic groups: clues to onset were severe headache beginning at the neck or tender point and numbness in arms and legs; headache brought on by neck position and arms overhead; and neck symptoms consisting of a tender point in the neck and feeling severe headache in the neck. Conclusions: Headache can and should be considered a frequent comorbid condition in PWCP. Because of the overlap data, more precise diagnostic criteria may be required to separate cervicogenic headache from migraine headache. Neck-associated symptoms seem to be important even to those PWCP diagnosed with migraine headache.

What Is the Evidence that Neuropathic Pain Is Present in Chronic Low Back Pain and Soft Tissue Syndromes? An Evidence‐Based Structured Review

OBJECTIVES The objectives of this evidence-based review were to review the evidence for whether neuropathic pain (NP) is associated with chronic low back pain (CLBP) and soft tissue syndromes (STS), and review the reported prevalence percentages for NP within these syndromes. METHODS Of 816 reports, 11 addressed the diagnosis of NP in CLBP and five of NP in STS. Studies were grouped by the method of arrival at an NP diagnosis, e.g., physical examination, type of NP inventory utilized, etc. The reported prevalence of NP was determined by aggregating all the patients in all the studies in each grouping. Similarly, the reported prevalence of NP within CLBP and STS was determined by aggregating all the patients with NP from all the studies in those groups. Each study was independently rated by two raters according to 11 quality criteria generating a quality score. The strength and consistency (SAC) of the evidence represented by each grouping was rated according to Agency for Health Care Policy and Research guidelines. RESULTS In each grouping, 100% of the studies reported some prevalence of NP (none reported zero prevalence). Aggregated NP prevalence for CLBP was 36.6% (SAC level A [consistent multiple studies]) and for STS 41.1% (SAC level A). There was significant variation in prevalence according to the method utilized to diagnose NP. CONCLUSION There is consistent evidence by all methods that NP is present in CLBP and STS. Reported prevalence percentages by all methods are substantial. This has significant implications for the treatment of CLBP and STS.

Does smoking status affect multidisciplinary pain facility treatment outcome

OBJECTIVES Smoking may be a major problem in chronic low back pain (LBP) patients. The goal of this study was to determine whether smoking status affected multidisciplinary pain facility treatment outcome. DESIGN As part of a grant study, chronic LBP patients identified themselves as either current smokers (N = 81) or current nonsmokers (N = 140), and were compared by chi-square for employment status at 1, 6, 12, and 24 months after multidisciplinary pain facility treatment. Smokers who were unemployed at each time interval were then compared with employed smokers for a large number of assessment scales and clinical variables of interest by chi-square or Students t-test. The significant independent variables from these analyses were then utilized in a logistic regression to determine predictors for smoker nonemployment. SETTING Pain facility. RESULTS Current smokers were less likely to be employed at each follow-up time point. Pain levels over the previous 24 hours predicted employment status for current smokers at 1-, 12-, and 24-month follow-up, while worker compensation status predicted employment status at 6 months. CONCLUSIONS Current smoking status appears to be associated with poorer treatment outcome after multidisciplinary pain facility treatment. Return to work within smokers is predicted by pain and worker compensation status. Pain facilities should target current smokers with significant perceived pain for close treatment monitoring in an attempt to improve treatment outcome.

Are Chronic Low Back Pain Patients Who Smoke at Greater Risk for Suicide Ideation

OBJECTIVES There is significant psychiatric literature indicating that smoking is associated with all forms of suicidality, including suicide ideation. The goal of this study was to determine if smoking is associated with suicide ideation in chronic low back pain (CLBP) patients. DESIGN CLBP patients identified themselves as either current smokers (N = 81) or nonsmokers (N = 140) and completed a number of evaluation instruments, which included the Beck Depression Inventory (BDI) and the Coping Strategies Questionnaire (CSQ). BDI question number 9 was utilized to define CLBP with suicide ideation and subsequently, in addition, items number 3 and number 6 from the CSQ were added to the BDI item number 9 in order to fully capture CLBP with suicide ideation. Utilizing this expanded definition of suicide ideation (BDI plus CSQ), CLBP smokers were compared with CLBP nonsmokers for the frequency of suicide ideation. Regression analysis was utilized to investigate the CLBP smoking suicide ideation group. Finally, we investigated whether heavy use of alcohol and coffee impacted on CLBP heavy smokers in terms of increasing suicide ideation risk. SETTING CLBP patients were recruited from a pain facility. RESULTS CLBP smokers were more likely to complain of suicide ideation, and this relationship correlated with the number of cigarettes smoked per day. Seventy-eight percent of the CLBP smokers were classified correctly in terms of the presence of suicide ideation by three variables: diagnosis of major depression, Function Assessment Questionnaire total score, and BDI total score. The relative risk of suicide ideation was increased by combining heavy smoking (greater than one pack per day) with heavy alcohol use. CONCLUSIONS CLBP smokers appear to be at greater risk for suicide ideation than nonsmoking CLBP patients. The risk of suicide ideation is even greater if the CLBP patient is a heavy smoker and has problems with alcohol.

Is Smoking Associated with Alcohol-Drug Dependence in Patients with Pain and Chronic Pain Patients? An Evidence-Based Structured Review

OBJECTIVE The objective of this study was to determine if there is consistent evidence for smoking to be considered a red flag for development of opioid dependence during opioid exposure in patients with pain and chronic pain patients (CPPs). METHODS Six hundred and twenty-three references were found that addressed the areas of smoking, pain, and drug-alcohol dependence. Fifteen studies remained after exclusion criteria were applied and sorted into four groupings addressing four hypotheses: patients with pain and CPPs who smoke are more likely than their nonsmoking counterparts to use opioids, require higher opioid doses, be drug-alcohol dependent, and demonstrate aberrant drug-taking behaviors (ADTBs). Each study was characterized by the type of study it represented according to the Agency for Health Care Policy and Research (AHCPR) guidelines and independently rated by two raters according to 13 quality criteria to generate a quality score. The percentage of studies in each grouping supporting/not supporting each hypothesis was calculated. The strength and consistency of the evidence in each grouping was rated by the AHCPR guidelines. RESULTS In each grouping, 100% of the studies supported the hypothesis for that grouping. The strength and consistency of the evidence was rated as A (consistent multiple studies) for the first hypothesis and as B (generally consistent) for the other. CONCLUSIONS There is limited consistent indirect evidence that smoking status in patients with pain and CPPs is associated with alcohol-drug and opioid dependence. Smoking status could be a red flag for opioid-dependence development on opioid exposure.

Modafinil for the treatment of pain-associated fatigue: review and case report.

Fatigue is a symptom that is frequently found in chronic pain patients with low back pain and/or neck pain. At the present time, no specific psychopharmacological treatment for this problem has been identified. Modafinil is a wakefulness-promoting agent that the FDA has approved for the treatment of excessive daytime sleepiness associated with narcolepsy. There have been reports on the use of modafinil for the treatment of fatigue in various neurological syndromes. This literature is reviewed. As such, modafinil treatment was initiated for a patient with severe fatigue associated with chronic low back pain and neck pain. There was dramatic improvement in fatigue and associated function. This case is described. It is the first such case report in the literature. The significance of this finding to the treatment of pain-associated fatigue is discussed.