HHS Public Access Author manuscript Author Manuscript
Pain. Author manuscript; available in PMC 2017 October 01. Published in final edited form as: Pain. 2016 October ; 157(10): 2208–2216. doi:10.1097/j.pain.0000000000000631.
Does Association of Opioid Use with Pain and Function Differ by Fibromyalgia/Widespread Pain Status? Judith A. Turnera,*, Susan M. Shortreedb,c, Kathleen W. Saundersb, Linda LeResched, Stephen Thielkea,e, and Michael Von Korffb a
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA
Author Manuscript
b
Group Health Research Institute, Seattle, Washington, USA
c
Department of Biostatistics, University of Washington, Seattle, Washington, USA
d
Department of Oral Medicine, University of Washington, Seattle, Washington, USA
e
Geriatric Research, Education, and Clinical Center, Puget Sound VA Medical Center, Seattle, Washington, USA
Abstract
Author Manuscript
Many consider chronic opioid therapy (COT) to be ineffective for fibromyalgia, but empirical evidence is limited. Among patients identified as initiating COT, we examined whether fibromyalgia was associated with different relationships of opioid use to pain and activity interference outcomes 12 months later. We obtained electronic data on diagnoses and opioid prescriptions. We obtained patient self-report data, including pain and activity interference measures, at baseline, 4 months, and 12 months. Among 1,218 patients, 429 (35%) met our definition of fibromyalgia. Patients with and without fibromyalgia who had intermittent/lowerdose or regular/higher-dose opioid use at 12 months had similar 12-month pain intensity scores. However, among patients with minimal/no opioid use at 12 months, 12-month pain intensity was greater for those with fibromyalgia (adjusted mean = 5.15 [95% CI = 4.80, 5.51]; 0-10 scale) than for those without (4.44 [4.15, 4.72]). Similar patterns were observed for 12-month activity interference. Among patients who discontinued opioids by 12 months, those with fibromyalgia were more likely to report bothersome side effects and less likely to report pain improvement as important reasons for discontinuation (P-values < 0.05). In sum, at 12 months, among patients who
Author Manuscript
*
Corresponding author. Address: University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences, Box 356560, Seattle, WA 98195, USA; Tel.: +1 206 543-3997; fax: +1 206 685-1139; [email protected] (J. Turner). Conflict of interest statement: The other authors report no conflicts.
List of Supplemental Digital Content Supplemental Digital Content 1. Supplemental Figure 1: Adjusted mean pain intensity at baseline, 4 months, and 12 months for individuals with baseline widespread pain scores at the 75th (A) and 25th (B) percentile by opioid use in the 120 days prior to the 12month assessment. pdf Supplemental Digital Content 2. Supplemental Figure 2: Adjusted mean activity interference at baseline, 4 months, and 12 months for individuals with baseline widespread pain scores at the 75th (A) and 25th (B) percentile by opioid use in the 120 days prior to the 12-month assessment. pdf Supplemental Digital Content 3. Supplemental Table: Association of 12-month characteristic pain intensity and activity interference with opioid use over the prior 120 days by widespread pain score at baseline. pdf
Turner et al.
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Author Manuscript
had discontinued opioids or used them minimally, those with fibromyalgia had worse outcomes and were less likely to have discontinued due to pain improvement. Among patients continuing COT, pain and activity interference outcomes were worse than those of patients with minimal/no opioid use and did not differ for those with fibromyalgia versus those with diverse other chronic pain conditions.
Keywords fibromyalgia; widespread pain; opioids; chronic opioid therapy; chronic pain
1. Introduction Author Manuscript
Although patients with fibromyalgia are often treated with chronic opioid therapy (COT)14,30 and often report it as helpful,1 COT is viewed by many experts as inappropriate for fibromyalgia.6,10,26 This argument is based largely on expert opinion and lack of evidence for efficacy of COT for fibromyalgia rather than on evidence that COT is ineffective or harmful for patients with fibromyalgia.6,26 A recent systematic review concluded that evidence was insufficient regarding whether opioid benefits and harms vary for different pain conditions.7
Author Manuscript
The conceptualization of fibromyalgia is evolving and the diagnosis is controversial.9 Current conceptualizations generally view fibromyalgia as a term for widespread musculoskeletal pain with the following characteristics: (a) no alternative cause can be identified; (b) frequently co-morbid with other chronic pain syndromes lacking specific identifiable causes; and (c) reflecting augmented pain or sensory processing in the central nervous system rather than a pathologic abnormality in the painful region of the body.10 The Modified American College of Rheumatology (ACR) 2011 Fibromyalgia Diagnostic Criteria self-report measure (which assesses pain in multiple body sites, fatigue, cognitive problems, and depression) can be scored dichotomously using cut-points. However, there is increasing appreciation that fibromyalgia is a constellation of symptoms and that an individual's degree of “fibromyalgianess” can be measured on a continuum.10 It has been proposed that higher scores on the ACR 2011 measure predict poor response to opioids.10
Author Manuscript
In parallel with these evolving conceptualizations of fibromyalgia, chronic widespread pain (CWP) is increasingly accepted as a diagnosis in its own right.11 Empirical data regarding meaningful clinical differences and consensus on operational definitions of CWP and fibromyalgia are lacking.4 For both diagnoses, although there are advantages of dichotomous definitions (e.g., in treatment decision-making and epidemiological studies), evidence supports a continuous distribution of the extent of pain in the body and cut-points for classification as arbitrary.11 To address the gap in knowledge concerning possible differential effects of opioids for patients with fibromyalgia or CWP, we used data from the Middle-Aged/Seniors Chronic Opioid Therapy (MASCOT)35 longitudinal study of patients initiating COT for chronic pain. We examined whether the relationships of opioid use to pain and function at 12-month follow-up differed depending on whether the patient had fibromyalgia at baseline. We also Pain. Author manuscript; available in PMC 2017 October 01.
Turner et al.
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Author Manuscript
examined whether these relationships differed according to baseline scores on a continuous patient-reported widespread pain measure. We previously observed worse pain and function outcomes at 12 months among patients who sustained COT as compared with patients who transitioned to minimal or no opioid use.35 For the current study, we hypothesized that the difference in 12-month outcomes for those with continued opioid use versus minimal/no opioid use would be greater for patients with fibromyalgia than for patients without fibromyalgia. In the subgroup of patients who sustained COT, we explored whether selfreported helpfulness of opioids differed by fibromyalgia status. In the subgroup of patients who discontinued opioids, we explored differences in reasons given for discontinuation.
2. Methods 2.1. Study participants, setting, and procedures
Author Manuscript Author Manuscript
We previously described the methods of the MASCOT study.35,40 In brief, study participants were members of Group Health, a large nonprofit healthcare system in Washington State. This study was approved by the Group Health Institutional Review Board and all participants provided informed consent. Participants enrolled in the study between November 1, 2010 and March 5, 2013. Potential study participants were identified from Group Health electronic pharmacy records. We identified patients aged 45 years or older who appeared to have recently started opioid therapy and to be transitioning to long-term use. We operationalized this by identifying patients who, within the past 4 months, had filled an index opioid prescription followed by at least 2 more opioid prescriptions and had at least 60 days’ supply of opioids within the 4-month period. The index prescription had to follow a period of at least 3 months without an opioid prescription fill. Preliminary analyses, conducted prior to enrolling study participants, indicated that about half of patients meeting these criteria would continue opioid use 1 year later. To ensure completeness of administrative data, we excluded patients not enrolled continuously at Group Health in the prior year. We also excluded patients with 2 or more visits for cancer diagnoses (other than non-melanoma skin cancer) in the prior year or receiving hospice or nursing home care. During telephone screening, we excluded patients who said that they had not taken prescription pain relievers on at least 7 days in the previous 2 weeks as well as those unable to speak English, unable to participate in a telephone interview, or planning to disenroll from Group Health in the next year. Trained survey staff conducted computer-assisted telephone interviews with study participants at baseline and again 4 and 12 months later.
Author Manuscript
Among 3,172 Group Health patients mailed MASCOT study invitation letters, 2,808 (89%) were contacted for eligibility screening; among these, 2,125 were not identified as ineligible for the study. Among these 2,125 patients, 1,477 (70%) enrolled and completed the baseline interview. Among the 1,477 MASCOT participants, 38 (3%) participants had missing information on important baseline covariates. Among the 1,439 individuals with relevant baseline information, 1,218 (85%) completed the 12-month interview and had complete data on the outcome and opioid use measures of interest in the current study.
Pain. Author manuscript; available in PMC 2017 October 01.
Turner et al.
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2.2. Measures
Author Manuscript
2.2.1. Independent variables
Author Manuscript
2.2.1.1. Fibromyalgia: We defined presence of fibromyalgia based on physician-assigned diagnostic codes and/or patient self-report. At the time of this study, Group Health physicians used the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)28 to code patient diagnoses at office visits. There is not a specific ICD-9-CM code for fibromyalgia, but 729.1 (myalgia and myositis NOS) was commonly used for fibromyalgia and converts to myositis, unspecified; myalgia; or fibromyalgia in ICD-10-CM. We defined presence of fibromyalgia as (a) assignment of an ICD-9-CM diagnostic code of 729.1 at a visit in the 2 years prior to the baseline interview or (b) patient indication at baseline on a self-report measure of widespread pain bothersomeness (described below) of being ‘bothered a lot’ by ‘widespread pain, pain in most of your body, or fibromyalgia.’ For parsimony, we hereafter refer to this variable as fibromyalgia. 2.2.1.2. Widespread pain score: As a secondary measure, we used the baseline score on a continuous measure ofwidespread pain bothersomeness. Participants used the Patient Health Questionnaire-15 (PHQ-15)21 rating scale to rate how much they had been bothered (not at all [0], a little [1], or a lot [2]) by pain in each of 7 different body sites during the past 4 weeks. The sites included 5 sites from the PHQ-15 (stomach; back; arms, legs, or joints; headaches; chest) plus ‘neck’ and ‘widespread pain, pain in most of your body, or fibromyalgia.’ The score was calculated as the sum of the ratings and could range from 0 to 14, with higher scores indicating more bothersome and widespread pain. For parsimony, we hereafter refer to this as the widespread pain score.
Author Manuscript
2.2.1.3. Opioid use: Because pharmacy records accurately capture information on medication dispensed, but not on how patients use the medication, we defined opioid use with a categorical classification that combined information from pharmacy records and selfreport.35 Using Group Health electronic pharmacy data, we identified prescription opioid medication fills (including information on quantity and strength of medication dispensed, days’ supply, and prescription fill date) in the 120-day period prior to the 12-month interview. We calculated the mean morphine-equivalent dose (MED) per day39 across the 120 days. We classified study participants into the following 3 opioid use groups at 12 months based on a combination of self-reported opioid use in the past 28 days as reported in the 12-month interview and opioid dose over the 120 days prior to the 12-month interview as calculated from pharmacy data:
Author Manuscript
Minimal/no use: Mean daily MED
Pain. Author manuscript; available in PMC 2017 October 01. Published in final edited form as: Pain. 2016 October ; 157(10): 2208–2216. doi:10.1097/j.pain.0000000000000631.
Does Association of Opioid Use with Pain and Function Differ by Fibromyalgia/Widespread Pain Status? Judith A. Turnera,*, Susan M. Shortreedb,c, Kathleen W. Saundersb, Linda LeResched, Stephen Thielkea,e, and Michael Von Korffb a
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA
Author Manuscript
b
Group Health Research Institute, Seattle, Washington, USA
c
Department of Biostatistics, University of Washington, Seattle, Washington, USA
d
Department of Oral Medicine, University of Washington, Seattle, Washington, USA
e
Geriatric Research, Education, and Clinical Center, Puget Sound VA Medical Center, Seattle, Washington, USA
Abstract
Author Manuscript
Many consider chronic opioid therapy (COT) to be ineffective for fibromyalgia, but empirical evidence is limited. Among patients identified as initiating COT, we examined whether fibromyalgia was associated with different relationships of opioid use to pain and activity interference outcomes 12 months later. We obtained electronic data on diagnoses and opioid prescriptions. We obtained patient self-report data, including pain and activity interference measures, at baseline, 4 months, and 12 months. Among 1,218 patients, 429 (35%) met our definition of fibromyalgia. Patients with and without fibromyalgia who had intermittent/lowerdose or regular/higher-dose opioid use at 12 months had similar 12-month pain intensity scores. However, among patients with minimal/no opioid use at 12 months, 12-month pain intensity was greater for those with fibromyalgia (adjusted mean = 5.15 [95% CI = 4.80, 5.51]; 0-10 scale) than for those without (4.44 [4.15, 4.72]). Similar patterns were observed for 12-month activity interference. Among patients who discontinued opioids by 12 months, those with fibromyalgia were more likely to report bothersome side effects and less likely to report pain improvement as important reasons for discontinuation (P-values < 0.05). In sum, at 12 months, among patients who
Author Manuscript
*
Corresponding author. Address: University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences, Box 356560, Seattle, WA 98195, USA; Tel.: +1 206 543-3997; fax: +1 206 685-1139; [email protected] (J. Turner). Conflict of interest statement: The other authors report no conflicts.
List of Supplemental Digital Content Supplemental Digital Content 1. Supplemental Figure 1: Adjusted mean pain intensity at baseline, 4 months, and 12 months for individuals with baseline widespread pain scores at the 75th (A) and 25th (B) percentile by opioid use in the 120 days prior to the 12month assessment. pdf Supplemental Digital Content 2. Supplemental Figure 2: Adjusted mean activity interference at baseline, 4 months, and 12 months for individuals with baseline widespread pain scores at the 75th (A) and 25th (B) percentile by opioid use in the 120 days prior to the 12-month assessment. pdf Supplemental Digital Content 3. Supplemental Table: Association of 12-month characteristic pain intensity and activity interference with opioid use over the prior 120 days by widespread pain score at baseline. pdf
Turner et al.
Page 2
Author Manuscript
had discontinued opioids or used them minimally, those with fibromyalgia had worse outcomes and were less likely to have discontinued due to pain improvement. Among patients continuing COT, pain and activity interference outcomes were worse than those of patients with minimal/no opioid use and did not differ for those with fibromyalgia versus those with diverse other chronic pain conditions.
Keywords fibromyalgia; widespread pain; opioids; chronic opioid therapy; chronic pain
1. Introduction Author Manuscript
Although patients with fibromyalgia are often treated with chronic opioid therapy (COT)14,30 and often report it as helpful,1 COT is viewed by many experts as inappropriate for fibromyalgia.6,10,26 This argument is based largely on expert opinion and lack of evidence for efficacy of COT for fibromyalgia rather than on evidence that COT is ineffective or harmful for patients with fibromyalgia.6,26 A recent systematic review concluded that evidence was insufficient regarding whether opioid benefits and harms vary for different pain conditions.7
Author Manuscript
The conceptualization of fibromyalgia is evolving and the diagnosis is controversial.9 Current conceptualizations generally view fibromyalgia as a term for widespread musculoskeletal pain with the following characteristics: (a) no alternative cause can be identified; (b) frequently co-morbid with other chronic pain syndromes lacking specific identifiable causes; and (c) reflecting augmented pain or sensory processing in the central nervous system rather than a pathologic abnormality in the painful region of the body.10 The Modified American College of Rheumatology (ACR) 2011 Fibromyalgia Diagnostic Criteria self-report measure (which assesses pain in multiple body sites, fatigue, cognitive problems, and depression) can be scored dichotomously using cut-points. However, there is increasing appreciation that fibromyalgia is a constellation of symptoms and that an individual's degree of “fibromyalgianess” can be measured on a continuum.10 It has been proposed that higher scores on the ACR 2011 measure predict poor response to opioids.10
Author Manuscript
In parallel with these evolving conceptualizations of fibromyalgia, chronic widespread pain (CWP) is increasingly accepted as a diagnosis in its own right.11 Empirical data regarding meaningful clinical differences and consensus on operational definitions of CWP and fibromyalgia are lacking.4 For both diagnoses, although there are advantages of dichotomous definitions (e.g., in treatment decision-making and epidemiological studies), evidence supports a continuous distribution of the extent of pain in the body and cut-points for classification as arbitrary.11 To address the gap in knowledge concerning possible differential effects of opioids for patients with fibromyalgia or CWP, we used data from the Middle-Aged/Seniors Chronic Opioid Therapy (MASCOT)35 longitudinal study of patients initiating COT for chronic pain. We examined whether the relationships of opioid use to pain and function at 12-month follow-up differed depending on whether the patient had fibromyalgia at baseline. We also Pain. Author manuscript; available in PMC 2017 October 01.
Turner et al.
Page 3
Author Manuscript
examined whether these relationships differed according to baseline scores on a continuous patient-reported widespread pain measure. We previously observed worse pain and function outcomes at 12 months among patients who sustained COT as compared with patients who transitioned to minimal or no opioid use.35 For the current study, we hypothesized that the difference in 12-month outcomes for those with continued opioid use versus minimal/no opioid use would be greater for patients with fibromyalgia than for patients without fibromyalgia. In the subgroup of patients who sustained COT, we explored whether selfreported helpfulness of opioids differed by fibromyalgia status. In the subgroup of patients who discontinued opioids, we explored differences in reasons given for discontinuation.
2. Methods 2.1. Study participants, setting, and procedures
Author Manuscript Author Manuscript
We previously described the methods of the MASCOT study.35,40 In brief, study participants were members of Group Health, a large nonprofit healthcare system in Washington State. This study was approved by the Group Health Institutional Review Board and all participants provided informed consent. Participants enrolled in the study between November 1, 2010 and March 5, 2013. Potential study participants were identified from Group Health electronic pharmacy records. We identified patients aged 45 years or older who appeared to have recently started opioid therapy and to be transitioning to long-term use. We operationalized this by identifying patients who, within the past 4 months, had filled an index opioid prescription followed by at least 2 more opioid prescriptions and had at least 60 days’ supply of opioids within the 4-month period. The index prescription had to follow a period of at least 3 months without an opioid prescription fill. Preliminary analyses, conducted prior to enrolling study participants, indicated that about half of patients meeting these criteria would continue opioid use 1 year later. To ensure completeness of administrative data, we excluded patients not enrolled continuously at Group Health in the prior year. We also excluded patients with 2 or more visits for cancer diagnoses (other than non-melanoma skin cancer) in the prior year or receiving hospice or nursing home care. During telephone screening, we excluded patients who said that they had not taken prescription pain relievers on at least 7 days in the previous 2 weeks as well as those unable to speak English, unable to participate in a telephone interview, or planning to disenroll from Group Health in the next year. Trained survey staff conducted computer-assisted telephone interviews with study participants at baseline and again 4 and 12 months later.
Author Manuscript
Among 3,172 Group Health patients mailed MASCOT study invitation letters, 2,808 (89%) were contacted for eligibility screening; among these, 2,125 were not identified as ineligible for the study. Among these 2,125 patients, 1,477 (70%) enrolled and completed the baseline interview. Among the 1,477 MASCOT participants, 38 (3%) participants had missing information on important baseline covariates. Among the 1,439 individuals with relevant baseline information, 1,218 (85%) completed the 12-month interview and had complete data on the outcome and opioid use measures of interest in the current study.
Pain. Author manuscript; available in PMC 2017 October 01.
Turner et al.
Page 4
2.2. Measures
Author Manuscript
2.2.1. Independent variables
Author Manuscript
2.2.1.1. Fibromyalgia: We defined presence of fibromyalgia based on physician-assigned diagnostic codes and/or patient self-report. At the time of this study, Group Health physicians used the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)28 to code patient diagnoses at office visits. There is not a specific ICD-9-CM code for fibromyalgia, but 729.1 (myalgia and myositis NOS) was commonly used for fibromyalgia and converts to myositis, unspecified; myalgia; or fibromyalgia in ICD-10-CM. We defined presence of fibromyalgia as (a) assignment of an ICD-9-CM diagnostic code of 729.1 at a visit in the 2 years prior to the baseline interview or (b) patient indication at baseline on a self-report measure of widespread pain bothersomeness (described below) of being ‘bothered a lot’ by ‘widespread pain, pain in most of your body, or fibromyalgia.’ For parsimony, we hereafter refer to this variable as fibromyalgia. 2.2.1.2. Widespread pain score: As a secondary measure, we used the baseline score on a continuous measure ofwidespread pain bothersomeness. Participants used the Patient Health Questionnaire-15 (PHQ-15)21 rating scale to rate how much they had been bothered (not at all [0], a little [1], or a lot [2]) by pain in each of 7 different body sites during the past 4 weeks. The sites included 5 sites from the PHQ-15 (stomach; back; arms, legs, or joints; headaches; chest) plus ‘neck’ and ‘widespread pain, pain in most of your body, or fibromyalgia.’ The score was calculated as the sum of the ratings and could range from 0 to 14, with higher scores indicating more bothersome and widespread pain. For parsimony, we hereafter refer to this as the widespread pain score.
Author Manuscript
2.2.1.3. Opioid use: Because pharmacy records accurately capture information on medication dispensed, but not on how patients use the medication, we defined opioid use with a categorical classification that combined information from pharmacy records and selfreport.35 Using Group Health electronic pharmacy data, we identified prescription opioid medication fills (including information on quantity and strength of medication dispensed, days’ supply, and prescription fill date) in the 120-day period prior to the 12-month interview. We calculated the mean morphine-equivalent dose (MED) per day39 across the 120 days. We classified study participants into the following 3 opioid use groups at 12 months based on a combination of self-reported opioid use in the past 28 days as reported in the 12-month interview and opioid dose over the 120 days prior to the 12-month interview as calculated from pharmacy data:
Author Manuscript
Minimal/no use: Mean daily MED
