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Opioid Use Among Adolescent Patients Treated for Headache

      Abstract

      Purpose

      To determine the pervasiveness of opioid prescribing for adolescents with headache and patient and provider characteristics associated with likelihood of opioid prescribing.

      Methods

      This observational cohort analysis used commercial medical and pharmacy claims between January 1, 2007 and December 31, 2008. Included were adolescents (13–17 years of age) with newly diagnosed headache, ≥2 distinct claims for headache, and ≥12 months health plan eligibility preindex and postindex. Adolescents with a trauma diagnosis at any point were excluded. The primary outcome was current practice patterns, measured by a number of opioid claims, a percentage of patients prescribed opioids, a number of opioid prescriptions per year, a length of opioid therapy, and a frequency of specific comorbidities. A secondary outcome characterized providers and practice settings, comparing patients who received opioids with those who did not.

      Results and conclusions

      Of 8,373 adolescents with headache, 46% (3,859 patients) received an opioid prescription. Nearly half (48%) received one opioid prescription during follow-up; 29% received ≥3 opioid prescriptions. Of those with opioid prescriptions, 25% (977 patients) had a migraine diagnosis at index date. Among adolescents who received opioids, 28% (1,076 adolescents) had an emergency department (ED) visit for headache during follow-up versus 14% (608 adolescents) who did not receive opioids (p < .01). ED visits with a headache diagnosis during follow-up were strongly correlated with opioid use after adjusting for other covariates (odds ratio, 2.02; 95% confidence interval, 1.79–2.29). Despite the treatment guidelines recommending against their use, a large proportion of adolescents with headache were prescribed opioids. ED visits were strongly correlated with opioid prescriptions.

      Keywords

      Implications and Contribution
      Adolescents often received opioids for treatment of headache contrary to recommendations. Rates of opioid prescription in this population were higher than previously reported, likely due to the use of medical and pharmacy claims that allowed for a more comprehensive capture of prescription drug use than medical record or facility-based studies.
      Headache commonly occurs in children. An estimated 37 million children aged 4–17 years had a notable headache in the previous year [
      • Strine T.W.
      • Okoro C.A.
      • McGuire L.C.
      • et al.
      The associations among childhood headaches, emotional and behavioral difficulties, and health care use.
      ], and 54% of school-aged children reported having a headache at least once weekly for 4 weeks in a row [
      • Nyame Y.A.
      • Ambrosy A.P.
      • Saps M.
      • et al.
      Recurrent headaches in children: An epidemiological survey of two middle schools in Inner City Chicago.
      ]. Headache not only causes physical pain and distress but also hampers social activities, interferes with school assignments, and potentially contributes to emotional or behavioral issues and difficulties relating to other children [
      • Cvengros J.A.
      • Harper D.
      • Shevell M.
      Pediatric headache: An examination of process variables in treatment.
      ,
      • Hershey A.D.
      Recent developments in pediatric headache.
      ,
      • Termine C.
      • Özge A.
      • Antonaci F.
      • et al.
      Overview of diagnosis and management of pediatric headache. Part II: Therapeutic management.
      ,
      • Kernick D.
      • Reinhold D.
      • Campbell J.L.
      Impact of headache on young people in a school population.
      ]. Despite the prevalence and related effects, treatment options for pediatric headache, including migraine, are limited. The few prospective, controlled clinical studies for serotonin 5-HT1 receptor antagonists (triptans) for the treatment of migraine in adolescents largely failed to duplicate the efficacy results seen in adults [
      • Dooley J.M.
      The evaluation and management of paediatric headaches.
      ,
      • Hämäläinen M.L.
      • Hoppu K.
      • Santavuori P.
      Sumatriptan for migraine attacks in children: A randomized placebo-controlled study. Do children with migraine respond to oral sumatriptan differently from adults?.
      ,
      • Winner P.
      • Lewis D.
      • Visser W.H.
      • et al.
      Rizatriptan for the acute treatment of migraine in adolescents: A randomized, double-blind, placebo-controlled study.
      ,
      • Linder S.L.
      • Dowson A.J.
      Zolmitriptan provides effective migraine relief in adolescents.
      ,
      • MacDonald J.T.
      Treatment of Juvenile migraine with subcutaneous sumatriptan.
      ,
      • Linder S.L.
      Subcutaneous sumatriptan in the clinical setting: The first 50 consecutive patients with acute migraine in a Pediatric Neurology Office Practice.
      ], although nasal sumatriptan has shown effectiveness in children [
      • Ueberall M.A.
      • Wenzel D.
      Intranasal sumatriptan for the acute treatment of migraine in children.
      ,
      • Winner P.
      • Rothner A.D.
      • Saper J.
      • et al.
      A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents.
      ,
      • Ahonen K.
      • Hämäläinen M.L.
      • Rantala H.
      • et al.
      Nasal sumatriptan is effective in treatment of migraine attacks in children: A randomized trial.
      ]. As a result, nonprescription analgesics are considered first-line treatment for pediatric migraine; nasal sumatriptan may also be considered [
      • Hershey A.D.
      Recent developments in pediatric headache.
      ,
      • Dooley J.M.
      The evaluation and management of paediatric headaches.
      ,
      • Kabbouche M.A.
      • Gilman D.K.
      Management of migraine in adolescents.
      ,
      • Lewis D.
      • Ashwal S.
      • Hershey A.
      • et al.
      Practice parameter: Pharmacological treatment of migraine headache in children and adolescents: Report of the American Academy of Neurology quality standards subcommittee and the practice committee of the Child Neurology Society.
      ].
      Headache, migraine in particular, is a common complaint in the emergency department (ED), and opioids are frequently prescribed for adults and children despite the guidelines endorsing nonsteroidal anti-inflammatory drugs or triptans as first-line therapy [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ,
      • Maizels M.
      Health resource utilization of the emergency department headache “repeater.”.
      ,
      • Friedman B.W.
      • Grosberg B.M.
      Diagnosis and management of the primary headache disorders in the emergency department setting.
      ,
      • Vinson D.R.
      • Hurtado T.R.
      • Vandenberg J.T.
      • et al.
      Variations among emergency departments in the treatment of Benign headache.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ,
      • Sheridan D.C.
      • Meckler G.D.
      • Spiro D.M.
      • et al.
      Diagnostic testing and treatment of pediatric headache in the emergency department.
      ]. In the ED, both adults and children with migraine receive opioids more often than any other recommended nonopioid medication, including triptans or antiemetics [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ]. Opioids, although effective in relieving pain, are not effective for treating migraine [
      • Tepper S.J.
      Opioids should not Be used in migraine.
      ], and the American Academy of Neurology states that opioids should be used only as rescue therapy for acute migraine in specific situations [
      • Silberstein S.D.
      Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review): Report of the quality standards subcommittee of the American Academy of Neurology.
      ].
      Definitive evidence-based treatment guidelines are lacking for children with headache [
      • Richer L.
      • Graham L.
      • Klassen T.
      • et al.
      Emergency department management of acute migraine in children in Canada: A practice validation study.
      ], a problem heightened by the fact that children who seek ED care tend to have treatment-resistant headache [
      • Richer L.P.
      • Laycock K.
      • Millar K.
      • et al.
      Treatment of children with migraine in emergency departments: National practice variation study.
      ]. In a study of treatment choices for pediatric headache in four EDs, opioids were used in 12% of cases overall and in 6% as first-line therapy [
      • Richer L.
      • Graham L.
      • Klassen T.
      • et al.
      Emergency department management of acute migraine in children in Canada: A practice validation study.
      ]. Pediatric and adolescent use of opioids is a concern. The risk of abuse is higher among young adults (from 18 to 30 years of age) compared with older adults (>65 years) [
      • Edlund M.J.
      • Martin B.C.
      • Fan M.-Y.
      • et al.
      Risks of opioid abuse and dependence among recipients of chronic opioid therapy: Results from the TROUP study.
      ] and also among those with mental health disorders [
      • Richardson L.P.
      • Russo J.E.
      • Katon W.
      • et al.
      Mental health disorders and long-term opioid use among adolescents and young adults with chronic pain.
      ]. Furthermore, frequent use of opioids or other acute pain medications may lead to the development of medication overuse headache in patients with previously episodic migraine [
      • Saper J.R.
      • Lake A.E.
      • Hamel R.L.
      • et al.
      Daily scheduled opioids for intractable head pain: Long-term observations of a treatment program.
      ].
      This study originated with discussions between leadership within the American Academy of Pediatrics and WellPoint, Inc. The question of interest presented to WellPoint was “to what extent do current practice patterns for treatment pediatric headache align with practice guidelines?” An advisory group was convened to address this issue, including representatives from the American Academy of Pediatrics, the American Academy of Neurology, and the American Academy of Family Physicians. The group met in person several times as well as through conference calls. The findings reported here highlight the analysis carried out as a result of this advisory group's initial questions.
      This study was designed to determine the pervasiveness of opioid prescribing in adolescents with headache and to determine patient and provider characteristics associated with a higher level of opioid prescribing. This study was unique in that we were able to capture prescription drug use in a more comprehensive fashion compared with a medical record or facility-based study; therefore, we observed much higher rates of opioid prescribing as compared to previous studies on opioid use in this population.

      Methods

      Study design and setting

      This retrospective, observational cohort analysis used commercial claims data compiled from the HealthCore Integrated Research Environment. HealthCore Integrated Research Environment is an integrated medical, pharmacy, and eligibility claims dataset of commercially insured patients, containing claims data for 14 major commercial health plans across the United States representing approximately 45 million total unique lives, with eligibility dating back to 2006.
      As a noninterventional, retrospective claims analysis, this study was conducted in compliance with state and federal laws, including the Health Insurance Portability and Accountability Act of 1996. All claims date were from a limited dataset with de-identified patient information. No patients were directly involved in the study; therefore, review by an Institutional Review Board was unnecessary.

      Selection of participants

      Claims data for adolescents aged 13–17 years on the date of the first headache diagnosis claim (index date) were included in the analysis. All patients had at least two distinct medical claims for headache as identified by diagnosis codes found in the International Classification of Diseases, Ninth Revision, Clinical Modification (Appendix A; all Appendices can be found in the online edition of this article) during the study identification period (January 1, 2007–December 31, 2008). To be included in the study, patients were required to have at least 12 months of health plan eligibility before and after the index date. The study cohort was identified and followed using claims data from their index date (for at least 1 year) until December 31, 2010 or disenrollment from the health plan.
      Patients were excluded if they had a claim with a headache diagnosis in the preindex period (12 months before the index date) or a diagnosis code indicating head trauma at any time from the preindex through the follow-up periods (Appendix B).

      Outcomes

      The primary outcome of interest was the current practice patterns related to the use of opioids among adolescent patients who experience chronic headache. The number of opioid claims per patient and overall during the follow-up period was calculated, along with the percentage of patients prescribed opioids. Additionally, the number of opioid prescriptions per year, the length of opioid therapy, and the frequencies of specific comorbidities were determined from the claims.
      A secondary outcome was a characterization of the providers and practice settings comparing the patients receiving opioids with those who did not.

      Analysis

      Descriptive summary statistics, including mean, standard deviation, and median, were provided for continuous variables; counts and percentages were provided for categorical variables. Unadjusted differences in baseline demographic characteristics were compared using nonparametric analysis of variance methods for continuous variables and Chi-square tests for categorical variables. All statistical tests were two sided and performed at a 5% level of significance. All confidence intervals (CIs) were two-sided 95% CIs.
      The variables of interest included age, gender, geographic region, length of patient follow-up, headache diagnosis on index date, change in headache diagnosis category following index date, provider specialty on index diagnosis, number of physician office visits since index date, days between first and last headache diagnosis, number of ED visits during follow-up period (inclusive of index date), diagnostic procedures (e.g., magnetic resonance imaging, lumbar puncture), headache treatment including use of abortive/rescue headache medications, preventive/prophylactic medications, nonpharmacologic treatment (e.g., acupuncture), and presence of comorbid conditions. The comorbid conditions of interest were identified during the 12-month preindex period and included diagnoses for attention-deficit hyperactivity disorder, anxiety, asthma, cerebral palsy, depression, epilepsy, pervasive developmental disorders, antisocial personality disorder, and acute reaction to stress (Appendix C).
      A binomial logistic regression model was used to measure the relationship between the outcome of interest (likelihood of receiving an opioid prescription) and the following variables: age, gender, geographic region, provider number of physician office visits, ED visits, diagnostic procedures (e.g., magnetic resonance imaging, lumbar puncture), use of abortive/rescue headache medications, and presence of comorbid conditions. Statistical analyses were conducted with SAS 9.1 software. Alpha was set at .05 for each test.

      Results

      Patient population

      A total of 8,373 children between the ages of 13 and 17 years who had a headache diagnosis during the study period without any trauma-related diagnoses were identified. Of these adolescents, 46.1% (3,859 adolescents) received an opioid prescription (Table 1). On the index date, 24.3% of the adolescents were diagnosed with migraine; of all adolescents who received opioids, 25.3% (977 adolescents) had a diagnosis of migraine at index. In the 12-month preindex period, adolescents who received opioids were more likely than those who did not receive opioids to have comorbid asthma (10.7% with opioids vs. 8.7% without, p < .01) and anxiety (4.2% with opioids vs. 3.2% without, p < .05). Furthermore, adolescents who received opioids during the follow-up period were more likely to have received an opioid medication prior to their diagnosis for headache (20.9% with opioids vs. 11.2% without, p < .001). During the follow-up period, 17.4% of all adolescents (1,458 adolescents) had five or more physician office visits with a diagnosis of headache: 22.0% (850 adolescents) who received opioids and 13.5% (608 adolescents) who did not receive opioids.
      Table 1Patient characteristics at index date
      CharacteristicsNonopioid patients (N = 4,514)Opioid patients (N = 3,859)p Value
      p Value is for two-sided test, α = .05; Chi-square or Fisher exact test is used for categorical variables and t-test or nonparametric test is used for continuous variables between nonopioid patients versus opioid patients.
      Age at index date (years), mean (SD)14.7 (1.1)14.7 (1.1).09
      Gender, n (%)
       Male1,610 (35.7)1,177 (30.1)<.0001
       Female2,904 (64.3)2,682 (69.5)
      Geographic region, n (%)
       Eastern United States: NY, CT, ME, NH, GA, VA2,005 (44.4)1,716 (44.5)<.0001
       Central United States: IN, WI, MO, KY, OH1,322 (29.3)1,270 (32.9)
       Western United States: CA, NV1,187 (26.3)873 (22.6)
      Postindex follow-up time in days, mean (SD)771 (281.2)822 (284.4)<.0001
      Index date headache category, n (%)
       Migraine (ICD-9: 346.xx)1,056 (23.4)977 (25.3)
       Head and neck symptoms: headache (ICD-9: 784.0)3,318 (73.5)2,765 (71.7).127
       Psychologically related tension headache (ICD-9: 307.81)134 (3.0)113 (2.9)
      Comorbid conditions in 12 months preindex, n (%)
       Asthma393 (8.7)413 (10.7).002
       ADHD243 (5.4)215 (5.6).706
       Depression253 (5.6)246 (6.4).138
       Anxiety144 (3.2)160 (4.2).020
       Epilepsy45 (1.0)33 (.9).501
       Pervasive developmental disorders21 (.5)7 (.2).025
       Cerebral palsy4 (.1)1 (.0).383
       Acute reaction to stress4 (.1)11 (.3).034
      Number of physician office visits with headache diagnosis during the follow-up period (including index date), n (%)
       0 (e.g., ED visits only)132 (2.9)142 (2.7)
       11,223 (27.1)848 (22.0)
       21,494 (33.1)1,041 (27.0)
       3679 (15.0)589 (15.3)
       4378 (8.4)389 (10.1)
       5 or more608 (13.5)850 (22.0)
       Mean (SD)2.7 (2.8)3.4 (3.3)<.0001
      Number of distinct providers treating an individual patient's headaches during follow-up time2, n (%)2.9 (1.8)3.8 (3.0)<.0001
      Days between index headache claim and last headache claim, mean (SD)246 (285.5)332 (332.1)<.0001
      Opioid prescriptions during year prior to index, n (%)
       04,010 (88.8)3,051 (79.1)<.0001
       1312 (6.9)410 (10.6)
       2140 (3.1)216 (5.6)
       335 (.8)84 (2.2)
       412 (.3)34 (.9)
       5 or more5 (.1)64 (1.7)
      Antidepressant prescriptions during year prior to index, n (%)
       04,175 (92.5)3,486 (90.3)<.0001
       170 (1.6)68 (1.8)
       247 (1.0)43 (1.1)
       327 (.6)41 (1.1)
       425 (.6)36 (.9)
       5 or more170 (3.8)185 (4.8)
      Asthma prescriptions during year prior to index, n (%)
       03,889 (86.2)3,149 (81.6)<.0001
       1263 (5.8)279 (7.2)
       2112 (2.5)155 (4.0)
       367 (1.5)66 (1.7)
       449 (1.1)39 (1.0)
       5 or more134 (3.0)171 (4.4)
      ADHD = Attention Deficit Hyperactivity Disorder; ED = emergency department; ICD-9 = International Classification of Diseases, Ninth Revision; SD = standard deviation.
      p Value is for two-sided test, α = .05; Chi-square or Fisher exact test is used for categorical variables and t-test or nonparametric test is used for continuous variables between nonopioid patients versus opioid patients.

      Opioid usage

      Nearly half (47.8%) of adolescents using opioids received only one opioid prescription during the follow-up period, 22.5% received two opioid prescriptions, and 29.3% received three or more opioid prescriptions (Table 2). The most common provider specialty at index date was pediatrics for the adolescents who received opioids and those who did not (30.1% vs. 34.0%, respectively), followed by family physicians (30.5% with opioids vs. 26.2% without). Compared with adolescents in the nonopioid group, fewer adolescents who received opioids saw a neurologist (5.7% with opioids vs. 7.2% without). Adolescents who received opioids saw more distinct providers for headache during the follow-up period (mean 3.8 providers) compared with those who did not receive opioids (mean 2.9 providers, p < .01; Table 1).
      Table 2Diagnostic procedures and abortive/preventive treatments
      CharacteristicsNonopioid patients (N = 4,514)Opioid patients (N = 3,859)p Value
      p Value is for two-sided test, α = .05; Chi-square or Fisher exact test is used for categorical variables between nonopioid patients versus opioid patients.
      Diagnostic procedures
       CT scan1,157 (25.6)1,374 (35.6)<.0001
       MRI scan1,088 (24.1)1,030 (26.7).0066
       EEG160 (3.5)161 (4.2).136
       X-ray131 (2.9)141 (3.6).0531
      Lumbar puncture54 (1.2)160 (4.2)<.0001
      Abortive/rescue headache prescriptions
      Pharmacy claims do not contain diagnoses; it is possible some of these drugs could have been prescribed for non-headache purposes.
       Anti-inflammatory/NSAIDs857 (19.0)1,736 (45.0)<.0001
       Triptans780 (17.3)1,055 (27.3)<.0001
       Other migraine-specific products302 (6.7)472 (12.2)<.0001
       Analgesics (non-narcotic)256 (5.7)440 (11.4)<.0001
      Any abortive/rescue prescription claim1,700 (37.7)3,859 (100.0)<.0001
      Number of opioid prescriptions during the follow-up period (including index date), mean (SD)
      Number of opioid prescriptions is not applicable to the non-opioid cohort.
      2.6 (3.6)
      Number of opioid prescriptions during the follow-up period (including index date), n (%)
       04,514 (100)0 (0)
       1
      Number of opioid prescriptions is not applicable to the non-opioid cohort.
      1,846 (47.8)
       2
      Number of opioid prescriptions is not applicable to the non-opioid cohort.
      884 (22.9)
       3–4
      Number of opioid prescriptions is not applicable to the non-opioid cohort.
      672 (17.4)
       5 or more
      Number of opioid prescriptions is not applicable to the non-opioid cohort.
      457 (11.8)
      Preventative/prophylactic headache prescriptions
      Pharmacy claims do not contain diagnoses; it is possible some of these drugs could have been prescribed for non-headache purposes.
       Oral contraceptives857 (41.9)2,278 (59.0)<.0001
       Select antidepressants1,006 (19.0)1,220 (31.6)<.0001
       Select antiepileptic drugs584 (12.9)871 (22.6)<.0001
       Beta blockers183 (4.1)266 (6.9)<.0001
       Calcium channel blockers45 (1.0)83 (2.2)<.0001
      Any headache preventive prescription claim1,891 (41.9)2,278 (59.0)<.0001
      Nonpharmacological headache treatment
       Physical therapy738 (16.4)1,056 (27.4)<.0001
       Chiropractic139 (3.1)119 (3.1).9908
       Acupuncture60 (1.3)49 (1.3).811
      Visits with headache diagnosis during follow-up period
      Including index date.
       11,096 (24.3)661 (17.1)<.0001
       21,567 (34.7)1,110 (28.8)
       3764 (16.9)637 (16.5)
       4414 (9.2)429 (11.1)
       5 or more673 (14.9)1,022 (26.5)
      Mean2.9 (2.9)4.0 (4.4)
      ED visits with headache diagnosis
       03,906 (86.5)2,783 (72.1)<.0001
       1518 (11.5)784 (20.3)
       2–385 (1.9)256 (6.6)
       4 or more5 (.1)36 (.9)
      CT = computer tomography; ED = emergency department; EEG = electroencephalography; MRI = magnetic resonance imaging; NSAIDs = nonsteroidal anti-inflammatory drugs; SD = standard deviation.
      a Number of opioid prescriptions is not applicable to the non-opioid cohort.
      b Pharmacy claims do not contain diagnoses; it is possible some of these drugs could have been prescribed for non-headache purposes.
      c Including index date.
      p Value is for two-sided test, α = .05; Chi-square or Fisher exact test is used for categorical variables between nonopioid patients versus opioid patients.
      During the follow-up period, adolescents who received opioids had more visits with a headache diagnosis than those who did not receive opioids (Table 2). Among adolescents who received opioids, 27.9% (1,076 adolescents) had an ED visit for headache during follow-up, compared with 13.5% (608 adolescents) who did not receive opioids (p < .01).
      Adolescents who received opioids also received more computed tomography scans (35.6% with opioids vs. 25.6% without, p < .01) and lumbar punctures (4.2% with opioids vs. 1.2% without, p < .01) than those who did not receive opioids (Table 2). This is likely due to the association with ED visits, given that ED use and computed tomography scans are also highly correlated [
      • DeVries A.
      • Young P.C.
      • Wall E.
      • et al.
      CT scan utilization in pediatric patients with recurrent headache.
      ]. Patients in the opioid treatment group were significantly more likely than adolescents who did not receive opioids to have also received abortive or rescue headache medications and prophylactic treatments for headache prevention, including nonpharmacologic treatments such as acupuncture (Table 2).

      Logistic regression results

      Consistent with the univariate results, the strongest association in the logistic regression was with ED use: ED visits with a headache diagnosis during the follow-up period were strongly correlated with opioid use (odds ratio [OR], 2.02; 95% CI, 1.79–2.29; Table 3). Females were somewhat less likely than males to receive opioid prescriptions (OR, .89; 95% CI, .80–.99; p < .05). Patients with asthma were more likely to receive opioid treatment than patients without (OR, 1.22; 95% CI, 1.04–1.42; p < .05). It is interesting to note that index provider specialty was associated with likelihood of receiving an opioid prescription. Receiving care from a neurologist was associated with a lower likelihood of opioid prescribing (OR, .79; 95% CI, .64–.97; p < .01), whereas receiving care from a family physician was associated with a higher likelihood of receiving an opioid prescription (OR, 1.2; 95% CI, 1.06–1.35; p < .01). Interestingly, among nonpharmacologic treatments, chiropractic services was associated with a lower likelihood of a patient receiving an opioid prescription (OR, .72; 95% CI, .64–.97; p < .02). Use of abortive agents or headache prophylaxis therapies was also associated with an increased risk of opioid use.
      Table 3Logistic regression model
      Reference category.
      EffectOdds ratios point estimateOdds ratios 95% wald confidence limitsβ estimatep > ChiSq
      Region
       Western (reference)1.000
      Exclude patients with trauma, unknown provider specialty at index date, no visits for headache since index date, or who are not newly diagnosed cases.
       Central1.005.8851.141.005.942
       Eastern.993.8831.117−.007.906
      Gender
       Male (reference)1.000
      Exclude patients with trauma, unknown provider specialty at index date, no visits for headache since index date, or who are not newly diagnosed cases.
       Female.886.796.987−.121.028
      Comorbid conditions in 12 months preindex
       Asthma1.2161.0391.424.196.015
      Provider specialty for index date diagnosis
       Pediatrics—all types (reference)1.000
      Exclude patients with trauma, unknown provider specialty at index date, no visits for headache since index date, or who are not newly diagnosed cases.
       Neurology.787.641.965−.240.021
       Family physician1.2011.0651.354.183.003
       Other
      Other provider specialty includes radiology, emergency medicine, internal medicine, ophthalmology, otolaryngology, allergy/immunology, surgery (all types), anesthesiology/pain management and other nonlisted.
      .991.8801.115−.009.878
      ED visits with headache diagnosis during the follow-up period (including index date)
       Diagnostic procedures2.0231.7872.289.704<.0001
       Lumbar puncture2.2941.6333.221.830<.0001
       X-ray1.3441.0371.743.296.026
      Preventative/prophylactic headache prescriptions
       Beta blockers1.2451.0061.541.220.044
       Select antiepileptic drugs1.3451.1771.537.297<.0001
       Select antidepressants1.2511.1201.397.224<.0001
       Oral contraceptives1.5881.4101.789.463<.0001
      Abortive/rescue headache prescriptions
       Triptans1.2821.1391.443.248<.0001
       Other migraine-specific products1.3321.1261.575.286.001
       Anti-inflammatory/NSAIDs2.7642.4943.0631.017<.0001
       Analgesics (non-narcotic)1.3871.1611.656.327.000
      Nonpharmacological headache treatment
       Physical therapy1.7371.5461.952.552<.0001
       Chiropractic.716.540.950−.334.020
      ChiSq = chi square; ED = emergency department; NSAIDs = nonsteroidal anti-inflammatory drugs.
      a Reference category.
      b Exclude patients with trauma, unknown provider specialty at index date, no visits for headache since index date, or who are not newly diagnosed cases.
      c Other provider specialty includes radiology, emergency medicine, internal medicine, ophthalmology, otolaryngology, allergy/immunology, surgery (all types), anesthesiology/pain management and other nonlisted.

      Discussion

      In this retrospective, observational analysis, nearly half (47.8%) of adolescents with headache received an opioid prescription despite evidence that opioids are inappropriate for the treatment of headache [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ,
      • Tepper S.J.
      Opioids should not Be used in migraine.
      ]. In addition to adverse physiological effects and the potential for dependence, opioid use may contribute to development of chronic daily headache in patients with episodic migraine [
      • Saper J.R.
      • Lake A.E.
      • Hamel R.L.
      • et al.
      Daily scheduled opioids for intractable head pain: Long-term observations of a treatment program.
      ] and may actually prevent reversal of the migraine process [
      • Tepper S.J.
      Opioids should not Be used in migraine.
      ]. We observed a moderate relationship between conditions such as asthma and anxiety and the cohort of patients who went on to receive opioids in the follow-up period. Corresponding to the relationship of comorbid conditions, we also observed a moderate relationship between opioid use in the follow-up period and medications used in the 12-month preindex period. Adolescents who received opioids were more likely than those who did not receive opioids to have had preindex asthma medications (18.4% with opioids vs. 13.9% without, p < .001) and preindex antidepressants (9.7% with opioids vs. 7.5% without, p < .001). A possible reason for this relationship could include differences in the complexity of the patient's condition; however, it is difficult to interpret the causes for this observed relationship without additional information.
      Use of opioids for acute headache is especially common in the ED [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ,
      • Maizels M.
      Health resource utilization of the emergency department headache “repeater.”.
      ,
      • Friedman B.W.
      • Grosberg B.M.
      Diagnosis and management of the primary headache disorders in the emergency department setting.
      ,
      • Vinson D.R.
      • Hurtado T.R.
      • Vandenberg J.T.
      • et al.
      Variations among emergency departments in the treatment of Benign headache.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ,
      • Sheridan D.C.
      • Meckler G.D.
      • Spiro D.M.
      • et al.
      Diagnostic testing and treatment of pediatric headache in the emergency department.
      ], often to the exclusion of migraine-specific therapies [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ]. Although previous studies of opioids for the treatment of headache in the ED have primarily been performed in adult populations [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ,
      • Maizels M.
      Health resource utilization of the emergency department headache “repeater.”.
      ,
      • Vinson D.R.
      • Hurtado T.R.
      • Vandenberg J.T.
      • et al.
      Variations among emergency departments in the treatment of Benign headache.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ,
      • Blumenthal H.J.
      • Weisz M.A.
      • Kelly K.M.
      • et al.
      Treatment of primary headache in the emergency department.
      ], the results of the current analysis in adolescent patients found similar results. ED visits during the follow-up period were strongly correlated with the prescription of opioids: patients with ED visits had twice the rate of opioid prescriptions as those without ED visits, and those who had three or more ED visits were four times more likely to have opioid prescriptions than those without ED visits. These findings agree with previous research that showed adult patients who received opioids for headache in the ED were more likely to return to the ED compared with patients who did not receive opioids [
      • Vinson D.R.
      • Hurtado T.R.
      • Vandenberg J.T.
      • et al.
      Variations among emergency departments in the treatment of Benign headache.
      ].
      Although patients visiting the ED for headache may have more severe symptoms or treatment-resistant headache than those who do not seek emergency care, other factors may contribute to the increased use of opioids for treatment of headache in the ED. Although prior articles have suggested that patients seeking emergency treatment for headache may in fact be misdiagnosed as having migraine when they may more accurately be diagnosed as seeking narcotics [
      • Maizels M.
      Health resource utilization of the emergency department headache “repeater.”.
      ,
      • Colman I.
      • Rothney A.
      • Wright S.C.
      • et al.
      Use of narcotic analgesics in the emergency department treatment of migraine headache.
      ], our data did not support this pattern. Interestingly, we did not observe a strong relationship between ED use and prior history of opioid use in our study. A subset analysis of the cohort of children who received opioids during the follow-up period showed 21.8% who visited the ED had evidence of prior opioid use, compared with 20.7% of those not treated in the ED. The relationship was not statistically significant. However, we did observe a relatively strong relationship between the use of opioids prior to the diagnosis of headache (20.9% in the opioid cohort vs. 11.2% in the nonopioid cohort), suggesting there may be some underlying level of drug-seeking behavior occurring within the population. Despite the strength of the relationship, it is important to note that nearly 80% of the population in the opioid cohort had no preindex opioid use, indicating drug-seeking behavior would be limited to a subset of patients as opposed to the majority. Migraine may be underdiagnosed and mistreated with opioids rather than migraine-specific medications, resulting in headache recurrence and subsequent ED visits [
      • Blumenthal H.J.
      • Weisz M.A.
      • Kelly K.M.
      • et al.
      Treatment of primary headache in the emergency department.
      ]. Perhaps most relevant is the aggressive manner in which pain is treated in emergency medicine. A stratified approach is taken where the treatment is matched to the patient's reported level of pain, with pain relief as the treatment goal [
      • Tamayo-Sarver J.H.
      • Dawson N.V.
      • Cydulka R.K.
      • et al.
      Variability in emergency physician decisionmaking about prescription opioid analgesics.
      ]. Emergency physicians must make treatment decisions for patients reporting severe pain without the benefit of an established relationship with the patient and without knowing the patient's full medical history, which may hinder their assessment of the patient's potential risk for abuse [
      • Tamayo-Sarver J.H.
      • Dawson N.V.
      • Cydulka R.K.
      • et al.
      Variability in emergency physician decisionmaking about prescription opioid analgesics.
      ].
      Prior research found the most important consideration for emergency physicians is the effectiveness of the medication in relieving pain, followed by factors such as experience in using a particular medication, patient allergies or contraindications, patient requests for opioids, and department protocols and practice patterns [
      • Hurtado T.R.
      • Vinson D.R.
      • Vandenberg J.T.
      ED treatment of migraine headache: Factors influencing pharmacotherapeutic choices.
      ]. Treatment guidelines and recommendations from professional societies were found to have no influence on physician choices of first-line pain medications, although physicians agreed medications recommended in headache treatment guidelines would be effective for their patients [
      • Hurtado T.R.
      • Vinson D.R.
      • Vandenberg J.T.
      ED treatment of migraine headache: Factors influencing pharmacotherapeutic choices.
      ].

      Limitations

      As a retrospective claims analysis, these data are subject to certain limitations. Administrative claims are designed for reimbursement purposes rather than research and may contain coding errors. Pharmacy claims do not contain diagnoses; therefore, it is not possible to definitively conclude that opioids were, in fact, prescribed for the treatment of headache. To assess the extent to which this limitation impacted the results, we examined opioid use in the nonheadache population using the same age group. We observed that 8% of this population received an opioid prescription during a 12-month period. Although the lack of diagnosis information was a limiting factor, it was clear that adolescent patients who were treated for headache were significantly more likely to receive opioid prescriptions. Finally, no data were available regarding headache severity or patient response to medications taken before visiting the ED; the patients who received opioids in the ED may have already unsuccessfully tried simple analgesics or migraine-specific medications, or these patients may have had treatment-refractory headache [
      • Vinson D.R.
      Treatment patterns of isolated Benign headache in US Emergency Departments.
      ]. A definitive conclusion cannot be drawn as to whether the correlation between ED visits and opioid prescription was due to headache severity at presentation or due to practice patterns. However, we believe practice patterns to be the driving factor based on a recent study demonstrating a greater likelihood of neuroimaging to diagnose pediatric headache in the ED despite a normal history [
      • DeVries A.
      • Young P.C.
      • Wall E.
      • et al.
      CT scan utilization in pediatric patients with recurrent headache.
      ]. Future studies may expand on the correlation between practice patterns and opioid prescription, as well as to compare the use of opioids for headache across treatment settings, such as academic medical centers versus community hospitals.
      In summary, opioids are frequently prescribed for adolescents presenting with acute headache, despite the treatment guidelines that recommend against their use. ED visits were strongly correlated with receipt of opioid prescriptions.

      Acknowledgments

      The authors extend a special thanks to Paul Young, M.D., Suk-Fong Tang, Ph.D., and John Barron, Pharm.D., for their valuable contributions to the study and suggestions for the manuscript. The authors acknowledge Cheryl Jones, an employee of HealthCore, Inc., for editorial assistance in preparing the manuscript. Funding for manuscript preparation was provided by WellPoint, Inc., to HealthCore, Inc., an independent research organization. These results have not been previously presented or published in full or in part.

      Funding Sources

      This study was funded by WellPoint, Inc . A. DeVries and C.-h. Li are employees of HealthCore, Inc., an independent research organization that received funding from WellPoint, Inc., for the conduct of the study. A. Rosenberg is an employee of WellPoint, Inc. Through A. Rosenberg, WellPoint, Inc., was indirectly involved in the design of the study; data analysis and interpretation; and preparation, review, and approval of the manuscript. T. Koch, E. Wall, and T. Getchius report no conflicts.

      Supplementary Data

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