Idiopathic intracranial hypertension carries a high medication overuse headache burden and a chronic-headache-like opioid related disorder risk: a nationwide cohort study

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Gajjar, Alexandra R. Paul This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8532079/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Idiopathic intracranial hypertension (IIH) is defined by elevated intracranial pressure of unclear cause. Headaches often mimic migraine. In addition to migraine-directed therapies, opioids and simple analgesics are frequently prescribed. Sustained analgesic use increases the risk for medication overuse headache (MOH) and opioid exposure raises concern for opioid-related disorders (ORD). Venous sinus stenosis is increasingly being identified as a possible etiology of IIH, and venous sinus stenting (VSS) has emerged as an alternative to ventriculoperitoneal shunting (VPS). Comparative data on headache medication use after VSS versus VPS are limited. Objectives Compare headache-medication use patterns and associated risks (MOH, ORD) in IIH versus migraine and population controls. Evaluate changes in headache-medication use in VSS-only and VPS-only cohorts. Methods Retrospective cohort study in Epic Cosmos. Primary outcomes were incident ORD and MOH. Crude odds ratios (ORs) were calculated. Using a stratification approach (Mantel-Haenszel), ORs were computed within strata of age, race, Social Vulnerability Index (SVI) quartile, and BMI class, then pooled. Heterogeneity within strata was assessed with the Breslow-Day test. Longitudinal medication utilization was summarized in yearly intervals from one year before diagnosis through six years after. For surgical analysis, we compared the year after the procedure with the year before. Results We identified 82,295 patients with IIH, 26,003,964 population controls, and 1,716,441 migraine controls. Opioid and non-opioid analgesic use peaked within one year after diagnosis. IIH was associated with higher odds of MOH vs. the population (OR 117.99, 95% CI 110.17-126.36) and migraine controls (OR 1.29, 95% CI 1.21–1.37), with these associations persisting after adjustment. ORD odds were elevated versus population controls (OR 3.72, 95% CI 3.54–3.92) but were similar to migraine controls after adjustment. Both VSS and VPS were associated with decreased acetazolamide and opioid use after surgery. Conclusions IIH is linked to substantial MOH risk beyond that seen in the general population and above migraine, while ORD risk appears characteristic of chronic headache populations. After either VSS or VPS, opioid reliance decreases, which may mitigate the downstream risk of MOH and ORD. Reliance on abortive and prophylactic headache therapies persists after surgery, emphasizing the importance of IIH-specific headache management and medication counseling. Idiopathic intracranial hypertension headache migraine venous sinus stenting ventriculoperitoneal shunting Epic Cosmos Figures Figure 1 Figure 2 Introduction Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP) of unclear cause, with predominance in obese women of childbearing age. 1 Management of IIH focuses on control of intracranial pressure (ICP) and weight reduction, but headaches can persist even after ICP control is achieved. 2 – 5 First-line medical treatment is acetazolamide, while surgical management includes CSF shunting and optic nerve sheath fenestration. 3 Headache is a common symptom, often pulsatile, and can mimic migraine. Although migraine-directed therapies are usually attempted, simple analgesics and opioids are frequently prescribed for symptom management. 3 , 6 , 7 Sustained analgesic use increases the risk of medication-overuse headache (MOH), defined by ICHD-3 as acute medication use on ≥ 10–15 days per month for more than three months, with lower thresholds for opioids and combination analgesics. 8 , 9 MOH can drive headache chronicity, disability, and treatment resistance. 6 , 9 The IIH Treatment Trial showed that medication overuse was frequent at baseline in this population, with more than one-third of patients overusing symptomatic headache treatments. 7 , 10 High opioid exposure in IIH also raises concern for opioid-related disorders (ORD), including misuse, dependence, and withdrawal. 11 , 12 Chronic opioid therapy may worsen pain via opioid-induced hyperalgesia, and migraine guidelines discourage routine use due to limited benefit, increased risk of MOH, and dependence. 6 , 12 , 13 We retrospectively evaluated whether analgesics and opioids are prescribed more frequently in IIH than in migraine controls in a large, national, multi-institutional cohort. We hypothesized that such prescribing patterns are associated with a higher incidence of MOH and ORD compared to the population and migraine controls. Venous sinus stenosis is increasingly recognized as a contributor to the pathophysiology of IIH. 14 Venous sinus stenting (VSS), in carefully selected patients, is an alternative to CSF shunting and has been associated with improvement in headaches in a systematic review. 15 However, a comparison of headache management after ventriculoperitoneal shunting (VPS) versus VSS is lacking. 3 We hypothesized that, following VSS, the frequency of medications to manage headache would be comparable to or lower than after VPS. Methods Study Design and Data Source We conducted a retrospective cohort study in Epic Cosmos (Epic Systems, Verona, WI), a national, multi-institution electronic health record resource compiled from participating health systems. 16 , 17 Cosmos integrates longitudinal patient charts across ambulatory and inpatient settings, representing over 300 million patient records from over 1,700 hospitals and 40,000 clinics. SlicerDicer is a data exploration tool in Cosmos that lets users create custom queries and retrieve aggregate results in a secure environment. The study was determined by Albany Medical College (AMC) as IRB exempt (IRB Determination #: R_115p9425BQVx4Ty). This study adhered to the STROBE guidelines. Patient Cohorts. We assembled four cohorts using the Patient data model in Cosmos SlicerDicer. We added a Base Patient filter to all cohorts, limiting searches to patients who have had at least two encounters within two years. Criteria used to define the cohorts were restricted to data from January 1, 2002, through June 25, 2025. The IIH cohort comprised patients with prevalent idiopathic (benign) intracranial hypertension (ICD-10-CM G93.2). The migraine control cohort comprised patients with prevalent migraine (ICD-10-CM G43.*) but without IIH. The population control cohort excluded diagnosis of IIH or migraine. To improve between-cohort comparability, all three cohorts were restricted to adult women aged 18–75 years with body mass index (BMI) ≥ 30 kg/m² (class I-III obesity). The VSS and VPS cohorts comprised patients ≥ 18 years with idiopathic (benign) intracranial hypertension (ICD-10-CM G93.2). VSS procedures were identified using CPT codes 37238, 37239, 61635 and ICD-10-PCS codes 05HL3DZ and 057L3DZ. 18 , 19 VPS procedures were identified using CPT code 62223 and ICD-10-PCS codes 009600Z, 009630Z, 0016076, 00160J6, 00160K6, 0016376, 00163J6, 00163K6, 0016476, 00164J6, 00164K6. 20 Eligibility required that patients undergo the procedure within three years of diagnosis (G39.2). Cases were excluded if a concurrent billing diagnosis of IIH did not accompany stenting codes, or if the alternate procedure was performed within the three-year timeframe. Measurements The Cosmos dataset includes demographic and clinical variables. BMI, recorded under vital signs, is calculated from documented height and weight and expressed in kg/m^2. Obesity class was defined as Obese [BMI 30-39.9] vs Morbidly Obese [≥ 40]. Age was determined using “Age at Time of Event”, restricting patients to those within a specified age range at the time of a corresponding event. Patients were categorized by age: 18–44, 45–75 years, and 75+. Race was documented at the local level by either self-reporting or staff entry. Race categories were American Indian/Alaska Native, Black/African American, White, and all other categories combined as “Other Race” (collapsed due to suppression of cell counts < 10 for minority categories). The Social Vulnerability Index (SVI) is available in Cosmos and is derived from census tract data from the US Centers for Disease Control and Prevention (CDC); higher percentiles indicate greater vulnerability. Disease incidence was represented by “New Diagnoses” and prevalent disease by “Active Diagnoses”. Procedures were ascertained under “Billed Procedures”, with corresponding diagnoses under “Billed Diagnoses”. The “All Medications” flag captures medication activity across prescriptions, pharmacy dispenses, administrations, and patient-reported use. Medication classes comprised Cosmos-native and user-defined sets including Analgesics (opioid analgesics; non-opioid analgesics), Triptans, and Migraine prevention (β-blockers; antiepileptics; tricyclic antidepressants (TCAs)). The full list of constituent medications is provided in Supplementary Table S1 . Outcomes and Statistical Analyses For longitudinal analyses of medication rates, we indexed women in the IIH and migraine-control cohorts on the incident diagnosis date. We summarized medication exposure in successive one-year intervals from one year before through six years after the index. For each cohort-interval-class, we obtained the percentage of the defined population meeting the medication-class criterion with 95% confidence intervals (CI). Exposure to a class was defined as any documented record during the interval. We conducted unadjusted analyses of the associations between binary IIH status and two incident binary outcomes, opioid-related disorders (ICD-10-CM F11.*) and medication-overuse headache (ICD-10-CM G44.41, G44.40). For each comparison, events were restricted to incident disease after cohort entry, and crude odds ratios (ORs) with 95% CIs were calculated. Baseline characteristics of the IIH and control cohorts were compared across age bands, race, SVI quartiles, and obesity classes. Global Pearson χ² tests comparing IIH with each control group, controlling for these covariates, were conducted. Residual imbalance was anticipated despite coarse matching, motivating stratified analysis using the Cochran-Mantel-Haenszel (CMH) test to evaluate conditional independence, i.e. an association between two binary variables (e.g., IIH and MOH), while controlling for a third categorical factor (e.g. BMI strata). 21 , 22 Using CMH, we generated a common weighted OR that estimates the exposure-outcome association accounting for stratification and serves a proxy for an adjusted OR in aggregate 2x2 analyses. An absolute difference ≥ 10% between the MH common OR and crude OR served as evidence of confounding (Δ vs crude = [(MH common OR – crude OR)/crude OR] ×100%)). The CMH test statistic was used to compute p-values. The common OR is an appropriate summary when the homogeneity assumption holds (i.e., stratum-specific ORs are homogenous). Homogeneity was assessed with the Breslow-Day (BD) χ² test, which evaluates the null that all stratum-specific ORs are equal. 23 , 24 When BD test was non-significant, the common OR is interpreted as a single conditional effect. When significant, the common OR is treated as a summary across heterogeneous strata. We conducted an exploratory pre-post study of medication use in adults with IIH who underwent VSS-only or VPS-only (i.e., no crossover). The procedure date served as the index date. Medication classes matched those used in the longitudinal analysis (Supplemental Table S1 ). For each class, we measured the proportion of patients with any documented use during the year before and the year after the procedure (allowing a ± 2-month window). We calculated odds ratios with 95% confidence intervals and used Pearson χ² tests for comparisons. Alpha was set at 0.05. All analyses were performed in R (R Foundation for Statistical Computing) using base stats and DescTools. 25 , 26 Results Baseline Characteristics. We analyzed 82,295 individuals with IIH, 26,003,964 population controls, and 1,716,441 migraine controls (Table 1 ). Across all cohorts, patients were adult women with obesity by study design. The IIH cohort was younger (approximately two-thirds aged between 18–44 and one-third 45–75) than population controls. Migraine controls exhibited intermediate age ranges. The IIH cohort included a higher proportion of Black/African American patients compared with controls. Where available, IIH patients demonstrated higher SVI scores than population controls. IIH patients were roughly split between class I-II (30–39 kg/m 2 ) and class III (≥ 40 kg/m 2 ) obesity. Population controls predominantly fell into class III, whereas migraine controls were more often in class I-II. Table 1 Baseline Characteristics IIH Population Control Migraine Control n (%) Total 82,295 26,003,964 1,716,441 Age categories 18–44 64,365 (69.19%) 11,371,608 (43.73%) 1,053,972 (53.23%) 45–75 28,658 (30.81%) 14,632,356 (56.27%) 926,062 (46.77%) Race White 54,118 (57.48%) 15,942,235 (56.74%) 1,318,117 (68.54%) Black or African American 25,481 (27.07%) 4,967,153 (17.68%) 278,533 (14.48%) Other Race 11,862 (12.60%) 4,103,862 (14.60%) 244,568 (12.72%) American Indian or Alaska Native 1,268 (1.35%) 314,209 (1.12%) 27,978 (1.45%) No value 1,417 (1.51%) 2,772,007 (9.86%) 53,975 (2.81%) Social Vulnerability Index 50% − 75% 11,930 (14.50%) 3,333,239 (12.82%) 240,913 (14.04%) > 75% (most vulnerable) 11,118 (13.51%) 3,359,077 (12.92%) 199,088 (11.60%) 25% − 50% 11,076 (13.46%) 3,284,370 (12.63%) 252,645 (14.72%) < 25% (least vulnerable) 9,293 (11.29%) 3,053,370 (11.74%) 236,758 (13.79%) No value 38,878 (47.24%) 12,973,908 (49.89%) 787,037 (45.85%) BMI categories Obese 30–39 68,905 (55.07%) 28,829,841 (31.33%) 2,241,954 (72.73%) Morbidly Obese > 40 56,213 (44.93%) 63,181,950 (68.67%) 840,576 (27.27%) Longitudinal Trends in Medical Headache Management in IIH versus Migraine Controls. Across all classes, utilization rose from the year before diagnosis to the first year after diagnosis, then declined through years 1 to 6 (Fig. 1 ). Peaks in the first post-diagnosis year were higher in IIH for opioids (32.4%, 95% CI 32.1–32.7 vs 26.0%, 95% CI 25.9–26.1) and non-opioid analgesics (26.1%, 95% CI 25.8–26.4 vs 18.9%, 95% CI 18.8–19.0). Triptan use was consistently greater in migraine controls across all intervals, peaking at 20.3% (95% CI 20.2–20.4) versus 10.7% (95% CI 10.5–10.9) in IIH during year 0–1, and remaining roughly twofold higher thereafter. Migraine preventive therapies were generally more common in migraine controls over time, except anti-epileptics. Beta-blockers and TCA migraine prevention in the first year after diagnosis were higher in migraine than IIH (beta-blockers: 11.10%, 95% CI 11.05–11.15 vs 8.30%, 95% CI 8.12–8.48; TCA: 13.50%, 95% CI 13.45–13.55 vs 10.90%, 95% CI 10.69–11.11) and remained approximately 40% higher for beta-blockers and 25% higher for TCAs throughout years 1 to 6 after diagnosis. Anti-epileptic agent use was higher in IIH than migraine in the first year after diagnosis (26.6%, 95% CI 26.3–26.9 vs 21.9%, 95% CI 21.8–22.0), and both fell to ~ 8% by year 6. A-C) headache abortive therapies (non-opioid analgesics, opioid analgesics, triptans) D-F) show headache prevention agents (beta-blockers, anti-epileptics, tricyclic antidepressants) Rates are plotted separately for IIH (red) and migraine controls (blue), with 95% CI. IIH versus population controls. Compared with population controls, IIH was associated with higher odds of both ORD (OR 3.72, 95% CI 3.54–3.92) and MOH (OR 117.99, 95% CI 110.17-126.36) (Table 2 ). After stratification and Mantel-Haenszel pooling, associations remained significant across age, race, SVI, and BMI (all CMH p < 0.0001). Stratified common ORs ranged from 3.46 to 4.52 for ORD and 90.26 to 135.11 for MOH. Compared with crude estimates, age stratification increased the pooled ORs (+ 21.5% for ORD; +14.5% for MOH), whereas BMI produced the greatest attenuation (-21.5% for ORD; -23.5% for MOH). ORD was homogeneous by age but heterogeneous by race, SVI, and BMI. MOH showed heterogeneity by age, race, SVI, and BMI. Full level-specific odds ratios with 95% CIs and BD statistics appear in Supplementary Tables S2 (ORD) and S3 (MOH). Table 2 Stratification-adjusted associations of idiopathic intracranial hypertension with opioid-related disorders and medication-overuse headache versus population controls Stratifier Opioid Related Disorder (Crude OR = 3.72) Medication Overuse Headache (Crude OR = 117.99) Common OR (95% CI) CMH p-value BD Homogeneity Test Δ vs crude OR Common OR (95% CI) CMH p-value BD Homogeneity Test Δ vs crude OR Age 4.52 (4.31–4.74) < 0.0001 , 21.5% 135.11 (126.25-144.59) < 0.0001 † 14.5% Race 3.46 (3.29–3.63) < 0.0001 † -7.1% 108.75 (102.04-115.89) < 0.0001 † -7.8% Social Vulnerability Index 3.61 (3.37–3.86) < 0.0001 † -3.1% 103.41 (94.17-113.55) < 0.0001 † -12.4% BMI 2.92 (2.82–3.02) < 0.0001 † -21.5% 90.26 (86.22–94.50) < 0.0001 † -23.5% Each stratifier, the CMH common odds ratio with 95% CI and associated p-value, the BD homogeneity test as a significance marker, and the percent change from the crude odds ratio. MH estimates are stratum-weighted pooled associations; when BD is significant (†, p < 0.05), the pooled value summarizes heterogeneous stratum-specific effects. Full Breslow-Day values (χ 2 , degrees of freedom, p) and all stratum-specific ORs within the levels of each stratifier are provided in Supplementary Tables S2-S3. IIH versus migraine controls. Compared with migraine controls, IIH showed lower odds of ORD overall (OR 0.88, 95% CI 0.84–0.93) (Table 3 ). Stratified estimates were null by age (OR 1.00, 95% CI 0.95–1.05) and modestly below one by race (OR 0.93, 95% CI 0.89–0.98), SVI (OR 0.88, 95% CI 0.82–0.95), and BMI (OR 0.90, 95% CI 0.87–0.94). In contrast, IIH was associated with higher odds of MOH (OR 1.29, 95% CI 1.21–1.37). Estimates remained significant after stratification by age, race, SVI, and BMI (all CMH p < 0.0001). ORD showed heterogeneity across race, SVI, and BMI but not by age. Heterogeneity was detected across race only for MOH. Full level-specific odds ratios with 95% CIs and homogeneity tests are provided in Supplementary Tables S4 (ORD) and S5 (MOH). Table 3 Stratification-adjusted associations of idiopathic intracranial hypertension with opioid-related disorders and medication-overuse headache versus migraine controls Opioid Related Disorder (Crude OR = 0.88) Medication Overuse Headache (Crude OR = 1.29) Stratifier Common OR (95% CI) CMH p-value BD Homogeneity Test Δ vs crude OR Common OR (95% CI) CMH p-value BD Homogeneity Test Δ vs crude OR Age 1.00 (0.95–1.05) 0.9686 , 13.5% 1.32 (1.25–1.40) < 0.0001 , 2.6% Race 0.93 (0.89–0.98) 0.0033 † 5.6% 1.32 (1.25–1.40) < 0.0001 † 2.4% Social Vulnerability Index 0.88 (0.82–0.95) 0.0006 † 0.5% 1.23 (1.13–1.34) < 0.0001 , 4.6% BMI 0.90 (0.87–0.94) < 0.0001 † 2.7% 1.39 (1.33–1.46) < 0.0001 , 8.0% Each stratifier, the CMH common odds ratio with 95% CI and associated p-value, the BD homogeneity test as a significance marker, and the percent change from the crude odds ratio. MH estimates are stratum-weighted pooled associations; when BD is significant (†, p < 0.05), the pooled value summarizes heterogeneous stratum-specific effects. Full Breslow-Day values (χ 2 , degrees of freedom, p) and all stratum-specific ORs within the levels of each stratifier are provided in Supplementary Tables S4-S5. Medication use around VSS and VPS. We compared post operative medication use in 4,109 patients who underwent VSS-only and 11,756 patients who underwent VPS-only within 3 years from diagnosis of IIH (Fig. 2 ; Supplementary Table S6). Acetazolamide use declined significantly after VPS (OR = 0.60; 95% CI 0.53–0.67; p < 0.001) and VSS (OR = 0.61; 95% CI 0.54–0.69; p < 0.001). Opioid use decreased following both VSS (OR = 0.84; 95% CI 0.75–0.93; p < 0.01) and VPS (OR = 0.92; 95% CI 0.86–0.98; p < 0.05). Non-opioid analgesic use was higher in the VPS cohort (OR = 1.24; 95% CI 1.16–1.33; p < 0.001) compared with the VSS cohort, in which non-opioid analgesic use was not significantly different from baseline (OR = 1.04; 95% CI 0.92–1.17; p = 0.56). Triptan use did not change significantly in both the VPS cohort (OR = 0.96; 95% CI 0.83–1.10; p = 0.52) or the VSS cohort (0R = 0.89; 95% CI 0.75–1.05; p = 0.17). For migraine preventive agents in the VPS cohort, use of anti-epileptic migraine preventives was modestly higher (OR = 1.09; 95% CI 1.01–1.18; p < 0.05), whereas beta-blockers (OR = 0.95; 95% CI 0.85–1.07; p = 0.40) and TCAs (OR = 1.10; 95% CI 0.99–1.22; p = 0.07) did not differ significantly. In the VSS cohort, no significant changes in migraine preventive medication use were observed following the procedure, including beta-blockers (OR = 0.92; 95% CI 0.77–1.10; p = 0.35), anti-epileptics (OR = 0.95; 95% CI 0.85–1.07; p = 0.38), and TCAs (OR = 0.96; 95% CI 0.83–1.11; p = 0.57). Discussion We confirm that women with IIH have higher exposure to opioids and analgesics around diagnosis than matched migraine comparators. This parallels the prescribing patterns reported in the UK cohort study, though suggesting a more moderate effect. 11 In the UK cohort, twice as many women with IIH were prescribed opioids compared to migraine controls. Our findings show a more moderate difference across a larger cohort, with approximately 25% higher opioid prescribing in IIH, likely reflecting broader opioid use in the United States. Preventive headache medications were more commonly prescribed to IIH patients in the UK, whereas in our cohort, this pattern was limited to anti-epileptic agents. In contrast, TCAs and beta-blockers were used more often in migraine patients and remained elevated for up to six years after diagnosis. These differences suggest that although migraine-directed therapies, particularly anti-epileptics, are used in IIH due to overlapping headache features, treatment in the U.S. more often relies on general analgesics and opioids. 7 , 11 IIH was significantly associated with increased odds of MOH compared to population controls. Although evidence of confounding by age, SVI, and BMI was observed, as indicated by > 10% changes in stratified odds estimates, the odds within these stratifications remained significantly elevated compared to the population controls. Age stratification resulted in an increased odds estimate, suggesting negative confounding due to the younger age distribution within the IIH cohort, whose lower risk of MOH likely attenuated the original estimate. Conversely, stratification by BMI and SVI led to a decreased odds estimate, indicating potential positive confounding. When compared to migraine controls, the adjusted odds of MOH were smaller but still significantly elevated. MOH is a likely downstream consequence of the absence of targeted and evidenced-based therapy for headache management in IIH, which has been identified as an urgent clinical need. 27 , 28 Because the IIH headache phenotype is influenced by intracranial pressure physiology, patients may not respond predictably to migraine-targeted therapies alone, and reliance on analgesics poses the risk of MOH. 7 Structured headache management and counseling, as a supplement to intracranial pressure management, may be necessary to reduce morbidity related to persistent headache. IIH demonstrated higher odds of ORD than population controls, which persisted after stratification. However, this risk appears to be characteristic of chronic headache populations rather than specific to IIH, as ORD risk became similar among the migraine and IIH cohorts after stratification by age. These findings suggest that ORD risk in IIH may reflect patterns common to both headache populations, underscoring the importance of opioid-sparing strategies in headache management more broadly rather than IIH-specific factors. The analysis of post-surgical medication reliance following VSS and VPS indicates potential similarities and differences in post-operative pain management patterns. Specifically, VSS was associated with a reduction in postoperative opioid use and no significant increase in triptan use, with similar postoperative patterns observed following VPS. Non-opioid analgesic use increased following VPS but did not significantly change after VSS. Since MOH is known to develop with opioids, triptans, and simple analgesics, and since VSS is minimally invasive and has been shown to be as safe as VPS, our findings suggest that VSS may mitigate the risk of postoperative medication overuse while achieving comparable clinical safety. 29,30 Importantly, this apparent reduction in medication overuse does not eliminate the need for ongoing abortive and prophylactic headache therapies, consistent with evidence that headache burden may persist despite ICP lowering. 31 , 32 Together, these findings support the need for randomized trials to identify effective, targeted headache treatments and optimize pain management strategies that reduce medication overuse risks in IIH patients. Several limitations exist. Cosmos enables large-scale longitudinal analyses across the U.S., increasing generalizability. However, Cosmos represents a convenience sample drawn from participating Epic systems, not a probability sample of the US population. Studies are retrospective and limited to aggregate, de-identified counts, with possible confounding and coding variability. Our focus on the majority IIH subgroup limits generalizability to men, adolescents, and those with BMI < 30, who represent a minority of cases. These limitations warrant cautious interpretation and necessitate prospective, patient level research. Conclusion This study reveals distinct medication patterns and risks in IIH patients compared to migraine sufferers and the general population. Key findings include higher opioid use in IIH than migraine control and increased odds of MOH than migraine and population control. Both VSS and VPS effectively manage ICP and may also reduce opioid reliance to prevent downstream morbidity from MOH or ORD. Reliance on abortive and prophylactic headache therapies persists after surgery, emphasizing the importance of IIH-specific headache management and medication counseling. Abbreviations AMC Albany Medical Center BD Breslow–Day BMI Body mass index CDC Center for Disease Control CI Confidence interval CMH Cochran–Mantel–Haenszel CPT Current Procedural Terminology CSF Cerebrospinal fluid EHR Electronic health record HIPAA Health Insurance Portability and Accountability Act ICD 10–CM–International Classification of Diseases, Tenth Revision, Clinical Modification ICD 10–PCS–International Classification of Diseases, Tenth Revision, Procedure Coding System ICHD 3–International Classification of Headache Disorders, 3rd edition ICP Intracranial pressure IIH Idiopathic intracranial hypertension/benign intracranial hypertension IHS International Headache Society IRB Institutional Review Board MH Mantel–Haenszel MOH Medication–overuse headache OR Odds ratio ORD Opioid–related disorder(s) SVI Social Vulnerability Index STROBE Strengthening the Reporting of Observational Studies in Epidemiology TCA Tricyclic antidepressant(s) VPS Ventriculoperitoneal shunting VSS Venous sinus stenting Declarations Ethics approval and consent to participate Albany Medical College determined the project to be IRB exempt (IRB Determination #: R_115p9425BQVx4Ty) given the deidentified nature of this study. Consent for publication Not applicable (aggregate, de-identified data). Competing Interests The authors declare no competing interests. Funding The authors received no specific funding for this work. Author Contribution Study concept/design: A.R.P., B.S.S.; Data curation and analysis: B.S.S.; Interpretation: all authors; Drafting: B.S.S., D.J.; Critical revision: A.R.P., A.A.G.; Supervision: A.R.P. All authors approved the final manuscript. Acknowledgements The authors thank Albany Medical Center for facilitating access to Epic Cosmos for this study. The authors acknowledge the health systems contributing data to Epic Cosmos. Data Availability This analysis used aggregate, de-identified counts from Epic Cosmos under a data-set agreement with participating health systems. Per those agreements, data cannot be publicly shared. Additional information may be available from the corresponding author upon reasonable request. 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Br J Anaesth 122(6):e114–e126. 10.1016/j.bja.2018.09.019 Dinkin MJ, Patsalides A (2023) Idiopathic Intracranial Venous Hypertension: Toward a Better Understanding of Venous Stenosis and the Role of Stenting in Idiopathic Intracranial Hypertension. J Neuroophthalmol 43(4):451–463. 10.1097/WNO.0000000000001898 Nicholson P, Brinjikji W, Radovanovic I et al (2019) Venous sinus stenting for idiopathic intracranial hypertension: a systematic review and meta-analysis. J NeuroInterventional Surg 11(4):380–385. 10.1136/neurintsurg-2018-014172 Epic Systems Corporation. About Cosmos. Cosmos website. Accessed August 8 (2025) https://cosmos.epic.com/about Gunderson MA, Dorr DA, Freedman H, Melton GB (2025) A Longitudinal Analysis of Institutional Adoption, Use, and Dissemination of an EHR Vendor-Based Data Sharing Program. 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Biometrics 10(4):417. 10.2307/3001616 Mantel N, Haenszel W (1959) Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease. JNCI J Natl Cancer Inst Published online April. 10.1093/jnci/22.4.719 Tarone RE (1985) On heterogeneity tests based on efficient scores. Biometrika 72(1):91–95. 10.1093/biomet/72.1.91 Breslow NE, Day NE (1980) Statistical methods in cancer research. I - The analysis of case-control studies. IARC Sci Publ. ;(32):5–338 The R Core Team R: A Language and Environment for Statistical Computing Signorell A, DescTools (2014) Tools for Descriptive Statistics. Published online January 7, :0.99.60. 10.32614/CRAN.package.DescTools Mollan SP, Grech O, Sinclair AJ (2021) Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: A narrative review. Headache J Head Face Pain 61(6):808–816. 10.1111/head.14125 Bonelli L, Menon V, Arnold AC, Mollan SP (2024) Managing idiopathic intracranial hypertension in the eye clinic. Eye 38(12):2472–2481. 10.1038/s41433-024-03140-y Intrapiromkul J, Rai AT, Lakhani DA Transverse venous sinus stenting versus cerebrospinal fluid shunting in idiopathic intracranial hypertension: a multi-institutional and multinational database study. J Neurointerventional Surg. Published online June 27, 2025:jnis–2025. 10.1136/jnis-2025-023699 Limmroth V, Katsarava Z, Fritsche G, Przywara S, Diener HC (2002) Features of medication overuse headache following overuse of different acute headache drugs. Neurology 59(7):1011–1014. 10.1212/wnl.59.7.1011 deSouza RM, Toma A, Watkins L (2015) Medication overuse headache - An under-diagnosed problem in shunted idiopathic intracranial hypertension patients. Br J Neurosurg 29(1):30–34. 10.3109/02688697.2014.950633 Patsalides A, Oliveira C, Wilcox J et al (2019) Venous sinus stenting lowers the intracranial pressure in patients with idiopathic intracranial hypertension. J NeuroInterventional Surg 11(2):175–178. 10.1136/neurintsurg-2018-014032 Additional Declarations No competing interests reported. Supplementary Files SupplementalIIHJNSManuscript.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":51046,"visible":true,"origin":"","legend":"\u003cp\u003eLongitudinal Medication Utilization in IIH versus Migraine Controls. \u003cbr\u003e\nA-C) headache abortive therapies (non-opioid analgesics, opioid analgesics, triptans)\u003cbr\u003e\nD-F) show headache prevention agents (beta-blockers, anti-epileptics, tricyclic antidepressants)\u003c/p\u003e\n\u003cp\u003eRates are plotted separately for IIH (red) and migraine controls (blue), with 95% CI.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8532079/v1/bda7ca665c9aabb3cb132328.jpg"},{"id":100010563,"identity":"35a6f5cf-8e8d-476b-a6eb-a2cb8b1d2fa4","added_by":"auto","created_at":"2026-01-12 06:07:01","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20777,"visible":true,"origin":"","legend":"\u003cp\u003eChange in medication use after VSS versus VPS. Forest plot of ORs comparing post-procedure vs pre-procedure medication use. Points denote ORs and horizontal bars indicate 95% CIs; the vertical dashed line marks OR = 1 (no change).\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8532079/v1/10e38197d344b76f434e976d.jpg"},{"id":100767139,"identity":"18dd6130-b57f-4dc9-99d2-ca04287d136e","added_by":"auto","created_at":"2026-01-21 09:09:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1004655,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8532079/v1/55a8259b-1eba-438d-8375-94479a02f96f.pdf"},{"id":100010565,"identity":"769595e6-4442-4053-b9b6-bd0e8ea6c0c6","added_by":"auto","created_at":"2026-01-12 06:07:01","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":39714,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalIIHJNSManuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8532079/v1/fc740978ad747e25facd2671.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Idiopathic intracranial hypertension carries a high medication overuse headache burden and a chronic-headache-like opioid related disorder risk: a nationwide cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP) of unclear cause, with predominance in obese women of childbearing age.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Management of IIH focuses on control of intracranial pressure (ICP) and weight reduction, but headaches can persist even after ICP control is achieved.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e First-line medical treatment is acetazolamide, while surgical management includes CSF shunting and optic nerve sheath fenestration.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Headache is a common symptom, often pulsatile, and can mimic migraine. Although migraine-directed therapies are usually attempted, simple analgesics and opioids are frequently prescribed for symptom management.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Sustained analgesic use increases the risk of medication-overuse headache (MOH), defined by ICHD-3 as acute medication use on \u0026ge;\u0026thinsp;10\u0026ndash;15 days per month for more than three months, with lower thresholds for opioids and combination analgesics.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e MOH can drive headache chronicity, disability, and treatment resistance.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e The IIH Treatment Trial showed that medication overuse was frequent at baseline in this population, with more than one-third of patients overusing symptomatic headache treatments.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e High opioid exposure in IIH also raises concern for opioid-related disorders (ORD), including misuse, dependence, and withdrawal.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Chronic opioid therapy may worsen pain via opioid-induced hyperalgesia, and migraine guidelines discourage routine use due to limited benefit, increased risk of MOH, and dependence.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e We retrospectively evaluated whether analgesics and opioids are prescribed more frequently in IIH than in migraine controls in a large, national, multi-institutional cohort. We hypothesized that such prescribing patterns are associated with a higher incidence of MOH and ORD compared to the population and migraine controls.\u003c/p\u003e \u003cp\u003eVenous sinus stenosis is increasingly recognized as a contributor to the pathophysiology of IIH.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Venous sinus stenting (VSS), in carefully selected patients, is an alternative to CSF shunting and has been associated with improvement in headaches in a systematic review.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e However, a comparison of headache management after ventriculoperitoneal shunting (VPS) versus VSS is lacking.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e We hypothesized that, following VSS, the frequency of medications to manage headache would be comparable to or lower than after VPS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Data Source\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study in Epic Cosmos (Epic Systems, Verona, WI), a national, multi-institution electronic health record resource compiled from participating health systems.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Cosmos integrates longitudinal patient charts across ambulatory and inpatient settings, representing over 300\u0026nbsp;million patient records from over 1,700 hospitals and 40,000 clinics. SlicerDicer is a data exploration tool in Cosmos that lets users create custom queries and retrieve aggregate results in a secure environment. The study was determined by Albany Medical College (AMC) as IRB exempt (IRB Determination #: R_115p9425BQVx4Ty). This study adhered to the STROBE guidelines.\u003c/p\u003e \u003cp\u003e \u003cb\u003ePatient Cohorts.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe assembled four cohorts using the Patient data model in Cosmos SlicerDicer. We added a Base Patient filter to all cohorts, limiting searches to patients who have had at least two encounters within two years. Criteria used to define the cohorts were restricted to data from January 1, 2002, through June 25, 2025.\u003c/p\u003e \u003cp\u003eThe IIH cohort comprised patients with prevalent idiopathic (benign) intracranial hypertension (ICD-10-CM G93.2). The migraine control cohort comprised patients with prevalent migraine (ICD-10-CM G43.*) but without IIH. The population control cohort excluded diagnosis of IIH or migraine. To improve between-cohort comparability, all three cohorts were restricted to adult women aged 18\u0026ndash;75 years with body mass index (BMI)\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; (class I-III obesity).\u003c/p\u003e \u003cp\u003eThe VSS and VPS cohorts comprised patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years with idiopathic (benign) intracranial hypertension (ICD-10-CM G93.2). VSS procedures were identified using CPT codes 37238, 37239, 61635 and ICD-10-PCS codes 05HL3DZ and 057L3DZ.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e VPS procedures were identified using CPT code 62223 and ICD-10-PCS codes 009600Z, 009630Z, 0016076, 00160J6, 00160K6, 0016376, 00163J6, 00163K6, 0016476, 00164J6, 00164K6.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Eligibility required that patients undergo the procedure within three years of diagnosis (G39.2). Cases were excluded if a concurrent billing diagnosis of IIH did not accompany stenting codes, or if the alternate procedure was performed within the three-year timeframe.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMeasurements\u003c/h3\u003e\n\u003cp\u003eThe Cosmos dataset includes demographic and clinical variables. BMI, recorded under vital signs, is calculated from documented height and weight and expressed in kg/m^2. Obesity class was defined as Obese [BMI 30-39.9] vs Morbidly Obese [\u0026ge;\u0026thinsp;40]. Age was determined using \u0026ldquo;Age at Time of Event\u0026rdquo;, restricting patients to those within a specified age range at the time of a corresponding event. Patients were categorized by age: 18\u0026ndash;44, 45\u0026ndash;75 years, and 75+. Race was documented at the local level by either self-reporting or staff entry. Race categories were American Indian/Alaska Native, Black/African American, White, and all other categories combined as \u0026ldquo;Other Race\u0026rdquo; (collapsed due to suppression of cell counts\u0026thinsp;\u0026lt;\u0026thinsp;10 for minority categories). The Social Vulnerability Index (SVI) is available in Cosmos and is derived from census tract data from the US Centers for Disease Control and Prevention (CDC); higher percentiles indicate greater vulnerability. Disease incidence was represented by \u0026ldquo;New Diagnoses\u0026rdquo; and prevalent disease by \u0026ldquo;Active Diagnoses\u0026rdquo;. Procedures were ascertained under \u0026ldquo;Billed Procedures\u0026rdquo;, with corresponding diagnoses under \u0026ldquo;Billed Diagnoses\u0026rdquo;. The \u0026ldquo;All Medications\u0026rdquo; flag captures medication activity across prescriptions, pharmacy dispenses, administrations, and patient-reported use. Medication classes comprised Cosmos-native and user-defined sets including Analgesics (opioid analgesics; non-opioid analgesics), Triptans, and Migraine prevention (β-blockers; antiepileptics; tricyclic antidepressants (TCAs)). The full list of constituent medications is provided in Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eOutcomes and Statistical Analyses\u003c/h3\u003e\n\u003cp\u003eFor longitudinal analyses of medication rates, we indexed women in the IIH and migraine-control cohorts on the incident diagnosis date. We summarized medication exposure in successive one-year intervals from one year before through six years after the index. For each cohort-interval-class, we obtained the percentage of the defined population meeting the medication-class criterion with 95% confidence intervals (CI). Exposure to a class was defined as any documented record during the interval.\u003c/p\u003e \u003cp\u003eWe conducted unadjusted analyses of the associations between binary IIH status and two incident binary outcomes, opioid-related disorders (ICD-10-CM F11.*) and medication-overuse headache (ICD-10-CM G44.41, G44.40). For each comparison, events were restricted to incident disease after cohort entry, and crude odds ratios (ORs) with 95% CIs were calculated. Baseline characteristics of the IIH and control cohorts were compared across age bands, race, SVI quartiles, and obesity classes. Global Pearson χ\u0026sup2; tests comparing IIH with each control group, controlling for these covariates, were conducted. Residual imbalance was anticipated despite coarse matching, motivating stratified analysis using the Cochran-Mantel-Haenszel (CMH) test to evaluate conditional independence, i.e. an association between two binary variables (e.g., IIH and MOH), while controlling for a third categorical factor (e.g. BMI strata).\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Using CMH, we generated a common weighted OR that estimates the exposure-outcome association accounting for stratification and serves a proxy for an adjusted OR in aggregate 2x2 analyses. An absolute difference\u0026thinsp;\u0026ge;\u0026thinsp;10% between the MH common OR and crude OR served as evidence of confounding (Δ vs crude = [(MH common OR \u0026ndash; crude OR)/crude OR] \u0026times;100%)). The CMH test statistic was used to compute p-values. The common OR is an appropriate summary when the homogeneity assumption holds (i.e., stratum-specific ORs are homogenous). Homogeneity was assessed with the Breslow-Day (BD) χ\u0026sup2; test, which evaluates the null that all stratum-specific ORs are equal.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e When BD test was non-significant, the common OR is interpreted as a single conditional effect. When significant, the common OR is treated as a summary across heterogeneous strata.\u003c/p\u003e \u003cp\u003eWe conducted an exploratory pre-post study of medication use in adults with IIH who underwent VSS-only or VPS-only (i.e., no crossover). The procedure date served as the index date. Medication classes matched those used in the longitudinal analysis (Supplemental Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). For each class, we measured the proportion of patients with any documented use during the year before and the year after the procedure (allowing a\u0026thinsp;\u0026plusmn;\u0026thinsp;2-month window). We calculated odds ratios with 95% confidence intervals and used Pearson χ\u0026sup2; tests for comparisons. Alpha was set at 0.05.\u003c/p\u003e \u003cp\u003eAll analyses were performed in R (R Foundation for Statistical Computing) using base stats and DescTools.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eBaseline Characteristics.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe analyzed 82,295 individuals with IIH, 26,003,964 population controls, and 1,716,441 migraine controls (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Across all cohorts, patients were adult women with obesity by study design. The IIH cohort was younger (approximately two-thirds aged between 18\u0026ndash;44 and one-third 45\u0026ndash;75) than population controls. Migraine controls exhibited intermediate age ranges. The IIH cohort included a higher proportion of Black/African American patients compared with controls. Where available, IIH patients demonstrated higher SVI scores than population controls. IIH patients were roughly split between class I-II (30\u0026ndash;39 kg/m\u003csup\u003e2\u003c/sup\u003e) and class III (\u0026ge;\u0026thinsp;40 kg/m\u003csup\u003e2\u003c/sup\u003e) obesity. Population controls predominantly fell into class III, whereas migraine controls were more often in class I-II.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIIH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePopulation Control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMigraine Control\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82,295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,003,964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,716,441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge categories\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u0026ndash;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64,365 (69.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11,371,608 (43.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,053,972 (53.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u0026ndash;75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28,658 (30.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14,632,356 (56.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e926,062 (46.77%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54,118 (57.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15,942,235 (56.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,318,117 (68.54%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlack or African American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25,481 (27.07%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,967,153 (17.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e278,533 (14.48%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther Race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,862 (12.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,103,862 (14.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e244,568 (12.72%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmerican Indian or Alaska Native\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,268 (1.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e314,209\u003c/p\u003e \u003cp\u003e(1.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27,978\u003c/p\u003e \u003cp\u003e(1.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,417 (1.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,772,007 (9.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53,975\u003c/p\u003e \u003cp\u003e(2.81%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eSocial Vulnerability Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50% \u0026minus;\u0026thinsp;75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,930 (14.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,333,239 (12.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e240,913 (14.04%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;75% (most vulnerable)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,118 (13.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,359,077 (12.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e199,088 (11.60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25% \u0026minus;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,076 (13.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,284,370 (12.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e252,645 (14.72%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25% (least vulnerable)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9,293 (11.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,053,370 (11.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e236,758 (13.79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38,878 (47.24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12,973,908 (49.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e787,037 (45.85%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBMI categories\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObese 30\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68,905 (55.07%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28,829,841 (31.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,241,954 (72.73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMorbidly Obese\u0026thinsp;\u0026gt;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56,213 (44.93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63,181,950 (68.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e840,576 (27.27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eLongitudinal Trends in Medical Headache Management in IIH versus Migraine Controls.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAcross all classes, utilization rose from the year before diagnosis to the first year after diagnosis, then declined through years 1 to 6 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Peaks in the first post-diagnosis year were higher in IIH for opioids (32.4%, 95% CI 32.1\u0026ndash;32.7 vs 26.0%, 95% CI 25.9\u0026ndash;26.1) and non-opioid analgesics (26.1%, 95% CI 25.8\u0026ndash;26.4 vs 18.9%, 95% CI 18.8\u0026ndash;19.0). Triptan use was consistently greater in migraine controls across all intervals, peaking at 20.3% (95% CI 20.2\u0026ndash;20.4) versus 10.7% (95% CI 10.5\u0026ndash;10.9) in IIH during year 0\u0026ndash;1, and remaining roughly twofold higher thereafter. Migraine preventive therapies were generally more common in migraine controls over time, except anti-epileptics. Beta-blockers and TCA migraine prevention in the first year after diagnosis were higher in migraine than IIH (beta-blockers: 11.10%, 95% CI 11.05\u0026ndash;11.15 vs 8.30%, 95% CI 8.12\u0026ndash;8.48; TCA: 13.50%, 95% CI 13.45\u0026ndash;13.55 vs 10.90%, 95% CI 10.69\u0026ndash;11.11) and remained approximately 40% higher for beta-blockers and 25% higher for TCAs throughout years 1 to 6 after diagnosis. Anti-epileptic agent use was higher in IIH than migraine in the first year after diagnosis (26.6%, 95% CI 26.3\u0026ndash;26.9 vs 21.9%, 95% CI 21.8\u0026ndash;22.0), and both fell to ~\u0026thinsp;8% by year 6.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA-C) headache abortive therapies (non-opioid analgesics, opioid analgesics, triptans)\u003c/p\u003e \u003cp\u003eD-F) show headache prevention agents (beta-blockers, anti-epileptics, tricyclic antidepressants)\u003c/p\u003e \u003cp\u003eRates are plotted separately for IIH (red) and migraine controls (blue), with 95% CI.\u003c/p\u003e \u003cp\u003e \u003cb\u003eIIH versus population controls.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCompared with population controls, IIH was associated with higher odds of both ORD (OR 3.72, 95% CI 3.54\u0026ndash;3.92) and MOH (OR 117.99, 95% CI 110.17-126.36) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After stratification and Mantel-Haenszel pooling, associations remained significant across age, race, SVI, and BMI (all CMH p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Stratified common ORs ranged from 3.46 to 4.52 for ORD and 90.26 to 135.11 for MOH. Compared with crude estimates, age stratification increased the pooled ORs (+\u0026thinsp;21.5% for ORD; +14.5% for MOH), whereas BMI produced the greatest attenuation (-21.5% for ORD; -23.5% for MOH). ORD was homogeneous by age but heterogeneous by race, SVI, and BMI. MOH showed heterogeneity by age, race, SVI, and BMI. Full level-specific odds ratios with 95% CIs and BD statistics appear in Supplementary Tables S2 (ORD) and S3 (MOH).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStratification-adjusted associations of idiopathic intracranial hypertension with opioid-related disorders and medication-overuse headache versus population controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStratifier\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eOpioid Related Disorder (Crude OR\u0026thinsp;=\u0026thinsp;3.72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eMedication Overuse Headache (Crude OR\u0026thinsp;=\u0026thinsp;117.99)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCommon OR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCMH\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eBD Homogeneity Test\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eΔ vs crude OR\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eCommon OR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eCMH p-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eBD Homogeneity Test\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eΔ vs crude OR\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.52 (4.31\u0026ndash;4.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e135.11 (126.25-144.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e14.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.46 (3.29\u0026ndash;3.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-7.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e108.75 (102.04-115.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-7.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial Vulnerability Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.61 (3.37\u0026ndash;3.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-3.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103.41 (94.17-113.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-12.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.92 (2.82\u0026ndash;3.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-21.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90.26 (86.22\u0026ndash;94.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-23.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEach stratifier, the CMH common odds ratio with 95% CI and associated p-value, the BD homogeneity test as a significance marker, and the percent change from the crude odds ratio. MH estimates are stratum-weighted pooled associations; when BD is significant (\u0026dagger;, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the pooled value summarizes heterogeneous stratum-specific effects. Full Breslow-Day values (χ\u003csup\u003e2\u003c/sup\u003e, degrees of freedom, p) and all stratum-specific ORs within the levels of each stratifier are provided in Supplementary Tables S2-S3.\u003c/p\u003e \u003cp\u003e \u003cb\u003eIIH versus migraine controls.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCompared with migraine controls, IIH showed lower odds of ORD overall (OR 0.88, 95% CI 0.84\u0026ndash;0.93) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Stratified estimates were null by age (OR 1.00, 95% CI 0.95\u0026ndash;1.05) and modestly below one by race (OR 0.93, 95% CI 0.89\u0026ndash;0.98), SVI (OR 0.88, 95% CI 0.82\u0026ndash;0.95), and BMI (OR 0.90, 95% CI 0.87\u0026ndash;0.94). In contrast, IIH was associated with higher odds of MOH (OR 1.29, 95% CI 1.21\u0026ndash;1.37). Estimates remained significant after stratification by age, race, SVI, and BMI (all CMH p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). ORD showed heterogeneity across race, SVI, and BMI but not by age. Heterogeneity was detected across race only for MOH. Full level-specific odds ratios with 95% CIs and homogeneity tests are provided in Supplementary Tables S4 (ORD) and S5 (MOH).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStratification-adjusted associations of idiopathic intracranial hypertension with opioid-related disorders and medication-overuse headache versus migraine controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eOpioid Related Disorder (Crude OR\u0026thinsp;=\u0026thinsp;0.88)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eMedication Overuse Headache (Crude OR\u0026thinsp;=\u0026thinsp;1.29)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStratifier\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCommon OR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCMH\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eBD Homogeneity Test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eΔ vs crude OR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eCommon OR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eCMH p-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eBD Homogeneity Test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eΔ vs crude OR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 (0.95\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9686\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.32 (1.25\u0026ndash;1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93 (0.89\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.32 (1.25\u0026ndash;1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial Vulnerability Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.88 (0.82\u0026ndash;0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.23 (1.13\u0026ndash;1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.90 (0.87\u0026ndash;0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.39 (1.33\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEach stratifier, the CMH common odds ratio with 95% CI and associated p-value, the BD homogeneity test as a significance marker, and the percent change from the crude odds ratio. MH estimates are stratum-weighted pooled associations; when BD is significant (\u0026dagger;, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the pooled value summarizes heterogeneous stratum-specific effects. Full Breslow-Day values (χ\u003csup\u003e2\u003c/sup\u003e, degrees of freedom, p) and all stratum-specific ORs within the levels of each stratifier are provided in Supplementary Tables S4-S5.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMedication use around VSS and VPS.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe compared post operative medication use in 4,109 patients who underwent VSS-only and 11,756 patients who underwent VPS-only within 3 years from diagnosis of IIH (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table S6). Acetazolamide use declined significantly after VPS (OR\u0026thinsp;=\u0026thinsp;0.60; 95% CI 0.53\u0026ndash;0.67; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and VSS (OR\u0026thinsp;=\u0026thinsp;0.61; 95% CI 0.54\u0026ndash;0.69; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Opioid use decreased following both VSS (OR\u0026thinsp;=\u0026thinsp;0.84; 95% CI 0.75\u0026ndash;0.93; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and VPS (OR\u0026thinsp;=\u0026thinsp;0.92; 95% CI 0.86\u0026ndash;0.98; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Non-opioid analgesic use was higher in the VPS cohort (OR\u0026thinsp;=\u0026thinsp;1.24; 95% CI 1.16\u0026ndash;1.33; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared with the VSS cohort, in which non-opioid analgesic use was not significantly different from baseline (OR\u0026thinsp;=\u0026thinsp;1.04; 95% CI 0.92\u0026ndash;1.17; p\u0026thinsp;=\u0026thinsp;0.56). Triptan use did not change significantly in both the VPS cohort (OR\u0026thinsp;=\u0026thinsp;0.96; 95% CI 0.83\u0026ndash;1.10; p\u0026thinsp;=\u0026thinsp;0.52) or the VSS cohort (0R\u0026thinsp;=\u0026thinsp;0.89; 95% CI 0.75\u0026ndash;1.05; p\u0026thinsp;=\u0026thinsp;0.17). For migraine preventive agents in the VPS cohort, use of anti-epileptic migraine preventives was modestly higher (OR\u0026thinsp;=\u0026thinsp;1.09; 95% CI 1.01\u0026ndash;1.18; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas beta-blockers (OR\u0026thinsp;=\u0026thinsp;0.95; 95% CI 0.85\u0026ndash;1.07; p\u0026thinsp;=\u0026thinsp;0.40) and TCAs (OR\u0026thinsp;=\u0026thinsp;1.10; 95% CI 0.99\u0026ndash;1.22; p\u0026thinsp;=\u0026thinsp;0.07) did not differ significantly. In the VSS cohort, no significant changes in migraine preventive medication use were observed following the procedure, including beta-blockers (OR\u0026thinsp;=\u0026thinsp;0.92; 95% CI 0.77\u0026ndash;1.10; p\u0026thinsp;=\u0026thinsp;0.35), anti-epileptics (OR\u0026thinsp;=\u0026thinsp;0.95; 95% CI 0.85\u0026ndash;1.07; p\u0026thinsp;=\u0026thinsp;0.38), and TCAs (OR\u0026thinsp;=\u0026thinsp;0.96; 95% CI 0.83\u0026ndash;1.11; p\u0026thinsp;=\u0026thinsp;0.57).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe confirm that women with IIH have higher exposure to opioids and analgesics around diagnosis than matched migraine comparators. This parallels the prescribing patterns reported in the UK cohort study, though suggesting a more moderate effect.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e In the UK cohort, twice as many women with IIH were prescribed opioids compared to migraine controls. Our findings show a more moderate difference across a larger cohort, with approximately 25% higher opioid prescribing in IIH, likely reflecting broader opioid use in the United States. Preventive headache medications were more commonly prescribed to IIH patients in the UK, whereas in our cohort, this pattern was limited to anti-epileptic agents. In contrast, TCAs and beta-blockers were used more often in migraine patients and remained elevated for up to six years after diagnosis. These differences suggest that although migraine-directed therapies, particularly anti-epileptics, are used in IIH due to overlapping headache features, treatment in the U.S. more often relies on general analgesics and opioids.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIIH was significantly associated with increased odds of MOH compared to population controls. Although evidence of confounding by age, SVI, and BMI was observed, as indicated by \u0026gt;\u0026thinsp;10% changes in stratified odds estimates, the odds within these stratifications remained significantly elevated compared to the population controls. Age stratification resulted in an increased odds estimate, suggesting negative confounding due to the younger age distribution within the IIH cohort, whose lower risk of MOH likely attenuated the original estimate. Conversely, stratification by BMI and SVI led to a decreased odds estimate, indicating potential positive confounding. When compared to migraine controls, the adjusted odds of MOH were smaller but still significantly elevated. MOH is a likely downstream consequence of the absence of targeted and evidenced-based therapy for headache management in IIH, which has been identified as an urgent clinical need.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Because the IIH headache phenotype is influenced by intracranial pressure physiology, patients may not respond predictably to migraine-targeted therapies alone, and reliance on analgesics poses the risk of MOH.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Structured headache management and counseling, as a supplement to intracranial pressure management, may be necessary to reduce morbidity related to persistent headache.\u003c/p\u003e \u003cp\u003eIIH demonstrated higher odds of ORD than population controls, which persisted after stratification. However, this risk appears to be characteristic of chronic headache populations rather than specific to IIH, as ORD risk became similar among the migraine and IIH cohorts after stratification by age. These findings suggest that ORD risk in IIH may reflect patterns common to both headache populations, underscoring the importance of opioid-sparing strategies in headache management more broadly rather than IIH-specific factors.\u003c/p\u003e \u003cp\u003eThe analysis of post-surgical medication reliance following VSS and VPS indicates potential similarities and differences in post-operative pain management patterns. Specifically, VSS was associated with a reduction in postoperative opioid use and no significant increase in triptan use, with similar postoperative patterns observed following VPS. Non-opioid analgesic use increased following VPS but did not significantly change after VSS. Since MOH is known to develop with opioids, triptans, and simple analgesics, and since VSS is minimally invasive and has been shown to be as safe as VPS, our findings suggest that VSS may mitigate the risk of postoperative medication overuse while achieving comparable clinical safety. \u003csup\u003e29,30\u003c/sup\u003e Importantly, this apparent reduction in medication overuse does not eliminate the need for ongoing abortive and prophylactic headache therapies, consistent with evidence that headache burden may persist despite ICP lowering.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Together, these findings support the need for randomized trials to identify effective, targeted headache treatments and optimize pain management strategies that reduce medication overuse risks in IIH patients.\u003c/p\u003e \u003cp\u003eSeveral limitations exist. Cosmos enables large-scale longitudinal analyses across the U.S., increasing generalizability. However, Cosmos represents a convenience sample drawn from participating Epic systems, not a probability sample of the US population. Studies are retrospective and limited to aggregate, de-identified counts, with possible confounding and coding variability. Our focus on the majority IIH subgroup limits generalizability to men, adolescents, and those with BMI\u0026thinsp;\u0026lt;\u0026thinsp;30, who represent a minority of cases. These limitations warrant cautious interpretation and necessitate prospective, patient level research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study reveals distinct medication patterns and risks in IIH patients compared to migraine sufferers and the general population. Key findings include higher opioid use in IIH than migraine control and increased odds of MOH than migraine and population control. Both VSS and VPS effectively manage ICP and may also reduce opioid reliance to prevent downstream morbidity from MOH or ORD. Reliance on abortive and prophylactic headache therapies persists after surgery, emphasizing the importance of IIH-specific headache management and medication counseling.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlbany Medical Center\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBreslow\u0026ndash;Day\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCenter for Disease Control\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCMH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCochran\u0026ndash;Mantel\u0026ndash;Haenszel\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCurrent Procedural Terminology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebrospinal fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectronic health record\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIPAA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHealth Insurance Portability and Accountability Act\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e10\u0026ndash;CM\u0026ndash;International Classification of Diseases, Tenth Revision, Clinical Modification\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e10\u0026ndash;PCS\u0026ndash;International Classification of Diseases, Tenth Revision, Procedure Coding System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICHD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e3\u0026ndash;International Classification of Headache Disorders, 3rd edition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntracranial pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIIH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIdiopathic intracranial hypertension/benign intracranial hypertension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIHS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Headache Society\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstitutional Review Board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMantel\u0026ndash;Haenszel\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMOH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMedication\u0026ndash;overuse headache\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eORD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOpioid\u0026ndash;related disorder(s)\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSVI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSocial Vulnerability Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTROBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTricyclic antidepressant(s)\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVentriculoperitoneal shunting\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVenous sinus stenting\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eAlbany Medical College determined the project to be IRB exempt (IRB Determination #: R_115p9425BQVx4Ty) given the deidentified nature of this study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable (aggregate, de-identified data).\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eStudy concept/design: A.R.P., B.S.S.; Data curation and analysis: B.S.S.; Interpretation: all authors; Drafting: B.S.S., D.J.; Critical revision: A.R.P., A.A.G.; Supervision: A.R.P. All authors approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors thank Albany Medical Center for facilitating access to Epic Cosmos for this study. The authors acknowledge the health systems contributing data to Epic Cosmos.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThis analysis used aggregate, de-identified counts from Epic Cosmos under a data-set agreement with participating health systems. Per those agreements, data cannot be publicly shared. Additional information may be available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMollan SP, Davies B, Silver NC et al (2018) Idiopathic intracranial hypertension: consensus guidelines on management. 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J NeuroInterventional Surg 11(2):175\u0026ndash;178. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/neurintsurg-2018-014032\u003c/span\u003e\u003cspan address=\"10.1136/neurintsurg-2018-014032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic intracranial hypertension, headache, migraine, venous sinus stenting, ventriculoperitoneal shunting, Epic Cosmos","lastPublishedDoi":"10.21203/rs.3.rs-8532079/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8532079/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIdiopathic intracranial hypertension (IIH) is defined by elevated intracranial pressure of unclear cause. Headaches often mimic migraine. In addition to migraine-directed therapies, opioids and simple analgesics are frequently prescribed. Sustained analgesic use increases the risk for medication overuse headache (MOH) and opioid exposure raises concern for opioid-related disorders (ORD). Venous sinus stenosis is increasingly being identified as a possible etiology of IIH, and venous sinus stenting (VSS) has emerged as an alternative to ventriculoperitoneal shunting (VPS). Comparative data on headache medication use after VSS versus VPS are limited.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eCompare headache-medication use patterns and associated risks (MOH, ORD) in IIH versus migraine and population controls. Evaluate changes in headache-medication use in VSS-only and VPS-only cohorts.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRetrospective cohort study in Epic Cosmos. Primary outcomes were incident ORD and MOH. Crude odds ratios (ORs) were calculated. Using a stratification approach (Mantel-Haenszel), ORs were computed within strata of age, race, Social Vulnerability Index (SVI) quartile, and BMI class, then pooled. Heterogeneity within strata was assessed with the Breslow-Day test. Longitudinal medication utilization was summarized in yearly intervals from one year before diagnosis through six years after. For surgical analysis, we compared the year after the procedure with the year before.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe identified 82,295 patients with IIH, 26,003,964 population controls, and 1,716,441 migraine controls. Opioid and non-opioid analgesic use peaked within one year after diagnosis. IIH was associated with higher odds of MOH vs. the population (OR 117.99, 95% CI 110.17-126.36) and migraine controls (OR 1.29, 95% CI 1.21\u0026ndash;1.37), with these associations persisting after adjustment. ORD odds were elevated versus population controls (OR 3.72, 95% CI 3.54\u0026ndash;3.92) but were similar to migraine controls after adjustment. Both VSS and VPS were associated with decreased acetazolamide and opioid use after surgery.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIIH is linked to substantial MOH risk beyond that seen in the general population and above migraine, while ORD risk appears characteristic of chronic headache populations. After either VSS or VPS, opioid reliance decreases, which may mitigate the downstream risk of MOH and ORD. Reliance on abortive and prophylactic headache therapies persists after surgery, emphasizing the importance of IIH-specific headache management and medication counseling.\u003c/p\u003e","manuscriptTitle":"Idiopathic intracranial hypertension carries a high medication overuse headache burden and a chronic-headache-like opioid related disorder risk: a nationwide cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:06:56","doi":"10.21203/rs.3.rs-8532079/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38dfc620-2447-4abc-b508-963b4a5c2b4b","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-21T08:28:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 06:06:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8532079","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8532079","identity":"rs-8532079","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}