Enhanced mindfulness-based stress reduction in episodic migraine-effects on sleep quality, anxiety, stress, and depression: a secondary analysis of a randomized clinical trial.

ABSTRACT: Patients with migraine suffer from high morbidity related to the repeated headache attacks, characteristic of the disorder, poor sleep, and a high prevalence of comorbid psychosocial disorders. Current pharmacological therapies do not address these aspects of migraine, but nonpharmacological treatments such as mindfulness-based stress reduction (MBSR) have been shown to improve both pain and psychological well-being. In this secondary analysis, we examined the change over time in sleep quality and psychosocial outcomes from the magnetic resonance imaging outcomes for mindfulness meditation clinical trial and assessed how these mediated treatment response (50% reduction in headache frequency postintervention). We also examined the relationship between baseline values and treatment response. The trial (primary outcomes previously reported) included 98 patients with episodic migraine randomized to either enhanced MBSR (MBSR+) or stress management for headache. They completed psychosocial questionnaires and headache diaries at baseline (preintervention), midintervention (10 weeks after baseline), and postintervention (20 weeks after baseline). There was a significant improvement in sleep quality from baseline to postintervention (P = 0.0025) in both groups. There were no significant changes from baseline or between groups in anxiety, depression, and stress. There was also no significant association between baseline scores and treatment response. Mediation analysis showed a significant indirect effect of 6% for sleep: In other words, small improvements in sleep may have contributed to the efficacy of MBSR+.Trial registration: NCT02133209.

Suicide Attempts in US Veterans with Chronic Headache Disorders: A 10-Year Retrospective Cohort Study.

OBJECTIVES: A large-scale retrospective analysis of veterans with chronic pain was conducted to examine (1) the annual incidence of suicide attempts (SA) in veterans with chronic headache and other chronic pain conditions, and (2) the risk of SA in men and women with chronic headache and chronic headache concurrent with traumatic brain injury (TBI) as compared to non-headache chronic pain. METHODS: This retrospective study (N=3,247,621) analyzed National Veterans Affair Health Administrative data of patients diagnosed with chronic head, neck, back and other chronic pain from 2000 to 2010. Multivariable Poisson regression was used to explore the relative risks of SA in veterans with chronic headache and chronic headache concurrent with TBI as stratified by sex. RESULTS: Veterans with chronic headaches had the highest annual incidence of SA (329 to 491 per 100,000) each year among all identified types of chronic pain conditions. Compared to other non-headache chronic pain, chronic headache is associated with increased risk of SA [men RR (1.48), CI (1.37,1.59); women RR (1.64), CI (1.28,2.09)], after adjusting for demographic factors, TBI, and psychiatric comorbidities. The risk increased further when chronic headache is comorbid with TBI [men RR (2.82), CI (2.60, 3.05); women RR (2.16, CI (1.67-2.78)]. CONCLUSION: Veterans with chronic headache have a higher risk of SA than those with other chronic pain and women with chronic headache are at a higher risk than men with chronic headache. Chronic headache concurrent with TBI further heightened this risk, especially in men. Our data underscore the importance of identifying specific types of chronic pain in veterans with comorbid TBI and sex disparity associated with SA when targeting suicide prevention measures.

Associations between adverse childhood experiences and migraine among teenage mothers in Peru.

OBJECTIVE: The objective of this study was to evaluate the association between (1) different types of ACEs and migraine, and (2) the number of ACEs and migraine among adolescent mothers in Lima, Peru. METHODS: Our cross-sectional study included 787 adolescent mothers (14- to 18-years of age) in Peru. In-person interviews were conducted postpartum, in hospital, within 2-days of delivery. Nine types of ACEs were assessed, including exposure to three categories of abuse, two categories of neglect, and four categories of household dysfunction. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between ACEs and migraine while adjusting for putative confounders. RESULTS: Approximately 75% of adolescent mothers reported having experienced at least one type of ACE. Adolescent mothers who reported any childhood abuse had 1.49-fold increased odds of migraine (aOR = 1.49; 95% CI 1.03-2.18) compared to those with no history of childhood abuse. Adolescent mothers who reported experiencing household dysfunction had 1.56-fold increase odds of migraine (aOR = 1.56; 95% CI 1.09-2.24). Compared to participants who reported no ACE, those who experienced four or more ACEs had 3.09-fold (aOR = 3.09; 95% CI 1.80-5.40) increased odds of migraine (ptrend < 0.001). CONCLUSION: Exposure to ACEs is highly prevalent in adolescent-aged mothers postpartum and is associated with increased odds of migraine. These findings support the importance of screening for ACEs and migraine among adolescent mothers; and the need for providing culturally appropriate, trauma-informed headache care.

Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes.

We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. Magnetic resonance imaging (MRI) outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula to DLPFC and cognitive task network, and gray matter volume of DLPFC, dorsal anterior insula, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95% CI, 6.9-8.8] to 4.6 [95% CI, 3.7-5.6]) than for SMH (7.7 [95% CI 6.7-8.7] to 6.0 [95% CI, 4.9-7.0]) (P = 0.04). Fifty-two percent of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P = 0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.

Migraine Age of Onset and Association With Ischemic Stroke in Late Life: 20 Years Follow-Up in ARIC.

BACKGROUND AND PURPOSE: To evaluate the association between cumulative exposure to migraine and incidence of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: In this ongoing, prospective longitudinal community-based cohort, participants were interviewed to ascertain migraine history at the third visit (1993-1995), followed for ischemic stroke incidence over 20 years. We performed a post hoc analysis to evaluate the association between the age of migraine onset and ischemic stroke. RESULTS: We identified 447 migraineurs with aura (MA) and 1128 migraineurs without aura (MO) among 11,592 black and white participants. There was an association between the age of MA onset ≥50 years old (average duration = 4.75 years) and ischemic stroke when compared to no headache group (multivariable adjusted HR = 2.17, 95% CI [1.39-3.39], P < .001). MA onset <50 years old (average duration = 28.17 years) was not associated with stroke (multivariable adjusted HR = 1.31, 95% CI [0.86-2.02], P = .212). These results were consistent with our logistic regression model. MO was not associated with increased stroke regardless of the age of onset. The absolute risk for stroke in migraine with aura is 37/447 (8.27%) and migraine without aura is 48/1128 (4.25%). CONCLUSION: As compared to the no headache participants, increased stroke risk in late life was observed in participants with late onset of MA. In this cohort, longer cumulative exposure to migraine with visual aura, as would be expected with early onset of migraine, was not associated with increased risk of ischemic stroke in late life. This study underscores the importance of the age of onset of MA in assessing stroke risk in older migraineurs.

Association Between Migraine and Suicidal Behaviors: A Nationwide Study in the USA.

BACKGROUND: Recent studies show migraineurs are at an increased risk of developing suicidal behaviors, even after controlling for comorbid depression. However, previous research has not examined the impact of psychiatric mood disorders on suicidal behaviors in migraineurs within a nationally representative sample. OBJECTIVE: A cross-sectional study was used to investigate the association between migraine and suicidal behaviors and determine whether psychiatric comorbidities modify this association in a nationwide inpatient cohort. METHODS: We analyzed the Nationwide Inpatient Sample of hospitalizations compiled from USA billing data. Migraine, suicidal behaviors, and psychiatric disorders were identified based on the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from hospitalization discharges (2007-2012). Weighted national estimates were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: 156,172,826 hospitalizations were included, of which 1.4% had a migraine diagnosis and 1.6% had a diagnosis of suicidal behavior. Migraineurs had a 2.07-fold increased odds of suicidal behaviors (95%CI: 1.96-2.19) compared with non-migraineurs. We repeated analyses after stratifying by depression, anxiety, or posttraumatic stress disorder (PTSD). Among hospitalizations with depression, migraine was associated with a 20% reduced odds of suicidal behaviors (95%CI: 0.76-0.85). Among hospitalizations without depression, migraine was associated with 2.35-fold increased odds of suicidal behaviors (95%CI: 2.20-2.51). In stratified analyses, we noted that among hospitalizations with anxiety, migraineurs had slightly increased odds of suicidal behaviors (OR: 1.07, 95%CI: 1.02-1.13). Among hospitalizations without anxiety, migraine was associated with a 2.06-fold increased odds of suicidal behaviors (95%CI: 1.94-2.20). Similarly, in analyses stratified by PTSD, migraine was not associated with an increased risk of suicidal behaviors (OR: 1.00, 95%CI: 0.94-1.07) among those with PTSD. However, the odds of suicidal behaviors were increased among hospitalizations without PTSD (OR: 1.95, 95%CI: 1.84-2.08). CONCLUSION: Chronic conditions that do not affect the current hospitalization may not have been reported. The presence of psychiatric diagnoses influences associations of suicidal behaviors with migraine in a national inpatient sample. Migraineurs with diagnosed comorbid psychiatric disorders may be receiving care that mitigates their risk for suicidal behaviors.

Modulation of salience network intranetwork resting state functional connectivity in women with chronic migraine.

Objective To investigate the intranetwork resting state fMRI connectivity within the Salience Network of chronic migraine with and without medication overuse headache. Methods We compared 351 pairs of intranetwork connectivity in chronic migraine (n = 13) and chronic migraine with medication overuse headache (n = 16) compared to matched controls, and between each chronic migraine subgroup. Results Compared to controls, 17 pairs of intranetwork connections in chronic migraine and 27 pairs in chronic migraine with medication overuse headache were decreased. When comparing chronic migraine with medication overuse headache versus chronic migraine, connectivity between bilateral extended amygdala, and between paracingulate to right ventral tegmental area/substantia nigra were decreased in chronic migraine (chronic migraine < chronic migraine with medication overuse headache). Connectivity between left dorsolateral prefrontal cortex to bilateral ventral striatum/pallidum, to bilateral dorsal anterior cingulate cortex; left anterior prefrontal cortex to contralateral orbitofrontal insula; and left ventral striatum/pallidum to ipsilateral supplementary motor area (SMA)/preSMA were decreased in chronic migraine with medication overuse headache (chronic migraine with medication overuse headache < chronic migraine). Conclusion Both chronic migraine subgroups had shared intranetwork connectivity abnormality, however, each subgroup had unique pattern of disruption within the salience network. The results suggest that the aberrant assignment of salience to external and internal stimuli plays an important role in chronic migraine and chronic migraine with medication overuse headache interictally, mostly involving mesolimbic pathways (especially bilateral extended amygdala) in chronic migraine, and prefrontal-subcortical limbic pathways in chronic migraine with medication overuse headache.

Migraine and the risk of post-traumatic stress disorder among a cohort of pregnant women.

BACKGROUND: Individually both migraine and post-traumatic stress disorder (PTSD) prevalence estimates are higher among women. However, there is limited data on the association of migraine and PTSD in women during pregnancy. METHODS: We examined the association between migraine and PTSD among women attending prenatal clinics in Peru. Migraine was characterized using the International Classification of Headache Disorders (ICHD)-III beta criteria. PTSD was assessed using the PTSD Checklist-Civilian Version (PCL-C). Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. RESULTS: Of the 2922 pregnant women included, 33.5% fulfilled criteria for any migraine (migraine 12.5%; probable migraine 21.0%) and 37.4% fulfilled PTSD criteria. Even when controlling for depression, women with any migraine had almost a 2-fold increased odds of PTSD (OR: 1.97; 95% CI: 1.64-2.37) as compared to women without migraine. Specifically, women with migraine alone (i.e. excluding probable migraine) had a 2.85-fold increased odds of PTSD (95% CI: 2.18-3.74), and women with probable migraine alone had a 1.61-fold increased odds of PTSD (95% CI: 1.30-1.99) as compared to those without migraine, even after controlling for depression. In those women with both migraine and comorbid depression, the odds of PTSD in all migraine categories were even further increased as compared to those women without migraine. CONCLUSION: In a cohort of pregnant women, irrespective of the presence or absence of depression, the odds of PTSD is increased in those with migraine. Our findings suggest the importance of screening for PTSD, specifically in pregnant women with migraine.

Modulation of intrinsic resting-state fMRI networks in women with chronic migraine.

OBJECTIVE: To evaluate the intrinsic resting functional connectivity of the default mode network (DMN), salience network (SN), and central executive network (CEN) network in women with chronic migraine (CM), and whether clinical features are associated with such abnormalities. METHODS: We analyzed resting-state connectivity in 29 women with CM as compared to age- and sex-matched controls. Relationships between clinical characteristics and changes in targeted networks connectivity were evaluated using a multivariate linear regression model. RESULTS: All 3 major intrinsic brain networks were less coherent in CM (DMN: p = 0.030, SN: p = 0.007, CEN: p = 0.002) as compared to controls. When stratified based on medication overuse headache (MOH) status, CM without MOH (DMN: p = 0.029, SN: p = 0.023, CEN: p = 0.003) and CM with MOH (DMN: p = 0.016, SN: p = 0.016, CEN: p = 0.015) were also less coherent as compared to controls. There was no difference in CM with MOH as compared to CM without MOH (DMN: p = 0.382, SN: p = 0.408, CEN: p = 0.419). The frequency of moderate and severe headache days was associated with decreased connectivity in SN (p = 0.003) and CEN (p = 0.015), while cutaneous allodynia was associated with increased connectivity in SN (p = 0.011). CONCLUSIONS: Our results demonstrated decreased overall resting-state functional connectivity of the 3 major intrinsic brain networks in women with CM, and these patterns were associated with frequency of moderate to severe headache and cutaneous allodynia.

Body composition status and the risk of migraine: A meta-analysis.

OBJECTIVE: To evaluate the association between migraine and body composition status as estimated based on body mass index and WHO physical status categories. METHODS: Systematic electronic database searches were conducted for relevant studies. Two independent reviewers performed data extraction and quality appraisal. Odds ratios (OR) and confidence intervals (CI) were pooled using a random effects model. Significant values, weighted effect sizes, and tests of homogeneity of variance were calculated. RESULTS: A total of 12 studies, encompassing data from 288,981 unique participants, were included. The age- and sex-adjusted pooled risk of migraine in those with obesity was increased by 27% compared with those of normal weight (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.16-1.37, p < 0.001) and remained increased after multivariate adjustments. Although the age- and sex-adjusted pooled migraine risk was increased in overweight individuals (OR 1.08; 95% CI 1.04, 1.12, p < 0.001), significance was lost after multivariate adjustments. The age- and sex-adjusted pooled risk of migraine in underweight individuals was marginally increased by 13% compared with those of normal weight (OR 1.13; 95% CI 1.02, 1.24, p < 0.001) and remained increased after multivariate adjustments. CONCLUSIONS: The current body of evidence shows that the risk of migraine is increased in obese and underweight individuals. Studies are needed to confirm whether interventions that modify obesity status decrease the risk of migraine.

Pain catastrophizing may moderate the association between pain and secondary hyperalgesia.

Catastrophizing, a persistent negative mental set characterized by helplessness, rumination, and magnification of pain sensations, has a potent effect on pain report and clinical outcomes. Previous studies have documented an association between cognitive factors and central sensitization. The current analysis sought to test the potential modulating effect of pain catastrophizing on the association between capsaicin pain and the region of secondary hyperalgesia. Thirty-eight healthy individuals (50% women, mean age = 25.7, SD = 5.3) completed the Pain Catastrophizing Scale (PCS), then underwent topical application of 10% capsaicin, which was covered by a thermode maintained at 40°C for 90-min. Following removal of the capsaicin, the region of secondary hyperalgesia was determined. Hayes' PROCESS macro was employed to examine catastrophizing's potential moderating effect, which did not reveal a significant association between capsaicin pain ratings and the region of secondary hyperalgesia (ß = 15.1, p = .06). Though PCS was not associated with area of secondary hyperalgesia (ß = 23.9, p = .29), a significant interaction was present between PCS and capsaicin pain ratings (ß = 3.7, p = .0004). Specifically, those endorsing higher catastrophizing levels and higher pain ratings experienced the greatest areas of secondary hyperalgesia. The Johnson-Neyman technique was used to determine the regional effect of the moderation, which indicated that when PCS scores were ≥10.6, capsaicin pain significantly moderated the association between pain and area of secondary hyperalgesia. These results suggest that catastrophizing plays an important role in the area of secondary hyperalgesia, and potentially central sensitization, warranting further testing in future research.

Ethnic Differences in the Effects of Naloxone on Sustained Evoked Pain: A Preliminary Study.

Ethnic differences in pain response have been well documented, with non-Hispanic Black (NHB) participants reporting enhanced clinical pain and greater laboratory-evoked pain sensitivity to a variety of quantitative sensory testing (QST) methods compared to non-Hispanic Whites (NHW). One potential mechanism that may contribute to these disparities is differential functioning of endogenous pain-regulatory systems. To evaluate endogenous opioid (EO) mechanisms in pain responses, we examined group differences in response to tonic capsaicin pain following double-blinded crossover administration of saline and the opioid antagonist, naloxone. Ten percent topical capsaicin cream and a thermode were applied to the dorsum of the non-dominant hand, maintaining a constant temperature of 40°C for 90 min. Naloxone (0.1 mg/kg) or saline placebo was administered at the 25 min mark and post-drug pain intensity ratings were obtained every 5 min thereafter. As an index of EO function, blockade effects were derived for each participant, reflecting the difference between mean post-drug pain intensity ratings under the saline versus naloxone conditions, with higher positive scores reflecting greater EO inhibition of pain. Thirty-nine healthy, young individuals (19 non-Hispanic Black [NHB], 20 non-Hispanic White [NHW]) participated. Group difference in EO function were identified, with NHB participants displaying lower EO function scores (mean=-10.8, SD=10.1) as compared to NHW participants (mean=-0.89, SD=11.5; p=0.038). NHB participants experienced significant paradoxical analgesia with naloxone. Thirty five percent of the NHW participants showed a positive blockade effect indicating EO analgesia (i.e., an increase in pain with naloxone), while only 10% of the NHB participants exhibited evidence of EO analgesia. These findings suggest differential functioning of the endogenous opioid pain regulatory system between NHB and NHW participants. Future research is warranted to examine whether these differences contribute to the disparities observed in clinical pain between groups.

Childhood Abuse, Intimate Partner Violence and Risk of Migraine Among Pregnant Women: An Epidemiologic Study.

OBJECTIVE: To examine the independent and joint associations of childhood abuse and intimate partner violence with migraine among pregnant women. BACKGROUND: Childhood abuse and intimate partner violence have each been associated with migraine headaches in previous studies, but these associations have not been explored among pregnant women. METHODS: A cross-sectional study was conducted among a cohort of 2970 pregnant women attending prenatal clinics in Lima, Peru. History of childhood abuse (ie, physical or sexual abuse) was assessed using the Childhood Physical and Sexual Abuse Questionnaire. Intimate partner violence (IPV) was assessed using the World Health Organization questionnaire. Migraine classification (including migraine and probable migraine) was based on International Classification of Headache Disorders (ICHD)-III beta criteria. Multivariable logistic regression analyses were performed to estimate odd ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The prevalence of any migraine was 33.5% while approximately 70% of participants reported a history of childhood abuse and 36.7% a history of IPV. Women with a history of any childhood abuse had a 38% increased odds of any migraine compared to women with no history of childhood abuse (OR = 1.38; 95% CI 1.15-1.64). The odds of migraine increased with increasing numbers of experienced childhood abuse events (Ptrend < .001). Additionally, after adjusting for confounders women with a history of IPV had a 43% increased odds of any migraine as compared to women without intimate partner violence (OR = 1.43; 95%CI 1.02-2.02). Women with a joint positive history of childhood abuse and IPV, as compared with the reference group, had a 88% increased odds of migraine (aOR = 1.88, 95%CI: 1.51-2.35). CONCLUSION: Childhood abuse and IPV are associated with increased odds of migraine in pregnant women. Our findings highlight the importance of screening for abuse among pregnant migraineurs to help guide treatment strategies.

Adipokines and Migraine: A Systematic Review.

BACKGROUND: Migraine is comorbid with obesity. Recent research suggests an association between migraine and adipocytokines, proteins that are predominantly secreted from adipose tissue and which participate in energy homeostasis and inflammatory processes. OBJECTIVES: In this review, we first briefly discuss the association between migraine and obesity and the importance of adipose tissue as a neuroendocrine organ. We then present a systematic review of the extant literature evaluating circulating levels of adiponectin and leptin in those with migraine. METHODS: A search of the PubMed database was conducted using the keywords "migraine," "adiponectin," and "leptin." In addition reference lists of relevant articles were reviewed for possible inclusion. English language studies published between 2005 and 2015 evaluating circulating blood concentration of adiponectin or leptin in those with migraine were included. CONCLUSIONS: While the existing data are suggestive that adipokines may be associated with migraine, substantial study design differences and conflicting results limit definitive conclusions. Future research utilizing carefully considered designs and methodology is warranted. In particular careful and systematic characterization of pain states at the time of samples, as well as systematic consideration of demographic (e.g., age, sex) and other vital covariates (e.g., obesity status, lipids) are needed to determine if adipokines play a role in migraine pathophysiology and if any adipokine represents a viable, novel migraine biomarker, or drug target.

Association of Migraine Headaches With Suicidal Ideation Among Pregnant Women in Lima, Peru.

BACKGROUND: Suicide is a leading cause of maternal death globally, and suicide prevalence rates have been shown to be increased in those with migraine. No previous study has examined the association between migraine and suicidal ideation during pregnancy. OBJECTIVE: To examine the association between migraine and suicidal ideation among a cohort of pregnant women. METHODS: A cross-sectional study was conducted among 3372 pregnant women attending prenatal care clinics in Lima, Peru. Suicidal ideation and depression were assessed using the Patient Health Questionnaire-9 (PHQ-9) scale during early pregnancy. Migraine classification (including migraine and probable migraine) was based on International Classification of Headache Disorders-III beta criteria. Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Suicidal ideation was more common among those with migraine (25.6%) as compared to those with probable migraine (22.1%, P < .001) or non-migraineurs (12.3%, P < .001). After adjusting for confounders, including depression, those with migraine or probable migraine had a 78% increased odds of suicidal ideation (OR = 1.78; 95% CI: 1.46-2.17), as compared with non-migraineurs. Women with both migraine and depression had a 4.14-fold increased odds of suicidal ideation (OR = 4.14; 95% CI: 3.17-5.42) compared to those with neither condition. CONCLUSION: Migraine is associated with increased odds of suicidal ideation in pregnant women even when controlling for depression. These findings support the consideration of screening women with comorbid migraine and depression for suicidal behavior during pregnancy.

A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine.

OBJECTIVE: To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine. METHODS: This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. RESULTS: Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. CONCLUSIONS: This study supports that ketorolac NS is superior to placebo and that it is non-inferior to sumatriptan NS for the acute abortive treatment of migraine.

The Impact of Post-Traumatic Stress Disorder on the Burden of Migraine: Results From the National Comorbidity Survey-Replication.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked with migraine in prior studies. OBJECTIVE: To evaluate the individual and joint burdens of migraine and PTSD in a population-based cohort. METHODS: The National Comorbidity Survey-Replication (NCS-R) is a general population study conducted in the United States from February 2001-April 2003. PTSD and migraine were assessed, and four groups defined based on their migraine and PTSD status. The four groups included those with no migraine and no PTSD (controls, n=4535), those with migraine and without PTSD (migraine alone, n=236), those with PTSD and without migraine (PTSD alone, n=244), and those with both migraine and PTSD (mig+PTSD, n=68). Logistic and Poisson regression models were used to assess the association between dichotomous/multilevel outcome variables indicating financial, health, and interpersonal burdens and each migraine/PTSD group. RESULTS: Compared to controls, those with Mig+PTSD were more likely to be in the low poverty index (48% vs 41%, AOR 2.16; CI: 1.10, 4.24) and were less likely to be working for pay or profit in the past week (50% vs 68%, AOR 0.42; CI: 0.24, 0.74) but not those with migraine or PTSD alone. Additionally, the number of days where work quality was cut due to physical or mental health or substance abuse in the past month was greater in all groups compared to controls: (1) migraine alone: mean 2.57 (SEM 0.32) vs mean 1.09 (SEM 0.08) days, ARR=2.39; CI: 2.19, 2.62; (2) PTSD alone: mean 2.43 (SEM 0.33) vs mean 1.09 (SEM 0.08) days, ARR=2.09; CI: 1.91, 2.29; (3) mig+PTSD: mean 8.2 (SEM 0.79) vs 1.09 (SEM 0.08) days, ARR 6.79; CI 6.16, 7.49; and was over 2.5-fold greater in those mig+PTSD than migraine alone (mean 8.0 [SEM 0.79] vs 2.6 days [SEM 0.72], ARR 2.77; CI: 2.45, 3.14). The likelihood of having difficulty getting along or maintaining a social life was also increased in all groups relative to controls: (1) migraine alone: 21% vs 5.4%, AOR 4.20; CI: 2.62, 6.74; (2) PTSD alone: 18% vs 5.4%, AOR 3.40; CI: 2.40, 4.82; (3) Mig+PTSD: 39% vs 5.4%, AOR 9.95; CI: 5.72, 17.32, and was 2-fold greater in those with Mig+PTSD as compared to those with migraine alone (AOR 2.32; CI: 1.15, 4.69). CONCLUSIONS: These findings support the need for those who treat migraine patients to be aware of the comorbidity with PTSD, as these patients may be particularly prone to adverse financial, health, and interpersonal disease burdens.

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness.

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline -2.743 ± 2.487 vs -1.377 ± 1.970; P < 0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline -1.925 ± 3.204 vs -0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline -2.738 ± 2.753 vs -1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures.