A population-health approach to characterizing migraine by comorbidity: Results from the Mindfulness and Migraine Cohort Study.

BACKGROUND: The heterogeneity of migraine has been reported extensively, with identified subgroups usually based on symptoms. Grouping individuals with migraine and similar comorbidity profiles has been suggested, however such segmentation methods have not been tested using real-world clinical data. OBJECTIVE: To gain insights into natural groupings of patients with migraine using latent class analysis based on electronic health record-determined comorbidities. METHODS: Retrospective electronic health record data analysis of primary-care patients at Sutter Health, a large open healthcare system in Northern California, USA. We identified migraine patients over a five-year time period (2015-2019) and extracted 29 comorbidities. We then applied latent class analysis to identify comorbidity-based natural subgroups. RESULTS: We identified 95,563 patients with migraine and found seven latent classes, summarized by their predominant comorbidities and population share: fewest comorbidities (61.8%), psychiatric (18.3%), some comorbidities (10.0%), most comorbidities - no cardiovascular (3.6%), vascular (3.1%), autoimmune/joint/pain (2.2%), and most comorbidities (1.0%). We found minimal demographic differences across classes. CONCLUSION: Our study found groupings of migraine patients based on comorbidity that have the potential to be used to guide targeted treatment strategies and the development of new therapies.

Response to Mindfulness-Based Cognitive Therapy Differs Between Chronic and Episodic Migraine.

OBJECTIVE: Evaluate whether the benefits of Mindfulness-Based Cognitive Therapy for Migraine (MBCT-M) on headache disability differs among people with episodic and chronic migraine (CM). METHODS: This is a planned secondary analysis of a randomized clinical trial. After a 30-day baseline, participants were stratified by episodic (6-14 d/mo) and CM (15-30 d/mo) and randomized to 8 weekly individual sessions of MBCT-M or wait list/treatment as usual (WL/TAU). Primary outcomes (Headache Disability Inventory; Severe Migraine Disability Assessment Scale [scores ≥ 21]) were assessed at months 0, 1, 2, and 4. Mixed models for repeated measures tested moderation with fixed effects of treatment, time, CM, and all interactions. Planned subgroup analyses evaluated treatment*time in episodic and CM. RESULTS: Of 60 participants (MBCT-M N = 31, WL/TAU N = 29), 52% had CM. CM moderated the effect of MBCT-M on Severe Migraine Disability Assessment Scale, F(3, 205) = 3.68, p = 0.013; MBCT-M vs WL/TAU reduced the proportion of people reporting severe disability to a greater extent among people with episodic migraine (-40.0% vs -14.3%) than CM (-16.4% vs +8.7%). Subgroup analysis revealed MBCT-M (vs WL/TAU) significantly reduced Headache Disability Inventory for episodic (p = 0.011) but not CM (p = 0.268). CONCLUSIONS: MBCT-M is a promising treatment for reducing headache-related disability, with greater benefits in episodic than CM. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02443519. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that MBCT-M reduces headache disability to a greater extent in people with episodic than CM.

The migraine signature study: Methods and baseline results.

OBJECTIVE: To characterize patients who utilize services for migraine in a large integrated health care network, and describe patterns of care and utilization. BACKGROUND: Within health care systems, migraine is a common reason for seeking primary and neurology care, but relatively little is documented about who seeks care and the factors that explain variation in utilization. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from Sutter Health primary care (PC) patients who had at least one office visit to a PC clinic between 2013 and 2017. Migraine status was ascertained from diagnosis codes and medication orders. Control status was assigned to those with no evidence of care for any type of headache. We divided the primary care migraine cohort into two groups: those who received all their care for migraine from PC (denoted PC-M) and those who had ≥1 encounter with a neurologist for migraine (denoted N-M). Migraine cases were also designated as having preexisting migraine if they had an encounter with a migraine diagnosis within (±) 6 months of their first study period PC visit and, otherwise, designated as first migraine consult. Two levels of contrasts included: patients with migraine and controls; and within the group of patients with migraine, PC-M and N-M groups. Comorbid conditions were determined from EHR encounter diagnosis codes. RESULTS: We identified 94,149 patients with migraine (including 21,525 N-M and 72,624 PC-M) and 1,248,763 controls. Comorbidities: Proportions of psychiatric [29.8% (n = 28,054) vs. 11.8% (n = 147,043)], autoimmune [(4.4% (n = 4162) vs. 2.6% (n = 31,981)], pain [13.2% (n = 12,439) vs. 5.8% (n = 72,049)], respiratory [24.6% (n = 23,186) vs. 12.3% (n = 153,692)], neurologic [2.9% (n = 2688) vs. 0.9% (n = 11,321)], and cerebrovascular [1.0% (n = 945) vs. 0.6% (n = 7500)] conditions were higher in the migraine group compared to controls, all p < 0.001. Among patients with migraine, the N-M group was similar to the PC-M group in sex, age, ethnicity, and marital status, but were more likely to have preexisting migraine (49.9% (n = 10,734) vs. 36.2% (n = 26,317), p < 0.001). Proportions of comorbid conditions were higher among the N-M group than the PC-M group {psychiatric [38.5% (n = 8291) vs. 27.2% (n = 19,763)], autoimmune [6.3% (n = 1365) vs. 3.9% (n = 2797)], pain [19.6% (n = 4218) vs. 11.3% (n = 8211)], respiratory [30.3% (n = 6516) vs. 23.0% (n = 16,670)], neurologic [6.0% (n = 1288) vs. 1.9% (n = 1400)], cardiovascular [9.7% (n = 2091) vs. 7.0% (n = 5076)], and cerebrovascular [2.3% (n = 500) vs. 0.6% (n = 445)], all p < 0.001}. Medications: During the study period, 82.6% (n = 77,762) of patients with migraine received ≥1 prescription order for an acute migraine medication [89.4% (n = 19,250) of N-M vs. 80.6% (n = 58,512) of PC]. Opioids were prescribed to 52.9% (n = 49,837) of patients with migraine [63.5% (n = 13,669) for N-M and 49.8% (n = 36,168) for PC-M patients). During the study period, 61.4% (n = 57,810) of patients received ≥1 prescription for a migraine preventive medication [81.4% (n = 17,521) of N-M and 55.5% (n = 40,289) of PC-M patients]. The most commonly prescribed classes of preventive medications were antidepressants. CONCLUSIONS: Among patients with migraine in a large health system, those who were also cared for in neurology were more likely to receive both acute and preventive medication migraine orders than those patients who did not see a neurologist, with triptans and antidepressants the most commonly prescribed classes of acute and preventive pharmacotherapies, respectively. Opioids were prescribed to approximately half of the total sample and more common in the N-M group. Adjusting for demographics, patients with migraine had higher rates of nearly every comorbidity we assessed and were more likely to utilize services compared to those without migraine. Overall, patients with migraine also cared for in neurology practices used more of all health care resource types under consideration and had more medical issues, which may be due in some part to a more severe, frequent and disabling disease state compared to those who sought care exclusively from PC practices.

Smartphone-Delivered Progressive Muscle Relaxation for the Treatment of Migraine in Primary Care: A Randomized Controlled Trial.

OBJECTIVE: Scalable, accessible forms of behavioral therapy for migraine prevention are needed. We assessed the feasibility and acceptability of progressive muscle relaxation (PMR) delivered by a smartphone application (app) in the Primary Care setting. METHODS: This pilot study was a non-blinded, randomized, parallel-arm controlled trial of adults with migraine and 4+ headache days/month. Eligible participants spoke English and owned a smartphone. All participants were given the RELAXaHEAD app which includes an electronic headache diary. Participants were randomized to receive 1 of the 2 versions of the app-one with PMR and the other without PMR. The primary outcomes were measures of feasibility (adherence to the intervention and diary entries during the 90-day interval) and acceptability (satisfaction levels). We conducted exploratory analyses to determine whether there was a change in Migraine Disability Assessment Scale (MIDAS) scores or a change in headache days. RESULTS: Of 139 participants (77 PMR, 62 control), 116 (83%) were female, mean age was 41.7 ± 12.8 years. Most patients 108/139 (78%) had moderate-severe disability. Using a 1-5 Likert scale, participants found the app easy to use (mean 4.2 ± 0.7) and stated that they would be happy to engage in the PMR intervention again (mean 4.3 ± 0.6). For the first 6 weeks, participants practiced PMR 2-4 days/week. Mean per session duration was 11.1 ± 8.3 minutes. Relative to the diary-only group, the PMR group showed a greater non-significant decline in mean MIDAS scores (-8.7 vs -22.7, P = .100) corresponding to a small-moderate mean effect size (Cohen's d = 0.38). CONCLUSION: Smartphone-delivered PMR may be an acceptable, accessible form of therapy for migraine. Mean effects show a small-moderate mean effect size in disability scores.

Seizure self-prediction in a randomized controlled trial of stress management.

OBJECTIVE: Using electronic diaries as part of a randomized controlled trial of stress reduction for epilepsy, we evaluated factors associated with successful seizure self-prediction. METHODS: Adults with medication-resistant focal epilepsy were recruited from 3 centers and randomized to treatment with progressive muscle relaxation or control focused attention. An 8-week baseline was followed by 12 weeks of double-blind treatment. Twice daily, participants rated the likelihood of a seizure in the next 24 hours on a 5-point scale from very unlikely to almost certain, along with mood, premonitory symptoms, stress ratings, and seizure counts. We analyzed the association of mood, premonitory symptoms, stress, and circadian influences on seizure self-prediction. RESULTS: Sixty-four participants completed the trial (3,126 seizures). Diary entry adherence was >82%. Participant self-prediction was associated with seizure occurrence at 6, 12, and 24 hours (p < 0.0001). Odds ratio (OR) of seizure prediction increased systematically with participants' prediction of seizure likelihood (p < 0.0001, all levels of prediction and all time intervals). For the 12-hour prediction window, median specificity for seizure prediction was 0.94 and negative predictive value 0.94; median sensitivity was 0.10 and positive predictive value 0.13. A subset of 13 participants (20% of sample) met criteria for good predictors (median OR for seizure prediction 5.25). Mood, stress, premonitory symptoms, seizure time, and randomized group were not associated with seizure occurrence. CONCLUSION: In this prospective study, participants' prediction of a high probability of seizure was significantly associated with subsequent seizure occurrence within 24 hours. Future studies should focus on understanding factors that drive self-prediction. CLINICALTRIALSGOV IDENTIFIER: NCT01444183.

Does Mindfulness-Based Cognitive Therapy for Migraine Reduce Migraine-Related Disability in People with Episodic and Chronic Migraine? A Phase 2b Pilot Randomized Clinical Trial.

OBJECTIVE: The current Phase 2b study aimed to evaluate the efficacy of mindfulness-based cognitive therapy for migraine (MBCT-M) to reduce migraine-related disability in people with migraine. BACKGROUND: Mindfulness-based interventions represent a promising avenue to investigate effects in people with migraine. MBCT teaches mindfulness meditation and cognitive-behavioral skills and directly applies these skills to address disease-related cognitions. METHODS: Participants with migraine (6-30 headache days/month) were recruited from neurology office referrals and local and online advertisements in the broader New York City area. During the 30-day baseline period, all participants completed a daily headache diary. Participants who met inclusion and exclusion criteria were randomized in a parallel design, stratified by chronic migraine status, to receive either 8 weekly individual MBCT-M sessions or 8 weeks of waitlist/treatment as usual (WL/TAU). All participants completed surveys including primary outcome evaluations at Months 0, 1, 2, and 4. All participants completed a headache diary during the 30-day posttreatment evaluation period. Primary outcomes were the change from Month 0 to Month 4 in the headache disability inventory (HDI) and the Migraine Disability Assessment (MIDAS) (total score ≥ 21 indicating severe disability); secondary outcomes (headache days/30 days, average headache attack pain intensity, and attack-level migraine-related disability [Migraine Disability Index (MIDI)]) were derived from the daily headache diary. RESULTS: Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%) and Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%) with a graduate degree (n = 35/60; 55.0%) who were working full-time (n = 38/60; 63.3%). At baseline, the average HDI score (51.4, SD = 19.0) indicated a moderate level of disability and the majority of participants (50/60, 83.3%) fell in the "Severe Disability" range in the MIDAS. Participants recorded an average of 16.0 (SD = 5.9) headache days/30 days, with an average headache attack pain intensity of 1.7 on a 4-point scale (SD = 0.3), indicating moderate intensity. Average levels of daily disability reported on the MIDI were 3.1/10 (SD = 1.8). For the HDI, mean scores decreased more from Month 0 to Month 4 in the MBCT-M group (-14.3) than the waitlist/treatment as an usual group (-0.2; P < .001). For the MIDAS, the group*month interaction was not significant when accounting for the divided alpha, P = .027; across all participants in both groups, the estimated proportion of participants falling in the "Severe Disability" category fell significantly from 88.3% at Month 0 to 66.7% at Month 4, P < .001. For diary-reported headache days/30 days an average headache attack pain intensity, neither the group*month interaction (Ps = .773 and .888, respectively) nor the time effect (Ps = .059 and .428, respectively) was significant. Mean MIDI scores decreased in the MBCT-M group (-0.6/10), whereas they increased in the waitlist/treatment as an usual group (+0.3/10), P = .007. CONCLUSIONS: MBCT-M demonstrated efficacy to reduce headache-related disability and attack-level migraine-related disability. MBCT-M is a promising emerging treatment for addressing migraine-related disability.

User Design and Experience Preferences in a Novel Smartphone Application for Migraine Management: A Think Aloud Study of the RELAXaHEAD Application.

OBJECTIVE: Scalable nonpharmacologic treatment options are needed for chronic pain conditions. Migraine is an ideal condition to test smartphone-based mind-body interventions (MBIs) because it is a very prevalent, costly, disabling condition. Progressive muscle relaxation (PMR) is a standardized, evidence-based MBI previously adapted for smartphone applications for other conditions. We sought to examine the usability of the RELAXaHEAD application (app), which has a headache diary and PMR capability. METHODS: Using the "Think Aloud" approach, we iteratively beta-tested RELAXaHEAD in people with migraine. Individual interviews were conducted, audio-recorded, and transcribed. Using Grounded Theory, we conducted thematic analysis. Participants also were asked Likert scale questions about satisfaction with the app and the PMR. RESULTS: Twelve subjects participated in the study. The mean duration of the interviews (SD, range) was 36 (11, 19-53) minutes. From the interviews, four main themes emerged. People were most interested in app utility/practicality, user interface, app functionality, and the potential utility of the PMR. Participants reported that the daily diary was easy to use (75%), was relevant for tracking headaches (75%), maintained their interest and attention (75%), and was easy to understand (83%). Ninety-two percent of the participants would be happy to use the app again. Participants reported that PMR maintained their interest and attention (75%) and improved their stress and low mood (75%). CONCLUSIONS: The RELAXaHEAD app may be acceptable and useful to migraine participants. Future studies will examine the use of the RELAXaHEAD app to deliver PMR to people with migraine in a low-cost, scalable manner.

Behavioral interventions as a treatment for epilepsy: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the effect of a stress-reduction intervention in participants with medication-resistant epilepsy. METHODS: Adults with medication-resistant focal epilepsy (n = 66) were recruited from 3 centers and randomized to 1 of 2 interventions: (1) progressive muscle relaxation (PMR) with diaphragmatic breathing, or (2) control focused-attention activity with extremity movements. Following an 8-week baseline period, participants began 12 weeks of double-blind treatment. Daily self-reported mood and stress ratings plus seizure counts were completed by participants using an electronic diary, and no medication adjustments were permitted. The primary outcome was percent reduction in seizure frequency per 28 days comparing baseline and treatment; secondary outcomes included stress reduction and stress-seizure interaction. RESULTS: In the 66 participants in the intention-to-treat analysis, seizure frequency was reduced from baseline in both treatment groups (PMR: 29%, p < 0.05; focused attention: 25%, p < 0.05). PMR and focused attention did not differ in seizure reduction (p = 0.38), although PMR was associated with stress reduction relative to focused attention (p < 0.05). Daily stress was not a predictor of seizures. CONCLUSIONS: Both PMR and the focused-attention groups showed reduced seizure frequency compared to baseline in participants with medication-resistant focal seizures, although the 2 treatments did not differ. PMR was more effective than focused attention in reducing self-reported stress. CLINICALTRIALSGOV IDENTIFIER: NCT01444183.

Caffeine in the management of patients with headache.

Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmacology, dietary and medical sources, clinical benefits, and potential safety issues of caffeine. In this review, we consider the role of caffeine in the over-the-counter treatment of headache. The MEDLINE and Cochrane databases were searched by combining "caffeine" with the terms "headache," "migraine," and "tension-type." Studies that were not placebo-controlled or that involved medications available only with a prescription, as well as those not assessing patients with migraine and/or tension-type headache (TTH), were excluded. Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients. The most common adverse events were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and dizziness (3.2%). This review provides evidence for the role of caffeine as an analgesic adjuvant in the acute treatment of primary headache with over-the-counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of ≥100 mg enhance benefits in migraine. Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine.

Transcutaneous and Percutaneous Neurostimulation for Headache Disorders.

Noninvasive and minimally invasive extracranial stimulation has now been widely investigated for the treatment of primary headache disorders, particularly migraine. In this review, we describe methodological challenges in studying occipital and supraorbital stimulation devices. We explore the efficacy and safety of implantable occipital nerve stimulation for primary headache disorders, including the 3 randomized, sham-controlled clinical trials for chronic migraine treatment. We also review noninvasive supraorbital transcutaneous stimulation as a preventive therapy for episodic migraine.

Female advantage in verbal memory: Evidence of sex-specific cognitive reserve.

OBJECTIVE: We investigated sex differences in verbal memory across different levels of neural dysfunction, measured by temporal lobe glucose metabolic rates (TLGluMR). METHODS: Three hundred ninety controls and 672 participants with amnestic mild cognitive impairment (aMCI) and 254 with Alzheimer disease (AD) dementia from the Alzheimer's Disease Neuroimaging Initiative completed the Rey Auditory Verbal Learning Test (RAVLT) and [18F]-fluorodeoxyglucose-PET. Cross-sectional analyses were conducted using linear regression to examine the sex by TLGluMR interaction on RAVLT performance in the overall sample and within diagnostic groups adjusting for age, education, and APOE ε4 genotype. RESULTS: Across groups, female sex and higher TLGluMR and their interaction were associated with better verbal memory (p values ≤ 0.005). The female advantage in verbal memory varied by TLGluMR such that the advantage was greatest among individuals with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group (p values = 0.009). The interaction was not significant in control and AD dementia groups. CONCLUSIONS: Women show better verbal memory than men in aMCI despite similar levels of brain hypometabolism. The lifelong advantage that females show over males in verbal memory might represent a form of cognitive reserve that delays verbal memory decline until more advanced pathology, as indexed by TLGluMR. This issue is clinically important because verbal memory scores are used in diagnosing aMCI and AD dementia.

Healthcare resource utilization and direct costs associated with frequent nausea in episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: Nausea is a common migraine symptom that is associated with impaired quality-of-life and functional disability. In this study, population-based data were used to elucidate the relationship between nausea frequency and headache-related healthcare utilization and costs in persons with migraine. RESEARCH DESIGN AND METHODS: Participants with episodic migraine who completed the 2009 American Migraine Prevalence and Prevention (AMPP) Study survey rated their headache-related nausea as occurring never, rarely,

Behavioral intervention as an add-on therapy in epilepsy: designing a clinical trial.

Many patients with epilepsy continue to experience seizures despite taking medication, and stress is a commonly reported trigger for seizures in these individuals. Therefore, a behavioral therapy proven to be effective in epilepsy could be a valuable adjunct to current pharmacotherapy. The challenges in testing such a behavioral intervention for epilepsy are numerous, including lack of consensus about sham designs, maintaining the blind, and powering the study absent known effect sizes. Herein, we present the design of a randomized, controlled, double-blind trial of progressive muscle relaxation as an add-on therapy for refractory epilepsy. Progressive muscle relaxation, which involves the tensing and releasing of muscle groups one at a time, is a well-established technique that relaxes the body and mind, reduces stress, and may improve seizure control. Study design issues discussed may provide insights that will inform future behavioral research in epilepsy.

Nonpharmacologic treatments for migraine and tension-type headache: how to choose and when to use.

OPINION STATEMENT: There are a variety of nonpharmacologic treatments for headache. Educating patients about headache and its management, identifying and managing triggers (via diaries), modifying lifestyles, and understanding the importance of adopting and adhering to interventions (either pharmacologic or nonpharmacologic) are relevant to all persons with headache. In addition, specific nonpharmacologic treatments can be used either alone or in conjunction with ongoing pharmacologic intervention. Strong candidates for nonpharmacologic treatment include individuals with significant headache-related disability, comorbid mood or anxiety disorders, difficulty managing stress or other triggers, medication overuse, and patients who prefer a specific treatment. Behavioral treatments (relaxation, biofeedback, and cognitive-behavioral therapy) possess the most evidence for successful headache management. They have a long history of randomized trials showing efficacy and are considered first-line preventive options. Among complementary and alternative treatments, recent positive findings from randomized trials using acupuncture provide evidence of its potential as a first-line intervention. Other complementary and alternative techniques do not have a consistent base of research to recommend them for headache prevention, but they may be used if the patient prefers this approach or when other first-line interventions (nonpharmacologic or pharmacologic) have not provided adequate results. Among "natural" treatments, both butterbur extract and vitamin B2 have shown efficacy in more than one randomized trial and are thus potentially useful first-line preventive interventions.

Patterns of use of peripheral nerve blocks and trigger point injections among headache practitioners in the USA: Results of the American Headache Society Interventional Procedure Survey (AHS-IPS).

BACKGROUND: Many clinicians use peripheral nerve blocks (NBs) and trigger point injections (TPIs) for the treatment of headaches. Little is known, however, about the patterns of use of these procedures among practitioners in the USA. OBJECTIVES: The aim of this study was to obtain information on patterns of office-based use of peripheral NBs and TPIs by headache practitioners in the USA. METHODS: Using an Internet-based questionnaire, the Interventional Procedures Special Interest Section of the American Headache Society (AHS) conducted a survey among practitioners who were members of AHS on patterns of use of NBs and TPIs for headache treatment. RESULTS: Electronic invitations were sent to 1230 AHS members and 161 provided usable data (13.1%). Of the responders, 69% performed NBs and 75% performed TPIs. The most common indications for the use of NBs were occipital neuralgia and chronic migraine (CM), and the most common indications for the use of TPIs were chronic tension-type headache and CM. The most common symptom prompting the clinician to perform these procedures was local tenderness at the intended injection site. The most common local anesthetics used for these procedures were lidocaine and bupivacaine. Dosing regimens, volumes of injection, and injection schedules varied greatly. There was also a wide variation in the use of corticosteroids when performing the injections. Both NBs and TPIs were generally well tolerated. CONCLUSIONS: Nerve blocks and TPIs are commonly used by headache practitioners in the USA for the treatment of various headache disorders, although the patterns of their use vary greatly.

Peripheral nerve blocks and trigger point injections in headache management - a systematic review and suggestions for future research.

Interventional procedures such as peripheral nerve blocks (PNBs) and trigger point injections (TPIs) have long been used in the treatment of various headache disorders. There are, however, little data on their efficacy for the treatment of specific headache syndromes. Moreover, there is no widely accepted agreement among headache specialists as to the optimal technique of injection, type, and doses of the local anesthetics used, and injection regimens. The role of corticosteroids in this setting is also debated. We performed a PubMed search of the literature to find studies on PNBs and TPIs for headache treatment. We classified the abstracted studies based on the procedure performed and the treated condition. We found few controlled studies on the efficacy of PNBs for headaches, and virtually none on the use of TPIs for this indication. The most widely examined procedure in this setting was greater occipital nerve block, with the majority of studies being small and non-controlled. The techniques, as well as the type and doses of local anesthetics used for nerve blockade, varied greatly among studies. The specific conditions treated also varied, and included both primary (eg, migraine, cluster headache) and secondary (eg, cervicogenic, posttraumatic) headache disorders. Trigeminal (eg, supraorbital) nerve blocks were used in few studies. Results were generally positive, but should be taken with reservation given the methodological limitations of the available studies. The procedures were generally well tolerated. Evidently, there is a need to perform more rigorous clinical trials to clarify the role of PNBs and TPIs in the management of various headache disorders, and to aim at standardizing the techniques used for the various procedures in this setting.

Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment.

OBJECTIVE: To evaluate the disability profile and patterns of treatment and health care use for chronic migraine (CM) in the general population, in contrast to episodic migraine. METHODS: We identified 24,000 headache sufferers, drawn from more than 165,000 individuals representative of the US population. This sample has been followed up with annual surveys using validated questionnaires for the diagnosis of episodic migraine and CM. As a part of the survey, subjects were asked to report the specific medications currently used for their most severe headaches, as well as level of satisfaction with treatment. RESULTS: Our sample consisted of 520 individuals with CM and 9,424 with episodic migraine. Over a 3-month period, more than half of the individuals with CM missed at least 5 days of household work, compared with 24.3% of those with episodic migraine (p < 0.001). Reduced productivity in household work for at least 5 days over 3 months was reported by 58.1% and 18.2% (p < 0.001); at least 5 days of missed family activities was reported by 36.9% and 9.5% (p < 0.001). The majority of the CM sufferers (87.6%) had previously sought care to discuss their headaches with a health professional. Migraine-specific acute treatments were used by 31.6% of respondents with CM and 24.8% with episodic migraine. Around 48% of the individuals with CM were satisfied with their acute therapies. Just 33.3% of those with CM were currently using preventive medications. CONCLUSION: Chronic migraine (CM) is more disabling than episodic migraine in the population. Although most individuals with CM sought medical care for this disorder, the majority did not receive specific acute or preventive medications.

The preventive treatment of migraine.

BACKGROUND: Migraine is a common, chronic, and disabling disorder. The treatment of migraine includes a combination of nonpharmacologic and pharmacologic techniques. Pharmacologic approaches are subdivided in preventive therapies and acute care. REVIEW SUMMARY: In this review article, we review the current approaches to the preventive treatment of migraine. Preventive treatment should be initiated in those with frequent or disabling headaches. The goals include (1) reducing attack frequency, intensity, and duration; (2) minimizing headache-related disability; (3) improving health-related quality of life; (4) avoiding headache escalation and medication misuse. In this article, we also discuss the principles of migraine prevention, as well as drugs available for this goal. We divide preventive medications on those of common use, nutraceutical compounds, and medications less frequently used. We close by briefly discussing some in-development potential preventive drugs. CONCLUSION: Preventive therapies are well suitable for migraineurs with attack-related disability despite appropriate acute care.

Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study.

OBJECTIVE: A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. BACKGROUND: Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). METHODS: The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (chi22= 11.56, P=.003). Both the diclofenac plus caffeine (P <.03) and diclofenac only (P <.03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. CONCLUSIONS: The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.