Reduction In Headache Frequency Research Articles

Treatment Options for Posttraumatic Headache: A Current Review of the Literature.

We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

Neuromodulation in Pediatric Migraine using Repetitive Neuromuscular Magnetic Stimulation: A Feasibility Study.

Migraine has a relevant impact on pediatric health. Non-pharmacological modalities for its management are urgently needed. This study assessed the safety, feasibility, acceptance, and efficacy of repetitive neuromuscular magnetic stimulation (rNMS) in pediatric migraine. A total of 13 patients with migraine, ≥6 headache days during baseline, and ≥1 myofascial trigger point in the upper trapezius muscles (UTM) received six rNMS sessions within 3 weeks. Headache frequency, intensity, and medication intake were monitored using headache calendars; headache-related impairment and quality of life were measured using PedMIDAS and KINDL questionnaires. Muscular involvement was assessed using pressure pain thresholds (PPT). Adherence yielded 100%. In 82% of all rNMS sessions, no side effects occurred. All participants would recommend rNMS and would repeat it. Headache frequency, medication intake, and PedMIDAS scores decreased from baseline to follow-up (FU), trending towards statistical significance (p = 0.089; p = 0.081, p = 0.055). A total of 7 patients were classified as responders, with a ≥25% relative reduction in headache frequency. PPT above the UTM significantly increased from pre- to post-assessment, which sustained until FU (p = 0.015 and 0.026, respectively). rNMS was safe, feasible, well-accepted, and beneficial on the muscular level. The potential to reduce headache-related symptoms together with PPT changes of the targeted UTM may underscore the interplay of peripheral and central mechanisms conceptualized within the trigemino-cervical complex.

Are manual therapies effective at reducing chronic tension headache frequency in adults?

MAYBE. Among patients with chronic tension headaches, manual therapies may reduce headache frequency more than sham manual therapy, usual care, or exercise treatments-by 1.5 to 4.2 headaches or days with headache per week (strength of recommendation, B; preponderance of evidence from primarily small, heterogeneous randomized controlled trials [RCTs]).

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study)

BackgroundMindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost.MethodsIn this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7–10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson’s Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models.ResultsOut of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs.ConclusionsA mindfulness-based treatment composed of six-week session and 7–10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH.Trial registrationMIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

Botulinum Toxin for Pediatric Migraine: A Retrospective Multisite Cohort Study

BackgroundOnabotulinum toxin A is effective in adult chronic migraine, but the efficacy is not well established in adolescent patients. The objective of this study is to describe the safety and efficacy of onabotulinum toxin A and incobotulinum toxin A for adolescent chronic migraine headache. MethodsWe performed a chart review of adolescents who received onabotulinum toxin A or incobotulinum toxin A for headache prevention. Demographic information and baseline headache characteristics were collected. The primary end point was a 50% reduction in headache frequency. Secondary outcome measures included reduction in headache frequency, repeat appointments for injections, reduction in other migraine medications, and adverse events. ResultsWe included 51 adolescents who received at least one injection of either incobotulinum toxin A or onabotulinum toxin A for chronic migraine. Mean age at first dose was 16.0 (1.1; 13 to 17), (S.D. and range). Patients averaged 24.0 headache days per month (7.6; 4 to 28), (S.D. and range) before injection. In addition, 36 of the 51 adolescents (71%) were experiencing continuous headaches. Thirty-five (69%) adolescents had experienced 50% reduction in headache days by the time of first follow-up, which occurred on average at 16.6 weeks from initial injection (11.5; 2 to 55.7) (S.D. and range). Adolescents reported an average decrease of 13.1 headaches days per month. Only two adolescents reported side effects (4%), which were neck soreness and headache following injection. ConclusionsBotulinum toxin had better efficacy in our adolescent migraine population than has been demonstrated in other studies.

Improving to Four or Fewer Monthly Headache Days Per Month Provides a Clinically Meaningful Therapeutic Target for Patients with Chronic Migraine.

Treatment target goals for patients receiving preventive migraine treatment are complicated to assess and not achieved by most patients. A headache "number" could establish an understandable treatment target goal for patients with chronic migraine (CM). This study investigates the clinical impact of reduced headache frequency to ≤ 4 monthly headache days (MHDs) as a treatment-related migraine prevention target goal. All treatment arms were pooled for analysis from the PROMISE-2 trial evaluating eptinezumab for the preventive treatment of CM. Patients (N = 1072) received eptinezumab 100mg, 300mg, or placebo. Data for the 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and acute medication use days were combined for all post-baseline assessments and analyzed by MHD frequency (≤ 4, 5-9, 10-15, > 15) in the 4weeks preceding assessment. Based on pooled data, the percentage of patient-months with ≤ 4 MHDs associated with "very much improved" PGIC was 40.9% (515/1258) versus 22.9% (324/1415), 10.4% (158/1517), and 3.2% (62/1936) of patient-months with 5-9, 10-15, and > 15 MHDs, respectively. Rates of patient-months with ≥ 10days of acute medication use were 1.9% (21/1111, ≤ 4 MHDs), 4.9% (63/1267, 5-9 MHDs), 49.5% (670/1351, 10-15 MHDs), and 74.1% (1232/1662, > 15 MHDs). Of patient-months with ≤ 4 MHDs, 37.1% (308/830) were associated with "little to none" HIT-6 impairment versus 19.9% (187/940), 10.1% (101/999), and 3.7% (49/1311) of patient-months with 5-9, 10-15, and > 15 MHDs, respectively. Participants improving to ≤ 4 MHDs reported less acute medication use and improved patient-reported outcomes, suggesting that 4 MHDs may be a useful patient-centric treatment target when treating CM. ClinicalTrials.gov (Identifier: NCT02974153) ( https://clinicaltrials.gov/ct2/show/NCT02974153 ).

Biopsychosocial treatment response among youth with continuous headache: A retrospective, clinic-based study.

Youth with continuous (always present) headache are vastly understudied; much remains to be understood regarding treatment response in this population. To describe and explore biopsychosocial factors related to initial clinical outcomes among treatment-seeking youth with continuous headache. This retrospective cohort study extracted data of 782 pediatric patients (i.e., aged <18 years) with continuous headache from a large clinical repository. Youth in this study had experienced continuous headache for ≥1 month before presenting to a multidisciplinary headache specialty clinic appointment. Extracted data from this appointment included patients' headache history, clinical diagnoses, and headache-related disability, as well as information about biopsychosocial factors implicated in headache management and/or maintenance (e.g., healthy lifestyle habits, history of feeling anxious or depressed). Additional data regarding patient headache characteristics, disability, and lifestyle habits were extracted from a subset of 529 youth who returned to clinic 4-16 weeks after their initial follow-up visit. After characterizing initial treatment response, exploratory analyses compared youth with the best and worst treatment outcomes on several potentially influential factors. Approximately half of youth (280/526; 53.2%) continued to have continuous headache at follow-up, ~20% of youth (51/526) reported a significant (≥50%) reduction in headache frequency. Improvements in average headache severity (e.g., percentage with severe headaches at initial visit: 45.3% [354/771]; percentage with severe headaches at follow-up visit: 29.8% [156/524]) and headache-related disability were also observed (e.g., percentage severe disability at initial visit: 62.9% [490/779]; percentage severe disability at initial follow-up visit: 34.2% [181/529]). Individuals with the worst headache frequency and disability had a longer history of continuous headache (mean difference estimate = 5.76, p = 0.013) and worse initial disability than the best responders (χ2 [3, 264] = 23.49, p < 0.001). They were also more likely to have new daily persistent headache (χ2 [2, 264] = 12.61, p = 0.002), and were more likely to endorse feeling depressed (χ2 [1, 260] = 11.46, p < 0.001). A notable percentage of youth with continuous headache show initial improvements in headache status. Prospective, longitudinal research is needed to rigorously examine factors associated with continuous headache treatment response.

Randomized controlled pilot trial of prazosin for prophylaxis ofposttraumatic headaches in active-duty service members and veterans.

Evaluate the efficacy and tolerability of prazosin for prophylaxis of headaches following mild traumatic brain injury in active-duty service members and military veterans. Prazosin is an alpha-1 adrenoreceptor antagonist that reduces noradrenergic signaling. An open-label trial in which prazosin reduced headache frequency in veterans following mild traumatic brain injury provided the rationale for this pilot study. A 22-week parallel-group randomized controlled trial which included 48 military veterans and active-duty service members with mild traumatic brain injury-related headaches was performed. The study design was based on International Headache Society consensus guidelines for randomized controlled trials for chronic migraine. Following a pre-treatment baseline phase, participants with at least eight qualifying headache days per 4 weeks were randomized 2:1 to prazosin or placebo. After a 5-week titration to a maximum possible dose of 5 mg (morning) and 20 mg (evening), participants were maintained on the achieved dose for 12 weeks. Outcome measures were evaluated in 4-week blocks during the maintenance dose phase. The primary outcome measure was change in 4-week frequency of qualifying headache days. Secondary outcome measures were percent participants achieving at least 50% reduction in qualifying headache days and change in Headache Impact Test-6 scores. Intent-to-treat analysis of randomized study participants (prazosin N = 32; placebo N = 16) demonstrated greater benefit over time in the prazosin group for all three outcome measures. In prazosin versus placebo participants, reductions from baseline to the final rating period for 4-week headache frequency were -11.9 ± 1.0 (mean ± standard error) versus -6.7 ± 1.5, a prazosin minus placebo difference of -5.2 (-8.8, -1.6 [95% confidence interval]), p = 0.005 and for Headache Impact Test-6 scores were -6.0 ± 1.3 versus +0.6 ± 1.8, a difference of -6.6 (-11.0, -2.2), p = 0.004. The mean predicted percent of participants at 12 weeks with ≥50% reduction in headache days/4 weeks, baseline to final rating, was 70 ± 8% for prazosin (21/30) versus 29 ± 12% for placebo (4/14), odds ratio 5.8 (1.44, 23.6), p = 0.013. The trial completion rate of 94% in the prazosin group (30/32) and 88% in the placebo group (14/16) indicated that prazosin was generally well tolerated at the administered dose regimen. Morning drowsiness/lethargy was the only adverse effect that differed significantly between groups, affecting 69% of the prazosin group (22/32) versus 19% of the placebo group (3/16), p = 0.002. This pilot study provides a clinically meaningful efficacy signal for prazosin prophylaxis of posttraumatic headaches. A larger randomized controlled trial is needed to confirm and extend these promising results.

The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis.

Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain. Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed. In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil. Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids.

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Headache Frequency and Pain Severity Following a Nerve Stimulator Implant for Chronic Migraine: A Systematic Review and Meta-Analysis

Migraines affect approximately one billion individuals worldwide. Implanted nerve stimulator devices can provide relief to some individuals who have chronic migraines refractory to other treatments. This study defines the change in headache pain severity and headache frequency following implanted nerve stimulator treatment in chronic migraineurs. A PRISMA-compliant systematic review of six databases was performed to identify all clinical trials treating at least 10 chronic migraineurs with an implanted nerve stimulator. Inverse variance random effects meta-analyses were performed to define the relative change in headache pain severity and headache frequency as compared to baseline. Nine studies met criteria, including 5 randomized controlled clinical trials and 4 uncontrolled clinical trials, and treated 559 individuals. Among studies that reported gender, 306 females and 154 males were treated. Mean patient ages ranged from 45 to 50 years. All included studies targeted the greater occipital nerve with an implanted nerve stimulator. Implanted nerve stimulator treatment reduced pain severity at 1 month by 36.42% (95%-CI: 28.35-44.49, I&lt;sup&gt;2&lt;/sup&gt; = 55%) and 3 months by 50.04% (95%-CI: 39.67-60.42%, I&lt;sup&gt;2&lt;/sup&gt; = 26%). Implanted nerve stimulators reduced headache frequency by 49.86% (95%-CI: 31.49-68.23, I&lt;sup&gt;2&lt;/sup&gt; = 92%) at 1 to 3 months and 27.43% (95%-CI: 17.68-37.18, I&lt;sup&gt;2&lt;/sup&gt; = 63%) at 6 to 97 months. Implanted nerve stimulator devices provide clinically and statistically significant improvements in headache severity and frequency in individuals with chronic migraines.

Erenumab and Possible CGRP Effect on Chronotype in Chronic Migraine: A Real-Life Study of 12 Months Treatment.

The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine.

D15. Non-pharmacologic Treatments for Chronic and Episodic Migraine: A Systematic Review and Meta-analysis

PURPOSE: Minimally invasive techniques for treatment-resistant migraine have been developed upon recent insights into the peripheral pathogenesis of migraines. Although there is a growing body of evidence supporting these techniques, no study has yet compared the effects of these treatments on headache frequency, severity, duration, and cost. METHODS: PubMed, Embase, and Cochrane Library databases were searched to identify randomized placebo-controlled trials that compared radiofrequency ablation, botulinum toxin-A (BT-A), nerve block, neurostimulation, or migraine surgery to placebo for preventive treatment. Data on changes from baseline to follow-up in headache frequency, severity, duration, and quality of life were analyzed. RESULTS: A total of 30 randomized controlled trials and 2680 patients were included. Compared to placebo, there was a significant decrease in headache frequency in patients with nerve block (p=0.04) and surgery (p<0.001). Headache severity decreased in all treatments. Duration of headaches was significantly reduced in the BT-A (p<0.001) and surgery cohorts (p=0.01). Quality of life improved significantly in patients with BT-A, nerve stimulator, and migraine surgery. Migraine surgery had the longest lasting effects (11.5 months) compared with nerve ablation (6 months), BT-A (3.2 months), and nerve block (11.9 days). CONCLUSION: Migraine surgery is a cost-effective, long-term treatment to reduce headache frequency, severity, and duration without significant risk of complication. BT-A reduces headache severity and duration, but is short lasting and associated with greater adverse events and lifetime cost. Although efficacious, radiofrequency ablation and implanted nerve stimulators have high risks of adverse events and explanation, while benefits of nerve blocks are short in duration.

Early Clinical Experience With Eptinezumab From a Retrospective, Observational Study of Real-World Patient Response (P6-12.008)

<h3>Objective:</h3> To describe the patient response, including effects on disability and function, to eptinezumab in a real-world setting after 6 months of preventive migraine treatment. <h3>Background:</h3> The anti-calcitonin gene-related peptide monoclonal antibody eptinezumab is approved for the prevention of migraine in adults. Evidence from post-marketing studies is needed to better understand how eptinezumab prevents migraine in the real-world setting. <h3>Design/Methods:</h3> This retrospective chart review examined data from adults who initiated preventive treatment and received at least 2 infusions of eptinezumab (100mg or 300mg) at headache clinics between April and October 2020. Demographic information, treatment history, migraine and headache frequency, disease characteristics, and disability assessment scores (e.g., Migraine Disability Assessment [MIDAS], Headache Impact Test [HIT-6]) were collected using standardized case-report forms completed by physicians. These report forms measured patient and clinician perspectives on eptinezumab treatment response. <h3>Results:</h3> This analysis includes data from 31 patients with migraine (mean age, 50.7 years; 100% white [27/27]; 81.5% female [22/27]; 93.5% chronic migraine [29/31]) had been collected across 8 sites. Relative to baseline, 6 months of preventive treatment with eptinezumab reduced mean monthly headache days (23.5 at baseline, 16.3 at Month 6), mean monthly migraine days (17.9 at baseline, 9.1 at Month 6), and patient-reported disability (50.0% [11/22] severe at baseline per MIDAS and/or HIT-6, 36.8% [7/19] severe at Month 6). Eptinezumab treatment was also associated with reduced acute headache medication use (16.7 mean acute medication days per month in the last 3 months prior to treatment and 8.3 at Month 6). Clinicians reported that treatment was well-tolerated (96.8%) and improved disability/function (77.4%) after 6 months of use. <h3>Conclusions:</h3> Early clinical experience with eptinezumab and the magnitude of improvement is consistent with results reported in controlled clinical trials, with reductions in headache frequency and associated disability evident during the first 6 months of treatment. <b>Disclosure:</b> Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Seema Soni-Brahmbhatt has nothing to disclose. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck.

Remotely Supervised tDCS for Persistent Post-Traumatic Headache in Veterans (ReStore) (P7-1.004)

<h3>Objective:</h3> Evaluate the feasibility and preliminary efficacy of a remotely supervised transcranial Direct Current Stimulation (RS-tDCS) intervention for persistent post-traumatic headache (PPTH) secondary to mild TBI (mTBI). <h3>Background:</h3> NA <h3>Design/Methods:</h3> Veterans with PPTH completed a 28-day baseline observation of headache days and received either active or sham RS-tDCS paired with mindfulness meditation. This 4-week intervention of 20-minutes daily (M-F) at home RS-tDCS was monitored via VA Video Connect. Feasibility was determined by the number of participants completing at least 80% of the intervention. Preliminary efficacy was measured by changes in number of moderate/severe headache days from baseline period to the end of treatment phase, and to at a 4-week post-treatment follow-up. Secondary endpoints included total number of headache days, acute pain medication use, as well as headache- and mTBI-related disability. <h3>Results:</h3> Twenty-six veterans (46.6±8.7 years) with PPTH completed baseline observations and were randomized to either active (n=13) or sham (n=13) treatment groups. A total of 22/26 (85%) participants fully completed either active (10/13) or sham (12/13) interventions (p=.0.59). Within-group analyses reveled significant reductions in moderate/severe headache days in the active (p=0.04) but not sham (p=0.54) groups. This resulted in a trend towards significant reductions in moderate/severe headache days in the active vs. sham groups (p = 0.07). Active participants also demonstrated a reduction in total number of headache days during treatment (p=0.04) where the sham group did not (p=0.70). This translated into a statistically significant reduction in total number of headache days during treatment for active vs. sham participants (p=0.03). No significant differences were maintained at the 4-week post-treatment follow-up (p’s&gt;0.05). <h3>Conclusions:</h3> RS-tDCS is feasible and effective for veterans with PPTH. Findings suggest that active RS-tDCS may reduce headache frequency and improve clinical outcomes. A larger phase II study is warranted to confirm these findings and inform evaluation for clinical use. <b>Disclosure:</b> Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson &amp; Johnson. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare. Dr. Charvet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for YBrain. Dr. Charvet has stock in Johnson&amp;Johnson. Miss Mangold has nothing to disclose. Taylor Marie Wynne has nothing to disclose. Dr. Moore has nothing to disclose. Dr. Guo has nothing to disclose. Dr. Zhang has nothing to disclose. Abhishek Datta has nothing to disclose. The institution of Dr. Androulakis has received research support from VA rehabilitation research .

The Be-Home Kids Program: An Integrated Approach for Delivering Behavioral Therapies to Adolescents with Episodic and Chronic Migraine.

Migraine disorders are common in populations of children and adolescents. There are different pharmacological treatments for migraine in young patients, but none have specific indications, and doubts about their efficacy exist. The feasibility and effectiveness of behavioral approaches have already been documented in clinical experiences, and they are generally associated with fewer or no unpleasant effects. Among them, mindfulness practice offers a suitable alternative to other adolescent treatments. We present the results of a pilot study, the Be-Home Kids program, performed during the COVID-19 emergency. It was delivered by web and included education on drug use, lifestyle issues, and six sessions of mindfulness-based behavioral practice. We assessed headache frequency, medication intake, and other psychological variables and followed twenty-one adolescents with chronic or high-frequency episodic migraine without aura for 12 months. Results indicated an overall clinical improvement, particularly a 64% reduction in headache frequency over 12 months. In conclusion, our results indicate that a combined treatment which includes patients' education and six sessions of mindfulness-based practice delivered over the web, can be of great support in reducing headache frequency, medication intake, and the associated psychological burden disability in adolescent migraine patients.

An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache.

Many patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective. To assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients. We prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3 months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies. 17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3 months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p < 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month. This study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies.

Nonpharmacologic Treatments for Chronic and Episodic Migraine: A Systematic Review and Meta-Analysis.

Minimally invasive techniques for treatment-resistant migraine have been developed on recent insights into the peripheral pathogenesis of migraines. Although there is a growing body of evidence supporting these techniques, no study has yet compared the effects of these treatments on headache frequency, severity, duration, and cost. PubMed, Embase, and Cochrane Library databases were searched to identify randomized placebo-controlled trials that compared radiofrequency ablation, botulinum toxin type A (BT-A), nerve block, neurostimulation, or migraine surgery to placebo for preventive treatment. Data on changes from baseline to follow-up in headache frequency, severity, duration, and quality of life were analyzed. A total of 30 randomized controlled trials and 2680 patients were included. Compared with placebo, there was a significant decrease in headache frequency in patients with nerve block ( P = 0.04) and surgery ( P < 0.001). Headache severity decreased in all treatments. Duration of headaches was significantly reduced in the BT-A ( P < 0.001) and surgery cohorts ( P = 0.01). Quality of life improved significantly in patients with BT-A, nerve stimulator, and migraine surgery. Migraine surgery had the longest lasting effects (11.5 months) compared with nerve ablation (6 months), BT-A (3.2 months), and nerve block (11.9 days). Migraine surgery is a cost-effective, long-term treatment to reduce headache frequency, severity, and duration without significant risk of complication. BT-A reduces headache severity and duration, but it is short-lasting and associated with greater adverse events and lifetime cost. Although efficacious, radiofrequency ablation and implanted nerve stimulators have high risks of adverse events and explantation, whereas benefits of nerve blocks are short in duration.

Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study.

Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks. We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH). A cross-sectional, prospective, randomized, open study with real-world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs. A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001). The addition of an anti-CGRP monoclonal antibody to the treatment for medication overuse headaches in chronic migraineurs may result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs.

Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.