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Description: Headache medicine and therapeutics evidence have been rapidly expanding and evolving since the 2020 U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) clinical practice guideline (CPG) for the management of headache. Therefore, the CPG was revised in 2023, earlier than the standard 5-year cycle. This article reviews the 2023 CPG recommendations relevant to primary care clinicians for treatment and prevention of migraine and tension-type headache (TTH)., Methods: Subject experts from the VA and the DoD developed 12 key questions, which guided a systematic search using predefined inclusion and exclusion criteria. After reviewing evidence from 5 databases published between 6 March 2019 and 16 August 2022, the work group considered the strength and quality of the evidence, patient preferences, and benefits versus harms on critical outcomes before making consensus recommendations., Recommendations: The revised CPG includes 52 recommendations on evaluation, pharmacotherapy, invasive interventions, and nonpharmacologic interventions for selected primary and secondary headache disorders. In addition to triptans and aspirin-acetaminophen-caffeine, newer calcitonin gene-related peptide (CGRP) inhibitors (gepants) are options for treatment of acute migraine. Medications to prevent episodic migraine (EM) include angiotensin-receptor blockers, lisinopril, magnesium, topiramate, valproate, memantine, the newer CGRP monoclonal antibodies, and atogepant. AbobotulinumtoxinA can be used for prevention of chronic migraine but not EM. Gabapentin is not recommended for prevention of EM. Ibuprofen (400 mg) and acetaminophen (1000 mg) can be used for treatment of TTH, and amitriptyline for prevention of chronic TTH. Physical therapy or aerobic exercise can be used in management of TTH and migraines., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Background: Tension-type headache (TTH) is the most common neurological disorder worldwide, incurring immense social and economic costs and affecting quality of life. However, due to adverse reactions and inadequate effectiveness, there is still an unmet need for treatment. Xuefu zhuyu oral liquid (XZOL) is a Chinese patent medicine widely used for TTH in China, but evidence of its efficacy remains scant., Purpose: The aim of this study was to assess the efficacy and safety of XZOL for TTH patients., Methods: This multicenter, double-blind, randomized placebo-controlled trial enrolled 174 patients with TTH in six centers in China from March 2020 to October 2021. Patients were randomly assigned to receive XZOL or a matched placebo for 4weeks. The primary outcome was the change in the mean headache intensity as measured by a visual analogue scale (VAS) from baseline to the end of treatment (Week 4). Secondary outcomes were the change in VAS from baseline to Week 12, the area-under-the-headache curve (AUC), response rate, number of headache days, average headache duration, rescue medication use proportion, etc. RESULTS: Of the 174 patients who were randomized, 160 completed the study. There was no significant difference in the mean change in VAS from baseline to the end of treatment between the XZOL group and the placebo group (-0.29; (95 % CI:0.81 to 0.23; p = 0.279) in the full analysis set (FAS), while there were statistically significant results (-0.9; 95 % CI:1.47 to -0.33; p = 0.002) in the per-protocol set (PPS). There were no significant differences in any of the secondary outcomes. The incidence of adverse events was similar in the two groups., Conclusion: XZOL may be an alternative option to relieve pain for TTH patients with high compliance in clinical practice. However, XZOL did not improve headache measurements in the FAS population., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this publication, and the study received no financial support that could have influenced its outcome. The medications were supplied by the Jilin Aodong Pharmaceutical Group Co., Ltd (Jilin, China). However, Aodong Pharmaceutical Group was not involved in the study design, data collection, analysis, or interpretation of the results. The company's role was limited to supplying the study medication and it did not influence the scientific validity or integrity of the trial. Any questions or concerns about our disclosure can be directed to the corresponding author., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults., Methods: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554., Results: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I 2 between the studies was low., Conclusions: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

Background: In this study, we aimed to evaluate the differing global access to acute and preventive medications for migraine and tension-type headache., Methods: A custom-built questionnaire created by members of the International Headache Society Juniors Group was sent to International Headache Society members worldwide, including a list of acute and preventive treatments for migraine and tension-type headache. This list was based on evidence-based medicine guidelines. For each treatment, participants were asked about availability, type of reimbursement and variability of access within their country., Results: Eighty-four members completed the questionnaire providing data for 84 countries. The majority were neurologists (88%) and worked at an academic/university hospital (62%). Of participants, 36% were located in high-income economy countries and 13% were located in low-income economies. Common preventive treatments such as propranolol and topiramate were available in most countries (respectively in 99% and 92% of responding countries). Sumatriptan was available in most countries (95%), whereas other triptan availability was lower. Novel migraine treatments such as rimegepant and erenumab were only available in 14% and 46% of the assessed countries, respectively., Conclusions: Availability of headache medications, ranging from simple analgesics to novel therapies migraine-specific drugs, varied greatly across the world. Actions are needed to improve effective drug availability in many countries to ensure an adequate management of people living with headache., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tension-type headache (TTH) and migraine are prevalent neurological conditions in children and adolescents that significantly impact activity of daily living (ADL) and quality of life (QOL). Although physical therapy targeting cervical myofascial trigger points (MTrPs) on TTH and migraine has been extensively studied in adults, the efficacy in pediatric patients remains unexplored. The aim of this study is to reveal the effect of physical therapy integrated with pharmacotherapy on TTH and migraine in children and adolescents., Methods: We conducted a prospective, observational cohort study recruiting consecutive patients aged 6 to 18 years with TTH and migraine with cervical MTrPs. They were classified into 4 types of headaches: frequent episodic TTH (FRTTH), chronic TTH (CTTH), episodic migraine (EM) and chronic migraine (CM). The once-weekly 40-minutes physical therapy session integrated with pharmacotherapy (integrated physical therapy) was continued until the treatment goals (headache days per week less than 2 days, headache impact test-6 (HIT-6) score to below of 50, and the ability to attend school daily) was achieved. Multifaceted assessments including headache frequency (headache days per week), headache intensity using the Visual Analogue Scale (VAS), pain catastrophizing score (PCS), hospital anxiety and depression scale (HADS) score, HIT-6 scores, and EuroQol 5 dimensions 5-level questionnaire (EQ-5D-5 L) scores, were conducted to evaluate the treatment effects., Results: 161 patients were enrolled in this study. 106 patients (65.8%) were diagnosed with TTH: 70 (66.8%) with FETHH, 36 (34.0%) with CTTH, and 55 patients (34.2%) were diagnosed with migraine: 43 patients (78.2%) with EM, 12 patients (21.8%) with CM. We observed significant improvements in headache frequency, headache intensity, PCS, HADS score, HIT-6 scores, and EQ-5D-5 L scores before and after the treatment in all 4 types of headaches. The average number of sessions required to achieve the treatment goals was 4 times (weeks) for patients with FETTH and EM, 5.5 for those with CTTH, and 7.5 for those with chronic migraine., Conclusion: The integrated physical therapy on pediatric TTH and migraine patients with the cervical MTrPs was significantly effective in reducing headache symptoms and improving ADL and QOL., (© 2024. The Author(s).)

Background: Headache disorders are globally prevalent and insufficient treatment contribute to low quality of life, increased disability, and socioeconomic costs. However, headache can to a large extent be treated appropriately by general practitioners., Objective: To explore general practitioners' (GPs') management of patients with headache lasting ≥6 months., Methods: In this retrospective descriptive cross-sectional study based on medical audit, all GPs practicing in Vejle municipality (population 116,992), Denmark, were invited to review their latest 20 patients with headache. Outcome measures were headache diagnostics, treatment, and referrals. Factors associated with referral to neurological treatment were examined by logistic regression., Results: Of 26 invited practices, 19 participated reporting on 367 patients with lasting headache (71.4% women; mean-age 48.5 years). One hundred and sixty-one patients had migraine (44%; IQR: 28-60%), 140 (38%; IQR: 25-44%) had tension-type headache; 243 (66%; IQR: 50-79%) used simple analgesics, 147 (40%; IQR: 29-59%) triptans, 37 (10%; IQR: 0-14%) opioids, 93 (25%; IQR: 20-35%) were prescribed preventive medication; 176 (48%; IQR: 48-59%) were referred to neurologist, and 92 (25%; IQR: 10-37%) were referred to CT or MRI scan. Associated factors for referral were >1 headache diagnosis (aOR 1.75 [95% CI: 1.05-2.95]; P = 0.03), post-traumatic headache (aOR 2.53 [95% CI: 1.25-5.38]; P = 0.01), unspecific headache (aOR 2.04 [95% CI: 1.08-3.93]; P = 0.03), and using preventive treatment (aOR 2.75 [95% CI: 1.68-4.57]; P < 0.001)., Conclusion: This study provides insights to how GPs manage patients with long-lasting headache. Focus should be on reducing opioids, increasing preventive treatment, and keeping more patients in primary care., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose of Review: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH., Recent Findings: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches., (© 2024. The Author(s).)

Background-Purpose : Low serum vitamin D (VD) has been already associated with a series of highly prevalent pain-related conditions, including fibromyalgia, migraine and chronic widespread pain. Considering the potential interplay between VD and pain signalling pathways, the association of VD with tension-type headache (TTH) was reviewed., Methods : A multifaceted narrative approach assessing the relationship of serum VD with TTH and TTH parameters, as well as the efficacy of VD supplementation for the prevention of TTH, was fostered. MEDLINE, CENTRAL and EMBASE were comprehensively searched for this purpose, while Google Scholar was also explored according to a structured approach. ClinicalTrials.gov and European Union Clinical Trials Register were explored for ongoing prevention trials., Results : Although available evidence was suggestive of an association between VD and TTH, mainly of the chronic type, the causal nature of the association remains to be determined. Considering the lack of longitudinal evidence, this relationship could arguably reflect behavioural patterns of headache sufferers. On the other hand, evidence principally originated from tertiary clinical settings (severe comorbidity burden) and researchers tend to report a concomitant association of both entities with generalized musculoskeletal compromise. In this context, the association between TTH and VD may represent nothing more than a secondary by-product of the simultaneous relationship of other comorbid diseases-conditions with both TTH and low serum VD. Regarding its efficacious properties, only one ongoing trial specifically designed to explore the efficacy of VD in chronic TTH in adults was retrieved., Conclusions : There is no evidenced based indication for VD supplementation in TTH.

Background: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis., Methods: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach., Results: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23)., Conclusion: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence., (© 2024. The Author(s).)

Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache Disorders. TTH is treated with over-the-counter medications, mostly paracetamol or ibuprofen. The purpose was to assess the effectiveness of paracetamol versus ibuprofen in treating episodic tension-type headache (ETTH) through direct and indirect comparisons of randomized controlled trials (RCTs). We included RCTs comparing paracetamol with a placebo, ibuprofen with a placebo, or paracetamol with ibuprofen for acute ETTH treatment that were published between 1988 and 2022. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Web of Science. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias. We identified 14 studies including 6521 people with ETTH. None of the studies had a low risk of bias for all domains; this was most likely due to inadequate reporting and a small sample size. Ibuprofen (odds ratio (OR): 1.73, 95% confidence interval (CI): 1.17-2.56) showed better efficacy than paracetamol (OR: 1.62, 95% CI 1.24-2.13) for pain-free status at 2 h, while paracetamol (OR: 1.42, 95% CI 0.87-2.30) showed better efficacy than ibuprofen (OR: 1.20, 95% CI 0.58-2.48) for pain-free status at 1 h. Paracetamol was associated with the lowest likelihood of rescue medication use (OR: 0.49, 95% CI 0.37-0.65). Ibuprofen was associated with a lower likelihood of the occurrence of any events and gastrointestinal adverse events compared with placebo and paracetamol (OR: 0.95, 95% CI 0.64-1.41 and OR: 0.81, 95% CI 0.44-1.50, respectively). Paracetamol and ibuprofen showed better efficacy than placebo in treating ETTH; there was no statistically significant difference in efficacy between the two drugs. For individuals at a higher risk (like renal insufficiency or risk of GI bleeding), paracetamol may be considered as a preferred option instead of Ibuprofen. Further meta-analyses of head-to-head trials are needed for direct comparisons in the future.PROSPERO registration number: CRD42022340936., (© 2023. The Author(s).)

Introduction: Tension-type headache (TTH) is the most prevalent headache disorder worldwide. Although current treatments for TTH are beneficial, they are not without adverse effects. Chaixiong Qiwei granule (CXQW) is an experienced prescription medicine for TTH management. This study will evaluate the efficacy and safety of CXQW for the treatment of TTH., Methods and Analysis: This study will be a multicentre, randomised, double-blind, placebo-controlled trial. A total of 148 eligible participants will be divided into the intervention (CXQW treatment) and control (placebo treatment) groups. The primary outcome will be the reduction in the number of headache days (headache-days reduction) within 9-12 weeks after randomisation, while secondary outcomes will include the number of headache days, headache intensity, responder rate, drug consumption for acute treatment, quality of life and symptoms related to traditional Chinese medicine use based on a symptom-observation table. This protocol describes the design of the randomised controlled trial., Ethics and Dissemination: The study design was approved by the Institutional Review Board of Human Research at Xiyuan Hospital, China Academy of Chinese Medical Sciences (No. 2020XLA030-2)., Trial Registration Number: ChiCTR2100042514., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists., Methods: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021., Results: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study., Conclusions: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Backgrounds: Tension-Type Headache (TTH) is one of the most common types of headache. In patients with TTH, manual therapy can be used to treat myofascial pain., Objectives: This study aimed to evaluate the effect of manual therapy on TTH in patients who did not respond to drug therapy., Methods: A total of 24 patients with TTH were randomly enrolled into this prospective trial. The participants were divided into an intervention and a control group. The intervention group received the common medication and manual therapy, while the control group only received the common medication. Headache pain intensity, frequency, and duration, tablet count, and Neck Disability Index (NDI) were measured in both groups before, after, and one week after the intervention., Results: There were significant differences between the two groups (treatment, control) regarding pain intensity (3.04, 6.75, P = 0.0001; effect size (ES) = 1.85), headache frequency (2.33, 5, P = 0.004; ES = 1.48) and duration (91.29, 284.74, P = 0.002; ES = 1.48), tablet count (1.83, 4.91, P = 0.01; ES = 1.04), and NDI (7.33, 20.16, P = 0.003; ES = 1.37). Within group differences were recorded in intervention group only for all dependent variables immediately after intervention and one week after the intervention (p < 0.05)., Conclusion: Manual therapy reduced headache pain intensity, frequency and duration, tablet count, and NDI score in patients with TTH.

We present the rationale and design of a master protocol study that clarifies the effectiveness and safety of Chinese herbal formulas on -stagnation and blood-stasis pattern (QBP). Three randomized controlled trials (RCTs) and real-world observational studies. Based on three registry cohorts of stable angina, tension-type headache and primary dysmenorrhea, patients with QBP will be enrolled in RCTs to receive either Xuefu Zhuyu (, XFZY) oral liquid or a placebo, while patients with non-QBP will be enrolled in the observational studies and experience follow-up. 1414 patients (RCTs: 574; observational studies: 840) will be recruited at seven centers in China over a 3-year period. The primary outcome is the visual analog scale of pain intensity. Adverse events will also be reported. The analysis will be undertaken separately in each sub-study, and then an overall analysis combining multiple subgroups will be performed to comprehensively investigate the effect of XFZY oral liquid. This study will provide high-quality evidence of XFZY oral liquid for QBP patients and show a paradigm of post-marketing evaluation of the effectiveness and safety for Chinese medicine following the notion of the pattern dominating different disease research models.

Headaches are one of the most frequent causes of consultations in general practice. Of more than 350 known headache tendencies, tension-type headache and migraine are particularly common in general practice. Medication overuse headache (MOH) is also common but rarely diagnosed. The medical consultation with a targeted anamnesis is the cornerstone of the diagnosis and correct classification. A detailed neurological examination completes the basic diagnosis. Additional laboratory and instrumental diagnostics follow in cases of atypical headache or clinical suspicion of secondary headache. This article focuses on the diagnosis and treatment of Tension-type Headache, migraine and Medication Overuse Headache., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache., Methods: Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the 'meta' package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences., Results: Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (-0.502 standard deviations [-0.945, -0.058]), headache frequency (-2.830 days/month [-4.082, -1.578]), daily headache duration (-0.965 [-1.860, -0.069]) and the frequency of acute pain medication use (-2.200 days/month [-3.485, -0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient., Conclusions: Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted., Registration: Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616).

Objectives: Tension-type headache (TTH) is the most prevalent type of primary headache disorder. Its acute pharmacotherapy is acetaminophen or non-steroidal anti-inflammatory drugs based on the Japanese Clinical Practice Guideline for Headache Disorders 2021. With Japan's aging population, however, the number of TTH patients with comorbidities that have been treated by analgesics is increasing. Under this context, it is sometimes difficult to select an acute pharmacotherapy for TTH. Kakkonto, Japanese traditional herbal kampo medicine, is empirically used for TTH. We hypothesized that kakkonto has efficacy for TTH with painful comorbidities., Materials and Methods: We prospectively collected 10 consecutive TTH patients who had already taken analgesics for comorbidities. We prescribed 2.5 g of kakkonto (TJ-1), and patients took it. A numerical rating scale for pain before and 2 hours after kakkonto intake was evaluated., Results: Eight women and 2 men were included. The mean age was 71.0 ± 13.4 years old. Four patients had lower back pain, 2 had lumbar spinal stenosis, 2 had knee pain, 1 had neck pain, and 1 had shoulder myofasciitis. Celecoxib was used for 4 patients, acetaminophen for 3, loxoprofen for 2, and a combination of tramadol and acetaminophen for 1, as routinely used analgesics. The median numerical rating scale statistically improved from the median of 4 to that of 0. There were no side effects of kakkonto., Conclusion: Kakkonto showed efficacy as an acute medication for TTH with comorbidities that have been treated by analgesic.

Objective: To assess the severity of anxiety, depression, insomnia and asthenia in patients with episodic migraine and tension-type headache before and after treatment., Material and Methods: 104 patients aged 18 to 74 years were examined. Patients were divided into two groups: the 1 st - 41 patients diagnosed with episodic migraine, the 2 nd - 63 patients with episodic tension-type headache. The intensity of headache was assessed using the visual analog scale (VAS). The Hospital Anxiety and Depression Scale (HADS), the Levin questionnaire, and the Multidimensional Fatigue Inventory scale (MFI-20) were used to identify comorbid affective pathology, insomnia, and asthenia, respectively., Results: Headache severity according to VAS in the 1 st group was higher (5.8±1.3 points) than in 2 nd (3.8±1.2 points). Clinical anxiety was detected in 66.3% of patients without statistically significant differences between groups. The mean HADS anxiety score was 13.9±3.5 in 1 st group, 12.7±3.7 - in 2 nd . Clinical depression was detected in 45.2% of patients, more often in the 2 nd group - 50.8% than in the 1 st (36.6%). The mean depression score according to HADS was 9.0±4.4 and 9.7±3.6 in the 1 st and 2 nd groups respectively. The intensity of headache was statistically significantly higher in patients with clinical anxiety. Both groups were found to have insomnia and asthenia. The majority of patients - 67.3% had myofascial pain syndrome. When re-evaluating the severity of disorders after treatment (using anxiolytics, antidepressants, muscle relaxants, magnesium and neurometabolics), a significant positive trend was noted. Reducing the intensity of headaches to 3.2±0.9 points (according to VAS scale) was in patients with migraine and 1.9±0.8 points in 2 nd group. Relief of anxiety and depressive disorders was observed (HADS) in 1 st (4.3±3.9) and 2 nd (4.5±3.3) groups, the severity of depression (HADS) - 2.1±2.2 in 1 st and 2.8±3.2 in 2 nd groups, as well as a decrease in asthenia and normalization of sleep. The decrease in the severity of asthenia during treatment was more significant in patients treated with Cytoflavin., Conclusion: Identification and treatment of comorbid pathology leads to positive results in the treatment of primary headaches such as episodic migraine and TTH.

Background: Headaches are common in childhood. Recently, there has been an increasing trend toward pharmacological treatment., Methods: Secondary causes were excluded first in patients who attended our clinic with headache. Those without a secondary cause were evaluated as primary headache and classified into subgroups. Behavior-modifying recommendations (adequate and regular sleep, adequate and regular nutrition, adequate fluid intake, and restriction of screen exposure) were given to all patients. Patients were re-evaluated at 1, 3, and 6 months. Pharmacologic treatment was started at the end of the first month with follow-up at the third and sixth months for those who did not benefit from the behavior-modifying recommendations., Results: A total of 875 patients presented with headache complaints, of which 30.6% were evaluated as primary headache. Behavior-modifying recommendations were beneficial for 23.1% with migraine with aura; 20.3% with migraine without aura, and 36.8% with tension-type headache., Conclusion: Secondary causes should be excluded first in patients who present to the pediatric neurology clinic with headache. Behavioral modifications to change the lifestyle of patients diagnosed with primary headache should be tried before giving pharmacologic treatment., (© 2022 Japan Pediatric Society.)

Background: Headache is a common neurological disorder, with a global prevalence of around 50%. It may affect people of any age, gender, education, socioeconomic status and occupation. Tension headache, migraine headache and cluster headache are commonly encountered headache types. The prevalence of headache problems is higher among medical students. This could potentially affect their academic performance and quality of life. The objective of this study is to find out the prevalence of headaches and their clinical characteristics among students of a medical college., Materials and Methods: An online, single-centre, cross-sectional study was conducted among undergraduate medical students in Nepal. Stratified sampling followed by a simple random sampling technique was adopted depending upon the academic years of students. For data collection, pre-tested semi-structured questionnaire was used. The data entry and analysis were done by using Statistical Package for the Social Sciences (IBM-SPSS), version-23. The prevalence of headache and its subtypes were calculated. All the clinical characteristics associated with headaches were also studied., Results: The prevalence of headache disorder was 65 (26.86%), with tension headache (69.23%) being the commonest one. It was highest among fourth-year students (37.84%) followed by first-year students (33.33%). Anxiety/stress (75.40%) was the most common precipitating factor. This problem stopped most of the students (63.09%) from doing daily activities. More than half of them (53.85%) practised self-medication in case of non-resolution of pain, and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently used., Conclusion: Headache was fairly prevalent among medical students. Anxiety/stress in medical life has led to headaches in the majority of students. The headache disturbed their daily activities and promoted self-medication practice. So, this problem should be properly looked into and addressed in time by the concerned authority., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Bhattarai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting., Methods: We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT., Results: Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (- 8.5, 95% CI - 14.6, - 2.5) were associated with AMT response., Conclusions: This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea., (© 2022. The Author(s).)

Objective: Investigation of onabotulinumtoxinA in a murine model of acute and persistent post-traumatic headache., Methods: Mild traumatic brain injury was induced with a weight drop method. Periorbital and hindpaw cutaneous allodynia were measured for 14 days. Mice were then exposed to bright light stress and allodynia was reassessed. OnabotulinumtoxinA (0.5 U) was injected subcutaneously over the cranial sutures at different post-injury time points., Results: After milt traumatic brain injury, mice exhibited periorbital and hindpaw allodynia that lasted for approximately 14 days. Allodynia could be reinstated on days 14-67 by exposure to stress only in previously injured mice. OnabotulinumtoxinA administration at 2 h after mild traumatic brain injury fully blocked both transient acute and stress-induced allodynia up to day 67. When administered 72 h post-mild traumatic brain injury, onabotulinumtoxinA reversed acute allodynia, but only partially prevented stress-induced allodynia. OnabotulinumtoxinA administration at day 12, when initial allodynia was largely resolved, produced incomplete and transient prevention of stress-induced allodynia. The degree of acute allodynia correlated positively with subsequent stress-induced allodynia., Conclusion: Mild traumatic brain injury induced transient headache-like pain followed by long lasting sensitization and persistent vulnerability to a normally innocuous stress stimulus, respectively modeling acute and persistent post-traumatic headache.. Administration of onabotulinumtoxinA following the resolution of acute post-traumatic headache diminished persistent post-traumatic headache but the effects were transient, suggesting that underlying persistent mild traumatic brain injury-induced maladaptations were not reversed. In contrast, early onabotulinumtoxinA administration fully blocked both acute post-traumatic headache as well as the transition to persistent post-traumatic headache suggesting prevention of neural adaptations that promote vulnerability to headache-like pain. Additionally, the degree of acute post-traumatic headache was predictive of risk of persistent post-traumatic headache.

Headaches are a very common condition that most people will experience many times during their lives. This article presents the primary headaches, which are a large group of diseases where the headache is not a symptom of another known disease. Tension-type headache affects approximately 80% of the general population, and the prevalence of migraine is estimated at 10-12%. Clinical data and experience to date have demonstrated that botulinum toxin may be an effective prophylactic treatment for chronic headache types. It has been used in neurology for the treatment of dystonia and blepharospasm. Now it has been approved to treat chronic migraine and has been shown to confer significant benefit in refractory cases. Based on clinical experience botulinum toxin has also been tried in other headache disorders. While it is intuitively attractive to think that due to its effect on pain by sensory modulation, there may also be efficacy in its use in chronic tension-type headache and cluster headache, so far, there is little evidence to support this. Botulinum toxin is effective in pain control through its interaction with the SNARE complex, which inhibits the release of neurotransmitters, such as glutamate, substance P and calcitonin gene-related peptide. OnabotulinumtoxinA is effective not only in headache frequency and pain intensity but in other parameters, including quality of life.

Rationale: Tension-type headache (TTH) is the most common type of primary headache, and trigger point injection (TPI) is frequently used for controlling pain originating from TTHs. In the current report, we introduce a TPI technique involving 4 neck muscles (upper trapezius, splenius capitis, semispinalis capitis, and inferior oblique capitis) and a greater occipital nerve (GON) block within the same sonographic view for the treatment of TTHs., Patient Concerns: A 44-year-old woman complained with pressing and tightening, nonpulsating, recurrent headaches, mainly in the bilateral occipital area, lasting for approximately 6 months (numeric rating scale: 5). The patient had no nausea, vomiting, photophobia, or phonophobia., Diagnoses: The patient was diagnosed as having a TTH., Interventions: Under ultrasound (US) guidance, a mixed solution of 2 mL of 2% lidocaine and 5 mL of normal saline was injected layer-by-layer into the 4 target muscles of the neck (upper trapezius, splenius capitis, semispinalis capitis, and inferior oblique capitis) and near the right GON within the same sonographic view bilaterally., Outcomes: Two- and 4-week follow-ups after administration of the injections revealed no headache. Our US-guided 5-in-1 TPI technique is viable for treating patients with TTH., Lessons: We believe that it can aid in reducing the procedure time and associated pain., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The aim of the present study was to assess the burden and health care use of adult patients with migraine and tension type headache in a post-conflict area of Serbia., Methods: This cross-sectional study was conducted on a representative sample of adults, living in predominantly Serb communities on the Kosovo and Metohija territory. The required data was obtained through a survey, utilizing a culturally-adapted questionnaire. The study sample comprised of 1,062 adults., Results: In the year preceding the study, 49.7% of included subjects suffering from migraines and 27.5% of those experiencing tension type headache sought medical assistance for their condition. The majority (88.5%) of the respondents utilized non steroid antiinfammatory drugs as analgesic, while 14.2% used prophylactic treatment. Migraine sufferers reported losing on average 11.1 days in a 3-month period, while those experiencing tension type headache lost 4.7 days (p < 0.001) due to headaches, preventing them from partaking in professional, family and social activities. On headache-free days, 24.5% of the respondents were anxious or tense in anticipation of a headache onset, while 30% did not feel that the headache had completely resolved. Moreover, 11.5% of the sample reported never or rarely feeling in control of the headache, while 20% of the respondents were of view that their headaches were not taken seriously by their employer and co-workers and rarely discuss them. Adverse effect of headaches on education is more frequently noted by migraine sufferers than those experiencing tension type headache (p = 0.001), and this disparity persists in relation to career (p < 0.001) and family planning (p = 0.001)., Conclusions: In Kosovo and Metohija, primary headaches exert a profound influence on the affected individuals and their community, and thus require recognition as one of the priorities of social initiatives aimed at the enhancement of public health.

A 74-year-old female subject with suboptimal management of episodic tension headache was treated with a daily dose of 1.5 g L-arginine and 1.2 g aged garlic extract (AGE). The aim of the intervention was to promote vasodilation of parenchymal cerebral blood vessels. Within 6 weeks of commencing treatment, her self-reported symptoms improved markedly and were sustained at 2 years following commencement. We propose that the putative beneficial effect of L-arginine and AGE in this patient is because of the well-established systemic vasodilatory effects of L-arginine and aged garlic extract. On the hypothesis that migraine is precipitated by cerebral microvascular constriction, we recommend a double-blind randomised controlled trial to clinically test this hypothesis in migraine patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Migraine and tension-type headache are among the most frequent diseases of the world. As pharmacological treatment often is associated with distinct side effects, there is an increasing need for non-pharmacological treatment options. However, there has been a striking lack of evidence with regards to the efficacy of the huge variety of non-pharmacological interventions. In this review, we present the available evidence for the most common non-pharmacological treatment options with focus on the national clinical guideline for non-pharmacological treatment of headache disorders published in 2021.

The review shows the relationship between tension-type headache (THT) and insomnia. The pathophysiological and psychological mechanisms of their mutual influence on each other are considered. Evidence is provided that the combination of these pathologies often leads to the development of maladaptive coping strategies that aggravate the patient's condition. The features and difficulties of therapy of patients suffering from TTH and insomnia are considered in detail. It has been shown that the treatment of such patients should include approaches aimed at stopping TTH, sleep disorders and associated emotional disorders using drug and non-drug methods of treatment.

Abstract: Roughly 90% of the U.S. population will develop a headache within their lifetime, and headache disorders account for more disability-adjusted life-years than all other neurologic disorders combined. Among primary headache disorders, the two most common are tension-type headache and migraine, with migraine identified as the most disabling. Here, the authors describe the importance of differentiating primary and secondary headache disorders and discuss the pathophysiology; clinical assessment; and outpatient management of the debilitating migraine headache, summarizing both acute and prophylactic treatment strategies that can substantially reduce associated disability., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)