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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.)

Background-Purpose: A bidirectional relationship appears to connect tension-type headache (TTH) and circadian dysregulation. The present systematic review examined the published evidence for melatonin (MT) supplementation in the prophylaxis of TTH. Initially, we reviewed case-control studies investigating nocturnal MT or 6-sulphatoxymelatonin (aMT6s, a urine-discarded metabolite) in TTH individuals and healthy controls (HC). Secondly, we reviewed studies appraising the use of MT in the prevention of TTH., Methods: The search strategy involved MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar and OpenGrey. Case-control studies were appraised according to the Newcastle-Ottawa-Scale, whereas randomised controlled trials were assessed based on the risk-of-bias Cochrane tool. Infrequent, as well as frequent, episodic, and chronic TTH patients were evaluated separately in children and adults., Results: Our search strategy yielded two case-control studies. One (high-quality) did not reveal any difference in morning salivary MT concentration between children with frequent episodic TTH and HC. The second (moderate-quality) was indicative of a disturbed nocturnal secretion pattern in adults with chronic TTH. For the second part, five uncontrolled studies were retrieved. In total, 94 adults with chronic TTH were assessed and results were suggestive of a beneficial effect of MT on headache frequency, intensity, induced disability, and induced analgesic consumption. However, the uncontrolled-unblinded designs may have induced an important placebo effect. Non-adult populations and frequent TTH were substantially understudied., Conclusions: There are not enough studies to designate the role of MT in the prevention of TTH. Given the disease's background, additional relevant research is warranted for chronic TTH., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.

This study aims to systematically evaluate the clinical efficacy and safety of Toutongning Capsules in the treatment of tension-type headache(TTH), so as to provide a corresponding basis for clinical treatment. Eight commonly used medical research databases and two clinical trial registration systems were retrieved with the time interval from the establishment of the database or system to November 2020. The randomized controlled trials of Toutongning Capsules in the treatment of TTH were screened out according to the pre-set criteria. The quality of the included papers was evaluated by the bias risk assessment tool in Cochrane Reviewers Handbook 6.1 and the data were statistically analyzed by RevMan v5.4 provided by Cochrane collaboration. A total of 13 studies were included and the quality of methodology was generally low. Meta-analysis showed that Toutongning Capsules assisted with western medicine therapy can effectively reduce the pain intensity(MD&#95;(VAS)=-1.94,95%CI[-2.50,-1.38],P&lt;0.000 01;MD&#95;(NRS)=-0.83,95%CI[-0.86,-0.80],P&lt;0.000 01), headache duration(SMD=-0.98,95%CI[-1.17,-0.79],P&lt;0.000 01), headache frequency(MD=-1.01,95%CI[-1.16,-0.85],P&lt;0.000 01), headache index(MD=-11.13,95%CI[-12.10,-10.16],P&lt;0.000 01), anxiety and depression scale score(MD&#95;(HAMA)=-4.02,95%CI[-6.58,-1.46],P=0.002;MD&#95;(HAMD)=-2.67,95%CI[-4.04,-1.29],P=0.000 1), while Toutongning Capsules as monotherapy only reduced the headache score(MD=-2.24,95%CI[-2.97,-1.51],P&lt;0.000 01). The available clinical studies demonstrate that Toutongning Capsules combined with western medicine in the treatment of TTH can improve the related outcome indicators, but the clinical safety and efficacy of Toutongning Capsules alone remain unclear. Due to the small number and low quality of the included studies, large-sample, multi-center, high-quality and strictly designed randomized controlled trials are still needed to verify the clinical efficacy in the future.

The article goes to describe clinical and pharmacological approaches to choosing a drug with an optimal efficacy/safety profile, providing the necessary analgesic effect in tension-type headache. TRPV1 brain receptors are considered the main action point of the mediator., Aim: The purpose of this study is a comparative analysis of the pharmacodynamic and pharmacokinetic parameters of ibuprofen and paracetamol as a part of fixed dose combination and as monotherapy in tension type headaches., Materials and Methods: Comparative dissolution kinetics test; Comparative analysis of pharmacokinetic parameters using the PubMed/MEDLINE database., Results: The median Tmax of ibuprofen as a part of a fixed-dose combination and as a monotherapy is 75 minutes. The median Tmax of paracetamol is 30 min when taken in a fixed dose combination and 40 min as a monotherapy. In patients who received the fixed dose combination, the concentration of ibuprofen in the blood plasma after 10 minutes 6.64 g/ml-1; after 20 minutes 16.81 g/ml-1, while when taken in the same dose in as a monotherapy, respectively, 0.58 and 9.00 g/ml-1. The mean plasma concentrations of paracetamol after 10 and 20 minutes in patients receiving the fixed combination were 5.43 and 14.54 g/ml-1, respectively, compared with 0.33 and 9.19 g/ml-1 for paracetamol as monotherapy. dissolution kinetics test of the Paracytolgin: after 5 minutes, 20% of paracetamol passed into the solution in a system with a pH of 1.2; in a system with a pH of 4.5 36.4%; in a system with a pH of 6.8 33.5%; after 10 minutes, respectively 68.5, 98.0 and 89.6%. After 15 minutes, almost complete dissolution was noted in all systems: 98.5, 98.8 and 100.5%, respectively., Discussion: The combination of ibuprofen and paracetamol makes it possible to enhance the analgesic effect as a result of additive action by the help of central mechanisms. The fixed dose combination of ibuprofen and paracetamol significantly increases the rate of absorption of paracetamol, which has potential therapeutic benefits in terms of a faster analgesias onset., Conclusion: The fixed dose combination of ibuprofen and paracetamol provides faster and long-term anaesthesia with a comparatively lower dosage of each analgesic.

A short-cut review of the literature was carried out to examine the benefits of caffeine as an analgesic adjunct in tension-type and migraine-type headache. Six papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that caffeine provides effective analgesia as an adjunctive treatment in the management of secondary headache syndromes., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking., Objective: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year., Methods: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year., Results: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported., Conclusions: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients., (© 2021 American Headache Society.)

Introduction: The International Headache Society criteria were written in order to help physicians establish a headache diagnosis. However, sometimes children with headache do not seem to fit any diagnosis. The purpose of our study was to assess the application of the criteria in a clinical setting., Methods: Medical records of children referred for primary headache to the pediatric neurology clinic at Bnai Zion Medical Center from 2008 to 2017 were assessed., Results: A total of 989 patients (range 6-18 years; 53% female) were assessed at our neurology clinic. Twenty-four percent (n = 241) were diagnosed with tension-type headache, 26% (n = 256) with migraine, and 4.5% (45) with mixed headache. In 41.5% (410), we were unable to reach a specific diagnosis. No differences in gender or age were found between the groups. Children in the migraine group used more analgesic treatments to stop the headache attacks compared with the tension-type headache group (50% vs 38%, P = .001). Patients diagnosed with tension-type headache reported having more emotional difficulties ( P = .001). No significant differences were found in headache characteristics (ie, location, sidedness, character), frequency, or intensity between the younger children (ages 6-11) and the adolescents (ages 12-18) within either the tension-type headache or migraine groups., Conclusions: Retrospective application of International Headache Society criteria in a large cohort of children with headaches failed to diagnose a specific type of headache in 41.5% of children. Migraine and tension-type headache were equally prevalent, and both constituted a major burden on our patients' everyday lives. We found no major differences in frequency, intensity, and characteristics of pain between younger children and adolescents.

Objectives: The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial nociceptors is suggested as a potential mechanism and injections of botulinum toxin (BONTA) have thus been used in the treatment for both headache conditions. BONTA inhibits the release of acetylcholine at the neuromuscular junction and inhibits contraction of skeletal muscles. If the pain is precipitated by increased tone in cervical muscles, local injections of BONTA could represent a prophylactic measure. However, the treatment is still controversial, and a thorough assessment of the current evidence is required. This review aims to assess the evidence of BONTA injection as a prophylactic treatment for CTTH and CEH by reviewing and examining the quality of placebo-controlled, randomized trials., Methods: Data sources: we searched in the following databases: PubMed (including Medline), Embase, Cochrane Central register of Controlled Trials, Cinahl, Amed, SCOPUS and Google Scholar including other repository sources. Both MeSH and free keywords were used in conducting the systematic search in the databases. The search covered publications from the root of the databases to November 2020., Study Eligibility Criteria: The review included RCTs, comparing single treatment of BONTA with placebo on patients with CTTH or CEH above 18 years of age, by measuring pain severity/relief or headache frequency., Data Extraction: The following data were extracted: year of publication, country, setting, trial design, number of participants, injection procedure, BONTA dosages, and clinical outcome measures., Study Appraisal: To assess validity and quality, and risk of bias, the Oxford Pain Validity Scale, Modified Jadad Scale, last version of Cochrane Collaboration's tool for assessing risk of bias (RoB 2), and the CONSORT 2010 Checklist were used. The trials were assessed, and quality scored independently by two of the reviewers. A quantitative synthesis and meta-analyses of headache frequency and intensity were performed., Results: We extracted 16 trials, 12 on prophylactic BONTA treatment for CTTH and four on CEH. Of these 12 trials (8 on CTTH and 4 on CEH) were included in the quantitative synthesis. A majority of the trials found no significant difference on the primary outcome measure when BONTA treatment was compared with placebo. Three "positive" trials, reporting significant difference in favor of BONTA treatment, but two of these were hampered by low validity and quality scores and high risk of bias., Conclusions: There is no clear clinical evidence supporting prophylactic treatment with BONTA for CTTH or CEH., (© 2021 Sissel Breivold Roland et al., published by De Gruyter, Berlin/Boston.)

Importance: Approximately 90% of people in the US experience headache during their lifetime. Migraine is the second leading cause of years lived with disability worldwide., Observations: Primary headache disorders are defined as headaches that are unrelated to an underlying medical condition and are categorized into 4 groups: migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headache disorders. Studies evaluating prevalence in more than 100 000 people reported that tension-type headache affected 38% of the population, while migraine affected 12% and was the most disabling. Secondary headache disorders are defined as headaches due to an underlying medical condition and are classified according to whether they are due to vascular, neoplastic, infectious, or intracranial pressure/volume causes. Patients presenting with headache should be evaluated to determine whether their headache is most likely a primary or a secondary headache disorder. They should be evaluated for symptoms or signs that suggest an urgent medical problem such as an abrupt onset, neurologic signs, age 50 years and older, presence of cancer or immunosuppression, and provocation by physical activities or postural changes. Acute migraine treatment includes acetaminophen, nonsteroidal anti-inflammatory drugs, and combination products that include caffeine. Patients not responsive to these treatments may require migraine-specific treatments including triptans (5-HT1B/D agonists), which eliminate pain in 20% to 30% of patients by 2 hours, but are accompanied by adverse effects such as transient flushing, tightness, or tingling in the upper body in 25% of patients. Patients with or at high risk for cardiovascular disease should avoid triptans because of vasoconstrictive properties. Acute treatments with gepants, antagonists to receptors for the inflammatory neuropeptide calcitonin gene-related peptide, such as rimegepant or ubrogepant, can eliminate headache symptoms for 2 hours in 20% of patients but have adverse effects of nausea and dry mouth in 1% to 4% of patients. A 5-HT1F agonist, lasmiditan, is also available for acute migraine treatment and appears safe in patients with cardiovascular risk factors. Preventive treatments include antihypertensives, antiepileptics, antidepressants, calcitonin gene-related peptide monoclonal antibodies, and onabotulinumtoxinA, which reduce migraine by 1 to 3 days per month relative to placebo., Conclusions and Relevance: Headache disorders affect approximately 90% of people during their lifetime. Among primary headache disorders, migraine is most debilitating and can be treated acutely with analgesics, nonsteroidal anti-inflammatory drugs, triptans, gepants, and lasmiditan.

Background and Purpose: Tension-type headache (TTH) is one of the most common primary headache diseases in the world and has a serious negative impact on the physical and mental health of patients. Tuina is now widely used to treat tension-type headaches. This article aims to systematically review the evidence about the effectiveness of Tuina on the effectiveness rate, pain intensity, and impact of headache in individuals with TTH., Methods: Eight databases for randomized controlled trials (RCTs) of Tuina were included in treatments for TTH. Cochrane Collaboration's tool was applied to evaluate the quality of the studies. Confidence in the effect estimates was determined with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We use the software STATA 12.0 for meta-analysis and TSA software for test sequence analysis., Results: Seven studies were included with a total sample of 1228 individuals. Meta-analysis results showed that Tuina was superior to drugs for improving the effectiveness rate (RR = 1.49, 95%CI: 1.25 to 1.77, p < 0.01, low evidence). A visual analog scale (VAS) score of Tuina was significantly lower than that of drugs (WMD = -0.738, 95% CI: -1.128 to -0.349, p < 0.01, moderate evidence). The trial sequential analysis showed that the effectiveness of Tuina for TTH was accurate. Adverse events were tolerable., Conclusion: Tuina has a certain effect in treating tension headache. However, due to the low level of methodological quality included in the article, this conclusion should be considered cautiously. More studies are necessary to strengthen the evidence regarding the effectiveness and safety of Tuina for subjects with TTH., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions., Study Design: Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo-controlled trials. Conduct of systematic reviews was assessed with AMSTAR-2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria., Data Sources: MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 - 30 April 2020., Data Synthesis: We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0-10-point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, -0.3 points; 95% CI, -0.6 to -0.1 points) and after craniotomy (MD, -0.8 points; 95% CI, -1.4 to -0.2 points); there is moderate quality evidence for its efficacy in tension-type headache (pain-free at 2 hours: RR, 1.3; 95% CI, 1.1-1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5-3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, -0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9-7.4)., Conclusions: For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required., Prospero Registration: CRD42015029282 (prospective)., (© 2021 AMPCo Pty Ltd.)

Background: Tension-type headache (TTH) is the most common form of primary headache., Objective: The aim of this study was to document and summarize the advances in the understanding of TTH in terms of pathogenesis and management., Material and Methods: We reviewed the available literature on the pathogenesis and management of TTH by searches of PubMed between 1969 and October 2020, and references from relevant articles. The search terms "tension-type headache", "episodic tension-type headache", chronic tension-type headache, "pathophysiology", and "treatment" were used., Results: TTH occurs in two forms: episodic TTH (ETTH) and chronic TTH (CTTH). Unlike chronic migraine, CTTH has been less thoroughly studied and is a more difficult headache to treat. Frequent ETTH and CTTH are associated with significant disability. The pathogenesis of TTH is multifactorial and varies between the subtypes. Peripheral mechanism (myofascial nociception) and environmental factors are possibly more important in ETTH, whereas genetic and central factors (sensitization and inadequate endogenous pain control) may play a significant role in the chronic variety. The treatment of TTH consists of pharmacologic and non-pharmacologic approaches. Simple analgesics like NSAIDs are the mainstays for acute management of ETTH. CTTH requires a multimodal approach. Preventive drugs like amitriptyline or mirtazapine and non-pharmacologic measures like relaxation and stress management techniques and physical therapies are often combined. Despite these measures, the outcome remains unsatisfactory in many patients., Conclusion: There is clearly an urgent need to understand the pathophysiology and improve the management of TTH patients, especially the chronic form., Competing Interests: None

Competing Interests: Declaration of competing interest The authors declare no competing interests to disclose.

In the "headache world," great attention has always been paid to migraine patients, especially for the research and development of new therapies. For the other forms of primary headaches, especially those of Chapters 2 and 3 of the classification, there are however therapies that, even if not specific, can give significant results. Tension-type headache recognizes in NSAIDs the most effective drugs to treat acute attack, while prevention is based on the use of tricyclic antidepressants and muscle relaxants. For TACs, the discussion is more complex: first of all, there are two forms of primary headache that respond absolutely to indomethacin. For these, the main problem is how to manage the possible side effects arising from prolonged treatments and possibly what to use as an alternative. For cluster headaches and short-lasting unilateral neuralgiform headache attacks, we have drugs with good efficacy as regards medical therapy, such as verapamil or lamotrigine, but in recent years, neuromodulation techniques, both surgical and non-invasive, have also been affirming themselves, which represent a more possibility for forms of headache that are often very disabling and resistant to common analgesics.

Arterial hypertension (AH) and exertional headache (EHA) are comorbidities. The article presents a nonsystematic review focused on studying the AH+EHA phenotype. The authors addressed the history of studying the phenotype, several theories about its pathophysiological causes (psychosomatic, neuroanatomical, and baroreflector). The protective "hypertension-associated hypoalgesia" phenotype, a mechanism of its change in AH chronization, and difficulties of differential diagnosis are described. The AH+EHA phenotype requires further study since its incidence is quite high. This will allow developing an individualized approach in prevention and treatment of EHA attacks, decreasing the risk of life-threatening cardiovascular complications, and avoiding iatrogenic complications in patients with AH. The main way to prevent the development of AH+EHA phenotype is patient's compliance, which can be provided by using combination hypotensive drugs to reduce the number of pills and dosing. It is important to take into account possible adverse reactions of the nervous system (medication-overuse headache or EHA aggravation). Considering these conditions, the drug Triplixam can be used for prevention of complications in the AH+EHA phenotype. Triplixam is a fixed triple combination of amlodipine/indapamide/perindopril, and its individual components have low and medium risk for development of headache.

Introduction: The purpose of this study was to clearly characterize the intramuscular nerve distributions of the splenius capitis and splenius cervicis muscles that are both responsible for the onset of a chronic tension type headache and to use this information to identify the effective botulinum toxin (BoNT) injection sites., Materials and Methods: Ten splenius capitis and splenius cervicis specimens were subjected to Sihler's staining to reveal intramuscular nerve arborization patterns and determined the optimal location for BoNT injection., Results: Nerve distribution patterns in the splenius capitis were identified as nerve pathways that travel down toward the origin point and others that travel up toward the insertion point. This neuromuscular innervation from the central (50%) point was distributed evenly in these two directions. The neural pathways of splenius cervicis traveled vertically from the insertion point to the origin point. If the length from the muscle origin point to the insertion point is normalized to 100%, motor neurons innervate the muscle from around the 30% to the 70% point., Conclusions: The safest and most-effective BoNT injection sites for the splenius capitis and splenius cervicis were found at around the 50% point and the 30% to the 70% point, respectively., (© 2020 Wiley Periodicals, Inc.)

The objective was to determine the pharmacological treatment patterns of headache disorders in a Colombian population. Cross-sectional study. The dispensations of drugs for the management of tension-type headache, migraine, and cluster headache in the first trimester of 2019 were reviewed from a national medication dispensing database. Sociodemographic, diagnostic, and treatment variables (acute or prophylactic; concomitant drugs) were analyzed. During the study period, 7450 patients were identified: 68.5% with migraine, 25.1% with tension-type headache, and 6.4% with cluster headache. A total of 79.7% (n = 5937) were women, and the mean age was 38.6 ± 14.7 years. The 87.8% (n = 6539) were prescribed drugs for acute pain management, mainly nonsteroidal anti-inflammatory drugs (n = 3559; 47.8%), acetaminophen (n = 3390; 45.5%), ergotamine (n = 2158; 29.0%), and opioids (n = 1750; 23.5%). The 50.3% (n = 3750) received at least one drug used for prophylaxis, mainly antidepressants (n = 1769, 23.7%), flunarizine (n = 927; 12.4%), and β-blockers (n = 764; 10.3%). The main comedication was proton pump inhibitors (n = 921; 12.4%). Patients with tension-type headache, migraine, and cluster headache receive mainly medications for acute management, some with low therapeutic value or not recommended, such as opioids or ergotamine. Prophylactic management is mainly directed to migraines, although patients with other kinds of headache also used it, even though it was not indicated.

Importance: Medication overuse headache (MOH) is a disabling, globally prevalent disorder representing a well-known and debated clinical problem. Evidence for the most effective treatment strategy is needed., Objective: To compare 3 treatment strategies for MOH., Design, Setting, and Participants: This open-label, randomized clinical trial with 6 months of follow-up was conducted in the tertiary sector at the Danish Headache Center, Glostrup, from October 25, 2016, to June 28, 2019. Of 483 patients with MOH referred during the inclusion period, 195 met the criteria consisting of migraine and/or tension-type headache, 18 years or older, eligibility for outpatient treatment, no severe physical or psychiatric disorder, no other addiction, and not pregnant or breastfeeding. Of these, 75 refused participation and 120 were included. Data were analyzed from July 3 to September 6, 2019., Interventions: Random assignment (1:1:1 allocation) to 1 of the 3 outpatient treatments consisting of (1) withdrawal plus preventive treatment, (2) preventive treatment without withdrawal, or (3) withdrawal with optional preventive treatment 2 months after withdrawal., Main Outcomes and Measures: The primary outcome was change in headache days per month after 6 months. Predefined secondary outcomes were change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cured MOH., Results: Of 120 patients, 102 (mean [SD] age, 43.9 [11.8] years; 81 women [79.4%]) completed the 6-month follow-up. Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal plus preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20). No difference was found in reduction of migraine days per month, use of short-term medication, or headache intensity. In the withdrawal plus preventive group, 23 of 31 patients (74.2%) reverted to episodic headache, compared with 21 of 35 (60.0%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group (P = .03). Moreover, 30 of 31 patients (96.8%) in the withdrawal plus preventive group were cured of MOH, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). These findings corresponded to a 30% (relative risk, 1.3; 95% CI, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = .03)., Conclusion and Relevance: All 3 treatment strategies were effective, but based on these findings, withdrawal therapy combined with preventive medication from the start of withdrawal is recommended as treatment for MOH., Trial Registration: ClinicalTrials.gov Identifier: NCT02993289.

Background: Pharmacological treatment of patients with tension-type headache (TTH) includes symptomatic (acute) and prophylactic (preventive) medication. No previous study has investigated variables associated to symptomatic medication intake in TTH. Our aim was to assess the association of clinical, psychological and neurophysiological outcomes with the use and timing of the use of symptomatic medication in TTH., Methods: A longitudinal observational study was conducted. One hundred and sixty-eight (n = 168) patients with TTH participated. Pain features of the headache (intensity, frequency, duration), burden of headache (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), anxiety/depression (Hospital Anxiety and Depression Scale), trait/state anxiety levels (State-Trait Anxiety Inventory), and bilateral pressure pain thresholds on the temporalis, C5-C6 joint, second metacarpal and tibialis anterior were assessed. Symptomatic medication intake was also collected for a 6-months follow-up period. Differences between patients using or not using symptomatic medication, depending on self-perceived effectiveness, and time (early during an attack, i.e., the first 5 min, or when headache attack is intense) when the symptomatic medication was taken were calculated., Results: One hundred and thirty-six (n = 136, 80%) reported symptomatic medication intake for headache (73% NSAIDs). Sixteen (12%) reported no pain relief, 81 (59%) experienced moderate relief and 39 (29%) total pain relief. Fifty-eight (43%) took 'early medication' whereas 78 (57%) took 'late medication'. Patients taking symptomatic medication in general showed lower headache frequency and lower depressive levels than those patients not taking medication. Symptomatic medication was more effective in patients with lower headache history, frequency, and duration, and lower emotional burden. No differences in pressure pain sensitivity were found depending on the self-perceived effectiveness of medication. Patients taking 'late symptomatic' medication exhibited more widespread pressure pain sensitivity than those taking 'early medication'., Conclusions: This study found that the effectiveness of symptomatic medication was associated with better headache parameters (history, frequency, or duration) and lower emotional burden. Further, consuming early symptomatic medication at the beginning of a headache attack (the first 5 min) could limit widespread pressure pain sensitivity.

Background: Botulinum toxin is approved to treat chronic migraine and has been shown to confer significant benefit in refractory cases. Due to its effect on pain by sensory modulation, there may also be efficacy in its use in chronic tension-type headache (CTTH)., Methods: A systematic review of the literature was performed using our predefined inclusion and exclusion criteria. We targeted prospective trials, randomized or nonrandomized, studying botulinum toxin in tension-type headaches (TTHs) in adults., Results: Twenty-two studies were included, including 9 nonrandomized, uncontrolled studies, 8 randomized, placebo-controlled and double-blinded trials (RCTs), 3 RCTs with a crossover, open-label period, 1 comparative, randomized, single-blinded evaluation, and 1 retrospective study with prospective evaluation of headache response to cosmetic botulinum toxin. Studies included 11 to 300 subjects, with duration typically less than 6 months and with only 1 treatment period. Results were mixed, likely due to variable study design, including toxin dosing, injection paradigms, duration/frequency of treatment, and outcome measures. There was moderate-quality evidence that botulinum toxin improved VAS scoring, and some studies demonstrated efficacy based on improved frequency/severity., Conclusion: This systematic review demonstrates variable study designs contributing to the low quality of evidence available regarding botulinum toxin in TTH, but some data suggest efficacy. There does not appear to be irrefutable evidence of a lack of efficacy of botulinum toxin in TTH. Using the paradigm for botulinum toxin in chronic migraine may prove fruitful in treating CTTH. Further studies are warranted to evaluate the utility of botulinum toxin in this common debilitating condition., (© 2019 World Institute of Pain.)