Correction to "Pituitary Cyclase-Activating Polypeptide Targeted Treatments for the Treatment of Primary Headache Disorders".

To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders. Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness. We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders. There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin's role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache. Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation.

Primary headache disorders, especially migraine, are commonly accompanied by neck pain or other symptoms. Because of this, physical therapy (PT) and other physical treatments are often prescribed. This review updates and synthesizes published clinical trial evidence, systematic reviews, and case series regarding the efficacy of selected physical modalities in the treatment of primary headache disorders. The National Library of Medicine (MEDLINE), The Cochrane Library, and other sources of information were searched through June 2004 to identify clinical studies, systematic reviews, case series, or other information published in English that assessed the treatment of headache or migraine with chiropractic, osteopathic, PT, or massage interventions. PT is more effective than massage therapy or acupuncture for the treatment of TTH and appears to be most beneficial for patients with a high frequency of headache episodes. PT is most effective for the treatment of migraine when combined with other treatments such as thermal biofeedback, relaxation training, and exercise. Chiropractic manipulation demonstrated a trend toward benefit in the treatment of TTH, but evidence is weak. Chiropractic manipulation is probably more effective in the treatment of tension-type headache (TTH) than it is in the treatment of migraine. Evidence is lacking regarding the efficacy of these treatments in reducing headache frequency, intensity, duration, and disability in many commonly encountered clinical situations. Many of the published case series and controlled studies are of low quality. Further studies of improved quality are necessary to more firmly establish the place of physical modalities in the treatment of primary headache disorders. With the exception of high velocity chiropractic manipulation of the neck, the treatments are unlikely to be physically dangerous, although the financial costs and lost treatment opportunity by prescribing potentially ineffective treatment may not be insignificant. In the absence of clear evidence regarding their role in treatment, physicians and patients are advised to make cautious and individualized judgments about the utility of physical treatments for headache management; in most cases, the use of these modalities should complement rather than supplant better-validated forms of therapy.

There is no sufficient evidence for opioids in the acute treatment of primary headache disorders. Controlled clinical trials using triptans as comparator are missing. Data show high frequent headache recurrence, typical side effects of opioids, increased risk of chronification, and development of addiction in primary headache patients treated with opioids. Chronic headache patients with opioid therapy often experience lengthy withdrawal treatment. On the basis of the current scientific data, opioids should be avoided in acute and prophylactic treatment of primary headache disorders.

Chapter 14 - Therapeutic guidelines for headache

BackgroundHeadache 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.MethodsIn 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.ResultsThe 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.ConclusionsWhile 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.

Medication overuse headache is a well-known complication in the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy and subsequent treatment of the primary headache disorder. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with medication overuse headache according to the International Headache Society criteria.

Guest Editorial Melatonin in the Treatment of Primary Headache Disorders Amy A. Gelfand MD, Amy A. Gelfand MDSearch for more papers by this author Amy A. Gelfand MD, Amy A. Gelfand MDSearch for more papers by this author First published: 08 June 2017 https://doi.org/10.1111/head.13138Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume57, Issue6June 2017Pages 848-849 RelatedInformation

Neuromodulation is a promising, novel approach for the treatment of primary headache disorders. Neuromodulation offers a new dimension in the treatment that is both easily reversible and tends to be very well tolerated. The autonomic nervous system is a logical target given the neurobiology of common primary headache disorders, such as migraine and the trigeminal autonomic cephalalgias (TACs). This article will review new encouraging results of studies from the most recent literature on neuromodulation as acute and preventive treatment in primary headache disorders, and cover some possible underlying mechanisms. We will especially focus on vagus nerve stimulation (VNS) and sphenopalatine ganglion (SPG) since they have targeted autonomic pathways that are cranial and can modulate relevant pathophysiological mechanisms. The initial data suggests these approaches will find an important role in headache disorder management going forward.

Primary headache disorders can be remarkably disabling and the therapeutic options available are usually limited to medication with a high rate of adverse events. Here, we discuss the mechanism of action of non-invasive vagal nerve stimulation, as well as the findings of the main studies involving patients with primary headaches other than migraine or cluster headache, such as hemicrania continua, paroxysmal hemicrania, cough headache, or short-lasting neuralgiform headache attacks (SUNCT/SUNA), in a narrative analysis. A bibliographical search of low-prevalence disorders such as rare primary headaches retrieves a moderate number of studies, usually underpowered. Headache intensity, severity, and duration showed a clinically significant reduction in the majority, especially those involving indomethacin-responsive headaches. The lack of response of some patients with a similar diagnosis could be due to a different stimulation pattern, technique, or total dose. The use of non-invasive vagal nerve stimulation for the treatment of primary headache disorders represents an excellent option for patients with these debilitating and otherwise refractory conditions, or that cannot tolerate several lines of preventive medication, and should always be considered before contemplating invasive, non-reversible stimulation techniques.

To evaluate the effectiveness of intravenous valproate in managing moderate to severe headaches. Despite major strides in the understanding of primary headache disorders, there have been few additions to acute headache management other than introduction of the triptans. An intravenous antiepileptic preparation, sodium valproate, has been reported to be effective in the management of status epilepticus and acute headache. Between March 13, 2000 and October 11, 2000, we prospectively treated, in a nonrandomized and open-label study, every patient with a moderate to severe headache (4 or greater on a visual analog scale of head pain from 1 to 10) who wanted treatment with intravenous valproate. Using a verbal visual analog scale for pain (0 = no headache and 10 = most severe headache), we measured head pain before treatment and at time of discharge. The treating nurse monitored vital signs and side effects. A positive response was defined as a 50% or greater reduction at discharge in baseline pain. Information was collected regarding patient demographics, type of headache (according to criteria of the International Headache Society and that recently proposed for chronic headache), observation time in the treatment suite, cumulative dose of valproate, and use of concurrent medications. Univariable and multivariable correlates of response to treatment were identified using logistic regression analysis. One hundred thirty treatments were given to 89 women and 17 men, aged 17 to 76 years; 92 patients received only one treatment. Valproate doses ranged between 300 and 1200 mg. Thirty-three patients (31%) presented with episodic migraine, with or without aura; 45 patients (42%) presented with chronic daily headache with a history of episodic migraine, with or without aura (transformed migraine); 22 (21%) with unclassifiable chronic headache; 2 (2%) with episodic cluster headache; and 4 (4%) with chronic tension-type headache. For first treatments only, 61 patients (57.5%) responded to treatment, whereas for all treatments, 82 patients (63.1%) responded. Age and gender did not affect likelihood of response, whereas increasing duration of treatment (P=.003) and the additional use of analgesics (P=.021) were each negatively associated with response. Among headache types, unclassifiable chronic headache segregated from all other classified headaches in terms of poor response. Aside from rare dizziness (n = 2) and one spell interpreted as a pseudoseizure, no side effects were noted. Intravenous valproate is a safe, rapidly effective, abortive headache agent. It appears to be an effective analgesic for identifiable primary headaches, especially episodic headache, and less effective for unclassifiable chronic headache. Randomized, double-blind, controlled studies are warranted.

ObjectivesCervical noninvasive vagus nerve stimulation (nVNS) emerged as an adjunctive neuromodulation approach for primary headache disorders with limited responsiveness to pharmacologic and behavioral treatment. This narrative review evaluates the safety and efficacy of invasive and noninvasive peripheral nerve stimulation of the cervical branch of the vagal nerve (afferent properties) for primary headache disorders (episodic/chronic migraine [EM/CM] and cluster headache [ECH/CCH]) and provides a brief summary of the preclinical data on the possible mechanism of action of cervical vagus nerve stimulation (VNS) and trigemino-nociceptive head pain transmission.Materials and methodsA systematic search of published data was performed in PubMed for randomized controlled trials (RCTs) and prospective cohort clinical studies assessing the efficacy/safety and cost-effectiveness of cervical VNS in primary headache disorders and related preclinical studies.ResultsThree RCTs were identified for ECH/CCH (ACT-1, ACT-2 and PREVA), one RCT for migraine (EVENT) and several prospective cohort studies and retrospective analyses for both headache disorders. In ACT-1, a significantly higher response rate, a higher pain-free rate and a decrease in mean attack duration were found in nVNS-treated ECH/CCH patients compared to sham stimulation. ACT-2 confirmed these findings (e.g., significantly higher pain-free attacks, pain severity decline and increased responder-rate [defined as ≥50% reduction]). The PREVA study demonstrated the superiority of adjunctive nVNS to standard care alone and observed a significantly higher attack reduction (p=0.02) and responder rate (defined as ≥50% reduction). For CM, the EVENT study assessed a significantly higher frequency of decline in the open-label phase. Mostly transient mild/moderate adverse events were recorded, and no severe device-related adverse events occurred.ConclusionCervical nVNS represents a novel, safe and efficient adjunctive treatment option for primary headache disorders. In particular, preliminary observations suggest enhanced nVNS responsiveness in favor of episodic subtypes (EM and ECH). However, preclinical studies are urgently warranted to dissect the mechanism of action.

Treatment of primary headache disorders (migraine, tension headache) with opioids is not recommended and is more likely to do harm than good.

This national postal survey aimed to examine Canadian emergency physicians' practice patterns with respect to drug treatment and perspectives on peripheral nerve blocks. The treatment of primary headache disorders in the emergency department is variable. We surveyed 500 emergency physicians listed in the Canadian Medical Directory according to a modified Dillman's method: an initial invitation was followed by up to four reminders to nonresponders. Physicians were asked questions regarding their frequency of medication administration and perspectives toward peripheral nerve blocks. Of 500 mailed surveys, 468 were delivered and 179 physicians responded (response rate = 38.2%). The majority of physicians were men (92/144, 63.9%); 80.6% (116/144) had been in practice for greater than or equal to 10years with 50.7% (75/148) in a community or district general teaching hospital. Commonly used pharmacotherapies for primary headaches were intravenous dopamine receptor antagonists (69%), co-administration of ketorolac and a dopamine receptor antagonist (54.2%), intravenous fluid boluses (54%), nonsteroidal anti-inflammatory drugs (NSAIDs) alone (53.5%), and acetaminophen (51.4%). Only 80 of 144 physicians (55.6%) reported previous experience with peripheral nerve blocks (95% confidence interval [CI] = 48%-65%). The majority (68/80, 85.0%) agreed peripheral nerve blocks are safe and 55.1% (43/78) agreed they are effective. The vast majority (118/140, 84.3%) would consider peripheral nerve blocks as a first-line treatment option given sufficient evidence from a future trial (95% CI = 78%-90%). NSAIDs alone, as well as dopamine receptor antagonists with or without ketorolac are commonly used for primary headache in Canadian emergency departments. A large proportion of physicians have never used a peripheral nerve block in their practice; among those who have experience with peripheral nerve blocks, the majority find them safe and effective. The majority of respondents would consider peripheral nerve blocks as a first-line treatment option given sufficient evidence from a future trial.

Complementary and alternative medicine (CAM) is increasingly common in the treatment of primary headache disorders despite lack of evidence for efficacy in most modalities. A systematic questionnaire-based survey of CAM therapy was conducted in 432 patients who attended seven tertiary headache out-patient clinics in Germany and Austria. Use of CAM was reported by the majority (81.7%) of patients. Most frequently used CAM treatments were acupuncture (58.3%), massage (46.1%) and relaxation techniques (42.4%). Use was motivated by 'to leave nothing undone' (63.7%) and 'to be active against the disease' (55.6%). Compared with non-users, CAM users were of higher age, showed a longer duration of disease, a higher percentage of chronification, less intensity of headache, were more satisfied with conventional prophylaxis and showed greater willingness to gather information about headaches. There were no differences with respect to gender, headache diagnoses, headache-specific disability, education, income, religious attitudes or satisfaction with conventional attack therapy. A higher number of headache days, longer duration of headache treatment, higher personal costs, and use of CAM for other diseases predicted a higher number of used CAM treatments. This study confirms that CAM is widely used among primary headache patients, mostly in combination with standard care.

Migraine and other chronic headache disorders are common and if inadequately treated, can lead to significant disability. The effectiveness of medications can be limited by side effects, drug interactions, and comorbid diseases necessitating alternative methods. Technological developments in the past 5 years have made it possible to use non-invasive methods of neuromodulation to treat primary headache disorders. This field includes technologies such as supraorbital transcutaneous stimulation (STS), transcranial magnetic stimulation (TMS), and non-invasive vagal nerve stimulation (nVNS). Existing trials show these modalities are safe and well tolerated and can be combined with standard pharmacotherapy. We review the technologies, biological rationales, and trials involving non-invasive neuromodulation for the treatment of primary headache disorders.