Summary:  Migraines are largely treated without studies.  The drugs used to treat migraines were found by chance.  Acupuncture may help but manipulation may not.  There is considerable overlap between migraines, tension headaches, and sinus headaches.  

Curr Pain Headache Rep. 2009 Aug;13(4):326-31.Links

Psychiatric comorbidities and migraine chronification.Smitherman TA, Rains JC, Penzien DB.

Department of Psychology, University of Mississippi, 207 Peabody, University, MS 38677, USA. tasmithe@olemiss.edu.

A growing body of literature has implicated comorbid psychopathology as a potential risk factor for the chronification of migraine. Of the psychiatric disorders, depressive and anxiety disorders have been most consistently associated with the chronification of migraine. A shared dysfunction of the serotonergic system, medication overuse, and psychological factors have been proposed to mediate this relationship, although the responsible mechanisms are still largely unclear. This article overviews literature on psychiatric comorbidities and migraine chronification, considers mechanisms underlying this relationship, and notes directions for future clinical and empirical work.

PMID: 19586598

Curr Pain Headache Rep. 2009 Aug;13(4):319-25.Links

Sinus problems as a cause of headache refractoriness and migraine chronification.Cady RK, Schreiber CP.

Headache Care Center, 3805 Kansas Expressway, Springfield, MO 65807, USA. rcady@headachecare.com.

Sinus headache is not a diagnostic term supported by the academia, yet it appears to be understood by the general public and larger medical community. It can be considered both a primary and secondary headache disorder. As a primary headache disorder, most of the patients considered to have sinus headache indeed have migraine (migraine with sinus symptoms). Yet it is also possible that some attacks of sinus headache may represent a unique clinical phenotype of migraine or be a unique clinical entity. Potentially, primary sinus headache can chronify and be refractory through immune-mediated mechanisms or as a catalyst for migraine chronification through ineffective treatment or medication overuse and misuse. As a secondary headache disorder, sinus headache can be associated with a wide range of underlying etiologies such as infection, anatomical abnormalities, trauma, and immunological disease or sleep disorders. It is possible that these underlying pathophysiological processes generate long-standing activation of nociceptive mechanisms involved in headache and can lead to chronification and refractoriness of the headache symptomatology. This article explores some of the potential mechanisms and the available scientific studies that may explain how sinus headache can become chronic and present to the clinician as a refractory headache disorder.

PMID: 19586597

Neurology. 2002 May 14;58(9 Suppl 6):S10-4. Links

Sinus headache or migraine? Considerations in making a differential diagnosis.Cady RK, Schreiber CP.

Headache Care Center, Springfield, Missouri 65804, USA.

Sinus headache is commonly diagnosed, and patients with headache often cite sinus pain and pressure as a cause of their headaches. A high frequency of diagnosis of sinus headache, which specialists consider to be relatively rare, among patients meeting International Headache Society (IHS) diagnostic criteria for migraine raises the possibility that migraine and perhaps other headache types are sometimes mistaken for sinus headache. This article considers clinical, epidemiologic, and pathophysiologic relationships between sinus headache and migraine and discusses the implications for clinical management of headache. Both historic and new data show that nasal symptoms frequently accompany migraine, although these symptoms are not part of the IHS diagnostic criteria for migraine. Parasympathetic activation, as well as the hypothesized mechanism of neurogenic or immunogenic switching (i.e., crossover interactions of neurogenic and immunogenic inflammation), may account for both the frequent occurrence of nasal symptoms in migraine and the possibility that sinus inflammation can sometimes act as a migraine trigger. Considered in aggregate, the data show that the occurrence of nasal symptoms associated with a headache should neither trigger a diagnosis of sinus disease nor exclude a diagnosis of migraine. It should, in fact, prompt diagnostic consideration of both conditions.

PMID: 12011268

Neurology. 2002 May 14;58(9 Suppl 6):S15-20. Links

Migraine and tension-type headache: an assessment of challenges in diagnosis.Kaniecki RG.

University of Pittsburgh Headache Center, Pittsburgh, Pennsylvania 15213, USA.

The difficulty in distinguishing episodic tension-type headache from migraine headache is widely acknowledged. The misdiagnosis of migraine as tension-type headache has potentially significant consequences because it may preclude patients with disabling headaches from receiving appropriate treatment. This article explores the symptomatologic, epidemiologic, and pathophysiologic relationships among migraine and tension-type headaches with the aim of elucidating ways to improve their diagnosis and treatment. Clinical, epidemiologic, and pharmacologic data converge to suggest that rigid adherence to the IHS criteria in diagnosing migraine and tension-type headache may result in misdiagnosis of some headaches. Many migraine attacks are accompanied by tension headache-like symptoms, such as neck pain. Conversely, IHS-defined tension-type headaches are often accompanied by migraine-like symptoms, such as photophobia or phonophobia and aggravation by activity. The health-care provider caring for patients with headache should be cognizant of these overlaps and their implications for the management of patients with headache.

PMID: 12011269

Headache. 1995 Mar;35(3):146-53.Links

Applicability of the 1988 IHS criteria to headache patients under the age of 18 years attending 21 Italian headache clinics. Juvenile Headache Collaborative Study Group.Gallai V, Sarchielli P, Carboni F, Benedetti P, Mastropaolo C, Puca F.

Interuniversity Center for the Study of Headache and Neurotransmitter Disorders, University of Perugia, Italy.

Seven hundred nineteen young patients attending 21 Italian headache care settings were evaluated by a diagnostic headache interview and a neurological examination. Headache disorders were classified according to the current 1988 criteria of the International Headache Society (IHS); 54.9% of the patients suffered from migraine, 33.9% from tension-type headache, 1.9% from secondary headache, and 3.4% had non-classifiable headache. A further 5.9% of the patients were not classified due to incomplete questionnaires. Of the 395 patients with migraine, 44.5% were affected by migraine without aura, 29.9% by migraine with aura, 1.3% from other migraine forms, and 24.3% by migrainous disorders which do not fulfill the 1988 IHS diagnostic criteria for headache. Among the 244 patients with tension-type headache, 51.6% had episodic tension-type headache, 15.2% chronic tension-type headache, and 33.2% headache of the tension-type which does not fulfill the 1988 IHS criteria for episodic and chronic tension-type headache. In young migraine patients, pain was of a pulsating type in 55.7%, severe in 57.8%, unilateral in 42.6%, and aggravated by routine physical activity in 38.9%. Tension-type headache was described as pressing in 73.8%, mild or moderate in 75.7%, bilateral in 87.4%, and not aggravated by routine physical activity in 85.5%. The duration of pain was less than 2 hours in 35% of the cases in migraine sufferers and less than 30 minutes in 26.7% of tension-type headache sufferers. Nausea, phonophobia, and photophobia were present in at least half of the migraine patients and in one third of tension-type headache patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 7721575

TREATMENTS

Pharmacotherapy. 2009 Jul;29(7):784-91. Links

Efficacy of botulinum toxin type A for the prophylaxis of episodic migraine headaches: a meta-analysis of randomized, double-blind, placebo-controlled trials.Shuhendler AJ, Lee S, Siu M, Ondovcik S, Lam K, Alabdullatif A, Zhang X, Machado M, Einarson TR.

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada.

STUDY OBJECTIVE: To assess the efficacy of botulinum toxin type A in lowering the frequency of migraine headaches in patients with episodic migraines. DESIGN: Meta-analysis of eight randomized, double-blind, placebo-controlled trials. PATIENTS: A total of 1601 patients with a history of episodic migraine headaches classified as those experiencing headaches fewer than 15 times/month over a 3-month period. MEASUREMENTS AND MAIN RESULTS: PubMed, Google Scholar, and the Cochrane Library were searched from inception to October 2007 in order to locate randomized, double-blind, placebo-controlled trials that compared the efficacy of pericranial botulinum toxin A injections with placebo in the prevention of migraines in patients with a history of episodic migraine headaches. The primary outcome of interest was change from baseline to end point in migraine frequency (number of migraines/month). A random effects model was used to combine study results, and the standardized mean difference (Cohen's d) in migraine frequency between the placebo and botulinum toxin A groups was reported. Effect sizes (d) less than 0.2 were considered small. Quality assessment was performed by using the Downs and Black scale. Eight randomized, double-blind, placebo-controlled clinical trials (1601 patients) presented a quantitative assessment of the efficacy of botulinum toxin A versus placebo. The overall treatment effect size of botulinum toxin A over placebo for 30, 60, and 90 days after injection was d -0.06 (95% confidence interval [CI] - 0.14-0.03, z=1.33, p=0.18), d -0.05 (95% CI -0.14-0.03, z=1.22, p=0.22), and d -0.05 (95% CI -0.13-0.04, z=1.07, p=0.28), respectively. Even after controlling for a high placebo effect, and after dose stratification, no significant effect of botulinum toxin A in reducing migraine frequency/month was seen over placebo. CONCLUSION: Botulinum toxin A for the prophylactic treatment of episodic migraine headaches was not significantly different from placebo, both from a clinical and statistical perspective.

PMID: 19558252

Headache. 2009 Jun 2. [Epub ahead of print] Links

The Relative Efficacy of Phenothiazines for the Treatment of Acute Migraine: A Meta-Analysis.Kelly AM, Walcynski T, Gunn B.

From the Joseph Epstein Centre for Emergency Medicine Research at Western Health, St. Albans, Vic., Australia (A.-M. Kelly); Department of Emergency Medicine, Western Health, St. Albans, Vic., Australia (T. Walcynski and B. Gunn).

(Headache 2009;**:**-**) Objective and Background.- Ranges of agents are used in the emergency departments to treat migraine headache. Some experts suggest that phenothiazines are among the most effective; clinical trials have been small with varied results. We performed a systematic review and meta-analysis to determine the relative effectiveness of phenothiazines compared with placebo and other active agents for the treatment of acute migraine. Methods.- We searched MEDLINE, EMBASE, CINAHL, Cochrane database, and international clinical trial registers for randomized controlled trials comparing parenteral phenothiazines with placebo or another active parenteral agent for treatment of acute migraine in adults. The primary outcome was relief of headache, and secondary outcome was clinical success. Analysis was for phenothiazines vs placebo, pooled other active agents, and metoclopramide for each outcome. Odds ratios (ORs) were calculated and pooled by using a random effects model (RevMan v5). Results.- Thirteen trials were appropriate and had available data. Phenothiazines were compared with placebo in 5 trials and to another active agent in 10 (metoclopramide 4). Phenothiazine was more effective than placebo for headache relief (OR 15.02, 95% confidence interval [CI] 7.57-29.82) and clinical success (OR 8.92, 95% CI 4.08-19.51). Phenothiazines were more effective than other agents combined (OR 2.04, 95% CI 1.25-3.31) and the metoclopramide subgroup (OR 2.25, 95% CI 1.29-3.92) for clinical success, but no differences were found for headache relief. The clinical success rate of phenothiazines was 78% (95% CI 74-82). Conclusion.- Phenothiazines are more effective than placebo for the treatment of migraine headache and have higher rates of clinical success than other agents against which they have been compared.

PMID: 19496829

Cochrane Database Syst Rev. 2009 Jan 21;(1):CD001218. Links

Update of:

Cochrane Database Syst Rev. 2001;(1):CD001218.

Acupuncture for migraine prophylaxis.Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR.

Centre for Complementary Medicine Research, Department of Internal Medicine II, Technische Universitaet Muenchen, Wolfgangstr. 8, Munich, Germany, 81667. Klaus.Linde@lrz.tu-muenchen.de

BACKGROUND: Acupuncture is often used for migraine prophylaxis but its effectiveness is still controversial. This review (along with a companion review on 'Acupuncture for tension-type headache') represents an updated version of a Cochrane review originally published in Issue 1, 2001, of The Cochrane Library. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than 'sham' (placebo) acupuncture; and c) as effective as other interventions in reducing headache frequency in patients with migraine. SEARCH STRATEGY: The Cochrane Pain, Palliative & Supportive Care Trials Register, CENTRAL, MEDLINE, EMBASE and the Cochrane Complementary Medicine Field Trials Register were searched to January 2008. SELECTION CRITERIA: We included randomized trials with a post-randomization observation period of at least 8 weeks that compared the clinical effects of an acupuncture intervention with a control (no prophylactic treatment or routine care only), a sham acupuncture intervention or another intervention in patients with migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility; extracted information on patients, interventions, methods and results; and assessed risk of bias and quality of the acupuncture intervention. Outcomes extracted included response (outcome of primary interest), migraine attacks, migraine days, headache days and analgesic use. Pooled effect size estimates were calculated using a random-effects model. MAIN RESULTS: Twenty-two trials with 4419 participants (mean 201, median 42, range 27 to 1715) met the inclusion criteria. Six trials (including two large trials with 401 and 1715 patients) compared acupuncture to no prophylactic treatment or routine care only. After 3 to 4 months patients receiving acupuncture had higher response rates and fewer headaches. The only study with long-term follow up saw no evidence that effects dissipated up to 9 months after cessation of treatment. Fourteen trials compared a 'true' acupuncture intervention with a variety of sham interventions. Pooled analyses did not show a statistically significant superiority for true acupuncture for any outcome in any of the time windows, but the results of single trials varied considerably. Four trials compared acupuncture to proven prophylactic drug treatment. Overall in these trials acupuncture was associated with slightly better outcomes and fewer adverse effects than prophylactic drug treatment. Two small low-quality trials comparing acupuncture with relaxation (alone or in combination with massage) could not be interpreted reliably. AUTHORS' CONCLUSIONS: In the previous version of this review, evidence in support of acupuncture for migraine prophylaxis was considered promising but insufficient. Now, with 12 additional trials, there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of 'true' acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment.

PMID: 19160193

Cochrane Database Syst Rev. 2004;(3):CD001878. Links

Non-invasive physical treatments for chronic/recurrent headache.Bronfort G, Nilsson N, Haas M, Evans R, Goldsmith CH, Assendelft WJ, Bouter LM.

Wolfe-Harris Center for Clinical Studies, Northwestern Health Sciences University, 2501 W 84th St, Bloomington, MN 55431, USA. gbronfort@nwhealth.edu

BACKGROUND: Non-invasive physical treatments are often used to treat common types of chronic/recurrent headache. OBJECTIVES: To quantify and compare the magnitude of short- and long-term effects of non-invasive physical treatments for chronic/recurrent headaches. SEARCH STRATEGY: We searched the following databases from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of the Cochrane Pain, Palliative Care and Supportive Care review group. Selected complementary medicine reference systems were searched as well. We also performed citation tracking and hand searching of potentially relevant journals. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing non-invasive physical treatments for chronic/recurrent headaches to any type of control. DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted trial information and scored trials for methodological quality. Outcomes data were standardized into percentage point and effect size scores wherever possible. The strength of the evidence of effectiveness was assessed using pre-specified rules. MAIN RESULTS: Twenty-two studies with a total of 2628 patients (age 12 to 78 years) met the inclusion criteria. Five types of headache were studied: migraine, tension-type, cervicogenic, a mix of migraine and tension-type, and post-traumatic headache. Ten studies had methodological quality scores of 50 or more (out of a possible 100 points), but many limitations were identified. We were unable to pool data because of study heterogeneity.For the prophylactic treatment of migraine headache, there is evidence that spinal manipulation may be an effective treatment option with a short-term effect similar to that of a commonly used, effective drug (amitriptyline). Other possible treatment options with weaker evidence of effectiveness are pulsating electromagnetic fields and a combination of transcutaneous electrical nerve stimulation [TENS] and electrical neurotransmitter modulation.For the prophylactic treatment of chronic tension-type headache, amitriptyline is more effective than spinal manipulation during treatment. However, spinal manipulation is superior in the short term after cessation of both treatments. Other possible treatment options with weaker evidence of effectiveness are therapeutic touch; cranial electrotherapy; a combination of TENS and electrical neurotransmitter modulation; and a regimen of auto-massage, TENS, and stretching. For episodic tension-type headache, there is evidence that adding spinal manipulation to massage is not effective. For the prophylactic treatment of cervicogenic headache, there is evidence that both neck exercise (low-intensity endurance training) and spinal manipulation are effective in the short and long term when compared to no treatment. There is also evidence that spinal manipulation is effective in the short term when compared to massage or placebo spinal manipulation, and weaker evidence when compared to spinal mobilization.There is weaker evidence that spinal mobilization is more effective in the short term than cold packs in the treatment of post-traumatic headache. REVIEWERS' CONCLUSIONS: A few non-invasive physical treatments may be effective as prophylactic treatments for chronic/recurrent headaches. Based on trial results, these treatments appear to be associated with little risk of serious adverse effects. The clinical effectiveness and cost-effectiveness of non-invasive physical treatments require further research using scientifically rigorous methods. The heterogeneity of the studies included in this review means that the results of a few additional high-quality trials in the future could easily change the conclusions of our review.

PMID: 15266458

Expert Opin Pharmacother. 2008 Oct;9(15):2565-73. Links

Treatment of migraine with prophylactic drugs.Evers S.

University of Münster, Department of Neurology, Albert-Schweitzer-Street 33, 48129 Münster, Germany. everss@uni-muenster.de

BACKGROUND: Migraine is among the 10 most disabling disorders worldwide. Besides acute attack treatment, drug prophylaxis of migraine is important in order to improve the quality of life. OBJECTIVE: The aim of this paper is to describe the indications, principles and appropriate drugs with published evidence for the prophylaxis of migraine in general and in specific situations. METHODS: Based on the American and European guidelines for the treatment of migraine, the evidence for different drugs in the prophylaxis of migraine was evaluated. In addition, all trials on migraine drug prophylaxis published since the publication of the guidelines were included in the evaluation. These trials were identified by a literature search in MedLine, Embase and the Cochrane library. RESULTS: The drugs of first choice are beta-blockers, flunarizine, valproic acid and topiramate and, in the US, amitriptyline is also grouped among the first-choice drugs. Drugs of second choice, with less efficacy or poorer evidence, are venlafaxine, gabapentin, naproxen, butterbur root, vitamin B(2) and magnesium. The potential side effects are considered when choosing the appropriate prophylactic drug. All drugs used in migraine prophylaxis have been detected by chance and not by pathophysiological considerations. In the future, drugs developed on the basis of the current knowledge of migraine pathophysiology will hopefully be more effective.

PMID: 18803445

Ann Pharmacother. 2007 Jul;41(7):1181-90. Epub 2007 Jun 5. Links

Pediatric migraine: pharmacologic agents for prophylaxis.Eiland LS, Jenkins LS, Durham SH.

Auburn University Harrison School of Pharmacy, Huntsville, AL, USA. eilanls@auburn.edu

OBJECTIVE: To identify and evaluate the data regarding medication use for migraine prophylaxis in the pediatric population. DATA SOURCES: Literature was obtained through searches in PubMed (Mid 1950s-March 2007), Iowa Drug Information Service/Web (1966-February 2007), International Pharmaceutical Abstracts (1970-February 2007), and the Cochrane Library. The terms migraine, prophylaxis, child, and children were used and cross referenced with all drug names. Reference citations from publications identified were also reviewed and included. STUDY SELECTION AND DATA EXTRACTION: Only trials that evaluated migraine headaches in the pediatric population were included. Trials including adolescent and adult populations are briefly listed, but not reviewed. Trials involving non-prescription medication were also included in the evaluation. Due to the limited information, all clinical trials, retrospective reviews, and abstracts evaluated were included in this review. DATA SYNTHESIS: Few controlled clinical trials regarding prophylaxis therapy are available. Currently, no medications are approved by the Food and Drug Administration for prophylaxis of migraines in children. Seventeen drugs were identified and included in the review. Of the drugs with available data, topiramate, valproic acid, flunarizine, amitriptyline, and cyproheptadine have shown efficacy in decreasing migraine frequency and duration in children. However, larger clinical trials are necessary to validate the utility of these agents. Conflicting data exist for propranolol and pizotifen, and additional data are needed for gabapentin, levetiracetam, zonisamide, naproxen, and trazodone. In clinical trials, nimodipine, clonidine, and natural supplements have shown a lack of efficacy versus placebo for prophylaxis of migraines in children. CONCLUSIONS: Topiramate, valproic acid, and amitriptyline have the most data on their use for prophylaxis of migraines in children. Numerous agents have limited data in this population and several agents lack efficacy. Prospective, well designed, controlled clinical trials that include quality-of-life and functional outcomes are needed for guiding therapy of migraine prophylaxis for children.

PMID: 17550953

Pain. 2007 Mar;128(1-2):111-27. Epub 2006 Nov 2. Links

Efficacy of biofeedback for migraine: a meta-analysis.Nestoriuc Y, Martin A.

Philipps-University of Marburg, Section for Clinical Psychology and Psychotherapy, Gutenbergstr. 18, 35032 Marburg, Germany. yvonne.nestoriuc@staff.uni-marburg.de <yvonne.nestoriuc@staff.uni-marburg.de>

In this article, we meta-analytically examined the efficacy of biofeedback (BFB) in treating migraine. A computerized literature search of the databases Medline, PsycInfo, Psyndex and the Cochrane library, enhanced by a hand search, identified 86 outcome studies. A total of 55 studies, including randomized controlled trials as well as pre-post trials, met our inclusion criteria and were integrated. A medium effect size (d =0.58, 95% CI=0.52, 0.64) resulted for all BFB interventions and proved stable over an average follow-up phase of 17 months. Also, BFB was more effective than control conditions. Frequency of migraine attacks and perceived self-efficacy demonstrated the strongest improvements. Blood-volume-pulse feedback yielded higher effect sizes than peripheral skin temperature feedback and electromyography feedback. Moderator analyses revealed BFB in combination with home training to be more effective than therapies without home training. The influence of the meta-analytical methods on the effect sizes was systematically explored and the results proved to be robust across different methods of effect size calculation. Furthermore, there was no substantial relation between the validity of the integrated studies and the direct treatment effects. Finally, an intention-to-treat analysis showed that the treatment effects remained stable, even when drop-outs were considered as nonresponders.

PMID: 17084028

J Orthop Sports Phys Ther. 2006 Mar;36(3):160-9.Links

Methodological quality of randomized controlled trials of spinal manipulation and mobilization in tension-type headache, migraine, and cervicogenic headache.Fernández-de-las-Peñas C, Alonso-Blanco C, San-Roman J, Miangolarra-Page JC.

Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain. cesar.fernandez@urjc.es

STUDY DESIGN: Literature review of quality of clinical trials. OBJECTIVE: To determine the methodological quality of published randomized controlled trials that used spinal manipulation and/or mobilization to treat patients with tension-type headache (TTH), cervicogenic headache (CeH), and migraine (M) in the last decade. BACKGROUND: TTH, CeH, and M are the most prevalent types of headaches seen in adults. Individuals who have headaches frequently use physical therapy, manual therapy, or chiropractic care. Randomized controlled trials are considered an optimal method with which to assess the efficacy of any intervention. METHODS: Computerized literature searches were performed in MEDLINE, EMBASE, COCHRANE, AMED, MANTIS, CINHAL, and PEDro databases. Randomized controlled trials in which spinal manipulation and/or mobilization had been used for TTH, CeH, and M published in a peer-reviewed journal as full text, and with at least 1 clinically relevant outcome measure (ie, headache intensity, duration, or frequency) were reviewed. The methodological quality of the studies was assessed independently by 2 reviewers using a set of predefined criteria. RESULTS: Only 8 studies met all the inclusion criteria. One clinical trial evaluated spinal manipulation and mobilization together, and the remaining 7 assessed spinal manipulative therapy. No controlled trials analyzing exclusively the effects of spinal mobilization were found. Methodological scores ranged from 35 to 56 points out of a theoretical maximum of 100 points, indicating an overall poor methodology of the studies. Only 2 studies obtained a high-quality score (greater than 50 points). No significant differences in quality scores were found based on the type of headache investigated. Methodological quality was not associated with the year of publication (before 2000, or later) nor with the results (positive, neutral, negative) reported in the studies. The most common flaws were a small sample size, the absence of a placebo control group, lack of blinded patients, and no description of the manipulative procedure. CONCLUSIONS: There are few published randomized controlled trials analyzing the effectiveness of spinal manipulation and/or mobilization for TTH, CeH, and M in the last decade. In addition, the methodological quality of these papers is typically low. Clearly, there is a need for high-quality randomized controlled trials assessing the effectiveness of these interventions in these headache disorders.

PMID: 16596892