Alternative Headache Treatments

[Guest guest]

Docs:

Here's the latest on "Alternative Headache Treatments" from

Medscape. Chiropractic is mentioned briefly (of course) in the

"Physical Treatments" section.

Lyndon McGill, D.C.

Salem, Oregon

www.SalemSpineClinic.com

Evolving Doctors

Authors and Disclosures

Sun-Edelstein, MD and Mauskop,

MD

Department of Clinical Neurosciences, St 's Hospital,

Melbourne, Vic., Australia (C. Sun-Edelstein); SUNY Downstate

Medical Center, New York, NY, USA (A. Mauskop).

Address all correspondence to

A.Mauskop, The New York Headache Center, 30 East 76th Street,

New York, NY 10021, USA.

From Headache

Alternative Headache Treatments

Nutraceuticals, Behavioral and Physical Treatments

Sun-Edelstein, MD; Mauskop, MD

Posted: 04/07/2011;

Headache. 2011;51(3):469-483. © 2011 Blackwell Publishing

Abstract and Introduction

Abstract

There is a growing body of evidence supporting the efficacy of

various complementary and alternative medicine approaches in the

management of headache disorders. These treatment modalities

include nutraceutical, physical and behavioral therapies.

Nutraceutical options comprise vitamins and supplements

(magnesium, riboflavin, coenzyme Q10, and alpha lipoic

acid) and herbal preparations (feverfew, and butterbur). Although

controversial, there are some reports demonstrating the benefit of

recreational drugs such as marijuana, lysergic acid diethylamide

and psilocybin in headache treatment. Behavioral treatments

generally refer to cognitive behavioral therapy and biobehavioral

training (biofeedback, relaxation training). Physical treatments

in headache management are not as well defined but usually include

acupuncture, oxygen therapy, transcutaneous electrical nerve

stimulation, occlusal adjustment, cervical manipulation, physical

therapy, massage, chiropractic therapy, and osteopathic

manipulation. In this review, the available evidence for all these

treatments will be discussed.

Introduction

The use of complementary and alternative medicine (CAM) has been

on the rise, as demonstrated by epidemiological studies in the USA

and Europe over the past few decades.[1,2] More

recently, the utilization of CAM has increased in patients with

neurological disorders, and now appears to be in widespread use

among patients even in tertiary headache care. In a recent

questionnaire-based survey conducted in Germany and Austria, the

majority (81.7%) of patients attending tertiary outpatient

headache clinics reported use of CAM.[3] CAM usage is

often motivated by dissatisfaction with conventional therapies and

medication side effects, or a desire to be proactive against a

disabling disorder.

Although there is no formal definition for CAM, the National

Center for Complementary and Alternative Medicine considers it to

be "a group of diverse medical and health care systems, practices,

and products that are not presently considered to be part of

conventional medicine."[4] For many patients, the

appeal of CAM is in the holistic, empowering, and educational

nature of the various treatment strategies. CAM modalities can

generally be divided into nutraceutical, physical, and behavioral

therapies. In the context of headache treatment, nutraceutical

options include vitamins, supplements and herbal preparations,

while non-pharmacological therapies include behavioral treatments,

physical therapies, and acupuncture. Behavioral treatments usually

comprise cognitive behavioral therapy (CBT) and biobehavioral

training (biofeedback [bFB], relaxation training).

There is increasing evidence for the efficacy and tolerability of

some CAM approaches in the management of headache disorders.

Although these strategies may be used instead of traditional

medications, using them in conjunction with conventional

pharmacological therapies as part of a multidisciplinary treatment

plan is more likely to result in optimum responses.[5–7]

In this review, the evidence for various CAM therapies in headache

treatment will be discussed.

Methods

The National Library of Medicine (PubMed), The Cochrane Library,

and the American Academy of Neurology's Evidence-Based Guidelines

were searched through August 2010 to identify studies, reviews,

case series, reports or other information that assessed the

alternative treatment of headache or migraine. The key words used

in the search were: alternative, complementary, magnesium,

riboflavin, coenzyme Q10 (CoQ10), alpha

lipoic acid, butterbur, feverfew, marijuana, lysergic acid,

psilocybin, nutraceutical, behavioral treatment, BFB, relaxation,

cognitive behavioral training, physical treatment, acupuncture,

and oxygen therapy, combined with the key words of headache or

migraine.

Nutraceuticals

Patients often seek nutraceuticals for headache treatment after

finding conventional therapies ineffective or limited by side

effects, believing that "natural" substances such as vitamins,

minerals, and herbal remedies are less toxic than prescription

medications. While the evidence for some of these nutraceuticals

is promising, especially for magnesium, many of the existing

studies are small and underpowered, sometimes showing inconsistent

results. The available evidence for these treatments is discussed

below, but larger, better-designed trials are necessary in order

to establish strong evidence of efficacy for any of them.

Magnesium

Magnesium, an essential cation that plays a vital role in

multiple physiological processes, may have several roles in

migraine pathogenesis. Deficiency in magnesium has been associated

with cortical spreading depression,[8] neurotransmitter

release,[9] platelet aggregation,[10] and

vasoconstriction,[11,12] all of which are important

aspects of our current understanding of migraine pathophysiology.

In addition, magnesium concentration influences serotonin

receptors, nitric oxide synthesis and release, inflammatory

mediators, and various other migraine-related receptors and

neurotransmitters.[13]Magnesium also plays a role in

the control of vascular tone and reactivity to endogenous hormones

and neurotransmitters, through its relationship with the NMDA

receptor.[14,15] Deficiency in magnesium results in the

generation and release of substance P,[16] which

subsequently acts on sensory fibers, resulting in headache pain.[17]

Magnesium Deficiency Although a relationship between

migraine and magnesium deficiency had long been postulated, it was

initially difficult to assess, owing to the absence of simple and

reliable ways of measuring magnesium levels in soft tissues. While

routine laboratory testing generally measures total magnesium

levels, it is the ionized magnesium level that truly reflects

perturbed magnesium metabolism.[18] The subsequent

development of an ion-selective electrode for magnesium has

allowed for the accurate and rapid measurement of serum ionized

levels.[18,19]

A pilot study of 40 patients with an acute migraine attack found

that 50% of the patients had low levels of ionized magnesium.[20]

When these patients were given 1 g of intravenous magnesium, basal

serum IMg2+ levels correlated with the efficacy of

treatment.[20,21] Of the patients in whom pain relief

was sustained over 24 hours, 86% had a low serum IMg2+

level; only 16% of patients who had no relief had a low IMg2+

level. Total magnesium levels in all subjects were within normal

range. Systemic magnesium deficiency in migraineurs has also been

suggested by magnesium retention after oral loading.[22]

Magnesium deficiency may be especially common in women with

menstrually related migraine. A prospective study[23]

with 270 women, 61 of whom had menstrually related migraine,

showed that the incidence of IMg2+ deficiency was 45%

during menstrual attacks, 15% during non-menstrual attacks, 14%

during menstruation without a migraine, and 15% between

menstruations and between migraine attacks.

Low levels of magnesium in the brain[24] and

cerebrospinal fluid[25] have also been reported, but

interictal studies on serum,[26–30] plasma,[31,32]

and intracellular[28,29,32–34] magnesium levels in

migraineurs and patients with tension-type headache (TTH) have

produced conflicting results. However, interictal levels of red

blood cell (RBC) magnesium have been shown to be decreased in

migraineurs with[33] and without aura,[28,31]

as well as in juvenile migraine patients with and without aura.[35]

These results were supported by a study[36] that showed

low total magnesium in erythrocytes and low ionized magnesium in

lymphocytes in migraine patients, both of which increased

significantly after a 2-week trial of drinking mineral water

containing 110 mg/L magnesium. Given its commercial availability,

the RBC magnesium assay may therefore be a good way of assessing

for deficiency. Future trials should focus on patients with

deficiencies in ionized or RBC magnesium, as improvements in

clinical symptoms correlating with corrected levels would clearly

demonstrate the benefits of magnesium supplementation.

Treatment with Oral Magnesium Several randomized

controlled trials (RCTs) have shown that Mg2+

supplementation is effective in migraine treatment. In the first,

24 women with menstrual migraine[31] received either

360 mg of magnesium pyrrolidone carboxylic acid or placebo in 3

divided doses. Women received 2 cycles of study medication, taken

daily from ovulation to the first day of flow. Magnesium treatment

resulted in a significant reduction of the number of days with

headache (P < .1), total pain index (P >

..03), as well as an improvement of the Menstrual Distress

Questionnaire score in the treatment group compared to placebo.

A larger study comprising 81 migraineurs also showed a

significant improvement in patients who received magnesium.[37]

Attack frequency was reduced by 41.6% in the magnesium group and

by 15.8% in the placebo group. The active treatment group received

600 mg of trimagnesium dicitrate in a water-soluble granular

powder taken every morning. More recently, Koseoglu et al[38]

studied the prophylactic effects of 600 mg/day of oral magnesium

citrate supplementation in patients with migraine without aura and

found that active treatment resulted in a significant decrease in

migraine attack frequency and severity. A 4th RCT showed no effect

of oral magnesium on migraine.[39] This negative result

was likely because of the use of a poorly absorbed magnesium salt,

as diarrhea occurred in almost half of patients in the treatment

group.

The most common adverse effect associated with oral magnesium

supplementation is diarrhea. While diarrhea itself usually

prevents the development of magnesium-related toxicity, patients

should be cautioned about this side effect. Magnesium toxicity is

marked by the loss of deep tendon reflexes followed by muscle

weakness. Severe toxicity can lead to cardiac muscle weakness,

respiratory paralysis, and death. Patients with kidney disease are

at higher risk of developing toxicity as magnesium is excreted

through the kidneys.[40]

Treatment with Intravenous Magnesium Several studies

have evaluated the use of intravenous magnesium in acute migraine

treatment, with conflicting results. In the pilot study[20]

described under "Magnesium Deficiency" a strong correlation

between the clinical response and the levels of serum IMg2+

was found (P < .01). Although the study was not

double-blinded or placebo-controlled, both the researchers and

subjects were blinded to the IMg2+ levels. A subsequent

study[21] showed that 1 g of magnesium sulfate resulted

in rapid headache relief in patients with low serum IMg2+

levels.

In a single-blind RCT involving 30 patients with moderate to

severe migraine attacks[41] treatment with 1 g

intravenous magnesium sulfate was superior to placebo in terms of

both response rate (100% for magnesium sulfate vs 7% for placebo)

and pain-free rate (87% for magnesium sulfate and 0% for placebo).

Mild side effects including flushing and a burning sensation in

the face and neck were common during the infusion, but subjects

were able to continue treatment. Of note, none of the subjects

reported headache recurrence during the 24 hours after treatment.

Bigal et al[42] in a double-blind RCT, showed that 1 g

of magnesium sulfate resulted in a statistically significant

improvement in pain and associated symptoms in subjects with

migraine with aura, as compared to controls. Although migraine

without aura patients did not show a significant difference in

pain relief compared to those receiving placebo, they did have a

significantly lower intensity of photophobia and phonophobia.

Two RCTs have been conducted in emergency room settings, neither

of which showed that magnesium was more effective than placebo in

aborting attacks.[43,44]

Supplements and Mitochondrial Dysfunction

Mitochondrial dysfunction, which leads to impaired oxygen

metabolism, has been speculated to play a role in migraine

pathophysiology[45,46] as migraineurs have been shown

to have reduced mitochondrial phosphorylation potential in between

headaches.[47,48] An impairment of mitochondrial

oxidative metabolism might influence neuronal information

processing, therefore reducing the threshold for migraine attacks.[49]

This is the rationale for the use of supplements that enhance

mitochondrial function in the treatment of migraine, such as

riboflavin, CoQ10, and alpha lipoic acid.

Riboflavin Riboflavin, also known as vitamin B2, is a

component of 2 coenzymes (flavin adenine dinucleotide and flavin

mononucleotide) that are cofactors in the electron transport chain

of the Krebs cycle. It plays a vital role in membrane stability

and the maintenance of energy-related cellular functions. One

well-designed RCT found that it is beneficial in migraine

prophylaxis, showing that daily use of 400 mg riboflavin for 3

months resulted in a 50% reduction in attacks in 59% of patients,

compared to 15% for placebo. Two minor adverse reactions, diarrhea

and polyuria, were reported in the treatment group.[50]

In a small study[51] investigating the effects of

different treatments on auditory evoked cortical potentials in

migrainers, riboflavin and beta-blockers were shown to act on 2

distinct aspects of migraine pathophysiology. The authors thus

suggested that combining these treatments might increase their

efficacy without concurrently increasing central nervous system

side effects.

A recent pharmacogenetic study[52] demonstrated that

riboflavin may be more effective in the treatment of migraine

patients with non-H mitochondrial DNA haplotypes. As riboflavin is

effective in deficiencies of the electron transport chain complex

I but not in mitochondriopathies related to an isolated complex IV

deficiency,[53,54] the authors suggested that

mitochondrial haplogroups differentially influence the activity of

the various complexes. These results may have ethnic implications,

in that haplogroup H is predominantly found in the European

population.

Coenzyme Q10 Coenzyme Q10 is an

endogenous enzyme cofactor involved in the mitochondrial electron

transport chain, generating energy through its role in aerobic

cellular respiration. Because of its activity in mitochondrial

function and as an antioxidant, it has been hypothesized to be

useful in migraine prevention. Two small studies thus far have

shown some benefit of CoQ10 in migraine treatment. In

the first, an open-label study[55] of 31 migraineurs

who used 150 mg daily of CoQ10 for 3 months, 61% had at

least a 50% reduction in migraine days. Notably, supplementation

was effective within the first month of treatment. No significant

adverse effects were noted. The second study,[56] a

small (n = 42) RCT assessing the efficacy of 100 mg of CoQ10

3 times daily, found that CoQ10 significantly decreased

attack frequency, headache days, and days with nausea.

Gastrointestinal disturbances and "cutaneous allergy" were

reported at a low rate.

Coenzyme Q10 supplementation may be especially

effective in the prophylaxis of pediatric migraine. CoQ10

levels were measured in a study[57] of 1550 pediatric

patients (mean age 13.3 ± 3.5 years) with frequent headaches.

Nearly one-third of subjects were below the reference range.

Patients with low CoQ10 received supplementation with 1

to 3 mg/kg per day of CoQ10 in liquid gel capsule

formulation, resulting in an improvement in total CoQ10

levels, headache frequency and degree of headache disability.

Alpha Lipoic Acid Alpha lipoic acid, also known as

thioctic acid, is a naturally occurring fatty acid that can be

found in many foods such as yeast, spinach, broccoli, potatoes,

and organ meats such as liver or kidney. Like riboflavin and CoQ10,

it augments mitochondrial oxygen metabolism and adenosine

triphosphate production.[58] In 1 small RCT,[59]

54 subjects received either 600 mg alpha lipoic acid or placebo

daily for 3 months. Although there was no significant difference

between treatment and placebo for the primary endpoint (50%

reduction of monthly attack frequency), there was a trend toward

reduction of migraine frequency after treatment with alpha lipoic

acid. Within-group analyses also showed a significant reduction in

attack frequency, headache days, and headache severity in the

treatment group. While these results suggest that alpha lipoic aid

may be effective in migraine prevention, larger trials are

necessary.

Herbal Preparations

Butterbur (Petasites Hybridus) In recent years, Petasites

hybridus root extract, also known as butterbur, has been

touted as a promising new treatment for migraine prevention. The

butterbur plant is a perennial shrub found throughout Europe and

parts of Asia. It was used for many centuries as a remedy for

pain, fever, spasms, and wound healing. Although its mechanism of

action is not fully understood, Petasites likely acts

through calcium channel regulation and inhibition of peptide

leukotriene biosynthesis, thus influencing the inflammatory

cascade associated with migraine.[60–62] The

pharmacologically active compounds in butterbur are sesquiterpenes

such as petasin and isopetasin. While the butterbur plant itself

also contains pyrrolizidine alkaloids, which are hepatotoxic and

carcinogenic, these substances are removed in the commercially

available preparations, such as those manufactured by Weber &

Weber (Inning am Ammersee, Germany; Petadolex® and others).

Nonetheless, patients should be advised to use only butterbur

products that are certified and labeled "PA-free."

The efficacy of Petasites hybridus in migraine

prevention has been evaluated in several studies. In the first

RCT,[63] 50 mg of Petadolex® twice daily showed a

significantly reduced number of migraine attacks and migraine days

per month compared to placebo. An independent re-analysis of

efficacy criteria was subsequently performed[64]

because of flawed statistical analyses in the original study, and

confirmed the superiority of the butterbur extract over placebo

for all primary variables of efficacy. Later, a 3-arm,

parallel-group RCT of 245 patients comparing Petasites extract 75

mg twice daily, Petasites extract 50 mg twice daily, and placebo

twice daily[65] showed that Petasites extract 75 mg

twice daily was more effective than placebo in decreasing the

number of monthly migraine attacks. Maximum response was achieved

after 3 months, resulting in an attack reduction of 58% with the

higher dose of Petadolex®, compared to the placebo response of

28%. Petadolex® was well tolerated in these studies, and no

serious adverse events occurred. The most frequently reported

adverse reactions were mild gastrointestinal events, especially

eructation (burping). Petasites, like most other herbal

preparations, should not be taken by pregnant women.

Given its safety and tolerability, Petadolex® may be a good

option in the treatment of pediatric migraine. In a multicenter

prospective open-label study[66] of Petadolex® in 109

children and adolescents with migraine, 77% of all patients

reported a reduction in migraine frequency of at least 50%.

Ninety-one percent of participants felt substantially or at least

slightly improved after 4 months of treatment.More recently, a

prospective, partly double-blind, RCT assessing the efficacy of

Petadolex® and music therapy in primary school children with

migraine[67] showed that at 6-month follow-up, both

music therapy and butterbur root extract were superior to placebo

(P = .018 and P = .044, respectively) in

reducing headache frequency, but only among those that completed

the study. In the analysis including all treated patients,

treatment groups did not differ significantly during follow-up.

Feverfew Feverfew is an herbal preparation that was used

for centuries in the treatment of fevers, headache, infertility,

toothaches, inflammation and arthritis. Although the feverfew

plant was originally native to the Balkan mountains in Eastern

Europe, it now grows throughout Europe, North America, and South

America. It is commercially available as the dried leaves of the

weed plant Tanacetum parthenium, and its anti-migraine

action is probably related to the parthenolides within these

leaves. Feverfew may act in migraine prophylaxis by inhibiting

platelet aggregation as well as the release of serotonin from

platelets and white blood cells. It may also act as an

anti-inflammatory agent through the inhibition of prostaglandin

synthesis and phospholipase A.[68–71]

The efficacy of feverfew in migraine prophylaxis has been

controversial, as many RCTs[72–77] conducted in the

past 3 decades have yielded contradictory results. In addition, a

2004 Cochrane review[78] of double-blind RCTs assessing

the clinical efficacy and safety of feverfew in migraine

prevention concluded that there was insufficient evidence to

suggest that feverfew is more effective than placebo in migraine

prophylaxis. No major safety or tolerability issues were

identified, although side effects reported in the RCTs included

gastrointestinal disturbances, mouth ulcers, and a "post-feverfew

syndrome" of joint aches.

Inconsistent results from the above studies were attributed to

wide variations in the strength of the parthenolides[79]

and differences in the stability of feverfew preparations[80]

and subsequently, a new, more stable feverfew extract (MIG-99) was

created. In an initial RCT involving 147 patients,[81]

none of the MIG-99 doses were significant for the primary

endpoint, although a subset of high-frequency migraineurs appeared

to benefit from treatment. In a follow-up multicenter RCT with 170

subjects[82] randomized to 6.25 mg t.i.d. of MIG-99 or

placebo, a statistically significant and clinically relevant

reduction in migraine frequency in the MIG-99 group compared to

placebo was reported.

Feverfew should not be used by pregnant women, as it may cause

uterine contractions resulting in miscarriage or preterm labor. It

can also cause allergic reactions; patients with allergies to

other members of the daisy family, including ragweed and

chrysanthemums, are more likely to be allergic to feverfew.

Recreational Drugs

Although controversial, the evidence for the use of recreational

drugs such as marijuana, lysergic acid diethylamide (LSD) and

psilocybin is worth mentioning for the insight it provides

regarding the pathophysiology of migraine and cluster headache.

Further research on the effects of these substances may result in

a greater understanding of the mechanisms of these headache

disorders.

Marijuana The recreational and medicinal use of

marijuana, or cannabis, has been documented for

thousands of years.[83] In the second half of the 19th

century, cannabis was a well-regarded acute and

preventative treatment for headache in USA and UK, and was even

included in the mainstream pharmacopeias for this use.[83]

Synthetic cannabinoids such as dronabinal and nabilone (used in

the UK) have been established as useful in the treatment of nausea

and vomiting associated with cancer chemotherapy. However, the

role of cannabinoids in pain management is less clear. Preclinical

evidence has shown that endogenous cannabinoids such as anandamide

and cannabinoid agonists are antinociceptive and antihyperalgesic,

reducing the allodynia associated with formalin, capsaicin,

carrageenan, nerve injury, and visceral persistent pain.[84]

After entering the bloodstream, cannabinoids are differentially

distributed in the brain and reach high concentrations in the

neocortex (especially the frontal cortex), limbic areas, sensory

areas, motor areas, and the pons.[85] Therefore,

cannabinoid receptors and endogenous cannabinoids may modulate

pain, psychomotor control, memory function, appetite, and emesis.

Cannabinoid receptors and endogenous cannabinoids are located

throughout the pain pathways in peripheral sensory nerve endings,

spinal, and supraspinal centers.[86] In migraine,

cannabinoids may be effective via an inhibitory effect on

serotonin type 3 (5-HT3) receptors[87] or

antinociceptive effects in the periaqueductal gray matter.[88]

Clinical data on therapeutic uses of marijuana have been

conflicting. A meta-analysis of clinical trials of cannabinoid

derivatives in the treatment of pain[89] showed that

cannabinoids are no more effective than codeine in pain

management, and that central nervous system depressant side

effects limit their use in clinical practice. The authors thus

concluded that more research is necessary before these treatments

could be recommended for neuropathic pain or spasticity. Later, a

small RCT[90] showed that the synthetic cannabinoid

1',1'dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid (CT-3)

was effective in reducing chronic neuropathic pain when compared

with placebo. With regard to headache, evidence thus far has been

limited to case reports describing the effective use of cannabis

or cannabinoids in "chronic headaches,"[91] migraine,[92]

pseudotumor cerebri[93] and cluster headache.[94]

Lysergic Acid Diethylamide and Psilocybin A 2006 report[95]

on 53 cluster headache patients who used either the ergot alkaloid

derivative LSD or the related indolalkylamine psilocybin for their

headaches described intriguing results. Twenty-two of 26

psilocybin users reported that psilocybin aborted attacks while 25

of 48 psilocybin users and 7 of 8 LSD users reported cluster

period termination. In addition, 18 of 19 psilocybin users and 4

of 5 LSD users reported remission period extension, meaning that

the next expected cluster period was delayed or prevented. These

results are interesting not only because they describe the

effective use of illicit drugs in cluster headache, but also

because no other medication has been reported to terminate a

cluster period. Furthermore, the drugs were effective at

subhallucinogenic doses and effective treatment required very few

doses of either drug. LSD reportedly terminated cluster periods

after only 1 dose, and psilocybin rarely required more than 3

doses. The study was unblinded, uncontrolled and limited by recall

and selection bias. However, further research on the effects of

LSD and psilocybin on cluster headaches may be warranted, given

the efficacy described in this report.

Behavioral and Physical Therapies

Behavioral treatments are divided into the categories of CBT and

biobehavioral training (BFB, relaxation training). Physical

treatments are not as well defined but generally include

acupuncture, cervical manipulation, transcutaneous electrical

nerve stimulation (TENS), occlusal adjustment, physical therapy,

massage, chiropractic therapy, and osteopathic manipulation.

Oxygen therapy is included in this section as well. Patient

education is a crucial part of any of these modalities.

In 2000, the US Headache Consortium issued evidence-based

guidelines for the treatment and management of migraine headache,

based on a review of the medical literature and expert consensus.[96]

According to these guidelines, behavioral and physical treatments

may be particularly beneficial in patients with one or more of the

following characteristics:

patient preference for non-pharmacological interventions;

poor tolerance for specific pharmacological treatments;

medical contraindications for specific pharmacological

treatments;

insufficient or no response to pharmacological treatment;

pregnancy, planned pregnancy, or nursing;

history of long-term, frequent, or excessive use of analgesic

or acute medications that can aggravate headache problems (or

lead to decreased responsiveness to other pharmacotherapies);

significant stress or deficient stress-coping skills.

Behavioral Treatments

Behavioral medicine involves the integration of behavioral,

psychosocial, and biomedical disciplines in the diagnosis,

treatment, rehabilitation, and prevention of illness. The

interactions of behavior with biology and the environment are

studied and taken into consideration in the treatment and

understanding of diseases and disorders. Migraine and other

primary headache disorders are particularly well suited to the

practice of behavioral medicine, in that complex relationships

between biology, environment, behavior, cognition, and emotion are

known to affect the course of the disorder. Once behavioral

treatments and techniques are learned, patients can utilize their

skills in recognizing and mediating the effects of stress at any

time and in any context.

Behavioral treatments have become standard components of

multidisciplinary treatment plans at headache centers and pain

management programs as guidelines, such as those published by the

US Headache Consortium,[96] established that they may

be considered as treatment options for migraine prevention. In its

evidence-based guidelines for behavioral and physical treatments

in migraine, the US Headache Consortium[96] recommended

that relaxation training, thermal BFB combined with relaxation

training, electromyography (EMG) BFB, and cognitive behavioral

therapy be considered as treatment options for prevention of

migraine, based on Grade A evidence. For TTH, the 2010 European

Federation of Neurological Societies guidelines on the treatment

of TTH[97] states that non-pharmacological modalities

should always be considered, although the scientific evidence is

limited. The available evidence shows that EMG BFB is effective,

and cognitive behavioral therapy and relaxation training most

likely are effective as well for TTH treatment.

Behavioral treatment may be administered in clinic-based,

limited-contact, and home-based formats, and patients may be seen

individually or as part of a group. Limited-contact treatment

usually involves 3 or 4 monthly treatment sessions during which

skills are introduced. Audiotapes and manuals are subsequently

used at home for practicing and refining skills, with clinicians

assisting occasionally via telephone. Limited-contact, home-based,

and clinic-based treatment formats have demonstrated similar

results when compared directly[98–100] or by

meta-analysis.[101] Furthermore, the cost-effectiveness

of home-based treatments has been found to be more than 5 times

that of clinic-based therapies.[101]

Biofeedback Biofeedback is a common intervention

utilized in the treatment of pain disorders. It involves the

monitoring and voluntary control of physiologic processes,

allowing patients to take an active role in managing their pain.

This in turn results in improved coping with the psychological and

psychosocial consequences of their condition. BFB is often

combined with relaxation and cognitive behavioral strategies such

as stress management.

Different types of BFB are used depending on the patient's

diagnosis. All forms of BFB involve the conversion of biologic or

physiologic information into a signal that is then "fed back" in

auditory form (such as clicks varying in rate) or visual form

(such as bars varying in length). In migraine, peripheral skin

temperature feedback (TEMP-FB), blood-volume-pulse feedback

(BVPFB) and electromyographic feedback (EMG-FB) are most commonly

used. For TTH, EMG-FB, which is directed at reducing pericranial

muscle activity, is the most frequently applied behavioral

treatment modality.[102] Relaxation skills such as

diaphragmatic breathing or visualization are usually taught in

conjunction with BFB to produce a relaxation response. BFB

training usually involves 8–12 office visits spaced 1 to several

weeks apart, although evidence suggests that treatment can be

effective in a reduced-contact or home-based approach.[101]

Once the patient has developed the skills necessary to control

targeted physiologic processes, the BFB device can be eliminated.

Biofeedback for Migraine Treatment A 2007

meta-analysis,[103] which included 55 studies, provided

strong evidence for the efficacy of BFB in the preventative

treatment of migraine. BFB demonstrated superior clinical results

when compared to waiting list control and was shown to be at least

equally effective in comparison to psychological placebo controls,

relaxation, and pharmacotherapy. Also noted were reductions in the

associated symptoms of depression and anxiety, and an increase in

patients' sense of self-efficacy. Additional home training

enhanced the direct and the follow-up treatment effect sizes, and

was an important predictor of long-term outcome. None of the

reviewed studies reported any adverse effects of BFB. The

different forms of BFB—BVP-FB, EMG-FB and TEMP-FB—all appeared to

be equally efficacious alone or in combination in the treatment of

migraine. However, BVP-FB showed the numerically highest effect

size of all examined feedback modalities.

Not only did BFB result in symptom reduction of over half a

standard deviation, the treatment effects remained stable over a

follow-up period of more than 1 year, on average. Furthermore,

these effects appeared to be amplified over the long term. This

may be explained by several factors, such as improved

self-efficacy[104] and the continued practice and

application of BFB at home.[105] Self-efficacy itself

yielded higher effect sizes than the actual pain-related outcome

measures of BFB, suggesting that the treatment effects of BFB may

be influenced by changes in coping strategies,[106]

illness perceptions, and subsequent improvements in treatment

compliance.[107]

The authors concluded that "BFB can be recommended to therapists,

physicians and health care providers as an efficacious non-medical

treatment alternative for highly chronified migraine patients;

suitable also for the long-term prevention of migraine attacks."

Biofeedback in Tension-type Headache A recent

meta-analysis of BFB in TTH[108] evaluated 53 outcome

studies, which included a total of more than 400 patients, and

found a significant medium-to-large effect size that was stable

over an average follow-up period of 15 months. Superior effect

sizes for BFB were noted when compared to psychological placebo

and relaxation therapies. This effect was clinically meaningful in

that they demonstrated symptoms improvements of nearly one

standard deviation. While the largest improvements were shown in

headache frequency, significant effects were also seen for muscle

tension, self-efficacy, symptoms of anxiety and depression, and

analgesic medication consumption. Using BFB in conjunction with

relaxation training increased treatment efficacy, and effects

appeared to be particularly notable in children and adolescents.

Furthermore, courses of BFB treatment were short and

cost-effective, taking place over an average of 11 sessions. The

authors concluded that the efficacy of BFB in TTH is supported by

scientifically sound evidence.

Biofeedback Efficacy Recommendations A 2008

comprehensive efficacy review,[102] which drew upon the

2 meta-analyses discussed above[103,108] and

incorporated one additional study,[109] provided

efficacy recommendations for BFB in the treatment of migraine and

TTH. These recommendations were in accordance with criteria

established by the Association for Applied Psychophysiology and

Biofeedback (AAPB) and the International Society for Neurofeedback

and Research (ISNR).[110]

For migraine, the evidence indicated that BFB can be supported as

an efficacious treatment option (Level 4 evidence according to the

AAPB/ISNR criteria[110]). Multiple studies using

clearly defined diagnostic criteria and outcome measures as well

as appropriate data analysis demonstrated the efficacy of BFB over

no-treatment control groups.

For TTH, the evidence indicated that BFB can be supported as an

efficacious and specific treatment option. The efficacy

recommendation given was Level 5, the highest level of evidence

according to the AAPB/ISNR criteria, granted in cases where Level

4 evidence has been established and additional superior treatment

results in comparison to credible sham therapy or alternative bona

fide treatments have been shown.

Relaxation Training Relaxation training can be

considered a core component of behavioral treatment, as it can be

used either alone or in conjunction with other behavioral

modalities.[111] Relaxation techniques are used to

decrease sympathetic arousal and physiologic responses to stress

by enhancing the awareness of tense and relaxed muscles. Several

techniques and procedures have been employed in relaxation

training. Progressive relaxation training is the classic form and

is still widely used. It promotes the recognition of tension and

relaxation in the course of daily life. Patients are taught to

sequentially tense and relax various muscle groups while taking

note of the opposing sensations. Initially 16 muscle groups are

involved, and as treatment proceeds, muscle groups are

progressively combined, resulting in 4 groups at the end of

therapy. Once this initial stage is learned, skills such as

relaxation by recall, cue-controlled relaxation, and differential

relaxation (in which relaxation of muscles not required for

current activities is maintained) are taught. Patients can

typically learn progressive relaxation training in less than 10

sessions. While techniques are usually learned in a dark, quiet

setting, they can be subsequently applied to everyday situations.[112]

Autogenic training is another popular form of relaxation

training. Autosuggestion, the process by which one induces

self-acceptance of an opinion, belief, or plan of action, plays a

central role in the process. In autogenic training, mental and

somatic functions are concurrently regulated by passive

concentration on formulas such as "my forehead is cool."[113]

Various other traditional relaxation techniques include visual or

guided imagery, cue-controlled relaxation, diaphragmatic

breathing, and hypnosis.[114] With regular practice,

patients often find that relaxation techniques become automatic

and are carried out without conscious effort.[111]

Cognitive Behavioral Therapy Cognitive behavioral

therapy is a form of psychotherapeutic treatment that addresses

the relationships between stress, coping, and headache using

cognitive and behavioral strategies. While cognitive strategies

focus on identifying and challenging dysfunctional thoughts and

the beliefs that give rise to these thoughts, behavioral

strategies aim to help identify behaviors that may trigger,

increase or perpetuate headaches. CBT is usually most beneficial

in patients with concurrent significant psychological or

environment problems that exacerbate headaches or prevent the

implementation of self-regulation skills, such as chronic work

stress, mood disorders, or adjustment problems. As such, it is

also used to address and manage headache co-morbidities such as

depression, anxiety, panic attacks, eating disorders, and sleep

disorders.[114,115]

Research has shown that low levels of self-efficacy and an

external locus of control (ie, a belief that only the physician or

medication can alter a cycle of pain) predict poorer outcome,[116,117]

and that "catastrophizing" thinking patterns that promote a sense

of hopelessness predict poor outcomes and reduced quality of life.[118]

Therefore, in headache-related CBT, goals include the development

of self-efficacy and an internal locus of control (the belief in

oneself as an agent of change) as well as a change in

"catastrophizing" thinking. Pain management strategies such as

imagery training and attention-diversion training are frequently

taught in conjunction with CBT. Patient education in the form of

dietary interventions, lifestyle modification, and contingency

management are usually provided as well.[112,119]

The US Headache Consortium found that CBT in the preventative

treatment of migraine was supported by Grade A evidence.[96]

While CBT can decrease TTH activity by 40–50% or more,[120]

combining it with relaxation training and BFB may increase

treatment efficacy, especially in patients with psychiatric

co-morbidities, high levels of stress, or poor coping.[121]

Furthermore, combining CBT with pharmacological treatment such as

amitriptyline may result in more improvement than either treatment

alone, as demonstrated in a large RCT for chronic TTH.[122]

Physical Treatments

Physical treatments in headache management include acupuncture,

TENS, occlusal adjustment, physical therapy, massage, chiropractic

therapy, and osteopathic manipulation. Many of these therapies are

prescribed in the treatment of migraine and TTH in an effort to

relieve the neck pain that frequently accompanies these headache

disorders.[123] High levels of muscle tenderness, as

well as postural and mechanical abnormalities, have also been

reported in tension-type and migraine headache.[124–126]

Analyses and reviews on physical treatments in headache are

fraught with difficulty owing to many factors, including

inconsistencies in the definitions of treatments such as physical

therapy, chiropractic, or osteopathic manipulations, and a

heterogeneity in the interventions and patient populations that

have been studied. Furthermore, many of the published case series

and controlled studies are of low quality. The US Headache

Consortium[96] found that evidenced-based treatment

recommendations were not yet possible regarding the use of

acupuncture, TENS, cervical manipulation, or occlusal adjustment

as preventive or acute therapy for migraine. The use of

acupuncture has since received considerable support and is

discussed in a separate section.

More recently, a structured review[123] on physical

treatments for headache was undertaken, and found only modest

support for the use of physical treatments in selected

circumstances. Positive recommendations could be made in only a

few clinical scenarios.[123] For migraine,

recommendations were made for physical therapy combined with

aerobic exercise, as well as physical therapy combined with

relaxation therapy and thermal BFB. For TTH, there was a trend

toward benefit from chiropractic manipulation in TTH, although the

evidence was weak. Physical therapy was recommended, especially in

high-frequency TTH cases. Cervical spinal manipulative therapy was

found to be as effective as amitriptyline in short-term use for

chronic tension-type headache (CTTH), and more effective than

massage for cervicogenic headache. Other recent studies[127,128]

have reported that physical therapy can be effective in reducing

headache frequency, intensity and duration in CTTH patients.

Overall, these physical treatments are most beneficial when

integrated into a multimodal treatment plan including exercise,

stretching, and ergonomics training for both the home and the

workplace. Patients who express an interest in physical treatments

are more likely to benefit from active strategies such as exercise

than passive ones such as massage and heat or cold application.[129]

Some have suggested that the insufficient evidence supporting or

refuting the effect of physical treatments on headache disorders

might be related to problems in identifying subgroups of patients

who might benefit from the intervention.[130]

Fernándezde-las-Peñas et al[131] thus devised a

preliminary clinical prediction rule to identify CTTH patients who

experience short-term success with muscle trigger point therapy,

using variables such as headache frequency, duration, bodily pain,

and vitality scores. The implementation of clinical decision rules

identifying these patients prior to carrying out randomized

clinical trials was therefore suggested as a way of attaining

stronger effect sizes.[131]

Although cervical spinal manipulative therapy may provide benefit

in some clinical cases as described above, it has been associated

with a 6-fold[132] increase in the risk of vertebral

artery dissection and stroke or transient ischemic attack. As

such, one should be cautious when considering a recommendation for

this treatment, and patients who express interest in chiropractic

maneuvers should be warned of this potential complication.[123]

Otherwise, the use of physical treatments in headache is unlikely

to be harmful in patients who express interest in these

modalities.

Acupuncture Acupuncture is a fundamental component of

traditional Chinese medicine, and is one of the most commonly

utilized complementary therapies in many countries.[133]

In recent years, interest in acupuncture in the Western world has

grown, with 2.13 million people in the USA currently undergoing

treatment.[134] Population-based studies in the USA

have shown that 4.1% of respondents report lifetime use of

acupuncture,[134] and in Germany, 8.7% of adults

surveyed reported that they had undergone acupuncture during the

previous year.[135] Acupuncture is used in the

treatment of a variety of conditions including addiction, stroke

rehabilitation, headache, menstrual cramps, fibromyalgia,

myofascial pain, osteoarthritis, low back pain, carpal tunnel

syndrome, and asthma, and may be particularly effective in

post-operative and chemotherapy-induced nausea and vomiting, and

post-operative dental pain.[136] Headache treatment

accounts for approximately 10% of visits to acupuncturists.[134]

The goal of acupuncture is to restore a state of equilibrium that

has been disrupted by illness. The concept of qi refers

to the life energy that normally flows through 12 organs and 12

meridians, arriving at the surface at 359 classical acupuncture

points. Various illnesses and disorders are thus described in

terms of too little qi or too much qi in

particular organs or areas of the body, resulting from blockages

in the flow of blood and qi. The activation of classic

acupuncture points, which are distributed along the meridians,

serves to clear the blockages, re-establishing the flow of qi.

However, as recent studies have offered a more scientific

explanation of the mechanism of acupuncture, some acupuncture

practitioners now conceptualize the treatment in terms of

conventional neurophysiology rather than in restoring the flow of

qi.[137]

Mechanism of Action While the mechanism by which

acupuncture provides an analgesic effect in migraine treatment is

not fully understood, several theories have been hypothesized.

Acupuncture has been shown to activate nervous system structures

in the control of pain perception, which include the prefrontal

cortex, the rostral anterior cingulated cortex and the brainstem,

as demonstrated by studies where acupuncture-induced analgesia was

inhibited by the experimental blockade of the pituitary gland,[138,139]

the arcuate nucleus of the hypothalamus,[140,141] and

the periaqueductal gray.[142] Other theories postulate

that serotonergic projections from the raphe nucleus to higher

areas of the brain as well as descending projections to the spinal

cord may contribute to the effectiveness of acupuncture,[143–145]

and an anti-inflammatory effect of acupuncture may also be

significant.[146,147]

However, other factors, including the psychological effects of

acupuncture and the physiological effects of sham acupuncture

related to superficial skin penetration, are likely to play an

important role in treatment efficacy.

Positive patient expectations about acupuncture, negative

experiences with traditional pharmacologic therapy, the intensity

of care provided by the acupuncturist, and many other

psychological variables may influence treatment outcome more so

than the treatment itself. Furthermore, given that sham

acupuncture provides a therapeutic effect in some patients,

unknown factors independent of acupuncture methodology must exist

that provide a reduction in migraine symptoms.[148]

Evidence Supporting the Use of Acupuncture in Headache

Treatment In a 2001 Cochrane review[149] of 16

randomized studies on acupuncture in the treatment of idiopathic

headache, the authors concluded that evidence in support of

acupuncture for migraine prophylaxis was considered promising but

insufficient. A meta-analysis of the studies could not be

performed because of the heterogenous nature of the available

data, differences in the choice of acupuncture points used, small

sample sizes, methodological problems, and insufficient reporting

of study details. In the intervening years between 2001 and an

updated Cochrane review in 2009, several large trials were

published. The largest of these studies,[150] which

enrolled 15,056 patients with primary headache, compared the

effectiveness of acupuncture in addition to routine care with

routine care alone. The effect of acupuncture in randomized

compared to nonrandomized patients was also studied. After 6

months, patients randomized to the acupuncture group showed a

decrease in the number of headache days (P < .001) as

well as improvements in pain intensity and quality of life (P

< .001). Non-randomized subjects showed outcome changes that

were similar to those in the randomized group. There were,

however, some methodological limitations of this study. It was

randomized but not blinded, and real acupuncture was not compared

with a sham acupuncture procedure. Also, the study groups included

patients with migraine, TTH, and a combination of both, and did

not differentiate between the headache types when reporting the

results.

The updated Cochrane review published in 2009 was split into

separate reviews on migraine[137] and TTH[151]

because of the increased number of studies and clinical

differences observed amongst study subjects. The migraine review[137]

included randomized trials comparing the clinical effects of

acupuncture with a control (no prophylactic treatment or routine

care only), a sham acupuncture intervention, or another

intervention in migraineurs. Results from the 22 trials,

comprising 4419 participants, showed consistent evidence that

acupuncture provides more benefit than routine care or acute

treatment alone. The available studies also indicated that

acupuncture is at least as effective as, or possibly more

effective than, traditional prophylactic therapy such as

metoprolol, with fewer side effects. Furthermore, there is no

evidence that "true" acupuncture is more effective than sham

interventions. As such, specific aspects of acupuncture

methodology such as point selection, needling stimulation, and

needling depth may not be as important as a regular needling

schedule of approximately 10 sessions carried out on a

twice-weekly basis. The authors thus concluded that acupuncture

should be considered a treatment option for patients willing to

undergo the treatment. The review on acupuncture in the treatment

of TTH[151] included 11 trials with 2317 participants.

Of these trials, 2 enrolled only patients with episodic TTH, 2

comprised only patients with CTTH, and 7 included both forms.

Results of 2 large-scale studies showed that adding acupuncture to

routine care or to acute treatment only reduces the short-term (3

months) frequency and intensity of headaches. Longer-term effects

were not investigated. Six trials compared acupuncture with

various sham interventions and collectively showed a small but

significant reduction of headache frequency for true acupuncture

as compared to sham procedures, over a 6-month period of time. The

remaining trials compared acupuncture with physiotherapy, massage,

or exercise, but none revealed any superiority of acupuncture. For

some outcomes better results were suggested in the control groups

but these findings were difficult to interpret because of

methodological or reporting issues. The authors concluded that

acupuncture "could be a valuable non-pharmacological tool in

patients with frequent episodic or chronic tension-type

headaches."

Acupuncture for Acute Migraine Treatment Few studies

have sought to evaluate the use of acupuncture in acute migraine

treatment. In practicality, patients are unlikely to seek

acupuncture as acute treatment in the early stages of migraine,

and acupuncture treatment on an emergency basis may not be readily

available.[148] Nonetheless, in the first study,[152]

subjects received acupuncture, subcutaneous sumatriptan, or

placebo (subcutaneous injection of NaCl solution); each group

included approximately 60 patients. Although the acupuncture

methodology was not well described, results showed that both

acupuncture and sumatriptan prevented a full migraine attack in

35–36% of patients, as compared to only 18% in the placebo group.

However, sumatriptan provided a faster response, and was also more

effective when used as a second intervention in patients who

developed a full attack.

A second RCT[153] was intended not only to investigate

the use of acupuncture in acute migraine treatment, but also to

examine whether verum acupuncture is more effective than sham

acupuncture in reducing migraine pain. In this multicenter trial,

175 subjects were randomized to a verum acupuncture treatment

group or to 1 of 2 sham acupuncture groups. The 2 sham acupuncture

groups were defined by different methods for locating the

non-acupuncture points. Sham acupuncture group 1 was treated with

acupuncture needles placed halfway between traditional acupuncture

points, and sham acupuncture group 2 was treated with acupuncture

needles placed outside the head region. The primary end point was

headache intensity on a visual analogue scale ranging from 0 (no

pain) to 10 (very severe pain) at 4 time points (0.5, 1, 2, and 4

hours).

Results demonstrated that verum acupuncture was more effective

than sham acupuncture in reducing the pain of acute migraine 2 and

4 hours after treatment, although sham acupuncture was equally as

effective at earlier time points (30 and 60 minutes post

treatment). However, based on descriptions of the treated attacks,

it is possible that up to 50% of patients did not actually have a

migraine headache as defined by the International Headache

Society. Furthermore, the clinical relevance of a 1-point

reduction in headache intensity after several hours, as reported

for the subjects who received true acupuncture, is debatable.[154]

Acupuncture is a viable treatment alternative for migraine

patients, especially those with contraindications to traditional

pharmacological therapy or those with headaches that remain

refractory to multiple trials of medications. Although the

evidence supporting its use in TTH is not as strong, acupuncture

could be beneficial in those patients with frequent episodic or

chronic forms of the disorder. Several studies have also

demonstrated that it is cost-effective in the treatment of

headache.[155–157] In order to continue improving our

understanding of acupuncture in headache treatment, the importance

of trial design cannot be over-stated, as discussed in a 2008

editorial byDiener.[158] Future studies must be held to

the same rigorous standards as those used in investigating the

efficacy of pharmacological therapies.

Oxygen and Hyperbaric Oxygen Therapy Oxygen therapy has

been widely observed to be effective in the treatment of cluster

headache, and is considered to be one of the standard acute

treatments for the disorder.[159,160] Its use in

cluster headache was described by Kudrow in 1981,[161]

when 75% of 52 randomly selected cluster patients demonstrated

significant pain relief after treatment with 100% oxygen inhaled

through a facial mask at 7 L/minute for 15 minutes. Although the

efficacy of high-dose, high-flow oxygen therapy has been commonly

observed in clinical practice since then, only 2 controlled

studies have undertaken to confirm its safety and efficacy in

aborting cluster attacks.[162,163] The use of oxygen

therapy is advantageous in that it can be combined with other

acute therapies, and used several times daily. It is also cheap,

safe, and easy to use. However, treatment may not be readily

available, and although small portable cylinders can be used, some

patients find them inconvenient and unwieldy.

While oxygen inhalation therapy usually refers to the

administration of oxygen at 1 atmosphere (normobaric oxygen), the

use of hyperbaric oxygen therapy (HBOT), which involves 100%

oxygen at environmental pressures greater than 1 atmosphere, has

also been suggested. The rationale for oxygen therapy in headache

treatment is based in the ability of oxygen to constrict distal

cerebral resistance vessels[164,165] while preserving

tissue oxygenation, even at pressures above 1 atmosphere.[166]

This observation led to the proposal that HBOT might be beneficial

in the treatment of vascular-related headaches refractory to

traditional pharmacological therapy. HBOT may be effective via its

effect on several aspects of migraine pathogenesis, via activity

as a serotonergic agonist and an immunomodulator of response to

substance P.[167,168] In addition, the role of HBOT in

moderating inflammatory pathways may be useful in targeting

migraine, both as acute and preventative treatment.[169,170]

Practical limitations of HBOT include the requirement of a

compression chamber and potential adverse effects such as

pressure-related damage to the ears, sinuses, and lungs, temporary

worsening of myopia, claustrophobia and oxygen poisoning.[171]

A recent Cochrane Review[171] assessing the safety and

effectiveness of HBOT and normobaric oxygen therapy (NBOT) in the

treatment and prevention of migraine and cluster headaches found

only 9 small randomized trials, with a total of 201 participants.

Five trials compared HBOT with sham therapy for acute migraine

treatment, 2 compared HBOT to sham therapy for cluster headache,

and 2 assessed NBOT for cluster headache. Although there was some

evidence suggesting that HBOT was effective in acute migraine

treatment as compared to sham therapy, there was no evidence that

it was useful in preventing migraine or reducing the incidence of

nausea, vomiting, or the need for rescue medication. The use of

NBOT in the termination of cluster headaches was supported only by

weak evidence from 2 small randomized trials, but given the safety

and ease of treatment, the use of NBOT will likely continue. There

is insufficient evidence from randomized trials to establish

whether HBOT is effective in the acute treatment of cluster

headache. Lastly, there was no evidence to suggest that either

NBOT or HBOT were effective in the prevention of either migraine

or cluster headaches.

Conclusions

There is a growing role for CAM treatment in the

multidisciplinary management of headache disorders. In addition to

their potential in decreasing headache frequency and intensity,

these modalities also serve to provide the patient with a greater

sense of self-efficacy. However, despite the supporting evidence

discussed in this review, there is still much to be learned about

these therapeutic options and how they influence the course and

outcome of headache disorders. Future research should focus on

extending the current evidence base using updated standards and

more rigorous methodology, and identifying which patients would be

responsive to such approaches.