Individual Enquiry

Research Paper 2010

Title: The efficacy of manual therapy in the treatment of migraine: a systematic review

Author: Denise Cuddigan D.O., B.Sc.

Supervisor: Thomas S. Mars B.Ost., M.A.

The British School of Osteopathy 275, Borough High Street, London SE1 1JE

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ABSTRACT

Background: Migraine is a prevalent neurological condition that may

necessitate longterm prophylactic medication and can lead to significant

absences from work and/or education. A proportion of migraine sufferers seek

treatment from manual therapists, however the benefits derived from the

variety of interventions used are unclear.

Objective: To assess the efficacy of manual therapy for the treatment of

migraine.

Methods: Systematic computerised and hand literature searches for

randomised controlled trials and methodological evaluation using ‘risk of bias’

criteria.

Results: The most methodologically robust trial in this review reported a

reduction in the frequency and severity of migraine headaches associated

with the use of spinal manipulation. Trials involving massage and physical

therapy were methodological weaker.

Conclusions: Despite a lack of methodologically robust trials there is some

evidence that spinal manipulative therapy may be effective for the treatment

of migraine. There is inconclusive evidence concerning the efficacy of

massage therapy and physical therapy. Further studies with larger sample

sizes; avoiding multicomponent interventions; using standardized, validated

outcome measures; and longer term follow-up are recommended.

Keywords: migraine; manual therapy; randomised controlled trial; systematic review.

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Introduction Migraine is a chronic neurological disorder that commonly presents with

nausea, headache and altered perception. (Linde 2006, Sacks 1992). The

classification of migraine is widely accepted and includes subtypes of

migraine both with aura and without aura (International Headache Society

1988).

Studies in North America have shown that 6% of men and 18% of women

suffer from migraine (Stewart et al. 1992). Migraineurs have higher medical

costs, consult physicians more frequently, and miss work and/or study as a

result of the disorder (Edmeads & Mackell 2002, Elston Lafata et al. 2004,

Linde & Dahlof 2004, Stang et al. 2004, Etemad et al. 2005). The aetiology of

migraine is now considered to be both vascular and neurological. It may

involve facilitation of the trigeminal ganglion, which extends caudally to the 3rd

segment of the cervical spine (Silberstein 2004).

There is a considerable body of research that has investigated the efficacy of

pharmacological approaches for prophylaxis of migraine (Gales et al. 2010,

Evers 2008, Stark R.J. & Stark C.D. 2008) and the treatment of acute attacks

(Pascual et al. 2007, Suthisisang et al. 2007, Poolsup et al. 2005). Non-

pharmacological interventions studied include biofeedback, relaxation and

emotional disclosure (Lacroix et al. 1983, Sorbi et al. 1989, D’Souza et al.

2008), acupuncture (Liang et al. 2009, Linde et al. 2009) and yoga (John et al.

2007) as well as manual therapies.

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This systematic review will for the first time focus on the efficacy of manual

therapies for the treatment of migraine independently from other causes of

headache or facial pain. Its aim is to draw together the current evidence and

to contribute to the formation of current best practices for the clinical and

osteopathic management of this prevalent condition.

Evidence based clinical guidelines

Current evidence based clinical guidelines in Scotland (Scottish Intercollegiate

Guidelines Network 2008) and North America (Silberstein 2000) report that

there is insufficient evidence to formulate recommendations about the use of

spinal manipulative therapy (SMT) or massage therapy for the treatment of

migraine.

A recently conducted report (Bronfort et al. 2010), published while this

research project was in progress, reviewed the effectiveness of manual

therapies. The study concluded that there is moderate quality evidence that

SMT is effective for the treatment of migraine, based primarily on the findings

from one randomised controlled trial (RCT) (Nelson 1998) and that evidence

is inconclusive for massage.

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A review of the evidence

The heterogeneous research that has been conducted on the efficacy of

manual therapy for the prophylaxis of migraine headache is reviewed below,

ordered by intervention type.

Spinal manipulative therapy

Three reviews focussed on the effectiveness of spinal manipulation in the

treatment of headache disorders (Vernon 1995, Bronfort et al. 2001, Astin &

Ernst 2002). They each reviewed randomised controlled trials on all types of

headaches including tension-type headache, cervicogenic headache and

migraine. One systematic review (Bronfort 2001) studied the efficacy of spinal

manipulation for chronic headache. The authors concluded that there is

moderate evidence that SMT has short-term efficacy similar to amitriptyline in

the prophylactic treatment of chronic tension-type headache and migraine.

Biondi (2005) reviewed literature covering several types of physical

treatments for all headache disorders. The author concludes that due to a lack

of empirical evidence therapists need to make careful individual assessment

of patients with migraine to ascertain the appropriateness of manual therapy.

Linde (2006) published a broad literature review concerning the non-

pharmacological and drug treatment of migraine prophylaxis and concluded

that both medication and non-pharmacological treatment for migraine may be

effective and that in complex cases a combination of both may be beneficial.

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A comprehensive, systematic review (Bronfort 2004) that evaluated non-

pharmacological treatments of five types of chronic/recurrent headache

concluded that spinal manipulation may be an effective treatment option for

migraine, with ‘a short-term effect similar to that of …amitriptyline…and fewer

side effects’ (Bronfort 2004, p 44).

Three RCTs have investigated the efficacy of SMT for the treatment of

migraine headache. Parker (1978) randomised 85 volunteers to three groups:

i) cervical spinal manipulation (CSM) by a medical doctor/physiotherapist, ii)

CSM by a chiropractor and iii) mobilisation without high velocity thrust (HVT)

by a medical doctor/physiotherapist. The study reported a reduction in

headache intensity and frequency in all three groups but noted that there was

insufficient statistical power to show differences between groups.

A large scale, placebo controlled RCT (Tuchin 2000) randomly allocated 127

participants to two groups: i) chiropractic spinal manipulative therapy (CSMT)

and ii) ‘detuned interferential therapy’, a placebo control. The authors reported

statistically significant reduction in migraine frequency, duration and severity

with the CSMT intervention.

A RCT (Nelson et al.1998) compared spinal manipulative therapy (SMT) to

amitriptyline, an effective, established pharmacological treatment for migraine

(Henry 2007). This study concluded that ‘SMT seemed to be as effective as

amitriptyline and, ‘on the basis of a benign side-effects profile, should be

considered as a treatment option for patients with frequent migraine

headaches’ (Nelson et al. 1998, p.518).

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A case series of 4 patients (Tuchin 1997) reported significant decrease in

migraine frequency and intensity in four adults with chronic migraine

headaches. Tuchin fully described the methods and discussed possible

limitations of research but the findings are weakened by selection bias as all

the patients included in the study were chosen because they responded very

positively to chiropractic treatment.

There are a number of studies evaluating chiropractic spinal manipulation for

the treatment of migraine. Four case reports (Cattley & Tuchin 1999, Davis

2003, Harris 2005, Tuchin 2008) have published accounts of single patient

studies. Each of them reported reduction in migraine frequency and intensity

after a course of chiropractic SMT. In one study (Cattley & Tuchin 1999)

treatment involved chiropractic SMT, massage of neck and shoulder muscles

and home stretching exercises, while another (Harris 2005) included

chiropractic SMT with moist heat, electrical muscle stimulation (EMS) and

trigger point massage. However as each of these studies employs different

multi-component interventions it is difficult to determine the active component

of each intervention and meaningful comparisons between studies are

problematic. Moreover while case studies can provide useful anecdotal

evidence and findings can suggest directions for future research, conclusions

based on the results of case studies cannot be generalised to a larger

population as they are histories of purposively selected individual patients.

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Massage Therapy

Although there are many anecdotal accounts of the efficacy of massage in the

treatment of migraine, little empirical research has been conducted.

A small RCT (Hernandez-Reif et al. 1998) randomised 26 participants to two

groups: i) massage and ii) a wait list control. The massage group had fewer

days of mild headache compared to the control group. As the control group

received no treatment, the degree of placebo, expectation and group effects

in the massage group is uncertain.

A larger RCT (Lawler & Cameron 2006) divided 48 participants randomly to a

group that received massage or a control group that had no treatment. The

massage group showed a moderate but significant decrease in headache

frequency compared to the control group.

A pilot study (Akbayrak et al. 2001) investigated the results of a manual

therapy program composed of hot pack, classical massage and connective

tissue massage in 30 female patients with migraine. The authors reported

statistically significant decreases in pain intensity, frequency and use of

analgesic drugs. As the study lacked a control group there is no comparison

of the manual therapy intervention with other types of manual therapy.

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Physical therapy treatment and exercises

One RCT studied the efficacy of physical therapy (PT) (Marcus 1998).

Participants (n = 88) were randomised to two groups: i) PT and ii) relaxation

and thermal biofeedback (RTB). Clinically significant improvement (defined as

50% or greater reduction in headache index score) was experienced by 13%

of the individuals in the PT group (n=4) and 51% of those in the RTB group

(n=20).

Osteopathic relevance

The General Osteopathic Council Snapshot Survey (2001) found that 17.2%

of patients consult osteopaths with presenting symptoms involving “the head”

(GOsC 2001, p 8). Migraine is a prevalent, often chronic, recurrent condition.

It is possible that a proportion of patients consulting osteopaths with

headache and/or facial pain may be suffering from migraine.

Pharmacological approaches to migraine prophylaxis are ineffective for some

patients or may result in unacceptable side-effects leading to poor patient

compliance with long-term therapy (Moja et al. 2005, D’Amico et al. 2008).

Medication-induced headache is common among patients on long-term drug

therapy for prophylaxis and acute treatment of chronic recurrent headache

and migraine (Zed et al. 1999).

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Studies in Germany and Austria, (von Peter et al. 2002, Gaul et al. 2009)

which surveyed patients attending headache or head and neck pain clinics,

found that complementary and alternative medicine (CAM) use was reported

by over 80% of patients for relief of head pain. The use of CAM has been

found to be more prevalent in patients with chronic recurrent headache (Gaul

et al. 2009).

The prevalence of migraine, the apparent side-effects of pharmacological

interventions, and the popularity of CAM with headache sufferers suggest that

an optimised osteopathic intervention may be appropriate and beneficial to

some individuals susceptible to migraine headaches.

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Methods

This systematic review was conducted between October 2009 and June 2010

adhering to current recommended methodological guidelines. (Furlan et al.

2009)

Search Methods for identification of studies

Electronic searches

A comprehensive search was conducted for relevant RCTs, utilizing eight

databases relevant to both conventional and complementary medical

literature. The following databases were included in the search: AMED

(Alternative Medicine); BNI (British Nursing Index); CINAHL (Cumulative

Index for Nursing and Allied Health Literature); CCTR (Cochrane Controlled

Trials Register); Embase (biomedical database); Highwire (Stanford

University database); PEDro (Physiotherapy Evidence Database); and

Pubmed. The databases were searched from the date of their inception to

April 2010.

Searches were performed using the following medical subject headings

(MeSH terms) and keywords: migraine AND manual therapy; osteopathy;

chiropractic; massage therapy; spinal manipulation; physiotherapy OR

musculoskeletal manipulation.

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The first search was conducted in November and December 2009. Searches

of all eight databases included in this study were updated in April 2010.

Searching other resources

1. Reference lists from all relevant RCTs and reviews were examined for

additional studies.

2. Citation searching using Google Scholar.

3. Hand searching of RCTs, reviews, observational studies and other

relevant literature identifying further related studies.

Eligibility criteria

Eligibility criteria for the study were:

Types of studies

Relevant randomised controlled trials published in peer-reviewed journals

were considered for this review.

Language of studies

The review was limited to studies written in English.

Types of participants

People diagnosed with migraine with aura or migraine without aura.

Types of interventions and controls

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Manual therapies including: osteopathy, chiropractic, physiotherapy and

massage therapy were admitted. Studies that evaluated manual therapy

compared to no therapy or a wait list control; one type of manual therapy

compared to another type of manual therapy; manual therapy compared to a

placebo; or manual therapy compared to an effective established treatment

for migraine were included.

Types of outcome measures

At least one of the following outcome measures was required: headache

frequency; headache intensity; and headache duration.

Assessment of risk of bias in individual studies

The selected RCTS were reviewed by two researchers – the author of this

review (DC) and another final year student at the British School of Osteopathy

(LP) who was also conducting a systematic review, using the criteria listed in

Table 1. (below), as recommended in the 2009 updated guidelines for

systematic reviews in the Cochrane Back Review Group (Furlan et al. 2009).

Disagreements about study eligibility were resolved by discussion between

the reviewers, if necessary consulting a third, experienced reviewer (TM) to

reach consensus.

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Table 1. Sources of Risk of Bias

A. 1. Was the method of randomisation adequate?

Yes/No/Unsure

B. 2. Was the treatment allocation concealed?

Yes/No/Unsure

C. Was knowledge of the allocated interventions adequately prevented during the study?

3. Was the patient blinded to the intervention? Yes/No/Unsure

4. Was the care provider blinded to the intervention?

Yes/No/Unsure

5. Was the outcome assessor blinded to the intervention?

Yes/No/Unsure

D. Were incomplete outcome data adequately addressed?

6. Was the drop-out rate described and acceptable?

Yes/No/Unsure

7. Were all randomised participants analysed in the group to which they were allocated?

Yes/No/Unsure

E. 8. Are the reports of the study free of suggestion of selective outcome reporting?

Yes/No/Unsure

F. Other sources of potential bias:

9. Were the groups similar at baseline regarding the most important prognostic indicators

Yes/No/Unsure

10. Were co-interventions avoided or similar? Yes/No/Unsure

11. Was the compliance acceptable in all groups?

Yes/No/Unsure

12. Was the timing of outcome assessment similar in all groups?

Yes/No/Unsure

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In accordance with current recommendations (Furlan et al. 2009) a study that

has no major flaws and meets 6 or more of the 12 assessment criteria is

considered to have a low risk of bias. A study that meets fewer than 6 of the

criteria or has serious flaws is rated as having a high risk of bias. This

recommendation is based on empirical evidence of the connection between

weak internal validity and over-estimates of effect size in RCTs (van Tulder et

al. 2009).

To pilot-test the risk of bias assessment the two authors reviewed three

similar articles, evaluating the efficacy of manual therapy for the treatment of

tension type headache and cervicogenic headache, that were not included in

this study (Boline et al. 1995, Nilsson et al. 1997, Bove & Nilsson 1998).

Data extraction

In accordance with methodological best practice (Furlan 2009) a standardised

data extraction form was used (See Appendix 1.).

Data from each RCT was independently extracted by the two review

researchers.

Results

Results of electronic and hand searches of literature

Searches were conducted using 8 databases – see Table 2 for search results.

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Table 2. Database search results

Database Number of hits

AMED 8

BNI 0

CINAHL

9

Cochrane

31

Embase

27

Highwire

8

PEDro

13

Pubmed

7

Total

103

Study selection process

Six studies were selected for inclusion in the review. See Figure 1 Study

selection flow chart.

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Fig 1. Study selection flow chart

RCT: randomised controlled trial TENS: transcutaneous electronic nerve stimulation

Merged searches of 9 databases

103

Rejections (62) Duplicate citations

Rejections (8) Migraine not main focus of study - tension headache - cervico-genic headache - cervical pain

Rejections (14) Non RCTs - case studies - pilot study - sysytematic review - literature review

Rejections (12) Not manual therapy interventions - pharmacological - TENS - thermal biofeedback - migraid device - kinesotherapy - acupuncture - psychotherapy

Rejection (1) RCT Lemstra et al (2002) Multicomponent Intervention: exercise, stress management, dietary information, and massage therapy combined

RCTs selected for full review: (6)

Parker et al (1978) Nelson et al (1998) Tuchin et al (2000) Hernadez-Reif et al (1998) Lawler & Cameron (2006) Marcus et al (1998)

6

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One RCT that evaluated massage therapy as a treatment for migraine

(Lemstra et al 2002) was excluded from the review because the intervention

included components that are not manual therapies. The study evaluated a

combined exercise, stress management, dietary information and massage

therapy intervention

Study categorization

The six randomised controlled trials included in the review were sub-divided

into three categories based on intervention type: spinal manipulative therapy;

massage therapy; and physical therapy (see Table 3). All six RCTs

investigated the efficacy different types of manual therapy for migraine

prophylaxis.

Descriptive overview of reviewed studies

See Table 3 Included randomised controlled trials grouped by intervention

type.

Table 3. Included randomized control trials grouped by intervention type.

Study/intervention Population N Age Mean % Male Intervention Control Follow up range age Type

Spinal manipulative therapy

Nelson et al (1998) US patients diagnosed by chiropractor having at least 4 headaches/month

218 18-65 37.9 21% Gp 1: amitriptyline /SMT Gp 2: amitriptyline

4 weeks

Gp 2: amitriptyline Gp 3: SMT

Parker et al (1978) Australian patients medically diagnosed migraine sufferers

85 <55 yrs

Gp 1: 40.5

Gp 1: 36%

Gp 1: chiropractic SMT

Gp 3: TTT by medical practitioner

2 months

Gp 2: 40.8

Gp 2: 52%

Gp 2: SMT by PT medical practitioner

or PT – mobilization not manipulation

Gp 3: 41.3

Gp 3: 29%

Tuchin et al (2000) Patients diagnosed by chiropractor having at least one migraine/month

127 10 to 70

TTT gp: 39.6

TTT gp: 42%

chiropractic SMT Sham detuned inter- ferential therapy-

2 months

Control gp:

37.8

Control gp:

52%

Massage therapy Hernandez-Reif et al (1998)

US patients diagnosed with or without aura/chronic headaches for at least 6 months

26 24-65 39.9 Not reported

Gp 1: massage therapy Gp 2: wait list conrol

5 weeks

Lawler & Cameron (2006)

Diagnosis meeting Int. HA Society classification of migraine

48 12 to 60

41.3 20% 45 minute weekly massage weeks 5 to 10

no treatment daily headache diary with medication use; and sleep

3 weeks

Physical therapy Marcus et al (1998) US patients medically

diagnosed having 1 migraine/week or headache 5days/month

PT gp:30

20-58 PT gp: 36.6

0% Gp 1. Non manipulative physical therapy/stretching and home exercises

Gp 2: RTB 3, 6 /12 months for those with 50% or >50% improvement in HIS

Legend: Gp= group; HIS= Headache Index Score: SMT= spinal manipulative therapy: TTT=Treatment; PT= Physical Therapy; RTB= Relaxation and thermal biofeedback

Spinal manipulative therapy

Three RCTs evaluated spinal manipulative therapy.

Parker (1978) investigated the efficacy of spinal manipulation for the treatment of

migraine sufferers in Australia. The population of 85 (age range 12 – 55 years) was

divided in to three groups and received: SMT by a chiropractor; SMT by a medical

practitioner or physiotherapist; or spinal mobilisation (not including high velocity

thrust) by a medical practitioner or physiotherapist. Patients completed a ‘migraine

form’ at the end of each migraine attack recording the duration of the attack, intensity

of pain, and disability. All three groups showed similar improvement in frequency of

attacks; duration of attacks; severity of pain; and degree of disability, however there

was greater reduction in severity of pain in the chiropractic SMT group.

Nelson et al (1998) conducted a RCT to evaluate the relative efficacy of amitriptyline,

spinal manipulative therapy (SMT) and a combination of both therapies for the

prophylaxis of migraine. A total of 218 patients (age range 18-65) diagnosed with

migraine, each experiencing at least four headaches a month, were randomly

divided into three groups. The interventions were an 8-week course of amitriptyline;

spinal manipulation; or a combination of both therapies. The primary outcome

measure was a Headache Index (HI) score calculated from daily headache diary

records. Clinically important improvement was observed in all three study groups

and results indicated that there was no advantage to combining amitriptyline and

spinal manipulation. The authors noted that the reduction in Headache Index score

may have been partly due to non-specific treatment factors such as the placebo

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effect. Another limitation they reported is that patients in the SMT group received

more attention (14 treatments) than the medication group (3 visits) which may have

affected the outcomes.

Tuchin (2000) assessed the efficacy of chiropractic SMT in the treatment of

migraine. One hundred and twenty-seven volunteers diagnosed with migraine

(having at least one migraine per month), were randomly allocated to two groups

(with a 2:1 ratio): one group received 2 months of chiropractic SMT; and the control

group received a placebo treatment of detuned interferential therapy (electrodes

placed on patients with no current passed through the circuit). Participants

completed a headache diary, recording headache frequency; intensity of pain;

headache duration; and degree of disability. The average response of the treatment

group showed a statistically significant improvement in migraine frequency, duration

and disability when compared to the control group. The authors acknowledged that

the relatively small sample size is a limitation. They noted that the study uses a

multicomponent intervention and does not consider which aspects of chiropractic

SMT had contributed to the reduction in the migraine frequency. Another limitation

discussed is the type of control group (placebo interferential) which does not mimic

SMT.

Massage therapy

Two studies investigated the efficacy of massage therapy in the treatment of

migraine. A small trail (Hernandez-Reif et al. 1998) studied a population of twenty-six

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volunteers who had each had migraine headaches over a period of at least 6

months. Participants were randomly allocated to two groups: massage therapy group

received 30 minute massages twice weekly for 5 weeks; or a wait-list control group.

Outcome measures included a visual analogue pain scale to assess intensity of pain;

Symptom Checklist-90-R (SCL-90-R) (Maruish 2000) to assess depression, anxiety

and depression often associated with headache, Headache log to assess frequency

and intensity of headache, sleep diary and urine serotonin level. Serotonin levels

may be reduced in patients experiencing chronic pain while decreased stress has

been found to be associated with increased production of serotonin (Tappen 1988).

The massage intervention subjects reported less pain, more headache free days,

fewer sleep disturbances and showed an increase in serotonin levels. The authors

concluded that that massage therapy may be ‘an attractive alternative to medication

because it does not produce undesirable side-effects’ (Hernandez-Reif et al 1998 p

9). They did not discuss possible limitations of the study.

A more recent RCT (Lawler & Cameron 2006) evaluated a population of 48

volunteers diagnosed with migraine, randomly allocated to either a massage therapy

group or a control group. The massage group received one 45 minute massage per

week for six weeks, while the control group did not receive any intervention but

completed the same headache diary. A daily headache diary was the main outcome

measure, rating migraine headache intensity four times a day. Other outcome

measures were a diary of over-the-counter (OTC) medication used, a diary recording

sleep quantity and quality rating, stress levels, using the Perceived Stress

Scale(PSS) (Cohen et al. 1983) and the Coping Efficacy Scale (Lawler 1999). It was

found that the massage group reported decreases in migraine frequency. There

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were no significant group differences found for migraine intensity and for use of OTC

medication. The authors noted that the no-treatment control group may have partly

affected the differences between the groups and suggested that further research

includes an appropriate comparison treatment for the control group.

Physical therapy

Marcus et al (1998) investigated the efficacy of physical therapy (PT) in the

treatment of migraine. The intervention involved treatment from a physical therapist

and a concurrent home exercise program. The participants were all females aged

20-58 years, diagnosed with migraine (having at least one headache a week or on a

total of 5 days each month). The participants were randomly assigned to two groups:

to receive PT or a relaxation/thermal biofeedback (RTB) control. Patients in each

group received four weekly one-hour treatment sessions. The PT subjects were

given a home exercise program and asked to do the exercises twice daily for 30

minutes each time. Participants in the RTB group were asked to do home practice

sessions for 20-30 minutes twice daily. Headache severity was recorded four times

each day. Two weeks of diary recordings were used to calculate a baseline

Headache Index (HI) equivalent to the mean headache severity over the 2-week

recording period. Other outcome measures included self-report inventories: The

West Haven-Yale Multidimensional Pain Inventory (MPI) (Kerns et al. 1985) and the

Center for Epidemiological Studies depression scale (CES-D) (Radloff 1979), both

administered by a psychologist. The authors considered clinically important

improvement in headache to be a 50% or more reduction in HI score. They found

that 13% of the PT group (n=4) and 51% of the RTB group (n=20) reported greater

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than 50% reduction in HI score suggesting that RTB has greater efficacy as a

treatment for migraine. The authors did not discuss limitation of the study but did

recommend future research with larger sample sizes.

Assessing risk of bias

Risk of bias in the reviewed studies was assessed following the updated guidelines

for systematic reviews from the Cochrane Back Review Group (CBRG) (Furlan et al.

2009) and the results are summarized in Table 4. The risk of bias assessment

criteria are listed in Table 1.

Table 4 The reviewed randomised trials scored and ranked according to the risk of bias criteria Criteria 1 2 3 4 5 6 7 8 9 10 11 12 Total Yes Total Total Rank Study(Year) Y/12 (%) N/12 U/12

Nelson et al (1998)

Y Y N N U Y Y Y Y Y U Y 8 67 2 2 1

Lawler & Cameron (2006)

Y U N N U Y U Y Y U Y U 5 47 2 5 2

Parker et al (1978)

U N N N U Y U U Y Y Y Y 5 47 3 4 2

Tuchin et al (2000)

N Y U N U Y U N Y U U Y 4 33 3 5 3

Marcus et al (1998)

U U N N U Y U U Y U U Y 3 25 2 7 4

Hernandez-Reif et al (1998)

Y U N N N U U U N U U Y 2 17 4 6 5

Y=yes, N=no, U=unclear

See Table 1 for risk of bias assessment criteria. Summary of the risk of bias criteria used

1. Was method of randomisation adequate? 7. Participants analysed in allocated groups? 2. Was treatment allocation concealed? 8. Free of suggestion of selective outcome reporting? 3. Was patient blinded to the intervention? 9. Were the groups similar at baseline? 4. Was the care provider blinded? 10. Were co-interventions avoided or similar? 5. Was the outcome assessor blinded? 11. Was compliance acceptable in all groups? 6. Was drop-out rate described and acceptable? 12. Was timing of outcome assessment similar in all groups?

All but one of the six trials included group profiles that were similar at baseline

(criteria 9) and met item 6 for description of drop-out rate and adequate drop-

out rate. Items 3, 4 and 5 concerning blinding of the patient to the intervention,

blinding of the care provider and blinding of the outcome assessor were not

met by any of the reviewed trials. In some cases it may not have been

practically possible to blind patients or care providers when the intervention

compared for example, SMT to amytriptyline (Nelson et al.1998).

The study conducted by Nelson et al (1998) met 8 of the 12 assessment

criteria and was the most methodologically robust trial in this review, having a

low risk of bias. The remaining 5 trials met between 2 and 5 of the

assessment criteria and are therefore rated as having a high risk of bias. More

than half of these trials did not use an adequate method of randomisation

(criteria 1). An adequate method of randomisation is important to ensure that

the baseline group profiles are similar (Hagino 2003).

The internal validity of these five studies was weakened by failure to conceal

the treatment allocation (criteria 2). There is empirical evidence that failure to

conceal treatment allocation can lead to significant exaggeration of the effects

of an intervention (Chalmers et al. 1983). Allocation concealment is frequently

unreported in published RCTs although it is a simple methodology to

implement and an important factor in reducing bias (Jadad & Eskin 2007).

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The five studies also failed to report clearly whether all randomised

participants were analysed in the group to which they were originally allocated

(criteria 7). If participants who withdraw from a trial is not analysed in the

group they were originally allocated to it may bias results, generally in favour

of the intervention (Greenhalgh 2006).

Four of the six trials were weakened by suggestion of selective outcome

reporting (criteria 8). This is a common source of bias in RCTs and generally

leads to reporting that highlights positive results that favour the intervention

investigated (Jadad & Eskin 2007).

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Discussion

An extensive search of eight databases yielded six RCTs evaluating manual

therapy for the prophylaxis of migraine. The six studies differed significantly in

baseline criteria as well as in the type of intervention; control therapy and

outcome measures used. Clinical heterogeneity prevented meta-analysis of

pooled data from the studies and limits the generalisability the findings.

The RCT that ranked most highly on the risk of bias assessment (Nelson et

al.1998) met 8 out of 12 of the assessment criteria. It was the only trial that

met the criteria for analysing all randomised participants in the group to which

they were allocated. The results of this methodologically robust study showed

that SMT was as effective as amitriptyline an established, effective

pharmacological treatment for migraine. The authors stated that spinal

manipulation has ‘a benign side effects profile’ (Nelson et al. 1998, p 518).

While this may be true in the majority of cases, cervical spinal manipulation

may have a very small potential risk of serious adverse events following

treatment, which must be considered in the formation of clinical guidelines

(Ernst 2007, Carnes et al. 2010).

Adverse events as a result of the treatment intervention were reported in only

one of the studies (Nelson et al. 1998). Poor reporting of adverse events can

lead to inaccurate conclusions about the interventions investigated (Ioannidis

2009, Pitrou et al. 2009).

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Two RCTs met 5 of the 12 risk of bias assessment criteria (Parker et al. 1978,

Lawler et al. 2006). Parker et al. (1978) found that cervical SMT was as

effective as cervical mobilization without manipulation. However the study was

weakened by failure to report the details of the method of randomisation and

there were suggestions of selective reporting of outcomes.

Lawler et al (2006) did use an adequate method of randomisation but the

study had methodological weaknesses including failing to clearly report if co-

interventions were avoided or similar, and not having the same timing of

outcome measures in all groups.

The lowest ranking 3 RCTs (Tuchin et al. 2000, Marcus et al. 1998,

Hernandez-Reif 1998) met between 2 and 4 of the 12 risk of bias assessment

criteria and evidence from these trials therefore cannot be considered reliable.

To summarise there is evidence of efficacy of SMT for the treatment of

migraine, based on the results of one high-quality RCT (Nelson et al. 1998).

There is inconclusive evidence of the efficacy of massage therapy for the

treatment of migraine based on the results of the study by Lawler et al (2006).

The only study investigating the efficacy of physiotherapy for the treatment of

migraine (Marcus et al.1998) is methodologically weak and shows unclear

reporting of methodology and results, and selective outcome reporting. There

is therefore currently no reliable evidence about the efficacy of physiotherapy

for the treatment of migraine.

30

A recent review ‘Effectiveness of manual therapies: the UK evidence report’

(Bronfort 2010) was published in February 2010, while this review was in

progress. The purpose of the report was to provide ‘a succinct but

comprehensive summary of the scientific evidence regarding the

effectiveness of manual therapy for the management of a variety of

musculoskeletal and non-musculoskeletal conditions’ (Bronfort 2010 p1).

The authors concluded that there is moderate evidence for the efficacy of

SMT for the treatment of migraine and inconclusive evidence of benefits of

massage. This current review confirms these findings, however it is important

to take into consideration that the evidence in favour of SMT for the treatment

of migraine is based on the findings of one high-quality RCT (Nelson et al.

1998) and another RCT of weaker methodological quality (Tuchin et al. 2000).

Clinical importance of manual therapy for migraine prophylaxis

One RCT in this review reported that the group that received chiropractic SMT

‘showed statistically significant improvement in migraine frequency’ (Tuchin

1998, p 93). Pre-treatment migraine frequency was 7.5/month compared to

6/month post-treatment. Though statistically significant the results of this

intervention may not represent a difference that is of clinical importance.

There is considerable heterogeneity between studies in the degree of

reduction in headache symptoms that the authors interpret as clinically

important. Marcus (1998) used a headache index representing the mean

headache severity over a 2 week recording period and described results as

clinically significant if there was a 50% or more reduction in headache index.

31

In another study (Nelson 1998) headache index was calculated as the weekly

sum of each patient’s daily headache score and the author reported results for

>20%, >40% and >60% reduction in headache index representing three levels

of clinical importance.

Some studies do not refer to clinical importance and simply report the

statistical significance of their findings (Hernandez-Reif et al.1998, Parker et

al. 1998, Tuchin et al. 2000, Lawler & Cameron 2006).

Implications for osteopathic practice

This systematic review of the efficacy of manual therapy for migraine

prophylaxis confirms that there is moderate evidence to support the efficacy of

spinal manipulation in the treatment of migraine. This is based primarily on

one methodologically strong RCT (Nelson 1998). In this RCT the intervention

group received spinal manipulation to the cervical spine and/or thoracic spine

as considered appropriate by the therapist as well as 5-10 minutes of soft

tissue or trigger point therapy. There is uncertainty about the active

component of this multicomponent intervention. Future research comparing

the efficacy of spinal manipulation and soft tissue may provide evidence

relevant to osteopaths. If for example soft tissue techniques are found to be

effective for the treatment of migraine this may be beneficial in cases where

manipulation is contraindicated. Furthermore the integration of current

empirical evidence with a distinctly structural osteopathic paradigm may

enable osteopaths to be more effective in treating patients with this prevalent

condition.

32

Limitations of this study

Despite the structured methodology of systematic reviews they are vulnerable

to many possible sources of bias (De Bei 1998). Cumulative methodological

scoring of the quality of clinical trials in systematic reviews may be

questionable (Joni et al.1999). Methodological evaluation may be more robust

if multiple scoring scales are used (Eggar et al. 2001).

The literature search for this study was restricted to articles in English as the

research project had no funding or facilities for translation. This review

included only RCTs published in peer-reviewed journals with no searching of

unpublished or ‘grey’ literature. There is a possibility of both language and

publication bias in the selection of studies for review.

The search identified studies which evaluated the use of manual therapy for

migraine prophylaxis. It is possible however that a broader search strategy

may have yielded studies concerning treatment to alleviate acute attacks of

migraine.

Reviewers were not blinded to the author, affiliation, journal and institution for

each of the six RCTs included. This was a pragmatic decision. However the

evidence regarding the significance of blinding is contradictory: one study

(Jadad et al.1996) reported that in the assessment of quality of RCTs blinding

lead to lower and more consistent evaluation; however another (Varhagen et

33

al.1998) reported that blinded and un-blinded assessment had little affect on

the quality scoring of clinical trials and therefore did not advocate blinding.

If sufficient data is not available in a published article ideally the authors of the

study would be contacted directly in order to request more information. Due to

the time constraints of this review contacting individual authors was not

possible. Many of the reviewed RCTs had a high number of ‘unclear’ criteria

in the risk of bias assessment (Table 4) due to omissions or lack of clarity in

the reporting of the trial. By contacting authors directly it may have been

possible to clarify these uncertainties.

Implications for research

The diagnosis of migraine may be complicated by the wide range of common

presenting signs and symptoms and the overlap of symptom pattern with

other headache types (Kaniecki 2002). In clinical trails there is a potential for

variation in reliability of diagnosis and a range of migraine severity in the study

population.

All of the RCTs in this review involved multicomponent interventions. This

results in uncertainty concerning the active component of the intervention and

evaluating clinical applicability and may limit the possibility of comparison

between studies.

34

The RCTs utilized heterogeneous controls which can lead to difficulties

interpreting results due to expectation or placebo effects. Appropriate control

groups are needed to minimise these effects.

There is considerable heterogeneity of outcome measures used in the RCTs

in this review. The use of robust, validated and reliable outcome measures

may facilitate the pooling data in future studies.

Most RCTs evaluating manual therapy for the treatment of migraine rely on

self-report inventories (a diary of headache frequency, intensity and duration)

as the primary outcome measures, these are subjective measures. “In trials

with subjectively assessed outcomes lack of adequate concealment and

blinding tend to produce over-optimistic estimates of the effect of

interventions.” (Wood et al 2008). Efforts to ensure appropriate concealment

and blinding where possible could help to minimise this potential for bias in

future research.

The fluctuating natural history of migraine makes ascription of clinical

significance to an intervention problematic. This highlights the relevance of

repeated follow-ups evaluating migraine frequency and severity for example

2, 4 and 6 months after the intervention phase of a study.

As there are a small number of published RCTs in this field a structured,

narrative review, including cohort studies, pilot studies and case studies,

would be helpful to provide a fuller context for clinicians.

35

Conclusion

There is moderate evidence that spinal manipulation is effective in the

treatment of migraine and inconclusive evidence that massage therapy may

be helpful.

High-quality studies with: larger sample sizes; simpler, more reproducible

interventions; standardized, validated outcome measures; and longer follow-

ups are needed to provide robust evidence to guide clinical practice for the

treatment of migraine.

Competing interests

The principal reviewer (DC) is a student of osteopathy conducting a research

project as part of an osteopathic degree. To minimise bias in future systematic

reviews it would be preferable to have reviewers who are not manual

therapists.

No funding was received for this research project.

36

Acknowledgements

I would like to express my gratitude to all who have helped to make this study

possible, including Will Podmore, James Barclay and Claire O’Donovan, our

invaluable librarians at the BSO, and Melanie Wright for her much appreciated

support and research advice.

Special thanks to my supervisor, Tom Mars, for his constant guidance,

inspiration and encouragement, which made this research project a rich

learning experience.

Appendix 1. Data Extraction Form. Date of extraction: Study citation: A. 1. Was the method of randomisation adequate?

Yes

No Unsure Page/ paragraph Reviewers comments

B. 2. Was the treatment allocation concealed?

C. Was knowledge of the allocated interventions adequately prevented during the study?

3. Was the patient blinded to the intervention?

4. Was the care provider blinded to the intervention?

5. Was the outcome assessor blinded to the intervention?

D. Were incomplete outcome data adequately addressed?

6. Was the drop-out rate described and acceptable?

7. Were all randomised participants analysed in the group to which they were allocated?

E. 8. Are the reports of the study free of suggestion of selective outcome reporting?

F. Other sources of potential bias:

9. Were the groups similar at baseline regarding the most important prognostic indicators

10. Were co-interventions avoided or similar?

11. Was the compliance acceptable in all groups?

12. Was the timing of outcome assessment similar in all groups?

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