cochrane database of systematic reviews (reviews) || herbal medicine for low back pain

Herbal medicine for low back pain (Review)

Gagnier JJ, van Tulder MW, Berman BM, Bombardier C

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2011, Issue 2

http://www.thecochranelibrary.com

Herbal medicine for low back pain (Review)

Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

10DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iHerbal medicine for low back pain (Review)


[Intervention Review]

Herbal medicine for low back pain

Joel J Gagnier1, Maurits W van Tulder2, Brian M Berman3, Claire Bombardier4

1Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. 2Department of Health

Sciences, Faculty of Earth and Life Sciences, VU University, Amsterdam, Netherlands. 3Center for Integrative Medicine, University of

Maryland School of Medicine, Baltimore, Maryland, USA. 4Institute for Work & Health, Toronto, Canada

Contact address: Joel J Gagnier, Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington

Heights, Rm M5158, Ann Arbor, MI, 48109-2029, USA. [email protected].

Editorial group: Cochrane Back Group.

Publication status and date: Edited (no change to conclusions), published in Issue 2, 2011.

Review content assessed as up-to-date: 14 December 2005.

Citation: Gagnier JJ, van Tulder MW, Berman BM, Bombardier C. Herbal medicine for low back pain. Cochrane Database of SystematicReviews 2006, Issue 2. Art. No.: CD004504. DOI: 10.1002/14651858.CD004504.pub3.


A B S T R A C T

Background

Low-back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients

with chronic low-back pain use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal

medicines have been purported for use in low-back pain.

Objectives

To determine the effectiveness of herbal medicine for non-specific low-back pain.

Search methods

We searched the following electronic databases: Cochrane Complementary Medicine Field Trials Register (Issue 3, 2005), MEDLINE

(1966 to July 2005), EMBASE (1980 to July 2005); checked reference lists in review articles, guidelines and retrieved trials; and

personally contacted individuals with expertise in this very specialized area.

Selection criteria

We included randomized controlled trials, examining adults (over 18 years of age) suffering from acute, sub-acute or chronic non-

specific low-back pain. The interventions were herbal medicines, defined as plants that are used for medicinal purposes in any form.

Primary outcome measures were pain and function.

Data collection and analysis

Two authors (JJG & MVT) conducted the database searches. One author contacted content experts and acquired relevant citations. Full

references and abstracts of the identified studies were downloaded. A hard copy was retrieved for final inclusion decisions. Methodological

quality and clinical relevance were assessed separately by two individuals. Disagreements were resolved by consensus.

Main results

Ten trials were included in this review. Two high quality trials examining the effects of Harpagophytum Procumbens (Devil’s Claw) found

strong evidence that daily doses standardized to 50 mg or 100 mg harpagoside were better than placebo for short-term improvements

in pain and rescue medication. Another high quality trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx).

Two trials examining the effects of Salix Alba (White Willow Bark) found moderate evidence that daily doses standardized to 120 mg or

1Herbal medicine for low back pain (Review)


mailto:[email protected]

240 mg salicin were better than placebo for short-term improvements in pain and rescue medication. An additional trial demonstrated

relative equivalence to 12.5 mg per day of rofecoxib. Three low quality trials on Capsicum Frutescens (Cayenne), examining various

topical preparations, found moderate evidence that Capsicum Frutescens produced more favourable results than placebo and one trial

found equivalence to a homeopathic ointment.

Authors’ conclusions

Harpagophytum Procumbens, Salix Alba and Capsicum Frutescens seem to reduce pain more than placebo. Additional trials testing

these herbal medicines against standard treatments are needed. The quality of reporting in these trials was generally poor. Trialists

should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

P L A I N L A N G U A G E S U M M A R Y

Herbal medicine for low-back pain

Significance of the review

Back pain is common, affecting as much as 35% of the population in a given month. Non-specific low-back pain is defined as pain

between the lowest rib and the bottom of the buttocks that is not caused by serious, underlying problems such as rheumatoid arthritis,

infection, fracture, cancer, or sciatica due to a herniated disc or other pressure on nerves. Oral and topical herbal medicines are being

used to treat many conditions; several are used for back pain and have been tested in clinical trials.

Description of the trials

Three oral herbal medications were tested in ten randomized controlled trials that included 1567 adults with non-specific acute or

chronic low-back pain. Two oral herbal medications, Harpagophytum Procumbens (Devil’s Claw) and Salix Alba (White Willow Bark),

were compared with placebo (fake pills) and with rofecoxib (Vioxx). Topical Capsicum frutescens (Cayenne) was compared with placebo

and a homeopathic gel.

Findings

Devil’s Claw, in a standardized daily dose of 50 mg or 100 mg harpagoside, seemed to reduce pain more than placebo; a standardized

daily dose of 60 mg reduced pain about the same as a daily dose of 12.5 mg of Vioxx. While Willow Bark, in a standardized daily dose

of 120 mg and 240 mg of salicin reduced pain more than placebo; a standardized daily dose of 240 mg reduced pain about the same as

a daily dose of 12.5 mg of Vioxx. Cayenne was tested in plaster form and reduced pain more than placebo and about the same as the

homeopathic gel Spiroflor SLR. Adverse effects were reported, but appeared to be primarily confined to mild, transient gastrointestinal

complaints.

Limitations

Most of the trials were of moderate or high quality, but they only tested the effects of short term use (up to six weeks). The authors

of half of the studies were judged to have a potential conflict of interest and two others did not discuss conflict of interest. Vioxx has

been withdrawn from the market because of adverse effects, so all three substances should be compared with readily available pain

medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, to test for relative effectiveness and safety.

Conclusion

Although there are good results with three herbal medicines in short-term trials, with strong evidence for a particular form of one of

the herbal medicines, there is no evidence yet that any of these substances are safe and useful for long term use.



B A C K G R O U N D

Low-back pain and related disability are major public health prob-

lems across industrialized nations. As a result, the past 15 years

have seen an intensive research effort to identify effective treatment

and management strategies for low-back pain (Mounce 2002).

The one-month prevalence of low-back pain is reported to be be-

tween 35% and 37%, with a lifetime prevalence between 70%

and 85%, peaking between 45 and 59 years of age (Papageorgiou

1995; Andersson 1999). In the United States, back pain is the

most common cause of disability in those under 45 years of age

(Borkan 1995) and back sprains and strains represent about one

quarter of work-related injuries resulting in lost work-days (Dept

Labor 1995). Low-back pain is the second most frequent cause

of work absence in industrialized nations (Praemer 1992) and is a

frequent reason for visits to a physician (Coste 1994; Andersson

1999). It has been estimated that in the United States, back pain

has associated direct costs of US $20 billion and indirect costs of

between US $75 and 100 billion (Borkan 1995). In the United

Kingdom, costs associated with low-back pain are estimated to

be over £500 million (Little 1996). This amounts to substantial

societal loss of productivity and an economic burden for health-

care systems in many industrialized countries (Mounce 2002).

The traditional treatment of low-back pain includes medication,

tissue stimulation (e.g. TENS, ultrasound), rest and orthotics (e.g.

braces; Cherkin 1993). Although systematic reviews suggest that

few of these have enough evidence to suggest benefit, it does appear

that acute low-back pain can usually be effectively managed by en-

couraging activity, reassurance and short-term symptom control

(analgesics or non-steroidal anti-inflammatory drugs (NSAIDs);

van Tulder 2002a). Treatments that demonstrate some effective-

ness for the management of chronic low-back pain include ex-

ercise therapy, behavioural treatment and multidisciplinary treat-

ment programs (van Tulder 2002b). To alter beliefs about back

pain that are correlated with impairment or disability is one of the

major challenges in low-back pain management (Borkan 1995).

Research in complementary and alternative medicine (CAM) has

blossomed in the past 10 years. Rigorous literature is growing

steadily and is subsequently clarifying the validity of these tech-

niques. Specifically, the number of randomised trials of comple-

mentary treatments has doubled approximately every five years

(Vickers 2000) and currently, the Cochrane Complementary

Medicine Field Trials Registry contains over 6500 randomized

and controlled clinical trials. In addition, CAM teaching insti-

tutions are now beginning to teach principles of evidence-based

medicine and clinical epidemiology (Mills 2002; Sierpina 2002).

These initiatives are well placed, given the large number of visits

to CAM practitioners (Millar 2001). A recent population survey

in Canada found that 2.2 million women and 1.6 million men

visited a CAM practitioner during 1998-1999 (Millar 2001). Of

these, more than 26% of individuals who reported chronic pain

visited an alternative practitioner during the previous year, com-

pared with only 15% of those who did not report chronic pain.

Those who reported back pain had a higher percentage of visits

to alternative practitioners than any other pain condition. More

specifically, 37% of the individuals who reported back pain visited

an alternative practitioner, compared with only 17% of the entire

population (Millar 2001). Similar percentages have been found in

surveys conducted in the United States (Astin 2000; Druss 1999;

Eisenberg 1998).

Several herbal medicines have been reported to be treatments

for various types of pain. These include: Camphora Molmol,

Capsicum Frutescens, Salix Alba, Maleluca Alternifolia, Angelica

Sinensis, Aloe Vera, Thymus Officinalis, Menthe Peperita, Arnica

Montana, Curcuma Longa, Tancaetum Parthenium, Harpago-

phytum Procumbens, and Zingiber Officinicalis (Blumenthal

1998). Many of these herbs have been the subject of extensive

biochemical research, resulting in the delineation of their pharma-

cological and physiological effects (Mills 2000). For example, the

mechanism of Capsicum Frutescens is partially related to its abil-

ity to deplete substance P (Keitel 2001). Salix Alba is a platelet in-

hibitor and analgesic, and Harpagophytum Procumbens has anal-

gesic and anti-inflammatory properties (Chrubasik 1996). In ad-

dition, some of these herbal species have been clinically tested for

the relief of symptoms of low-back pain (Mills 2000; Stam 2001;

Laudahn 2001a; Krivoy 2000).

Given the large public health and economic burden low-back pain

causes and the large number of such sufferers who regularly visit

CAM practitioners, a systematic review of these practices was war-

ranted.

O B J E C T I V E S

To determine the effectiveness of herbal medicine compared to

placebo, no intervention, or other interventions in the treatment

of non-specific low-back pain.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Only randomized controlled trials (RCTs) were included.

Types of participants

Trials included adults (older than 18 years of age), suffering from

acute (lasting up to six weeks), sub-acute (lasting six to 12 weeks)

or chronic (lasting longer than 12 weeks) non-specific low-back

pain.



Low-back pain was defined as pain localized to the area between

the costal margin or the 12th rib to the inferior gluteal fold.

Non-specific low-back pain indicated that no specific cause was

detectable, such as infection, neoplasm, metastasis, osteoporosis,

rheumatoid arthritis, fracture, inflammatory process or radicular

syndrome (Waddell 1996).

Types of interventions

For the purpose of the present review, an herbal medicine was de-

fined as all or part of a plant that was used for medicinal purposes,

administered orally (ingestion) or applied topically. This definition

did not include plant substances that were smoked (e.g. Cannabis

Sativa), individual chemicals that were derived from plants or syn-

thetic chemicals that were based on constituents of plants. How-

ever, Cannabis Sativa, or other plants that can be smoked, will be

considered herbal medicines for this review if they were ingested.

Various forms of oral herbal medicine include: standardized ex-

tracts (encapsulated or tablet form), tinctures (alcohol, glycerine,

etc), dried herb (encapsulated or tablet form), raw whole herb infu-

sion (e.g. tea) and decoction (e.g. boiled down tea). Topical herbal

applications include: ointments, essential oils, creams (petroleum

or glycerine based), powders, plasters, and poultices. Opioids will

be excluded from this review, given they bridge the definitions of

herbal medicine and analgesic.

Types of outcome measures

1. Pain intensity [e.g., visual analogue scale (VAS), numerical rat-

ing scale (NRS)] and proportion of pain free patients.

2. Back pain specific functional status measured by validated in-

struments [e.g. Roland Disability Questionnaire (RDQ), Owestry

Disability index (ODI)]

3. Overall improvement (% reporting subjective improvement,

NRS)

4. Return to Work or Work Status (% of population, number of

days of absenteeism).

Search methods for identification of studies

We searched the following electronic databases:

1. Cochrane Complementary Medicine Field Trials Registry (Issue

3, 2005)

2. MEDLINE (1966 to July 2005)

3. EMBASE (1980 to July 2005)

4. Clinical Evidence (January 2005)

We used the search strategy recommended by the Cochrane Back

Review Group for both MEDLINE and EMBASE (van Tulder

2003; van Tulder 1997). Terms included: low back pain, backache,

lumbago. The specific search terms for randomized controlled tri-

als (Robinson 2002) and herbal medicine for both MEDLINE and

EMBASE are listed in Appendix 1 and Appendix 2. The search

terms were modified as necessary for the Cochrane Complemen-

tary Medicine Field Trials Registry.

We also reviewed reference lists in review articles, guidelines and

in the retrieved trials and contacted individuals with expertise in

herbal medicine and low-back pain (JJG) to identify additional

trials. Non-English articles were translated and discussed by JJG

and MvT following the same procedures described below.

Data collection and analysis

One author (JJG) conducted the electronic searches. Two authors

(JJG & MvT) independently selected studies based on title, ab-

stract, and keywords. Studies that met the inclusion criteria were

included in the review. If it was not clear from the title and abstract

if a study fulfilled the inclusion criteria, a full copy was retrieved

for final selection. A consensus method was used to resolve dis-

agreements.

Methodological quality assessment

Methodological quality was independently assessed by two authors

(JJG & MvT). Given one of the authors’ (JJG) familiarity with

the literature, studies were not blinded for authors, institution or

journal. The eleven items reflecting internal validity, together with

operational definitions, recommended by the Back Group in their

updated method guidelines for systematic reviews were used to

assess methodological quality (van Tulder 2003; Table 1). Each

criterion was scored as “yes”(Y), “no”(N) or “don’t know”(DK).

’Yes’ indicated that the criterion was met. ’No’ reflected the lack

of fulfilment of that criterion. ’Don’t know’ reflect the fact that

there was insufficient information to determine if this criterion

was fulfilled or not. A trial was considered high quality if more

than 50% (6/11) of internal validity items were met.

Data extraction

Two authors (JJG & MvT) independently extracted the data from

each trial, using a standardized form. The following data were ex-

tracted from each study: recruitment, characteristics of the study

population (age, gender), setting (e.g. year, country of origin),

duration of low-back pain (acute, subacute, or chronic), previous

treatment for low-back pain, number of patients initially recruited,

number of patients randomized, number of drop-outs or with-

drawals, duration of intervention, type of herbal medicine used

(plant name and form of delivery and dosage), standardization in-

formation (e.g. percentage of active constituent per delivery unit),

characteristics of the control intervention (type and duration),

types of outcome measures, summary statistics, timing of outcome

assessments, compliance, adverse effects due to intervention, and

author’s conclusions as to the effectiveness of the intervention.



Clinical relevance

The clinical relevance of each study was independently assessed by

two authors, using these five questions:

1. Are the patients described in detail so that you can decide

whether they are comparable to those that you see in your prac-

tice?

2. Are the interventions and treatment settings described well

enough so that you can provide the same for your patients?

3. Were all clinically relevant outcomes measured and reported?

4. Is the size of the effect clinically important?

5. Are the likely treatment benefits worth the potential harms?

Data analysis

Due to insufficient data and clinically heterogeneity, a qualitative

analysis was conducted, using a rating system consisting of five

levels of evidence (van Tulder 2003):

1. Strong evidence - consistent findings among multiple high

quality RCTs

2. Moderate evidence - consistent findings among multiple low

quality RCTs and/or one high quality RCT

3. Limited evidence - one low quality RCT

4. Conflicting evidence - inconsistent findings among multiple

RCTs

5. No evidence from trials - no RCTs

Sensitivity analyses were carried out to explore the results when

definitions of high quality trials were 40% and 60% fulfilment of

internal validity criteria. We also conducted an additional sensi-

tivity analysis, assuming the validity criteria that were scored as

“DK” were, in fact, positive.

Subgroup analyses were conducted separately for acute low-back

pain (lasting less than six weeks), subacute low-back pain (lasting

from six to 12 weeks) and chronic low-back pain (lasting longer

than 12 weeks).

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies.

A total of 295 references were identified from Cochrane Comple-

mentary Medicine Field Trials Registry, MEDLINE, EMBASE,

Clinical Evidence searches and by contacting content experts. Af-

ter reviewing titles and abstracts, 266 citations were excluded for

not meeting the predetermined inclusion criteria. Twenty-nine

papers were retrieved in full, 19 of which were excluded due to

improper study design (not RCT). A total of 10 citations met in-

clusion criteria and were included in this review (Chrubasik 1996;

Chrubasik 1999; Chrubasik 2000; Chrubasik 2001; Chrubasik

2003; Frerick 2003; Ginsberg 1987; Krivoy 2001; Keitel 2001;

Stam 2001).

Three studies used an oral form of the herbal species Harpago-

phytum Procumbens (Devil’s Claw; Chrubasik 1996; Chrubasik

1999; Chrubasik 2003), three used oral Salix Alba (White Wil-

low Bark; Chrubasik 2000; Chrubasik 2001; Krivoy 2001) and

four used topical Capsicum Frutescens (Cayenne; Frerick 2003;

Ginsberg 1987; Keitel 2001; Stam 2001).

Four studies compared various oral herbal medicines with placebo

(Chrubasik 1996; Chrubasik 1999; Chrubasik 2000; Krivoy

2001). Two studies compared oral herbal medicines to standard

pain medications (Chrubasik 2001; Chrubasik 2003). Three stud-

ies compared topical herbal medicines to placebo (Frerick 2003;

Ginsberg 1987; Keitel 2001). One study compared a topical herbal

medicine to a topical homeopathic medicine (Stam 2001).

The three studies using Harpagophytum Procumbens included

patients with acute exacerbations of chronic non-specific low-back

pain (Chrubasik 1996; Chrubasik 1999; Chrubasik 2003). Sim-

ilarly, the three trials examining the effects of Salix Alba prepara-

tions included homogeneous populations with acute episodes of

chronic non-specific low-back pain (Chrubasik 2001; Chrubasik

2000; Krivoy 2001). One of the trials using a topical Capsicum

Frutescens ointment included patients with acute mechanical low-

back pain (Ginsberg 1987). Two additional trials using a Cap-

sicum pain plaster included participants with chronic non-specific

low-back pain (Frerick 2003; Keitel 2001). One trial using a top-

ical Capsicum ointment included a sample of patients with either

newly occurring acute low-back pain or acute episodes of chronic

low-back pain (Stam 2001).

Three of these studies (Chrubasik 1996; Chrubasik 1999; Frerick

2003) used a relatively unknown low-back pain scale, the Arhus

Index, which was designed to monitor outcomes of clinical trials of

low-back pain. The Arhus Index is a back-pain specific index that

includes physical impairment, pain, and disability scores, which

are summed into a total score (Manniche 1994). The pain scale

is rated by the patient and includes back pain and leg pain, with

a score that ranges from 0 to 60. The disability scale consists of

a questionnaire that asks about 15 daily tasks, with a score that

ranges from 0 to 30. The physical impairment score is obtained

by scoring on a deep knee bend, a modified Schober’s test, a low-

back strength test and a measure of analgesic use, with a total

combined score ranging from 0 to 40. The higher the scores,

the more physical impairment, pain and disability. This test takes

approximately 15 minutes to complete. It has been shown to be a

valid and reliable measure of low-back pain (Manniche 1994).

In the trials using Harpagophytum Procumbens, Chrubasik 1996

used a standardized dosage of 50 mg harpagoside per day or 2400

mg of the crude extract; Chrubasik 1999 used daily dosages of the

proprietary extract WS 1531 at 600 and 1200 mg of the crude

herb, which was the equivalent of 50 and 100 mg harpagoside;

and Chrubasik 2003 used a proprietary extract of Doloteffin, con-

taining a daily dose of 60 mg harpagoside, or 12.5 mg rofecoxib



(Vioxx).

In the trials using White Willow Bark extract, Chrubasik 2000

utilized an extract containing 0.153 mg salicin per mg and made

comparisons between daily dose of 120 mg salicin, 240 mg of

salicin and a matched placebo; Chrubasik 2001 used Salix Alba

containing a daily dose of 240 mg salicin and compared it to

12.5 mg rofecoxib; and Krivoy 2001 used a daily dose of Salix

Alba containing 240 mg salicin compared to placebo and 100 mg

acetylsalicyliate.

The four trials using topical Capsicum Frutescens preparations

used a topical plaster application containing 11 mg of capsaici-

noids per plaster (Keitel 2001); a plaster containing an ethonolic

extract of Cayenne Pepper standardized to 22 ug/cm2 of capsai-

cinoids (Frerick 2003); a gel called Cremor Capsici Compositus

FNA, which contains 100 mg of Capsicum Oleoresin (BPC), 10

g of glycol salicylate, 1 g of methylnictinate, and a combined 1 g

of histamine hydrochloride, sorbitol, methylprahydroxybenzoate,

triethanolamine, lanette wax, stearic acid, and purified water (Stam

2001); or another gel, Rado-Sailil, containing 17.64 mg acetylsal-

icylate, 26.47 mg methylsalicylate, 8.82 mg glycosalicylate, 8.82

mg salicylic acid, 4.41 mg camphor, 55.14 mg menthol and 15.44

mg Capsicum Oleoresin per gram (Ginsberg 1987).

Nine of the ten studies reported adverse events associated with

the study medication. One trial did not report any information

regarding adverse events. All details of each trial are reported in

the table of included studies.

Conflict of interest was assessed by looking at funding sources

(public vs. private) and whether an author was employed by a

private pharmaceutical, nutraceutical, or herbal medicine man-

ufacturer. Two trials reported no conflict of interest (Ginsberg

1987; Chrubasik 1999). A conflict of interest was deemed possible

in six trials (Chrubasik 1996; Chrubasik 2000; Chrubasik 2003;

Frerick 2003; Keitel 2001; Stam 2001). In three trials, an author

was employed by a pharmaceutical company (Keitel 2001; Frerick

2003; Stam 2001), one trial was funded by a professional academy

(Chrubasik 2000), one trial was funded by a pharmaceutical com-

pany (Chrubasik 2003), and for one trial, the experimental herbal

medicine was supplied by a company (Chrubasik 1996). In the

final two trials (Chrubasik 2001; Krivoy 2001), we felt a conflict

of interest was unlikely.

Risk of bias in included studies

Initially, several ratings for the fulfilment of methodological quality

criteria for individual studies varied between authors. Specifically,

there were 28 disagreements on 110 individual ratings, for a raw

agreement of 74.5%. A total 19 of the disagreements resulted from

disparate interpretations of the methodological quality items and

the additional nine disagreements resulted from reading errors

in the trials. These disagreements were easily resolved through

discussion between the raters without the need for a third party.

The agreement between the two authors (JJG, MVT) regarding

total methodological quality scores for individual trials was fair, as

indicated by a Cohen’s kappa statistic of 0.42. Contact with one

primary author clarified one ’don’t know’, changing the item to a

’yes’ in one trial (Chrubasik 2003).

The mean score for methodological quality of all included studies

was 6.6, with a median score of seven and a range of five to nine.

Using a cut-off point of six fulfilled criteria out of 11, eight of the

10 trials (80%) were of high quality (Chrubasik 1996; Chrubasik

1999; Chrubasik 2003; Chrubasik 2000; Chrubasik 2001; Frerick

2003; Keitel 2001; Stam 2001).

The main methodological shortcomings of the Harpagophytum

trials included a lack of reporting of allocation concealment, com-

pliance rates, controls for co-interventions and acceptability of

withdrawal or drop-out rates during the follow-up period. Of the

Salix trials, one was an open-label trial and the additional two did

not report allocation concealment, compliance rates, controls for

co-interventions or the acceptability of withdrawal or drop-out

rates during the follow-up period. The Capsicum trial by Stam

2001 was assessed to be of high methodological quality. The addi-

tional Capsicum trials failed to report the type of randomization,

allocation concealment, similarity of baselines, outcome assessor,

investigator and participant blinding, comparability of co-inter-

ventions, and acceptability of compliance. Details regarding the

fulfilment of specific criteria for each individual trial are given in

Figure 1.



Figure 1. Summary of risks of bias



Clinical relevance

There were 15 disagreements on 50 individual ratings of clini-

cal relevance, but these were easily resolved during the consen-

sus meeting. Three trials met all five clinical relevance criteria

(Chrubasik 1996; Chrubasik 2000; Ginsberg 1987). Of the tri-

als testing Harpagophytum Procumbens, two trials did not meet

items four and five (Chrubasik 1999; Chrubasik 2003). Of the

Salix Alba trials, one did not meet item one (Krivoy 2001), one

did not meet items four and five (Chrubasik 2001) and it was

not possible to tell if one trial fulfilled items four and five or not

(Krivoy 2001). Of the Capsicum Frutescens trials, two did not

meet item one (Ginsberg 1987; Keitel 2001), two did not meet

items four and five (Stam 2001; Frerick 2003), and for one trial,

it was not possible to tell if items four and five were met or not

(Keitel 2001).

Effects of interventions

1a) Harpagophytum Procumbens (Devil’s Claw)

verses placebo

Three trials were identified, all of which included participants

suffering from acute exacerbations of chronic low-back pain lasting

longer than six months.

Chronic LBP

50 mg Harpagoside dose

A total of 325 patients were included in two four-week trials,

which tested extracts of Harpagophytum Procumbens standard-

ized to 50 mg harpagoside (H) per day verses placebo (Chrubasik

1999; Chrubasik 1996). Both trials found a significant increase in

the number of pain-free patients in the 50 mg H group (9% to

17%) over placebo (2% to 5%). One trial found that for patients

taking 50 mg H, the percentage with no pain or mild low-back

pain increased over the four week period (from 2% in week 1, to

24% in week 4), whereas the percentage with unbearable or severe

pain decreased over the four weeks (from 59% in week 1, to 35%

in week 4, Chrubasik 1999). Though tramadol consumption de-

creased more in both trials in the group that received 50 mg H than

in the group that received placebo, this did not reach statistical sig-

nificance in one trial (Chrubasik 1999) and the other trial did not

perform a statistical test on this measure (Chrubasik 1996). Both

trials used the Arhus Index. The overall Arhus score improved by

21% in both the 50 mg H group and the placebo group, with

no significant difference between groups. The pain subscale was

significantly improved in favour of the 50 mg H group in both tri-

als (median change for those with current low-back pain of 43%,

Chrubasik 1999; median change of 34%, Chrubasik 1996), which

was a greater improvement than that of the group that received an

additional 100 mg H in one trial (median change for those with

current low-back pain of 37%, Chrubasik 1999).

Therefore, there is strong evidence that a daily dose of 50 mg

harpagoside in an aqueous extract of Harpagophytum Procumbens

reduces pain more than placebo in the short-term, in patients with

acute episodes of chronic non-specific low-back pain. Long-term

treatment data are not yet available.

100 mg Harpagoside dose

A total of 197 patients were included in one four-week trial,

which tested Harpagophytum Procumbens standardized to 100

mg harpagoside (H) per day verses placebo (Chrubasik 1999). The

number of patients who were pain free for at least five days in the

fourth week of treatment was significantly higher (n = 10) than

in either the placebo (n = 3) or lower dose (50 mg H) groups (n

= 6). Half of the pain free patients in the 100 mg H group had a

neurological deficit at the start of the trial. The changes from base-

line in the overall Arhus Index, the pain index, invalid index and

physical impairment index were not different between the three

groups. The percentage of patients with no or mild low-back pain

increased over the four-week period, whereas the percentage with

unbearable or severe pain decreased.

Therefore, there is moderate evidence that a daily dose of 100 mg

harpagoside in an aqueous extract of Harpagophytum Procumbens

leads to a greater number of patients who are pain free for at least

five days, in the fourth week of treatment of acute episodes of

chronic non-specific low-back pain. Superiority of the higher dose

has not been shown.

1b) Salix alba versus placebo

Two trials were identified, both of which included participants

suffering from acute exacerbations of chronic low-back pain lasting

longer than six months.

CHRONIC LBP

120 mg Salicin dose

A total of 210 patients were included in a four-week trial, which

tested two doses of Salix Alba, standardized to either 120 mg or

240 mg salicin (S) per day, against placebo (n = 70 for each group;

Chrubasik 2000). The number of patients who were pain free for



at least five days in the fourth week of treatment increased from

baseline in the placebo (n = 4), 120 mg salicin group (n = 15) and

the 240 mg salicin group (n = 27), with the trend for dose being

significant. The number of patients requiring relief medication

(tramadol) during each week decreased to 33 during week four for

the placebo group, 10 for the 120 mg salicin group and three for

the 240 mg salicin group, with the trend for dose being significant.

The total Arhus Index, pain index, invalid index, and physical

impairment index did not change from baseline for the placebo

group but improved in the groups receiving either 120 mg or 240

mg salicin. The trend for dose was significant, with the group

receiving 240 mg salicin showing more improvement in the total

Arhus Index score and the pain index than the group receiving

120 mg salicin group.

Therefore, there is moderate evidence that a daily dose of 120

mg salicin from an extract of Salix Alba results in more pain-free

patients in the short-term for individuals with acute episodes of

chronic non-specific low-back pain.

240 mg Salicin dose

A total of 261 patients were included in two trials (Chrubasik

2000; Krivoy 2001). Results for the Chrubasik 2000 trial are re-

ported above. In summary, for the group that received 240 mg

salicin per day, there were more patients who were pain free for five

days during the fourth week of treatment, fewer patients required

relief medication. There was a trend of greater improvements with

higher dose for all outcomes and significant differences between

the groups receiving 120 mg and 240 mg salicin for the total Arhus

Index score and the pain index. The additional trial by Krivoy

2001, which was designed to test platelet aggregation of salix alba

extract, did not measure clinically relevant outcomes. Although

the authors stated that fewer patients in the group receiving 240

mg salicin required rescue medication (i.e. tramadol) than in the

placebo group, they did not provide any data.

Therefore, there is moderate evidence that a daily dose of 240 mg

salicin from an extract of Salix Alba reduces pain more than either

placebo or a daily dose of 120 mg of salicin in the short term for

individuals with acute episodes of chronic non-specific low-back

pain.

1c) Capsicum Frutescens versus placebo

Two trials were identified, one with acute low-back pain (Ginsberg

1987), though the actual duration of low-back pain was not de-

scribed, and one with chronic low-back pain that had lasted longer

than three months (Keitel 2001).

Acute LBP

In the trial by Ginsberg 1987, 40 subjects with acute mechanical

low-back pain were given either a cream called Rado-Salil, contain-

ing salicylate and capsicum (n = 20) or a placebo cream containing

bergamont and lavender (n = 20) for a period of 14 days. At day

three, there was an improvement in pain score in the Rado-Salil

group of almost 2 cm on the VAS, which was significantly better

than the placebo group. By day 14, the improvement increased

to 3.79 cm, which was also significantly greater than the placebo

group. In addition, both patients and physicians rated the effect

of Rado-Salil more favourably than the placebo group rated the

effect of their cream.

Therefore, there is limited evidence that Rado-Salil cream reduces

pain more than placebo in the short-term (14 days) for individuals

with newly occurring episodes of acute non-specific low-back pain.

Chronic LBP

Keitel 2001 included 154 patients with acute episodes of chronic

non-specific low-back pain who were randomly allocated to a

placebo plaster group (n = 77) and a Capsicum plaster group (n =

77) for a period of three weeks. A reduction in pain by at least 30%

was achieved in 60.9% of the Capsicum group and 42.1% of the

placebo group. A reduction in pain by at least 50% was achieved

in 35.1% of the Capsicum group and 17.1% of the placebo group.

The total Arhus score improved significantly more in the group

using Capsicum (38.5%) than in the group using placebo (28%).

Physician global ratings of efficacy were considered “excellent” or

“good” in 75.7% of those using Capsicum and 47.4% of those

using the placebo. After treatment, 13.5% of the those using Cap-

sicum and 6.6% of those using the placebo were completely symp-

tom-free. Compliance was 90.6% in the group using Capsicum

and 88.1% in the group using placebo.

In the study by Frerick 2003, 320 participants suffering from

chronic non-specific low-back pain were randomly allocated to a

placebo plaster group (n = 180) and a Capsicum plaster group (n =

180) for a period of 21 days. The total Arhus Index score decreased

significantly more in the group using Capsicum (33%) than in

the group using placebo (22%). The Arhus compound pain score

decreased significantly more in the group using Capsicum (42%)

than in those using placebo (31%). A reduction in pain by at least

30% was achieved in 67% of those using Capsicum and 49% in

those using placebo, and a reduction in pain by at least 50% was

seen in 45% and 24%, respectively. The Arhus subscale for physical

impairment also decreased significantly more in the Capsicum

group (21%) than in the placebo group (10%). Similar results

were found for the disability subscale (35% vs. 22%, respectively).

The capsicum treatment was rated as either ’excellent’ or ’good’

by investigators in 74% of cases compared to 36% for the placebo

group. Compliance was reported as being ’very good’ or ’good’ in

both groups (91% and 93%, respectively).

Therefore, there is moderate evidence that a plaster of Capsicum

Frutescens reduces pain and improves function more than placebo

in the short-term for individuals with acute episodes of chronic

non-specific low-back pain.



2a) Harpagophytum Procumbens verses rofecoxib

Chronic LBP

A total of 88 patients with acute episodes of chronic non-spe-

cific low-back pain were included in a six-week trial, which tested

Harpagophytum Procumbens standardized to 60 mg harpagoside

per day verses 12.5 mg rofecoxib per day (Chrubasik 2003). There

were no statistically significant differences in the number of pa-

tients who were pain free for at least five days in the sixth week of

treatment in the 60 mg Harpagophytum Procumbens group (10/

44) than in the rofecoxib group (5/44). The number of patients

with improvements in pain scores was not different between the

two groups. This study may lack power due to its small sample

size. The number of patients using rescue medication (tramadol)

decreased from baseline in both groups, but did not differ be-

tween groups at week six. At the end of six weeks, there were no

differences between groups for current low-back pain, scores on

the Arhus pain index, invalid index, functional index, or the total

score for the Arhus Index. The health assessment questionnaire

(HAQ) improved in both groups during the six-week period, with

no differences between groups.

Therefore, there is moderate evidence that there are no statisti-

cally significant or clinically relevant differences in effectiveness

between a daily dose of 60 mg harpagoside in an aqueous extract of

Harpagophytum Procumbens and daily dose of 12.5 mg rofecoxib

the short-term for individuals with acute episodes of chronic non-

specific low-back pain.

2b) Salix alba versus rofecoxib

Chronic LBP

A total of 228 subjects with acute episodes of chronic non-spe-

cific low-back pain were included in a four-week trial (Chrubasik

2001), which tested Salix Alba standardized to provide a daily dose

of 240 mg salicin against 12.5 mg per day of rofecoxib. Both the

rofecoxib and the 240 mg salicin groups improved by 44% on

the pain scale, the Arhus invalid index, pain index, and physical

impairment index. The percentage of patients requiring NSAIDs,

tramadol, or both was 10% for the Salix Alba group and 13% for

the rofecoxib group. Approximately 90% of physicians and pa-

tients rated either treatment as effective and close to 100% rated

either treatment as acceptable.

Therefore, there is moderate evidence that there are no differences

in effectiveness between a daily dose of 240 mg salicin of an extract

of Salix Alba and a daily dose of 12.5 mg rofecoxib in the short

term, for individuals with acute episodes of chronic non-specific

low-back pain in the short-term.

3) Capsicum Frutescens verses homeopathic

treatment

Acute and chronic LBP

The trial by Stam 2001 included 161 subjects who were a mixed

group of patients with new acute low-back pain and acute episodes

of chronic low-back pain. Participants were randomly allocated to

either a Spiroflor SLR homeopathic gel (SLR) group (n = 83) or

a Cremor Capsici Compositus FNA, the Capsici Oleoresin gel,

(CCC) group (n = 78) for a period of seven days. Each of the gels

was applied at 3 g/day. Both groups showed a significant reduction

in pain on the VAS scale, with a decrease of 38.2 mm in the

SLR group and 36.6 mm in the CCC group. In the SLR group,

50% of subjects reported that treatment was 80% effective and

18% reported total (100%) effectiveness. In the CCC group, this

was 55% and 15%, respectively. There were also no differences in

the proportion of subjects using paracetamol, the proportion of

subjects still unable to work at the end of the study, and overall

efficacy.

Therefore, there is moderate evidence that there are no statistically

significant or clinically relevant differences in effectiveness between

Spiroflor SLR homeopathic gel and Cremor Capsici Compositus

FNA gel.

Sensitivity Analysis

The definition of high quality given above is somewhat arbitrary.

Therefore, the cutoff of 50% for the internal validity item score

was modified to 40% and 60% to determine if conclusions of this

review changed.

With a 40% cutoff (up to 5/11), all 10 trials included in this

review were high quality. With a 50% cutoff (up to 6/11), all trials

examining the effects of Harpagophytum extracts were of high

quality (Chrubasik 1996; Chrubasik 1999; Chrubasik 2003), two

trials examining Salix alba extracts were of high quality (Chrubasik

2000; Chrubasik 2001) while one was low quality (Krivoy 2001),

three Capsicum Frutescens trials were high quality (Frerick 2003;

Keitel 2001; Stam 2001) while one was low quality (Ginsberg

1987). With a 60% cutoff for high quality (up to 7/11), two of

the Harpagophytum trials were high quality (Chrubasik 1999;

Chrubasik 2003) while one was low quality (Chrubasik 1996),

none of the Salix Alba trials were high quality (Chrubasik 2000;

Chrubasik 2001; Krivoy 2001), and one of the Capsicum trials was

high quality (Stam 2001) while the three others were low quality

(Ginsberg 1987; Keitel 2001, Frerick 2003).

D I S C U S S I O N



Methodological Quality

A total of 10 RCTs were included in this review. Three exam-

ined Harpagophytum Procumbens (Devil’s Claw), three Salix Alba

(White Willow Bark), and four Capsicum Frutescens (Cayenne).

The sensitivity analysis for methodological quality revealed that

the Harpagophytum trials were generally of high quality, the Salix

Alba trials were generally of moderate quality, and the Capsicum

trials were generally of low quality.

Although the reporting quality in these trials was poor, it is known

that methodological quality is not directly related to reporting

quality (Huwiler-Muntener 2002). Therefore, the methodological

quality of trials that were poorly reported remains unclear. The

present authors did not contact all trial authors to clarify method-

ological aspects of trials that were inadequately reported in the

published manuscripts.

Efficacy

The results of these 10 trials suggest that specific herbal medicines

may be effective for short-term (4 to 6 weeks) improvement in

pain and functional status for individuals with acute episodes of

chronic non-specific low-back pain. Seven of the trials included

in the review were placebo-controlled while three trials were com-

parative. There is insufficient evidence to make definitive con-

clusions regarding those trials comparing herbal medicine inter-

ventions with standard drugs. Two of the comparative trials used

Vioxx as a comparator and the other used a homeopathic topical

preparation. Given the recent findings of severe adverse effects of

Vioxx and its subsequent removal from the retail market, addi-

tional trials testing these herbal medicines against standard drugs

(acetaminophen, NSAIDs) are needed.

Although eight of these studies were considered to have homoge-

nous LBP populations, statistical pooling was not possible due

to lack of reporting of sufficient raw data. Therefore, we could

not provide quantitative evidence of efficacy of herbal medicine in

general, or of any of the three individual herbal medicines used in

these trials. Instead, we used levels of evidence to synthesize. Long

term efficacy (e.g. return to work, recurrence) was not assessed in

any of these trials and therefore remains to be determined.

Given the overwhelming evidence that conflicts of interest may

bias trial results, we assessed the potential for conflict of interest

in these trials. We determined that a conflict of interest was a

possibility in six trials included in this review. At this point, it is

not possible to determine the specific influence of these potential

conflicts on results of this review.

This review highlights research that, when combined, indicates

that there are at least two herbal medicines that have good evidence

for the short-term treatment of acute episodes of non-specific low-

back pain. These interventions are reported to have very few side

effects, but more research is required to more extensively explore

the safety of these herbals. The adverse effects appear to be primar-

ily confined to mild, transient gastrointestinal complaints. Large

observational studies are needed to explore the relative safety of

these herbals to standard medications such as acetaminophen and

NSAIDs.

This review has several strengths, including the comprehensive

search strategy, the inclusion of only the highest quality trial design

and use of suggested methods for systematic reviews of interven-

tions for low-back pain (van Tulder 2003). One obvious drawback

of this review is that many of the trials included were authored by

the same trialists (Chrubasik and colleagues). It is possible that the

results may be systematically biased in some way. It is imperative

that trials of these herbal medicines be repeated by other research

groups and in different settings.

The qualitative analysis used here may be regarded as a strength

and drawback. That is, though it would have been incorrect to

statistically combine data from heterogeneous trials, the qualita-

tive method used does not provide information on the size of the

treatment effect. Without this quantitative data it is hard to de-

termine whether these herbal interventions cause clinically signifi-

cant effects on patients suffering from non-specific low-back pain.

Quantitative analyses were precluded by incomplete reporting in

these trials. Recent evidence suggests that reporting of clinical tri-

als, irrespective of the intervention, is poor (e.g. Moher 2001).

Specifically, randomised controlled trials of herbal interventions

have been found to report less than half of the required informa-

tion as outlined by the CONSORT statement (Gagnier 2006a).

An extension of the CONSORT statement for the reporting of

RCTs of herbal medicine interventions has been developed and

should be referred to when reporting such trials (Gagnier 2006b).

These guidelines will aid trialists in planning, implementing, and

reporting controlled clinical trials.

Another drawback of this review results from the known hetero-

geneity of herbal medicine products. That is, herbal medicines

often vary the in the type of preparation (liquid, VS dried, VS

topical) and thus in the amount of chemical constituents per dose.

These variations influence the pharmacokinetics and therefore the

relative efficacy of these products.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

An aqueous extract of Harpagophytum Procumbens at a stan-

dardized daily dosage of 50 mg harpagoside, an extract of Salix

Alba at a standardized dosage of 240 mg salicin/day, and a plaster

of Capsicum Frutescens seem to reduce pain more than placebo.

These herbal medicines could be considered as treatment options

for acute episodes of chronic low-back pain.

Implications for research

Additional high quality trials must be done to determine if



Harpagophytum Procumbens standardized to 100 mg harpagoside

and Salix Alba standardized to 120 mg salicin are effective in the

treatment of low-back pain. Also, more trials are needed to more

accurately determine the efficacy of topical Capsicum Frutescens

in any kind of low-back pain. Additional trials testing these herbal

medicines against standard treatments (acetaminophen, NSAIDs)

will clarify their equivalence in terms of efficacy and effectiveness.

The quality of reporting in these trials was generally poor and thus

trialists should refer to the CONSORT statement in designing

and reporting clinical trials of herbal medicines.

A C K N O W L E D G E M E N T S

The primary author (JJG) is supported with a post-graduate fel-

lowship by the Canadian Institutes of Health Research and the

Natural Health Products Directorate, both public funding bodies

within Health Canada. Brian Berman’s work on this review was

partially funded by Grant Number R24 AT001293 from the Na-

tional Center for Complementary and Alternative Medicine (NC-

CAM). The contents of this article are solely the responsibility of

the authors and do not necessarily represent the official views of

the NCCAM, or the National Institutes of Health

R E F E R E N C E S

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H. Effectiveness of Harpagophytum extract WS 1531 in the

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Puska P. Does folk medicine work? A randomized clinical

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C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Chrubasik 1996

Methods RCT with two groups. Patients were placed in groups by random number allocation.

Period: 4 weeks

Participants 118 patients were allocated to a Harpagophytum (H) group (n=59) and a placebo (P)

group (n=59) . 109 completed the trial (H; n=54; P; n=55). Inclusion Criteria: between

18 an 75 years of age, at least 6 months of low back pain not attributable to identifiable

causes, suffering from acute increases in pain, and who were expected to require at least

four weeks of symptomatic treatment. Exclusion criteria: participation in other clinical

studies or had done so in past 30 days, pregnancy, lactation, insufficient contraception,

difficulties with language or cooperation, known allergy to proposed trial medication,

history of drug or alcohol abuse, requirement of psychotherapeutic agents, or a serious

organic illness affecting any of the organ systems

Interventions Oral form of Harpagophytum procumbens (Devil’s Claw) standardized to a dosage of

50 mg harpagoside per day or 2400 mg of the crude extract.

Matched placebo.

Outcomes Primary: cumulative requirement for Tramadol (an oral opiate-based analgesic) over the

last three weeks of the study period. Secondary: number of pain free patients based on

a 5 point visual rating scale and the Arhus low back pain index

Notes Total Quality Score: 7/12

Adverse Events: A total of 4 adverse effects occurred in the Harpagophytum group

with only two of these potentially being due to the treatment (i.e. repeated coughs and

tachycardia). A total of 10 adverse events occurred in the placebo group

Risk of bias

Bias Authors’ judgement Support for judgement

Adequate sequence generation? Low risk Patients were placed in groups by random

number allocation.

Allocation concealment? Unclear risk B - Unclear

Blinding?

All outcomes - patients?

Low risk

Blinding?

All outcomes - providers?

Low risk

Blinding?

All outcomes - outcome assessors?

Low risk



Chrubasik 1996 (Continued)

Incomplete outcome data addressed?

All outcomes - drop-outs?

Low risk


All outcomes - ITT analysis?

High risk

Similarity of baseline characteristics? Low risk

Co-interventions avoided or similar? Unclear risk Unclear from text

Compliance acceptable? Unclear risk Unclear from text

Timing outcome assessments similar? Low risk

Chrubasik 1999

Methods RCT with 3 groups. Period: 4 weeks

Participants 197 patients allocated to Harpagophytum at 600 mg (n=65), or 1200 mg (n=66) or

matched placebo (n=66). Inclusion criteria: 18-75 years of age, 6 months of non-specific

low back pain, a current exacerbation of their complaint that was effecting both rest

and movement, which was giving rise to pain greater than 5 on a 1-10 VAS and was

expected to require at least 4 weeks of symptomatic treatment. Exclusion criteria: current

or recent participation in any other clinical study, serious organic illness effecting any

organ system, a history of drug or alcohol abuse or requirement for psychotherapeutic

agents, pregnancy (actual or possible), or lactation, known allergy to any the proposed

trial medications, difficulties with language or anticipated co-operation

Interventions Harpagophytum Extract WS 1531 600 mg (50 mg harpagoside), 1200 mg (100 mg

harpagoside)

Outcomes Primary outcome: proportion of pain free patients without tramadol for at least 5 days

during the last week of treatment. Secondary outcomes: Arhus index, percentage requir-

ing tramadol, verbal pain ratings


Adverse effects included: 9 with gastrointestinal upset (4 in each active group and 1 in

the placebo group)

Risk of bias


Adequate sequence generation? Low risk





Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk





Chrubasik 2000

Methods RCT with three groups. No report of randomization method. Period: 4 weeks

Participants Patients were recruited from the Haifa area in Israel between May and November. 210

patients were randomized into three groups (n=70 in each group). 191 completed the

trial (P; n= 59; 120; n=67; 240; n=65).

Inclusion criteria: Between 18 and 75 years of age, at least 6 months of intermittent

low back pain that was not attributable to identifiable causes, a current exacerbation

of their complaint at rest and with movement that caused pain of at least 5 out of 10

on a VAS and that was expected to require at least 4 weeks of treatment. Exclusion

Criteria: participation in other clinical studies or had done so in past 30 days, pregnancy,

lactation, insufficient contraception, difficulties with language or cooperation, known

allergy to proposed trial medication, history of drug or alcohol abuse, requirement of

psychotherapeutic agents

Interventions Extract of dry Willow Bark (Salix Alba): 120 mg salicin, 240 mg salicin. Matched placebo

Outcomes Primary outcome: the proportion of patients who responded to treatment by being pain

free without tramadol for at least 5 days during the last week of treatment. Secondary

outcome: The Arhus Low Back Pain Index scores

Notes Total quality score: 7/12

Adverse events: one adverse reaction (exanthem, swollen eyes, pruritis) could be at-

tributed to the 120 mg willow bark extract group. A total of two patients in the 240




mg group reported short lasting adverse events (dizziness attributed to tramadol, dizzi-

ness and fatigue). These patients dropped-out for seemingly unrelated reasons. A total 6

adverse events were reported in the placebo group including 3 attributable to tramadol

(dizziness/headache, dizziness/ vomiting/diarrhea, dry mouth) and the 3 others reported

mild abdominal pain 2 of whom dropped out on the first day of the trial

Risk of bias




Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk

Similarity of baseline characteristics? High risk




Chrubasik 2001

Methods Open RCT with two groups comparing an herbal medicine (Salix alba) to a synthetic

anti-rheumatic (rofecoxib).

Period: 4 weeks.

Participants 228 individuals divided equally in to two groups (n=114 per group).

Inclusion criteria: age 18 to 80, 6 at least 6 months non-specific low back pain.

Exclusion criteria: recent trauma, a history of cancer or risk factors for spinal infection,

unexplained weight loss or recent fever or chills, pain exacerbated by being supine or

severe nocturnal pain, perineal anaesthesia, recent onset of bladder dysfunction or severe




progressive neurological deficit in the lower extremity, recent participation in other clin-

ical trial, serious organic illness affecting any organ system, a history of drug or alcohol

abuse or requirement for psychotherapeutic drugs, pregnancy or lactation, known allergy

to salicylates, difficulties with language or expected corporation

Interventions A proprietary extract of Salix Alba called Assalix at four capsules per day providing a

total of 240 mg of salicin per day, or a single 12.5 mg tablet of rofecoxib per day

Outcomes Pain on a VAS, modified Arhus index, its pain component and the total pain index.,

physician and patient rated success and the acceptability of the treatment on a verbal

scale (very good, good, moderate, poor)


Adverse events: 23 in the Salix alba group (13 of Gastrointestinal origin, 5 cutaneous

allergy, remaining undefined) and 27 in the rofecoxib group (17 GI effects, 1 asthma, rest

undefined). GI adverse events were judged as more severe and caused more withdrawals

in the rofecoxib group

Risk of bias



Allocation concealment? Low risk A - Adequate

Blinding?


High risk

Blinding?


High risk

Blinding?


High risk



Low risk



High risk


Co-interventions avoided or similar? Low risk





Chrubasik 2003

Methods RCT with two groups. Period: 6 weeks

Participants 88 subjects allocated to Harpagophytum Procubens (n=44) group or rofecoxib (n=44).

Inclusion criteria: age 45 to 75, at least 6 months of non-specific low back pain, current

exacerbation of complaints for 8 weeks that was affecting both rest and movement,

was causing pain of at least 5 out of 10 on a visual analogue scale and was judged to

require symptomatic treatment for 6 weeks. Exclusion criteria: red flags for low back

pain, participation in any other clinical study within the last 30 days, serious organic

illness affecting any organ system, a history of drug or alcohol abuse or requirement of

psychotherapeutic drugs, pregnancy or lactation, known allergies to trial medication,

and anticipated difficulties with language or corporation

Interventions Harpagophytum Procumbens in a proprietary aqueous extract called Doloteffin (stan-

dardized to contain 60 mg harpagoside) or 12.5 mg rofecoxib per day

Outcomes Primary outcome: proportion of patients who recorded “no pain” without using tra-

madol for at least 5 days in the final week or treatment. Secondary and other outcomes:

proportion of patients in whom the averaged daily pain scores in the 6th week had

decreased by 20 to 50% of the average in the first week; the percentage change from

baseline of a modified Arhus low back pain index; the percentage change from baseline

on the Health Assessment Questionnaire; tramadol requirement


Adverse effects: 14 participants in each group. GI: 8 in the Devil’s claw group, 9 in

the Vioxx group which tended to be more severe. Two serious adverse events occurred

in the Devil’s claw group but were judged as being unrelated to the study medication.

Circulatory and laboratory variables were not affected by either treatment

Risk of bias




Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk






Low risk





Frerick 2003

Methods RCT with two groups. Period: 3 weeks

Participants 320 subjects with chronic non-specific low back pain divided equally between capsicum

plaster group and placebo group

Interventions Topical plaster containing an ethonolic extract of Cayenne Pepper standardized to 22

ug/cm2 of capsaicinoinds or placebo plaster

Outcomes Outcomes: Arhus Low Back Pain Rating Scale, global assessment of efficacy by patient

and investigator, global assessment of safety by patient and investigator


Adverse effects: 14 participants in each group. GI: 8 in the Devil’s claw group, 9 in

the Vioxx group which tended to be more severe. Two serious adverse events occurred

in the Devil’s claw group but were judged as being unrelated to the study medication.

Circulatory and laboratory variables were not affected by either treatment

Risk of bias




Blinding?


Unclear risk Unclear from text

Blinding?



Blinding?





Frerick 2003 (Continued)



Low risk



Low risk

Similarity of baseline characteristics? Unclear risk Unclear from text


Compliance acceptable? Low risk

Timing outcome assessments similar? Unclear risk Unclear from text

Ginsberg 1987

Methods RCT with 40 patients assigned to 1 of 2 groups for period of 14 days

Participants 40 patients with acute mechanical low back pain were assigned to either the Rado-Salil

(a capsicum containing cream) group (n=20) or a placebo group (n=20). Each patient

was also given 45 paracetamol 250 mg tablets. No other analgesic, anti-inflammatory

drug or physical treatment was allowed during the 12 week period.

Method of patient selection: clinical examination, standard radiological examination of

the lumber spine, routine laboratory tests

Interventions Rado-Salil ointment (containing 17.64 mg ethysalicylate, 26.47 mg methylsalicylate, 8.

82 mg glycosalicylate, 8.82 mg salicylic acid, 4.41 mg camphor, 55.14 mg menthol and

15.44 mg capsicum oleoresin per 1 g) in the form of a 40 g stick applied as needed or

a placebo (containing only the excipient with three times the amount of lavendula and

bergamot essences) matched for appearance

Outcomes Outcomes: pain evaluation on a 10 cm linear scale, duration of confinement to bed,

muscular reflex contracture evaluation by the physician on a scale of 0 to 4, and spine

mobility by determination of Schober’s index, the finger to floor distance, the degree of

lumbar extension, global appreciation of treatment by patient and physician


Adverse events: Pruritis, 1 in placebo, 1 in Rado-Salil group. Local erythema and burning,

3 in the Rado-Salil group

Risk of bias


Adequate sequence generation? Unclear risk Unclear from text




Ginsberg 1987 (Continued)

Blinding?


Low risk

Blinding?



Blinding?


Low risk



Low risk



Low risk





Keitel 2001

Methods RCT with two groups. No report of randomization method. Period: 1 plaster per day at

maximum pain site for 4 to 12 hours for 3 weeks

Participants 154 patients were randomly allocated to a placebo plaster group (n=77) and a capsicum

plaster group (n=77) A total of 132 patients completed the study with data being available

for the intention to treat (ITT) analysis on 150 patients (P=0.002). A total 22 exclusions

occurred due to premature discontinuation of the treatment (n=19) failure to meet the

inclusion criteria (n=2) or unauthorized concurrent treatment (n=1). Inclusion criteria:

subjective back pain rating of 5 or more on an 11 grade visual analogue scale as well as

a duration of back pain for a minimum of 3 months at enrolment. Exclusion criteria:

alcohol abuse, drug dependence, forms of specific back pain, concomitant systemic

inflammatory rheumatic condition, no concurrent therapy for back pain

Interventions Topical plaster type application of Capsicum Frutescens (Cayenne) containing 12 mg of

capsaicinoids per plaster. Matched placebo plaster

Outcomes Primary outcome measure: Arhus Low Back Rating Scale. Secondary outcome measures:

global assessment of efficacy and tolerance by physician and patient


Adverse events: A total of 24 adverse events were reported (C=15; P=9). Most of these

were warmth and itching locally. The C group had 5 cases of severe adverse events



Keitel 2001 (Continued)

(inflammatory contact eczema, urticaria, minute haemorrhagic spots, and vesiculation

or dermatitis) and the P group had two such cases (vesiculation or allergic dermatosis).

A total of 16 patients withdrew because of adverse events (C=10; P=6). Also, 95.9% of

the C group and 48.7% of the P group experienced sensations of warmth locally. Pruritis

was mentioned in 45.9% of the C group and 31.6% of the P group

Risk of bias


Adequate sequence generation? Unclear risk No report of randomization method


Blinding?


Low risk

Blinding?



Blinding?





Low risk



Low risk



Compliance acceptable? Low risk


Krivoy 2001

Methods 35 subjects randomized to two groups and a further 16 acted as controls. Period: 4 weeks

Participants 51 subjects with 19 in the salix alba group, 16 in a placebo group, and 16 in an acetyl-

salicylate group.

Inclusion criteria:acute exacerbations of chronic low back pain, stable ischemic heart

disease. Exclusion criteria: NSAID use

Interventions 786.48 mg twice per day of an ethanol extract of the bark of Salix Daphnoides (240 mg

salicin content per day), matched placebo, or 100 mg acetylsalicylate



Krivoy 2001 (Continued)

Outcomes Primary outcome: platelet aggregation


Adverse events: none reported

Risk of bias


Adequate sequence generation? Unclear risk Unclear from text


Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk




Timing outcome assessments similar? Unclear risk Unclear from text

Stam 2001

Methods RCT with two groups (No placebo). Randomisation was performed using RCODE

software (version 3.4) in blocks of four. Period: 7 days

Participants 161 subjects who were randomly allocated to either group. A total of 6 subjects were

lost to follow-up (SLR=2; CCC=4). 21 subjects met all per protocol criteria. Inclusion

criteria: Between the ages of 18 and 65, acute attack of low back pain within previous 72

hours, free from back pain during the previous three months, at least moderately painful

limitation of movement on physical examination. Exclusion criteria: radicular symptoms,

pain above T12, rheumatoid arthritis, ankylosing spondylitis, known hypersensitivity to



Stam 2001 (Continued)

treatment compounds, use of analgesics other than paracetamol during the treatment

period, use of NSAIDs during the treatment period, receiving other treatment for acute

low back pain, pregnancy, more than 96 hours elapsed since onset of pain, including

washout for analgesic and/or NSAIDs

Interventions Spiroflor SLR homeopathic gel (SLR) group (n=83) or a Cremor Capsici Compositus

FNA, the Capsici Oleoresin gel, (CCC) group (n=78). Each of the gels was applied at 3

g per day

Outcomes Primary outcome: reduction in visual analogue scale (VAS) scores for pain (100 mm scale)

and the proportion of treatment success (a VAS reduction of at least 80%). Secondary

outcome measures: proportion of subjects using paracetamol, number of nights with

disturbed sleep, duration of absence from work and an overall assessments of treatment

efficacy/usefulness by the general practitioners (GP) and the patients

Notes Total quality score: 9/12.

Adverse Events: Approximately 12% of SLR and 26% of the CCC group experienced an

adverse event. Adverse drug reactions were reported by 4% of the SLR group and 24%

of the CCC group. A total of four adverse drug reactions in the CCC group and none

in the SLR group were considered “severe”. A total of 8 patients in CCC group and 0 in

th SLR group withdrew due to adverse drug reactions

Risk of bias


Adequate sequence generation? Low risk Randomisation was performed using

RCODE software (version 3.4) in blocks

of four


Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk




Stam 2001 (Continued)


Compliance acceptable? High risk


Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Blank 1970 not an RCT

Chrubasik 2001a not an RCT

Chrubasik 2002 not an RCT

Chrubasik 2002a not an RCT

Chrubasik 2002b not an RCT

Gensthaler 2000 not an RCT

Gobel 2001 not an RCT

Harden 2000 not an RCT

Hemmila 1997 not an herbal medicine

Hogeboom 2001 not an RCT, not an herbal medicine

Jiang 1986 not an herbal medicine

Kunzel 2002 not an RCT

Laudahn 2001a not an RCT

Marz 2002 not an RCT

Sherman 2001a not an RCT, not an herbal medicine

Sherman 2001b not an RCT, not an herbal medicine

Takabayashi 1990 not low back pain

Wimmer 1997 not low back pain, not an herbal medicine



(Continued)

Xu 1993 not an RCT



D A T A A N D A N A L Y S E S

This review has no analyses.

A D D I T I O N A L T A B L E S

Table 1. Criteria for the Risk of Bias Assessment

Criteria for a judgment of yes for the sources of risk of bias

Was the method of randomisation adequate? A random (unpredictable) assignment sequence. Examples of adequate methods are

computer generated random number table and use of sealed opaque envelopes. Methods of allocation using date of birth, date of

admission, hospital numbers, or alternation should not be regarded as appropriate.

Was the treatment allocation concealed? Assignment generated by an independent person not responsible for determining the eligibility

of the patients. This person has no information about the persons included in the trial and has no influence on the assignment

sequence or on the decision about eligibility of the patient.

Was the patient blinded to the intervention? The review author determines if enough information about the blinding is given in order

to score a “yes.”

Was the care provider blinded to the intervention? The review author determines if enough information about the blinding is given

in order to score a “yes.”

Was the outcome assessor blinded to the intervention? The review author determines if enough information about the blinding is

given in order to score a “yes.”

Was the withdrawal/drop-out rate described and acceptable? The number of participants who were included in the study but did

not complete the observation period or were not included in the analysis must be described and reasons given. If the percentage

of withdrawals and drop-outs does not exceed 20% for short-term follow-up or 30% for long-term follow-up and does not lead to

substantial bias a “yes” is scored. (note: these percentages are arbitrary and not supported by the literature)

Did the analysis include an intention-to-treat analysis? All randomized patients are reported/analyzed in the group to which they

were allocated by randomization for the most important moments of effect measurement (minus missing values) irrespective of

noncompliance and co-interventions

Were the groups similar at baseline regarding the most important prognostic indicators? In order to receive a “yes,” groups have to

be similar at baseline regarding demographic factors, duration and severity of complaints, percentage of patients with neurologic

symptoms, and value of main outcome measure(s).

Were co-interventions avoided or similar? Co-interventions should either be avoided in the trial design or be similar between the

index and control groups.

Was the compliance acceptable in all groups? The review author determines if the compliance to the interventions is acceptable, based

on the reported intensity, duration, number and frequency of sessions for both the index intervention and control intervention(s).

Was the timing of the outcome assessment in all groups similar? Timing of outcome assessment should be identical for all intervention

groups and for all important outcome assessments



W H A T ’ S N E W

Last assessed as up-to-date: 14 December 2005.

Date Event Description

19 January 2011 Amended Contact details updated.

H I S T O R Y

Protocol first published: Issue 4, 2003

Review first published: Issue 2, 2006

Date Event Description

23 November 2009 Amended Contact details updated.

11 June 2008 Amended Converted to new review format.

15 December 2005 New citation required and conclusions have changed Substantive amendment

C O N T R I B U T I O N S O F A U T H O R S

JJG: Wrote the body of the review, searched the literature, contacted experts for trials and clarification of methods, screened trials for

inclusion, assessed methodological quality. Prepared submission for Cochrane Back Review Group.

MVT: Searched the literature, screened trials for inclusion, assessed methodological quality, edited and contributed to the body of the

review.

CB: Edited final versions of protocol and review

BB: Screened trials for inclusion, edited final version of protocol and review.

D E C L A R A T I O N S O F I N T E R E S T

One of the authors (Claire Bombardier) is Co-ordinating Editor of the Cochrane Back Review Group. Editors are required to conduct

at least one Cochrane review. Dr. Bombardier is not the first authors of the review. An editor who is an author is excluded from editorial

decisions on the review in which they are contributors. Therefore, this involvement does not seem to be a source of conflict of interest

in the Cochrane Collaboration.



S O U R C E S O F S U P P O R T

Internal sources

• No sources of support supplied

External sources

• Natural Health Products Directorate/Canadian Institutes of Health Research, Canada.

• National Center for Complementary and Alternative Medicine, USA.

I N D E X T E R M S

Medical Subject Headings (MeSH)

∗Phytotherapy; Benzyl Alcohols [therapeutic use]; Capsicum; Cyclooxygenase 2 Inhibitors [therapeutic use]; Glucosides; Harpago-

phytum; Herbal Medicine; Lactones [therapeutic use]; Low Back Pain [∗drug therapy]; Randomized Controlled Trials as Topic; Salix;

Sulfones [therapeutic use]

MeSH check words

Adult; Humans



cochrane database of systematic reviews (reviews) || herbal medicine for low back pain

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