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Does Devil’s Claw (Harpagophytum procumbens) have a place in the conventional medicine system as a treatment for osteoarthritis?
Abstract
Traditional Western Herbal Medicine
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This highly successful textbook is now available in its third edition. Over the years it has become the standard textbook in the field world-wide. It mirrors the huge expansion of the field of economic evaluation in health care, since the last edition was published in 1997. This new edition builds on the strengths of previous editions, being clearly written in a style accessible to a wide readership. Key methodological principles are outlined using a critical appraisal checklist that can be applied to any published study. The methodological features of the basic forms of analysis are then explained in more detail with special emphasis of the latest views on productivity costs, the characterisation of uncertainty and the concept of net benefit. The book has been greatly revised and expanded especially concerning analysing patient-level data and decision-analytic modelling. There is discussion of new methodological approaches, including cost effectiveness acceptability curves, net benefit regression, probalistic sensitivity analysis and value of information analysis. There is an expanded chapter on the use of economic evaluation, including discussion of the use of cost-effectiveness thresholds, equity considerations and the transferability of economic data. This new edition is required reading for anyone commissioning, undertaking or using economic evaluations in health care, and will be popular with health service professionals, health economists, pharmacand health care decision makers. It is especially relevant for those taking pharmacoeconomics courses.
Extracts of the secondary roots of the southern African plant, Devil’s Claw (Harpagophytum procumbens) provide a herbal drug with a variety of traditional indications. One area of its use that has become very popular in recent years is in the treatment of inflammatory disorders of the musculoskeletal system and of low back pain. There have been several clinical studies recently published that generally support its use in treating osteoarthritis although more studies are required in order to establish this drug as a definite therapeutic option. Here in this review, the pharmacological properties of Devil’s Claw are reviewed in detail and the clinical evidence is briefly summarised. There is good in vitro and in vivo pharmacological evidence of the anti-inflammatory and analgesic properties of this drug, although some negative findings have also been reported. Generally, the pharmacological properties of Devil’s Claw is supportive of its therapeutic potential, but more evidence from clinically relevant models, as well as at the cellular and molecular level, should be sought. Such studies may provide evidence in support of additional indications, both traditional and novel. The clinical data on Devil’s Claw is also very promising.
Extract of Harpagophytum procumbens (devil's claw) has become the focus of research as a potential therapeutic agent in the treatment of rheumatic arthritis and pain due to its favorable side effects profile compared to synthetic alternatives. This superior safety of treatment is very valuable, especially in view of that in mandatory long duration of therapy in chronic diseases. None of NSAIDs is ideal in controlling or modifying the signs and symptoms of inflammation, particularly in the common inflammatory joint dis-eases. Many studies evaluated the anti-inflammatory and analgesic effects of Harpagophytum procum-bens with inconsistent and contradictory results. The aim of this study was to investigate the effect of Harpagophytum procumbens on both acute and chronic inflammatory processes in rats and pain re-sponses in mice. In addition, its safety on gastric and duodenal mucosa was evaluated histopathologi-cally. Eighty rats of both sexes weighing 150-200 g each and twenty-four mice of both sexes weighing 25-30 grams each, were used in this work. For a pharmacological study, these animals were classified for induction of the different experimental models. The acute model of inflammation includes Carrageenan-induced rat back-paw edema test. The chronic models of inflammation include Complete Freund's adju-vant-induced arthritis test and cotton pellet-induced granuloma test. The analgesic model includes writh-ing test in mice. A biochemical study was done on the Complete Freund's adjuvant-induced arthritis test group. Blood samples were taken for measuring acute phase proteins; C-reactive protein & serum albu-min, and serum cortisol. Histopathological assessment of gastric and duodenal mucosa for the effect of Harpagophytum procumbens in comparison with the effect of indomethacin was done in the Complete Freund's adjuvant-induced arthritis test group. In Carrageenan-induced rat back-paw edema test; Carra-geenan sub-plantar injection in right back-paw in rats induced highly significant increase in paw thickness (p ≤ 0.001). Harpagophytum procumbens pre-treatment induced highly significant reduction (p ≤ 0.001) in right back-paw thickness, an effect similar to indomethacin. In Complete Freund's adjuvant-induced arthri-tis test; Freund's adjuvant-induced arthritis in rats induced highly significant increase in paw thickness of rats ( p ≤ 0.001), significant decrease in serum cortisol (p ≤ 0.05), highly significant decrease in serum albumin ( p ≤ 0.001) and significant increase in C-reactive protein (p ≤ 0.05). Harpagophytum procum-bens and indomethacin administration caused insignificant effects on these parameters and caused only significant reduction of paw thickness (p ≤ 0.05). In cotton pellet-induced, granuloma test; Harpagophytum procumbens and indomethacin intra-peritoneal administration in cotton pellet-induced granuloma in rats caused a reduction of inflammation manifested by marked and highly significant decrease of cotton pellet weight (p ≤ 0.001). In Writhing test in mice, Harpagophytum procumbens and acetyl salicylic acid had an analgesic effect manifested by highly significant reduction in the number of writhing reactions (p ≤ 0.001). The results of the histopathological study revealed the greater safety of Harpagophytum procumbens on GIT mucosa in comparison to the more injurious effect of indomethacin as a NSAID.
Out-of-pocket expenditures of over 34 billion dollars per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations.
The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding).
A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients.
Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated.
Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects approximately 1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports approximately 60-90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely accepted in vitro models that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases.
Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder. Conventional treatment (i.e., the use of nonsteroidal anti-inflammatory drugs-NSAIDs) is associated with well-documented adverse effects. Devil's Claw (Harpagophytum procumbens) a traditional South African herbal remedy used for rheumatic conditions, may be a safer treatment option. To date, 14 clinical trials have assessed its efficacy/ effectiveness in OA.
To address the two main questions of importance to clinicians: (1) Does Devil's Claw work for the treatment of OA, and (2) Is it safe?
A review of the literature on Devil's Claw and OA from 1966 to 2006 was performed using multiple search databases, monographs, and citation tracking. Relevant trials in all languages were identified and included. Both internal validity (i.e., adequacy of the dosage and period of treatment for this condition, reporting of randomization, rates of dropout, blinding, and statistical analysis) and external validity (i.e., inclusion/ exclusion criteria, baseline characteristics of the study populations, trial setting, and the appropriateness of the outcome measures of the trials) were assessed.
Fourteen studies were identified: eight observational studies; 2 comparator trials (1 open, the other randomized to assess clinical effectiveness); and 4 double-blinded, placebo-controlled, randomized controlled trials to assess efficacy. Many of the published trials lacked certain important methodological quality criteria. However, the data from the higher quality studies suggest that Devil's Claw appeared effective in the reduction of the main clinical symptom of pain. The assessment of safety is limited by the small populations generally evaluated in the clinical studies. From the current data, Devil's Claw appears to be associated with minor risk (relative to NSAIDs), but further long-term assessment is required.
The methodological quality of the existing clinical trials is generally poor, and although they provide some support, there are a considerable number of methodologic caveats that make further clinical investigations warranted. The clinical evidence to date cannot provide a definitive answer to the two questions posed: (1) Does it work? And (2) is it safe? A definitive high-quality trial that addresses the necessary methodologic improvements noted is needed to answer these important clinical questions.
The upsurge of interest in health-status measurement an outline of the development of health-status measures methodology quality as an issue the measurement process implications for decision-making trends and issues concluding remarks.
In a study that indicates more definitive investigation is needed, 118 patients with chronic back problems seeking treatment for acute attacks of pain were included in a 4-week randomised double-blinded study on the safety and effectiveness of an extract of Harpagophytum procumbens. Both, the treatment and the placebo were administered in the form of two tablets taken three times per day; the treatment group had a daily consumption equal to 6,000 mg of crude preparation (50 mg harpagoside, the putative active ingredient). The treatment and placebo groups were well matched in physical characteristics; in the severity, duration, nature and accompaniments of their pain; and in laboratory indices of organ system function. 109 patients completed the study. The study was originally designed to measure Harpagophytum's effectiveness by measuring the use of supplementary pain-killer Tramadol over its final 3 weeks. However, this did not differ between the Harpagophytum and placebo groups nor was the consumption closely related to the amount of pain. Further analysis, though, revealed that 9 out of 51 patients who received the extract were pain free at the end of treatment compared to only 1 out of 54 patients who received placebo. A modification of the Arhus index was used as an additional measure, covering the more global impact. The percentage change was greater in those patients who received Harpagophytum extract than in those who received placebo, but inferential testing (Mann Whitney) allowed only 94% degree of confidence that this had not arisen by chance. The Arhus index reduction was based on improvement in pain. This indication of effectiveness, and the absence of demonstrable adverse effects show that more definite clinical studies of Harpagophytum extract will be worthwhile.
The iridoids of Harpagophytum procumbens and Harpagophytum zeyheri were studied by CLHP. Harpagoside is the main iridoid for both drugs whereas 8-p-coumaroylharpagide is a representative iridoid of Harpagophytum zeyheri only. The ratio harpagoside/8-p-coumaroylharpagide can be used to distinguish chemically both species. For commercial dried aqueous extracts this ratio is intermediate because they are probably prepared from a mixture of H. procumbens and H. zeyheri drugs. The aqueous extracts of both drugs show similar analgesic and anti-inflammatory properties. Harpagophytum procumbens and Harpagophytum zeyheri should be accepted as sources for the drug Harpagophyti radix.
To evaluate the efficacy and safety of Harpagophytum in the treatment of hip and knee osteoarthritis comparatively with the slow-acting drug for osteoarthritis, diacerhein.
A multicenter, randomized, double-blind, parallel-group study was conducted in 122 patients with hip and/or knee osteoarthritis. Treatment duration was four months and the primary evaluation criterion was the pain score on a visual analog scale. Harpagophytum 2,610 mg per day was compared with diacerhein 100 mg per day.
After four months, considerable improvements in osteoarthritis symptoms were seen in both groups, with no significant differences for pain, functional disability, or the Lequesne score. However, use of analgesic (acetaminophen-caffeine) and nonsteroidal anti-inflammatory (diclofenac) medications was significantly reduced in the Harpagophytum group, which also had a significantly lower rate of adverse events.
In this study, Harpagophytum was at least as effective as a reference drug (diacerhein) in the treatment of knee or hip osteoarthritis and reduced the need for analgesic and nonsteroidal anti-inflammatory therapy.
In a double-blind, randomized, multicentre clinical study, the efficacy and tolerance of a herbal medicine product, Harpadol (6 capsules/day, each containing 435 mg of powdered cryoground powder Harpagophytum procumbens), was compared with diacerhein 100 mg/day in the treatment, for 4 months, of 122 patients suffering from osteoarthritis of the knee and hip. Assessments of pain and functional disability were made on a 10 cm horizontal visual analogue scale; severity of osteoarthritis was evaluated by Lequesne's index. Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments. Similarly, there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein. At completion of the study, patients taking Harpadol were using significantly less NSAIDs and antalgic drugs. The frequency of adverse events was significantly lower in the Harpadol group. The most frequent event reported was diarrhea, occurring in 8.1% and 26.7% of Harpadol and diacerhein patients respectively. The global tolerance assessment by patients at the end of treatment favoured Harpadol. The results of this study demonstrate that Harpadol is comparable in efficacy and superior in safety to diacerhein.
Pain is the most common reason for patients seeking advice from their physician. One adult in five suffers from chronic pain. In general, musculoskeletal pain, often in the form of arthritis, non-articular rheumatism, peripheral neuropathies and low back disorders, represents the most common cause of chronic non-malignant pain (CNMP). Exposure to low social support, low social anchorage or low social participation significantly increases the odds of a high level of pain. Most patients do not attribute chronic musculoskeletal pain to injury, but those who do report significantly higher levels of emotional distress. Pain is the third leading reason for absence from work in the United States, where the problem of chronic pain translates into an annual expenditure of at least $50 billion. The effectiveness of opioids for chronic pain goes unchallenged, but issues of potential dependence, abuse, and social and legal concerns have rendered their use in CNMP controversial. Numerous consensus statements, guidelines and policies have been issued by a variety of advocate organisations for the treatment of CNMP with opioids. Undertreatment of chronic pain persists despite the availability of drugs and other therapies for effective pain management.
Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patient's global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.
This randomized, double-dummy, double-blind pilot study of acutely exacerbated low back pain was aimed to inform a definitive comparison between Doloteffin, a proprietary extract of Harpagophytum, and rofecoxib, a selective inhibitor of cyclo-oxygenase-2 (COX-2).
Forty-four patients (phyto-anti-inflammatory drug-PAID-group) received a daily dose of Doloteffin containing, inter alia, 60 mg of harpagoside for 6 weeks and 44 (non-steroidal anti-inflammatory drug-NSAID-group) received 12.5 mg/day of rofecoxib. All were allowed rescue medication of up to 400 mg/day of tramadol. Several outcome measures were examined at various intervals to obtain estimates of effect size and variability that might be used to decide the most suitable principal outcome measure and corresponding numbers required for a definitive study.
Forty-three PAID and 36 NSAID patients completed the study. Ten PAID and 5 NSAID patients reported no pain without rescue medication for at least 5 days of the 6th week of treatment. Eighteen PAID and 12 NSAID patients had more than a 50% reduction in the week's average of their pain scores between the 1st and 6th weeks. The mean percentage decrease from baseline in the pain component of the Arhus Index was 23 (S.D. 52) in PAID and 26 (S.D. 43) in NSAID. The corresponding measures for the overall Arhus Index were 11 (31) and 16 (24) and, for the Health Assessment Questionnaire, 7 (8) and 6 (7). Tramadol was used by 21 PAID patients and 13 NSAID patients. Fourteen patients in each group experienced 39 adverse effects, of which 28 (13 in PAID) were judged to some degree attributable to the study medications.
Though no significant intergroup differences were demonstrable, large numbers will be needed to show equivalence.
Preparations made from the secondary tubers of Devil's claw (Harpagophytum procumbens) are successfully used in patients with rheumatic diseases (arthrosis and low back pain). In order to add data on the efficacy and long-term safety of an aqueous extract (Doloteffin; 2400 mg extract daily, corresponding to 50 mg harpagoside), which has been tested successfully in patients with low back pain, an uncontrolled multicentre drug surveillance study for about 12 weeks was conducted in 75 patients with arthrosis of the hip or knee. To standardize the assessment of treatment effects, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (10 point scale) as well as the 10 cm VAS pain scale were used. The results of the study revealed a strong reduction of pain and the symptoms of osteoarthritis. There was a relevant improvement of each WOMAC subscale as well as of the total WOMAC index: 23.8% for the pain subscale, 22.2% for the stiffness subscale and 23.1% for the physical function subscale. The WOMAC total score was reduced by 22.9%. VAS pain scores were decreased by 25.8% for actual pain, 25.2% for average pain, 22.6% for worst pain and 24.5% for the total pain score. The physicians reported a continuous improvement in typical clinical findings such as 45.5% for pain on palpation, 35% for limitation of mobility and 25.4% for joint crepitus. Only two cases of possible adverse drug reactions were reported (dyspeptic complaints and a sensation of fullness). Although this was an open clinical study, the results suggest that this Devil's claw extract has a clinically beneficial effect in the treatment of arthrosis of the hip or knee.
The purpose is to examine what is known about the efficacy of selected complementary and alternative medicine (CAM) therapies for pain from arthritis and related conditions based on systematic reviews and meta-analyses.
Results specifically related to pain were retrieved from review articles of acupuncture, homeopathy, herbal remedies, and selected nutritional supplements.
Evidence exists to support the efficacy of reducing pain from osteoarthritis (OA) for acupuncture; devil's claw, avocado/soybean unsaponifiables, Phytodolor and capsaicin; and chondroitin, glucosamine, and SAMe. Strong support exists for gamma linolenic acid (GLA) for pain of rheumatoid arthritis (RA).
Despite support for some of the most popular CAM therapies for pain from arthritis-related conditions, additional high quality research is needed for other therapies, especially for herbals and homeopathy.
Herbal medicine boom threatens plants
- R Edwards
Edwards, R. (2004). Herbal medicine boom threatens plants. [online] Available at:
http://www.newscientist.com [Accessed on 17 August 2007].
Integrated or evidence-based medicine. Alternate Remedies
- E Ernst
Ernst, E.
Integrated or evidence-based medicine. Alternate Remedies [online]
National institute of clinical excellence (NICE) A guide to the NICE
National institute of clinical excellence (NICE). (2005). A guide to the NICE. NHS.
MidCity Place, London.
- D Loew
- J Mollerfeld
- A Schrodter
Loew, D., Mollerfeld, J., Schrodter, A., Puttkammer, S. and Kaszkin, M (2001).