Overview of Complementary and Overview of Complementary and Alternative Medicine (CAM) and Alternative Medicine (CAM) and Its Role in Caring for Veterans Its Role in Caring for Veterans with Post-Deployment Health with Post-Deployment Health

ConcernsConcernsAn-Fu Hsiao, MD, PHD

September 15, 2010WRIISC: Caring for Veterans with Post-

Deployment Health Concerns

OverviewOverview

Introduction of Complementary and Alternative Medicine (CAM)

Philosophical discussion about Evidence-Based approach

Literature review of the efficacy of acupuncture and herbs/supplements for treatment of headaches and osteoarthritis

Popularity of Popularity of Complementary and Complementary and

Alternative Medicine (CAM) Alternative Medicine (CAM) in General Populationin General Population CAM Is defined as “a group of therapies that are

not taught in conventional medical school or are outside of mainstream, conventional medicine”

Total 1997 out-of-pocket expenditures related to CAM were estimated at $27 billion

42% of general population used at least one type of CAM within past 12 months

Popularity of Popularity of Complementary and Complementary and

Alternative Medicine (CAM) Alternative Medicine (CAM) in Veteransin Veterans Headaches and osteoarthritis are common

health concerns for post-deployment Veterans

Estimated that 30% to 50% of Veterans used CAM

OEF/OIF, female, and younger Veterans are more likely to use CAM and their use will increase in the future

CAM vs. Integrative CAM vs. Integrative MedicineMedicine

CAM and Integrative Medicine are two different paradigms

Integrative Medicine can be defined as “integrating best elements of conventional medicine and CAM and combining them into a safer and more effective model of healing”

Our talk will focused on CAM because there is little high-quality research and data on integrative medicine

Potential Barriers to Potential Barriers to Integration of CAM with Integration of CAM with

Conventional TreatmentsConventional Treatments Lack of knowledge on the effectiveness

and safety of CAM treatments. Lack of know-how in referring to high-

quality CAM practitioners. “Turf battles” between physicians and

CAM practitioners.

Lack of Safe and Effective Lack of Safe and Effective Conventional Medical Conventional Medical

Treatment for Headaches and Treatment for Headaches and OsteoarthritisOsteoarthritis

The treatment goals for headaches and osteoarthritis focus on controlling pain and improving health-related quality of life.

Pharmacological therapies include NSAIDS, COX-2 inhibitors, topical analgesics, opioid analgesics, and intra-articular steroid and hyaluronate injections. These treatments are expensive May cause dangerous side effects

Not All CAM Modalities Not All CAM Modalities Are Created EqualAre Created Equal

Some CAM modalities are evidence-based, while others are based on anecdotes and tradition.

Some CAM modalities may have adverse effects.

Some CAM modalities may cause adverse herb-drug interactions.

Is Randomized Controlled Trial the Is Randomized Controlled Trial the Best Research Design to Evaluate Best Research Design to Evaluate

the the Efficacy of CAM?Efficacy of CAM? Randomized Controlled Trial (RCT) is

considered the gold standard and the strongest research design in evaluating efficacy of conventional treatment

RCT may not be the best way to evaluate the efficacy of CAM because they are individualized, multi-components, and difficult to double blind

Is It Fair to Require CAM Is It Fair to Require CAM Use to Be Evidence-Based?Use to Be Evidence-Based?

Is it fair to ask CAM to be held at such high standard when only 20-25% of conventional medicine is evidence-based?

Lack adequate funding to support CAM research (NCCAM budget is $100 million and NIH budget is $24 billion)

AcupunctureAcupuncture

One part of the ancient, rich system of Traditional Chinese Med, generally combined w/ Chinese herbs

Yin-Yang - opposing forces in the body. Goal of acupuncture is to restore their balance.

Qi - Life energy. Runs along channels (meridians). Acupuncture relieves blockages, improves flow

Overarching goal: rebalance, redistribute Yin-Yang and allow Qi to flow more freely.

Western Acup – needles only (without Chinese herbs)

Acupuncture Hair-thin, solid, needles: safe, sterile, disposable. Not painful. Patients often describe tingling warmth.

Chinese Herbs Centuries-old formulas. Usually 6-12 herbs mixed together. Exact formulas individualized, which makes it harder to study.

Question: Do studies of “Western acupuncture” miss efficacy of the whole TCM system?

Clinical HA Trials 1980’s + Clinical HA Trials 1980’s + 1990’s 1990’s 16 trials of true vs. sham acupuncture -

generally very small trials: n range from 10 to 52, most <30

Almost all had serious methodological problems 8 trials had positive results, 8 statistically

negative Summary data likely skewed to falsely positive

by missing negative trials (publication bias) Conclusion: possible benefit, data extremely

weak Melchart et al. Cochrane Reviews 2001; PMID 11279710

Clinical HA Trials 2000-Clinical HA Trials 2000-2008 2008

In the past 8 years there have been 16 more trials

Three of these trials have been much larger and of much higher quality than those which came before

All 3 used sound, careful, reliable methodology These trials create a new, quite robust, evidence

in assessing the efficacy of acupuncture for HA in more than 900 patients

ART - Migraine Germany 2005

n=302 True vs. sham acupuncture vs. wait list

ART - Tension Germany 2005

n=270 True vs. sham acupuncture vs. wait list

NHS trial - Mixed England 2004

n=401 True acupuncture vs. “usual care”

Sham = superficial / minimal needling of random non-acupuncture points

Linde: JAMA 2005 - PMID 15870415Melchart: BMJ 2005 - PMID 16055451Vickers: BMJ 2004 - PMID 15023828

Best High Quality RCT’s Best High Quality RCT’s

ART - Migraine Germany 2005

n=302 True vs. sham acupuncture vs. wait list

Linde: JAMA 2005 - PMID 15870415

HA days / monthp<.001

Largest High Quality RCT’s Largest High Quality RCT’s

ART - Tension HA’s Germany 2005

n=270 True vs. sham acupuncture vs. wait list

Melchart: BMJ 2005 - PMID 16055451

HA days / monthp<.001

Largest High Quality RCT’s Largest High Quality RCT’s

NHS trial - Mixed England 2004

n=401 True acupuncture x 3 mos vs. “usual care”

Vickers: BMJ 2004 - PMID 15023828

Weekly HA scorep=.0002

Largest High Quality RCT’sLargest High Quality RCT’s

Acupuncture for OA Acupuncture for OA

Large positive RCT in the Annals (Berman, 2004) Diverse group of pts (n=570), very few exclusions Patients were randomized into three arms:

1) true acup 2) sham acup 3) control - educ only

Elaborate sham acup. Survey showed successful blinding (equal # guessed they got “sham” in both arms)

2 months of full treatment, followed for 6 months

Berman. Ann Intern Med 2004:141:901

Improvement in Pain Scores

Ann Intern Med 2004:141:901

P=.003

Acupuncture for Other Acupuncture for Other ConditionsConditions

Take Home Points: Take Home Points: AcupunctureAcupuncture

There is strong evidence to show that acupuncture is effective for treatment of headaches and osteoarthritis.

For soldiers and Veterans who have headache, acupuncture is an effective adjunctive therapy for conventional medical treatment.

Caffeine

Opioids Ergot alkaloids Willow bark

- salicylates

Herbs & Supplements: Best Herbs & Supplements: Best EvidenceEvidence

(Most evidence is for Migraine (Most evidence is for Migraine Headaches)Headaches) Herbal medicines

Feverfew Butterbur

Supplements Riboflavin (vit B2) Coenzyme Q10

FeverfewFeverfew(Tanacetum parthenium)(Tanacetum parthenium)

Daisy family (asteraceae) Ragweed, marigold,

chrysanthemum, echinacea

Traditionally for HA, fever, arthritis, menstrual irregularities…

1980’s: gained popularity in Great Britain as a migraine HA remedy (chew on leaves)

Feverfew StudiesFeverfew Studiesfor migraine prophylaxis (non-for migraine prophylaxis (non-

U.S.)U.S.)DBRCTs n duration preparation results

Johnson 1985 17 6 mo Dried leaf HA freq, N/V

Murphy 1988 59 4 mo Dried leaf cap HA freq, #, N/V

Abstract 1994 20 NEGATIVE STUDY

De Weerdt 1996 50 4 mo Extract NEGATIVE STUDY

Palevitch 1997 57 2 mo Leaf capsule HA pain, N/V

Pfaffenrath 2002 147 3 mo Extract MIG-99

(3 doses)

NEGATIVE STUDY

(+ subset freq HAs)

Deiner 2005 170 4 mo Extract MIG-99 HA freq

Feverfew SEsFeverfew SEs

Mouth ulcerations (fresh leaves) Mild GI Affects platelet activity in vitro Allergic rxns Abortions in cattle

Butterbur (Petasites Butterbur (Petasites hybridus - sweet coltsfoot)hybridus - sweet coltsfoot)

Daisy family (asteraceae) Ragweed, marigolds,

chrysanthemum, echinacea

Traditionally for F, cough, GI/GU cramps, dysmenorrhea…

Affects PGs, LTs, histamine receptor

RCT evidence for allergic rhinitis = cetirizine (Zyrtec®)

Also studied for migraine prevention, after anecdotal reports

Butterbur evidenceButterbur evidence(from Germany)(from Germany)

Petadolex® German standardized proprietary extract of root Extract process reduces hepatotoxic/carcinogenic

pyrrolizidine alkaloids to < limit of detection (0.01 ppm)

DBRCTs n duration preparation results

Grossman 2000 60 3 mo. Petadolex® 50 mg BID

# attacks

Lipton 2004 245 4 mo. Petadolex®

75, 50 mg BID

75 mg BID # attacks

Butterbur SEsButterbur SEs

Petadolex® - GI (burping)

C/I Raw herb

(pyrrolizidine alkaloids) Liver disease,

pregnancy/lactation

Riboflavin (vit B2)Riboflavin (vit B2)

Mitochondrial electron transport dysfxn ~ migraines Riboflavin is utilized by mitochondria

DBRCTs n duration preparation results

Schoenen 1998 55 3 mo. 400 mg/dy # attacks >50%: 59% vs. 15%

Maizels 2004 49 3 mo. Vit B2 400 mg

Feverfew 100 mg

Mag 300 mg

Placebo=25mg B2

Negative study

> 50%: 44% vs 42%

Coenzyme Q10Coenzyme Q10

Also critical for mitochondrial fxn

DBRCT n duration preparation results

Sandor 2005 42 3 mo. 100 mg TID # attacks

>50%: 48% vs. 14%

Supplement Supplement Recommendation for Recommendation for Migraine Prevention?Migraine Prevention?

Standardized butterbur extract e.g. Petadolex® 75 mg BID

Combination product containing: Feverfew leaf 100 mg/dy Riboflavin (Vit B2) > 25 mg Coenzyme Q10 300 mg/dy Magnesium? (diarrhea)

Avoid: Butterbur raw herb - toxic Feverfew extracts - less effective?

Glucosamine & ChondroitinGlucosamine & Chondroitin

Europe: Researched since the 1960s

and used for osteoarthritis for decades

US: “The Arthritis Cure” in 1997--->

GAIT TrialGAIT Trial

Glucosamine/chondroitin Arthritis Intervention Trial NIH funded, rigorous DBRCT (NEJM Feb. 23, 2006) 1583 pts followed for 6 months, in 16 US centers Symptomatic knee OA

Well matched; withdrawal rate equal; good compliance; ITT

All patients, mild pain, mod-severe pain

PlaceboGlucosamine

500mg tid

Chondroitin

400mg tid

Glucosamine+

Chondroitin

Celebrex

200mg qd

All subjects Mod-Severe

Placebo 60% 54%

Glucosamine 64% 66%

Chondroitin 65% 61%

Glucosamine + Chondroitin 67% P=0.09 79% P<0.01

Celebrex 70% P<0.01 69% P=0.06

* WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index

GAIT TrialGAIT Trial Primary outcome = >20% reduction in WOMAC* Score (secondary outcomes = similar results)

Adverse Effects & CostAdverse Effects & Cost

Both products very well tolerated Mild GI (dyspepsia, D, C) = placebo Shellfish allergy?

No known drug interactions Cost: ~ $20-40/month

Take Home Points: Take Home Points: Supplements and HerbsSupplements and Herbs

Appear to have analgesic activity for OA Both = safe and well-tolerated Slow onset of action (2 month trial) Combination preferred [GAIT] Best for pts with mod-severe pain [GAIT]

Some evidence G&C are “disease modifying” agents

Mixed quality of products always a problem www.ConsumerLab.com

INFORMATION INFORMATION RESOURCESRESOURCES

•ConsumerLab.com

•ConsumerLab.com

DiscussionDiscussion Veterans with post-deployment health concerns, such as

headaches and osteoarthritis, are commonly using CAM as an adjunctive therapy with conventional medical treatment

There is strong evidence to support the use of acupuncture as an adjunctive therapy for treatment of headaches and osteoarthritis.

There is preliminary evidence to support use of feverfew and butterbur for treatment of headaches and glucosamine and chondroitin for treatment of osteoarthritis

Policy Implications for VHA Policy Implications for VHA and DODand DOD

Clinicians need to openly inquire Veterans about their CAM use to help them successfully integrate CAM with their conventional treatment.

VHA and DOD need to establish guideline for CAM use and credentialing and privileging standards for CAM practitioners

VHA and DOD need to allocate more resources to deliver CAM modalities, provide educational training for clinicians, and conduct research