Overview of Complementary and Alternative Medicine CAM and

Overview of Complementary and Alternative Medicine (CAM) and Its Role in Caring for Veterans with Post -Deployment Health Concerns An-Fu Hsiao, MD, PHD September 15, 2010 WRIISC: Caring for Veterans with Post-Deployment Health Concerns

Overview § 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 Complementary and Alternative Medicine (CAM) in 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 Complementary and Alternative Medicine (CAM) in 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 Medicine § 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 Integration of CAM with Conventional Treatments § Lack of knowledge on the effectiveness and safety of CAM treatments. § Lack of know-how in referring to highquality CAM practitioners. § “Turf battles” between physicians and CAM practitioners.

Lack of Safe and Effective Conventional Medical Treatment for Headaches and Osteoarthritis § 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 Are Created Equal § Some CAM modalities are evidencebased, 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 Best Research Design to Evaluate the 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 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)

Acupuncture § 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 + 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 -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

Best High Quality RCT’s 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 15870415 Melchart: BMJ 2005 - PMID 16055451 Vickers: BMJ 2004 - PMID 15023828

Largest High Quality RCT’s ART - Migraine Germany 2005 n=302 HA days / month True vs. sham acupuncture vs. wait list p<. 001 Linde: JAMA 2005 - PMID 15870415

Largest High Quality RCT’s ART - Tension HA’s Germany 2005 n=270 HA days / month True vs. sham acupuncture vs. wait list p<. 001 Melchart: BMJ 2005 - PMID 16055451

Largest High Quality RCT’s NHS trial - Mixed England 2004 n=401 Weekly HA score True acupuncture x 3 mos vs. “usual care” p=. 0002 Vickers: BMJ 2004 - PMID 15023828

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 P=. 003 Ann Intern Med 2004: 141: 901

Acupuncture for Other Conditions

Take Home Points: Acupuncture § 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.

Opioids Ergot alkaloids Willow bark - salicylates Caffeine

Herbs & Supplements: Best Evidence (Most evidence is for Migraine Headaches) § Herbal medicines § Feverfew § Butterbur § Supplements § Riboflavin (vit B 2) § Coenzyme Q 10

Feverfew (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 Studies for migraine prophylaxis (non-U. S. ) DBRCTs n duration preparation results HA freq, N/V Johnson 1985 17 6 mo Dried leaf Murphy 1988 59 4 mo Dried leaf cap Abstract 1994 20 De Weerdt 1996 50 4 mo Extract Palevitch 1997 57 2 mo Leaf capsule Pfaffenrath 2002 147 3 mo Extract MIG-99 NEGATIVE STUDY (3 doses) (+ subset freq HAs) Deiner 2005 170 4 mo Extract MIG-99 HA freq, #, N/V NEGATIVE STUDY HA pain, N/V HA freq

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

Butterbur (Petasites 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 evidence (from Germany) DBRCTs n Grossman 2000 60 Lipton 2004 duration 3 mo. 245 4 mo. preparation results Petadolex® # attacks 50 mg BID Petadolex® 75 mg BID 75, 50 mg BID # attacks § Petadolex® § German standardized proprietary extract of root § Extract process reduces hepatotoxic/carcinogenic pyrrolizidine alkaloids to < limit of detection (0. 01 ppm)

Butterbur SEs § Petadolex® - GI (burping) § C/I § Raw herb (pyrrolizidine alkaloids) § Liver disease, pregnancy/lactation

Riboflavin (vit B 2) § Mitochondrial electron transport dysfxn ~ migraines § Riboflavin is utilized by mitochondria DBRCTs n duration preparation results # attacks >50% : 59% vs. 15% Schoenen 1998 55 3 mo. 400 mg/dy Maizels 2004 Vit B 2 400 mg Negative study Feverfew 100 mg > 50% : 44% vs 42% Mag 300 mg Placebo=25 mg B 2 49 3 mo.

Coenzyme Q 10 § Also critical for mitochondrial fxn DBRCT Sandor 2005 n duration preparation 42 3 mo. results 100 mg TID # attacks >50% : 48% vs. 14%

Supplement Recommendation for Migraine Prevention? § Standardized butterbur extract § e. g. Petadolex® 75 mg BID § Combination product containing: § § Feverfew leaf 100 mg/dy Riboflavin (Vit B 2) > 25 mg Coenzyme Q 10 300 mg/dy Magnesium? (diarrhea) § Avoid: § Butterbur raw herb - toxic § Feverfew extracts - less effective?

Glucosamine & Chondroitin § Europe: Researched since the 1960 s § and used for osteoarthritis for decades § US: “The Arthritis Cure” in 1997 --->

GAIT 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 Placebo Glucosamine 500 mg tid Chondroitin 400 mg tid Glucosamine + Chondroitin Celebrex 200 mg qd § Well matched; withdrawal rate equal; good compliance; ITT § All patients, mild pain, mod-severe pain

GAIT Trial § Primary outcome = >20% reduction in WOMAC* Score § (secondary outcomes = similar results) 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 Mc. Master Universities Osteoarthritis Index

Adverse 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: Supplements 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. Consumer. Lab. com

INFORMATION RESOURCES • Consumer. Lab. com

Discussion § 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 and 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