Pain and Supplements: How to Incorporate the Guidelines

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Pain and Supplements: How to Incorporate the Guidelines Robert A. Bonakdar, MD FAAFP Director of Pain Management Scripps Center for Integrative Medicine

Assistant Clinical Professor University of California, San Diego, School of Medicine


Disclosure • Research Support – Johnson and Johnson

• Consultant – Mcneil Consumer Health – Quadrant Healthcomm


Learning Objectives • Recognize why its important to discuss dietary supplements (4 P’s) • Describe the prevalence and patterns of use • Review Guidelines that endorse Clinically Tested Dietary Supplements • Describe how to apply point of care tools to improve discussion and coordination of care


Journal of the AMERICAN DIETETIC ASSOCIATION, 2010 doi: 10.1016/j.jada.2010.07.024


Dietary Supplements - Why bother? 4 P’s CAM discussion • Protect • Promote • Permit • Participate Jonas, W.B., Chez, R.A. Complementary & alternative medicine. In Current Diagnosis & Treatment in Family Medicine. South-Paul, JE, Matheny, SC and Lewis, EL (Eds). New York: McGraw-Hill 2007; pp.549-557.


Where NOT to get your Information •


KEY Trends– Dietary Supplements 1. 2. 3. 4. 5.

HOW often are patients using DS WHAT DS they are using and WHY? WHICH patients are using DS? HOW they are using DS? WHO are they discussing DS with?


The New Pharmacy


Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008 Dec10;(12):1-23.


NHANES* Trends NHANES

Male

Female TOTAL

I (1971–1974)

28%

38%

23%

II (1976–1980)

32%

43%

35%

III (1988–1994)

35%

43%

40%

1999-2000

47%

57%

52%

2003–2006

44%

53%

49%

Note: Use increases with age *National Health and Nutiritonal Education Survey J. Nutr. 141: 261–266, 2011. Am J Epidemiol 2004;160:339–349


Other Supplement Surveys • The US Food and Drug Administration sponsored Health and Diet Survey National – 73% of US adults were found to use supplements

• Dietary Supplement Use Within a Multiethnic Population – 83% of men and 73% of women J Am Diet Assoc. 2006 Dec;106(12):1966-74. J Am Diet Assoc. 2011;111:1065-1072.


Bottom-line on use • “About one-half of the U.S. population and 70% of adults > 70 y.o. use dietary supplements…”

J. Nutr. 141: 261–266, 2011.



KEY Trends– Dietary Supplements 1. 2. 3. 4. 5.

HOW often are patients using DS WHAT DS they are using and WHY? WHICH patients are using DS? HOW they are using DS? WHO are they discussing DS with?



Top Non-Herbals 2011 1. 2. 3. 4. 5. 6. 7. 8.

ESSENTIAL FATTY ACID GLUCOSAMINE & CHONDROITINS PROBIOTIC/ACIDOPHILUS COENZYME Q10 MELATONIN AMINO ACID LUTEIN SAM-E

Source: Nutrition Business Journal 2012



Demographics of the DS Utilizer • Education level: Higher • Health condition: Varies / Dichotomy – Lower BMI / Chronic – Higher physical activity / End-Stage

• • • •

Sex: ~ Slightly to much greater use F > M Race: ~ Higher in certain ethnic group “Holistic Health View” “Active Coping Behavior” Am J Clin Nutr 2007;85(suppl):277S–9S. /Journal of Nutrition. 2001;131:1339S-1343S Why Patients Use Alternative Medicine: Results of a National Study. Astin JAMA, 1998 Patterns of alternative medicine use by cancer patients. Med J Aust. 1996;165:545-548.

Begbie SD et a


HOW Are Supplements Being Used? • Sub-optimal: – Confusion – Low Disclosure – Low Discussion – Minimal participatory decision making


Can Patients Read Labels? • Knowledge of dietary supplement label • “misconceptions regarding the term "natural," … product claims, and testing for product safety existed among participants. • Supplement users need additional education about supplement claims . . .to make informed health care choices.” Patient Educ Couns. 2004 Mar;52(3):291-6.


Supplement Stare


Can We Help Patients? • Analysis of 256 PCP visits at UCSF • Despite differential knowledge about CAM treatments, physicians helped patients assess the risks and benefits of CAM treatments and made recommendations based on patient preferences • PRACTICE IMPLICATIONS: • Providers do not have to possess extensive knowledge about … CAM to have meaningful discussions with patients and to give patients a framework for evaluating CAM treatment Koenig CJ, Ho EY, Yadegar V, Tarn DM. Negotiating complementary and alternative medicine use in primary use.care visits with older patients. Patient Educ Couns. 2012 Apr 5.


A Framework for Approaching the Patient: HERBAL Mnemonic Hear Educate and Evaluate Record Be aware Agree to Discuss Learn Re-evaluate

Bonakdar R. The H.E.R.B.A.L. Guide: Dietary Supplement Resources for the Clinician. Lippincott 2010.


How to Practically Communicate and Coordinate Dietary Supplements

1. Assume all patients are using Supplements 2. Hear the patient out: Create an open environment for discussion & use face to face questioning


Complete The Care


All In The Asking • A traditional H & P including medication questions yields a 5% CAM use • Direct questioning reveals > 40% use • 30.5% reported use of DS on a standard medical questionnaire as part of an H&P • During a more intensive survey, 61% of the same patients reported use of supplements

Metz J et al. Cancer Patients use unconventionsl medical therapies far more frequently than starndard history and physical examination suggests. Proc Am Soc Clini Oncol 19:602a, 2000 (absr 2368)..


Practical Communication and Coordination of Dietary Supplements 1. Assume all patients are using Supplements 2. Hear: Create an open environment for discussion with face to face questioning 3. Educate and Evaluate in time-effective ways to increase informed choices


Educate on Good Resources

http://www.nal.usda.gov/fnic/pubs/bibs/gen/dietarysupplementsconsumers.pdf



Office of Dietary Supplements http://ods.od.nih.gov


Educate – Key Details On Use • How to use: – “You need to use this for 3-4 months before we would expect to see benefit” – Timing of supplementation – Formulation/Brand and Dosage

• Why you are using: – Glucosamine example: Joint space preservation


Educate – When to expect benefit, example: Riboflavin


Finding Evidence • http://dietary-supplements.info.nih.gov – NIH Office of Dietary Supplements • www.nlm.nih.gov/nccam/ camonpubmed.html

– CAM on PubMed

• www.naturaldatabase.com – An objective, subscriber funded database of supplement information / interactions

• WWW.CTDSD.com – Clinically Tested Dietary Supplement Database


PubMed Dietary Supplement Subset •

http://ods.od.nih.gov/Research/PubMed_Dietary_Supplement_Subset.aspx


Searching • Natural Medicines Comprehensive Database • www.naturaldatabase.com

• Natural Standard • www.naturalstandard.com

• Dynamed – http://ebscohost.com/dynamed

All AAFP recognized source of Evidence-Based Information


Finding a Reliable Brand • Consumer Lab – www.consumerlab.com

• NSF www.nsf.org • USP www.uspverified.org – Dietary Supplement Verification Program

• “Prescription” brands • Clinical Trial brands


Educate: WHAT to use FORMULATION IS CRITICAL Well made brand (safety seals) “Prescription Brand” Clinically Tested Brand May be the difference between whether a supplement is going to be beneficial or not


Prescription Brands • Brands which are recognized as prescription medications in other countries but which are categorized as dietary supplements in the US • Examples – SAMe – Glucosamine sulfate

www.CTDSD.com


Clinically Tested • Supplements which has been evaluated for efficacy and monitored for safety in controlled trials – Clinically Tested Dietary Supplement Database – WWW.CTDSD.com


Educate and Evaluate • Examples: – Protect – – Promote – Butterbur in Migraine – Permit – Omega-3 in spinal pain – Permit – SAMe and Omega-3s in refractory OA / depression *Assumes focus on supplements and that other treatments (diet, meds, activity, etc) have been reviewed


Clinical Scenario - Promote • Female patient with ongoing migraines and difficulty tolerating numerous previous preventatives • “What else can I try?” – Natural Database – ODS / Pubmed Supplement subset – CTDSD.com


ďƒŞ

Headache. 2003 Jan;43(1):76-8.



Butterbur (Petasites hybridus root) • Constituents – Sesquiterpene – Petasin – Isopetasin – Volatile oils – Flavonoids – Tannins – Pyrrolizidine alkaloids*

• Activity • Antispasmodic effects on smooth muscle •  leukotriene & histamine synthesis • Used traditionally for allergy disorders


Butterbur - not all are created equally • Wild butterbur may have liver toxicity which has not been noted with prescription brand • Not all butterbur brands been evaluated for safety or efficacy in migraine • Most all + trials on butterbur (petasites) in migraine done on Petadolex brand • From a safety and efficacy standpoint important to use clinically tested brands and not assume that what’s on the shelf matches. Headache. 2003 Jan;43(1):76-8.


Butterbur (Petadolex)

Lipton RB, Gobel H, Einhaupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology 2004;63(12):2240–2244.


Feverfew Studies • 3 (+): Reduced severity, duration, and frequency ( ~ 24%) of migraine headaches.1-3 (employed dried, powdered leaves). • 1 (-): study which used an alcohol extract4 • Cochrane: “Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine.”5 1. Johnson ES. Br Med J 1985;291:569–73. 2. Murphy JJ, Lancet 1988;2:189–92. 3. . Palevitch D, Phytother Res 1997;11:508–11. 4. De Weerdt CJ, Phytomed 1996;3:225–30.5. 5. Cochrane Database Syst Rev. 2004;(1):CD002286.


Stable extract reproducibly manufactured with supercritical CO2 from feverfew

• Appeared to be effective in subgroup of patients with >4 migraines per month

Cephalalgia 2002; 22:523–532. Cephalalgia 2005; 25:1031–1041.


Clinically Tested for Migraine Supplement

Formula Name

Avail Manuf. in US?

Butterbur petasites hybridus Feverfew

Tanacetum parthemium

Petadolex Mig-99

Webber Webber Schape r& Br端mm er

Daily Adult Dose

Daily Ped. Dose

LOE/Stud Freq ies

BID/TI Yes 150 mg 100 mg D Level I Yes

WWW.CTDSD.com

6.25 mg TID

TID

Level II


Clinical Scenario - Permit • Patient with discogenic back pain • Also has elevated triglycerides and history of prior MI currently on a statin • “Should I take a fish oil supplement, I’ve heard it may (not) help?”



• “Insufficient evidence…” • Editorial: • Among 14 RCTs included in the metaanalysis, most were very small short-term studies and were not designed to evaluate CVD end points. Arch Intern Med. 2012;172(9):686-694.


• Among 1,050 patients with prior myocardial infarction (MI), the incidence of MCE in the EPA group (15.0%) was significantly lower than that in the control group (20.1%, adjusted hazard ratio =0.73, 95%CI 0.54–0.98, P=0.033, NNT =19).


Japan EPA Lipid Intervention Study (JELIS) • N = 18,645 with  cholesterol (70% women) • Received statin or statin + EPA (1.8 g/d) • At 5-years, EPA reduced major adverse CV events by an additional 19%


Is it available? Avail Supplement Formula Name Manuf. in US? Omega-3

Daily Adult Dose

LOE/Stu Freq dies

Mochida EPA (ethyl Pharma icosapentate) (Japan) NO 1800 mg QD Level II

WWW.CTDSD.com


• 250 patients on NSAIDs for lumbar and/or cervical spine pain • Omega-3 essential fatty acids (EPA and DHA), 2.4 gms for 2 weeks then 1.2 gms thereafter: ProEPA by Nordic Naturals • 59% were able to d/c NSAIDs


Not a perfect situation • Science is not perfect • Brand availability not perfect • Permit: – Discuss approaches including dietary approaches and available similar brands (predominantly EPA) which he may use  handout provided


Is it available? Avail Supplement Formula Name Manuf. in US? Omega-3

Omega-3

Daily Adult Dose

LOE/Stu Freq dies

Mochida EPA (ethyl Pharma icosapentate) (Japan) NO 1800 mg QD Level II 2 caps: Pro-EPA

Nordic Naturals

WWW.CTDSD.com

900 mg EPA / Yes 200 mg DHA BID

Level II


Practical Communication and Coordination of Dietary Supplements 1. Assume all patients are using Supplements 2. Hear: Create an open environment for discussion 3. Educate and Evaluate in time-effective ways 4. Record


If its not written down…. • Geriatrics Study: – Only 35% of all self-reported supplements were documented in the charts.

• Mayo Clinic Interaction Study: – Use of dietary supplements was documented in only 26% of the medical records.

• Recording in the clinic chart one of the easiest ways to prevent interactions… J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):M223-7 The American Journal of Medicine (2008) 121, 207-211 .


Practical Communication and Coordination of Dietary Supplements

1. Assume all patients are using Supplements 2. Hear: Create an open environment for discussion 3. Educate and Evaluate in time-effective ways 4. Record 5. Be Aware for Reactions / Interactions a. Know the common culprits b. Have quick reference guides c. Point of Care Confirmation


Scenario • Patient with history of arthritis and depression with suboptimal response to current anti-depressant: • “I have heard that St. Johns Wort may help?”


• N=1818 Mayo Clinic; 39.6% using supplements • In total, 107 interactions with potential clinical significance were identified • No patient had serious harm from the possible interactions during the study period

The American Journal of Medicine (2008) 121, 207-211


HDI • 5 DS accounted for 68% of the potential interactions (garlic, valerian, kava, ginkgo, SJW) • 4 classes of RX accounted for 94% of the potential interactions (antithrombotics, sedatives, antidepressants, antidiabetic agents) • A small number of Rx medications and DS accounted for most of the interactions. The actual potential for harm was low… • This information likely will help educate patients and physicians about these potential interactions.


Confirming Interactions • Ex: www.naturaldatabase.com



http://reference.medscape.com/druginteractionchecker http://www.drugs.com/drug_interactions.html

•


•

http://ods.od.nih.gov/Research/PubMed_Dietary_Supplement_Subset.aspx


• Level 1 evidence to support light therapy in seasonal MDD and St. John's wort in mild to moderate MDD. • also some evidence for the use of exercise, yoga and sleep deprivation, as well as for omega-3 fatty acids and SAM-e. • Some CAM treatments have evidence of benefit in MDD. However, problems with standardization and safety concerns may limit their applicability in clinical practice.


• The combination therapy demonstrated significantly greater improvement in HAMD scores over time (P = 0.008) beginning at week 4 (P = 0.014) (versus citalopram + placebo) J Clin Psychopharmacol. 2012 February; 32(1): 61–64.


• 6-week, RDBPC trial of SAMe 800 mg BID • The HAM–D response and remission rates were higher for those receiving SAMe (36.1% & 25.8%, respectively) than placebo (17.6% &11.7%, • The NNT for response and remission was 6 and 7 respectively. • Adverse events similar for placebo & SAMe Am J Psychiatry 2010; 167:942–948



SAMe Conclusion • Review of 11 studies: • “SAMe appears to be as effective as NSAIDs in reducing pain and improving limitations in patients with OA, without the adverse effects often associated with NSAIDS”

Soeken K et al. Safety and Efficacy of SAMe for Osteoarthritis. J of Fam Pract. 2002. 51(5). 425-30.


Clinically Tested Supplements for Depression Augmentation Supplement

SAMe Omega-3

Formula Name

Manuf.

SAMe Complete

Pharmavite

Pro-EPA

Nordic Naturals

WWW.CTDSD.com

Avail Daily Adult in US? Dose

Yes Yes

800 mg 2 caps:

LOE/Studi Freq es

BID Level II

900 mg EPA / 200 mg DHA BID

Level II


What about Glucosamine /Chondroitin in this patient? •

http://www.rheumatology.org/practice/clinical/guidelines/osteoarthritis.asp


NICE Guidelines

www.nice.org.uk/CG059


A Review of the Guidelines

•



• 18. Treatment with glucosamine and/or chondroitin sulphate may provide symptomatic benefit in patients with knee OA. If no response is apparent within 6 months treatment should be discontinued. • 19. In patients with symptomatic knee OA glucosamine sulphate and chondroitin sulphate may have structure-modifying effects …


EULAR Knee OA Recommend. •

http://www.eular.org/


Why The Difference? • Longer history of use • Availability of prescription versions • Longer research track record with available formulations • Look at benefits beyond short-term: – Joint preservation


• 8 primary trials of > 12 mo. duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate • In 2 studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. Health Technology Assessment 2009; Vol. 13: No. 52 DOI: 10.3310/hta13520



Arthritis Rheum. 2009 Feb;60(2):524-33.


Clinically Tested Supplements for Osteoarthritis Supplement

Formula Name

Glucosamine Sulphate Dona Chrondroitin 4 & 6 Sulphate Condrosulf

Manuf.

Avail Daily Adult in US? Dose

LOE/Studi Freq es

Rotta

Yes

1500mg

QD

Level I

IBSA

No

800 mg

QD

Level I

WWW.CTDSD.com


Practical Communication and Coordination of Dietary Supplements

1. Assume all patients are using Supplements 2. Hear: Create an open environment for discussion 3. Educate and Evaluate in time-effective ways 4. Record 5. Be Aware for Reactions / Interactions 6. Agree to Discuss


Agree to Discuss • As soon as the clinic interaction is over, there may be a desire to re-consider supplement choices: – New Information/research (Good and Bad) – Condition / Reasons for Supplementation Changes

• Create an avenue for ongoing discussion: – – – –

Nurse Dietician Pharmacist Other Healthcare providers . . .


Put new information in perspective • Patient: An informed media filter – How reliable is this information, does it agree with other information I have read/discussed? – How hyped is the report? (Office of DS guides)

• Provider: – Have reliable office handouts or internet links regarding the most common questions: • “Regarding the recent study on _____” • “Regarding the recent report of interactions. . ”


•

http://ods.od.nih.gov/


Practical Communication and Coordination of Dietary Supplements

1. Assume all patients are using Supplements 2. Hear: Create an open environment for discussion 3. Educate and Evaluate 4. Record 5. Be Aware for Reactions / Interactions 6. Agree to Discuss 7. Learn


Learning • Find sources that come to you that: • Keep you updated / alerted on – Research – Details (Brands / Formulations) – Interactions – Regulations / Recalls


Ongoing Learning • Newsletters from reputable sources – Office of Dietary Supplements – NCCAM – HerbalGram American Botanical Council Web site: http://www.herbalgram.org

• Conferences – American College of Nutrition • http://www.americancollegeofnutrition.org

– Natural Supplements an Evidence Based Update • http://www.scripps.org/events/natural-supplements-anevidence-based-update


Practical Communication and Coordination of Dietary Supplements 1. 2. 3. 4. 5. 6. 7. 8.

Assume all patients are using Supplements Hear: Create an open environment for discussion Educate and Evaluate Record Be Aware for Reactions / Interactions Agree to Discuss Learn Re-evaluate


r e-evalute periodically - TIPS • Set up a feasible time-frame to re-evaluate supplementation • Have patient monitor symptoms during trial • Don’t expect too much too fast – Supplements may take several months to have expected effect

• Monitor pros/cons of ongoing therapy – Is it a keeper?  avoid stockpiling



Summary: A Framework for Approaching the Patient Hear Educate and Evaluate Record Be aware Agree to Discuss Learn Re-evaluate

Bonakdar R. The H.E.R.B.A.L. Guide: Dietary Supplement Resources for the Clinician. Lippincott 2010.


Conclusions – DS • DS used by a majority of our pain patients while communication and coordination is not optimal • Our patients need and desire our input to help guide their choices in this arena • Time effective strategies are available to to improve discussion and evidence-based incorporation of dietary supplement



Pain and Supplements: How to Incorporate the Guidelines Robert A. Bonakdar, MD FAAFP Director of Pain Management Scripps Center for Integrative Medicine

Assistant Clinical Professor University of California, San Diego, School of Medicine


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