BOTANICALS & THE BRAIN: AN UPDATE ON DIETARY SUPPLEMENTS Kelly Orr, PharmD Clinical Associate Professor Department of Pharmacy Practice College of Pharmacy The University of Rhode Island

Disclosures • Kelly Orr declares she has received research grant funding from Pfizer.

Learning Objectives • Cite evidence-based data describing the risks and benefits of selected dietary supplements for use in migraine and insomnia • Educate patients about the safe use of dietary supplements for or use in migraine and insomnia • Explain regulatory requirements related to dietary supplements and issues related to quality • Technician: List potential safety concerns with dietary supplements used for migraine and insomnia

© 2013 by the American Pharmacists Association. All rights reserved.

Background • Three-fourths of world relies on natural medicines • Journal of the American Medical Association (JAMA) study1 • 1990 - 34% used > 1 alternative therapy • 1997 - 42% used > 1 alternative therapy

• Current use approximately 40-62%2,3 • $34 billion spent out of pocket annually on Complementary and Alternative Medicine (CAM) 3 • Products, classes, visits to providers

• $15 billion spent on herbs and dietary supplements 3

1. Eisenberg et al. JAMA 1998;280:1569-75. 2. Barnes PM et. CDC Advance Data from Vital and Health Statistics No 343; May 2004 3. Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2008.

Trends in Consumer Use of Herbs/Dietary Supplements • 2010 NIH and AARP surveyed Americans over the age of 50 years old 1 • 37% used herbs and dietary supplements • 67% never discuss CAM use with a health care provider

• 2011 Harvard Opinion Research Program 2 • Conducted telephone survey of 1579 respondents • Approximately 4 out of 10 Americans reported using supplements in past 2 years

1.

AARP/NCCAM Survey of U.S. Adults 50+, 2010. Available at URL: http://nccam.nih.gov/news/camstats/2010/findings1.htm. [Accessed April 28, 2015]. 2. Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

Trends in Consumer Use of Herbs/Dietary Supplements • 2011 Harvard Opinion Research Program 1 • 36% had not told physician about use of supplements • 5% had been told by physician or nurse to stop supplement • 25% reported that they would stop using supplement if public health authorities found it was ineffective

1. Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

© 2013 by the American Pharmacists Association. All rights reserved.

Popular Herbs and Dietary Supplements: 2011 Harvard Survey 1 • Fish oils or omega-3 supplements • Herbal supplements like ginseng • Probiotics like acidophilus • Any other supplements like amino acids, algae derivatives or combination products • Supplements derived from foods like garlic supplements

1. Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

2012 National Health Interview Survey • Supplement to the Census Survey • Asked about use of 18 non-conventional health care practices • Results: 1,2 • Found that use of non-vitamin/non-mineral dietary supplements was highest used CAM modality • Increase in use of fish oil, probiotics/prebiotics and melatonin • Decrease in use of echinacea, garlic, glucosamine/chondroitin

• Use of yoga doubled from 2002 to 2012 survey • Use of these dietary supplements highest in Pacific, Mountain, and West North Central Regions 1. Peregoy JA al. \. NCHS data brief, no 146. Hyattsville, MD: National Center for Health Statistics. 2014. Available at URL: http://www.cdc.gov/nchs/data/databriefs/db146.pdf. [Accessed April 28, 2015]. 2. Clarke TC, Black LI, Stussman BJ, et al. Trends in the use of complementary health approaches among adults: United States, 2002-2012. National health statistics reports; no 79. Hyattsville, MD: National Center for Health Statistics. 2015

2012 National Health Interview Survey1

1.

Peregoy JA al. \. NCHS data brief, no 146. Hyattsville, MD: National Center for Health Statistics. 2014. Available at URL: http://www.cdc.gov/nchs/data/databriefs/db146.pdf

© 2013 by the American Pharmacists Association. All rights reserved.

REGULATIONS OF HERBS AND DIETARY SUPPLEMENTS

DSHEA: Dietary Supplement and Health Education Act • Signed into law on October 25, 1994 • Herbal supplements, vitamins and minerals considered dietary supplements not drugs • Dietary ingredients in supplements no longer subject to premarketing safety evaluations • Labeling criteria • • • • •

Body structure and function claims Cannot make therapeutic claims Must state not approved by FDA Must have manufacturer’s name and address Not required to have lot numbers, expiration dates or contraindications

Regulatory Role of FDA • FDA responsible for taking action against any unsafe dietary supplement product after it reaches the market • Post-marketing responsibilities: • Monitoring safety • Product Information • • • •

Labels Claims Package insert Accompanying literature

© 2013 by the American Pharmacists Association. All rights reserved.

Background: CAM in Migraine Prevention • > 45 million people in US seek medical attention for headaches • Direct costs: $ 11 billion • Indirect costs: $12 billion • Annual loss of 157 million workdays

• Popular CAM modalities for headaches: • Mind body interventions • Massage therapy • Spinal manipulation • Dietary supplements 1.

Headaches and Complementary Health Approaches. Available at URL: http://nccam.nih.gov/health/pain/headachefacts.htm [Accessed January 28, 2014].

Dietary Supplements for Migraine Prevention

BUTTERBUR FEVERFEW VITAMIN B2 MAGNESIUM

Butterbur Background • Origin • Petasites hybridus L. (Gaertner, Meyer & Scherb) • Member of Compositae/Asteracea family

• Uses • Migraine prevention, allergic rhinitis

• Mechanism • Petasin may reduce smooth muscle spasms, leukotriene synthesis • Isopetasin decreases prostaglandin synthesis, antiinflammatory properties Sutherland A, Sweet BV.. Am J Health Syst Pharm. 2010;67(9):705-11.

© 2013 by the American Pharmacists Association. All rights reserved.

Butterbur Evidence • Level Evidence A for Migraine Prevention • American Academy of Neurology and the American Headache Society consider effective • Level A = established as effective and should be offered for migraine prevention • Based on two well – designed (Class I) studies

Holland S, Silberstein SD, Freitag F, et. al. Neurology. 2012;78(17):1346-53

Butterbur Evidence • Three-arm, parallel-group, randomized trial of 245 • Petasites extract 75 mg twice daily, • Petasites extract 50 mg twice daily, or • Placebo twice daily for a 4 month period

• Primary outcome of decrease frequency as a percentage change from baseline • Results: • 48% reduction for Petasites 75 mg (p = 0.0012 vs placebo) • 68% reported a reduction of ≥ 50% at 4 months (p