Too Many Meds: The Problem—and the Solution
1: About half of us are now taking at least one: National Center for Health Statistics (NCHS). “Health, United States, 2013: With Special Feature on Prescription Drugs.” Hyattsville, MD, 2014. http://www.cdc.gov/nchs/data/hus/hus13.pdf.
2: Use of over-the-counter (OTC) medications has exploded just as dramatically: American College of Preventive Medicine (ACPM). “Over-the-counter medications: use in general and special populations, therapeutic errors, misuse, storage and disposal.” 2011. http://www.acpm.org/?OTCMeds_ClinRef.
3: And more of us than ever are consuming dietary supplements, herbal remedies, and other products: National Center for Health Statistics (NCHS). “Dietary supplement use among U.S. adults has increased since NHANES III (1998–2004).” Last updated April 13, 2011. http://www.cdc.gov/nchs/products/databriefs/db61.htm.
4: Much evidence links the Mediterranean diet with good health, longevity, and low risk of disease: Salas-Salvadó J, Guasch-Ferré M, Lee CH, et al. “Protective effects of the Mediterranean diet on type 2 diabetes and metabolic syndrome.” J Nutr 2016;146:920S–927S.
5: The DASH diet is an effective intervention for lowering high blood pressure: Craddick SR, Elmer PJ, Obarzanek E, et al. “The DASH diet and blood pressure.” Curr Atheroscler Rep 2003;5:484–91.
6: Hundreds of thousands of deaths occur each year in the United States as a result of adverse drug reactions: Lazarou J, Pomeranz BH, Corey PN. “Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.” JAMA 1998;279:1200–1205.
7: Per-person spending on drugs in our country is close to $1,000 annually: Organization for Economic Co-operation and Development (OECD). “Health at a Glance 2015. Pharmaceutical expenditure.” http://www.keepeek.com/Digital-Asset-Management/oecd/social-issues-migration-health/health-at-a-glance-2015/pharmaceutical-expenditure_health_glance-2015-65-en#page1.
8: US spending for prescription drugs is close to $300 billion per year: Kessler G. “Trump’s truly absurd claim he would save $300 billion a year on prescription drugs.” Washington Post, February 18, 2016. https://www.washingtonpost.com/news/fact-checker/wp/2016/02/18/trumps-truly-absurd-claim-he-would-save-300-billion-a-year-on-prescription-drugs/.
9: fecal microbial transplant (FMT), a cutting-edge treatment for digestive infections resistant to antibiotics: Zanella Terrier MC, Simonet ML, Bichard P, et al. “Recurrent Clostridium difficile infections: the importance of the intestinal microbiota.” World J Gastroenterol 2014;20:7416–23.
10: Every year about 500,000 people in the United States acquire C. diff infections; about 30,000 people die as a result: Centers for Disease Control and Prevention (CDC). “Healthcare-associated infections (HAIs).” Last updated September 23, 2015. http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_clinicians.html.
11: In 2009, Americans spent almost $11 billion on antibiotic therapy Suda KJ, Hicks LA, Roberts RM, et al. “A national evaluation of antibiotic expenditures by healthcare setting in the United States, 2009.” J Antimicrob Chemother (2012) doi: 10.1093/jac/dks 445.
12: Resistant infections now account for $20 billion in annual health care costs. Tracy T, “White House proposes doubling spending on antibiotics.” Wall Street Journal, January 27, 2015.
13: livestock consumed a whopping 32 million pounds of antibiotics in 2012: Food and Drug Administration (FDA). “2012 Summary report on antimicrobials sold or distributed for use in food-producing animals.” September 2014. http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UCM416983.pdf.
14: she reacted to it in much the same way as she had responded to the blueberry pie: Graham F, Begin P, Paradis L, et al. “Streptomycin in a blueberry pie? Risk of allergic sensitization and reaction to antibiotics contained in foods.” J Allerg Clin Immunol 2013;131:AB215.
15: Those that had received the antibiotic reacted much more strongly to the spores: Noverr MC, Noggle RM, Toews GB, et al. “Role of antibiotics and fungal microbiota in driving pulmonary allergic responses.” Infect Immunol 2004;72:4996–5003.
16: one of the important roles of normal gut flora is to resist colonization by pathogenic organisms: Blaser M. “Antibiotic overuse: stop the killing of beneficial bacteria.” Nature 2011;476:393–94.
17: One study found that after a single treatment with intravenous antibiotics, fecal bacteria tests demonstrated a significant change in the variety of bacterial strains, as well as the presence and growth of C. difficile: Ambrose NS, Johnson M, Burdon DW, et al. “The influence of single dose intravenous antibiotics on faecal flora and emergence of Clostridium difficile.” J Antimicrob Chemother 1985;15:319–26.
18: Changes in the microbiome due to antibiotics have even been linked with obesity: Gerard P. “Gut microbiota and obesity.” Cell Mol Life Sci 2016;73:147–62.
19: A review of thirty-one randomized studies found that when probiotic supplements are given along with antibiotics, they reduce the risk of developing digestive symptoms: Goldenberg JZ, Ma SSY, Saxton JD, et al. “The use of probiotics to prevent C. difficile diarrhea associated with antibiotic use.” Cochrane Libr 2013. doi: 10.1002/14651858.CD006095.pub3.
20: And several studies show that spending sustained time in the forest boosts immune function: Li Q. “Effect of forest bathing trips on human immune function.” Environ Health Prev Med 2010;15:9–17.
21: These protective phytonutrients enhance immunity: Lee RJ, Cohen NA. “Role of bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis.” Curr Opin Allergy Clin Immunol 2015;15:14–20.
22: Raw, unprocessed honey also can boost immunity: Asama T, Arima T-H, Gomi T, et al. “Lactobacillus kunkeei YB38 from honeybee products enhances IgA production in healthy adults.” J Appl Microbiol 2015;119:818–26.
23: Some botanicals can also boost immunity and help prevent infection: Schapowal A, Klein P, Johnston SL. “Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials.” Avd Ther 2015;32:187–200. Cho WC, Leung KN. “In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus.” J Ethnopharmacol 2007;113:132–41.
24: So can medicinal mushrooms: Wachtel-Galor S, Yuen J, Buswell JA, et al. “Ganoderma lucidum (Lingzhi or Reishi): a medicinal mushroom.” In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. (Boca Raton, FL: CRC Press/Taylor & Francis, 2011), chapter 9. Coy C, Standish LJ, Bender G, et al. “Significant correlation between TLR2 agonist activity and TNF-α induction in J774.A1 macrophage cells by different medicinal mushroom products.” Int J Med Mushrooms 2015;17:713–22.
25: Thyme and sage, as extracts or infusions in honey, also have antimicrobial properties: Seibel J, Pergola C, Werz O, et al. “Bronchipret syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis.” Phytomedicine 2015;22:1172–77.
26: Studies done on essential oils of eucalyptus, tea tree, lemongrass, and others: Warnke PH, Lott AJ, Sherry E, et al. “The ongoing battle against multi-resistant strains: in-vitro inhibition of hospital-acquired MRSA, VRE, Pseudomonas, ESBL E. coli and Klebsiella species in the presence of plant-derived antiseptic oils.” J Craniomaxillofac Surg 2013;41:321–26.
27: Also learn to use natural products that are safe and effective treatments for minor infections, like tea tree oil (Melaleuca alternifolia) for skin and periodontal problems: Pazyar N, Yaghoobi R, Bagherani N, et al. “A review of applications of tea tree oil in dermatology.” Int J Dermatol 2013;52:784–90.
28: and Oregon grape root (Mahonia aquifolium) for the gastrointestinal tract: “Berberine.” Altern Med Rev 2000;5:175–77.
29: a whopping 26 percent of adults in the United States are now taking a statin, at an annual cost to the health care system of more than $20 billion: Gu Q P-RR, Burt VL, Kit, BK. “Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012.” Hyattsville, MD: National Center for Health Statistics, 2014.
30: as many as half of all adult Americans are candidates for statin therapy: Pencina MJ, Navar-Boggan AM, D’Agostino RB, Sr., et al. “Application of new cholesterol guidelines to a population-based sample.” N Engl J Med 2014;370(15):1422–31.
31: according to pediatric guidelines that now call for drug treatment in children as young as ten years old: National Heart, Lung, and Blood Institute (NHLBI). “Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report.” Pediatrics 2011;128(suppl 5):S213–56.
32: In the best studies, statins reduce the chance of a heart attack in those at risk by no more than one-third: Gutierrez J, Ramirez G, Rundek T, et al. “Statin therapy in the prevention of recurrent cardiovascular events: A sex-based meta-analysis.” Arch Intern Med 2012;172(12):909–19.
33: In one recent study, 25 percent of individuals on statin therapy experienced it: Cohen JD, Brinton EA, Ito MK, et al. “Understanding Statin Use in America and Gaps in Patient Education (USAGE): An Internet-based survey of 10,138 current and former statin users.” J Clin Lipidol 2012;6(3):208–15.
34: among patients who reported muscle symptoms, 47 percent of the time physicians immediately dismissed the possibility that the drug was to blame: Golomb BA, McGraw JJ, Evans MA, et al. “Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance.” Drug Saf 2007;30(8):669–75.
35: only one new case of statin-induced diabetes will occur among 250 patients after four years of treatment: Shah RV, Goldfine AB. “Statins and risk of new-onset diabetes mellitus.” Circulation 2012;126(18):e282–84.
36: Although some CoQ10 studies have shown an improvement in statin side effects, most have not: Banach M, Serban C, Sahebkar A, et al. “Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.” Mayo Clin Proc 2015;90(1):24–34.
37: Meditation is also remarkably beneficial: Schneider RH, Grim CE, Rainforth MV, et al. “Stress reduction in the secondary prevention of cardiovascular disease: randomized, controlled trial of transcendental meditation and health education in Blacks.” Circ Cardiovasc Qual Outcomes 2012;5(6):750–58.
38: In a randomized trial, 85 percent of patients who could not tolerate prescription statins were able to take red yeast rice without side effects: Becker DJ, Gordon RY, Halbert SC, et al. “Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial.” Ann Intern Med 2009;150(12):830–39, W147–839.
39: except in very rare circumstances, overproduction of acid is not to blame: Dunbar KB, Agaston T, et al. “Association of acute gastroesophageal reflux disease with esophageal histologic changes.” JAMA 2016;315(19):2104–12.
40: About 113 million prescriptions for them are filled globally each year: Perks, B. “Proton pump inhibitors are associated with increased risk of heart attack.” Pharmaceut J June 16, 2015. http://www.pharmaceutical-journal.com/news-and-analysis/proton-pump-inhibitors-are-associated-with-increased-risk-of-heart-attack/20068748.article.
41: Several years ago the total cost expenditure on PPIs was more than $13 billion: Chubineh S, Birk J. “Proton pump inhibitors: the good, the bad, and the unwanted.” S Med J 2012;105:613–18.
42: upon cessation, most of them experienced acid-related symptoms: Reimer C, Søndergaard B, Hilsted L, et al. “Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.” Gastroenterol 2009;137:80–7, 87.e1.
43: Long-term use of acid-suppressing drugs can inhibit normal, beneficial organisms, while encouraging overgrowth of harmful bacteria: Imhann F, Bonder MJ, Vich Vila A, et al: “Proton pump inhibitors affect the gut microbiome.” Gut 2016;65:740–48.
44: Some studies suggest there may be a higher rate of pneumonia in those taking H2s and PPIs: Eom CS, Jeon CY, Lim JW, et al. “Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis.” CMAJ 2011;183:310–9.
45: Reduced gastric acidity can promote bacterial overgrowth in the small intestine: Freedberg DE, Toussaint NC, Chen SP, et al. “Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial.” Gastroenterol 2015;149:883–85.e9
46: PPI therapy can block calcium absorption, leading to osteoporosis and fractures: Khalili H, Hunag ES, Jacobson BC, et al. “Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study.” BMJ 2012;344 e372.
47: A recent study brought to light the possibility of an increased risk of heart attack in patients using PPIs long term: Shah NH, LePendu P, Bauer-Mehren A, et al. “Proton pump inhibitor usage and the risk of myocardial infarction in the general population.” PLoS One 2015;10:e0124653.
48: Evidence suggests an association between PPI use, kidney inflammation, and increased risk of chronic kidney disease: Lazarus B, Chen Y, Wilson FP, et al. “Proton pump inhibitor use and the risk of chronic kidney disease.” JAMA Intern Med 2016;285:2583–93.
49: “The results emphasize the importance of limiting PPI use to only when it is medically necessary, and also limiting the duration of use to the shortest duration possible.”: Harrison P. “PPIs and kidney injury: longer use tied to higher risk.” Medscape April 14, 2016. http://www.medscape.com/viewarticle/861991. Xie Y, Bowe B, Li T, et al. “Proton pump inhibitors and risk of incident CKD and progression to ESR.” J Am Soc Nephrol 2016. Published online before print. doi: 10.1681/ASN.2015121377.
50: A study examining the use of PPIs in people age seventy-five and older showed that taking the medication was associated with a 44 percent increased risk of dementia: Gomm W, von Holt K, Thome F, et al. “Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis.” JAMA Neurol 2016;73:410–16.
51: Following a gluten-free diet improves symptoms of GERD in those with celiac disease: Nachman F, Vázquez H, Gonzalez A, et al. “Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet.” Clin Gastroenterol Hepatol 2011;9:214–9.
52: A recent study of GERD patients showed that feeling stressed was the most common lifestyle factor correlated with the disorder, present in 45.6 percent of 12,653 patients surveyed: Haruma K, Kinoshita Y, Sakamoto S, et al. “Lifestyle factors and efficacy of lifestyle interventions in gastroesophageal reflux disease in patients with functional dyspepsia: primary care perspectives from the LEGEND study.” Intern Med 2015;54:695–701.
53: Ginger has been shown in numerous studies to help with nausea: Wu K-L, Rayner CK, Chuah S-K, et al. “Effects of ginger on gastric emptying and motility in healthy humans.” Eur J Gastroenterol Hepatol 2008;20:436–40.
54: one study showed it [melatonin] to be as effective as a PPI when used in combination with other supplements: Pereira Rde S. “Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and amino acids: comparison with omeprazole.” J Pineal Res 2006;41:195–200.
55: an anti-inflammatory diet: Weil A. Healthy Aging (New York: Alfred A. Knopf, 2005), chapter 9, 140–60. http://www.drweil.com/drw/u/ART02012/anti-inflammatory-diet.
56: Among the most commonly sold OTC medications in the United States are cough-cold and allergy remedies, many of which are, or include, antihistamines: Kaufman DW, Kelly JP, Rosenberg L, et al. “Recent patterns of medication use in the ambulatory adult population of the United States: the Slone Survey.” JAMA 2002;287(3):337–44.
57: In fact, they [these older antihistamines] can impair driving ability as much as or more than alcohol: Weiler JM, Bloomfield JR, Woodworth GG, et al. “Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: a randomized, placebo-controlled trial in the Iowa driving simulator.” Ann Intern Med 2000;132(5):354–63.
58: Taking such medications for the equivalent of three years or more increased the risk of developing dementia by 54 percent: Gray SL, Anderson ML, Dublin S, et al. “Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.” JAMA Intern Med 2015;175(3):401–407.
59: several studies show that people who report regular long-term use of antihistamines are nearly three times as likely as non-users to develop these tumors: Scheurer ME, Amirian ES, Davlin SL, et al. “Effects of antihistamine and anti-inflammatory medication use on risk of specific glioma histologies.” Int J Cancer 2011;129:2290–96.
60: an inverse relationship between allergies and glioma is one of the most consistent associations in the brain tumor literature: McCarthy BJ, Rankin K, Il’yasova D, et al. “Assessment of type of allergy and antihistamine use in the development of glioma.” Cancer Epidemiol Biomarkers Prev 2011;20(2);370–8.
61: Drug therapy for allergies, taken as a whole and including OTC medications, costs more than $6 billion per year. An individual taking a second-generation antihistamine could spend anywhere from $8 to more than $200 per month. Goodman MJ, Jhaveri M, Saverno K, et al. “Cost-effectiveness of second-generation antihistamines and montekulast in relieving allergic rhinitis symptoms.” Am Health Drug Benefits 2008:1:26–34. Consumer Reports. 2013. “Best buy drugs. Using the antihistamines to treat allergies, hay fever & hives: comparing effectiveness, safety, and price.” http://consumerhealthchoices.org/wp-content/uploads/2012/02/BBD-Antihistamines-Full.pdf.
62: In a randomized, double-blind study of nearly one hundred patients, 57 percent rated nettle effective: Mittman P. “Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis.” Planta Med 1990;56:44–7.
63: A study of 132 people with hay fever found that an extract of this herb [butterbur] was as effective as cetirizine (Zyrtec) with fewer side effects: Schapowal A, Petasites Study Group. “Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis.” BMJ 2002;324(7330):144–6.
64: emotions can powerfully mitigate the effects of allergen exposure: Kimata H. “Effect of humor on allergen-induced wheal reactions.” JAMA 2001;285(6):738.
65: Colds are also the most common acute human illness: Heikkinen T, Järvinen A. “The common cold.” Lancet 2003;361:51–9.
66: colds are associated with an enormous economic burden: Frendrick AM, Monto AS, Nightengale B, et al. “The economic burden of non-influenza-related viral respiratory tract infection in the United States.” Arch Intern Med 2003;163:487–94.
67: According to World Health Organization estimates, between three and five million cases of flu-related illness occur annually, as well as 250,000 to 500,000 flu-related deaths: World Health Organization (WHO). “Influenza Fact Sheet.” March 2014. http://www.who.int/mediacentre/factsheets/fs211/en/.
68: the flu leads to more than 400,000 hospitalizations and thousands of deaths each year, most involving the elderly: Gasparini R, Amicizia D, Lai PL, et al. “Compounds with anti-influenza activity—present and future of strategies for optimal treatment and management of influenza. Part 1: Influenza life-cycle and currently available drugs.” J Prev Health Hyg 2014;55:69–85.
69: Most experts believe that vaccination provides some measure of protection: Centers for Disease Control and Prevention (CDC). “Key facts about seasonal flu vaccine.” Last updated October 2, 2015. http://www.cdc.gov/flu/protect/keyfacts.htm.
70: Studies suggest that it can reduce the risk of heart attack: Hebsur S, Vakil E, Oetgen WJ, et al. “Influenza and coronary artery disease: exploring a clinical association with myocardial infarction and analyzing the utility of vaccination in preventing myocardial infarction.” Rev Cardiovasc Med 2014;15:168–75.
71: reviews of data from healthy vaccinated individuals suggest a modest benefit at best and question the wisdom of widespread annual flu vaccination: Demicheli V, Jefferson T, Al-Ansary LA, et al. “Vaccines for preventing influenza in healthy adults.” Cochrane Database Syst Rev 2014;3:CD001269.
72: A list of vaccines and their thimerosal content is available from the US Food and Drug Administration: Food and Drug Administration (FDA). “Vaccine safety: thimerosal in vaccines.” Last updated October 27, 2015. http://www.cdc.gov/vaccinesafety/concerns/thimerosal/.
73: Nor do antibiotics have a role in preventing complications: Kenealy T, Arroll B. “Antibiotics for the common cold and acute purulent rhinitis.” Cochrane Database Syst Rev 2013;6:CD000247.
74: In fact, a whopping 41 percent of all antibiotic prescriptions are directed against respiratory infections: Shapiro DJ, Hicks LA, Pavia AT, et al. “Antibiotic prescribing for adults in ambulatory care in the USA, 2007–2009.” J Antimicrob Chemother 2014;69:234–40.
75: Studies show that NAIs shorten the duration of flu by about one day only: Jefferson T, Jones MA, Doshi P, et al. “Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children.” Cochrane Database Syst Rev 2014;10:4:CD008965. doi: 10.1002/14651858. Dobson J, Whitley RJ, Pocock S, et al. “Oseltamivir treatment for influenza in adults: a meta-analysis of randomized controlled trials.” Lancet 2015;385:1729–37.
76: And just as bacteria have become resistant to antibiotics, the flu virus is beginning to develop resistance to NAIs, specifically to oseltamivir: Spanakis N, Pitiriga V, Gennimata, V, et al. “A review of neuraminidase inhibitor susceptibility in influenza strains.” Expert Rev Anti Infect Ther 2014;12:1325–36. Nitsch-Osuch A, Brydak LB. “Influenza viruses resistant to neuraminidase inhibitors.” ACTA BP 2014;61:505–8.
77: Chronic stress, lack of social support, and depression can all interfere with immune function, increasing risk of infection: Kiecolt-Glaser J, Cohen S, Janicki-Deverts D, et al. “Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk.” PNAS 2012;109:5995–99.
78: Mindfulness meditation has been shown to reduce the incidence, severity, and duration of cold symptoms, as has moderate exercise: Barrett B, Hayney MS, Muller D, et al. “Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.” Ann Fam Med 2012;10:337–46.
79: Women, the elderly, and highly educated people use more of them: Chong Y, Fryar CD, Gu Q. “Prescription sleep aid use among adults: United States, 2005–2010.” NCHS data brief no. 127. Hyattsville, MD: National Center for Health Statistics, 2013.
80: 40 million Americans have a chronic sleep disorder and 62 percent of American adults experience a sleep problem a few nights per week: Statistic Brain. “Sleeping disorder statistics.” Research date April 12, 2015. http://www.statisticbrain.com/sleeping-disorder-statistics/.
81: Poor sleep has been linked to chronic inflammation and increased risk for a broad range of illnesses: Kryger MM, Roth T, Dement WC. Principles and practice of sleep medicine. 5th ed. (Philadelphia: Saunders, 2010).
82: Medical conditions that cause pain or discomfort, or disrupt energy, as well as many commonly used medications, can also predispose us to, precipitate, or perpetuate insomnia: Kryger, Roth, Dement, Principles and practice of sleep medicine.
83: the National Sleep Foundation, the leading nonprofit organization dedicated to improving sleep health, has received substantial funds from numerous pharmaceutical companies: Griffith D, Wiegand S. “A little too cozy? Not-for-profits may have undisclosed funding ties to for-profit companies.” Sacramento Bee. July 13, 2005. http://www.pharmadisclose.org/spgppd/sb050713.html.
84: More specifically, they [BDZs] increase light sleep at the expense of deep sleep, and they suppress dream sleep (REM): Saddichha S. “Diagnosis and treatment of chronic insomnia.” Ann Indian Acad Neurol 2010;13:94–102.
85: Z-drugs should not be combined with alcohol or other sedating medications: Huedo-Medina TB, Kirsch I, Middlemass, J, et al. “Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the FDA.” BMJ 2012;345:e8343.
86: trazodone is one of the most popular sleep aids in use today and may be useful in treating insomnia caused by SSRI antidepressants: Saddichha, “Diagnosis and treatment of chronic insomnia.”
87: Overdosing on SADs is potentially lethal: Saddichha, “Diagnosis and treatment of chronic insomnia.”
88: Suvorexant can also cause sleep paralysis: Farkas R. (2013) “Suvorexant safety and efficacy.” FDA Peripheral and Central Nervous System Drugs Advisory Committee. Available at: http://www.fda.gov.
89: BDZs reduced sleep-onset time by 10 minutes and increased total sleep time by 32 minutes: Buscemi N, Vandermeer B, Friesen C, et al. “The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs.” J Gen Intern Med 2007;22:1335–50.
90: And suvorexant decreased sleep-onset time by a mere 2.3 minutes, with an increase in total sleep time of 21 minutes: Kripke DF. “Is suvorexant a better choice than alternative hypnotics?” F1000Research 2015;4:456.
91: a representative of the pharmaceutical industry commented, “If you forget how long you lay in bed tossing and turning, in some ways that’s just as good as sleeping.”: Saul S. “Sleep drugs found only mildly effective, but wildly popular.” New York Times, October 23, 2007. http://www.nytimes.com/2007/10/23/health/23drug.html.
92: Long-term use of BDZs, Z-drugs, OTC sleep aids, and especially SADs results in tolerance: Saddichha, “Diagnosis and treatment of chronic insomnia.”
93: Rebound insomnia can last from days to months, perpetuating dependence and addiction: Saddichha, “Diagnosis and treatment of chronic insomnia.”
94: in reality, the two [Z-drugs and BDZs] are similar in terms of these adverse reactions: Saddichha, “Diagnosis and treatment of chronic insomnia.”
95: These drugs [BDZs, SADs, and OTC sleep aids] have been linked to depression, dementia, and Alzheimer’s disease, conditions also associated with impaired REM sleep: Billioti de Gage S, Moride Y, Ducruet T, et al. “Benzodiazepine use and risk of Alzheimer’s disease: case-control study.” BMJ 2014;349:g5205. Lim AS, Kowgier M, Yu L, et al. “Sleep fragmentation and the risk of incident Alzheimer’s disease and cognitive decline in older persons.” Sleep 2013;36:1027–32.
96: Even people taking fewer than eighteen pills per year had increased mortality: Kripke DF, Langer RD, Kline LE. “Hypnotics’ association with mortality or cancer: a matched cohort study.” BMJ Open 2012;2:e000850.
97: This is reinforced by the medicalization of sleep: Lim, Kowgier, Yu, “Sleep fragmentation.”
98: Noise reduction is about identifying and managing the kinds of excessive stimulation that interfere with our innate tendency to sleep: Naiman R. “Insomnia.” In: Rakel D, ed. Integrative medicine. 3rd ed. (Philadelphia: Elsevier, 2015).
99: A lack of adequate physical activity as well as chronic muscle tension, which is usually rooted in anxiety, are also examples of body noise: Naiman, “Insomnia.”
1: Mindfulness-based stress reduction (MBSR) is a structured form of meditation that has been shown to be very useful in improving sleep: Naiman, “Insomnia.”
101: CBT-I is particularly useful to mitigate excessive sleep effort: Saddicha, “Diagnosis and treatment of chronic insomnia.”
102: Some botanical medicines and nutraceutical sleep supplements can help reduce insomnia: Saddicha, “Diagnosis and treatment of chronic insomnia.”
103: Life magazine, December 12, 1949.
104: he continued to suffer severe flares that forced him to use crutches and finally a wheelchair: Régnier C. “Hygeia versus Polymnia: Some French painters and their diseases.” Medicographia 2005;27(3):279–87.
105: Dufy accepted Homburger’s offer and was admitted to Jewish Memorial Hospital in Boston in April 1950: Homburger F, Bonner CD. “The treatment of Raoul Dufy’s arthritis.” N Engl J Med 1979;301(12):669–73.
106: Dr. Homburger noted that Dufy’s response was “rapid, gratifying, and sustained”: Homburger, Bonner, “The treatment of Raoul Dufy’s arthritis.”
107: Under anesthesia, more than 800 milliliters of pus were drained: Homburger, Bonner, “The treatment of Raoul Dufy’s arthritis.”
108: On March 12, 1953, Dufy wrote in his last letter to Dr. Homburger: Mongan A. “Selections from the collection of Freddy and Regina T. Homburger; a loan exhibition, Harvard University, Fogg Art Museum [Cambridge, Mass.], April 2–24, 1971.”
109: Less than two weeks later, at the age of seventy-six, Raoul Dufy died: Homburger, Bonner, “The treatment of Raoul Dufy’s arthritis.”
110: As the most powerful anti-inflammatory agent yet discovered, cortisone transformed the practice of rheumatology almost overnight: Le Fanu J. The rise and fall of modern medicine. Rev. ed. (New York: Basic Books, 2012).
111: An estimated 1.2 percent of the US population over the age of twenty—more than 2.5 million people—received oral steroids between 1999 and 2008: Overman RA, Yeh JY, Deal CL. “Prevalence of oral glucocorticoid usage in the United States: a general population perspective.” Arthritis Care Res (Hoboken) 2013;65(2):294–8.
112: The simple convenience of writing a prescription for a steroid has supplanted the traditional scientific method: Le Fanu, The rise and fall of modern medicine.
113: When initiating steroid treatment, experts agree on using the smallest dose for the shortest time: Singh JA, Saag KG, Bridges SL, Jr., et al. 2015 “American College of Rheumatology guideline for the treatment of rheumatoid arthritis.” Arthritis Care Res (Hoboken) 2015.
114: In 1950, at the age of seventy-three, Raoul Dufy was the oldest patient ever to be treated with cortisone: Homburger, Bonner, “The treatment of Raoul Dufy’s arthritis.”
115: Between 1997 and 2014, the FDA received reports of ninety serious neurologic events, some fatal, related to epidural injection of steroids: Racoosin JA, Seymour SM, Cascio L, Gill R. “Serious neurologic events after epidural glucocorticoid injection: the FDA’s risk assessment.” N Engl J Med 2015;373(24):2299–301.
116: Currently, there are at least twenty prescription-only formulations, as well as a multitude of brand-name and generic versions of OTC NSAIDs: Consumer Reports. “The nonsteroidal anti-inflammatory drugs: treating osteoarthritis and pain: comparing effectiveness, safety, and price.” July 2013.
117: Improved diet and exercise can lead to weight loss, and weight loss often reduces chronic pain: Narouze S, Souzdalnitski D. “Obesity and chronic pain: systematic review of prevalence and implications for pain practice.” Reg Anesth Pain Med 2015;40:91–111.
118: Except for fish, eggs, and high-quality dairy products, animal foods are minimized: Minihane AM, Vinoy S, Russell WR, et al. “Low-grade inflammation, diet composition and health: current research evidence and its translation.” Br J Nutr 2015;114:999–1012.
119: it is well established that improved sleep can result in decreased chronic pain: Passos GS, Pyares D, Santana M, et al. “Exercise improves immune function, antidepressive response, and sleep quality in patients with chronic primary insomnia.” BioMed Res Internat 2014:Article 498961, 7p.
120: Smoking is associated with increased chronic pain: Petre B, Torbey S, Griffith JW, et al. “Smoking increases risk of pain chronification through shared corticostriatal circuitry.” Hum Brain Map 2015;36:683–94.
121: It [arnica] has also been shown to decrease pain and swelling after surgery: Brinkhaus B, Wilkens JM, Ludtke R, et al. “Homeopathic arnica therapy in patients receiving knee surgery: results of three randomised double-blind trials.” Compl Ther Med 2006;14:237–46.
122: Additionally, arnica has been shown to decrease pain associated with mild to moderate osteoarthritis: Widrig R, Suter A, Saller R, et al. “Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomized double-blind study.” Rheumatol Internat 2007;27:585–91.
123: curcumin supplementation has been found to be as effective as ibuprofen for osteoarthritis of the knee: Kuptniratsaikul V, Daipratham P, Taechaarpornkul W, et al. “Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.” Clin Interv Aging 2014;9: 451–58.
124: Extracts of a familiar relative of turmeric—ginger—have been shown to modestly improve pain associated with osteoarthritis of the knee: Altman RD, Marcussen KC. “Effects of a ginger extract on knee pain in patients with osteoarthritis.” Arthrit Rheumatol 2001;44:2531–538.
125: Acupuncture can also work as an alternative to chronic NSAID use: Vickers A, Phil D, Cronin A, et al. “Acupuncture for chronic pain: individual patient data meta-analysis.” Arch Intern Med 2012;172:1444–53.
126: Mind-body approaches, such as hypnosis, guided imagery, and guided meditation, can provide relief by teaching patients to change their perception of painful sensations: Astin JA. “Mind-body therapies for the management of pain.” Clin J Pain 2004;20:27–32.
127: Adverse reactions to drugs are the fourth leading cause of death in our country: Institute of Medicine (IOM). “To err is human: building a safer health system.” Washington, DC: National Academy Press, 2000. Lazarou J, Pomeranz BH, Corey PN. “Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies.” JAMA 1998;279:1200–1205. Gurwitz JH, Field TS, Avorn J, et al. “Incidence and preventability of adverse drug events in nursing homes.” Am J Med 2000;109:87–94.
128: In 2010, antidepressants were the second most commonly prescribed medications: National Institute of Mental Health (NIMH). Director’s Blog: “Antidepressants: a complicated picture.” December 6, 2011. http://www.nimh.nih.gov/about/director/2011/antidepressants-a-complicated-picture.shtml.
129: The rate of antidepressant use across all age groups exploded from 1988 to 2008, increasing nearly 400 percent: Pratt L, Brody DJ, Gu Q. “Antidepressant Use in Persons Aged 12 and Over: United States, 2005–2008.” NCHS Data Brief. No 76. October 2011. Centers for Disease Control and Prevention (CDC). NCHS Data Brief No. 76, October 2011. http://www.cdc.gov/nchs/data/databriefs/db76.htm. National Center for Health Statistics (NCHS). “Health, United States, 2010: with special feature on death and dying.” Table 95. Hyattsville, MD, 2011.
130: One study showed that medical professionals other than psychiatrists write 80 percent of antidepressant prescriptions: Mark T, Levit K, Buck J. “Datapoints: psychotropic drug prescriptions by medical specialty.” Psychiatry Svc 2009;60:1167.
131: Use by pregnant women may increase the risk of autism in their children, as well as birth defects: Bérard A, Iessa N, Chaabane S, et al. “The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis.” Br J Clin Pharmacol 2016. doi: 10.1111/bcp.12849.
132: Although they have a better side-effect profile, the efficacy of SGAs is not as good as that of the first-generation drugs: Leucht S, Corves C, Arbter D, et al. “Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis.” Lancet 2009;373:31–41.
133: In 2013, Abilify was the number one prescribed psychotropic medication and the overall top drug by sales: Brooks, M. “Top 100 selling drugs of 2013.” Medscape, January 30, 2014. http://www.medscape.com/viewarticle/820011.
134: Between 2001 and 2011, the US Veterans Health Administration and Department of Defense spent almost $850 million on Seroquel: “VA/Defense mental health drug expenditures since 2001. May 2012 drug totals.” http://cdn.govexec.com/media/gbc/docs/pdfs_edit/051712bb1_may2012drugtotals.pdf.
135: Furthermore, physicians prescribe these medications off label for insomnia, anxiety, stress, and mild mood disorders: Alexander GC, Gallagher SA, Mascola A, et al: “Increasing off-label use of antipsychotic medications in the United States, 1995–2008.” Pharmacoepidemiol Drug Saf 2011;20:177–84.
136: More importantly, long-term use of antipsychotic medication does not provide more benefits than short-term use: Wunderink L, Nieboer RM, Wiersma D, et al. “Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.” JAMA Psychiatry 2013;70:913–20.
137: Together, they [anxiety disorders] cost the United States more than $42 billion a year: Anxiety and Depression Association of America (ADAA). “Facts and statistics.” Last updated September 2014. http://www.adaa.org/about-adaa/press-room/facts-statistics.
138: A 2013 survey showed that Xanax has consistently been the number one prescribed psychiatric medication, with Ativan at number five and Valium in eleventh place: Grohol J. “Top 25 psychiatric medication prescriptions for 2013.” Psych Central. http://psychcentral.com/lib/top-25-psychiatric-medication-prescriptions-for-2013/.
139: Many options are available for managing depression and anxiety without drugs: Weil A. Spontaneous Happiness (New York: Little, Brown, 2011).
140: There is good scientific evidence, for example, for the antidepressant effects of exercise: Archer T, Josefsson T, Lindwall M. “Effects of physical exercise on depressive symptoms and biomarkers in depression.” CNS Neurol Disord Targets 2014;13:1640–53.
141: and supplemental fish oil: Grosso G, Galvano F, Marventano S, et al. “Omega-3 fatty acids and depression: scientific evidence and biological mechanisms.” Oxid Med Cell Longev 2014; 2014: 313570. doi: 10.1155/2014/313570.
142: The costs add up to more than $240 billion in annual spending to cover health care, educational services, and decreased productivity: Perou R, Bitsko RH, Blumberg SJ, et al. “Mental health surveillance among children—United States, 2005–2011.” MMWR 2013;62(suppl 2):1–35.
143: According to the US National Health and Nutrition Examination Survey, 6 percent of US teens reported using a psychiatric medication in the past month: Jonas B, Gu Q, Albertorio-Diaz JR. “Psychotropic medication use among adolescents: United States, 2005–2010.” NCHS data brief no. 135, December 2013. http://www.cdc.gov/nchs/data/databriefs/db135.pdf.
144: A 2014 report from the Agency for Healthcare Research and Quality: Agency for Healthcare Research and Quality (AHRQ). Medical expenditure panel survey, 2014. http://meps.ahrq.gov/mepsweb/data_files/publications/st434/stat434.pdf.
145: In depressed children twelve or younger, antidepressants were found to be less effective than in adolescents: Bridge JA, Iyengar S, Salary CB, et al. “Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials.” JAMA 2007;297:1683–96.
146: Also, these rats [rats treated with Prozac before maturity] show problems with sexual behavior as adults: Iñiguez SD, Alcantara LF, Warren BL, et al. “Fluoxetine exposure during adolescence alters responses to aversive stimuli in adulthood.” J Neurosci 2014;34:1007–21.
147: A study of children diagnosed with bipolar disorder found that about 60 percent had been treated previously with an antidepressant or a stimulant medication: Cicero D, Rif S, El-Maliakh et al. “Antidepressant exposure in bipolar children.” Psychiatry 2003;66:317–22.
148: the majority of SGAs are prescribed off label for depression, anxiety, insomnia, and disruptive behavior—without much being known about their long-term risks versus benefits: Rettew DC, Greenblatt J, Kamon J, et al. “Antipsychotic Medication Prescribing in Children Enrolled in Medicaid.” Pediatrics 2015;135:658–65.
149: Only a small percentage of children and teens who are prescribed these powerful drugs also receive psychotherapy: Olfson M, King M, Schoenbaum M. “Treatment of young people with antipsychotic medications in the United States.” JAMA Psychiatry 2015;72:867–74.
150: Some studies even suggest a reduction in brain volume over time with the use of these medications: Ho B-C, Andreasen NC, Ziebell S, et al. “Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia.” Arch Gen Psychiatry 2011;68:128–37.
151: in one study, Abilify use resulted in a weight gain of 10 pounds after eleven weeks; Zyprexa, 19 pounds; Seroquel, 13 pounds; and Risperdal, 12 pounds: Correll CU, Manu P, Olshanskiy V, et al. “Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.” JAMA 2009;302:1765–73.
152: In one study, teens prescribed benzodiazepines were ten times more likely to misuse these medications to get high: Boyd CJ, Austic E, Epstein-Ngo Q, et al. “A prospective study of adolescents’ nonmedical use of anxiolytic and sleep medication.” Psychol Addict Behav 2015;29:184–91.
153: A diet of unprocessed whole foods… limits inflammation in the body and promotes better mental health: Jacka FN, Kremer PJ, Berk M, et al. “A prospective study of diet quality and mental health in adolescents.” PloS One 2011;6:e24805.
154: Recent research links depression with increased inflammation: Miller AH and Raison CL. “The role of inflammation in depression: from evolutionary imperative to modern treatment target.” Nature Rev Immunol 2016: 16, 22–34; doi: 10.1038/nri.2015.5.
155: according to the latest government statistics, about 4.2 million of them [children] are taking a psychostimulant medication: Centers for Disease Control and Prevention (CDC). “New data: Medication and behavior treatment.” Last updated March 15, 2015. http://www.cdc.gov/ncbddd/adhd/data.html.
156: In 2010, a researcher showed that children born in August were more than twice as likely to be diagnosed with ADHD: Elder T. “The importance of relative standards in ADHD diagnoses: Evidence based on exact birth dates.” J Health Econ 2010;29:641–56.
157: Another study, described in the book The ADHD Explosion: Hinshaw S, Sheffler R. The ADHD Explosion: myths, medication, money, and today’s push for performance (Oxford: Oxford University Press, 2014).
158: in 2011 the ADHD rate in Indiana was 13.8 percent, almost double that of neighboring Illinois: Centers for Disease Control and Prevention (CDC). “New data: medication and behavior treatment.” Last updated March 15, 2015. http://www.cdc.gov/ncbddd/adhd/data.html.
159: One study showed that of children who were rated by one teacher as having inattention symptoms of ADHD, fewer than 50 percent were so rated by their teacher in the following year: Rabiner DL, Murray DW, Rosen L, et al. “Instability in teacher ratings of children’s inattentive symptoms: implications for the assessment of ADHD.” J Dev Behav Pediatr 2010;31:175–80.
160: The cost of ADHD drugs ranges from $15 to $500 a month. Brody B. “The shocking cost of your child’s ADHD.” Fiscal Times, April 1, 2013.
161: Even though children are still the primary users, in recent years the greatest increase in expenditure on them has been among adults. Express Scripts Report. “Turning attention to ADHD: US medication trends for attention deficit hyperactivity disorder.” March 2014.
162: A recent study showed that 62 percent of children of parents with a history of major depression, bipolar disorder, or schizophrenia developed psychotic symptoms while taking psychostimulants: Mackenzie L, Abidi S, Fisher HL, et al. “Stimulant medication and psychotic symptoms in offspring of children with mental illness.” Pediatrics 2016;137:1–10.
163: The most famous of these was the so-called Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) study: Jensen PS, Arnold LE, Swanson JM, et al. “3-year follow-up of the NIMH MTA study.” J Am Acad Child Adolesc Psychiatry 2007;46:989–1002.
164: “The modest significant advantages we found at the twenty-four-month assessment for the MTA Medication Algorithm… were completely lost by thirty-six months”: Jensen et al., “3-year follow-up of the NIMH MTA study.”
165: Results of another long-term investigation, the Preschool Attention Deficit Hyperactivity Treatment Study: Riddle MA, Yershova K, Lazzaretto D, et al. “The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up.” J Am Acad Child Adolesc Psychiatry 2013;52:264–78.
166: One study measured the thickness of the cerebral cortex in the frontal lobe of the brain as children grew: Shaw P, Malek M, Watson B, et al. “Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder.” Biol Psychiatry 2013;74:599–606.
167: The long-term studies that could give us answers are hard to do with children, but they have been done with rats, and the results should give us pause: Marco E, Adriani W, Ruocco LA, et al. “Neurobehavioral adaptations to methylphenidate: the issue of early adolescent exposure.” Neurosci Biobehav Rev 2011;35:1722–39.
168: The conclusions… highlighted the “urgent need for large randomized controlled trials of non-pharmacological treatments”: Storebø OJ, Ramstad E, Krogh HB, et al. “Methylphenidate for children and adolescents with attention deficit hyperactivity disorder.” Cochrane Database Syst Rev 2015 Nov 25;11:CD009885.
169: In one survey, nearly two-thirds of students at a large mid-Atlantic university had been offered stimulant medication, and 31 percent admitted to abusing ADHD drugs: Watson GLF, Arcona AP, Anotonuccio DO. “The ADHD drug abuse crisis on American college campuses” Ethical Hum Psychol Psychiatry 2015;17:1–16.
170: As quoted in one study, a young college student said, “You swallow Adderall to study and snort it for fun”: Varga MD. “Adderall abuse on college campuses: a comprehensive literature review.” J Evid Based Soc Work 2012;9:293–313.
171: a 2011 study published in the prestigious British medical journal the Lancet showed that 64 percent of children improved significantly when placed on an elimination diet: Pelsser LM, Frankena K, Toorman J, et al., “Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial.” Lancet 2011;377:494–503.
172: Omega-3 fatty acids, found primarily in fish, are generally deficient in affected children; supplementation with fish oil can be beneficial: Bloch M, Qawasmi A. “Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis.” J Am Acad Child Adolesc Psychiatry 2011;50:991–1000.
173: one study did find that giving supplemental probiotics to infants significantly decreased their chances of developing ADHD: Pärtty A, Kalliomäki M, Wacklin P, et al. “A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial.” Pediatr Res 2015;77:823–28.
174: in 2010 American physicians prescribed enough [opioids] to treat every adult in the country around the clock for a month: Centers for Disease Control and Prevention (CDC). “Prescription painkiller overdoses in the US.” http://www.cdc.gov/vitalsigns/PainkillerOverdoses/index.html. Last updated November 1, 2011.
175: for more than 1.5 billion people worldwide and more than 100 million Americans, the problem lasts more than several months, becoming chronic: IOM (Institute of Medicine). Relieving pain in America: a blueprint for transforming prevention, care, education, and research. (Washington, DC: The National Academies Press, 2011).
176: Involvement of these other brain regions appears to be related to difficult symptoms that often accompany chronic pain: Tsang A, Von Korff M, Lee S, et al. “Common chronic pain conditions in developed and developing countries: Gender and age differences and comorbidity with depression-anxiety disorders.” J Pain 2008;9:883–91. Smallwood RF, Laird AR, Ramage AE, et al. “Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume.” J Pain 2013;14:663–75.
177: “It is remarkable that opioid treatment of long-term/chronic non-cancer pain does not seem to fulfill any of the key outcome opioid treatment goals.”: Eriksen J, Sjøgren P, Bruera E, et al. “Critical issues on opioids in chronic non-cancer pain: an epidemiological study.” Pain 2006;125:172–79.
178: This followed a call by noted pain clinicians to not undertreat pain: Apkarian AV, Baliki MN, Farmer MA. “Predicting transition to chronic pain.” Curr Opin Neurol 2013;26:360–7.
179: Overall, opioid prescriptions have quadrupled since 1999, with a similar sharp increase in opioid-related overdoses, injuries, and deaths: Deyo RA, Mirza SK, Turner JA, et al. “Overtreating chronic back pain: time to back off?” J Am Board Fam Med 2009;22:62–8.
180: Prescription opioid abuse and misuse cost the United States more than $60 billion each year: Gusovsky D. “America’s painkiller epidemic grips the workplace.” CNBC. December 15, 2015. http://www.cnbc.com/2015/12/15/80-percent-of-workplaces-face-this-drug-scourge.html.
181: Dr. Richard A. Friedman… wrote in a New York Times editorial in 2015: PBS. “The opium kings: opium throughout history.” Frontline. Accessed February 11, 2015 at http://www.pbs.org/wgbh/pages/frontline/shows/heroin/etc/history.html.
182: By 2011, many of the clinicians involved in promoting increased opioid use were publicly acknowledging that there were significant problems: Catan T, Perez E. “A pain drug champion has second thoughts.” Wall Street Journal, December 11, 2011. http://online.wsj.com/news/articles/SB10001424127887324478304578173342657044604.
183: A recent review of more than twenty lower-back-pain studies: Kizhakkeveettil A, Rose K, Kadar GE. “Integrative therapies for low back pain that include complementary and alternative medicine care—a systematic review.” Glob Adv Health Med. 2014;3(5):49–64.
184: the Oregon Pain Management Commission’s integrative initiative: The Oregon Pain Management Commission (OPMC). http://www.oregon.gov/oha/OHPR/PMC/pages/index.aspx.
185: In 2014, 32.5 percent of American adults had a diagnosis of high blood pressure: National Center for Health Statistics (NCHS), “Health, United States, 2014: with special feature on adults aged 55–64.” Hyattsville, MD, 2015.
186: Research continues to indicate that careful blood pressure control markedly decreases risk: Siu, AL. “Screening for high blood pressure in adults: US Preventive Services Task Force recommendation statement.” Ann Intern Med. 2015;163(10):778–86.
187: Recent research findings suggest that it is desirable to lower pressures that are even slightly above the 120/80 previously considered normal: Sundstrom J, Arima H, Jackson R, Turnbull F, RahimiK, Chalmers J, Woodward M, Neal B. “Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis.” Ann Intern Med. 2015;162:184–91.
188: In 2010, the United States spent nearly $42.9 billion on the management of hypertension: Davis K. “Expenditures for hypertension among adults age 18 and older, 2010: estimates for the UW civilian noninstitutionalized population.” Statistical brief no. 404. April 2013. Agency for Healthcare Research and Quality (AHRQ). http://www.meps.ahrq.gov/mepsweb/data_files/publications/st404/stat404.shtml.
189: Recent studies indicate that beta blockers are probably not the best first choice for blood pressure management in most people: Farooq U. “2014 guideline for the management of high blood pressure (Eighth Joint National Committee): take-home messages.” Med Clin N Am. 2015;99:733–8.
190: There are any number of ways to treat—and prevent—high blood pressure: Plotnikoff GA, Dusek J. “Hypertension.” In Rakel D, ed. Integrative medicine. 3rd ed. (Philadelphia: Elsevier, 2010).
191: And several recent studies indicate that eating unsalted nuts can lower blood pressure: Mohammadifard N, Salehi-Abargouei A, Salas-Salvado J, Guasch-Ferre M, Humphries K, Sarrafzadegan N. “The effect of tree nut, peanut, and soy nut consumption on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials.” Am J Clin Nutr. 2015; 101(5):966–82.
192: A 2013 review found that reducing sodium from between 9 and 12 grams daily to between 5 and 6 grams daily has a significant beneficial effect: Aburto NJ, Ziolkovska A, et al., “Effect of lower sodium intake on health: systematic review and meta-analyses.” BMJ 2013:346:f1326.
193: A number of lifestyle factors favorably influence blood pressure: Oza R, Barcellano M. “Nonpharmacologic management of hypertension: what works?” Am Fam Physician. 2015;91(11):772–6.
194: Yoga shows promise in what little research we have so far: Posadzki P, Cramer H, Kuzdzal A, Lee MS, Ernst E. “Yoga for hypertension: a systematic review of randomized clinical trials.” Complement Ther Med. 2014;22(3):511–22.
195: as does tai chi: Hartley L, Flowers N, Lee MS, Ernst E, Rees K. “Tai chi for primary prevention of cardiovascular disease.” Cochrane Database Syst Rev. 2014;9;4:CD010366. doi: 10.1002/14651858.CD010366.pub2.
196: Relaxation training, such as breathing exercises, meditation, and biofeedback, lowers blood pressure: Plotnikoff, “Hypertension.”
197: Research indicates that people who are less isolated and more connected with others are less likely to be hypertensive: Yang YC, Boen C, Mullan HK. “Social relationships and hypertension in late life: evidence from a nationally representative longitudinal study of older adults.” J Aging Health. 2015;27(3):403–31.
198: A number of supplements have shown promise in lowering blood pressure: “Natural medicines in the clinical management of hypertension.” http://naturaldatabase.therapeuticresearch.com.
199: The cost of diabetes in 2007 was estimated at $174 billion and growing: American Diabetes Association (ADA). “Economic costs of diabetes in the U.S. in 2007.” Diabetes Care 2008;31:596–615.
2: Treatment plans are provided to doctors, nurses, and other health professionals to help optimize care: Garber AJ, et al. “AACE/ACE comprehensive diabetes management algorithm 2015.” Endocr Practice 2015;21:438–47.
201: A 2007 summary of the known science on the safety of rosiglitazone stunned the medical community: Nissen SE, Wolski K. “Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.” N Engl J Med 2007;356:2457–71.
202: Based on this definition, more than half of women and a third of men over age fifty in the United States are believed to have osteopenia: Looker AC, Melton LJ, et al. “Prevalence and trends in low femur bone density among older US adults: NHANES 2005–2006 compared with NHANES III.” J Bone Miner Res 2010;25:64–71.
203: Today the drugs [bisphosphonates] are also given to children with inherited skeletal disorders, such as osteogenesis imperfecta: Francis MD, Valent DJ. “Historical perspectives on the clinical development of bisphosphonates in the treatment of bone diseases.” J Musculoskelet Neuronal Interact 2007;7:2–8.
204: Decades of research have shown the bisphosphonates act in the body as anti-resorptive agents: Rodan GA, Fleisch HA. “Bisphosphonates: mechanisms of action.” J Clin Invest 1996;97:2692–96.
205: Among the many adverse reactions to [bisphosphonates] are atypical fractures of the thigh bones: Odvina CV, Zerwekh JE, et al. “Severely suppressed bone turnover: a potential complication of alendronate therapy.” J Clin Endocrinol Metab 2005;90:1294–1301.
206: osteonecrosis of the jaw: Khosla S, Burr D, et al. “Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research.” J Bone Miner Res 2007;22:1479–91.
207: the number of osteoporotic patients needed to receive treatment for three years to prevent one hip fracture is forty-five for vitamin D, forty-eight for strontium ranelate, and ninety-one for bisphosphonates: Sweet MG, Sweet JM, et al. “Diagnosis and treatment of osteoporosis.” Am Fam Physician 2009;79:193–200.
208: For managing the precondition osteopenia with bisphosphonates, the number needed to treat is very high, meaning the drugs are not very effective: Ringe JD, Doherty JG. “Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat.” Rheumatol Int 2010;30:863–869. Eriksen EF. “Treatment of osteopenia.” Rev Endocr and Metab Disord 2012;13:209–23.
209: When hormones are advised, the transdermal application of bioidentical products (those with the same chemical structures as the body’s own hormones) may cause fewer side effects and have a somewhat lower risk profile than other forms of estrogen: Holtorf K. “The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?” Postgrad Med 2009;121:73–85.
210: Research indicates that the trace element strontium stimulates bone formation and is effective for preventing bone loss: Reginster JY, Deroisy R, et al. “Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year-double-masked, dose-ranging, placebo-controlled PREVOS trial.” Osteoporos Int 2002;13:925–31.
211: Research shows that weight-bearing exercises like walking are effective for increasing bone density of the hips and spine: Iwamoto J, Sato Y, et al. “Effectiveness of exercise in the treatment of lumbar spinal stenosis, knee osteoarthritis, and osteoporosis,” Aging Clin Exp Res 2010;2:116–22.
212: Research shows that diet and exercise are twice as effective as the drug metformin (Glucophage, Glumetza) for reducing the progression of pre-diabetes to diabetes: Knowler WC, Barrett-Connor E, et al. “Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.” New Engl J Med 2002;346:393–403.
213: An estimated 263.6 million prescriptions were written for children and adolescents in the United States in 2010: Chai G, Governale L, McMahon AW, et al. “Trends of outpatient prescription drug utilization in US children, 2002–2010.” Pediatr 2012;130(1):23–31.
214: studies show that use [of OTC cough and cold medicines] in the two-to six-year-old age group has actually increased: Mazer-Amirshahi M, Rasooly I, Brooks G, et al. “The impact of pediatric labeling changes on prescribing patterns of cough and cold medications.” Pediatr 2014;165(5):1024–8.e1.
215: Nonetheless, the 2012 annual report of the American Association of Poison Control Centers lists OTC cough-cold medications among the top three products associated with fatality in children under age five: Mowry JB, Spyker DA, Cantilena LR Jr, et al. “2012 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 30th Annual Report.” Clin Toxicol (Phila) 2013;51(10):949–1229.
216: guaifenesin is ineffective; large randomized studies have shown it to have no measurable effect: Hoffer-Schaefer A, Rozycki HJ, Yopp MA, et al. “Guaifenesin has no effect on sputum volume or sputum properties in adolescents and adults with acute respiratory tract infections.” Respir Care 2014;59(5):631–6.
217: Phenylephrine also lacks demonstrated effectiveness, and there are no studies of its safety in children: Hatton RC, Winterstein AG, McKelvey RP, et al. “Efficacy and safety of oral phenylephrine: systematic review and meta-analysis.” Ann Pharmacother. 2007;41(3):381–90.
218: AAP clinical policy statements dating from 1997 have found no studies to support the safety or efficacy of dextromethorphan in pediatrics and no indications for its use: American Academy of Pediatrics (AAP). Committee on Drugs. “Use of codeine-and dextromethorphan-containing cough remedies in children.” Pediatr 1997;99(6):918–20.
219: According to the 2007 National Health Interview Survey, an estimated 2.9 million children and adolescents use some type of dietary supplement: Wu CH, Wang CC, Kennedy J. “The prevalence of herb and dietary supplement use among children and adolescents in the United States: results from the 2007 National Health Interview Survey.” Complement Ther Med 2013;21(4):358–63.
220: Buckwheat (dark) honey, in those over one year of age for reducing nighttime cough: Oduwole O, Meremikwu MM, Oyo-Ita A, et al. “Honey for acute cough in children.” Cochrane Database Syst Rev 2014;12:CD007094.
221: Use of oral zinc in liquid or lozenge form is associated with fewer colds in children: Fashner J, Ericson K, Werner S. “Treatment of the common cold in children and adults.” Am Fam Physician 2012;86(2):153–9.
222: A 2011 AAP statement cautioned that children and adolescents should not consume energy drinks: Committee on Nutrition and the Council on Sports Medicine and Fitness. “Sports drinks and energy drinks for children and adolescents: are they appropriate?” Pediatr 127(6):1182–9.
223: Insufficient sleep has been linked to overweight and obesity in children and may be treated with prescription or OTC medications: Gurnani M, Birken C, Hamilton J. “Childhood obesity: causes, consequences, and management.” Pediatr Clin North Am 2015;62(4):821–40.
224: In adults, long-term treatment with metformin has been shown to increase the risk of vitamin B12 deficiency: Gurnani, “Childhood obesity.”
225: We have very limited data on the impact of statins in children: Gurnani, “Childhood obesity.”
226: Long-term studies on its [orlistat’s] effects in children and adolescents are lacking: Gurnani, “Childhood obesity.”
227: surgery… should be reserved for carefully screened, dangerously obese adolescents: Inge TH, Courcoulas AP, Jenkins TM, et al. “Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents.” N Engl J Med 2016 ;374(2):113–23.
228: These OTC remedies [for sleep] are particularly attractive to older people, many of whom find good sleep elusive: McCall, WV. “Sleep in the elderly: burden, diagnosis, and treatment.” Prim Care Companion J Clin Psychiatry 2004;6(1).
229: Studies of older hip fracture patients have shown that 16 to 62 percent develop delirium: Kyziridis T. “Post-operative delirium after hip fracture treatment—a review of the current literature.” Psychosoc Med. 2006;3: Doc01(PMC2736510).
230: Moreover, benzodiazepines also increase the risk of falls and can even precipitate delirium by making people groggy and confused: Sithamparanathan, K, Sadera, L, Leung, L. “Adverse effects of benzodiazepine use in elderly people: a meta-analysis.” Asian J Gerontol Geriatr 2012;7(2):107–11.
231: The American Geriatrics Society felt so strongly about avoiding benzodiazepine use in the elderly: American Geriatrics Society. “Ten things physicians and patients should question.” Choosing Wisely by ABIM. Released February 21, 2013 (1–5), and February 27, 2014 (6–10); Revised April 23, 2015 (2, 3, 6, 7, 8, and 10). http://www.choosingwisely.org/societies/american-geriatrics-society/.
232: long-term suppression of it [stomach acid] with drugs like omeprazole can have serious consequences: McDonald EG, Milligan J, Frenette C, Lee TC. “Continuous proton pump inhibitor therapy and the associated risk of recurrent Clostridium difficile infection.” JAMA Intern Med. 2015;175(5):784–91.
233: tricyclic antidepressants, like their antihistamine relatives, can cause urinary obstruction and constipation as well as increase the risk of falls and delirium: American Geriatrics Society. “American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.” J Am Geriatr Soc 2015;63(11):22227–46.
234: Among those over the age of sixty-five, the incidence of polypharmacy, defined as being on five or more medications at one time, rose from 30.6 percent to 35.8 percent from 2005 to 2011: Qato DM, Wilder J, Schumm LP, et al. “Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011.” JAMA Intern Med 2016;176:473–82.