Disease-a-Month 60 (2014) 323–331
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Clinical pearls in complementary and integrative medicine (CIM) Brent A. Bauer, MD, Scott C. Litin, MD, John B. Bundrick, MD
Case 1 A 52-year-old female patient presents for a general medical evaluation. She has mild hyperlipidemia, which she controls with diet and exercise. She is married and works as a business analyst for a small local company. She takes no medications. Question What is the likelihood that this patient is using CIM? A. B. C. D. E.
o 10% Around 20% Around 30% Around 40% 4 50%
Discussion A large (N 4 30,000) 2007 study found that approximately 40% of US adults are currently using some form of CIM as part of their ongoing health care. Thus, in a typical medical practice, it is reasonable to expect that at least 40% of patients will be using CIM. Because CIM therapies can have both positive as well as negative effects, this is an important statistic that highlights the need to query every patient about the use of CIM as part of the routine history. While this statistic holds for the general population, it is important to note that other studies that have evaluated the use of CIM in specific patient populations (e.g., patients with cancer, arthritis, or other chronic conditions) have found usage rates approaching 70% or 80%. Thus, determining whether patients are using CIM, and how it may affect their health and interact with any
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planned medical interventions, is an important element of practice for anyone caring for patients. Clinical pearl Approximately 40% of US adults use CIM. Usage is higher among patients with chronic conditions or significant disease states (e.g., cancer). Be sure to query all patients about the use of CIM. References 1. Barnes PM, Bloom B, Nahin R. Complementary and alternative medicine use among adults and children: United States, 2007. CDC Natl Health Stat Report #12. 2008. 2. Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18(13):2505–2514. Case 2 A 36-year-old woman with depression and hypercholesterolemia presents with an unexpected pregnancy confirmed by ultrasound. She states that she has taken her daily OCP faithfully during the past year. The only other change has been the use of a dietary supplement, which she started last year to help with her symptoms of depression. Question Failure of her OCP was most likely caused by which of the following dietary supplements? A. B. C. D. E.
S-adenosylmethionine (SAMe) Saffron (Crocus sativus) St. John’s wort (Hypericum perforatum) 5-HTP (5-hydroxytryptophan) Folic acid
Discussion Dietary supplements remain the most commonly used CIM therapies in the United States. Some can have beneficial effects with relatively minor adverse effects (e.g., fish oil for hypertriglyceridemia), while others impart risk of adverse effects but have limited/no benefits (e.g., colloidal silver). However, the majority fall somewhere in between these extremes—i.e., possessing both potential risks and potential benefits. St. John’s wort is a good example. It improves symptoms of mild to moderate depression (superior to placebo and comparable to some SSRI medications in several clinical trials). But it also induces the cytochrome P450 enzyme system and, in particular, the CYP3A4 subenzyme system. Other studies have shown that it has a similar impact on intestinal P-glycoprotein. As a result, there are numerous case reports of adverse effects when St. John’s wort has been added to a stable regimen of a drug metabolized by these pathways (e.g., antiretrovirals, digoxin, OCP’s, and anticonvulsants), leading to subtherapeutic levels of the prescription medication. Mixing St. John’s wort and cyclosporine has resulted in two high-profile cases of heart transplant rejection due to this mechanism.
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Clinical pearl St. John’s wort is a popular dietary supplement that induces the CYP3A4 subenzyme system and intestinal P-glycoprotein and can result in significant drug level reductions of medications metabolized by this pathway. References 1. Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol. 2003;55(1):112–113 [PMID 12534648]. 2. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a metaanalysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118–127. doi: 0.1016/j. pnpbp.2008.10.018. [Epub 2008 Nov 12. PMID: 19028540].
Case 3 A 65-year-old male undergoes uncomplicated CABG and AVR. On post-op day #2, he complains of upper back and neck pain. Examination and laboratory studies rule out cardiac causes, and he is diagnosed with musculoskeletal pain secondary to rib cage expansion. Question Which of the following CIM therapies has evidence of safety and efficacy in addressing this symptom? A. B. C. D. E.
Reiki Ginkgo Garlic Healing Touch Massage therapy
Discussion Therapeutic massage has been a part of most medical models since antiquity. Until fairly recently, a back massage was considered a routine part of the care of hospitalized patients. Altered practice demands of the past 30 years have caused the decline of the use of this modality. In the past decade, researchers and clinicians have been re-evaluating the role of massage therapy, especially in the management of post-operative patients. A number of trials have demonstrated that massage can be delivered safely in the post-operative period, and with beneficial effects on pain and anxiety. Complementing the routine care of patients with evidence-based CIM therapies can improve care of the patient while also addressing the growing interest in (and use of) such therapies by a substantial portion of the US population. Having skilled massage therapists, who are trained to work safely in the hospital environment, is key to successfully incorporating massage into the hospital setting. None of the listed herbal therapies would be expected to have a significant impact on pain, and all should be avoided in the perioperative period to avoid potential bleeding risks. Healing Touch and Reiki have not been sufficiently evaluated in cardiac surgery patients to recommend their use. Studies on other patient population groups suggest that these modalities
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are generally safe and may promote relaxation. But until additional studies are completed, they cannot be actively recommended as a treatment in cardiac surgery patients postoperatively. Clinical pearl Incorporating massage therapy into the routine care of hospitalized patients can improve important outcomes such as pain, anxiety, and satisfaction. References 1. Bauer BA, Cutshall SM, Wentworth LJ, et al. Effect of massage therapy on pain, anxiety, and tension after cardiac surgery: a randomized study. Complement Ther Clin Pract. 2010;16(2):70–75. doi: 10.1016/j.ctcp.2009.06.012. [Epub 2009 Jul 14. PMID: 20347836]. 2. Braun LA, Stanguts C, Casanelia L, Spitzer O, Paul E, Vardaxis NJ, Rosenfeldt F. Massage therapy for cardiac surgery patients—a randomized trial. J Thorac Cardiovasc Surg. 2012;144(6):1453– 1459, 1459.e1. doi: 10.1016/j.jtcvs.2012.04.027. [Epub 2012 Sep 7. PMID: 22964355].
Case 4 A 35-year-old woman presents with a history of fibromyalgia of 3 years duration. She is on duloxetine and low-dose ibuprofen (200 mg TID). She is doing well but would like to try and improve her overall quality of life using non-pharmacologic means. In particular, she is interested in incorporating a CIM therapy into her current care plan. Question Utilizing an evidence-based approach, you could encourage her to explore the use of all of the following except? A. B. C. D. E.
Qi gong Acupuncture Homeopathy Tai Chi Yoga
Discussion Fibromyalgia is a complex disorder that causes pain and fatigue while affecting sleep and health-related quality of life. Despite recent advances in pharmaceutical treatments, fibromyalgia remains a frustrating illness to both patients and clinicians. A number of CIM therapies have been tried as treatments to mitigate some of the chronic effects of the disorder. The German Interdisciplinary Association for Pain Therapy (Deutsche Interdisziplinaren Vereinigung fur Schmertztherapie) conducted an extensive collaborative review of the literature (though December 2010) and made recommendations based on the level of evidence, efficacy (pain, fatigue, sleep, and Health-related quality of life), risks, and acceptability for various CIM therapies in the treatment of fibromyalgia. Meditative movement therapies (such as qi gong, tai chi, and yoga) received strong recommendations, while acupuncture was considered to be reasonable to try on a case-by-case approach. There was insufficient evidence of a significant effect from homeopathy, and its use was not endorsed for the treatment of fibromyalgia.
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Clinical pearl CIM therapies are popular among patients with fibromyalgia. Recognizing those which are evidence-based (e.g., meditative movement therapies) can allow physicians to guide their patients to helpful therapies while avoiding those that do not have such evidence. References 1. Langhorst J, Häuser W, Bernardy K, et al. Complementary and alternative therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline. Schmerz. 2012;26 (3):311–317. doi: 10.1007/s00482-012-1178-9. 2. Wahner-Roedler DL, Elkin PL, Vincent A, et al. Use of complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center. Mayo Clin Proc. 2005;80(1):55–60.
Case 5 A 45-year-old female physician colleague approaches you to discuss challenges she is facing in regard to the demands of her practice. She feels the pressures of meeting productivity targets are beginning to impact her health. She feels fatigued much of the time and notes that stress is becoming ubiquitous—with practice demands increasingly intruding on her home life. She feels that these demands are outstripping her coping skills. She is increasingly finding it easy to think of her patients as “problems.” You both agree she is developing signs consistent with burnout. Question In addition to guiding her to services provided at your facility, which of the following CIM therapies could you recommend as a complement to those services? A. B. C. D. E.
Reiki Mindfulness Homeopathy St. John’s wort Coenzyme Q10
Discussion Physician burnout is a growing problem that will likely require ongoing, multi-pronged approaches to reverse. Many CIM modalities may provide some temporary relief, especially in regard to the stress component of burnout (e.g., Reiki and massage). But only mindfulness-based therapies so far have been specifically shown to have measurable impact on physician burnout. Mindfulness is a form of meditation and has been described as a state of active, open attention focused on the present. “Living in the moment” is another frequent description for mindfulness. A specific form of mindfulness, mindfulness-based stress reduction (MBSR), was developed by Dr. Jon Kabat-Zinn and colleagues at the University of Massachusetts Medical Center over 30 years ago. It has been tested in a number of conditions and diseases and usually results in substantial reduction in stress and stress-related symptoms.
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Clinical pearl Caring for patients requires physicians to care for themselves. Stress management is a key component to an overall approach to health and wellness promotion that also focuses on nutrition, exercise, sleep, and community. References 1. Goodman MJ, Schorling JB. A mindfulness course decreases burnout and improves well-being among health care providers. Int J Psychiatry Med. 2012;43(2):119–128. 2. Krasner MS, Epstein RM, Beckman H, et al. Association of an educational program in mindful communication with burnout, empathy, and attitudes among primary care physicians. J Am Med Assoc. 2009;302(12):1284–1293. doi: 10.1001/jama.2009.1384. Case 6 A 70-year-old man is a long-standing patient of yours, with stable CHF (NYHA Class 2). Medications include a beta-blocker, an ACE-inhibitor, and ASA. Over the past 5 years, he has been interested in using Coenzyme Q10 (CoQ10) as an adjunct to his existing therapy. You have reviewed several studies with him, some of which appeared mildly positive and some of which appeared to be negative. You decided together that the evidence was not strong enough to recommend adding CoQ10 to his regimen. At an office visit this week, however, he brings the results of a new study (a systematic review) that seems to indicate that CoQ10 may improve EF in patients with CHF. Question What do you advise him? A. B. C. D. E.
One study does not change your opinion—you tell him he should not start CoQ10. Not everything on the internet is true—you tell him he should not start CoQ10. It is just a supplement—you tell him he can do whatever he wants. You take his word for it—you tell him to start CoQ10. You agree to review the study and discuss it in more detail at his next visit.
Discussion It is important to understand some of the frequently seen limitations of CIM research. First, due in part to limited funding, many CIM trials are small in scope, often including only 50 or fewer. While this does not mean that the quality of the research is necessarily suspected, it does mean that the likelihood is low that any one study of a particular intervention is going to be definitive. Also, because of lack of standardization across therapies (e.g., there are at least 11 different major forms of yoga) and products (e.g., “ginseng” needs to be distinguished between American and Asian and between water and ethanol extraction), evaluating study results is even more complex. Thus, caution must be used in applying results of a single study to other populations or to other forms of the intervention. Finally, because of the challenges brought on by small studies, systematic reviews and meta-analyses are quite common in the CIM scientific literature. While these can be helpful, they ultimately are still limited by the quality of the original studies. Thus, even well-done reviews still require caution in their interpretation and application. Helping patients to understand the strengths and weaknesses of such statistical approaches helps them be informed consumers and will hopefully lead to better choices to use (or not to use) CIM therapies.
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A readily available resource for addressing such patient questions is PubMed. It has a “filter” that can be turned on to limit search results to CIM topics. Further limiting searches to “Cochrane” can quickly highlight high-quality systematic reviews and meta-analyses. For clinicians who routinely encounter patients with questions about specific supplements, subscribing to a database (e.g., Natural Medicines Comprehensive Database, Natural Standard) can be an effective way to access information quickly. In the case of CoQ10 and CHF, the 2013 meta-analysis does suggest a statistically significant improvement in ejection fraction. Apart from rare GI side effects, CoQ10 has been well tolerated in hundreds of clinical trials. Drug–supplement interactions have not been noted, with the exception of four case reports of possible decreased warfarin efficacy. Thus, for this patient, a trial of CoQ10 supplementation may be warranted. Clinical pearl CoQ10 may modestly improve EF in patients with CHF. It is generally well tolerated with one caution being its use concomitantly with warfarin. References 1. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013;97(2):268–275. doi: 10.3945/ ajcn.112.040741. [Epub 2012 Dec 5. PMID: 23221577]. 2. Sander S, Coleman CI, Patel AA, Kluger J, White CM. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006;12(6):464–472. Case 7 A 68-year-old patient presents complaining of continuing knee pain. He has previously been evaluated and found to have advanced osteoarthritis of both knees. A trial of NSAID therapy was discontinued due to hypertension and renal failure. He has not found acetaminophen to be satisfactory and presents now wanting to know if there is any “natural” product he can try. Question Which of the following has been shown to have efficacy in treating the pain of OA? A. B. C. D. E.
SAMe Horse chestnut extract Vitamin E Shiitake mushroom Passionflower
Discussion SAMe has been studied extensively for a variety of symptoms and conditions, including osteoarthritis. In a number of clinical trials, SAMe was found to be superior to placebo and comparable to NSAIDs in treating pain due to osteoarthritis. Improvements in functional limitations were also noted in most of these trials. The mechanism of action is not fully understood, but it appears to have both analgesic and anti-inflammatory properties. Clinical trials have also demonstrated significant efficacy for depression as well.
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SAMe is generally well tolerated with mild GI symptoms noted in a small percentage of participants using high doses. SAMe should generally not be combined with other antidepressant medications because of possible additive serotonergic effects. It should not be used in patients taking levodopa as there is a theoretical concern that it might reduce the efficacy and result in worsening of Parkinson symptoms. Horse chestnut extract is typically used as a treatment for treating symptoms of venous insufficiency and would not be expected to have any significant impact on osteoarthritis symptoms. Vitamin E has been evaluated specifically for symptoms of osteoarthritis and was found to be ineffective both as a treatment and as a preventative measure. Shiitake mushroom is popularly thought of as an “immune stimulator,” making it a popular supplement among patients with cancer. But there are no clinical trial data to suggest it has any beneficial effect on arthritis symptoms. Passionflower is typically used to treat anxiety symptoms, with limited clinical trial supporting its efficacy in this application. But there are no studies that show any efficacy for treatment of osteoarthritis. Clinical pearl SAMe can be a useful therapy for patients with symptoms related to osteoarthritis who are intolerant of NSAID’s or who are seeking a non-drug approach to dealing with their symptoms. References 1. Najm WI, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind crossover trial. BMC Musculoskelet Disord. 2004;5:6. 2. Glorioso S, Todesco S, Mazzi A, et al. Double-blind, multicentre study of the activity of Sadenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res. 1985;5:39–49.
Case 8 Your group practice has been tracking the growing use of acupuncture among your patients. The Practice Committee has asked you to evaluate the literature and report on which conditions have high level evidence of efficacy. Question You find that meta-analyses have shown efficacy of acupuncture in all of the following conditions except one. Which condition does not have high level data supporting acupuncture as a treatment? A. B. C. D. E.
Migraine headache prophylaxis Tension-type headache Low back pain Premenstrual syndrome Irritable bowel syndrome
Discussion A search of PubMed using the term “acupuncture” produces over 18,000 hits. Limiting the search to “clinical trials” still yields over 3000 hits. This reflects the near-exponential growth in
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acupuncture research in the past decade. This growth has also brought some maturity to the field, with the quality of studies improving significantly in that same period. Meta-analyses done on this burgeoning research field in the past 5 years have concluded that acupuncture can be a useful treatment for migraine prophylaxis, treatment of tension-type headache, low back pain, as an adjunct to smoking cessation and as a treatment for premenstrual syndrome. Despite a number of studies on IBS, meta-analysis of these trials has concluded that the evidence to support the use of acupuncture in this condition is lacking. Clinical pearl Acupuncture can be a helpful tool in the management of many common problems—including migraine headache prophylaxis and management of pain symptoms across a number of conditions. References 1. Manheimer E, Wieland LS, Cheng K, et al. Acupuncture for irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2012;107(6):835–847. [Quiz 848. doi: 10.1038/ajg.2012.66. Epub 2012 Apr 10. Review. PMID: 22488079]. 2. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009;(1):CD001218. doi: 10.1002/14651858.CD001218. pub2. [Review. PMID: 19160193].
Answers: 1—D; 2—C; 3—E; 4—C; 5—B; 6—E; 7—A; 8—E.
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Clinical pearls in complementary and integrative medicine (CIM) Brent A. Bauer, MD, Scott C. Litin, MD, John B. Bundrick, MD
Case 1 A 52-year-old female patient presents for a general medical evaluation. She has mild hyperlipidemia, which she controls with diet and exercise. She is married and works as a business analyst for a small local company. She takes no medications. Question What is the likelihood that this patient is using CIM? A. B. C. D. E.
o 10% Around 20% Around 30% Around 40% 4 50%
Discussion A large (N 4 30,000) 2007 study found that approximately 40% of US adults are currently using some form of CIM as part of their ongoing health care. Thus, in a typical medical practice, it is reasonable to expect that at least 40% of patients will be using CIM. Because CIM therapies can have both positive as well as negative effects, this is an important statistic that highlights the need to query every patient about the use of CIM as part of the routine history. While this statistic holds for the general population, it is important to note that other studies that have evaluated the use of CIM in specific patient populations (e.g., patients with cancer, arthritis, or other chronic conditions) have found usage rates approaching 70% or 80%. Thus, determining whether patients are using CIM, and how it may affect their health and interact with any
http://dx.doi.org/10.1016/j.disamonth.2014.04.009 0011-5029/& 2014 Mosby, Inc. All rights reserved.
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planned medical interventions, is an important element of practice for anyone caring for patients. Clinical pearl Approximately 40% of US adults use CIM. Usage is higher among patients with chronic conditions or significant disease states (e.g., cancer). Be sure to query all patients about the use of CIM. References 1. Barnes PM, Bloom B, Nahin R. Complementary and alternative medicine use among adults and children: United States, 2007. CDC Natl Health Stat Report #12. 2008. 2. Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18(13):2505–2514. Case 2 A 36-year-old woman with depression and hypercholesterolemia presents with an unexpected pregnancy confirmed by ultrasound. She states that she has taken her daily OCP faithfully during the past year. The only other change has been the use of a dietary supplement, which she started last year to help with her symptoms of depression. Question Failure of her OCP was most likely caused by which of the following dietary supplements? A. B. C. D. E.
S-adenosylmethionine (SAMe) Saffron (Crocus sativus) St. John’s wort (Hypericum perforatum) 5-HTP (5-hydroxytryptophan) Folic acid
Discussion Dietary supplements remain the most commonly used CIM therapies in the United States. Some can have beneficial effects with relatively minor adverse effects (e.g., fish oil for hypertriglyceridemia), while others impart risk of adverse effects but have limited/no benefits (e.g., colloidal silver). However, the majority fall somewhere in between these extremes—i.e., possessing both potential risks and potential benefits. St. John’s wort is a good example. It improves symptoms of mild to moderate depression (superior to placebo and comparable to some SSRI medications in several clinical trials). But it also induces the cytochrome P450 enzyme system and, in particular, the CYP3A4 subenzyme system. Other studies have shown that it has a similar impact on intestinal P-glycoprotein. As a result, there are numerous case reports of adverse effects when St. John’s wort has been added to a stable regimen of a drug metabolized by these pathways (e.g., antiretrovirals, digoxin, OCP’s, and anticonvulsants), leading to subtherapeutic levels of the prescription medication. Mixing St. John’s wort and cyclosporine has resulted in two high-profile cases of heart transplant rejection due to this mechanism.
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Clinical pearl St. John’s wort is a popular dietary supplement that induces the CYP3A4 subenzyme system and intestinal P-glycoprotein and can result in significant drug level reductions of medications metabolized by this pathway. References 1. Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol. 2003;55(1):112–113 [PMID 12534648]. 2. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a metaanalysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118–127. doi: 0.1016/j. pnpbp.2008.10.018. [Epub 2008 Nov 12. PMID: 19028540].
Case 3 A 65-year-old male undergoes uncomplicated CABG and AVR. On post-op day #2, he complains of upper back and neck pain. Examination and laboratory studies rule out cardiac causes, and he is diagnosed with musculoskeletal pain secondary to rib cage expansion. Question Which of the following CIM therapies has evidence of safety and efficacy in addressing this symptom? A. B. C. D. E.
Reiki Ginkgo Garlic Healing Touch Massage therapy
Discussion Therapeutic massage has been a part of most medical models since antiquity. Until fairly recently, a back massage was considered a routine part of the care of hospitalized patients. Altered practice demands of the past 30 years have caused the decline of the use of this modality. In the past decade, researchers and clinicians have been re-evaluating the role of massage therapy, especially in the management of post-operative patients. A number of trials have demonstrated that massage can be delivered safely in the post-operative period, and with beneficial effects on pain and anxiety. Complementing the routine care of patients with evidence-based CIM therapies can improve care of the patient while also addressing the growing interest in (and use of) such therapies by a substantial portion of the US population. Having skilled massage therapists, who are trained to work safely in the hospital environment, is key to successfully incorporating massage into the hospital setting. None of the listed herbal therapies would be expected to have a significant impact on pain, and all should be avoided in the perioperative period to avoid potential bleeding risks. Healing Touch and Reiki have not been sufficiently evaluated in cardiac surgery patients to recommend their use. Studies on other patient population groups suggest that these modalities
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are generally safe and may promote relaxation. But until additional studies are completed, they cannot be actively recommended as a treatment in cardiac surgery patients postoperatively. Clinical pearl Incorporating massage therapy into the routine care of hospitalized patients can improve important outcomes such as pain, anxiety, and satisfaction. References 1. Bauer BA, Cutshall SM, Wentworth LJ, et al. Effect of massage therapy on pain, anxiety, and tension after cardiac surgery: a randomized study. Complement Ther Clin Pract. 2010;16(2):70–75. doi: 10.1016/j.ctcp.2009.06.012. [Epub 2009 Jul 14. PMID: 20347836]. 2. Braun LA, Stanguts C, Casanelia L, Spitzer O, Paul E, Vardaxis NJ, Rosenfeldt F. Massage therapy for cardiac surgery patients—a randomized trial. J Thorac Cardiovasc Surg. 2012;144(6):1453– 1459, 1459.e1. doi: 10.1016/j.jtcvs.2012.04.027. [Epub 2012 Sep 7. PMID: 22964355].
Case 4 A 35-year-old woman presents with a history of fibromyalgia of 3 years duration. She is on duloxetine and low-dose ibuprofen (200 mg TID). She is doing well but would like to try and improve her overall quality of life using non-pharmacologic means. In particular, she is interested in incorporating a CIM therapy into her current care plan. Question Utilizing an evidence-based approach, you could encourage her to explore the use of all of the following except? A. B. C. D. E.
Qi gong Acupuncture Homeopathy Tai Chi Yoga
Discussion Fibromyalgia is a complex disorder that causes pain and fatigue while affecting sleep and health-related quality of life. Despite recent advances in pharmaceutical treatments, fibromyalgia remains a frustrating illness to both patients and clinicians. A number of CIM therapies have been tried as treatments to mitigate some of the chronic effects of the disorder. The German Interdisciplinary Association for Pain Therapy (Deutsche Interdisziplinaren Vereinigung fur Schmertztherapie) conducted an extensive collaborative review of the literature (though December 2010) and made recommendations based on the level of evidence, efficacy (pain, fatigue, sleep, and Health-related quality of life), risks, and acceptability for various CIM therapies in the treatment of fibromyalgia. Meditative movement therapies (such as qi gong, tai chi, and yoga) received strong recommendations, while acupuncture was considered to be reasonable to try on a case-by-case approach. There was insufficient evidence of a significant effect from homeopathy, and its use was not endorsed for the treatment of fibromyalgia.
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Clinical pearl CIM therapies are popular among patients with fibromyalgia. Recognizing those which are evidence-based (e.g., meditative movement therapies) can allow physicians to guide their patients to helpful therapies while avoiding those that do not have such evidence. References 1. Langhorst J, Häuser W, Bernardy K, et al. Complementary and alternative therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline. Schmerz. 2012;26 (3):311–317. doi: 10.1007/s00482-012-1178-9. 2. Wahner-Roedler DL, Elkin PL, Vincent A, et al. Use of complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center. Mayo Clin Proc. 2005;80(1):55–60.
Case 5 A 45-year-old female physician colleague approaches you to discuss challenges she is facing in regard to the demands of her practice. She feels the pressures of meeting productivity targets are beginning to impact her health. She feels fatigued much of the time and notes that stress is becoming ubiquitous—with practice demands increasingly intruding on her home life. She feels that these demands are outstripping her coping skills. She is increasingly finding it easy to think of her patients as “problems.” You both agree she is developing signs consistent with burnout. Question In addition to guiding her to services provided at your facility, which of the following CIM therapies could you recommend as a complement to those services? A. B. C. D. E.
Reiki Mindfulness Homeopathy St. John’s wort Coenzyme Q10
Discussion Physician burnout is a growing problem that will likely require ongoing, multi-pronged approaches to reverse. Many CIM modalities may provide some temporary relief, especially in regard to the stress component of burnout (e.g., Reiki and massage). But only mindfulness-based therapies so far have been specifically shown to have measurable impact on physician burnout. Mindfulness is a form of meditation and has been described as a state of active, open attention focused on the present. “Living in the moment” is another frequent description for mindfulness. A specific form of mindfulness, mindfulness-based stress reduction (MBSR), was developed by Dr. Jon Kabat-Zinn and colleagues at the University of Massachusetts Medical Center over 30 years ago. It has been tested in a number of conditions and diseases and usually results in substantial reduction in stress and stress-related symptoms.
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Clinical pearl Caring for patients requires physicians to care for themselves. Stress management is a key component to an overall approach to health and wellness promotion that also focuses on nutrition, exercise, sleep, and community. References 1. Goodman MJ, Schorling JB. A mindfulness course decreases burnout and improves well-being among health care providers. Int J Psychiatry Med. 2012;43(2):119–128. 2. Krasner MS, Epstein RM, Beckman H, et al. Association of an educational program in mindful communication with burnout, empathy, and attitudes among primary care physicians. J Am Med Assoc. 2009;302(12):1284–1293. doi: 10.1001/jama.2009.1384. Case 6 A 70-year-old man is a long-standing patient of yours, with stable CHF (NYHA Class 2). Medications include a beta-blocker, an ACE-inhibitor, and ASA. Over the past 5 years, he has been interested in using Coenzyme Q10 (CoQ10) as an adjunct to his existing therapy. You have reviewed several studies with him, some of which appeared mildly positive and some of which appeared to be negative. You decided together that the evidence was not strong enough to recommend adding CoQ10 to his regimen. At an office visit this week, however, he brings the results of a new study (a systematic review) that seems to indicate that CoQ10 may improve EF in patients with CHF. Question What do you advise him? A. B. C. D. E.
One study does not change your opinion—you tell him he should not start CoQ10. Not everything on the internet is true—you tell him he should not start CoQ10. It is just a supplement—you tell him he can do whatever he wants. You take his word for it—you tell him to start CoQ10. You agree to review the study and discuss it in more detail at his next visit.
Discussion It is important to understand some of the frequently seen limitations of CIM research. First, due in part to limited funding, many CIM trials are small in scope, often including only 50 or fewer. While this does not mean that the quality of the research is necessarily suspected, it does mean that the likelihood is low that any one study of a particular intervention is going to be definitive. Also, because of lack of standardization across therapies (e.g., there are at least 11 different major forms of yoga) and products (e.g., “ginseng” needs to be distinguished between American and Asian and between water and ethanol extraction), evaluating study results is even more complex. Thus, caution must be used in applying results of a single study to other populations or to other forms of the intervention. Finally, because of the challenges brought on by small studies, systematic reviews and meta-analyses are quite common in the CIM scientific literature. While these can be helpful, they ultimately are still limited by the quality of the original studies. Thus, even well-done reviews still require caution in their interpretation and application. Helping patients to understand the strengths and weaknesses of such statistical approaches helps them be informed consumers and will hopefully lead to better choices to use (or not to use) CIM therapies.
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A readily available resource for addressing such patient questions is PubMed. It has a “filter” that can be turned on to limit search results to CIM topics. Further limiting searches to “Cochrane” can quickly highlight high-quality systematic reviews and meta-analyses. For clinicians who routinely encounter patients with questions about specific supplements, subscribing to a database (e.g., Natural Medicines Comprehensive Database, Natural Standard) can be an effective way to access information quickly. In the case of CoQ10 and CHF, the 2013 meta-analysis does suggest a statistically significant improvement in ejection fraction. Apart from rare GI side effects, CoQ10 has been well tolerated in hundreds of clinical trials. Drug–supplement interactions have not been noted, with the exception of four case reports of possible decreased warfarin efficacy. Thus, for this patient, a trial of CoQ10 supplementation may be warranted. Clinical pearl CoQ10 may modestly improve EF in patients with CHF. It is generally well tolerated with one caution being its use concomitantly with warfarin. References 1. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013;97(2):268–275. doi: 10.3945/ ajcn.112.040741. [Epub 2012 Dec 5. PMID: 23221577]. 2. Sander S, Coleman CI, Patel AA, Kluger J, White CM. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006;12(6):464–472. Case 7 A 68-year-old patient presents complaining of continuing knee pain. He has previously been evaluated and found to have advanced osteoarthritis of both knees. A trial of NSAID therapy was discontinued due to hypertension and renal failure. He has not found acetaminophen to be satisfactory and presents now wanting to know if there is any “natural” product he can try. Question Which of the following has been shown to have efficacy in treating the pain of OA? A. B. C. D. E.
SAMe Horse chestnut extract Vitamin E Shiitake mushroom Passionflower
Discussion SAMe has been studied extensively for a variety of symptoms and conditions, including osteoarthritis. In a number of clinical trials, SAMe was found to be superior to placebo and comparable to NSAIDs in treating pain due to osteoarthritis. Improvements in functional limitations were also noted in most of these trials. The mechanism of action is not fully understood, but it appears to have both analgesic and anti-inflammatory properties. Clinical trials have also demonstrated significant efficacy for depression as well.
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SAMe is generally well tolerated with mild GI symptoms noted in a small percentage of participants using high doses. SAMe should generally not be combined with other antidepressant medications because of possible additive serotonergic effects. It should not be used in patients taking levodopa as there is a theoretical concern that it might reduce the efficacy and result in worsening of Parkinson symptoms. Horse chestnut extract is typically used as a treatment for treating symptoms of venous insufficiency and would not be expected to have any significant impact on osteoarthritis symptoms. Vitamin E has been evaluated specifically for symptoms of osteoarthritis and was found to be ineffective both as a treatment and as a preventative measure. Shiitake mushroom is popularly thought of as an “immune stimulator,” making it a popular supplement among patients with cancer. But there are no clinical trial data to suggest it has any beneficial effect on arthritis symptoms. Passionflower is typically used to treat anxiety symptoms, with limited clinical trial supporting its efficacy in this application. But there are no studies that show any efficacy for treatment of osteoarthritis. Clinical pearl SAMe can be a useful therapy for patients with symptoms related to osteoarthritis who are intolerant of NSAID’s or who are seeking a non-drug approach to dealing with their symptoms. References 1. Najm WI, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind crossover trial. BMC Musculoskelet Disord. 2004;5:6. 2. Glorioso S, Todesco S, Mazzi A, et al. Double-blind, multicentre study of the activity of Sadenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res. 1985;5:39–49.
Case 8 Your group practice has been tracking the growing use of acupuncture among your patients. The Practice Committee has asked you to evaluate the literature and report on which conditions have high level evidence of efficacy. Question You find that meta-analyses have shown efficacy of acupuncture in all of the following conditions except one. Which condition does not have high level data supporting acupuncture as a treatment? A. B. C. D. E.
Migraine headache prophylaxis Tension-type headache Low back pain Premenstrual syndrome Irritable bowel syndrome
Discussion A search of PubMed using the term “acupuncture” produces over 18,000 hits. Limiting the search to “clinical trials” still yields over 3000 hits. This reflects the near-exponential growth in
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acupuncture research in the past decade. This growth has also brought some maturity to the field, with the quality of studies improving significantly in that same period. Meta-analyses done on this burgeoning research field in the past 5 years have concluded that acupuncture can be a useful treatment for migraine prophylaxis, treatment of tension-type headache, low back pain, as an adjunct to smoking cessation and as a treatment for premenstrual syndrome. Despite a number of studies on IBS, meta-analysis of these trials has concluded that the evidence to support the use of acupuncture in this condition is lacking. Clinical pearl Acupuncture can be a helpful tool in the management of many common problems—including migraine headache prophylaxis and management of pain symptoms across a number of conditions. References 1. Manheimer E, Wieland LS, Cheng K, et al. Acupuncture for irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2012;107(6):835–847. [Quiz 848. doi: 10.1038/ajg.2012.66. Epub 2012 Apr 10. Review. PMID: 22488079]. 2. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009;(1):CD001218. doi: 10.1002/14651858.CD001218. pub2. [Review. PMID: 19160193].
Answers: 1—D; 2—C; 3—E; 4—C; 5—B; 6—E; 7—A; 8—E.
