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Disease-a-Month

Disease-a-Month 60 (2014) 323–331

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journal homepage: www.elsevier.com/locate/disamonth

Clinical pearls in complementary andintegrative 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 mildhyperlipidemia, which she controls with diet and exercise. She is married and works as abusiness analyst for a small local company. She takes no medications.

Question

What is the likelihood that this patient is using CIM?

A.

o10% B. Around 20% C. Around 30% D. Around 40% E. 450%

Discussion

A large (N 4 30,000) 2007 study found that approximately 40% of US adults are currentlyusing some form of CIM as part of their ongoing health care. Thus, in a typical medical practice, itis reasonable to expect that at least 40% of patients will be using CIM. Because CIM therapies canhave both positive as well as negative effects, this is an important statistic that highlights theneed to query every patient about the use of CIM as part of the routine history. While thisstatistic holds for the general population, it is important to note that other studies that haveevaluated the use of CIM in specific patient populations (e.g., patients with cancer, arthritis, orother chronic conditions) have found usage rates approaching 70% or 80%. Thus, determiningwhether patients are using CIM, and how it may affect their health and interact with any

x.doi.org/10.1016/j.disamonth.2014.04.00929/& 2014 Mosby, Inc. All rights reserved.

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planned medical interventions, is an important element of practice for anyone caring forpatients.

Clinical pearl

Approximately 40% of US adults use CIM. Usage is higher among patients with chronic conditionsor 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 adultsand children: United States, 2007. CDC Natl Health Stat Report #12. 2008.

2.

Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE. Complementary/alternativemedicine use in a comprehensive cancer center and the implications for oncology. J ClinOncol. 2000;18(13):2505–2514.

Case 2

A 36-year-old woman with depression and hypercholesterolemia presents with anunexpected pregnancy confirmed by ultrasound. She states that she has taken her daily OCPfaithfully 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.

S-adenosylmethionine (SAMe) B. Saffron (Crocus sativus) C. St. John’s wort (Hypericum perforatum) D. 5-HTP (5-hydroxytryptophan) E. 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 forhypertriglyceridemia), 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. Itimproves symptoms of mild to moderate depression (superior to placebo and comparable tosome SSRI medications in several clinical trials). But it also induces the cytochrome P450enzyme system and, in particular, the CYP3A4 subenzyme system. Other studies have shownthat it has a similar impact on intestinal P-glycoprotein. As a result, there are numerous casereports of adverse effects when St. John’s wort has been added to a stable regimen of a drugmetabolized by these pathways (e.g., antiretrovirals, digoxin, OCP’s, and anticonvulsants),leading to subtherapeutic levels of the prescription medication. Mixing St. John’s wort andcyclosporine has resulted in two high-profile cases of heart transplant rejection due to thismechanism.

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Clinical pearl

St. John’s wort is a popular dietary supplement that induces the CYP3A4 subenzyme systemand intestinal P-glycoprotein and can result in significant drug level reductions of medicationsmetabolized by this pathway.

References

1.

Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s wortdespite 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 majordepressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. 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, hecomplains of upper back and neck pain. Examination and laboratory studies rule out cardiaccauses, 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 thissymptom?

A.

Reiki B. Ginkgo C. Garlic D. Healing Touch E. Massage therapy

Discussion

Therapeutic massage has been a part of most medical models since antiquity. Until fairlyrecently, 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 thismodality. In the past decade, researchers and clinicians have been re-evaluating the role ofmassage therapy, especially in the management of post-operative patients. A number of trialshave demonstrated that massage can be delivered safely in the post-operative period, and withbeneficial effects on pain and anxiety. Complementing the routine care of patients withevidence-based CIM therapies can improve care of the patient while also addressing the growinginterest in (and use of) such therapies by a substantial portion of the US population. Havingskilled massage therapists, who are trained to work safely in the hospital environment, is key tosuccessfully 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 torecommend 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, theycannot be actively recommended as a treatment in cardiac surgery patients postoperatively.

Clinical pearl

Incorporating massage therapy into the routine care of hospitalized patients can improveimportant outcomes such as pain, anxiety, and satisfaction.

References

1.

Bauer BA, Cutshall SM, Wentworth LJ, et al. Effect of massage therapy on pain, anxiety, andtension 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 therapyfor 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 onduloxetine and low-dose ibuprofen (200 mg TID). She is doing well but would like to try andimprove her overall quality of life using non-pharmacologic means. In particular, she isinterested 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 thefollowing except?

A.

Qi gong B. Acupuncture C. Homeopathy D. Tai Chi E. Yoga

Discussion

Fibromyalgia is a complex disorder that causes pain and fatigue while affecting sleep andhealth-related quality of life. Despite recent advances in pharmaceutical treatments, fibromyal-gia remains a frustrating illness to both patients and clinicians. A number of CIM therapies havebeen tried as treatments to mitigate some of the chronic effects of the disorder. The GermanInterdisciplinary Association for Pain Therapy (Deutsche Interdisziplinaren Vereinigung furSchmertztherapie) conducted an extensive collaborative review of the literature (thoughDecember 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 CIMtherapies in the treatment of fibromyalgia. Meditative movement therapies (such as qi gong, taichi, and yoga) received strong recommendations, while acupuncture was considered to bereasonable to try on a case-by-case approach. There was insufficient evidence of a significanteffect 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 areevidence-based (e.g., meditative movement therapies) can allow physicians to guide theirpatients 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 forfibromyalgia 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 medicaltherapies 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 facingin regard to the demands of her practice. She feels the pressures of meeting productivitytargets are beginning to impact her health. She feels fatigued much of the time and notes thatstress 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 iteasy to think of her patients as “problems.” You both agree she is developing signs consistentwith burnout.

Question

In addition to guiding her to services provided at your facility, which of the following CIMtherapies could you recommend as a complement to those services?

A.

Reiki B. Mindfulness C. Homeopathy D. St. John’s wort E. Coenzyme Q10

Discussion

Physician burnout is a growing problem that will likely require ongoing, multi-prongedapproaches to reverse. Many CIM modalities may provide some temporary relief, especially inregard to the stress component of burnout (e.g., Reiki and massage). But only mindfulness-basedtherapies 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 attentionfocused 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 byDr. Jon Kabat-Zinn and colleagues at the University of Massachusetts Medical Center over 30years ago. It has been tested in a number of conditions and diseases and usually results insubstantial 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 keycomponent to an overall approach to health and wellness promotion that also focuses onnutrition, exercise, sleep, and community.

References

1.

Goodman MJ, Schorling JB. A mindfulness course decreases burnout and improves well-beingamong 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 mindfulcommunication with burnout, empathy, and attitudes among primary care physicians. J AmMed 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 beeninterested in using Coenzyme Q10 (CoQ10) as an adjunct to his existing therapy. You have reviewedseveral studies with him, some of which appeared mildly positive and some of which appeared tobe negative. You decided together that the evidence was not strong enough to recommend addingCoQ10 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.

One study does not change your opinion—you tell him he should not start CoQ10. B. Not everything on the internet is true—you tell him he should not start CoQ10. C. It is just a supplement—you tell him he can do whatever he wants. D. You take his word for it—you tell him to start CoQ10. E. 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, duein 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 meanthat 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 majorforms of yoga) and products (e.g., “ginseng” needs to be distinguished between American and Asianand 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 ofthe intervention. Finally, because of the challenges brought on by small studies, systematic reviewsand 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 reviewsstill require caution in their interpretation and application. Helping patients to understand thestrengths and weaknesses of such statistical approaches helps them be informed consumers andwill 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. Forclinicians 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 significantimprovement in ejection fraction. Apart from rare GI side effects, CoQ10 has been well toleratedin hundreds of clinical trials. Drug–supplement interactions have not been noted, with theexception of four case reports of possible decreased warfarin efficacy. Thus, for this patient, atrial of CoQ10 supplementation may be warranted.

Clinical pearl

CoQ10 may modestly improve EF in patients with CHF. It is generally well tolerated with onecaution being its use concomitantly with warfarin.

References

1.

Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation onheart 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 systolicfunction 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 beenevaluated and found to have advanced osteoarthritis of both knees. A trial of NSAID therapy wasdiscontinued due to hypertension and renal failure. He has not found acetaminophen to besatisfactory 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.

SAMe B. Horse chestnut extract C. Vitamin E D. Shiitake mushroom E. Passionflower

Discussion

SAMe has been studied extensively for a variety of symptoms and conditions, includingosteoarthritis. In a number of clinical trials, SAMe was found to be superior to placebo andcomparable to NSAIDs in treating pain due to osteoarthritis. Improvements in functionallimitations were also noted in most of these trials. The mechanism of action is not fullyunderstood, but it appears to have both analgesic and anti-inflammatory properties. Clinicaltrials 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 ofparticipants using high doses. SAMe should generally not be combined with otherantidepressant medications because of possible additive serotonergic effects. It should not beused in patients taking levodopa as there is a theoretical concern that it might reduce theefficacy and result in worsening of Parkinson symptoms.

Horse chestnut extract is typically used as a treatment for treating symptoms of venousinsufficiency and would not be expected to have any significant impact on osteoarthritissymptoms. Vitamin E has been evaluated specifically for symptoms of osteoarthritis and wasfound to be ineffective both as a treatment and as a preventative measure. Shiitake mushroom ispopularly thought of as an “immune stimulator,” making it a popular supplement amongpatients with cancer. But there are no clinical trial data to suggest it has any beneficial effect onarthritis symptoms. Passionflower is typically used to treat anxiety symptoms, with limitedclinical trial supporting its efficacy in this application. But there are no studies that show anyefficacy for treatment of osteoarthritis.

Clinical pearl

SAMe can be a useful therapy for patients with symptoms related to osteoarthritis who areintolerant 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 thetreatment of osteoarthritis symptoms: a double-blind crossover trial. BMC MusculoskeletDisord. 2004;5:6.

2.

Glorioso S, Todesco S, Mazzi A, et al. Double-blind, multicentre study of the activity of S-adenosylmethionine 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 conditionshave high level evidence of efficacy.

Question

You find that meta-analyses have shown efficacy of acupuncture in all of the followingconditions except one. Which condition does not have high level data supporting acupuncture asa treatment?

A.

Migraine headache prophylaxis B. Tension-type headache C. Low back pain D. Premenstrual syndrome E. Irritable bowel syndrome

Discussion

A search of PubMed using the term “acupuncture” produces over 18,000 hits. Limiting thesearch 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 onthis burgeoning research field in the past 5 years have concluded that acupuncture can be a usefultreatment for migraine prophylaxis, treatment of tension-type headache, low back pain, as anadjunct to smoking cessation and as a treatment for premenstrual syndrome. Despite a number ofstudies on IBS, meta-analysis of these trials has concluded that the evidence to support the use ofacupuncture in this condition is lacking.

Clinical pearl

Acupuncture can be a helpful tool in the management of many common problems—includingmigraine 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 migraineprophylaxis. 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.