Published May 19, 2009 PAIN MANAGEMENT Massage Therapy: Implications for Pharmaceutical Care Wendy D. Smith, PharmD, BCPS Drug Information Clinical Pharmacy Specialist The University of Texas MD Anderson Cancer Center Division of Pharmacy Houston, Texas Lincy S. Lal, PharmD, PhD Pharmacoeconomics Research Specialist The University of Texas MD Anderson Cancer Center Division of Pharmacy Houston, Texas US Pharm. 2009;34(5):Epub. One in six American adults received massage therapy in 2006, with nearly 40% of the population having received at least one massage in their lifetime.1 The age group with the highest usage is between the ages of 21 and 34 years, suggesting that the popularity of massage therapy will only continue to grow.1 In 2007, there were over 240,000 trained massage therapists in the United States, which represents a 27% increase in 2 years.2 In 2004, the U.S. Department of Health and Human Services reported that nearly one-half of all people take at least one prescription medication and one in six take three or more medications.3 Unlike those that receive massages, the largest consumer of prescription medications are those over the age of 65. A recent systematic review of ambulatory patients found the median incidence of adverse drug events (ADEs) to be 14.9 (range 4.0-91.3) per 1,000 person-months.4 One mechanism to reduce to the likelihood for ADEs is for health care professionals to perform an adequate medication history.5,6 In 2007, the Joint Commission included reconciliation of medications a National Patient Safety Goal for hospitalized patients.7 In order to reduce the potential for ADEs, an adequate medication history should be taken before any treatment is started, including massage therapy.8 Little information is available describing the potential impact of massage therapy on medications and visa versa. The purpose of this review is to examine the impact that several classes of medications may have on massage therapy and the effect that massage therapy may have on those medications. Practice of Massage Therapy Various forms of massage, traction, and manipulation have been practiced for thousands of years across many cultures, with the Chinese use of massage dating back to 1600 BC. Massage spread through Europe during the Renaissance. George and Charles Taylor introduced massage therapy to the U.S. in the 1850s. In 1873, the term massage entered the Anglo-American medical lexicon. By the early 1930s, massage became a less prominent part of American medicine and was displaced by a focus on the biological sciences. Interest resurged in the 1970s, particularly in sports medicine and as a complementary therapy to promote well-being, relaxation, pain-reduction, stress relief, musculoskeletal injury healing, sleep enhancement, and quality of life.9,10 The American Massage Therapy Association defines massage as “manual soft tissue manipulation that includes holding, causing movement, and/or applying pressure to the body.” Massage therapy is defined as “a profession in which the practitioner applies manual techniques, and may apply adjunctive therapies, with the intention of positively affecting the health and well-being of the client.”11 Two main categories of massages exist—Western and Eastern. Western massage is the most common type practiced in the U.S. today and includes: 1) effleurage. the focus of pressure is moved by the hands gliding over the skin, along the length of the muscle; 2) petrissage, soft tissue is compressed between the hands or between the fingers and thumb, across the width of the muscle; 3) tapotement, the skin or muscle is impacted by repetitive and compressive blows (i.e., hacking); and 4) deep friction massage, shearing stresses are created at tissue interfaces below the skin.12 Examples of Eastern massages include Shiatsu, Chi, reflexology, and auriculotherapy.9 Scope of Benefits Massages are mainly used to promote relaxation, treat painful muscular conditions, and reduce anxiety. Massage may be utilized as the primary therapeutic intervention or as an adjunct to other therapeutic techniques. Therapeutic uses include mobilization of intertissue fluids, reduction or modification of edema, increase of local blood flow, decrease of muscle soreness and stiffness, moderation of pain, facilitation of relaxation, and prevention or elimination of adhesions. Psychological benefits of massage therapy include improvements in mood, body image, self-esteem, and perceived levels of anxiety and may be accompanied by decreased tension, anxiety, and pain.9 Very few controlled clinical trials have evaluated the impact of massage therapy. Most published trials are limited by a small sample size, nonrandomization, and other concurrent treatment modalities.13,-19 In a nonrandomized study by Cassileth and Vickers, 1,290 patients at a major cancer center were evaluated on self-reported symptom severity pre- and postmassage.20 Symptom scores were reduced by approximately 54% and symptoms of pain and fatigue improved by approximately 40%, while anxiety improved by about 52%. A Cochrane meta-analysis evaluated the effect of massage on neck pain in 19 trials.21 Six stand-alone trials that examined massage as a sole treatment exhibited inconsistent results in the impact of massage therapy on neck pain. Fourteen trials that utilized massage therapy as part of a multimodal intervention were evaluated; however, none were designed to determine the relative contribution of massage versus the other modalities. Therefore, further research on the impact of massage therapy is needed, prior to resolving the role of massage therapy in the treatment of various ailments. Adverse effects due to massage therapy are rare but have been reported. A review of 20 adverse event case reports or series reported occurrences of cerebrovascular accidents, displacement of stents, embolizations, hematomas, leg ulcers, nerve damage, pseudoaneurisms, thyrotoxicosis, and various pain syndromes.8 The causality of these events was scored as likely or certain in a majority of the cases, and the majority was conducted by nonprofessional therapists involving techniques not commonly utilized in the U.S. Absolute contraindications to massage therapy include deep vein thrombosis (DVT), acute infection, bleeding, and new and open wounds. Relative contraindications include incompletely healed scar tissue, fragile skin, calcified soft tissue, skin grafts, atrophic skin, inflamed tissue, inflammatory muscle disease, and pregnancy.9 Direct firm pressure over sites of active tumor should also be avoided.12 Impact of Medications on Massage Treatment Planning Medications may affect several aspects of treatment planning including the scheduling of treatment, treatment focus and duration, techniques used during treatment, and client cooperativeness.22 Treatment planning strategies can vary according to the patient and/or medication. Patients receiving drug therapy for chronic diseases (e.g., insulin for diabetes, beta-blockers for hypertension) are less likely to require treatment schedule modification because their condition is usually stable, and they have achieved stable levels of the medication. Patients who are receiving new drug therapy or drug therapy for an acute condition (e.g., opiates for pain) may require more extensive treatment planning in order to receive safe and effective massage therapy.22 Patients receiving analgesics (i.e., non steroidal anti-inflammatory drugs [NSAIDs]), narcotic analgesics, and central nervous system (CNS) depressants may not be able to provide accurate feedback regarding the comfort of techniques and modalities used during massage therapy. These medications alter the normal pain responses that warn of potential tissue injury. Techniques or modalities that would normally cause discomfort may become more tolerable than they should. For example, a patient who is taking ibuprofen 800 mg four times daily for a minor injury may seek massage therapy in order to help with the healing process. The patient, who has a reduced perception of pain, may provide misleading information to the therapist, saying things like, “You can go deeper if you want.” If the therapist responds by doing deeper massage, this may cause more tissue damage and/or bruising. For patients taking medications for short-term minor conditions, the patient should take their medications just before or soon after their massage. This ensures that that the plasma levels of the drug will be at their lowest during the massage.22 Some medications may require the massage to be adapted or shortened. Fatigue is a common adverse effect of many medications, including antihypertensives and chemotherapy.22 Patients taking fatigue-inducing medications may become even more fatigued after massage therapy begins. The treatment session may need to be shortened and more specific. Many medications cause anxiety, depression, and mood fluctuations. These may become worse during massage therapy.22 The massage therapist should be aware of this potential and discuss it with the client to develop a plan of action if this was to occur. Medications may have a wide variety of effects and may alter blood-clotting mechanisms, neurosensory feedback, tissue integrity, and pain perception. The effects of these medications should be taken into account when the massage therapist is selecting the manual technique to be used. Examples of medications that may influence manual techniques are listed in TABLE 1.22 Impact of Administration Site and Devices Massaging on or around injection sites, skin patches, and implanted devises pose challenges because very little is known about how massage affects the release and uptake of medication from these administration sites. Being conservative, it should always be assumed that any manipulation on or around such a site, in particular an injection site or skin patch, has the potential to alter the pharmacokinetics of the drug being administered. In a study by Linde, it was reported that during massage the first-order elimination rate constant of insulin from subcutaneous tissue increased six-fold, indicating an increase in insulin absorption. Plasma glucose also fell significantly faster on the day of the massage, starting from 10 minutes after massage compared to the control day without massage.23 Impact of Commonly Prescribed Drugs Analgesics/Anti-Inflammatory Agents: Analgesics work either by inhibiting the inflammatory processes or by altering the pain perception in the CNS. In all instances, a conservative approach to massage therapy should be utilized because information about tissue response, muscle guarding, and other signs will be altered in this patient population.24 In general, patient feedback about pain and depth of pressure may be misleading and potential for over treatment of massage therapy exists. It is best to schedule treatments toward the end of the dosing period, prior to the next dose, when the drug is at the lowest levels in the body to maximize the accuracy of feedback and to optimize the medical stability. Side effects of these agents commonly include dizziness, drowsiness, and postural hypotension, all which can be potentiated by massage therapy. Therefore, always determine the impact of massage therapy during future visits and adjust the treatment course accordingly.24 Some NSAIDS have anticoagulant properties and patients taking these agents may be more susceptible to bruising if treated too aggressively. Muscle relaxants and narcotic analgesics depress neural responses and, therefore, attention must be given to avoid overtreatment. Corticosteroids can impair the tissue strength, resilience, and sensitivity and lead to reduced skin integrity. Therefore, massage techniques that place stress on muscles, bones, and joints should be avoided or modified. Since corticosteroids also depress the patient’s immune system, hygienic practices and measures become even more important.24,25 Cardiovascular Agents: Many of the drugs utilized for managing cardiovascular disease have an impact on the sympathetic nervous system. For a patient taking these agents, massage therapy may exacerbate the parasympathetic system, increasing the potential for orthostatic hypotension and related symptoms such as dizziness, lightheadedness, fatigue, and lethargy. Patients should be advised to sit up and move slowly to minimize the dizziness and discomfort. Other medications may affect renal function and electrolyte balance. Symptoms of these disorders may manifest as musculoskeletal symptoms and therefore necessitate careful consideration. In addition, patients with diseases such as angina pectoris or cardiac dysarrhythmias maybe at higher risk for destabilization with vigorous massage techniques.24 All patients receiving antihypertensive therapy should have a blood pressure reading at every visit to the massage therapist. The positioning of the patients warrants careful consideration, since many of these agents may induce orthostatic hypotension and exacerbate other adverse events. One example is angiotensin-converting enzyme (ACE) inhibitors. Approximately 20% of patients will develop a dry continuous cough with these agents and lying in a supine positive can aggravate these coughing episodes. Treating these patients in a semiseated position may be an alternative strategy. Patients receiving calcium channel blockers (CCBs) may be at a higher risk for developing DVT due to their ability to cause edema of the lower extremities. Patients receiving treatment for an active DVT with anticoagulants who choose to receive massage therapy have an increased risk of mobilization of the thromboembolism and, therefore, increased risk of pulmonary embolism or excessive bruising. These patients should avoid strenuous massage treatments. Other drugs such as statins may cause musculoskeletal pain and/or weakness. Massage therapy may mask the need for further work-up and evaluation by a medical professional.24 Antidiabetic Agents: The implications of massaging a client with diabetes can be significant since massage therapy has been shown to decrease blood glucose.26 This poses a challenge since homeostasis may not be maintained between the impact of the medications and the impact of the massage therapy and may potentially trigger a hypoglycemic episode. Patients new to massage therapy should be advised to check their blood sugar before and/or after sessions and also keep a supply of high-sugar snack handy in case of a hypoglycemic episode.26 Common symptoms of hypoglycemia include headaches, blurred vision, tingling in extremities, and increased perspiration. As a general rule, massage therapy should be avoided during periods of medication changes and dose adjustments. It is best to wait at least 1 week prior to restarting the massage treatments. Ideally, treatment should be done in the middle of a dosing schedule, since many of the products may impact the blood sugar in the short- and long-term of the dosing schedule, such as a mixture of short-acting and long-acting insulins.23 The sulfonylureas may cause paresthesias that can alter sensation and reduced accuracy of patient feedback. Biguanides, such as metformin, may cause muscle cramps, muscle weakness, numbness, and tingling, which may require further medical attention and rarely may be due to the lactic acidosis associated with this class of medications. The biguanides are also associated with easy bruising, so more aggressive techniques should be avoided. Gas and bloating are common side effects of alpha-glucosidase inhibitors and may be heightened due to massage therapy. Thiazolidinediones use is associated with development of edema, which may be improved with massage treatments. However, easy bruising is also noted with this class, so aggressive techniques should be avoided.22 Insulin injection sites and infusion pump devise placement sites should be locally avoided during massage treatments. The various types of insulins have specific onsets of actions and massaging can alter the pharmacokinetics, especially the absorption parameters, of these agents and increase the potential for hypoglycemic events.23,26 Old injection sites may develop into fibrous tissue and may require modalities like deep heat or friction therapy to address management of these areas. At the same time, long-term diabetes affects the viability of connective tissues and the nervous system, leading to fragile skin, potential for sensory loss, and high risk of infections. Therefore, careful consideration of the patient’s health status should occur at each treatment visit before starting the therapy measures.22 Antineoplastic Agents: Massage therapy has been increasingly utilized to relieve symptoms in patients with cancer. As mentioned earlier, in a study by Cassileth et al, 1,290 patients were treated with massage therapy and their symptoms scores were assessed pre- and posttherapy using a 0-10 rating scale of pain, fatigue, stress/anxiety, nausea, depression, and “other.” The symptom scores were reduced by 50%, even in patients reporting baseline high scores. Outpatients improved about 10% more than inpatients. The improvement was a persistent benefit and was evident through the duration of follow-up of 48 hours.20 However, chemotherapy and supportive adjuvant therapy can cause severe adverse effects that should be evaluated during the therapy session.20 Examples include dehydration, blood dyscrasias, orthostatic hypotension, peripheral neuropathy, immunosuppression, liver and kidney dysfunctions, and skin hypersensitivity reactions. The patient’s overall status should always be evaluated. If needed, the therapy session may be either postponed or shortened or lighter treatments may be used. The alkylating agents and antitumor antibodies can cause pulmonary fibrosis, which can result in poor oxygen delivery and decreased carbon dioxide removal, leading to weakened body tissues. These patients should avoid deep manual techniques. Peripheral neuropathy and subsequent sensory perception alteration may occur and if symptoms are severe, avoid massaging the area; if the problem is mild, employ light techniques. The antimetabolites and antitumor antibiotics have a number of cardiovascular and blood disorders, and again it is important to adjust the depth of the manual techniques. Hormonal agents may cause orthostatic hypotension and, therefore, rapid positional changes should be avoided. Tamoxifen is related to increased risk of developing DVT, and local massage of the area may result in dislodging of the clot. This can result in myocardial infarctions, cerebrovascular accident, or pulmonary embolisms. Drugs that are classified as antimitotics can cause paralytic ileus. Patients may present with symptoms such as constipation and distension. Massage therapy is contraindicated in this situation.24 Antiretrovirals: Many studies have been published demonstrating that patients with HIV infection and AIDS often seek complementary therapy for their disease.27 Although these drugs have revolutionized treatment of HIV, they are often associated with serious adverse effects relevant to massage therapy. Patients receiving therapy with nucleoside reverse transcriptase inhibitors (NRTIs) are at an increased risk of developing lactic acidosis.28 Muscle manipulation may increase lactic acid levels and is contraindicated while a patient is acidotic. NRTIs are known to cause bone marrow suppression, resulting in severe anemia and/or neutropenia. The massage therapist should observe the patient receiving these therapies for bruising and modify the massage technique accordingly. NRTIs commonly result in muscle wasting and subsequent extremity edema. The massage therapist should observe for varicosities and exercise caution when massaging distended veins. The edematous tissues should be positioned to facilitate drainage. NRTIs are also associated with the development of hypertension and CNS depression, which may also affect the type and duration of massage therapy used.28 The most common side effect reported with all non-nucleoside reverse transcriptase inhibitors (NNRTIs) is rash. The rash usually occurs within the first 6 weeks of initiation of therapy and has been noted in up to one-third of patients receiving these agents.28 Care should be taken not to agitate the affected area. NNRTIs are also commonly associated with CNS adverse effects, ranging from dizziness to hallucinations, insomnia, nightmares, and worsening of psychiatric conditions. These effects tend to occur during the first 2 weeks of therapy, when patients may be more sensitive physically and emotionally.28 Lipodystrophy, nephrolithiasis, and hyperglycemia are commonly reported adverse effects caused by protease inhibitors (PIs).28 The affected areas may be more sensitive to touch and any aggressive approach to dissolve the lipid accumulation is contraindicated. Patients who complain of acute flank pain should be suspect for the development of kidney stones and referred for medical treatment as soon as possible. Some patients may also experience microhemorrhaging while taking PIs.28 Enfuvirtide, a fusion protein inhibitor, is administered as a subcutaneous injection.28 Injection site reactions are common, so these areas should be avoided during massage to avoid altering the pharmacokinetics of the drug. The HIV integrase strand transfer inhibitors are a new class of antiretrovirals. The most commonly reported adverse effect is diarrhea, and myopathy has also been reported.28 This may result in increased sensitivity to touch. Massage therapy should be avoided if the patient is experiencing myopathy or substantial increases in creatinine kinase. Antipsychotics: Psychotherapeutics consist of antidepressants and antipsychotics. Patients taking these medications may be at an increased risk of bleeding and sedation.29 The depth of pressure should be modified to avoid bruising. Caution should be exercised when stretching muscles and mobilizing joints. Stretch receptor responses may be depressed. The phenothiazine class of antipsychotics cause muscle spasms, dystonia, and various other types of movement disorders. Deep massage into affected muscles is not appropriate. Heat applications should also be avoided because these drugs alter the patient’s responsiveness to temperature stimuli. Atypical antipsychotics may cause orthostatic hypotension, which may be of concern. These agents may also cause agranulocytosis, which will result in an increased risk of infection. These patients should avoid massage therapy until their blood counts improve. Benzodiazepines are usually given orally, and massage does not affect the absorption of the drug. However, if the drug is given by injection, the area should not be massaged for at least 2 hours.29 Implications on Pharmaceutical Care As pharmacists, the primary goal of evaluating the impact of medications on massage therapy, and vice-versa, is based on safety concerns. If the potential for patient risk exists at a low or moderate level, then there are three options to consider: 1) recommend a change in the scheduling of massage therapy; 2) recommend a change in the technique utilized for massage therapy; or 3) proceed with caution and assess for adverse events intermittently. In patients with a potential of high risk, the recommendation is to cancel the massage therapy session all together. Table 1 also summarizes the recommendations for specific pharmacologic classes of medications. Performing a thorough medication history is vital in order to capture changes in the patient’s medication profile since the last visit. Therefore, it is important for the pharmacist to get information on alternative modalities of care, including massage therapy, since there are important considerations to address in combining the various forms of treatment. REFERENCES 1. Brunner N. 2007 survey results: massage therapy continues to earn consumer respect. Massage Bodywork. 2007;April/May:20-21. 2. Massage therapy statistics. Massage Magazine. 2007;128:40. 3. National Center for Health Statistics. Almost half of Americans use at least one prescription drug annual report on nation’s health shows. HHS News. December 2, 2004. www.cdc.gov/nchs/pressroom/ 04news/hus04.htm. Accessed March 6, 2009. 4. Thomsen LA, Winterstein AG, Sondergaard B, et al. 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The implications of non-steroidal anti-inflammatory drugs in massage therapy. Massage Australia. 2000;32:30. 26. Linde B, Philip A. Massage-enhanced insulin absorption—increased distribution or dissociation of insulin? Diabetes Res. 1989;11:191-194. 27. Kaufman K, Gregory W. Discriminators of complementary and alternative medicine provider use among men with HIV/AIDS. Am J Health Behav. 2007;31:591-601. 28. Warnke D, Barreto J, Temesgen Z. Antiretroviral drugs. J Clin Pharmacol. 2007;47:1570-1579. 29. Wible JM. Pharmacology for massage therapy: psychiatric drugs. Massage Magazine. 2007;135: 96-103. To comment on this article, contact rdavidson@jobson.com.