Note. Abbreviation: M-S-D = Merck, Sharp & Dohme.

Corticosteroids may have additional significant adverse effects; although they are not generally seen following short-term steroid use, they may occur in any patient. The side effects encountered most frequently include gastric irritation with possible ulceration and hemorrhage, increased appetite, increased energy, insomnia, mild mucosal drying, blurred vision, mood change (euphoria, occasionally psychosis), irritability, and fluid retention. These side effects can range from mild to severe depending on the dosage given and the patient’s metabolism and response to the medication.

The author (RTS) routinely prescribes ranitidine (Zantac, Concordia Pharmaceuticals, Barbados, W.I.) when treating patients with steroids, as prophylaxis against gastric irritation. Patients that are already taking H2 blockers and/or proton pump inhibitors (PPIs) might require increased dosages of their medication while on steroids. Long-term effects such as muscle wasting and fat redistribution are generally not encountered with appropriate short-term use of steroids.

Another potential problem peculiar to professional voice users is steroid abuse. Because the side effects of steroids generally are uncommon and because steroids work extremely well, there is a tendency (especially among singers) to overuse or abuse them and to share their medication with other performers. This practice must be avoided.

Diuretics and Other Medications for Edema

Diuretics are potent medications that help the body eliminate excess fluid and should be taken only with a physician’s prescription and supervision. Like steroids, they should be taken only by the individual for whom they were prescribed. Diuretics are indicated and used to treat certain illnesses, such as heart or kidney failure, when the body is unable to excrete fluids at a rate needed to maintain its fluid and electrolyte balance. Diuretics also are used in conjunction with antihypertensive agents for the treatment of high blood pressure.

The premenstrual period is a temporary physiological condition in which women retain fluid as a result of decreased estrogen and progesterone levels associated with altered pituitary activity. An increase in circulating antidiuretic hormone results in fluid retention in Reinke’s space as well as in other tissues. The fluid retained in the vocal fold during inflammation and hormonal fluid shifts is protein bound, not free water.⁴ Diuretics do not remobilize this fluid effectively and can dehydrate the performer, resulting in decreased lubrication and thickened secretions and persistently edematous vocal folds, and thus should not be used for vocal fold symptoms related to these conditions. If diuretics must be used for other medical purposes, the voice should be monitored closely.

Topical and systemic decongestants such as oxymetazoline hydrochloride (Afrin, Bayer HealthCare LLC, Tarrytown, New York) and pseudoephedrine (Sudafed, McNeil-PPC, Inc. Fort Washington, Pennsylvania) have also been used to treat edema/congestion in the upper respiratory tract. Oxymetazoline hydrochloride (Afrin) applied by a large particle mist to the larynx is particularly helpful in treating severe edema immediately prior to performance, but it should be used only under emergent and extreme circumstances. Afrin is more commonly used as a nasal spray to treat nasal congestion. Its primary action involves reduction in the diameter and volume of vascular structures in the submucosal area; however, it may also produce “rebound” phenomena and thus requires use with caution.

Sprays, Mists, and Inhalants

Diphenhydramine hydrochloride 0.5% (Benadryl, McNeil-PPC Inc., Fort Washington, Pennsylvania) in distilled water, delivered to the larynx as a mist may be helpful for its vasoconstrictive properties, but it is also dangerous because of its topical anesthetic effect and is not recommended by the author (RTS). However, Punt advocated this mixture and several modifications of it.⁵

Five percent propylene glycol in a physiologically balanced salt solution may be delivered by large particle mist and can provide lubrication, particularly helpful in cases of laryngitis sicca after air travel or as associated with dry climates. Such treatment is harmless and may also provide a beneficial placebo effect. Water, saline, or other physiologically balanced solutions delivered via a vaporizer or steam generator are frequently effective and sufficient. This therapy should be augmented by oral hydration, which is the mainstay of treatment for dehydration.

Nasal steroid sprays such as beclomethasone dipropionate (Beconase AQ, GlaxoSmithKline, Brentford, United Kingdom, and Qnasl, Teva Pharmaceuticals USA, Inc., North Wales, Pennsylvania), budesonide (Rhinocort Aqua, AstraZeneca Pharmaceuticals, LP, Wilmington, Delaware), triamcinolone (Nasacort, Chattem, Inc., Chattanooga, Tennessee), and mometasone (Nasonex, Merck & Co., Inc., Kenilworth, New Jersey) do not appear to harm the voice. The steroid in the nasal spray works topically on the nasal mucosa and is not absorbed systemically. However, certain propellants in these nasal sprays may cause mucosal drying. For this reason, the author (RTS) generally prescribes steroid nasal sprays that have an aqueous medium, such as budesonide (Rhinocort Aqua).

Most oral steroid inhalers, such as triamcinolone acetonide (Azmacort, Abbott Laboratories, Chicago, Illinois) used to treat asthma are not recommended for use in professional voice users.^6,7 Dysphonia caused by contact inflammation from oral steroid inhalers occurs in up to 50% of patients and is related to the aerosolized steroid itself and not to the Freon propellant. Steroid inhalers used for prolonged periods may result in Candida laryngitis; and as is common in asthmatics, prolonged use of steroid inhalers can cause atrophy of the vocalis muscle.^7,8

Antibiotics

When antibiotics are used in professional voice users, high doses are recommended to achieve therapeutic blood levels rapidly, especially if important performances are imminent. When there is little time between initial treatment and performance, starting treatment with an intramuscular injection may be helpful. Selecting oral antibiotics that are absorbed rapidly and achieve optimal blood levels faster may also be helpful.

When patients have no pressing engagements, antibiotic use should be based on cultures whenever appropriate (eg, throat culture for streptococcus infection). However, in the common situation in which a performance must proceed and when there is clinical evidence of bacterial infection, antibiotics should be instituted after cultures are taken, without waiting for the results. The potential damage of delayed treatment in an active performer is greater than the potential harm of antibiotic use for an unproven organism.

Antiviral Agents

A limited number of antiviral agents are available commercially. Acyclovir (Zovirax, GlaxoSmithKline, Brentford, United Kingdom) is used specifically for treating the herpes simplex virus (HSV) types I and II and may be appropriate in patients with recurrent herpetic superior laryngeal nerve paresis or paralysis. Oseltamivir (Tamiflu, Genentech Inc., San Franscisco, California) is a relatively new antiviral drug that can be effective in the treatment of acute influenza and for prophylaxis of influenza in adults and children, 13 years and older. It is not a substitute for a flu vaccination. Voice problems have not been reported with Tamiflu; however, rash and swelling of the face and tongue have been reported, which could have a negative impact on vocal performance. Zanamivir (Relenza, GlaxoSmithKline, Brentford, United Kingdom) is another antiviral medication administered by oral inhalation, which delivers the medication directly to the respiratory tract. Relenza is indicated for treatment of influenza A and B in patients who have been symptomatic for no more than 2 days, and in adults and children 7 years or older. However, it is generally not recommended for patients with underlying airway disease; bronchospasm and decreased lung function have been reported with use of this drug. Recently, a new medication to reduce the length and degree of symptoms of the common cold has been introduced and should be available in less than 1 year pending FDA approval. Pleconaril (Picovir, Schering-Plough, Kenilworth, New Jersey) specifically attacks the rhinovirus, which is the most common cause of the common cold. Pending FDA approval of this medication, it will be available by prescription only and its brand name will be Picovir.

Vistide (cidofovir, Gilead Sciences, Foster City, California) is now being used as an intralesional injection in treating human papilloma virus (HPV) involving the larynx. An in-depth discussion of its use can be found in Chapter 55. Patients with human immunodeficiency virus (HIV) are also treated with antivirals such as zidovudine (Retrovir, ViiV Healthcare, Brentford, United Kingdom), which was previously called azidothymidine (AZT). This drug has the potential to cause very severe side effects; however, it is often difficult to determine what is a side effect of a medication, because many of the side effects can be manifestations of the HIV disease process itself. Zi­dovudine can cause hoarseness, cough, pharyngitis, nervousness, muscle spasm, tremor, and many other systemic side effects, all of which can have a negative impact on vocal performance.

Amantadine (Symmetrel, Endo Health Solutions Inc., Malvern, Pennsylvania) used in the treatment of Parkinson’s disease, also has been found to be effective against influenza^9–12 and other viruses. If a performer must work in an area in which there is a flu epidemic, it may be reasonable to use this drug. However, agitation, tachycardia, and extreme xer­ostomia and xerophonia may occur. When these side effects occur, they are generally severe enough to require cancellation of a performance.

Antitussive Medications

Cough suppressants (antitussives) often contain an antihistamine and codeine, a narcotic, that can have a secondary drying effect on vocal tract secretions.^13,14 Benzonatate (Tessalon, Pfizer Inc., New York, New York) is a non-narcotic antitussive that acts peripherally by anesthetizing stretch receptors in the upper respiratory tract, thereby suppressing the cough reflex. However, severe hypersensitivity reactions including laryngospasm and bronchospasm have been reported. Dextromethorphan is a non-narcotic, antitussive agent found in most cough syrups and has pharmacologic actions similar to those of codeine. Generally, the over-the-counter preparations that contain dextromethorphan and guaifenesin (Robitussin DM, Pfizer Inc., Richmond, Virginia) work well for voice professionals. All patients, including singers, should be instructed to read the labels on all OTC medications. If there is any question regarding safety or ingredients of a product, it should be discussed with their primary physician and/or laryngologist.

Antihypertensive Agents

Almost all of the antihypertensive agents used currently have a parasympathomimetic action of varying degrees and thus dry mucous membranes of the respiratory tract. Often, they are used in combination with a diuretic that promotes dehydration. The authors have frequently noted dryness with reserpines and agents of the methyldopa group, and occasionally a dry cough with some of the newer medications used to treat hypertension. When mucosal drying and a dry, nonproductive cough are thought to be a side effect of an antihypertensive medication, the laryngologist may recommend that the patient’s internist prescribe another antihypertensive agent. Beta-blockers such as propranolol (Inderal, Akrimax Pharmaceuticals, Cranford, New Jersey) are also used in the treatment of hypertension but are not recommended treatment for preperformance anxiety.¹⁵

Gastroenterologic Medications

Medical management of gastroesophageal reflux disease (GERD) generally includes neutralization of gastric acid with antacids; suppression of acid secretion with histamine receptor antagonists (H2 blockers), such as ranitidine (Zantac, Concordia Pharmaceuticals, Inc., Oakville, Ontario); blocking of the gastric proton pump enzyme (H+/K+ATPase) with antagonists such as omeprazole (Prilosec, Astra-Zeneca Pharmaceuticals, LP, London, United Kingdom); and modifications in lifestyle and diet. In the laryngologist’s (RTS) practice, the authors frequently encounter patients who misunderstand their medical treatment for laryngopharyngeal reflux despite receiving oral and written explanations and instructions by the authors and being reinforced by other members of our voice team involved in a patient’s care. The most common misconception is that H2 blockers and/or proton pump inhibitors (PPIs) eliminate the need for antacids and other lifestyle modifications. It is especially important for singers and all patients to understand the correct rationale for use of their medications, because inadequately treated reflux laryngitis can have deleterious effects on the voice over time including cancer of the larynx or esophagus. A more in-depth discussion of reflux management can be found in Chapter 59. Laryngeal cancer and its treatment can be found in Chapter 103.

Antacids can cause constipation, diarrhea, or bloating in some people, which may affect performance by impairing the support mechanism vital to singers and other musicians. Occasionally, they also have a drying effect. However, it is usually possible to find an antacid that can be tolerated by any individual. It is also possible to select antacids that do not contain chemicals (eg, aluminum) that some people wish to avoid (Tables 15–2 and 15–3).

H2 receptor antagonists have revolutionized the treatment of gastroesophageal reflux disease and proved beneficial for the treatment of reflux laryngitis (RL) and are now used widely by most laryngologists who treat a large number of professional voice users.

H2 receptor antagonists inhibit the stimulation of gastric acid secretion and are generally effective in reducing acid output from gastric parietal cells, although they have little affect on the basal rate of acid production. The H2 blockers most commonly used include ranitidine (Zantac, Concordia Pharmaceuticals, Inc., Oakville, Ontario), famotidine (Pepcid, Merck & Co., Inc., Kenilworth, New Jersey), cimetidine (Tagamet, Prestige Brands Holdings, Inc., Greenburgh, New York), and nizatidine (Axid, Braintree Laboratories, Inc., Braintree, Massachusetts) have been deregulated by the FDA and are now available OTC, but in much lower doses than prescription doses. Patients should be made aware of this. Although drying of the laryngeal mucosa (from its antihistamine action) is not a major side effect of the H2 blockers, it does occur and must be considered. Occasionally, the drying effects of H2 blockers can be severe enough to cause not only dry mouth, but also dry and irritated eyes. This condition makes it difficult to read scores and causes excessive blinking, especially under spotlights, which can be misinterpreted by an audience as nervousness.

Gastric proton pump (H+/K+ATPase) inhibitors (PPIs) suppress gastric acid production and are generally highly effective in the management of GERD and RL. Medications such as omeprazole (Prilosec, AstraZeneca Pharmaceuticals, LP, London, United Kingdom), lansoprazole (Prevacid, Takeda Pharmaceuticals, Osaka, Japan), rabeprazole (Aciphex, Janssen Pharmaceuticals, Horsham, Pennsylvania), pantoprazole (Protonix, Pfizer Inc., New York, New York), and esomeprazole (Nexium, AstraZeneca Pharmaceuticals, LP, London, United Kingdom) inhibit the H+/K+ATPase system, which is virtually unique to the gastric parietal cell. H+/K+ATPase competitive inhibitors cause inactivation of the H+/K+ATPase enzyme, suppressing both basal and stimulated gastric acid secretion for prolonged periods of time. In most patients, once or twice daily dosing usually provides excellent control of acid production. Proton pump inhibitors do not adversely affect the lower esophageal sphincter or esophageal motility, but they do slow the linear emptying rate of solids from the stomach.¹⁶ Although the incidence of side effects of PPIs is low, they can cause diarrhea, abdominal pain, and nausea and elevation of liver enzymes (this is also true of most H2 blockers). Dry mouth, esophageal candidiasis, muscle cramps, depression, tremors, dizziness, fatigue, and headaches have also been reported. Resistance to omeprazole has also been reported.¹⁷

Hyperkinetic agents improve motility and help prevent reflux by increasing the rate of gastric emptying. For several years, metoclopramide (Reglan, ANI Pharmaceuticals, Inc., Baudette, Minnesota) was the only such agent available. Because of troublesome side effects, particularly neurological abnormalities in approximately 10% of patients, the drug was never used extensively in professional singers; and it has now been largely replaced by newer agents. At present, the most commonly prescribed medication in this drug class is cisapride (Propulsid, Janssen Pharmaceuticals, Inc., Horsham, Pennsylvania). Cisapride increases lower esophageal sphincter pressure and lower esophageal peristalsis, which significantly accelerates gastric emptying of liquids and solids. The most common side effects are headache, abdominal pain, nausea, diarrhea, constipation, dizziness, pharyngitis, depression, dehydration, and rhinitis. Dry mouth, tremor, and somnolence have been reported in less than 1% of patients, and numerous other adverse reactions are seen uncommonly.

Other medications used to treat disorders of the gastrointestinal tract include phenobarbital (many manufacturers), prochlorperazine (Compazine, GlaxoSmithKline, Brentford, United Kingdom), isopropamide (many manufacturers), and propantheline bromide (many manufacturers). Members of the belladonna alkaloid group, including scopolamine (Scopace, Hope Pharmaceuticals, Scottsdale, Arizona) and atropine (AtroPen, Meridian Medical Technologies, Columbia, Maryland), are widely used and prescribed for their antispasmodic effects. All of these agents have a significant drying effect on secretions in the vocal tract.

Not infrequently the laryngologist may encounter a patient who consumes large amounts of vitamin C (ascorbic acid) in an effort to maintain health or to prevent the common cold. However, large amounts of ascorbic acid can irritate the stomach lining and consequently aggravate gastroesophageal reflux laryngitis. In some patients, a drying effect may occur when vitamin C is taken in large doses, probably due to a mild diuretic effect.¹⁸ Additionally, in patients with impaired renal function, high doses of vitamin C may produce acidic urine and possibly renal calculi.

Sleeping Pills

Sleeping pills generally should not be necessary for healthy people. Occasionally, the stresses of a tour and the aggravations of travel, along with frequent changes in time zones, can disturb sleep patterns. For this reason it is appropriate to take a small supply of a mild sleeping medication when traveling and to use it with great caution. These should be prescribed with instructions regarding rebound insomnia and the risk of habituation and physical dependence. Performers should avoid using diphenhydramine (Benadryl, McNeil-PPC, Inc. Fort Washington, Pennsylvania), an antihistamine that is a common ingredient in many OTC sleep aids. It is a safe drug and works well, but it produces excessive drying of mucosal membranes.

Analgesics

Aspirin and other analgesics such as ibuprofen (many manufacturers) are prescribed frequently for relief of minor to moderate pain. The platelet dysfunction caused by aspirin (many manufacturers) predisposes an individual to bleeding and even hemorrhage, especially in vocal folds traumatized by excessive voice use in the face of vocal dysfunction. A vocal fold hemorrhage can be devastating to a professional voice user; and for this reason, the laryngologist (RTS) prohibits aspirin use and recommends minimal use of NSAIDs in his singers and all voice patients. However, the author (RTS) has one exception to the aspirin rule for singers and other professional voice users. A low daily dose of aspirin, generally one children’s aspirin (81 mg), is used commonly in the treatment of patients with known coronary artery disease and for the prevention of heart disease in others. Because this dosage of aspirin is so small, its potential for jeopardizing the voice is low; and treatment of heart disease always takes precedence over maintenance of a healthy voice. Acetaminophen (Tylenol, McNeil-PPC, Inc., Fort Washington, Pennsylvania) is the recommended analgesic for mild to moderate pain. The nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen (Motrin, McNeil-PPC, Inc., Fort Washington, Pennsylvania) and ketoprofen (Oruvail, Sanofi, Malvern, Pennsylvania similar to ibuprofen, but taken only once daily) may interfere with the clotting mechanism, and their use is also discouraged in professional voice users.

A new class of analgesics, selective COX-2 inhibitors, is now being used to treat acute and chronic pain. These medications do not interfere with the COX-1 pathway and, do not cause bleeding dyscrasias or gastrointestinal side effects as seen with traditional NSAIDs.

Caruso used a spray of ether and iodoform on his vocal folds when he had to sing with laryngitis. However, such use of analgesics is extremely dangerous and should be avoided. Pain has an important protective physiologic function. Masking it risks incurring significant vocal damage that may not be recognized until after the analgesic wears off. If a singer requires analgesics taken orally or topical anesthetics to alleviate laryngeal discomfort, the laryngitis is severe enough to warrant canceling a performance. If the analgesic is used for headache or some other discomfort not directly associated with voice production, symptomatic treatment should be discouraged until singing commitments have been completed or cancelled.

Narcotic analgesics should not be used for any reason shortly before performance, especially if the medications are being used for laryngeal discomfort. Even when the pain is outside the head and neck, narcotics may cause sufficient change in sensorium to impair performance and risk vocal fold injury through unconscious technical voice abuse. As Damsté reported, sedatives and narcotics, in addition to impairing intellectual function, may cause an uninhabited drive to speak and symptoms of dysarthria.¹⁹ Occasional exceptions can be made. For example, if a low dose of codeine early on a performance day is sufficient to control moderate menstrual cramping, its use is certainly not unreasonable. However, if menstrual cramps are so severe that high doses of codeine (in the 60 mg range) are required within a few hours of performance, cancellation may be more appropriate.

Hormones

The most significant group of drugs that can adversely affect the voice are hormones such as androgens and anabolic steroids.^20–25 These drugs cause changes in voice quality by alterations in fluid content and structural changes. Structural alterations in laryngeal architecture seldom occur as the result of pharmacologic influences, but androgens are an exception. They may produce irreversible lowering of fundamental frequencies and coarsening of the voice, especially in females.^22–30 Androgenic agents such as Danocrine (danazol, Sanofi, Malvern, Pennsylvania) are used in the treatment of endometriosis, as part of chemotherapy regimens for some breast cancers, and to treat postmenopausal sexual dysfunction and other problems.^31–40 Birth control pills with relatively high progesterone content are most likely to produce androgen-like changes in the voice.^41–48 Most oral contraceptives marketed in the United States now have an appropriate estrogen-progesterone ratio, and voice changes are seen in only about 5% of women who use birth control pills (C. Carroll, MD, and H. von Leden, MD personal communication, September 1992). These changes generally are temporary, abating when oral contraceptive use is discontinued.

Estrogen replacement is helpful in forestalling the typical voice changes that follow menopause. The conjugated estrogen preparation used most frequently in the United States is Premarin (Prempro, Pfizer Inc., New York, New York). Until recently, the conjugated estrogens were thought to be preferable to estradiol; however, it now appears that there is no real difference with regard to the effect on the voice (J. Abitbol, personal communication, 2001). The progesterone, Provera (Pfizer Inc., New York, New York) is often prescribed in combination with Premarin (Prempro). In low doses, natural progesterones usually do not cause significant voice problems. However, some of the synthetic progesterone substitutes have androgenic effects and the potential for permanent virilization of the voice. Unless medical contraindications are present, professional voice users should be offered hormone replacement under appropriate medical supervision at the time of menopause.

Other hormone replacement medications may also affect the voice, often beneficially. Thyroid replacement may restore vocal efficiency and “ring” lost with even a mild degree of hypothyroidism. Agents used to treat maladies in any part of the diencephalic pituitary axis should be presumed to have laryngeal effects and warrant close monitoring of voice function.

Bronchoactive Medications

Phonation depends on the availability of a powerfully supported airstream passing between the vocal folds. Impairment of pulmonary function can cause severe problems for professional voice users. Pulmonary function is affected deleteriously by bronchoconstriction, which occurs in allergic reactions and asthma. These conditions may hamper or prevent vocal performance unless recognized and treated promptly. Bronchodilators can be used to counteract the bronchoconstrictive effects of such environmental factors as house dust, pollen, other inhalant allergens, and common air pollutants produced by our increasingly industrialized society. Bronchodilators often are used to treat patients with reactive airway disease, although inhaled bronchodilators may produce chronic laryngitis, as discussed previously. Clinically, inhaled cromolyn sodium (Intal, Pfizer, Inc., New York, New York) appears to cause fewer problems than most of the other inhalant bronchodilators commonly used in the treatment of asthma. The bronchodilator used most often is epinephrine and its related compounds, including xanthines (aminophylline is an example). In professional voice users, the author (RTS) favors asthma management primarily with oral medications and minimal inhaler use, as discussed in Chapter 46 in greater detail.

Cystic fibrosis is an autosomal recessive disorder in which systemic dysfunction of the exocrine glands causes excessive mucus production in the airways and reduced pulmonary function. Dornase alfa (Pulmozyme, Genenctech, Inc., San Franscisco, California), an enzyme used in the treatment of cystic fibrosis, has been reported to cause sore throat, hoarseness and other voice alterations, laryngitis, and chest pain.⁴⁹ However, these side effects are not severe and generally will subside without adjustment of dosage.

Beta-Blockers

Propranolol (Inderal, Akrimax Pharmaceuticals, Cranford, New Jersey) and other beta-blockers have been used successfully in the treatment of hypertension, cardiac tachyarrhythmias, and migraine headaches. Beta-blockers also have been used to treat stage fright. British investigators⁵⁰ found that instrumental musicians given propranolol did, in fact, exhibit less anxiety during performance; however, a significant response was not seen in voice professionals or musicians.

A subsequent study reported that propranolol, given for preperformance anxiety, lessened anxiety and also produced an increase in salivation.⁵¹ This investigation was conducted by measuring the weight increase in saliva-saturated dental rolls of cotton placed in the mouth during performance. This indicated that the problem of upper respiratory tract secretion dryness had been avoided and that some of the parasympathomimetic effects of performance anxiety had been negated.

Today, laryngologists generally agree that these drugs should not be used by singers or other voice professionals. Beta-blockers are potentially dangerous because they can slow the heart rate, decrease blood pressure, and cause bronchospasm that can trigger asthma attacks in susceptible patients. In addition, when given in doses sufficient to ameliorate stage fright, they produce a lackluster performance.¹⁵ Any professional voice user who requires an ingested substance to perform the daily activities of his or her chosen profession is manifesting a more significant psychological problem and should be referred for appropriate counseling and treatment and not merely medicated.

Neurologic Medications

Professional voice users may be diagnosed with a neurologic disease during evaluation of their voice complaint or have a coexisting illness. A number of highly potent medications are used in the medical management of neurologic disorders. The side effects of some of these medications and/or the course of the illness itself may ultimately force the end of a performance career or, at the very least, require significant modifications. Some of the most common neurologic diseases and the medications used to treat them are discussed. Parkinson’s disease is treated with medications having anticholinergic properties such as L-dopa (and L-dopa in combination with other agents), dopamine receptor agonists, and monamine oxidase inhibitors (MAOIs). Parkinsonian syndrome, not secondary to Parkinson’s disease, may also be a focus of treatment with these drugs.

The MAOIs are also used in the treatment of de­ pression. However, many other drugs used in the treatment of depression also have anticholinergic properties and have been associated with speech disorders, hoarseness, and aphonia.^52,53 Side effects are related to a drug’s mechanism of action on the central nervous system and peripheral target organs.⁵⁴ Anticholinergic side effects include blurred vision, dryness, impaired urination, constipation, nervousness, dizziness, and drowsiness, as well as confusion, memory loss, headache, hallucinations, and delusions.⁵⁵ Side effects most commonly associated with L-dopa are gastrointestinal disturbance, orthostatic hypotension, syncope, oral dryness, blurred vision, and cardiac arrhythmia. Dyskinesias, nightmares, confusion, agitation, psychosis, depression, increased libido, and end-of-dose akinesia have been reported.⁵⁵ L-dopa in combination with other agents is used to decrease peripheral and systemic side effects. Amantadine (Symmetrel, Endo Health Solutions, Inc., Malvern, Pennsylvania) used in the treatment of Parkinson’s disease is also used as an antiviral drug to treat influenza.

Dopamine receptor agonists can cause gastrointestinal (GI) disturbance, postural hypotension, and fatigue as well as skin rash, headache, involuntary movements, depression, and sometimes confusion or hallucinations.⁴⁹

Myasthenia gravis is an autoimmune disease in which serum antibodies impair synaptic transmission at the neuromuscular junction by disturbance of the neurotransmitter acetylcholine.⁵⁶ Pyridostigmine bromide (Mestinon, Valeant Pharmaceuticals International, Inc., Bridgewater, New Jersey) is used to treat myasthenia. Mestinon enhances the action of acetylcholine by inhibiting the enzyme acetylcholinesterase. Excessive salivation and gastrointestinal disturbances are common side effects of acetylcholinesterase inhibitors. Skin rash, nervousness, confusion, or weakness is also reported. Attention deficit disorder (ADD) is a commonly diagnosed medical problem that affects children and adults. Once the diagnosis is confirmed and symptoms persist, medication is indicated. The medication prescribed most often is methylphenidate hydrochloride (Ritalin, Novartis Pharmaceuticals, Inc., Philadelphia, Pennsylvania). Most of the time, Ritalin, in appropriate doses, does not cause significant voice problems even in singers. However, it may produce a slight tremor that could, theoretically, be audible in singing.

Multiple sclerosis (MS) involves the progressive loss of myelin in white matter adjacent to the ventricles of the brain, optic nerves, brainstem, cerebellum, and spinal cord.⁵⁶ Drug therapy aims at reducing the frequency of exacerbations and/or reducing the degree of myelin loss during an attack. Medications are also used to treat associated symptoms such as spasticity, cerebellar dysfunction, and depression.⁵⁵ These medications include immunosuppressants such as corticosteroids, adrenocorticotrophic hormone, azothioprine, and cyclophosphamide. Corticosteroid side effects have been previously discussed. Other immunosuppressants may also be used in patients with an inability to tolerate corticosteroids, but these side effects are potentially extremely serious. Beta-interferon (Avonex, Biogen, Weston, Massachusetts) is a potent immunosuppressant given by injection; its side effects include local inflammation, flu-like syndrome, fever, chills, muscle aches, and asthenia. The incidence of these side effects will diminish with continued treatment. The side effects of medications used to treat MS, along with symptoms of the disease, can affect performance but are reported to rarely cause speech disturbance.

Herbs and Supplements

Over the past decade or so, more and more individuals, including singers, are seeking alternatives to medications in the form of herbs and dietary supplements. Many common herbs have potential side effects for voice users; additionally, some herbs should never be taken by anyone because of potentially severe consequences. Some are highlighted in Table 15–4, and selected substances are summarized in greater detail in Table 15–5. In addition, it is helpful to be familiar with some of the most common dietary supplements and their intended usage (Table 15–6).

These dietary supplements are not to be considered prevention, treatment, or cure for any medical problem. Some supplements are dangerous. For example, glucosamine, which is extracted from shellfish, should not be taken by individuals with shellfish allergy. The ingredients of all supplements must be studied carefully, and patients should be encouraged to discuss the use of dietary supplements with their physician before using them. Nevertheless, their use is ubiquitous.

Complementary, Alternative, and Integrative Medicine

Millions of Americans spend billions of dollars annually on complementary alternative medicine (CAM), and many of these are herbal products. Some CAM herbal preparations are useful, others have no proven efficacy. Some are safe, others are potentially harmful. The quality of the product may vary from one manufacturing company to another. Occasionally, the ingredients listed on the label do not correspond to the product in the bottle. The recommended dosage is not uniformly agreed on, and the manufacturers of herbal products are not regulated sufficiently at this time. Some singers and other voice patients use CAM indiscriminately; and it behooves them, their teachers, and their health care providers to become familiar with the potential benefits and risks of taking complementary and alternative remedies.

Complementary medicine uses therapies “along with” conventional medicine (eg, the use of massage for low back pain “along with” muscle relaxants). Alternative medicine uses therapies “in place” of conventional medicine (eg, homeopathy to treat rheumatoid arthritis or the unsuccessful attempt to treat cancer with laetrile). Integrative medicine incorporates proven effective outcomes of CAM with conventional medicine.

CAM is not limited to herbal products. Homeopathy uses principles of similars and dilutions. Similars work on the concept that if a specific substance causes symptoms in a healthy person similar to that of an ill patient, that substance can be used to cure the sick individual (“like cures like”). Dilutions use the principle that small doses “stimulate” a beneficial immune response or “vital force” in the body.

Traditional Chinese medicine incorporates acupuncture and herbal remedies. Chiropractors and osteopaths use manipulation techniques. Some CAM practitioners utilize massage, hypnosis, biofeedback, or meditation; others use prayer and spirituality, energy, or naturopathy as well as a host of other modalities.

The field of alternative and complementary medicine is vast. As of December 2016, the online research resource PubMed of the National Library of Medicine (https://www.ncbi.nlm.nih.gov/pubmed/) cites more than 26 million publications, abstracts, or full articles. The challenge is to weed out the useful from the useless and the safe from the dangerous.

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