Otolaryngol Clin N Am

40 (2007) 1081–1090

Effects of Medications on the Voice

Mona M. Abaza, MDa, Steven Levy, MDb,
Mary J. Hawkshaw, BSN, RN, CORLNc,
Robert T. Sataloff, MD, DMAc,*
a
Department of Otolaryngology, University of Colorado School of Medicine,
Denver, CO 80262, USA
b
Philadelphia Ear, Nose and Throat Associates, 1721 Pine Street,
Philadelphia, PA 19103, USA
c
Department of Otolaryngology-Head and Neck Surgery, Drexel University College
of Medicine, 1721 Pine Street, Philadelphia, PA 19103, USA

Otolaryngologists should be familiar with the potential side effects and

interactions of medications that are prescribed commonly to professional
voice users. Because some of these side effects are atypical and can be psy-
chiatric symptoms, their relationship to medications might not be obvious.
Oropharyngeal dryness, voice changes, movement changes, mood distur-
bances (eg, agitation, anxiety, depression, and mania), perceptual
disturbances (eg, hallucinations and delusions), cognitive disturbances (eg,
delirium and confusion), behavioral disturbances (eg, insomnia), and drug
interactions are all important possibilities of which the prudent practitioner
should be aware. Drug-induced symptoms can occur even with standard
dosages and at any time during the course of treatment. An awareness of
the potential for side effects caused by adrenocorticoids, antihistamines,
decongestants, antisecretory drugs, and other medications will help the
clinician to avoid or detect and treat drug-induced disorders, as will an
awareness of the potential for side effects caused by combinations of medi-
cations. Identification of individual risk factors, such as age, preexisting or-
ganic brain disease, a history of drug abuse or dependence, or coexisting or
preexisting psychiatric disorders, is important in preventing and detecting
drug-induced disorders. The drugs discussed in this article can have seriousd
and even fataldinteractions with certain medications.
The combination of some of the medications prescribed by several practi-
tioners, including otolaryngologists, psychiatrists, and naturopathic care givers,

* Corresponding author.
E-mail address: rtsataloff@phillyent.com (R.T. Sataloff).

0030-6665/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.otc.2007.05.010 oto.theclinics.com
1082 ABAZA et al

has the potential to enhance or interfere with the therapeutic effects of one or
the other. In addition to psychiatric side effects, other adverse reactions can
occur (eg, cardiac arrhythmias, hypertension, and local effects). Certainly, all
reactions, particularly psychiatric symptoms, are not caused by medication;
however, some can be a manifestation of a coexisting or preexisting psychiatric
or other disorder that has been aggravated by a combination of medications.

Drug-induced psychiatric disorders

The manifestations of drug-induced psychiatric disorders can be related
to direct drug toxicity or to interference with the brain’s metabolism of cer-
tain drugs. The most common psychiatric symptoms include delirium
(an acute reaction with fluctuating awareness of self and environment), con-
fusion, disorientation, tremor, ataxia, and mania. Associated behavioral signs
include increased physical activity, rapid speech, insomnia, and mood eleva-
tion. Psychiatric symptoms that occur during the course of treatment also
may be related to the medical or psychiatric condition being treated. For
example, anxiety disorders and panic attacks are known to occur in asso-
ciation with thyroid, parathyroid, and adrenocortical disorders; Langhan’s
cell endocrinopathies; collagen vascular disorders (eg, systemic lupus eryth-
ematosus, rheumatoid arthritis, temporal arteritis, and periarteritis no-
dosa); neurologic (eg, multiple sclerosis) and neurotologic (eg, Ménière’s
disease) [1]. Delusions (the perception that one’s environment and circum-
stances seem unfamiliar) can occur in association with certain endocrino-
pathies [1]. Derealization (the feeling that familiar events seem unreal,
strange, or dream-like and that colors, objects, and shapes appear to be
distorted) and delusions have been reported in systemic lupus erythemato-
sus [1].
A detailed history aids in the clinician’s assessment of each patient’s risk.
The history should include the following questions:
 What prescription medications, over-the-counter (OTC) medications,
and herbal remedies are the patient taking?
 Are there any coexisting medical conditions?
 Is there a personal or family history of a psychiatric disorder?
 Is there a history of a reaction to a psychiatric drug?
 Is there a history of drug or alcohol abuse?
The patient’s age also is an important factor when deciding which med-
ications to prescribe. Elderly patients have a greater risk for drug-induced
psychiatric disorders because they tend to be taking more medications
and, therefore, are more likely to experience drug interactions. Older
patients also tend to have other medical conditions that can prolong drug
metabolism and increase systemic drug levels.
Preexisting organic brain disease and drug abuse also can be risk factors
for the development of psychiatric side effects. Patients who have a history
 EFFECTS OF MEDICATIONS ON THE VOICE 1083

of drug dependence or abuse often manifest delirium. The presence or

history of a mood disorderddepression or maniadalso is a risk factor
for psychiatric side effects to medications [2]. Adrenocorticoids can aggra-
vate or unmask depression or mania in these patients. Even a family history
of mania is a risk factor for the development of mania as a side effect [2].
Assessment of all risk factors is important because multiple factors in
a particular patient can be additive. The overall low incidence of psychiatric
side effects with a particular medication might increase in the presence of
other factors. An understanding of the risks in each individual patient is
essential in selecting medications. Physicians should routinely ask patients
to bring in or to make a list of all medications that they have taken during
the previous 2 months. Clinicians also should inquire if a patient has ever ex-
perienced any side effects or abnormal reactions from medication (Table 1).

Side effects of specific common medications

Steroids
Adrenocorticoids are known to cause side effects. Gastrointestinal upset
and ulcers, increased appetite, mucosal drying, blurred vision, and
Table 1
Selected drugs and their possible psychiatric side effects
Drug Side effect
Adrenocorticoids Agitation, anxiety, confusion, delirium, depression,
hallucinations, mania, paranoia, psychoses, sleep
disturbances
Antihistamines and decongestants
Azatadine Agitation, anxiety, euphoria, hallucinations,
hypomania, mania, nervousness, somnolence
Loratadine Agitation, anxiety, confusion, delirium, depression,
nervousness
Fexofenadine Somnolence
Phenylpropanolaminea/guaifenesin Agitation, anxiety, nervousness
Pseudoephedrineb/guaifenesin Hallucinations
Antisecretory agents
Cimetidine Confusion, delirium, depression, hallucinations,
mania, paranoia
Famotidine Agitation, anxiety, depression, nervousness
Lansoprazole Hallucinations
Nizatidine Agitation, anxiety, nervousness, somnolence
Omeprazole Aggression, agitation, anxiety, depression,
hallucinations, hostility, nervousness, violence
Ranitidine Confusion, delirium, depression, hallucinations,
mania
a
Agents containing phenylpropanolamine also can cause confusion, delirium, depression,
euphoria, hallucinations, hypomania, mania, and paranoia.
b
Agents containing pseudoephedrine also can cause agitation, anxiety, euphoria, hypoma-
nia, mania, nervousness, and paranoia.
1084 ABAZA et al

aggravation of blood glucose levels, particularly in diabetics, are docu-

mented side effects [3]. Delirium, depression, insomnia, mania, and
psychoses are not uncommon psychiatric effects. Symptoms tend to be pro-
portional in incidence to the dosage and duration of steroid use. Iatrogenic
Cushing’s syndrome, which can be caused by long-term steroid use, also can
manifest these signs [2,4]. A personal or family history of affective mental
illness can predispose a patient to the psychiatric side effects of steroids.
Some drugs, such as corticotropin, can cause an increase in endogenis
corticosteroids causing similar effects. The potential for steroid abuse in
professional voice users cannot be overemphasized, and the side effects
should not be dismissed as insignificant.
Treatment of side effects may need to be considered when steroid use is
required. A concomitant use of a histamine-2 receptor antagonist
(H2 blocker) or proton pump inhibitor (PPI) can assist with gastrointestinal
upset. A carefully titrated insulin sliding scale can help to control blood
sugar elevation in diabetics [3]. Severe depression might require antidepres-
sant treatment, and an antipsychotic medication or a mood stabilizer may
become necessary to treat steroid-induced mania. Insomniadas an isolated
side effect or as part of a manic episodedalso could require medical
intervention.
Inhaled steroids are used primarily for respiratory disorders and present
more local than systemic effects. Nasal steroids have had few documented
effects on the voice; however, orally inhaled steroids have demonstrated
oral candidiasis, dysphonia, pharyngitis, and cough and often are not rec-
ommended for use in professional voice users unless absolutely needed for
asthma control because of the common voice effects [3,5]. Ipratropium bro-
mide, a nasally or orally inhaled medication used primarily for pulmonary
symptoms, has shown side effects that include hoarseness and cough. Fluti-
casone, one of the more common medications used for asthma and used also
as a primary nasal steroid, lists a prevalence of 2% for hoarseness and sore
throat for the orally inhaled preparation. Salmeterol xinafoate and flutica-
sone propionate (Advair) lists the same incidence of hoarseness and throat
irritation, attributing it to either drug. It does not seem to be dose depen-
dent. Triamcinolone, pirbuterol acetate, and albuterol list voice changes
as part of their common side effects. Voice difficulties due to lack of respi-
ratory support in uncontrolled asthma need to be taken into consideration
when evaluating the use of these medications in professional voice users.

Antihistamines and decongestants

These medications can be particularly troublesome because many antihis-
tamines and decongestants can be purchased and are consumed without
physician supervision. Moreover, some patients do not realize that their
OTC medications include antihistamine and decongestant components;
they are part of several OTC sleep aids as well. Some patients do not regard
 EFFECTS OF MEDICATIONS ON THE VOICE 1085

OTC medications as ‘‘real medicines’’; therefore, they do not report them as

part of their medical history unless they are asked specifically about them.
Often, antihistamines are paired with sympathomimetic or parasympa-
tholytic medications, which thicken and reduce mucosal secretions, causing
significant drying and consequent voice changes and pathologies. Sedation
also is a side effect of these medications, with some preparations, such as lor-
atadine and fexofenadine, causing less. Medications that contain phenylpro-
panolamine, pseudoephedrine, and phenylephrine are contraindicated in
patients who are taking monoamine oxidase inhibitors (MAOIs) [2]. These
medications can produce dangerously high levels of norepinephrine because
the MAOIs impair the metabolism of sympathomimetic medications [2].
Sympathomimetic medications by themselves also can cause psychiatric
side effects. Young children and elderly patients who have organic brain
syndrome are the most vulnerable. It may become necessary to discontinue
the suspected culprit medication or to prescribe sedation or treatment with
a high-potency antipsychotic, such as haloperidol. Low-potency antipsy-
chotics, such as thioridazine or chlorpromazine, should not be taken with
phenylpropanolamine because the combination can cause hypotension.
The antihistamine and anticholinergic components of a combination
antihistamine and decongestant can produce an atropine-like psychosis, typ-
ically manifesting as confusion, disorientation, agitation, hallucinations,
and memory deficits. Agitation can be treated with a short-acting, nonanti-
cholinergic sedative, such as lorazepam. Severe agitation or psychotic symp-
toms can be treated with low doses of haloperidol. Recovery of the patient’s
mental status following the administration of physostigmine confirms the
diagnosis of atropine-like psychosis [2]. Symptoms should resolve com-
pletely after the suspected medication is discontinued.
The hepatic metabolism of many medications is mediated by certain
cytochrome P-450 enzymes, and the antidepressants fluvoxamine and nefa-
zodone interfere with certain P-450 enzymes [6]. When these antidepressants
are prescribed with other medications that are metabolized by the same
P-450 enzymes, competition between the medications for the enzymes im-
pairs the liver’s ability to metabolize each as efficiently as usual. This can
cause blood levels of these medications to become dangerously high and
lead to significant side effects or even a fatal reaction [6]. These antidepressants
cannot be used in combination with astemizole for the same reason. Lorata-
dine, fexofenadine, and cetirizine can be used with these antidepressants
because they are metabolized by a different cytochrome P-450 isozyme [6].

Reflux medications
Laryngopharyngeal reflux is a common disorder treated in otolaryngol-
ogy [7,8]. The condition is often detected in patients who have voice
complaints. Antisecretory medications, which decrease stomach acid
production, are commonly used in the treatment of reflux laryngitis. The
1086 ABAZA et al

two primary classes of drugs prescribed for this condition are the PPIs and
the H2 blockers. The former includes agents such as omeprazole, lansopra-
zole, and esomeprazole; the latter includes drugs such as famotidine, nizati-
dine, ranitidine, and cimetidine. Even OTC antacids demonstrate significant
side effects, including constipation, bloating, diarrhea, and a drying effect
[3].
Documented side effects of PPIs include diarrhea, abdominal pain,
nausea, elevation of hepatic enzymes, dry mouth, esophageal candidiasis,
muscle cramps, depression, tremors, dizziness, fatigue, and headaches.
H2 blockers can cause dryness, but it usually is not significant. A recent
study from England indicated an increased risk for hip fractures with
long-term and high-dose PPIs and, to a lesser extent, H2 blockers, particu-
larly in men. The investigators recommended that in patients older than 50
years of age, an absorbable form of calcium should be taken with high-dose
or long-term use of these medications [9].
All H2 blockers have been associated with some psychiatric side effects
[2]. Although the overall prevalence of these side effects in outpatients is
less than 0.2%, it is significantly higher among hospitalized patients, the
elderly, the seriously ill, and patients who have hepatic or renal failure
[10]. These effects of the H2 blockers vary with respect to their time of onset,
but they usually resolve within 3 days of discontinuing the drug. For exam-
ple, ranitidine can cause depression beginning at 4 to 8 weeks after the ini-
tiation of treatment. Cimetidine was reported to cause adverse events within
2 to 3 weeks and even caused delirium within 24 to 48 hours [2]. The discon-
tinuation of ranitidine and cimetidine has been associated with a withdrawal
syndrome that includes anxiety, insomnia, and irritability [11]. Cimetidine
can increase the blood level and action of tricyclic antidepressants, such
as amitriptyline, doxepin, imipramine, and nortriptyline; blood levels of
these antidepressants can reach toxic levels, resulting in tachycardia and
other side effects. The inhibition of the cytochrome P-450 enzymes by rani-
tidine or cimetidine also can lead to potentially dangerous side effects with
certain other cytochrome P-450 metabolized medications. Cimetidine is the
more potent inhibitor of the two; ranitidine is one fifth to one tenth as
potent. Famotidine and nizatidine do not inhibit this enzyme system at all [2].
Cimetidine lengthens the half-life of the antianxiety medications cloraze-
pate, chlordiazepoxide, and diazepam to a greater degree than does raniti-
dine [2]. Lower dosages of these long-acting benzodiazepines should be
considered when they are prescribed for a patient who is taking cimetidine.
An alternative is to use a short-acting benzodiazepine, such as oxazepam or
lorazepam. The metabolism of these short-acting antianxiety medications is
not affected by ranitidine or cimetidine [2]. Cimetidine also can increase the
blood levels of serotonin reuptake inhibitors and antipsychotic medical
anticonvulsants [2,4]. Whenever possible, lower dosages of these medica-
tions should be given when they are used in combination with cimetidine.
The blood levels of these medications should be monitored periodically,
 EFFECTS OF MEDICATIONS ON THE VOICE 1087

and their dosages should be adjusted accordingly. Another option is to use

a different H2 blocker, such as famotidine or nizatidine.

Hormones
Significant voice effects have been documented with androgens and ana-
bolic steroids [3]. Irreversible lowering of the fundamental pitch and coars-
ening of the voice can be the result of danazol, which is commonly used in
the treatment of endometriosis and postmenopausal sexual dysfunction [12].
High-dose progesterone birth control pills, generally not available in the
United States, can cause similar androgen-like changes in the voice [13].
Most low-dose contraceptives have a significantly lower chance of voice
changes, usually reversible when the medication is discontinued. Van Lierde
and colleagues [14] evaluated 24 professional voice users during the use of
oral contraceptives and found no objective voice differences. Depo-Provera
(medroxyprogesterone acetate) has demonstrated hoarseness as a side effect.
Estrogen replacement has become a controversial area in medicine for
numerous health reasons. In professional voice users, estrogen replacement
may help to prevent postmenopausal voice changes [3]. Low-dose progester-
one supplements, such as found in Premarin, are not believed to cause sig-
nificant voice changes; however, some synthetic substitutes may cause
androgenic effects [3].
Hypothyroidism, with thyroid hormone replacement, is one of the more
common disorders found in women. Sometimes diagnosed in professional
voice users by voice changes alone, careful monitoring of supplemental thy-
roid hormone replacement can be particularly important in a professional
voice user.

Antivirals
Antivirals are used for many disorders. Their use in chronic disease
(eg, HIV and herpes) and in acute viral illnesses is common. Several of the
medications cause side effects. Hoarseness, cough, pharyngitis, nervousness,
muscle spasm, and tremor have been reported with zidovudine; because
HIV disease alone can demonstrate these signs, it can be difficult to differen-
tiate. More common antivirals, such as oseltamivir, have not shown docu-
mented voice changes; however, swelling of the face and tongue has been
reported. Oseltamivir phosphate is not recommended in patients who have
airway disease, secondary to reports of bronchospasm and decreased lung
capacity. Amantadine hydrochloride, used in Parkinson’s disease, has antivi-
ral effects with side effects of agitation, tachycardia, and xerostomia [3].

Analgesics
Aspirin, several nonsteroidal anti-inflammatory medications (NSAIDs),
and acetaminophen are OTC medications that are used commonly for the
1088 ABAZA et al

relief of minor pain and fever. Delay in clotting is a known complication of

aspirin and all NSAIDs, so avoidance of these medications is recommended
often for professional voice users. A low dosage of aspirin is used often for
cardiac prevention and is a situation where the minimal bleeding risk likely
is outweighed by the cardiac prevention benefit. Newer cyclooxygenase-t
inhibitors, now available by prescription, do not have the same bleeding is-
sues or gastrointestinal upset because of a different pathway, but they do
have other significant cardiac side effects [15].
Topical anesthesia and narcotic use in professional voice users, particularly
before a performance, should be discouraged. Narcotics can be associated
with signs of dysarthria, in addition to mental impairment [16]. Impairment
of physical feedback of the voice by these types of agents can predispose the
user to injury and more significant long-term voice disabilities and can be
more career-ending than a performance cancellation may be.

Diuretics
Diuretics are used to eliminate fluid in medical conditions such as cardiac
or renal failure. In premenstrual women, excess fluid can be found in Rein-
ke’s space and other tissues because of increased circulation of antidiuretic
hormone. This fluid is bound and not affected by the use of diuretics. In fact,
diuretics can add to the dehydration of the performer. Diuretics also are
used in conjunction with other antihypertensive medications. Several angio-
tensin-converting enzyme inhibitors, such as captopril and enalapril, have
had case reports of hoarseness, cough, and aphonia [17]. Careful monitoring
of the voice is important when these medications are needed for other health
concerns.

Other medications
Numerous other medications have had hoarseness reported as a side
effect [17]. Antineoplastic agents (eg, vincristine), tricyclic antidepressants
(eg, amitriptyline and nortriptyline), clonazepam (Klonopin), and ropinirole
hydrochloride (Requip) are a few of the more common medications that list
hoarseness as a potential side effect. The evaluation of voice changes in a per-
former needs to involve a detailed review of new and old medications, as
well as dosage changes.

Homeopathic medications
The realm of homeopathic and herbal remedies is beyond the scope of this
article but it warrants a mention. Professional singers often use what they view
as natural solutions to medical problems. Often, patients are reluctant to
inform their physician about the use of these medications; therefore, it is
 EFFECTS OF MEDICATIONS ON THE VOICE 1089

Table 2
Some herbal medications side effects
Herbal medication Side effect
Echinacea Allergic response, immunosuppressive after 8 weeks of use
Ephedra Dehydration, cardiac events, stroke
Fennel Anticoagulation activity
Garlic, ginger, Ginkgo Anticoagulation activity
Ginseng Agitation, insomnia, vaginal bleeding
Licorice root Hormonal (estrogen/progesterone) activity, hypertension, reflux
Milk thistle Laxative effects
Nettles Diuretic effects
Primrose Anticoagulation activity
St John’s wort Insomnia, gastrointestinal upset, fatigue, bleeding

important for the otolaryngologist to stress the impact that these substances
may have on the body and on the efficacy of other medications. A few common
substances and their side effect profile are listed in Table 2.

References
[1] Othmer E, Othmer SC. The clinical interview using DSM-IV, vol. 1. Washington, DC:
American Psychiatric Press; 1994. p. 252–9.
[2] Bernstein JG. Handbook of drug therapy in psychiatry. St. Louis (MO): Mosby; 1995.
p. 370–1, 546, 353, 384, 380–1, 346, 359.
[3] Sataloff RT, Hawkshaw MJ, Anticaglia J. Medications and the voice. In: Sataloff RT, editor.
Professional voice. The science and art of clinical care. San Diego (CA): Plural Publishing;
2006. p. 905–24.
[4] Bazire S, Benefield WH Jr. Psychotropic drug directory: the mental health professionals’
handbook. West Orange (NJ): Quay Books; 1997. p. 217–36, 179, 166.
[5] Buhl R. Local oropharyngeal side effects on inhaled corticosteroids inpatients with asthma.
Allergy 2006;61(5):518–26.
[6] Stahl SM. Psychopharmacology of antidepressants. London: Dunitz Ltd.; 1997. p. 101–8.
[7] Sataloff RT, Castell DO, Sataloff DM, et al. Reflux and other gastroenterologic conditions
that may affect the voice. In: Sataloff RT, editor. Professional voice. The science and art of
clinical care. 2nd edition. San Diego (CA): Singular Publishing Group; 1997. p. 319–29.
[8] Sataloff RT, Castell DO, Katz PO, et al. Reflux laryngitis and related disorders. San Diego
(CA): Singular Publishing Group; 1999.
[9] Yang Y, Lewis JD, Epstein S, et al. Long term proton pump inhibitor therapy and risk of hip
fracture. JAMA 2006;296(24):2947–53.
[10] Canter TG, Korek JS. Central nervous system reactions to histamine-2 receptor blockers.
Ann Intern Med 1991;114:1027–34.
[11] Rampello L, Nicoletti G. The H2-antagonist therapy withdrawal syndrome: the possible role
of hyperprolactinemia [Italian]. Medicina (Firenze) 1990;10:294–6.
[12] Slayden SM. Risks of menopausal androgen supplement. Semin Reprod Endocrinol 1998;
16(2):145–52.
[13] Abitbol J, Abitbol P, Abitbol B. Sex hormones and the female voice. J Voice 1999;13(3):
424–46.
[14] Van Lierde KM, Claeys S, De Bodt M, et al. Response of the female vocal quality and
resonance in professional voice users taking oral contraceptive pills: a multiparameter
approach. Laryngoscope 2006;116(10):1894–8.
1090 ABAZA et al

[15] Marwali MR, Mehta JL. COX-2 inhibitors and cardiovascular risk. Inferences based on
biology and clinical studies. Thromb Haemost 2006;96(4):401–6.
[16] Damste PH. Changes in the voice caused by drugs. In: Meyer L, Pach HM, editors. Drug
induced diseases. Amsterdam (The Netherlands): Excerpta Medica; 1978. p. 543–8.
[17] MicromedexÒ healthcare series [Internet database]. Greenwood Village (CO): Thomson
Micromedex. Updated periodically.