The Impact of Pharmaceutical Side Effects on Audiological and Vestibular Measurements

Abstract

There are over 2,000 drugs with a combined total of over 400 side effects that could result in obtaining inaccurate case history information or inaccurate test results that may lead to misdiagnosing the patient's hearing or vestibular problem. The recommendations that are made could be inappropriate and thus can lead to management errors. A review of the auditory, vestibular, and cognitive side effects of many of the drugs patients take regularly (including drugs that can cause tinnitus) is provided. This article offers suggestions to obtain a more accurate case history. A review of preferred Web sites to obtain drug side effect information is included. Suggestions for improved communication strategies between the audiologist, the physician, the patient, and the pharmacist are highlighted.

Hearing loss and vestibular or cognitive impairments are known side effects of many drugs. There are over 2,000 drugs and more than 400 side effects that could impact the accuracy of the audiometric or vestibular evaluation as well as impacting the recommendations made for intervention and management. ¹

Adverse Drug Reactions—an Overview

Clinical trials established by the U.S. Food and Drug Administration (FDA) are specifically designed to determine efficacy and safety of a new pharmaceutical. ² From proof of concept to the final approval, the process can take years. According to The Tufts Center for the Study of Drug Development (Tufts CSDD), an independent, academic, nonprofit research center, drug manufacturers can plan on spending $2.6 billion dollars during this process. ³ In this process, clinical data are collected by independent research centers under the supervision of the chief investigator. The coinvestigators follow a rigorous reporting system which includes identifying any adverse drug reaction (ADR) or side effect—an unplanned physiological or psychological reaction to the drug by any of the test subjects. Incidence figures are collected and ADRs are reported along with the other efficacy data from the coinvestigators. ADR data are used as guidance since not all patients will experience the reported ADRs during clinical trials.

Audiologists and other technical support staff should be aware that these ADRs—in some cases extremely rare—may influence the patient's ability to perform a specific task (i.e., pressing the response button as instructed, repeating words during a word recognition test, staying focused on a particular task during a vestibular evaluation).

Internet Resources

There is a wealth of drug information on the internet. Although any individual or organization can build a Web site offering drug information, the American Medical Association offers guidelines for developing a Web site offering drug information. ⁴ Table 1 lists several reliable, noncommercial and commercial Web sites for drug information. These are offered to the reader as a resource but are not specifically endorsed by the author.

Table 1. Noncommercial and Commercial Web sites Offering Reliable Drug Information.

Noncommercial

www.fda.gov

https://druginfo.nlm.nih.gov

drugs@fda

Commercial

www.drugs.com/professionals.html

www.rxlist.com

www.pdr.net

www.express-scripts.com/medco/consumer/ehealth/druginfo/dlmain.jsp

www.epocrates.com

Mobile Apps

www.skyscape.com/mobilePDR/

www.skyscape.com/estore/ProductDetail.aspx?ProductId=1189

www.empr.com/physician-assistant-edition/section/1217/

Pharmacist/Audiologist Relationship

Pharmacists play a critical role in patient management. These allied health professionals can provide many missing pieces of the diagnostic puzzle with just one phone call. Whether you are conducting an audiometric evaluation, a vestibular study, or a tinnitus evaluation, establishing a time line from when the symptoms first began and when a new drug was started should be the focus of your case history and differential diagnosis.

Even if you believe that the patient is a good historian, memory impairment can be a drug side effect. Patients might report that they have been taking a particular drug for “about 6 months.” A phone call to the referring physician or the patient's pharmacist will help you get the start date of the particular drug in question (they might have been taking it for over a year!). Your need to know does not violate the Health Insurance Portability and Accountability Act (HIPAA) of 1996.

The Case History

During clinical training, healthcare professionals are taught to ask specific questions about a patient's communication or balance complaint(s) in an effort to establish a possible etiology of the complaint. Patients with hearing loss can struggle during this part of the visit which is why a family member or friend should always accompany the patient. Dates and circumstances may not be recalled accurately, or the patient might not fully understand the questions. Provision of a simple amplifier may assist the patient in participating in this interaction. Some answers will be straightforward, while other answers require the skills of a detective to ascertain even the slightest piece of information that would be critical to the clinical investigation. Although the clinician has no reason not to trust the patient, in any given patient recall abilities may be poor. The clinician must consider whether patients are just poor historians, or if their ability to recall dates and facts is being influenced by one or more medications they were taking for an unrelated medical condition.

Every case history form has a section related to past and current mediations for any body system ailment. Audiologists typically are concerned about medications that can cause hearing loss, tinnitus, and/or vestibular problems. Historically, audiologists rarely focused on the side effects of the patient's medication(s) as being a player in their auditory/vestibular complaints.

Typical case history questions to the patient are as follows: “ What medications are you currently taking ?” “ Why are you taking them ?” “ How long have you been taking them ?” As simple as these questions are, they are the first step in setting up the clinician for possible problems. The most common problem is mispronouncing the drug's name. Many drugs have similar sounding names (e.g., Zoloft and Zocor). It is not unusual for patients to confuse either the brand name or generic name of the medication(s) they are taking (i.e., “hydro-something”). The Institute for Safe Medication Practices (ISMP) has published a list of sound-alike drug names that is an excellent reference when you encounter patients who struggle with the names of their medications. This list can be printed out for reference. Keep in mind that confusion is not an unusual side effect of many drugs.

A survey in the United States of a representative sampling of 2,206 community-dwelling adults (aged 62–85 years) was conducted by in-home interviews and use of medication logs between 2010 and 2011. At least one prescription medication was used by 87% of those surveyed. Five or more prescription medications were used by 36% and 38% used over-the-counter medications. ⁵ The Centers for Disease Control and Prevention estimates 75% of persons older than 60 years take two or more drugs and those older than 90 years take five or more medications. ⁶

Among ambulatory people ≥ 65 years, adverse drug effects occur at a rate of approximately 50 events per 1,000 person-years. Hospitalization rates due to adverse drug effects are four times higher in elderly patients (∼17%) than in younger patients (4%). ⁷ Some of these medication side effects may cause an older patient to misunderstand your question(s) or the test instructions. They may not be able to stay focused on the required task for a particular test. Some medications may have an obvious auditory (i.e., tinnitus), vestibular (oculomotor dysfunction), or cognitive side effect (confusion). The possibility of an adverse drug event (ADE) should always be considered when evaluating an older adult; any new symptom should be considered drug related until proven otherwise. Pharmacokinetic changes lead to increased plasma drug concentrations and pharmacodynamic changes lead to increased drug sensitivity in older adults. ⁸

As the U.S. population ages and lives longer, chronic disease management becomes more of a challenge to the primary care physician. The use of multiple drugs, or polypharmacy, adds a new element in our differential diagnosis especially when reviewing a patient's drug regimen. Bushardt et al ^{9 10} provided an excellent overview of the problem of polypharmacy.

Audiogram Accuracy

Audiologists and ENT physicians rely heavily on the audiogram which is a subjective test. Our training and experience in the assessment process prepares us to be sure that the patient fully understands the test directions. We know from experience that an older patient's ability to listen for the soft sounds is not as accurate as someone half their age or younger. Changes in perception and their ability to stay on task may result in a misdiagnosis of degree of hearing loss. Cross-checks for accuracy are essential. Is that 60 dB HL (hearing level) loss real or is it actually a 35 to 40 dB HL loss that has been influenced by poor listening skills (following directions) or an inability to stay focused on the task because of an ADR?

Cognitive Side Effects

Humes ¹¹ reported that threshold elevation can account for nearly all of the changes in speech perception with age (in quiet or in less demanding listening environments). Sweetow ¹² reported that the speed of word recognition is reduced with age as is the patient's working memory. There are attentional difficulties as well as a decrease in sentence identification because of changes in working memory. Confusion, as a medication side effect, can be exacerbated when masking is used during air or bone conduction testing as well as speech audiometry. If there is a decrease in the word recognition score, how sure are you that it is not from a drug side effect?

Word recognition scores may be used to discuss hearing aid candidacy. Many drugs have cognitive side effects (see Table 2 ) that may impact these scores. The possibility exists that these medications might be influencing the test scores. A change in word recognition might not be a true change but rather a transient change produced by a medication side effect.

Table 2. Reported Cognitive Side Effects of Drugs and Herbal Medicines that could Affect Audiometric/Vestibular Testing ¹² .

Awareness, altered	Cognition, decreased	Cognition dysfunction
Concentration, impaired	Confusion	Dementia
Disorientation	Forgetfulness	Memory impairment
Mental acuity, loss of	Mental clouding	Mental perception, altered
Mental performance	Mental slowness	Mental status, altered
Impairment	Proprioception, loss of	Sensorium, clouded/dull
Sensory deficit	Sensory disturbances	Stupor
Thinking, slowed	Thinking abnormality

Auditory Side Effects

Table 3 shows some of the reported drug side effects that can affect the auditory system. ¹²

Table 3. Reported Auditory Side Effects of Prescription Medicines ¹³ .

Auditory disturbances	Cerumen, increased	Cochlear damage
Deafness	Deafness, transient	Ear, discomfort
Ear drainage	Ears, roaring	Hearing, impaired
Hearing, loss of	Nerve deafness	Otitis externa
Otorrhea	Ototoxicity	Pain, ear
Tingling, ears	Tinnitus

Vestibular Side Effects

There are over 400 audiology-related side effects of FDA-approved drugs. More than one-third of them have some vestibular/ocular side effect that could influence a balance assessment. ¹ Sedatives, recreational drugs, and other stimulants can impact the accuracy of vestibular assessment data. Visual evoked myogenic potential (VEMP) testing is probably the only test that is unaffected by drugs. ¹³

Every vestibular assessment laboratory has protocols designed to obtain the most accurate objective data on their patients. Pretest questionnaires have been designed to focus on the patent's issue(s). A list of pretest guidelines prepares the patient for the procedures. This pretest guide includes what to wear and what to eat (and not to eat) for a certain period of time prior to the examination to even not wearing makeup (video goggle positioning can be affected). Also on the pretest guideline list would be a list of medications that must be stopped for at least 48 hours prior to the procedure (i.e., sedatives, stimulants, etc.). However, there are certain medications patients are allowed to take—usually any drug that if stopped would be considered life-threatening (i.e., cardiac medications). The examiner must review those medications allowed to be taken and determine if there may be a vestibular-related side effect. Table 4 shows the side effects that could affect a balance assessment.

Table 4. Drug Side Effects that could Affect a Balance Assessment ^{1 13} .

Attention disturbances	Balance, loss of	Blood pressure changes
CNS depression	CNS reactions	CNS stimulation, paradoxical
CNS toxicity	Cognition, decreased	Concentration, impaired
Confusion	Demyelination	Dim vision
Diplopia	Disorientation	Dizziness
Equilibrium dysfunction	Extraocular muscles	Eye abnormality, unspecified
Eye movements, abnormal permanent injury to	Eye swelling	Eyes, nonreactive
Eyes, “spots” before	Eyes, swollen	Falling
Feeling, drugged	Feeling, high	Feeling, intoxicated
Floating feeling	Forgetfulness	Frequent blinking
Grogginess	Hallucinations, visual	Hyperactivity
Inebriated feeling	Inflammation, ocular	Intoxication, state of
Intracranial pres, increase	Intraocular disorders	Ischemia
Ischemia, cerebral	Ischemia, recurrent	Ischemia, transient
Ischemic attacks, transient	Labyrinth disorder	Labyrinthitis
Lesions, neuro-ocular	Lightheadedness	Listlessness
Memory impairment	Memory loss, short term	Meniere's syndrome
Motion sickness	Motor skills, impairment	Movement, abnormal
Movement disorder	Myopia	Nausea
Nausea, acute/severe	Neuritis, optic	Neurological disability
Neuromotor, unspecified	Neuropathy	Neuropathy, optic
Neuropathy, optic	Neurosensory, unspecified	Neurotoxicity
Nystagmus	Nystagmus, horizontal	Ocular, foreign body sensation
Ocular discomfort	Ocular irritation	Ocular lesions
Ocular palsies	Ocular pressure	Ocular toxicity
Oculogyric crises	Oculomotor disturbances	Ophthalmitis
Ophthalmoplegia	Optic atrophy	Optic nerve damage
Optic nerve infarction	Ototoxicity	Palsy, extra ocular
Palsy, optic nerve	Papilledema	Papillitis
Paralysis, extra ocular muscles	Paralysis, ocular motor nerve	Proprioception, loss of
Pupil enlargement	Retinal artery occlusion	Retinal atrophy
Retinal damage	Retinal degeneration	Retinal detachment
Retinal disorder, unspecified	Retinal vascular disorder	Retinal vein occlusion
Retinitis	Retinitis, bilateral	Retinitis, cytomegalovirus
Retinopathy	Retinopathy, pigmentary	Retinopathy of prematurity
Retrolental fibroplasias	Romberg test, positive	Scotoma/Scotomata
Scotomata, scintillating	Sensation, lightness	Sensation, numbness
Sensory deficit, persistent	Sensory disturbances	Strabismus
Swelling, periorbital	Temporal bone, swelling	Vertigo
Vestibular disturbances	Vestibular dysfunction	Vision, blurred
Vision, double	Vision, loss of	Vision, partial loss
Vision, peripheral, decreased	Vision, temporary loss of	Vision, tunnel
Visual acuity, decreased	Visual acuity, defects	Visual disturbances
Visual field defect	Visual impairment	Vitreous detachment
Vitreous disorder, unspec.	Vitreous floaters	Vitreous opacity
Vomiting	Walking disorders	Weakness, feet
Weakness, legs

If a vestibular-related side effect has been identified, then the patient's physician or pharmacist should be notified to obtain the start date of the medication. The etiology of the vestibular complaint may not be pathological but an adverse reaction. This information should be noted in the patient's report if test results are discrepant.

In an interview, Dr. Richard Gans ( http://www.dizzy.com , 2016), director of the American Institute of Balance , and an authority on balance testing, stated that (when looking at a patient's eye movements) saccadic pursuit, bilateral, bithermal caloric weaknesses, or reduced gain using rotary chair is never a unilateral event. The conjugate movement of the eyes during active head rotation is never drug related. Dr. Gans also recommended a thorough review of the patient's current drug and herbal medicine regimen and establishing symptom/drug time lines as a critical component of the case history.

Tinnitus Side Effects

In 2018, the Side Effect Resource Database reported a total of 996 drugs with a total combined side effect of 4,192. Of these, 275, or 6.5%, listed tinnitus as a reported side effect using synonyms such as ringing in ears and ear noise. ¹⁴ More than 220 drugs listed in the Physician's Desk Reference have tinnitus as a reported side effect. ^{1 13 15}

Oftentimes we rely on the patient to remember the start date of a new symptom. Questions to ask your patient are as follows: When did the symptom start? Was there a drug introduced or a dosage increased at the same time? If tinnitus has been identified as a drug side effect, then the patient's physician or pharmacist should be notified to obtain the start date of the medication. The etiology of the tinnitus complaint may not be pathological but an adverse reaction. This information should be noted in the patient's report.

Wrong Diagnosis = Wrong Intervention

Confidence levels must be very high when making recommendations for medical or surgical intervention or hearing aid intervention. Some questions to ask are as follows:

• Did the patient fully understand the test instructions or response task?

• Do the test results support the patient's complaint(s)?

• Is the loss truly sensorineural, conductive, or mixed?

• Have you ruled out a nonorganic problem?

• Is there good test/retest reliability?

• Are the abnormal eye movements truly peripheral or central in origin?

Reporting Your Findings and Suspicions

Document everything—including phone calls and electronic communications. Report your patient's alertness, test accuracy, or other different or unusual observations before, during, and after the testing. Report the time of day that the testing occurred (some medications need to be taken at specific times). Report your discovery of any drug timelines. Report any observations of behaviors during the testing that you believe might have influenced the test results. If it is not documented, it did not happen.

Reporting an Adverse Drug Event

The FDA requires all pharmaceutical companies to keep records on any adverse event reported by professionals or consumers for a period of 10 years after final approval. The MedWatch Program is the FDA's Safety Information and Adverse Event Reporting Program ( www.fda.gov/safety/medwatch ). Professionals and consumers can report an adverse event on any pharmaceutical. A form is available online. In addition, a person can send an email to drug-info@fda.hhs.gov or call 1.855.543.3784. Another source is the pharmaceutical's manufacturer. Every pharmaceutical company has a Web site and possibly a dedicated Web site for a particular drug (usually written for the consumer). On the main page, there will be a Contact tab or a link to send an inquiry at the very bottom of the main page. Your inquiry will be reviewed by a product specialist (usually a pharmacologist) who will reach out to you for additional information. There is a reporting form that will need to be completed if it is determined that you have come across new information about the company's product.

Summary

No one is knowledgeable of all the FDA-approved drugs and their side effects; however, there are reliable (and valuable) Web sites available that provide accurate and up-to-date information about side effects. If in doubt, call the patient's pharmacist.

The following may help reduce the possibility of a drug's influence on audiological/vestibular testing:

1. Spend more time getting an accurate case history. If the patient cannot recall the name(s) of the drug(s) they are taking, call their pharmacist.

2. Reference www.rxlist.com , www.drugs.com , www.earservsecure.com/drugs for drug side effects.

3. Establish time lines from when the problem began and when the drug(s) were prescribed.

4. Make certain that your patient understands the test instructions and/or response task.

5. Never forget what you learned in Audiology 101 about test/retest reliability.