Medication-Related Dizziness

Dizziness is highly prevalent among adults aged 65 years and older in primary care or family practice settings (see Chapter 17 ), with estimates of prevalence greater than 30% in community-dwelling older adults and a higher prevalence in women than men. A study of emergency department visits (1993–2005) from the National Hospital Ambulatory Medical Care Survey is in agreement with these prevalence rates from studies conducted in single institutions. From a total of 9472 patients presenting to the emergency department with dizziness sampled during this period, the study demonstrated that dizziness is an extremely common emergency department symptom that preferentially affects older adults and a greater proportion of women. From an epidemiologic standpoint, it can be hypothesized that the incidence of dizziness-associated complications is expected to increase in the future based on the increasing US population projections for persons aged 65 years and older. According to the US Census Bureau, it is projected that 20% of Americans will be aged 65 years and older by 2030, and by 2060, this age group is projected to increase to 98 million from 46 million in 2014. Similarly, the 85 years and older population is expected to increase to 20 million by 2060 from 6 million in 2014.

Although dizziness seems to increase with aging, normal aging is not the cause of dizziness, but other factors associated with aging make older adults more susceptible to dizziness. Comorbid conditions, drug-related problems (due in part to altered pharmacokinetics and pharmacodynamics), polypharmacy, larger number of doses of medications per day, low body weight, and a history of adverse drug reactions predispose older adults to dizziness.

Pharmacokinetics describes the relationship between the dose of the drug administered and the resulting drug concentrations achieved in the systemic circulation. Aging is generally characterized by changes in all pharmacokinetic processes, including absorption, distribution, metabolism and excretion, although the most clinically important changes are those affecting hepatic and renal drug elimination. Hepatic metabolism may be reduced in older adults, particularly for drugs metabolized primarily by oxidative pathways. Impaired renal function with aging results in reduced renal clearance for drugs eliminated by the kidneys. Altered pharmacokinetics with aging increases the risk of adverse drug events (ADEs), such as dizziness in older adults.

Pharmacodynamics describes the relationship between drug concentrations in the systemic circulation and drug response. Aging also affects pharmacodynamics through several mechanisms including altered concentrations of the drug at the receptor, altered interactions between the drug and its receptor, and changes in homeostatic regulation. Pharmacodynamic changes often result in increased sensitivity to medications, especially for drugs acting on the central nervous system (CNS). Altered pharmacodynamics can also contribute to increased risk of ADEs, such as dizziness in older adults.

Polypharmacy refers to the use of multiple medications and/or the administration of more medications than is clinically indicated, representing unnecessary drug use. Polypharmacy is associated with higher risk of ADEs, inappropriate use of medications, nonadherence, geriatric syndromes, and mortality in older adults. In addition, ADEs can result from prescriber-related factors, such as therapeutic duplication, that is, prescriptions for one patient initiated by more than one prescriber. Such uncoordinated care further increases the risk of ADEs.

There are a number of serious consequences associated with dizziness, and these may significantly affect the quality of life and health care burden, not only for the individual, but for the family as well. For example, Cigolle and colleagues performed a cross-sectional study to examine the prevalence of geriatric conditions (e.g., dizziness) among older adults and the association of these conditions with activities of daily living dependency (e.g., cognitive impairment contributing to dependency for bathing and dressing). In this study, data were obtained from the year 2000 from the Health and Retirement Study, a biennial longitudinal health interview survey of a cohort of adults aged 50 years or older in the United States. The results showed a strong and significant association, suggesting that geriatric conditions are associated with disability.

Considerable progress has been made in the clinical setting to describe and define dizziness and its potential causes. Dizziness is a common symptom reported by older patients during physician visits. Dizziness often is a multifactorial symptom associated with various diseases affecting sensory organs, the CNS, or both. It may also be induced by processes outside the CNS or sensory organs, such as cardiovascular diseases, or by medications. Dizziness is a complex subjective complaint. In fact, difficulty diagnosing dizziness in older adults in family practice and specialty practice settings has been reported. The term “dizziness” can describe many different sensations that can be categorized by subtypes. These subtypes include vertigo, presyncope, disequilibrium, and non-specific dizziness. In a medical chart audit study, it was recommended that documentation of selected key quality indicators in the management of dizziness could improve clinical diagnosis.

Medication-related dizziness can be difficult to diagnose, especially in older persons in whom it can masquerade as a geriatric syndrome. Geriatric syndromes are difficult to define, but they are characterized by symptoms with multifactorial causes, which become more common with aging, and are in fact often mistaken for normal aging. Shared risk factors are likely to contribute to geriatric syndromes. The common geriatric syndromes associated with a high degree of morbidity include incontinence, falls, pressure ulcers, delirium, and functional decline. Dizziness is considered by some geriatricians to meet the definition of a geriatric syndrome. ADEs in older patients often present as non-specific symptoms or geriatric syndrome indicators, such as cognitive impairment or falls. Falls may be related to osteoarthritis, poor visual acuity, neurodegenerative disease, altered proprioception (e.g., diabetic peripheral neuropathy), and/or prescription medication affecting balance, cognitive function, and hemodynamics and cardiovascular function; therefore, discovering the underlying cause can be challenging. Similarly, other health issues associated with dizziness are often multifactorial. Involvement of cardiovascular, neurologic, sensory, and psychological domains, as well as medication-related ADEs, suggest that dizziness may be a geriatric syndrome. Results from the emergency department study cited earlier support these associations. The study showed that otovestibular, cerebrovascular, metabolic, and cardiovascular disorders were at least twice as likely among patients presenting with dizziness.

Because dizziness in the elderly may be more serious than in any other age group, accurate diagnosis and appropriate intervention are crucial. A key component in the evaluation and general management of dizziness in older adults is patient history. A complete medication history is considered critical to the evaluation. For this reason, Salles and colleagues suggest that an interdisciplinary treatment approach to minimize contributive causes of dizziness in the elderly should include adjustment of the medication regimen. Medication history should take into account prescription medications, over-the-counter medications, herbal medicines, and nutraceuticals, as well as recreational drugs (including smoking and alcohol). Common drug categories implicated in dizziness in older adults are listed in Table 18.1 .

In a report by Karatas examining 13 causes of central vertigo and dizziness, medication-related dizziness was not considered or discussed in detail. Perhaps the omission was because of the paucity of published literature associating medication and dizziness or because medications are simply considered the least consequential factor associated with dizziness. Yet according to the US Food and Drug Administration (FDA) safety information data contained in the Adverse Event Reporting System (AERS) database between the years 2004 and 2009, dizziness was reported to be associated with a wide variety of medications. The authors’ preliminary analysis identified more than 70,000 reports. Because AERS reporting is voluntary, it has been suggested that there is a high degree of under-reporting, and thus the actual number of patients with medication-associated dizziness may be considerably higher than previously thought.

In fact, Kroenke and colleagues, in a review of the frequency of various causes of dizziness, categorized medication-related causes as “other causes,” accounting for only 16% of the causes of dizziness. Other causes of dizziness included anemia and metabolic sources (e.g., hypoglycemia, hyperglycemia, electrolyte disturbances, thyroid disease). This possible underestimation is not consistent with findings from the most recent cross-sectional diagnostic study assessing the contributory causes of dizziness in older adult patients in a primary care setting. In this study, 417 older adult patients in the Netherlands, aged 65–95 years, who consulted their family physician for persistent dizziness, underwent a comprehensive evaluation by a panel of specialists. It was found that an ADE was considered to be the most common minor contributory cause of dizziness, occurring in 23% of their study sample. In contrast to the results from the study by Kroenke and colleagues, the conclusion drawn from this study was that medications are a significant cause of dizziness in some patients.

This chapter provides an overview of the available literature regarding medication-related dizziness in adults aged 65 years and older.

Literature Search Strategy

We searched MEDLINE/PubMed to identify potential studies of drug-induced dizziness in older adults for inclusion in this review. The search strategy included all articles published between January 1996 and April 2017 and used various MeSH terms, including dizziness, combined with one of the following search terms at a time: pharmaceutical preparations, psychotropic drugs, histamine antagonists, benzodiazepines, cholinergic antagonists, antihypertensive agents, anticonvulsants, hypnotics and sedatives, and polypharmacy. Additional articles were also obtained by searching databases such as CINAHL and PsycINFO and by manually reviewing the bibliographies of retrieved articles. Relevant English-language articles that studied adults aged 65 years and older were included. All studies were required to have medications as a predictor variable and dizziness as an outcome variable. Articles in foreign languages, including Chinese and German, were excluded. Relevant articles were selected by reviewing the abstracts to ensure that inclusion and exclusion criteria were met.

The following were excluded: studies that focused on relationships between dizziness and other outcomes not related to the objective of this article, case studies and case series, studies only assessing efficacy of drugs and not their safety or tolerability, studies of investigational drugs, studies of drug assays and pharmacokinetic evaluation, Phase 1 clinical studies, and studies focusing on drug use (rather than dizziness) as a predictor for falls and fractures. After applying these criteria, a total of 12 unique original research studies and systematic reviews were found to be suitable for conducting this review, which we organized by the class of medication: antihypertensives, benzodiazepines, hypnotics, anxiolytics, and antiepileptics.

Antihypertensive Drugs

Antihypertensive drug use among older adults is common. According to one study, the proportion of persons in 2003 reporting treatment of hypertension increased with age and was highest (49.6%) among those aged 65 years and older. Generally, women were more likely than men to report treatment of hypertension. Box 18.1 provides a list of all FDA-approved antihypertensive medications available at present. Of the adverse effects associated with antihypertensives, dizziness is more frequent among users than non-users of these drugs. Information from the FDA indicates that dizziness is a common side effect associated with the classes of medications listed in Box 18.1 , except for calcium channel blockers and renin inhibitors.

Several other studies investigated in detail the potential association between antihypertensive medication use and dizziness in older adults. Hale and colleagues performed a prospective study to evaluate CNS effects in older subjects using antihypertensive drugs. In this study, older adult participants were first screened on an annual basis for undetected medical disorders, and those in whom medical disorders were detected were referred to private physicians for 2 years of follow-up care. Findings from this study showed that dizziness was identified significantly more often in women than in men, and an association with antihypertensive medication dose was noted. This trend was particularly observed among women using propranolol, diuretics alone, and diuretics in combination with another antihypertensive agent, such as hydralazine, reserpine, or clonidine. Clearly, this information seems to suggest that the use of multiple medications (polypharmacy) contributes to the incidence of dizziness observed among women. This finding is in agreement with results from a study by Hussain and colleagues, which showed that the occurrence of adverse drug reactions to antihypertensive drugs was high among women and was further increased among those on combination therapy compared with monotherapy. However, for men, propranolol was the only antihypertensive drug associated with a significant increase in episodes of dizziness.

Cleophas and colleagues examined whether using the combination of a β-blocker with a negative chronotropic calcium channel blocker (amlodipine, diltiazem, or mibefradil) would cause intolerable side effects in 335 patients (aged 18–75 years) with chronic stable angina pectoris. This study was a 10-week, double-blind, parallel-group comparison of amlodipine (5 and 10 mg), diltiazem (200 and 300 mg), and mibefradil (50 and 100 mg) treatment added to stable (i.e., baseline) β-blocker treatment. Serious symptoms of dizziness occurred in 14% of patients, resulting in their withdrawal from therapy: 19 patients were taking mibefradil (8 on low dose, 11 on high dose); 4 patients were taking diltiazem (1 on low dose, 3 on high dose); and 9 patients were taking amlodipine (4 on low dose, 5 on high dose). Doses of diltiazem in this trial were low compared with doses used in standard practice in the United States. It was observed that low-dose diltiazem caused fewer symptoms of dizziness, and fewer patient withdrawals were observed among low-dose mibefradil users. Therefore, these data suggest that patients in the United States (with higher dose standards) might experience more pronounced symptoms or a higher incidence of dizziness with this combination of medications and dosage.

On the other hand, Ko and colleagues studied adverse cardiovascular effects of β-blockers individually (carvedilol, metoprolol, bisoprolol, and bucindolol) in comparison with placebo. In this study, the investigators analyzed randomized trials on β-blockers in patients with heart failure and systolic dysfunction. The analysis included nine trials involving 14,594 patients, with follow-up periods ranging from 6 to 24 months. Results showed that β-blocker use was associated with a significant relative increase in reported dizziness (relative risk, 1.37; 95% confidence interval [CI], 1.09–1.71) and an absolute increase with a risk of 57 per 1000 cases (95% CI, 11–104). Results further indicated that the increased risk of dizziness was accompanied by hypotension because β-blockers lower blood pressure using various mechanisms. In addition, the study assessed withdrawal from therapy due to dizziness in 7789 patients from four trials. Overall, the investigators concluded that most patients in this study did not experience cardiovascular adverse effects (including dizziness) because the trials that were reviewed enrolled healthier and relatively fewer female and older adult patients.

Angiotensin-converting enzyme (ACE) inhibitors have also been associated with dizziness. Blakley and Gulati illustrated the use of a practical new technique that may be useful in identifying groups of medications associated with dizziness. The patient group for this study included those who had electronystagmography at the Health Sciences Centre, Winnipeg, Canada. The mean age of the study group of 102 dizzy patients was 60 (±16) years, and these patients were taking a total of 173 drugs in 22 categories. ACE inhibitors were shown to be associated with dizziness.

A similar association was not found with other antihypertensive agents. In general, results indicate that antihypertensive drug use is more common in dizzy patients, and that the pattern of drug use in dizzy patients is different from that of non-dizzy patients. In other words, dizzy patients take more medications, and the dizziness they experience may be attributed to polypharmacy.

Ensrud and colleagues performed a cross-sectional examination of the prevalence and correlates of postural hypotension, postural dizziness, and associated risk factors, including medical conditions, medications, and physical findings in 9704 patients. The patients were non-black, ambulatory women, aged 65 years and older, living in a general community setting, participating in the multicenter Study of Osteoporotic Fractures. Of the risks identified, use of medications, specifically diuretics (odds ratio [OR], 1.15; 95% CI, 1.03–1.28), was associated with postural dizziness. However, these associations were only age-adjusted and might have been confounded by other covariates or risk factors.

Finally, in an Oslo Health Study by Tamber and Bruusgaard, a multipurpose health survey was conducted to explore the association between dizziness and factors such as self-reported diseases and medicines used. Results from the self-administered questionnaire showed increased likelihood of faintness or dizziness with the use (weekly or more frequent use) of blood pressure medications (OR, 1.27; 95% CI, 1.11–1.45). However, the investigators did not provide the details of the type of high blood pressure medication used, making it unclear which particular class or classes of antihypertensives are directly associated with dizziness.