Abstract
This cross-sectional study investigates the relationship between loneliness and high-risk medication use in adults older than 65 years.
Loneliness, the emotional distress resulting from a discrepancy between one’s actual and desired level of social connection, is associated with physical and psychological symptoms in older adults, including pain, insomnia, depression, and anxiety.1 The relationship of loneliness to these symptoms is likely bidirectional; in some situations it acts as a risk factor for the symptoms and in others it is the consequence of symptoms. In either case, lonely older adults may be at risk for using high-risk medications commonly prescribed for physical or psychological symptoms.2 Our objective was therefore to investigate the relationship between loneliness and high-risk medication use.2 A better understanding of this relationship might inform strategies for addressing symptoms and deprescribing potentially risky medications through the use of nonpharmacologic, social interventions.
Methods
We used cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP), waves 1 through 3 (2005, 2010, 2015), an in-home nationally representative survey of community-dwelling adults older than 65 years.3 We included 6336 participants who responded to the NSHAP leave-behind questionnaire (85% response rate among 7045 total participants), and excluded an additional 254 participants (4%) with incomplete responses to the loneliness scale and 65 participants (1%) with missing medications data, resulting in a final sample of 6017 participants. Loneliness was categorized as none, low/moderate, or high based on the 3-item UCLA Loneliness Scale.4
In-home medication logs were conducted by asking participants to physically bring to the interviewer all medications they take “on a regular schedule, like every day or every week.” A clinical pharmacist reviewed unique drug entries and facilitated matching to a drug database and coding by type.5 We examined medications commonly prescribed for physical and psychological symptoms associated with loneliness and on the American Geriatrics Society Beers Criteria of potentially inappropriate medications,2 including opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, antidepressants, and sleep medications. We examined polypharmacy (≥5 medications), which may result from accumulated medication burden. We additionally assessed medications used to treat common chronic conditions (lipid-lowering agents, antihypertensives, and salicylates) where we would not expect an association with loneliness.
We first determined the unadjusted association of loneliness with medication use using χ2 tests. We then used multivariable logistic regression to determine the probability of medication use by loneliness level after adjusting for age, sex, race/ethnicity, education, and multimorbidity. We did not adjust for physical or psychological symptoms given their high correlation with loneliness and because they may lie on the causal pathway. Statistical analyses were conducted using Stata 16.1, used national survey weights accounting for the likelihood of survey participation, and accounted for clustered responses among individuals participating in multiple waves of NSHAP. All respondents provided written informed consent and the protocol was approved by the institutional review boards at the University of Chicago and National Opinion Research Center (NORC).
Results
The mean age of participants (SD) was 73 (7.1) years; 3243 (54%) were women; 4556 (84%) were non-Hispanic White; 2388 (40%) were classified as low/moderately lonely; and 396 (7%) were classified as highly lonely. In unadjusted analyses, loneliness was significantly associated with self-reported pain, insomnia, depression, anxiety, multimorbidity, and medications of interest (Table). After adjustment, loneliness was significantly associated with use of NSAIDs (no loneliness, 14%; 95% CI, 11%-16%; low/moderate, 17%; 95% CI, 14%-20%; high, 22%; 95% CI, 16%-28%), benzodiazepines (no loneliness, 5%; 95% CI, 4%-6%; low/moderate, 7%; 95% CI, 6%-9%; high, 11%; 95% CI, 7%-15%), anxiolytics/sedatives (no loneliness, 9%; 95% CI, 7%-10%; low/moderate, 12%; 95% CI, 10%-14%; high, 20%; 95% CI, 15%-25%), antidepressants (no loneliness, 14%; 95% CI, 12%-16%; low/moderate, 19%; 95% CI, 16%-21%; high, 27%; 95% CI, 21%-33%), and polypharmacy (no loneliness, 41%; 95% CI, 38%-43%; low/moderate, 44%; 95% CI, 41%-47%; high, 50%; 95% CI, 44%-56%) (Figure), and there was a nonsignificant trend for opioid use (no loneliness: 7%; 95% CI, 5%-8%; low/moderate, 7%; 95% CI, 6%-9%; high, 10%; 95% CI, 6%-14%).
Table. Survey-Weighted Sample Characteristics Overall and by Loneliness Level.
| Characteristics | No. (%) | P valuea | |||
|---|---|---|---|---|---|
| Overall (n = 6017) | Loneliness levelb | ||||
| None (n = 3233 [53%]) | Low/moderate (n = 2388 [40%]) | High (n = 396 [7%]) | |||
| Age, mean (SD) | 73.5 (7.1) | 73.2 (6.7) | 73.8 (7.5) | 74.1 (7.5) | .004 |
| Gender | <.001 | ||||
| Men | 2774 (46) | 1626 (50) | 994 (41) | 154 (40) | |
| Women | 3243 (54) | 1607 (50) | 1394 (59) | 242 (60) | |
| Race/ethnicity | <.001 | ||||
| White | 4556 (84) | 2547 (86) | 1709 (81) | 300 (86) | |
| Black | 748 (7) | 302 (5) | 396 (10) | 50 (6) | |
| Hispanic, non-Black | 551 (6) | 299 (6) | 219 (6) | 33 (5) | |
| Other | 143 (2) | 77 (2) | 57 (3) | 9 (2) | |
| Education | <.001 | ||||
| <High school | 1057 (15) | 500 (13) | 474 (17) | 83 (22) | |
| High school/equivalent | 1563 (26) | 805 (25) | 633 (27) | 125 (29) | |
| Some college | 1900 (33) | 1051 (34) | 736 (32) | 113 (29) | |
| Bachelor’s or more | 1497 (26) | 877 (28) | 545 (24) | 75 (20) | |
| Health insurance | .09 | ||||
| None | 130 (3) | 53 (2) | 65 (4) | 12 (4) | |
| Medicare | 3402 (91) | 1816 (92) | 1352 (91) | 234 (89) | |
| Private only | 131 (4) | 70 (4) | 56 (4) | 5 (3) | |
| VA/Medicaid/other | 76 (2) | 39 (2) | 26 (1) | 11 (3) | |
| Medical conditionsc | |||||
| Pain | 1957 (50) | 953 (46) | 842 (53) | 162 (64) | <.001 |
| Insomnia | 1290 (34) | 584 (30) | 578 (38) | 128 (50) | <.001 |
| Depression | 710 (11) | 141 (4) | 389 (16) | 180 (46) | <.001 |
| Anxiety | 346 (6) | 100 (3) | 165 (7) | 81 (20) | <.001 |
| Multimorbidity | 3094 (52) | 1572 (49) | 1286 (54) | 236 (58) | <.001 |
| Medicationsd | |||||
| NSAIDs | 731 (13) | 340 (11) | 324 (14) | 67 (19) | <.001 |
| Opioids | 438 (7) | 201 (6) | 198 (8) | 39 (11) | .03 |
| Benzodiazepines | 399 (7) | 163 (5) | 184 (8) | 52 (14) | <.001 |
| Anxiolytics/sedativese | 649 (11) | 278 (9) | 288 (13) | 83 (23) | <.001 |
| Antidepressants | 890 (15) | 385 (12) | 402 (17) | 103 (26) | <.001 |
| Polypharmacyf | 2985 (49) | 1525 (46) | 1234 (51) | 226 (58) | .002 |
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; VA, Veterans Affairs. Percentages in the table are column percentages; percentages shown in the table are adjusted for survey weights and thus may not correspond directly to the unadjusted number listed in each cell.
P values were determined using Rao-Scott χ2 tests.
Loneliness is measured using the 3-item UCLA Loneliness Scale (range: 0-6 points; no loneliness: 0 points, mild loneliness: 1-3 points, high loneliness: 4-6 points).
Definitions of self-reported symptoms or medical conditions included: pain (“moderate or severe” pain in the last 4 weeks), insomnia (trouble falling asleep “most of the time”), depression (12+ points corresponding with moderate/severe symptoms on modified Center for Epidemiologic Studies-Depression Scale, range 0-44 points), anxiety (11+ points corresponding with moderate/severe symptoms on modified General Anxiety Disorder-7 Scale, range: 0-28 points), and multimorbidity (2 or more chronic medical conditions, including hypertension, coronary artery disease, heart failure, arthritis, cancer, metastatic cancer, diabetes, emphysema, asthma, prior stroke, or dementia).
Medications were obtained from an in-home medication log and mapped to a proprietary drug database (Lexicon Plus; Cerner Multum).
Anxiolytics/sedatives category includes benzodiazepines as well as buspirone, butalbitol, diphenhydramine, doxepin, doxylamine, eszopiclone, hydroxyzine, phenobarbital, ramelteon, zaleplon, and zolpidem.
Polypharmacy was defined as ≥5 medications, not including vitamins or dietary supplements.
Figure. Adjusted Probability of Medication Use by Loneliness Level.
NSAIDs indicates nonsteroidal anti-inflammatory drugs. Adjusted probabilities were derived from multivariate logistic regression models adjusting for age, gender, race/ethnicity, education, and multimorbidity (2 or more medical conditions, including hypertension, coronary artery disease, heart failure, arthritis, cancer, metastatic cancer, diabetes, emphysema, asthma, prior stroke, or dementia). P values represent an overall test of trend. Bars represent 95% CIs. Loneliness is measured using the 3-item UCLA Loneliness Scale (range: 0-6 points; no loneliness: 0 points, mild/moderate loneliness: 1-3 points, high loneliness: 4-6 points). Medication classes were defined using a proprietary drug database (Lexicon Plus; Cerner Multum). Polypharmacy was defined as ≥5 medications (not including dietary supplements or vitamins).
Discussion
In this nationally representative cohort of older adults, loneliness was a powerful predictor of use of medications used to treat physical and psychological symptoms. Loneliness was associated with higher pain medication use, including use of opioids and NSAIDs, and more than twice the frequency of use of antidepressants, sleep medications, and benzodiazepines. These medications are associated with adverse consequences among older adults, including opioid dependence, gastrointestinal bleeds, falls, fractures, delirium or cognitive impairment, new functional disability, and death. In circumstances in which loneliness is a risk factor for the development of physical or psychological symptoms, medications may not treat the underlying social experience of loneliness. In circumstances in which loneliness is a consequence of symptoms such as pain or depression, loneliness may amplify the intensity of these symptoms. In both circumstances, clinicians should consider initiating social interventions for lonely older adults or “social prescribing” to local community-based support programs.6 Identifying and addressing loneliness may have the added benefit of allowing clinicians to reduce or avoid prescription of high-risk medications. A primary limitation of this study is the cross-sectional analysis, which limits our ability to draw causal conclusions on the directionality of our findings.
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