What Predicts CNS-active Medication Use and Polypharmacy in Depressed Homebound Older Adults?

Abstract

OBJECTIVE:

To assess CNS polypharmacy among low-income, racially diverse, depressed, homebound older adults (N=277) and its associations with depressive symptoms and pain ratings.

METHODS:

CNS-active and other psychotropic and analgesic medications intake was collected from patients’ medication containers. Depressive symptoms were assessed with the 24-item Hamilton Rating Scale for Depression, and pain intensity was measured on an 11-point numerical rating scale. Covariates were disability (World Health Organization Disability Assessment Schedule 2.0) and perceived social support (Multidimensional Scale of Perceived Social Support).

RESULTS:

16.3% engaged in CNS polypharmacy, taking 3+ CNS-active medications. Of these, 68.9%, 68.9%, and 88.9% were using selective serotonin reuptake inhibitors, benzodiazepines, and opioids, respectively. Higher pain intensity ratings were associated with CNS polypharmacy (RRR=1.20, 95% CI=1.01–1.45). Benzodiazepine use was associated with 3.36 (95% CI=1.65–6.84) greater odds of opioid use.

CONCLUSIONS:

Medication reviews and improving access to evidence-based psychotherapeutic treatments are needed for these low-income, depressed, older individuals.

INTRODUCTION

The rates of outpatient care visits in which older adults were prescribed antidepressant, anxiolytic, sedative-hypnotic, or analgesic medications have risen over the past decade.¹ Especially notable has been the increase in central nervous system (CNS)-active medication polypharmacy, defined by the Beers Criteria as ≥3 CNS-active medications—antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and opioids.¹ Opioid prescribing rates were declining overall in recent years;² however, benzodiazepine and continuing (versus new) antidepressant prescriptions continued to increase in primary care visits.^3,4

Although CNS-active medications are prescribed and used for symptom relief, risks (e.g., development of frailty, hepatotoxicity, falls, fractures, delirium) associated with their long-term use, misuse and polypharmacy are well-documented.^5,6 Despite extensive research on polypharmacy and its adverse effects on older adults in general, however, little research has focused on increasing numbers of homebound older adults who, along with chronic illness and disability, suffer from depression and other psychiatric comorbidities at significantly higher rates and tend to be more socioeconomically disadvantaged than nonhomebound peers.⁷

The purposes of this study were to examine patterns of CNS polypharmacy among homebound older adults enrolled in a clinical trial of short-term psychosocial treatment for depression; associations between CNS polypharmacy with their depressive symptoms and pain ratings; and associations among use of different medication groups. Our hypotheses were, first, that CNS polypharmacy would be associated with more severe depressive symptoms and higher self-reported pain intensity; and, second, that antidepressant, benzodiazepine, and opioid analgesic medication intake would be significantly associated with one another. Covariates were sociodemographic characteristics, number of chronic illnesses, emergency department (ED) visits, disability and perceived social support. The findings of this study provide a valuable insight into one of the most disadvantaged groups of older adults with respect to CNS-active medication use and polypharmacy.

METHODS

Participants were 277 depressed, homebound individuals aged 50+ enrolled in a randomized clinical trial of clinical effectiveness of short-term, videoconferenced depression treatments (ClinicalTrials.gov identifier: NCT02600754). They were referred to the study by case managers of a large, home-delivered meals program in Central Texas. Inclusion criteria were moderate-to-severe depressive symptoms and willingness to participate. Exclusion criteria were high suicide risk, probable dementia, bipolar disorder, psychotic disorder, and substance abuse. Written informed consent, approved by the authors’ university institutional review boards, was obtained from each participant after the study procedures had been fully explained. Following informed consent, participants were administered the baseline assessment at their own home by trained assessors. To examine the study questions, we used baseline data, collected between February 2016 and April 2019.

Participants’ current intake, dose, and intake frequency of CNS-active medications (antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, SSRIs, tricyclic antidepressants, and opioids) were collected from their medication containers. Data on other classes of antidepressant medications, sedative-hypnotic/sleep medications, and nonsteroidal anti-inflammatory drugs (NSAIDs) were collected in the same manner. CNS polypharmacy referred to taking 3+ CNS-active medications.

Depressive symptoms were assessed with the 24-item Hamilton Depression Rating Scale (HAMD); the GRID-HAMD-21 Structured Interview Guide⁸ augmented with 3 additional items (hopelessness, helplessness and worthlessness) by Moberg et al.⁹ HAMD ≥15 was the study inclusion criterion. Participants self-reported intensity of bodily pain “during the past 6 months” on a 0 (no pain) to 10 (pain as bad as it could be) scale, along with the pain frequency and interference with daily activities.

Sociodemographic variables included age, gender, race/ethnicity, education, financial situation. The number of chronic illnesses included up to 9 chronic medical conditions that have ever been diagnosed by a healthcare professional (arthritis, diabetes, hypertension, heart disease, stroke, emphysema/chronic bronchitis/other lung problems, kidney disease, liver disease and cancer). Emergency department visit (ED) was coded 1 (vs. 0) if the participant visited an ED at least once in the past 90 days. Disability (in the past 30 days) was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0¹⁰) to determine the activity limitations and activity-participation restrictions (0 = none; 4 = extreme/cannot do), irrespective of medical diagnosis. Perceived social support was assessed using the 12-item Multidimensional Scale of Perceived Social Support (MSPSS¹¹) on a 7-point scale (1 = very strongly disagree; 7 = very strongly agree), with higher scores indicating higher perceived support. Living arrangement, household income, impairments in activities of daily living (0–6) and instrumental activities of daily living (0–6), and overnight hospitalization within the past 90 days are reported for descriptive purposes only.

All analyses were performed using Stata 15/MP (StataCorp LLC, College Station, TX). We used descriptive statistics to examine participants’ characteristics, specifics of each CNS-active medication group, and other psychotrophic and analgesic medication intake. To test H1 (associations of CNS polypharmacy with depression severity and pain intensity), we fit a multinomial logistic regression model with CNS-active medication use (0, 1–2, and 3+) as the dependent variable. To test H2 (associations among use of different medication groups), we fit 2 logistic regression models with antidepressant and opioid use, respectively, as dependent variables. In multivariable models, we excluded 22 participants undergoing cancer treatment. Multinomial and binary logistic regression results are presented as relative risk ratios (RRR) with 95% confidence intervals (CI) and adjusted odds ratios with 95% CIs, respectively. Statistical significance was set at p<.05.

RESULTS

Supplemental Table 1 shows that participants were 68 years old on average; and most were female, non-Hispanic Black or Hispanic, lacked a bachelor’s degree, had income ≤ $25,000, and reported financial difficulty (cannot make ends meet or just about manage to get by). They had, on average, 4 chronic illnesses, moderately severe disability, and moderate social support, and almost one third had 1+ ED visit in the preceding 90 days.

Supplemental Table 2 shows that 77% of participants (n=214) were taking psychotropic or analgesic medication, including antidepressants (51%, n=142), benzodiazepines (22%, n=62), sedative-hypnotic/sleep medications (21%, n=57), and opioids (42%, n=115). Although the median lengths of medication use were 3 to 4 years, there were long-term (32–37 years) users. As expected from the study inclusion criteria, there was no association between any antidepressant use and depression severity (r=.050; p=.406); however, opioid use was associated with significantly higher pain intensity, frequency, and interference. Most (91% of antidepressant users [n=129], 80% of benzodiazepine and sedative-hypnotic/sleep medications users [n=95], and 76% of opioid users [n=87]) reported that they used their medications always or mostly as prescribed. No association was found between assessment years (2016–2019) and any medication use rate, although opioid use rates were higher among those assessed in 2016 than in those assessed between 2017 and 2019 (50% [n=48] vs. 37% [n=67], p=.056).

Supplemental Table 2 also shows that 65% (n=180) used 1+ CNS-active medication. Among those with any CNS-active medication use, 6% (n=82), 39% (n=70), and 64% (n=115) were using SSRIs, benzodiazepines, and opioids, respectively; and 16% (n=45) engaged in CNS polypharmacy. Among those with CNS polypharmacy, 69% (n=31), 69% (n=31), and 89% (n=40) were using were using SSRIs, benzodiazepines, and opioids, respectively.

Table 1 shows that higher pain intensity ratings were associated with use of 1–2 or 3+ CNS-active medications (RRR=1.14, 95% CI=1.01–1.28 and RRR=1.20, 95% CI=1.01–1.45 for 1–2 and 3+ CNS-active medication use) as opposed to no CNS-active medication use. Depression severity was not a significant factor. Only financial difficulty was a significant covariate and associated with lower risk of CNS-active medication use.

Table 1.

Associations of CNS polypharmacy with depressive symptoms (HAMD score) and pain intensity: results from multinomial logistic regression analysis (N=245).

	Compared to nonuse of CNS-active medication use
	Use of 1–2 CNS-active medication(s)			Use of 3+ CNS-active medications
	RRR	95% CI	p	RRR	95% CI	p
HAMD score	1.00	.95–1.06	.966	1.00	.92–1.08	.968
Pain intensity rating	1.14	1.01–1.28	.043	1.20	1.01–1.45	.048
Age	1.00	.97–1.03	.966	0.99	.94–1.03	.566
Female (vs. male)	1.03	.53–2.00	.923	1.22	.47–3.14	.682
African American (vs. non-Hispanic White)	0.72	.34–1.52	.390	0.51	.18–1.46	.209
Hispanic (vs. non-Hispanic White)	0.76	.36–1.59	.465	0.62	.22–1.73	.357
Bachelor’s degree (vs. no bachelor’s degree)	1.41	.67–12.95	.369	1.51	.56–4.07	.420
Cannot make ends meet/just manage to get by (vs. have enough/money is not a problem)	0.27	.10–.70	.007	0.26	.08–.86	.027
No. of chronic illnesses	1.21	1.00–1.47	.050	1.20	.92–1.56	.182
ED visit (vs. no ED visit)	0.74	.38–1.43	.372	0.96	.40–2.36	.937
Disability (WHODAS score)	0.98	.95–1.02	.336	1.00	.95–1.05	.933
Perceived social support	1.00	.99–1.02	.570	1.00	.97–1.02	.769
Model statistics	Likelihood ratio χ2=26.43, p=.331

HAMD = Hamilton Depression Rating Scale; ED = emergency department; WHODAS = World Health Organization Disability Assessment Schedule

Supplemental Table 3 shows that sedative-hypnotic/sleep medication use was associated with 5.04 (95% CI=2.11–12.05) greater odds and NSAID use was associated with 2.32 (95% CI=1.25–4.32) greater odds of antidepressant use. Antidepressant use was associated with 1.99 (95% CI=1.06–3.74) greater odds, and benzodiazepine use was associated with 3.36 (95% CI=1.65–6.84) greater odds, of opioid use. Of the covariates, financial difficulty was associated with lower odds of antidepressant use; and the number of chronic illnesses and higher pain intensity ratings were associated with greater odds of opioid use.

DISCUSSION

This study found CNS polypharmacy among one sixth of the study participants, which is higher than the 1.3% in all outpatient visits by those aged 65+ between 2004 and 2013.¹ Likely causes for the higher rate are that low-income, depressed, homebound older adults are more likely than older adults in general to have complex medical and psychological conditions, visit the ED, receive prescriptions from multiple healthcare providers, and to have lower health literacy^12,13 that is a barrier to their questioning healthcare providers about polypharmacy. The high rate of CNS polypharmacy, coupled with potential unintentional misuse due to their lack of understanding, are especially concerning for the safety of homebound older adults, given their multiple chronic illnesses and associated frailty.

Homebound older adults who suffer from depression need effective depression treatments, as untreated depression will further aggravate their physical and functional health, social isolation and quality of life. However, pharmacotherapy for these older adults requires special attention to certain safety issues associated with antidepressant use (e.g., increased bleeding risk, hyponatremia, decreased bone density, and falls),¹⁴ as consequences (side-effects and adverse outcomes) may be more severe, given their frailty and polypharmacy.

The high odds of benzodiazepine use by opioid users among these homebound older adults are also worrisome, given the safety issues related to poisoning from intentional or unintentional overdose and greater mortality associated with their concomitant use.¹⁵ In line with a national downward trend in opioid prescribing in recent years, opioid use rates among the study participants appear to have declined to a certain extent but not to a significant degree. Higher pain intensity ratings among opioid users may signal opioid-induced hyperalgesia among long-term opioid users.^33,34 When possible, nonpharmacological, psychotherapeutic treatment of late-life depression, anxiety and sleep problems and pain should be used to provide these older adults with more effective self-management strategies.

The study has limitations. First, given the geographically limited, relatively small, and largely racial/ethnic minority sample, the findings may not be generalizable to other low-income, homebound older adults. Second, self-reported data (e.g., medication adherence, disability, social support) may have been affected by social disability and recall biases. Third, the cross-sectional data could show only association, not causation. Thus, it was not clear whether depressive symptoms and pain intensity ratings could have been worse for some participants without antidepressant and analgesic medications.

CONCLUSIONS AND IMPLICATIONS

Although polypharmacy for these older adults may be necessary to manage their multiple conditions, medication reviews and education about each medication are in order, especially for long-term users of benzodiazepines, opioids and NSAIDs. Healthcare providers should also be aware of CNS polypharmacy problems among these vulnerable older adults and take steps to minimize co-prescriptions of multiple medication groups and monitor toxicity and efficacy among polydrug users. Finally, given the strong evidence base of psychotherapeutic treatments for depression, anxiety, insomnia/other sleep problems, and chronic pain, improving access to these treatment options among low-income, homebound older adults should be a national goal in a rapidly aging society.

Highlights:

• More than half of 277 low-income, depressed, homebound individuals aged 50+ were using antidepressants, more than two fifths were using opioids, more than one fifth were using benzodiazepines, more than one fifth were using sedative-hypnotic/sleep medications, and one sixth were using three+ CNS-active medications.

• Higher pain intensity ratings were associated with CNS polypharmacy than no CNS-active medication use; benzodiazepine use was associated with greater odds of opioid use.

  The high rate of CNS polypharmacy, along with many other medications that older adults are taking for chronic illnesses, raises significant safety concerns.