Lauren B. Gerlach

Opioids and Other Central Nervous System–Active Polypharmacy in Older Adults in the United States

To determine patterns of and trends in contributions to central nervous system (CNS) polypharmacy, defined by the Beers Criteria as three or more CNS‐active medications of each medication class, of adults aged 65 and older seen in U.S. outpatient medical practices.

Trends in Central Nervous System–Active Polypharmacy Among Older Adults Seen in Outpatient Care in the United States

LESS IS MORE Trends in Central Nervous System–Active Polypharmacy Among Older Adults Seen in Outpatient Care in the United States With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown. Opioids have recently been included in a Beers measure of central nervous system (CNS) polypharmacy.1 Prescribing related drug combinations also received increased regulatory attention when the US Food and Drug Administration recently ordered a black-box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants. While evidence builds concerning harms of CNS polypharmacy, little is known about the trends in relevant prescribing practices. Methods | This analysis used data from the 2004 through 2013 National Ambulatory Medical Care Survey (NAMCS), an annual survey of office-based physicians.2 We limited our analysis to patients aged 65 years or older (n = 97 910). Because this research is on publicly available, deidentified data, the University of Michigan Medical School institutional review board did not require approval. An outpatient visit met Beers CNS polypharmacy criteria if 3 or more of the following medications were initiated or continued: antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, and opioids. We recorded up to 3 visit diagnoses and included NAMCS-collected information such as chronic medical conditions, whether psychotherapy was provided or ordered, whether stress management or other mental health

Unintended Consequences of Adjusting Citalopram Prescriptions Following the 2011 FDA Warning

OBJECTIVES In 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement cautioning providers against prescribing citalopram above 40 mg per day given concerns for QT prolongation. We assessed the impact of a health system quality improvement initiative to identify patients taking higher than the recommended dose of citalopram. DESIGN Retrospective cohort study. SETTING Nine primary care clinics within the University of Michigan from March 2012 to February 2013. PARTICIPANTS Adult patients taking a higher-than-recommended dose of citalopram following the FDA warning in 2011 (N = 199). MEASUREMENTS Frequency of EKG monitoring, clinical factors associated with patients whose citalopram dose or use was adjusted, and potential impact of these changes on overall health care utilization was assessed. RESULTS In patients prescribed higher-than-recommended doses of citalopram and who received a note from a pharmacist regarding the FDA warnings, only 8.5% received electrocardiogram (EKG) monitoring. Patients who were converted to an alternative antidepressant from citalopram were more likely to receive subsequent new prescriptions for benzodiazepines and sedative hypnotics (χ2 = 7.9, p = 0.048). Patients who had any adjustments to their antidepressant medication had greater overall health care utilization (OR: 25.0; 95% CI: 5.7-109.6; p < 0.001) than patients remaining on the same dose of citalopram. CONCLUSIONS Despite a targeted quality intervention to address the FDA warning regarding citalopram, the warning was associated with low levels of EKG monitoring, increased anxiolytic and sedative medication use, and higher healthcare utilization. This finding may represent destabilization of patients on previously therapeutic doses of their antidepressant and an unintended consequence of the FDA warning.

Learning Their Language: The Importance of Detecting and Managing Pain in Dementia

Mr. S is a 73-year-old man who presented to the hospital with confusion and memory loss and was subsequently found to have suffered multiple bilateral posterior circulation strokes with thalamic involvement. He was admitted to the acute rehabilitation service with a diagnosis of vascular dementia. His coursewas complicated by significant agitation, irritability, and impulsivity. Mr. S would intermittently become physically aggressive, causing injury to several staff memberswho reported being afraid toworkwith him. In addition to significant expressive aphasia, despite speaking English fluently before his stroke, he reverted solely to his native language of German, limiting his communication with staff. He was placed on increasing doses of antipsychotic andmood-stabilizing medications by his primary team, aswell as having frequent episodes of restraint placement. Haloperidol, quetiapine, olanzapine, risperidone, valproic acid, lorazepam, and trazodone were all tried with limited improvement in his symptoms anddevelopment of significant side effects, including sedation, recurrent falls, and extrapyramidal symptoms. Notably, the combinationof agitation and sedation fromuseofpsychotropic medications precluded him from participating in rehabilitative therapies. Mr. S was evaluated by geriatric psychiatry roughly a month into his admission. His Mini-Mental State Examwas estimated at less than 10. He appeared to be very sensitive to touch and would physically withdraw during care tasks. Given thalamic involvement of his stroke, adiagnosis of a thalamic (central) pain syndrome was considered. An empiric trial of gabapentin for presumedhyperalgesiawas tried with resulting significant improvement in his level of agitation. As gabapentin was titrated, antipsychotics were discontinued, and his dose of valproic acid was significantly reduced. He was eventually able to participate more in rehabilitation and was ultimately discharged to a long-term care facility. As illustrated in the real-life case of Mr. S, the detection and management of pain in people with dementia is a huge challenge for physicians caring for older adults. By virtue of age, people with dementia are at risk for the same pain-causing conditions as older people without cognitive impairment, and medical comorbidity is found to increase with dementia severity. In addition, although dementia itself is not believed to cause pain by physiologic mechanisms, because dementia can be associated with being sedentary and inactive, people with the condition may be at increased susceptibility to some pain-causing conditions. Pain is estimated to affect one-third to one-half of people with dementia. Although people with dementia are believed to experience pain in the same way as people without cognitive impairment, the abilities to interpret and respond to pain are both altered. Discomfort may instead be manifested as behavioral and psychological symptoms of dementia (BPSD), including verbal or physical aggression, withdrawal, resistance to care, depression, anxiety, decreased appetite, and sleep disturbances, causing distress for both patients and their caregivers. Too often, instead of using an organized assessment approach or algorithm such as DICE (Describe, Investigate, Create, Evaluate) when such BPSD

Assessing Responsiveness of Health Systems to Drug Safety Warnings

OBJECTIVE In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety announcements cautioning providers against prescribing high doses of citalopram given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA) national trends in citalopram use and dose compared with alternative antidepressants after the FDA warnings. METHODS Time series analyses estimated the effect of the FDA warnings on citalopram and other antidepressant across three periods: before the first FDA warning in August 2011, after the 2011 FDA warning until the second warning in March 2012, and after the 2012 FDA warning. In a National VA health system, adult VA outpatients prescribed citalopram or alternative antidepressants from February 2010 to September 2013 were studied. Outpatient use of high-dose citalopram (>40 or >20 mg daily in adults aged > 60 years) including the proportion of patients prescribed citalopram and difference between study periods. RESULTS Between the first and second FDA warnings, among patients aged 18-60, high-dose citalopram use decreased by 2.0% per month (p < 0.001) and by 1.9% per month (p < 0.001) for older adults. After the second FDA warning in 2012, 30.7% of older patients remained on doses higher than the newly recommended dose of 20 mg. Reductions in overall use of citalopram were accompanied by significant increases in prescriptions of alternative antidepressants, with sertraline most widely prescribed. CONCLUSION Although trends in high-dose citalopram use declined after the 2011-2012 FDA warnings, roughly one-third of older adults still remained on higher than recommended doses. Concomitant increases in sertraline and other antidepressant prescriptions suggest potential substitution of these medications for citalopram.

Electrocardiogram Monitoring After the Food and Drug Administration Warnings for Citalopram: Unheeded Alerts?: Citalopram and EKG Monitoring

To evaluate national trends in electrocardiogram (EKG) monitoring in Veterans Affairs (VA) beneficiaries prescribed high‐dose citalopram before and after the 2011–12 Food and Drug Administration (FDA) safety warnings.

Responsiveness of Veterans Affairs Health Care System to Zolpidem Safety Warnings

STUDY OBJECTIVES Sedative hypnotic medications are routinely prescribed for insomnia treatment, but have been associated with significant risks of morning-after impairment. We evaluated responsiveness in the Veterans Health Administration (VHA) facilities to two drug safety warnings recommending against high-dose zolpidem use-a 2007 Veterans Administration Pharmacy Benefits Management Service warning and a 2013 Food and Drug Administration (FDA) warning. METHODS We used interrupted time-series design to assess how the two warnings influenced prescribing within the VHA in outpatients from 2005 to 2014. We assessed two outcomes: monthly outpatient use of (1) higher-than-recommended dose of zolpidem among zolpidem users and (2) any-dose zolpidem among all VHA users. In sensitivity analyses, we compared zolpidem prescribing to prescribing other sleep medications not subject to safety warnings. RESULTS After the 2007 VHA warning, high-dose zolpidem use decreased significantly among both sexes from approximately 10% to 2%. Following the 2013 FDA warning, high-dose zolpidem use declined again; however, approximately half of women Veterans remained on high doses. Overall zolpidem use nearly quadrupled between the 2007 VHA and 2013 FDA warnings, but the overall use declined after the 2013 FDA warning. Increase in sedating antidepressant use was seen after the FDA warning, suggesting potential substitution. CONCLUSIONS Higher than recommended dose use within the VHA decreased after each zolpidem high dose warning. Although overall use also decreased after the FDA warning, almost 50% of high-dose use among women Veterans is concerning. Different strategies to communicate the warnings should be examined. COMMENTARY A commentary on this article appears in this issue on page 1093.

Factors Associated With Long-term Benzodiazepine Use Among Older Adults

LESS IS MORE Factors Associated With Long-term Benzodiazepine Use Among Older Adults Benzodiazepine use among older adults is common despite evidence for many potential risks. While treatment guidelines recommend short-term use of benzodiazepines, up to one-third of use is long term, which is most common among older adults.1 To reduce benzodiazepine prescribing to older adults, one potential point for intervention is at the transition from new to long-term use, yet little is known about the factors that predict conversion to long-term use.2,3

Managing Behavioral and Psychological Symptoms of Dementia

Behavioral and psychological symptoms of dementia (BPSD) are universally experienced by people with dementia throughout the course of the illness and cause a significant negative impact on quality of life for patients and caregivers. Nonpharmacologic treatments have been recommended as first-line treatment of BPSD by multiple professional organizations and should target patients with dementia factors, caregiver factors, and environmental factors. Psychotropic medications are often prescribed off-label without significant evidence to support their use. The Describe, Investigate, Create, Evaluate approach can provide a structured method to investigate and treat BPSD with flexibility to use in multiple treatment settings.

With a little help from my friends?: Racial and gender differences in the role of social support in later-life depression medication adherence

BACKGROUND Social support has been shown to be an important factor in improving depression symptom outcomes, yet less is known regarding its impact on antidepressant medication adherence. This study sought to evaluate the role of perceived social support on adherence to new antidepressant medication prescriptions in later-life depression. METHODS Data from two prospective observational studies of participants ≥60 years old, diagnosed with depression, and recently prescribed a new antidepressant (N = 452). Perceived social support was measured using a subscale of the Duke Social Support Index and medication adherence was assessed using a validated self-report measure. RESULTS At four-month follow up, 68% of patients reported that they were adherent to antidepressant medication. Examining the overall sample, logistic regression analysis demonstrated no significant relationship between perceived social support and medication adherence. However, when stratifying the sample by social support, race, and gender, adherence significantly differed by race and gender in those with inadequate social support: Among those with low social support, African-American females were significantly less likely to adhere to depression treatment than white females (OR = 4.82, 95% CI = 1.14-20.28, p = 0.032) and white males (OR = 3.50, 95% CI = 1.03-11.92, p = 0.045). CONCLUSIONS There is a significant difference in antidepressant medication adherence by race and gender in those with inadequate social support. Tailored treatment interventions for low social support should be sensitive to racial and gender differences.