The U.S. Food and Drug Administration (FDA) has not approved any drugs for behavioral and psychological symptoms of dementia (BPSDs), although the widespread prescribing of psychotropic and opioid medications to persons with dementia could represent off-label attempts to address BPSDs (
1–
3). Based on mortality concerns, the FDA issued black box warnings for mortality risk associated with atypical antipsychotics (2005) and conventional antipsychotics (2008) when used to treat dementia-related psychosis (
4). Given these safety concerns, providers may prescribe alternative CNS-active medications in lieu of antipsychotics. However, commonly used alternatives, such as benzodiazepines and antiepileptics, have even poorer risk-to-benefit ratios (
5). Ultimately, among psychotropic medications, atypical antipsychotics have the strongest evidence base for treatment of BPSDs, although their benefits may prove moderate at best (
6). Numerous expert bodies and professional organizations, including the American Geriatrics Society, the American Association of Geriatric Psychiatry, and the American Psychiatric Association, have recommended nonpharmacological strategies as first-line treatments for addressing BPSDs (
7,
8).
Prior to the first black box warning in 2005, 24%–32% of nursing home residents received antipsychotics (
9–
11). The Centers for Medicare and Medicaid Services (CMS) launched the National Partnership to Improve Dementia Care in Nursing Homes (CMSNP) in 2012 to address concerns about persistently high rates of antipsychotic use and the quality of care provided to nursing home residents with dementia (
12). The CMSNP included training materials and online resources with the goal of reducing antipsychotic prescribing in nursing homes. The CMSNP appeared to lower antipsychotic prescribing in nursing homes from 24% in 2011 to 15% in 2018 (
13). Starting in 2015, the CMS Five Star Quality Rating System for nursing homes included a publicly reported measure of antipsychotic drug use by nursing homes through the Nursing Home Compare website, thus incentivizing facilities to reduce their antipsychotic prescribing (
14).
Whether the CMSNP recommendations translated into reductions in antipsychotic prescribing within the Veterans Health Administration (VHA), which provides care to many veterans with dementia in VHA nursing homes, named Community Living Centers (CLCs), remains unknown. The VHA maintains over 130 CLCs across the United States, which provide both short- and long-term nursing and medical care for veterans (
15). In addition to the potential impact of the CMSNP within the VHA, in December 2013, the VHA launched the Psychotropic Drug Safety Initiative (PDSI), a nationwide psychopharmacology quality improvement initiative. From 2013 through 2017, the PDSI included two targets relevant to veterans with dementia: the proportion for whom antipsychotics were prescribed and the proportion for whom benzodiazepines were prescribed. Further, similar to community nursing homes, CLCs complete the CMS Minimum Data Set 3.0 for clinical assessment of veterans’ health and behaviors as well as to report CMS quality indicators. In 2018, the VHA developed a similar publicly reported rating system adapted from the CMS Nursing Home Compare website, called CLC Compare, to help evaluate the quality of care received by veterans in CLCs (
16).
Therefore, both Medicare and the VHA have used antipsychotic use as a proxy measure for quality of care among patients with dementia in nursing home settings (
17). In community settings, antipsychotic reduction led to an increase in other types of CNS-active medication prescribing (
18); it remains unknown whether this also occurred within the VHA. In this study, we sought to evaluate national trends in antipsychotic and other CNS-active medication prescriptions for veterans with dementia residing in VHA nursing homes as well as to understand how the use of specific agents has changed over time.
Discussion
This study provides data on national trends in CNS-active medication prescribing for veterans with dementia in VHA CLCs. We found that antipsychotic use among veterans with dementia declined over time, and the decline was most significant following the VHA PDSI. Antidepressant prescribing increased following the VHA PDSI while antiepileptic prescribing increased following both the CMSNP and the VHA PDSI. Overall prescribing of non-antipsychotic psychotropic medications in VHA CLCs remained high, with over 80% of veterans with dementia receiving prescriptions for a non-antipsychotic psychotropic medication at the end of the study period. Gabapentin, valproate derivatives, and sedative antidepressants had the largest contributions to the growth in CNS-active medication prescribing. Anxiolytic prescribing declined following the VHA PDSI, and memory medication prescribing declined across all study periods and had a lower prescribing rate than any of the other medication classes observed. Lastly, opioid prescribing remained common and increasing prior to and during the CMSNP, only decreasing following the start of the VHA PDSI.
Our findings in the VHA are consistent with previous studies in non-VHA settings (one in the community, two in nursing homes) (
2,
18,
24), which found that initiatives focused on reducing antipsychotic use may have contributed to providers shifting to alternative medication classes with similar risks and even less evidence of benefit. A Canadian study (
24) showed that decreased antipsychotic use in nursing homes between 2004 and 2013 was offset by increased sedative antidepressant and antiepileptic use. A recent U.S. study examining Medicare beneficiaries found that antiepileptic prescriptions for nursing home residents increased and accelerated after the initiation of the CMSNP (
18). It appears that these trends also extend to the VHA CLC population, where antiepileptic prescribing occurred at even higher rates compared with rates outside of the VHA.
When evaluating change in specific medications, we found that quetiapine was the most commonly prescribed antipsychotic among patients with dementia, consistent with findings from community long-term care populations (
25). While quetiapine has been found to have a lower mortality risk in dementia (
26), studies also suggest that it may have less evidence of benefit in reducing BPSDs (
27). Increases in antidepressant use were largely driven by prescribing of sertraline and sedating antidepressants (e.g., trazodone and mirtazapine), which may be used for treatment of depression or BPSDs. Notable decreases in citalopram were observed following the 2011 FDA drug safety warning regarding concerns about QT prolongation with high-dose citalopram use, as has been reported in other studies (
28,
29).
The growth of antiepileptic use was largely driven by gabapentin, for which prescribing doubled during the study period, likely off-label for pain, anxiety, or BPSDs, rather than for seizure disorders (
25). Significant increases in prescription opioid use were observed before and during the CMSNP. This is consistent with studies demonstrating high rates of opioid prescribing for patients with dementia in the community (
2) as well as population-based studies demonstrating significant growth in opioid prescribing for patients with dementia (
3). While such treatment may reflect improved recognition and treatment of pain in dementia or palliative approaches to dementia end-of-life care, it may also reflect another attempt to reduce BPSDs (
3,
30). In addition to measures of the percentage of long-stay residents with dementia for whom an antipsychotic is prescribed, VHA CLCs also have a publicly reported quality measure of percentage of long-stay CLC residents who self-report moderate or severe pain (
16), further incentivizing treatment of pain.
A recent international panel of geriatric psychiatry and dementia care experts noted that antipsychotics are the most effective pharmacotherapy for BPSDs, including psychosis, agitation, and aggression (
31). Studies reviewing the use of other medication classes, such as antidepressants, benzodiazepines, antiepileptics, and opioids, for treatment of BPSDs show minimal benefit in reducing such symptoms (
5,
30,
32). Additionally, these alternative medication classes substituted for antipsychotics can yield significant risks. Benzodiazepines can contribute to falls, worsened cognition, respiratory depression, and paradoxical disinhibition (
33). Antiepileptics such as valproate derivatives can cause gait disturbances, tremor, cognitive changes, and mortality (
26,
34). Gabapentin use can lead to ataxia, dizziness, drowsiness, fatigue, falls, and increased risk of respiratory suppression when combined with opioids (
35). Reductions in prescribing of memory medications may reflect provider concerns about limited therapeutic benefit for patients with advanced dementia as well as concerns regarding side effects, including nausea, loss of appetite, and diarrhea (
36).
The VHA may have achieved declines in several classes of CNS-active medications as a result of its multipronged efforts. In contrast with the CMSNP, which focused on antipsychotic use only, the VHA PDSI, in addition to an antipsychotic prescribing measure, addresses benzodiazepine use, which may explain the observed anxiolytic reductions in the VHA. Further VHA initiatives, including the 2013 Opioid Safety Initiative, may explain reductions in opioid prescribing as well as increased recognition of the dangers of opioid prescribing in patients with dementia (
37). Additionally, in 2010, the VHA launched an initiative to adapt an evidenced-based behavioral approach (Staff Training in Assisted Living Residences, or STAR [
38]) for the VHA to increase uptake of nonpharmacological strategies for BPSDs. We do not know whether CLCs with STAR implementation decreased antipsychotic use, and if so, whether the decrease reflected increased use of nonpharmacological strategies (
39). Reports from long-term care staff outside of the VHA suggest considerable challenges in implementing such interventions given staff turnover as well as the time and resources needed to implement nonpharmacological strategies (
40).
Our study has several limitations. First, our results on prescription rates may not be directly comparable to those in community nursing homes given the differences in the structure of VHA CLCs, including the presence of a national formulary and the range of psychosocial services available to veterans (
15). Next, our sample includes a high proportion of men, and our study results may not generalize to other clinical populations. Third, prescriptions filled from pharmacy data can be an imprecise measure of actual drug exposure; medication fills may not reflect day-to-day use. However, this study focused on the impact of initiatives that influence prescribing rather than medication use. Next, we do not know the indication for medication prescribing (e.g., gabapentin could be prescribed for pain, seizures, or BPSDs) or the appropriateness of such prescribing. However, the potential for medication-related harms remains regardless of clinical indication. Further, prescribing trends may reflect changes in patient characteristics over time; however, our approach is consistent with the CMSNP and VHA PDSI, neither of which use case-mix adjustment. Lastly, administrative data do not include reliable measures of nonpharmacological interventions, limiting our ability to examine whether increased use of such interventions was associated with declines in antipsychotic prescribing.