Use of Antipsychotics and Benzodiazepines in Dementia: A Push Down the Hill of Frailty?
Vol 8 #9
Shyam Maharaj BSc, PhD1,✉, Linda Dam RN2, Ana Hategan MD3, Jonathan Crowson MD4
1 Adjunct Assistant Clinical Professor, Pharmacist, Department of Medicine, McMaster University, Inpatient Pharmacy, West 5th Campus, St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada. ✉ [email protected]
2 Hamilton Health Sciences, Hamilton, ON, Canada
3 Clinical Professor, Geriatric Psychiatrist, Division of Geriatric Psychiatry, Department of Psychiatry and Behavioural Neurosciences, Michael G. DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
4 Assistant Professor, Psychiatrist, Division of Geriatric Psychiatry, Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
To the Editor: Clinicians who treat patients with behavioral and psychological symptoms of dementia (BPSD) are faced with little or no choices for approved pharmacological treatment when the preferred method of behavioral approaches has failed [1, 2]. One approach is the use of benzodiazepines as an “off label” treatment and the use of antipsychotics for brief periods to control symptoms that are severe, dangerous, and/or cause distress to the patient as outlined by the American Psychiatric Association practice guideline . However, the authors questioned whether the use of antipsychotics or benzodiazepines may be related to a negative outcome of increased frailty in this population. While it is well understood that avoidance of these medications in the older adults leads to less adverse events such as falls which sometimes leads to fractures, worsening cognition, and increased risk of cerebrovascular accidents , it is yet unknown whether use of these medications is also related to a change in frailty. The authors herein explored the impact on frailty of the use of benzodiazepines and antipsychotics in patients with severe BPSD (agitation and aggression) in a tertiary care seniors mental health inpatient unit at a Canadian teaching hospital in Hamilton, Ontario.
We performed a retrospective chart review of consecutive admissions (n = 45) during a 1-year period, with 37 patients meeting the inclusion criteria. All patients had a diagnosis of severe dementia of varying etiology and were at least 65 years old. Each patient was continually maintained on a scheduled or frequently used, as-needed benzodiazepine or an antipsychotic drug (either a first generation or second generation) regardless of the dosage for the management of BPSD. We confirmed the indication for their use of benzodiazepine or antipsychotic medication to be the presence of persistent agitation or aggression, which was refractory to non-pharmacological approaches. All patients enrolled into this study were seen by an occupational therapist on admission and on a weekly basis throughout their admission. Occupational therapy functional assessments and weekly progress notes from the patient’s chart were used as a priori by the study clinicians to assign a score according to a modified Rockwood clinical frailty scale  and to measure changes in ambulation as well as basic activities of daily living, which were interpreted as progression according to this scale (see Table 1). The Cohen Mansfield Agitation Inventory (CMAI)  was used to orient the investigator collecting data to specific patient behaviors, which indicated changes in BPSD. Changes in BPSD during admission were assessed at 3 months, 6 months, and upon discharge.
Table 1. Modified clinical frailty scale used in this study (Derived from ).
BADLs: eating, dressing, bathing, grooming, transferring, toileting/hygiene.
As shown in Table 2, no change in frailty was seen in patients using antipsychotics, irrespective of the number of concurrent antipsychotics prescribed, and stratified by age. The patients recruited did not suffer any fractures as a result of falls nor was there any worsening of behaviors suggesting further impairment in cognition; no specific mention of other known adverse outcomes of antipsychotic and benzodiazepine use were documented in the patient’s progress notes. There was no significant change in frailty with either a longer duration of use of antipsychotics or longer stay in hospital. We found no difference between younger vs older adult patients who were prescribed 1 or more benzodiazepines (in addition to antipsychotic therapy). The most pronounced change in frailty for patients treated with 1 or more antipsychotics was trending between ages 65-75 and 86-95; however, this did not reach statistical significance. In this study, prescribing benzodiazepines to patients in addition to antipsychotics was not responsible for an increase in frailty.
Table 2. Study demographics and frailty changes with the use of benzodiazepines and antipsychotics.
|Age||65-75 years old||76-85 years old||86-95 years old|
|Length of stay ≤ 4 months (n = 16)||13%||56%||31%|
|Length of stay > 4 months (n = 21)||29%||52%||19%|
|Average change in frailty score for patient prescribed ≥ 1 antipsychotic||1.58||1.91||0.22|
|Average change in frailty score for patient prescribed ≥ 1 benzodiazepine||1.1||1.69||2.83||0.28|
|Number of antipsychotics prescribed||1||2||> 2|
|Patients with increased frailty (n = 23)||39%||39%||22%|
|Patients with no change in frailty (n = 14)||43%||36%||21%|
|Average change in frailty score||1.94 (n = 9)||2.11 (n = 9)||2.40 (n = 5)||0.87|
|Duration of antipsychotic use||< 1 month||1-3 months||> 3 months|
|Average change in frailty score||1.62||2.28||2.20||0.75|
|Number of benzodiazepines prescribed||1||2|
|Average change in frailty score||1.82||1||0.5|
Despite the range of ages enrolled into the study, dementia remains a condition mainly affecting older adults, with more than 70% of patients included in this study being aged 76 or older. We speculate the upward trend in frailty is multifactorial including cumulative disease burden; however, there was no statistically significant increase seen in patient frailty with an increase in the number of antipsychotics in this small, uncontrolled, retrospective study. Further larger prospective controlled studies are needed to fully estimate whether use of these medications play a causative role in frailty in this population.
Conflict of Interest and Source of Funding:
The authors report no source of funding and no conflicts of interest concerning the subject matter of this article.
- American Geriatric Society. American Geriatric Society 2019 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694.
- Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;1;173(5):543-546.
- Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489-495.
- Cohen-Mansfield J, Marx MS, Rosenthal AS. A description of agitation in a nursing home. J Gerontol. 1989;44(3): M77-84.