Low Dose Trazodone, Benzodiazepines, and Fall-Related Injuries in Nursing Homes: A Matched-Cohort Study

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Clinical Question

In nursing home residents, is low-dose trazodone more effective at preventing fall related injuries compared to benzodiazepines?

Bottom Line

In nursing home residents, there is no significant difference in fall incidence between benzodiazepines and low dose trazodone

Major Points

  • Benzodiazepine use in elderly patients, specifically those in nursing homes, has been criticized and is currently on a downward prescribing trend. The reason for this is due to the known fact that these medications can have many adverse effects, especially in the elderly population. One of the most prominent is the fall risk in elderly patients. Low dose trazodone has commonly been the medication to replace benzodiazepines for off-label treatment for insomnia and behavioral and psychological symptoms of dementia. Both medications present a fall risk in the elderly posing the question if low dose trazodone is more effective at preventing fall related injuries than benzodiazepines in nursing home patients.
  • This matched, retrospective cohort study with linked population-based administrative data in Ontario, Canada showed that there is no significant difference between the fall risk of low dose trazodone compared to benzodiazepines in nursing home patients.
  • In nursing home patients, the use of low dose trazodone compared to the use of benzodiazepines, shows no difference in fall related injuries. The results of this study were insignificant and warrants further research to be done before basing clinical decisions on the results. The study took into account may variables and sources of bias providing a moderate quality evidence for a cohort study. A higher quality study design, such as a randomized controlled trial, that would include standardization of medication indication, dose, and frequency could potentially generate significant results.

Guidelines

AGS Beers Criteria

  • Elderly patients are at an increased risk of adverse drug events with benzodiazepines including higher fall incidence.
  • No recommendations on trazodone

The Journal of clinical Sleep Medicine

  • The recommendation of benzodiazepines has efficacy for a short term treatment only in insomnia
  • There is evidence, though weak, to suggest trazodone should not be recommended as treatment, and it is also not an FDA approved indication of the drug.
  • NOTE: the study being assessed does not specify the indication of trazodone for insomnia, but due to it being low-dose, it is assumed to be use off-label for insomnia. Benzodiazepines at the dose studied can be used for treatment of insomnia and other indications as well.

Design

  • Trial Type: Retrospective matched cohort study in linked population-based administrative data
  • N=15,582
    • propensity score matched pairs of new low-dose trazodone users (N=7,791) to new benzodiazepine users (N=7,791)
  • Setting: Nursing homes in Ontario, Canada (information from Continuing Care Resident Reporting Database)
  • Enrollment: April 1, 2010 - March 31, 2015
    • Mean follow-up: N/A Cohort
  • Analysis: Intention-to-treat
  • Primary outcome: Fall-related emergency department or acute care hospitalization within 90 days

Population

Inclusion Criteria

  • Canadian nursing home patients
  • New low dose benzodiazepine or trazodone users who had no history of previous use of either drug in last 90 days
  • Age of greater than 66 between the dates of April 1, 2010 and March 31, 2015

Exclusion Criteria

  • Patients who have taken no medications in the year prior to assessment
  • Comatose patients
  • Completely bed-bound on date of assessment
  • Patients receiving palliative care within 180 days prior to assessment date or on the date of assessment

Baseline Characteristics

  • Mean age of each pair: 83.9 +/- 7.1
  • 63.9% were female
  • 65% of patients in each pair had Alzheimer's disease and related dementia
  • 48.7% of patients in each pair were regarded as frail
  • 43.3% of new low-dose trazodone users and 44.3% of new low-dose benzodiazepine users had unsteady gait, a risk factor for falls
  • 46.3% of new low-dose trazodone users and 47% of new low-dose benzodiazepine users had a fall in the past 180 days
  • 53.1% of new low-dose trazodone users and 53% of new low-dose benzodiazepine users had an ED visit or hospitalization for a fall-related injury in the past 5 years

Interventions

  • Newly initiated low dose (150 mg or lower per day) trazodone OR newly initiated benzodiazepines (reference: lorazepam 2.5 mg per day)

Outcomes

Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

Emergency department visit or acute care hospitalization due to a fall within 90 days of the initiation of new low dose trazodone (5.74%) or new benzodiazepine (6.03%)
Difference in Outcomes -0.29%, 95% CI (-1.02-0.44)
HR = 0.95, 95% CI(0.83-1.08)
P = 0.43

Secondary Outcomes

Emergency department visit or acute care hospitalization due to a fall specifically with a hip or wrist fracture diagnosis within 90 days of initiation of new low doe trazodone (1.22%) or new benzodiazepine (1.54%)
Difference in Outcomes -0.32%, 5% CI (0.68-0.04)
HR of 0.79, 95% CI (0.60-1.04)
P = 0.09
Censoring based upon stopping the studied drug, or a drug therapy change
Difference in Outcomes: 0.05%, 95% CI (-1.01-1.11)
HR of 0.96, 95% CI (0.82-1.14)
P = 0.67
Subgroup of patients selected that were studied using newly prescribed low dose trazodone or newly prescribed low dose benzodiazepine
Difference in Outcomes: -0.08%, 95% CI (-1.00-0.83)
HR of 0.99, 95% CI (0.84-1.16)
P = 0.86

Subgroup Analysis

Subgroup analyses were conducted for sex, bone frailty, dementia, and days between initiation of therapy and incidence of fall, and no significant results were exhibited in any of these analyses.

Adverse Events

Not Assessed

Criticisms

External

  • Trazodone is off label for insomnia though this study implied the use of this medication for this indicator

Internal

  • Doses of the drugs studied were all low, which could contribute to a lower incidence of falls
  • Divided doses vs hole doses, targeted disease state, and time of day medications were taken were not standardized
  • Results failed to include falls that did not end in hospitalization

Funding

  • Canadian Frailty Network, supported by the Canadian Government through the Networks of Centres of Excellence Program and Canadian Institutes of Health Research
  • Institute of Clinical Evaluative Sciences, supported by the Ontario Ministry of health and Long-Term Care annual grant

Further Reading

1. American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for potentially Inappropriate Medication Use in Older Adults. J Am Geria(r Soc. 2019; 67: 674-694. https://nicheprogram.org/sites/nighe/files/2019-02/Panel-2019-Journal_of_the_American_Geriatrics_Society.pdf

2. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL, Clinical practice guideline for the pharmacologic treatment of chronic insomina in adults: an American Academy of Sleep Medicine clinical practice guideline J clin Sleep Med. 2017;13(2): 307-349 http://jcsm.aasm.org/ViewAbstract.aspx?pid=30954