Risk of head and traumatic brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer’s disease: a nationwide matched cohort study

Abstract

BackgroundAntidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer’s disease.MethodsA matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer’s disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer’s disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident.ResultsAntidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49–3.06) during use and 2.43 (95% CI 2.06–2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20–1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13–1.53) during use and 1.10 (95% CI 1.00–1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06–1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10–2.66 for head injuries; HR 2.06, 95% CI 1.12–3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries.ConclusionsAntidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer’s disease. Antidepressant use should be carefully considered and the association confirmed in future studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0285-3) contains supplementary material, which is available to authorized users.

<p>Antidepressants and the risk of traumatic brain injury in the elderly: differences between individual agents</p>

“…So far, the association between TBI and AD use has been investigated in only one study that was restricted to a high-risk group, that is, patients with Alzheimer’s disease 19. In that study, the risk in current users of SSRIs was 17%, which was lower than in our study and did not reach statistical significance due to the limited number of TBIs among SSRIs users.…”

“…To our knowledge, only one study has specifically evaluated the association of TBI with AD use so far. That study, however, was restricted to patients with Alzheimer’s disease 19. Given that patients with Alzheimer’s disease or other dementias are a high-risk group for falls, the results are not generalizable to elderly without dementia 20,21.…”

Brain Injury–Mediated Neuroinflammatory Response and Alzheimer’s Disease

“…Certain drugs also affect TBI-induced AD pathogenesis. Antidepressant use is associated with consistently increased risk of falling and head injuries in community-dwelling persons with AD (Taipale and others 2017). Innate immune targeted therapy could improve AD symptoms.…”

Association of recent hospitalisation with antidepressant initiation among community dwellers with Alzheimer's disease

“…It is concerning as psychotropic polypharmacy is associated with higher risks of adverse events 54 . Antidepressants, antipsychotics, benzodiazepines and related drugs and opioids are all associated with an increased risk of falls and subsequent head injuries and hip fractures in older persons which is an important safety concern as persons with cognitive impairment already have increased risk of falling 22,55–60 . Moreover, psychotropic drugs are often used for a long period of time among persons with dementia 61–63 even though guidelines recommend limited duration of use 7,11…”