Antidepressant use was associated with an increased risk of head and brain injuries in individuals with Alzheimer’s disease in a Finnish nationwide matched cohort study.
Researchers used the MEDALZ (Medication and Alzheimer’s disease) cohort — a cohort of all community-dwelling individuals in the country who were diagnosed with the disease between 2005 and 2011 — to compare 10,910 new antidepressant users with a group of 21,820 nonusers (two for each user) who were matched based on age, gender, and time since Alzheimer’s diagnosis.
The age-adjusted incidence rate for head injuries per 100 person-years was 2.98 in antidepressant users and 2.43 in nonusers, they calculated. Similarly, the event rate for traumatic brain injuries was 1.33 in users and 1.10 in nonusers.
The risk for both categories of injury was highest during the first 30 days of antidepressant use, and for head injuries the increased risk lasted for over 2 years of antidepressant use. For traumatic brain injuries, the increase in risk was significant only early on, “although the risk estimates were also suggestive” of increased risk with longer durations of use, said Heidi Taipale, PhD, and her colleagues at the University of Eastern Finland in Kuopio (Alzheimer’s Res Ther 2017;9:59).
“Our findings are particularly concerning in light of recent studies reporting an increasing trend of antidepressant use among persons with dementia,” they wrote, noting that antidepressants may be used as the “safer choice” instead of antipsychotics for various behavioral and psychotic symptoms — a practice that “may prove problematic.”
The investigators included only a first diagnosis of head injury or traumatic brain injury, as determined from the hospital discharge register or data on causes of death. (Individuals with a head injury between 1972 and the time of their Alzheimer’s diagnosis were excluded.) Antidepressant use was identified through register-based dispensing data, with a 1-year washout period before the Alzheimer’s diagnosis.
Unknown for the study were indications for drug use and factors such as the severity and duration of symptoms. However, the investigators conducted various analyses, including sensitivity analyses with case-crossover design to control for unmeasured confounders such as problems with balance. Analyses were also adjusted for the use of other psychotropic drugs and opioids.
For head injuries, selective serotonin reuptake inhibitor (SSRI) use specifically — in contrast to the use of other antidepressants — was significantly associated with an increased risk. However, “it is unlikely that the risk of head injuries would be limited to SSRIs,” the authors wrote, because “many antidepressants [in the ‘other antidepressant’ category of the analysis] have more pronounced sedative effects.”
Other Finnish research has shown that antidepressant use is three times more prevalent among people who have Alzheimer’s disease than people of the same age who do not have the disease. Moreover, use has been shown to peak at 6 months after the diagnosis of Alzheimer’s, with SSRIs being the most frequently prescribed type of antidepressant.
Previous studies have also demonstrated that individuals with Alzheimer’s disease are at increased risk of falling — and of having injurious falls involving hip fractures — compared with cognitively intact older individuals.
Because antidepressant use has also been associated in other research with an increased risk of falls and fractures — and given these new study findings — “clinicians should [continue] carefully considering the indications and use of antidepressants for the safety of vulnerable patients,” Dr. Taipale and her associates said.
Christine Kilgore is a freelance writer in Falls Church, VA.
More and more research is suggesting that SSRIs, once thought to be very safe and well-tolerated in the elderly — especially when compared to their predecessors, tricyclic antidepressants — do carry some significant risks, including falls and head injuries. We should be judicious when choosing patients, especially those diagnosed with dementia, for whom to prescribe this class of antidepressant. On the other hand, many of us have seen rather remarkable improvement in some of these patients when they are placed on an SSRI, and significant worsening if a dose reduction or discontinuation is attempted. Let’s continue to consider SSRIs part of our armamentarium, but carefully consider risks, benefits, and alternatives (including other classes of antidepressants) and discuss them with patients and their families before indiscriminately prescribing them.
—Karl Steinberg, MD, CMD, HMDC
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