Review of: Heath L et al, JAGS 2018;66(10):1948–1955

Type of study: Prospective cohort study

Depression is a risk factor for dementia, but can antidepressants change that risk? Some, like paroxetine (Paxil), have anticholinergic properties that can impair cognition. This study looked at what that means for the risk of dementia.

This was a prospective cohort study of 3,049 patients without dementia in the Kaiser Permanente Washington system. All subjects were over 65 (average age 75); the majority were white, and 60% were female. Patients were screened for dementia at baseline and evaluated with the Cognitive Abilities Screening Instrument every 2 years. Average follow-up was 8 years. The outcome—a diagnosis of ­dementia—was assessed by clinical evaluation, objective testing, and multidisciplinary conferences.

Half of the patients filled an antidepressant prescription, as assessed by the system’s pharmacy database. By the end of the study, 25% had developed dementia, the majority of whom (85%) were thought to have Alzheimer’s disease. Non-paroxetine SSRIs and tricyclics did not increase the dementia risk. The serotonin antagonist and reuptake inhibitors (trazodone and nefazodone) were associated with a lower risk of dementia, but this may have been due to the tendency to prescribe trazodone to non-depressed patients with insomnia.

The big story here, though, was paroxetine. It was associated with a higher risk of dementia in a non-dose-dependent manner (hazard ratio 1.7–2.1). This association held up after controlling for other factors such as anxiety, insomnia, and cerebrovascular disease.

This is not the first study to look at the association between antidepressants and dementia, but it is one of only 2 studies that has controlled for depression, which itself is a risk factor. The other, a case-control study comparing anticholinergic drugs in 40,000 patients, also implicated paroxetine, as well as the tricyclic amitriptyline (Richardson K et al, BMJ 2018;361:k1315).

TCPR’s Take
Anticholinergic antidepressants can cause a number of problems in the elderly, including urinary retention, constipation, temperature imbalance, confusion, blurry vision, and tachycardia. Dementia may be added to that list, at least with paroxetine and possibly the tricyclics. However, more data are needed. As for other antidepressants, it was refreshing to learn they didn’t increase dementia risk.