Antidepressant use and cognitive decline in patients with dementia: a national cohort study

Abstract

Background: Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose.

Methods: This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose-response.

Results: We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = - 0.30(- 0.39, - 0.21) points/year), in particular sertraline (- 0.25(- 0.43, - 0.06) points/year), citalopram (- 0.41(- 0.55, - 0.27) points/year), escitalopram (- 0.76(- 1.09, - 0.44) points/year), and mirtazapine (- 0.19(- 0.34, - 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0-9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed.

Conclusions: In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia.

Keywords: Antidepressants; Cognitive decline; Cohort; Dementia; Mortality.

Fig. 1

Estimated MMSE trajectories between use of antidepressants and non-use by dementia subtypes^a. Abbreviations: SveDem, the Swedish Registry for Cognitive/Dementia Disorders; CIs, confidence intervals; MMSE, Mini-Mental State Examination; AD, Alzheimer’s disease; Mixed, mixed dementia; VaD, vascular dementia; LBD, Parkinson’s disease with dementia and dementia with Lewy bodies; FTD, frontotemporal dementia.^a, Estimated MMSE trajectories from mixed model, adjusted for age, sex, calendar year of diagnosis, the type of dementia, MMSE score at diagnosis, coresident status, care unit, depression, fracture, Charlson Comorbidity Index score , medications (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), β-blocking agents, calcium channel blockers, nonsteroidal anti-inflammatory drugs, diuretics, lipid-modifying agents, antiplatelets, antipsychotics, anxiolytics, and hypnotics). For patients with AD and mixed dementia and LBD, models further adjusted for cholinesterase inhibitors and memantine

Fig. 2

Estimated MMSE trajectories between use of antidepressants and non-use by antidepressant class and individual drugs^a. Abbreviations: SveDem, the Swedish Registry for Cognitive/Dementia Disorders; CIs, confidence intervals; MMSE, Mini-Mental State Examination; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin and norepinephrine reuptake inhibitors; TCAs, Tricyclic antidepressants; Others, other antidepressants. ^a, Estimated MMSE trajectories from mixed model, adjusted for age, sex, calendar year of diagnosis, the type of dementia, MMSE score at diagnosis, coresident status, care unit, depression, fracture, Charlson Comorbidity Index score, medications (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), β-blocking agents, calcium channel blockers, nonsteroidal anti-inflammatory drugs, diuretics, lipid-modifying agents, antiplatelets, antipsychotics, anxiolytics, and hypnotics)

Fig. 3

Estimated MMSE trajectories across antidepressant classes and individual drugs^a. Abbreviations: SveDem, the Swedish Registry for Cognitive/Dementia Disorders; CIs, confidence intervals; MMSE, Mini-Mental State Examination; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin and norepinephrine reuptake inhibitors; TCAs, Tricyclic antidepressants; Others, other antidepressants. ^a, Estimated MMSE trajectories from mixed model, adjusted for age, sex, calendar year of diagnosis, the type of dementia, MMSE score at diagnosis, coresident status, care unit, depression, fracture, Charlson Comorbidity Index score, medications (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), β-blocking agents, calcium channel blockers, nonsteroidal anti-inflammatory drugs, diuretics, lipid-modifying agents, antiplatelets, antipsychotics, anxiolytics, and hypnotics)