Effects of Antidepressant Drug Classes on Dementia Risk: A 23-Year Cohort Study Using Akrivia Health Secondary Mental Health Data
Author(s)
Panagiota Kontari, PhD1, Maxime Taquet, PhD, MD2, Will Pettersson-Yeo, PhD, BM BCh2, Judith Harrison, MBChB MRCPsych PhD3, Ana Todorovic, PhD1, Sophie Turner, MSc1, Dalila Monica Moisescu, MPhil1, Ceyda Uysal, MSc1, Benjamin Fell, PhD1.
1Akrivia Health, Oxford, United Kingdom, 2Oxford University, Oxford, United Kingdom, 3Newcastle University, Newcastle, United Kingdom.
1Akrivia Health, Oxford, United Kingdom, 2Oxford University, Oxford, United Kingdom, 3Newcastle University, Newcastle, United Kingdom.
OBJECTIVES: Depression has been suggested as a modifiable risk factor for dementia. However, the impact of different types of antidepressants on dementia risk remains unclear. This study aims to assess the effects of different antidepressant drug classes on dementia risk, exploring the potential for drug repurposing as a risk reduction strategy.
METHODS: Using Akrivia Health’s database of anonymised electronic secondary mental healthcare records for 6.3 million patients in the UK, we identified individuals with major depressive disorder (MDD) diagnosed between January 2000 and April 2023, aged 40 or older at diagnosis, without comorbid bipolar disorder and/or schizophrenia, and dementia-free two years post-diagnosis. Patients were grouped into seven categories based on treatment type: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), other antidepressants, combined pharmacotherapy (≥ 2 antidepressants), and untreated patients as reference. Cox proportional hazards regression models estimated hazard ratios (HR) for dementia, adjusted for age, gender, and ethnicity.
RESULTS: A total of 57,713 individuals were included in the analysis (59% female, mean [SD] age: 67.7 [10.7]), with 6,904 (12%) developing dementia over a median follow-up of eight years. All antidepressant treatments, particularly MAOIs (HR=1.78, 95% confidence interval [CI] 1.18−2.69) and TCAs (HR=1.68, 95% CI 1.43−1.97), were associated with a significantly higher dementia risk compared to untreated patients. TCAs conferred a significantly greater risk than SSRIs (HR=1.27, 95% CI 1.18−1.35) and SNRIs (HR = 1.31, 95% CI 1.18−1.45).
CONCLUSIONS: This study shows that antidepressants, particularly MAOIs and TCAs, are linked to an increased risk of dementia, potentially due to anticholinergic effects of these antidepressants and residual confounding related to depression severity. Further research is needed to clarify drug-specific pathways and co-medication effects to help clinicians balance the benefits of depression treatment with the risk of dementia.
METHODS: Using Akrivia Health’s database of anonymised electronic secondary mental healthcare records for 6.3 million patients in the UK, we identified individuals with major depressive disorder (MDD) diagnosed between January 2000 and April 2023, aged 40 or older at diagnosis, without comorbid bipolar disorder and/or schizophrenia, and dementia-free two years post-diagnosis. Patients were grouped into seven categories based on treatment type: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), other antidepressants, combined pharmacotherapy (≥ 2 antidepressants), and untreated patients as reference. Cox proportional hazards regression models estimated hazard ratios (HR) for dementia, adjusted for age, gender, and ethnicity.
RESULTS: A total of 57,713 individuals were included in the analysis (59% female, mean [SD] age: 67.7 [10.7]), with 6,904 (12%) developing dementia over a median follow-up of eight years. All antidepressant treatments, particularly MAOIs (HR=1.78, 95% confidence interval [CI] 1.18−2.69) and TCAs (HR=1.68, 95% CI 1.43−1.97), were associated with a significantly higher dementia risk compared to untreated patients. TCAs conferred a significantly greater risk than SSRIs (HR=1.27, 95% CI 1.18−1.35) and SNRIs (HR = 1.31, 95% CI 1.18−1.45).
CONCLUSIONS: This study shows that antidepressants, particularly MAOIs and TCAs, are linked to an increased risk of dementia, potentially due to anticholinergic effects of these antidepressants and residual confounding related to depression severity. Further research is needed to clarify drug-specific pathways and co-medication effects to help clinicians balance the benefits of depression treatment with the risk of dementia.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EPH70
Topic
Epidemiology & Public Health, Methodological & Statistical Research
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Geriatrics, Mental Health (including addition), Neurological Disorders