Research report Antidepressants and dementia Lars Vedel Kessing a, ⁎, Lars Søndergård a , Julie Lyng Forman b , Per Kragh Andersen b a Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Denmark b Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark article info abstract Article history: Received 6 October 2008 Received in revised form 19 November 2008 Accepted 19 November 2008 Available online 12 January 2009 Background: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. Method: Linkage of registers of all prescribed antidepressants and diagnoses of dementia in Denmark during a period from 1995 to 2005. Results: Persons who purchased antidepressants once (N =687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N = 779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non-SSRI antidepressants and older antidepressants). All findings were replicated in sub-analyses with Alzheimer's disease as outcome. Limitations: Methodological reasons for the findings cannot be excluded due to the non- randomized nature of data. Conclusions: Continued long-term antidepressant treatment was associated with a reduced rate of dementia, however, not to the same level as the rate for the general population. © 2008 Elsevier B.V. All rights reserved. Keywords: Antidepressants Depressive disorder Dementia Alzheimer's disease 1. Introduction Studies suggest that depressive disorder is associated with increased risk of developing cognitive dysfunction (Kessing, 1998; Castaneda et al., 2008) and eventually dementia (Kessing et al., 1999; Kessing and Nilsson, 2003; Ownby et al., 2006) and that this risk increases with every new affective episode (Kessing, 1998; Kessing and Andersen, 2004). On the other hand, antidepressants may have neuroprotective abilities by increasing the proliferation of neural progenitors in the subgranulate zone of the hippo- campus as well as the survival of these newborn neurons (Dranovsky and Hen, 2006; Banasr and Duman, 2007) and therefore improve memory processes and cognition (Schmitt et al., 2006). Further, it has been suggested that treatment with an SSRI may improve cognitive function and daily living in patients with Alzheimer's dementia (Mowla et al., 2007). However, the association between antidepressant consump- tion and the risk of developing dementia has never been investigated. It would be difficult to undertake a prospective longitudinal and controlled study investigating this associa- tion as a large number of patients with depression without symptoms on dementia and with and without antidepressant treatment would had to be followed longitudinally for at least 5–10 years. An alternative approach is to use register-based data as done in the present study. We hypothesized that continued treatment with antidepressants decreases the risk of developing dementia. The aim of the present study was to investigate whether continued treatment with antidepressants is associated with reduced risk of dementia by linkage of Danish nation-wide Journal of Affective Disorders 117 (2009) 24–29 ⁎ Corresponding author. Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen Ø, Denmark. Tel.: +45 3545 6237; fax: +45 3545 6218. E-mail address: lars.kessing@rh.dk (L.V. Kessing). 0165-0327/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2008.11.020 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad