Research report
Antidepressants and dementia

https://doi.org/10.1016/j.jad.2008.11.020Get rights and content

Abstract

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.

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 hippocampus 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 consumption and the risk of developing dementia has never been investigated. It would be difficult to undertake a prospective longitudinal and controlled study investigating this association 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 registers of all prescribed antidepressants and all diagnoses of dementia given at hospital in- or outpatient settings in Denmark. It was hypothesized that 1) the use of antidepressants is associated with increased risk of dementia (as depressive disorder is associated with dementia) 2) continued treatment with antidepressants is associated with a decreased risk of developing dementia and further that 3) the risk of dementia decreases with the number of prescriptions of antidepressants.

Section snippets

The registers

Data were obtained by linking Danish population-based registers using the unique personal identification number, which is assigned to all 5.3 million persons living in Denmark, thus ensuring accurate linkage of information between registers, irrespective of changes in name etc. (Malig, 1996). In this way, the Medicinal Product Statistics (Danish National Board of Health, 2002) was linked with the Danish Medical Register on Vital Statistics (Juel and Helweg-Larsen, 1999), the Danish National

Results

During the study period from January 1, 1995 to December 31, 2005 a total of 1,467,383 persons who were older than 40 years were included in the study. Among the included persons, 687,552 persons purchased antidepressants at least once (exposed) and 779,831 persons did not purchase antidepressants (unexposed) according to data from the Medicinal Product Statistics. Characteristics of persons exposed and unexposed to antidepressants can be seen from Table 1. Table 2 shows the use of various

Discussion

This is the first study investigating the association between continued treatment with antidepressants and the risk of subsequently developing dementia. We confirmed our first hypothesis but not, or only partly, our second and third hypotheses, i.e., 1) the use of antidepressants was associated with increased risk of dementia but 2) continued treatment with antidepressants was not systematically associated with a decrease in the risk of developing dementia and 3) the risk of dementia did not

Role of funding source

Nothing declared.

Conflict of interest

No conflict declared.

Acknowledgement

Lars Vedel Kessing had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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