The use of antidepressants for patients with dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. Many of the individual trials of antidepressants have been too small to provide precise estimates of the moderate benefits that might realistically be expected. Combining the information from all appropriate trials may provide a better estimate of the likely effects of treatment.
To determine whether antidepressants are clinically effective and acceptable for the treatment of patients with depression and also dementia.
The CDCIG Specialized Register was last searched on 27 April 2005. This register contains records from major health care databases and many ongoing trials databases and is updated regularly. Medical information departments of pharmaceutical companies were asked to search their databases for any relevant clinical trials. Where necessary authors of trials were approached with requests for additional information.
All relevant unconfounded, double-blind, randomized trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression, according to established criteria.
Data collection and analysis
Two reviewers extracted data independently and settled any differences by agreement.
There were seven included studies with a total of 1140 subjects of which 769 met inclusion criteria. Four included studies reported sufficiently detailed results to enter into meta-analyses, with a total of 137 subjects. Two of these studies investigated the properties of drugs not commonly used in this population with only two studies (Petracca 2001and Lyketsos 2003) using the more common selective serotonin reuptake inhibitors (SSRIs). Lyketsos 2003 produced two significant differences in favour of treatment in the Cornell Scale for Depression in Dementia (CSDD) at 12 weeks and in the psychiatrists’ global rating. However, the CSDD was not used in any of the other studies and no statistical differences were found with the other measures used in the meta-analysis. The meta-analysis of the number of patients suffering at least one adverse event, one event of the nervous system, one event of the gastrointestinal system and one event of dry mouth at 6 to 12 weeks showed a significant difference in favour of placebo. There were no other significant results.
Available evidence offers weak support to the contention that antidepressants are effective for patients with depression and dementia. However, only four studies are included in the meta-analysis relating to efficacy, and sample sizes are small. Moreover, only two included studies investigated the properties of the more commonly used SSRIs and no studies investigated the properties of newer classes of antidepressants (e.g. selective noradrenergic reuptake inhibitors). This review draws attention to the paucity of research and evidence in this area.
Plain language summary
Insufficient evidence for the efficacy and safety of antidepressants for depression in dementia
Depression is common in people with dementia and many patients are prescribed antidepressants. Current evidence offers only weak support for this practice. However, this conclusion is based on a very small number of studies with small sample sizes, predominately investigating classes of antidepressants not routinely used in clinical practice. Perhaps the main value of this review is to draw attention to this issue. It is not that antidepressants are necessarily ineffective but rather that there is not much evidence to support their efficacy. Given that they may produce serious side-effects clinicians should therefore prescribe with due caution.