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  1. Nik Bhandari


Objective In the last 2 decades, data from neuroimaging and post-mortem studies has consistently demonstrated that postsynaptic receptor deficits in Frontotemporal dementia (FTD) specifically affect the serotonergic system. This contrasts with multi-receptor pathology seen in other types of dementia. Further, the behavioural symptoms of FTD are similar to the ones seen in functional psychiatric disorders such as depression and obsessive-compulsive disorder. The neural pathways linked to such behavioural symptoms rely on serotonin, and hence a decrease in serotonin system function is associated with decreased frontal activity and mood dysfunction, while serotonergic drugs tend to improve these symptoms. Thus, there is a need to systematically study the evidence for the drugs which explicitly target the dysfunctional serotonergic system in FTD, and which have shown improvement in functional psychiatric disorders presenting with similar behavioural symptoms. The systematic review aims to assess the efficacy and safety of serotonergic drugs for treatment of behavioural symptoms of FTD.

Method A systematic review of all available primary data on the topic was done. Records from health care databases, ongoing trials and grey literature were checked, and relevant articles reviewed. The data was collected and analysed using RevMAN software tool from the Cochrane Collaboration.

Results All the 10 studies included in the review were prospective studies, of which 4 were placebo-controlled and 3 had double blind and cross-over study design. The 10 studies trialled 6 serotonergic drugs, on a total of 214 subjects. 9 of the 10 studies showed improvement in FTD symptoms, with statistically significant improvement in total NPI score recorded in 7 studies. Trazodone showed improvement in all 4 studies in which it was tested, though significant improvement was noted in 3 of the studies. Paroxetine showed significant improvement in 2 out of the 3 studies. Fluvoxamine and Citalopram showed significant improvement in the 1 study each. The overall effect size for serotonergic drugs (Paroxetine and Trazodone) in comparison with placebo was not significant, with value of −2.38 (−5.21, 0.45). The serotonergic drugs were well tolerated in all the included trials.

Conclusion The systematic review provides evidence for use of serotonergic drugs for management of behavioural symptoms of FTD, though the overall effect size for the drugs was found to be statistically non-significant. There is paucity of research data on the topic, and scope for evidence from large pragmatic randomised controlled trials, to further inform clinical practice.

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