Steven
Any thoughts on LEF comments:
"There is a chemical made in the brain called glial cell-line derived neurotrophic factor
(GDNF). It typically aids the survival of neurons after injury. The
problem is that it also helps brain tumor cells survive, and, in
particular, gliomas. It also helps tumor cells migrate and invade
surrounding brain tissue (Lu DY et al 2010, Song H et al 2006, Wan G et
al 2010).
Many antidepressants increase GDNF and thus may help tumor cells
survive treatment. A 2007 paper reported that amitriptyline, a tricyclic
antidepressant, did so (Hisaoka K et al 2007). Serotonin itself
increases GDNF (Tsuchioka M et al 2008). Antidepressants classified as
selective serotonin reuptake inhibitors (SSRIs) which increase serotonin
levels in the brain, may therefore increase GDNF, increasing tumor
survival and helping it spread further into the brain."
My thinking is based on the data available, prozac and sertraline, both being SSRI's seem to have an effect different than being suggested here and at this point the "proof" of negative vs positive effects from these SSRI's is in favor of benefit.
GDNF indeed has pro-tumor activity. It is an attractant for microglia, which aid tumor expansion by releasing pro-invasive factors etc. Genetic knockdown of GDNF improved survival in the GL261 mouse glioma model.
ReplyDeleteHowever, in at least one clinical study, sertraline did not increase GDNF:
http://www.ncbi.nlm.nih.gov/pubmed/25172025
The key words in the LEF article is "may therefore increase", not the same as DOES increase.
I would agree with your conclusion, at least for fluoxetine, that the weight of evidence is on the favorable side. I haven't seen sertraline tested in an intracranial glioma model.