> Various meta-analyses have consistently reported increased IL-6 and TNF-α concentrations in depressed patients compared to healthy controls. IL-6 and TNF-α are associated with specific symptoms and behaviors that co-occur with depression. [1]
They also increase the levels of brain-derived neurotrophic factor (BDNF) and BDNF-TrkB signalling is also implicated in depression, especially major depression. [2]
Second, GLP-1 RAs yield similar changes in BDNF, TNF-alpha and interleukin levels you see in atypical antidepressants and anxiolytics like the old Soviet-era Semax [3] and Selank [4]. The former is a peptide analog of ACTH and the latter a peptide analog of tuftsin. Consequently it makes perfect sense to me that GLP-1 RAs would also have atypical antidepressant activity via the same pathway.
There's a lot more to GLP-1 RAs and depression than just making you feel better about yourself as a result of your weight loss, and I suspect we're going to hear a lot more about this in the coming years.
They also get you to the point where you feel good enough to exercise, which increases the levels of serotonin, dopamine and noradrenaline, and is also as effective as antidepressants. Unfortunately, depressed people can't bring themselves to exercise. Breaking that cycle so you can and do can only help more.
I've done a lot of digging on all this stuff over the last few years, it's really fascinating.
tl;dr: There's definitely something to your lived experience. Congratulations on getting started on your journey.
[1] https://www.nature.com/articles/s41598-025-85514-0
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/
[3] https://www.cambridge.org/core/journals/cns-spectrums/articl...
As an obese depression-sufferer currently taking Mounjaro, these new weight loss drugs seem way more effective at treating the depression than SSRIs.
Actually losing a bit of weight with previously-unimaginable ease actually offers some genuine hope. It's not quite a miracle drug, the side-effects can be unpleasant, but when you're severely overweight they seem a small price to pay.