6 ms·

> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. As an obese depress

> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. 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.

IX-103 2y ago
Yeah, the new "weight-loss" drugs seem to have significant psycho-active effects on the dopamine reward pathway. That seems like it may provide a more direct treatment than SSRIs.
- deleted 2y ago
  [deleted]
- arcticbull 2y ago
  Yeah calling them weight-loss drugs seems to really be under-selling them. I suspect the anti-depressant action has more to do with BDNF-TrkB and IL-6 signaling though!
arcticbull 2y ago
Yep they do, in part because of the depression-obesity axis but also likely via an independent mechanism. They do a couple of interesting things. For one, they seem to have a systemic anti-inflammatory effect. They lower the levels of TNF-alpha and interleukins like IL-6. High levels of TNF-alpha and IL-6 are implicated in depression. > 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 https://www.nature.com/articles/s41598-025-85514-0 [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ [3] https://www.cambridge.org/core/journals/cns-spectrums/article/therapeutic-possibility-of-semax-for-depression/E2293226BFBE224272AA7C8CE60AD7C0 https://www.cambridge.org/core/journals/cns-spectrums/articl... [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/

IX-103 2y ago

Yeah, the new "weight-loss" drugs seem to have significant psycho-active effects on the dopamine reward pathway. That seems like it may provide a more direct treatment than SSRIs.

deleted 2y ago
[deleted]
arcticbull 2y ago
Yeah calling them weight-loss drugs seems to really be under-selling them. I suspect the anti-depressant action has more to do with BDNF-TrkB and IL-6 signaling though!

arcticbull 2y ago

Yep they do, in part because of the depression-obesity axis but also likely via an independent mechanism. They do a couple of interesting things. For one, they seem to have a systemic anti-inflammatory effect. They lower the levels of TNF-alpha and interleukins like IL-6. High levels of TNF-alpha and IL-6 are implicated in depression. > 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 https://www.nature.com/articles/s41598-025-85514-0 [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ [3] https://www.cambridge.org/core/journals/cns-spectrums/article/therapeutic-possibility-of-semax-for-depression/E2293226BFBE224272AA7C8CE60AD7C0 https://www.cambridge.org/core/journals/cns-spectrums/articl... [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/