Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer
It noted that hormone therapy (like first gen Lupron) has a higher incidence of depression as a side effect but that the 2nd-generation meds for castration-resistant cases is even worse. This goes to my and several other posts concerning depression from ADT.
From the paper: "Conclusions and relevance: In this cohort study, patients with prostate cancer who received a second-generation AA had a large and clinically significant increased risk of depression compared with patients who received traditional HT alone or no HT, including when limiting our analysis to individuals with metastatic disease at diagnosis."
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maggiedrum
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From the article you note: "Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity."
I am not an expert but have been studying depression for decades. One thing that can be said about it is that blanket statements can never be used in any discussion about it. There is absolutely no agreement on what causes it or how to best treat it. My personal experience, backed up by some of the posters here, suggest that hormones outside of the nervous system may have a bigger impact on depression than do the "usual suspect" - serotonin, dopamine, etc.
This is too large and complicated an area to really even scratch the surface of cause and effects of depression and all the types of depression. What I have tried to point out is that I have experienced severe depression directly related to my ADT. And others on here have had similar experiences. But anecdotal experiences do not a conclusion make.
Low serotonin in depression is a myth. The evidence is pretty clear, there’s not a deficit—there’s an excess. Findings from a study that measured metabolite levels from blood in the brain, which indicate how much serotonin the brain is using.
Results from this study revealed that serotonin levels were elevated among those with clinical depression, and returned to normal levels following medication treatment. Other studies (e.g., Gjerris et al., 1987, and Sulllivan et al., 2006) using different methods have found similar results.
These findings sound paradoxical, given that depression medications tend to increase the amount of serotonin in the synapse, at least initially. But they within a week to ten days, you increase the amount of serotonin so high that the regulatory mechanisms push back. As a result, serotonin levels fall. It’s like holding a match up to a thermostat to turn the furnace down, You’re tricking the system into kicking back in and regulating serotonin levels.
Like smutaw, estradiol has helped me so much. I started zytiga-pred in April because I seem to be deeper in the woods now, and everything is a bit harder. I feel discouraged from time to time, but fortunately no depression.
One of the side effects of my depression is that it demotivates me to get exercise on purpose. I do fine when I get good exercise as part of a project, or yard work, or hiking. I get bored walking around on streets. But the real problem is the feeling of fatigue (not psychosomatic I assure you). Depression affects your body, including the muscles and nervous system, as well as the upper level cognition system. Someone with severe depression cannot necessarily force themselves to get regular exercise. I try walking a few miles each week. I no longer bike because of my balance issue. I never run because of my knees, nor do I hike in the mountains nor ski, two of my previously most favorite forms of exercise. I find just getting outside in sunshine helps as much as exercise so both together is the best possible tonic.
I'm really sorry about the balance issues, because your activities are all the ones that I partake in. Except my bike has a motor. I've been working with my therapist and find that what's helping me most right now, is trying to learn new things, or re-learn a couple of old things I have dropped. This is engaging my mental processes and my cognitive abilities and I find myself much more willing to go out to do things. I'm still considering exercise on purpose, but I live in the Northwest USA and the winters here are the time I'll really need that exercise. Outdoors for the time being is really good!
I'm sorry about your depression. You're doing what you can, as much as you can. The air and sun I'm a little envious of this time of year, I spend too much time indoors, very hot and humid here. So that's my weakness. Stay with it!
My MO never brought up the possibility of using estradiol in counteracting my depression. I am seeing him for the last time next week and I will ask him why. I also want to know why he undervalued my concerns about my depression getting much worse on ADT.
I've been working with a therapist since starting ADT - I'd really rather not deal with many of the pills (I take so many already) or the estrogen, but I have also read that the estradiol may help with the hot flashes which are truly bad for me. I agree with the sentiment that unless you have experienced it...
Depression is a natural reaction to life; for some of us it's worse than for others. It's just one more thing to deal with.
The existential reaction to knowing you have cancer is completely understandable. Depression is more mysterious than it used to be. It's no longer a chemical imbalance necessarily and scientists aren't sure why anti-depressant medications work.
Given the choice between adapting medications to the cancer and being more depressed and just giving up and letting the cancer run its course, I'd take the former.
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Timing is everything with docetaxel (and hormone therapy and probably with immunotherapy and radiopharmaceuticals too)
1/4 dose enzalutamide for MCRPc working for 4 years in 87 yr. old
FYI: from the VA research information on Veterans 
Masofaniten +Enzalutamide This could be a game changer...Science is coming to our aid
