i agree with all you said. i just wanna say this about fluoxetine as i have trialed it, and i dont like the fact it takes such a long time to notice either negative or positive effect and all SSRIs are guilty of this delay bullshit. i believe an antidepressant should be instant! like for example, alcohol cigs opiates and various psychedelics where they work quite fast as antidepressants BUT being addictive and detrimental in nature are logically not recommended long term. but do we really have to step so low as to take a drug for weeks to feel better? that is NOT PROGRESS.
i have been exploring new antidepressant territories relation to this and it seems NMDA antagonists like DXM and ketamine are the way to go. one dose, it works fast, and it lasts long. problem is, one is only present in cough syrups and has bad reputation and the other is not available commercially yet, and it might take years to release. but from what i researched, lots of research is being put into NMDA dysregulation and fix as antidepressant action and i wanna put money on those as future antidepressants and i hate anything made so far honestly
You have lots of company in your dissatisfaction with the current state of the art. This is one reason there is so much interest in and research devoted to finding better treatments, from TMS to NSI-189. That's par for the course for treatment of most chronic disease; treatments for things like cancer, diabetes, etcetera also leave a lot to be desired. For clinical depression, we would like to have something that works instantly and permanently.
Simultaneously meeting those last two goals though may be a tough nut to crack. We get the feeling there may be a fundamental conflict lurking in there. There seems to be a pattern ... things that make you feel better right way, like opioids, wear out fast and cause longer term problems. The system adjusts to them, and ever escalating doses are required just to maintain effect, and at some point you run into toxicity. A similar things happens with anxiety drugs; the system quickly adapts to the ones that work the best and before long tolerance and addiction sets in. The underlying mechanism is homeostasis, a tendency for living systems to restore equilibrium when disturbed by an outside influence. The flip side of this is that things that work long term are just generally not likely to be effective right away.
This might even be intrinsic to the mechanism of serotonergic drugs. Some researchers, for example Wiley and Formby in the book Lights Out, contend that serotonin is not the "happy" neurohumor it's assumed to be. That to the contrary, serotonin is a downer. They suggest that SSRIs work by increasing serotonin, forcing the homeostatic mechanism to cut back. At first you have an excess of serotonin, making you even more depressed, until the homeostatic response kicks in and reduces it so that you become less depressed. Then because you have homeostasis working in your favor instead of against you, the therapeutic response is more sustainable. Others have theorized that the serotonin surge works by spurring neurogenesis, which also also intrinsically takes time to work. So even drugs that target neurogenesis, like NSI-189, are also inherently going to take time to get up to power.
Technological development may yet find ways to mitigate this short-term-long-term tradeoff, maybe through multimodal strategies. I just wouldn't expect a whole lot of progress any time soon, especially with the glacial pace imposed by government regulation. And probably the whole model of jostling around neurotransmitters will have to be superseded by a new paradigm before much more progress is made.
You have lots of company in your dissatisfaction with the current state of the art. This is one reason there is so much interest in and research devoted to finding better treatments, from TMS to NSI-189. That's par for the course for treatment of most chronic disease; treatments for things like cancer, diabetes, etcetera also leave a lot to be desired. For clinical depression, we would like to have something that works instantly and permanently.
Simultaneously meeting those last two goals though may be a tough nut to crack. We get the feeling there may be a fundamental conflict lurking in there. There seems to be a pattern ... things that make you feel better right way, like opioids, wear out fast and cause longer term problems. The system adjusts to them, and ever escalating doses are required just to maintain effect, and at some point you run into toxicity. A similar things happens with anxiety drugs; the system quickly adapts to the ones that work the best and before long tolerance and addiction sets in. The underlying mechanism is homeostasis, a tendency for living systems to restore equilibrium when disturbed by an outside influence. The flip side of this is that things that work long term are just generally not likely to be effective right away.
This might even be intrinsic to the mechanism of serotonergic drugs. Some researchers, for example Wiley and Formby in the book Lights Out, contend that serotonin is not the "happy" neurohumor it's assumed to be. That to the contrary, serotonin is a downer. They suggest that SSRIs work by increasing serotonin, forcing the homeostatic mechanism to cut back. At first you have an excess of serotonin, making you even more depressed, until the homeostatic response kicks in and reduces it so that you become less depressed. Then because you have homeostasis working in your favor instead of against you, the therapeutic response is more sustainable. Others have theorized that the serotonin surge works by spurring neurogenesis, which also also intrinsically takes time to work. So even drugs that target neurogenesis, like NSI-189, are also inherently going to take time to get up to power.
Technological development may yet find ways to mitigate this short-term-long-term tradeoff, maybe through multimodal strategies. I just wouldn't expect a whole lot of progress any time soon, especially with the glacial pace imposed by government regulation. And probably the whole model of jostling around neurotransmitters will have to be superseded by a new paradigm before much more progress is made.
