Posted by linkadge on August 23, 2018, at 14:18:07
In reply to Re: carbamazepine (tegretol) for social anxiety, posted by farshad on August 23, 2018, at 8:16:19
>last left is the crh-crhr1 system
Not really. The brain has neurotransmitters / neuromodulators that we don't even know about yet!
There are literally thousands of signaling molecules in the brain that could get out of whack in depression. Endocannabinoids, PEA, trace amines, CCK, substance P, TREK, NPY, neurohormones, neurotrophins (BDNF, GDNF, NGF, NT-3) protein kinases, GSK3, AMPA, NMDA, Ion channels (sodium, calcium, potassium), 2nd messengers, IP3, opioid (sigma, delta, kappa, mu), sigma receptors (sig1/2), monoamine oxidases, individual receptor dysregulation, plus a kazillion more that I can't list (or that we don't have drugs that directly target).We know, perhaps, 1% of the mechanisms and targets of the medications we take. The medications were discovered by their effects, not their mechanisms. It is only after the fact, that we try and pin down the effects. We may discover one target or another, but, in many ways, we have a very incomplete picture of how the drugs actually work.
For example, it was only discovered a few years ago that amitriptyline acts as a direct trk-b agonist. This is despite several decades of clinical use as a very effective antidepressant. We knew it worked as an antidepressant, but didn't fully know (and still don't fully know) how.
Why is nortriptyline (a NRI) a very effective antidepressant, yet atomoxetine (a NRI) not? On paper, they should both work the same, but they don't.
CRH blockers have been developed and tested as treatments for anxiety and/or depression. However, despite much clinical research, they don't show much effect vs. placebo.
There are feedback loops for the CRH - ACTH - cortisol system. ACTH itself, for example, can suppress CRH. Also, ACTH stimulates DHEA release. DHEA tends to be low in depression. DHEA promotes neurogenesis, has antidepressant effects (through sigma-1r) and may itself help regulate cortisol.
Effective treatments for anxiety / depression can strengthen this feedback loop without directly supressing CRH. In other words, you're not supressing the whole system, as cortisol is critical for regulating energy and its release can actually help extinguish fears.
Again, I'm not saying don't try carbamazepine. It may work well. I'm just saying that you can't just focus on one target of the drug and use process of elimination. We don't know all the targets of the drugs. We don't know all the causes of depression / anxiety. It's not like you can go through a checklist (serotonin, norepinephrine, dopamine, gaba, CRH, etc. etc. to find what is wrong). This process *may* work for some, but again, most drugs are not selective.
When you change serotonin, you change everything. An SSRI indirectly affects norepinephinre, dopemine, cortisol, melatonin, glutamate, gaba, you name it. Likely everything changes. Is it the serotonin, or is it a downstream effect? Who knows. Perhaps somebody had high glutamte, or hight norepinephrine (not low serotonin) and the SSRI helped lower these, leading to improvement.
Linkadge
poster:linkadge
thread:1100299
URL: http://www.dr-bob.org/babble/20180728/msgs/1100557.html