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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 3 of 3. This is the beginning of the thread.
Posted by jay2112 on July 6, 2021, at 23:20:04
Ever since the advent of SRI's, it seems much research has intensified, and concluded, that SRI's are highly effective for depression/anxiety. Yet, newer research (post-2010) suggests they are only about 40 percent effective, after a full-length trial. Many people complain of the 'flatness', and lack of affect.
For myself, on a full course of all SRIs, I was scared to go outside, and laid in my bed, whenever (at all hours) I was at home, feeling dead, and ruminating about *anything and everything*, glossy eyed, staring at the ceiling. I was scared to take a shower, take out the garbage, heck, do anything!! It was just bland, still scared though, to even have ANY social contact. Benzo's just dulled everything even more.
OK, that is just anecdotal, my experience. But, I have read the many mental health message boards, and on social media, and for the most part, doctors still cram SRI's on patients. SNRI's, Effexor, helped a wee bit more. But, eventually, it gave that SRI effect of feeling trapped in my body, with maybe a spurt here or there, but not much. Even Pristiq, and Cymbalta, did exactly the same thing.
It was weird when I tried 5HTP multiple times. It intensified that 'spidey tingling sense', where I could intensely feel ANY stimuli. Interesting, because that is the same description for what people feel, who are Autistic/Aspergers..the Autism Spectrum Disorders. Too much serotonin, called Hyperserotonemia, has been rigorously, scientifically implicated in Autism and ASD related. I have worked with, and university researched, people with Autism for decades. As researchers have described it, Autistic people have those 'tingling spidey senses', and feel EVERYTHING social and stimuli, intensively..which is an understatement. It leads to Autistic people experiencing off-the-charts anxiety, and as a result, anti-social behaviour, isolation, rage, meltdowns..etc. The two drugs found highly, scientifically efficacious for Autism, are risperidone and nefazodone. The reason: very strong 5ht2c antagonism of both drugs, which results in a slight dopamine increase, and slightly reduced serotonin levels overall. It seems that 5htc receptor is the culprit, but Autistic people have overall increased serotonin receptor sensitivity.
As well, in a peer-reviewed finding that I posted before, there is a very strong co-relation between pregnant mothers who take SRI's during pregnancy, and the chances of birthing a child who will develop Autism.
The takeaway: Not EVERYBODY who takes an SRI will become autistic!..lol. But, there seems to be some kind of relation between SRI's (and maybe SNRI's) and pseudo-autistic characteristics, in particular in long term, high dose cases...which could cause hyperserotonemia (not the same as serotonin-syndrome.) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824539/
Which brings me to my last point...as many clinicians have commented..serotonin is far, far from the end all and be all. As well, though, YMMV, and as well, genetics play a role in all of this, obviously, too. Maybe it is all about balance? This seems likely. There are many case examples of people combining SRI's with good old norepinephrine tricyclics, with a certain amount of success. Some, like nortriptyline, also muck around with anticholinergic, and various other neurochemicals, many with antidepressant properties as well. Imipramine still has some of the serotonin agonist properties, and desipramine just has mostly norepinephrine agonist properties. Really, as many clinicians have noted, the more chemicals you muck around with, the better outcome it often seems. Acetylcholine has been shown to be hyperactive in depressed and anxious people. Both amitriptyline and nortriptyline (a metabolite of the previous, but amitriptyline works more on serotonin...nortriptyline works on mostly norepinephrine and various smaller neurochemicals) are strong anticholinergics, calming and dampening acetylcholine, and downstream, increasing dopamine. The balancing of these, including serotonin, is some kind of key that probably leads to some other keys in a cognitive map not yet discovered. The answer might be all a combination of genetics and environment, with the use of multiple antidepressants and nootropics,, until we discover better treatments with scientific backing. But, for now, (many of us have more life behind us than ahead) we have to use the tools currently available. And, that could mean anything...microdoses of antidepressants, mdma, phycobilin, (which you can openly buy on Facebook)
etc...unique combinations...discoveries...etc.Sorry for length..I need an editor, lol.
Jay
Jay
Posted by SLS on July 7, 2021, at 7:59:52
In reply to Major Serotonin Bias..., posted by jay2112 on July 6, 2021, at 23:20:04
Hi, Jay.
The length of your post was easily readable. Perfect length for the amount of information and your thoughts.
I empathize with your plight. It is sad and frustrating for me to read about.
It is not surprising that you should have had any kind of positive response to Effexor. Are there any drugs that produced any kind of brief or mild response for you?
At the NIH, their "ace in the hole" drug was an MAOI-A *specific* (not just selective) inhibitor called clorgyline. It is still the most potent (statistically) antidepressant in the world. They no longer provide it for human consumption because of reports of treatment-emergent cardiac events. It has never been available anywhere else in the world. At a time when my depression wouldn't budge, clorgyline helped knock a few bricks out of the wall. I don't have time to research it, but it is my impression that Nardil is the closest thing to clorgyline that is still available. Because your reaction to SSRIs includes social anxiety / phobia, Nardil seems to be worth a look at. If you tried Nardil already, and experienced any kind of positive response, you might consider using it in combination with other medications. Of course, I have a bias for using this strategy because I am having such a dramatic response to it.
- Scott
Posted by linkadge on July 8, 2021, at 6:34:17
In reply to Re: Major Serotonin Bias... » jay2112, posted by SLS on July 7, 2021, at 7:59:52
Yeah, MAO-A inhibitors are really triple amine boosting drugs. MAO-A breaks down serotonin, norepinephrine and dopamine.
I have been taking licorice extract recently, which (purportedly) is one of the strongest herbal MAO-B inhibitors. It seems to be having the effect I anticipated.
Linkadge
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