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Re: Which antidepressants are 'less' activating? Lamdage22

Posted by Mtom on August 27, 2021, at 10:06:26

In reply to Re: Which antidepressants are 'less' activating?, posted by Lamdage22 on August 27, 2021, at 7:21:24

> Even the less activating antidepressants activate me enough. Tend to tolerate them much better. I actually take Trazodone in the daytime without any sleepyness.

So interesting and inexplicable how we all react so hugely differently to the same medication. I took very low dose Trazodone briefly about 5 years ago when going through a period of nightly insomnia (waking at 2 and unable to get back to sleep). Doctor said dose was too low to have any antidepressant side effects, but I did. I slept through the night but upon waking my anxiety skyrocketed, felt spacey (not tired) all day, really intense Tinnitus and other stuff I cant remember.

SSRIs, even at low doses, also skyrocket my anxiety even more along with agitation and jitteriness. Also cause Tinnitus (not quite as intense as Trazodone) and at moderate doses sleep disturbances, nightmares, restless legs at night, and others.

Mirtazapine is somewhat more tolerable, if I keep the dose low. But still get a variety of side effects, and only partial response. Higher (still quite low) doses make me feel ill in a way thats difficult to describe, and also increase my anxiety I suspect the Norepinephrine/Noradrenaline affect kicks in too much when I increase the dose. Or maybe the Serotonin effect gets too strong (considering my intolerance to SSRIs).

I wonder if in some of us Serotonin is not the issue at all and if so, increasing Serotonin activity not only is ineffective but brings on adverse effects.

Also Im sure individual genetics come into play. Interestingly I had Genetic testing for medications 3 years ago, I am an intermediate metabolizer for the liver P450 CYP2D6 enzyme (1 active and 1 inactive allele) which, puzzlingly, is not thought to be the main metabolic route for Citalopram or Escitalopram which I could not tolerate, but is the major enzyme metabolizing Mirtazapine which I tolerate better.

One important enzyme in metabolism of about 60% of all drugs is CYP3A4 and they did not test for that. Explanation was that there are too many variations/mutations in the populace for this enzyme and inadequate data on most of them to draw any conclusions. This is the enzyme that is inhibited by Grapefruit and thus why people on certain medications are told to avoid grapefruit or juice.

Many drugs are also inhibitors of the various P450 CYP Enzymes which effectively could increase drug concentrations by slowing down their metabolism. Im reading increasing numbers of papers discussing drug interactions (not just with Antidepressants), and the general lack of knowledge about these.

The Genetic report did not show I would have any issues with Citalopram or Escitalopram, which I did. Data was pretty limited though e.g. as above they dont test for or even yet know all the genes involved in drug metabolism and adverse effects.

My Doctor spoke to others at Conferences about these genetic tests, and while they show great promise for the future of personalized medicine, she found the consensus generally seems to be that right now theyre not quite ready for prime time. Two PDocs I talked to a couple of years ago didnt even know these tests existed.




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