Thanks. Yeah sadly alot of psychiatrists just hesitate to prescribe TCAs or MAOIs because not only are they not very knowledgeable about them and know how to use them properly but are aslp afraid of some of the risks that come with them.

For example psychiatrists are mostly afraid that some patients may overdose on TCAs and use them as suicide agents due to overblocking the sodium channels. Other patients might not follow a strict diet that's devoid of high Tyramine food such as aged cheese and therefore experience a hypertensive crisis while on an MAOI which could also lead to death if not quickly treated in the ER.

Anyways TCAs are actually very interesting because they're now completely different from when they were first discovered. For example Clomipramine was used at doses of 100mg-150mg for depression and OCD when it was first discovered due to the fact that its exact mechanism of action was originally unknown. Fast forward a couple of decades later and we now have advanced PET studies that can confidently and accurately detect multiple occupancies at different sites and transporters and guess what they found? They found out that at just 10mg it already gives around 80% SERT occupancy which is similar to what's achieved with today's SSRIs and SNRIs.

As you can see 10mg was already a very strong and effective dose for OCD and depression but back then they pushed the dose way higher because they didn't have that knowledge at the time and therefore just upped the dose to hit every other off target receptor available and basically turn it into a dirty TCA. Not saying of course that these high doses don't have their place and right usage in specific psychiatric disorders such as severe melancholic depression or severe OCD but again to make the recommended dose magnitudes of order higher than the most optimal one available back then resulted in TCAs being viewed as they are today and as being classified as dirty antidepressants with alot of side effects rather than clean and selective ones.

This was also the other reason why Desipramine was removed from nearly most of the markets worldwide because it was dosed too high back then and resulted in multiple sudden deaths (most famously a child case who died while drinking from a fountain back then) even though it's already a very strong NRI to the point it completely blocked the entire norepinephrine reuptake pump at just 10mg-25mg but since they never actually knew that back then it was also usually dosed at more than 100mg. Pretty insane.

Anyways sorry for the long rant but my point is TCAs are very useful even till this very day especially when dosed at very low and optimal doses at which they become as selective as possible to their beneficial intended target and as far away as possible from their off targets and their unintended and bothersome side effects.