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Re: Vortioxetine (Brintellix-Trintellix) SLS

Posted by undopaminergic on November 18, 2021, at 14:21:50

In reply to Re: Vortioxetine (Brintellix-Trintellix) undopaminergic, posted by SLS on November 18, 2021, at 12:21:53

> > > That's a great perspective.
> > What are you referring to?

You did not comment. I was wondering what you thought was a great perspective.

> > > Prior to the 1950s, there were no true antidepressants.
> > Well, the classification as antidepressant or something else is pretty arbitrary. For example, some primarily antihistaminic drugs have been classified as antidepressants.
> Arbitrary? In what way?

It does not always follow pharmacological facts about a compound. It "just so happens" that it is classified as one thing and not another.

> I think the most histaminergic tricyclic is doxepin. Were the clinical trial directors providing the drug company with fraudulent information when the company reported sufficient efficacy for the FDA to approve it as an antidepressant?

I'm not saying there is anything fraudulent, just arbitrary. From a look at the pharmacological profile of doxepine, it is obviously more of an antihistamine than it is any kind of antidepressant, especially if you expect such a drug to have monoaminergic actions. Yet it came to be classified as an antidepressant. That is arbitrary. I'm not saying it cannot be employed as an antidepressant.

> How many antipsychotics are histaminergic?

I have the impression that most of them are *anti*histaminergic. That is not to say they shouldn't have been approved as antipsychotics. There seems to be only one property all antipsychotics have in common, and that is dopamine D2-receptor antagonism. In other words it's not all that arbitrary to classify dopamine antagonists as antipsychotic. There are even some antihistamines (eg. promethazine) that might have been better classified as antipsychotics.

> Is the classification of quetiapine as an antipsychotic arbitrary?

Frankly, yes. It's such a weak dopamine antagonist and it is not very effective as an antipsychotic. I have it prescribed as a hypnotic as needed myself. Clozapine may be ever weaker, but it has proven very effective.

> How many drugs, after their FDA approval for one indication, were found to be effective for another indication? Drugs are repurposed all of the time.

Sure, nothing wrong with that.

> Prazosin (Minipress) was approved for hypertension decades ago. In the last 10 years, it has been used to treat PTSD, especially nightmares. I don't think the FDA has approved prazosin for PTSD yet.

No problem.

Sometimes one drug that shares most pharmacodynamic properties with another drug gets singled out and popularised for a particular purpose whereas the other drug does not. That is arbitrary.

> By the way, if you know anyone who is taking prazosin 3 mg at bedtime only for nightmares, and they suffer residual anxiety or depression during the day, prazosin can significantly relieve those symptoms by taking it 5-10 mg t.i.d. 30 mg/day is probably the sweet-spot, but a few researchers have gone as high as 40 mg/day.

OK. Personally I love to dream, and nightmares are some of the most interesting.

> I don't know why you challenge the FDA for its approval practices and established indications.

I never explicitly challenged the FDA. I just said that drug classification is often arbitrary. But that said, FDA approval of certain drugs for certain purposes often has more to do with the applicant's commercial interests. Ie. one company applies for approval of a certain indication for its drug that is pharmacologically equivalent to another company's drug for which the same indication is not sought. That is arbitrary.

> > Right. And they had chloral hydrate before barbiturates!
> Chloral hydrate is not pleasant. I have taken it.

You mean it lacks recreational potential in contrast to barbiturates and benzodiazepines?

> Doxepin is a pretty crappy antidepressant. It had become used more often as a sleep-aid than an antidepressant. However, you never know how any many individuals will respond to an approved antidepressant - like doxepin. I don't happen to know how many respond to doxepin. Maybe no one, but that is not the issue you brought up.

Actually it had a lot to do with that. I suggested the classification of doxepin is arbitrary. It not a very good antidepressant, even though it is classified as such. Note that arbitrary does not mean indefensible. It might even be reasonable from some point of view.

> I don't mind your scrutinization. It makes for good dialectic.

I made a comment in passing, without much, if any, intention to challenge you. But I'm glad you don't mind.





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