TCAs

[asecin]

i dont know of any advanced guide to Tricyclic antidepressants, safety profile, usefulness and tolerability as least side effects comparison in between them. if someone knows of such guide please url me, if not can you help me compile which TCA is the most tolerable, active (helpful) with least side effects (best safety profile) among those many types within this class ?

 

[sekio]

It's variable between individuals, but amitryptiline (75-125mg) and doxepin (10-20mg) both have studies indicating their efficacy in major depression. I think it's realyl a matter of what's avialable and what works for you based on experience.

Some of them will produce antihistaminic/antimuscarinic side effects (dry mouth, sleepiness etc) that will wear off with time.

 

[pizzystrizzy]

Interesting question, although I think the category of efficacy has to be a little more specific, as it depends in part on the nature of problem being treated (i.e., melancholia vs anxious depression vs atypical depression vs OCD etc). For the most part, the TCAs that still are prescribed with any regularity are prescribed primarily for their (potentially desirable) side effects, e.g., amitriptyline for sleep and/or migraine prophylaxis, nortriptyline when an especially activating medication is desired, etc. I've seen several authoritative mentions of clomipramine being the 'strongest,' though I'm not sure if that is in terms of effect size, response rates generally, response rates in treatment resistant cases, etc.

The wikipedia page (I suspect you may have already looked there) has a table of binding profiles for most of the TCAs

This edited volume looks like a pretty compilation of relevant articles for your purposes, and even though it is a bit dated I think that isn't too much of a problem in this case. My library will pdf a portion (generally approx 2 chapters) of any book on request, so if there's something you want from there I can grab it for you.

This article also looks like it has much of the information you seek (let me know if you need help accessing it).

 

[asecin]

hey man tnx for infos. that book looks like its from 1977, is this even worth bothering with ? do you think they have released updated version of it ?

 

[asecin]

It's variable between individuals, but amitryptiline (75-125mg) and doxepin (10-20mg) both have studies indicating their efficacy in major depression. I think it's realyl a matter of what's avialable and what works for you based on experience.

Some of them will produce antihistaminic/antimuscarinic side effects (dry mouth, sleepiness etc) that will wear off with time.

sekio, the whole restricted diet is what sucks when it comes to those meds. i was curious which TCA has least problems when not following the strict diet that many antidepressants require.

 

[sekio]

strict diet that many antidepressants require.

Elaborate? I always thought the only antidepressants that warrant dietary restrictions were the older, unselective MAO inhibitors.

 

[pizzystrizzy]

hey man tnx for infos. that book looks like its from 1977, is this even worth bothering with ? do you think they have released updated version of it ?

I don't think the date is too much of a problem in this case because as far as I understand there haven't really been many new developments in TCAs. The newer drugs lack the anticholinergic side effects and are much more difficult to use to intentionally kill yourself, so interest in TCAs has waned. Also after the catecholamine hypothesis of affective disorders began to fall out of favor, people became interested in more 'selective' compounds, and the more recent multi-monoamine affecting antidepressants have not been TCAs. Clomipramine wasn't approved in the united states until 1990 but it was available elsewhere much earlier (the FDA didn't want to approve it initially because they thought it was just a me-too analogue of imipramine -- another indication, OCD, had to be found to make it viable in the US).

This isn't to say that there haven't been developments, but it looked to me like that book was pretty comprehensive and would be adequate for the kinds of questions you were asking.

 

[pizzystrizzy]

sekio, the whole restricted diet is what sucks when it comes to those meds. i was curious which TCA has least problems when not following the strict diet that many antidepressants require.

No TCA has any dietary restriction. The only antidepressants that have dietary restrictions are the MAO-Is.

 

[asecin]

yeh i have been reading quite a bit for while now about TCAs and it seems they are just horrible. no wonder they have been replaced by the weaker much unhelpful SSRIs. kind of sad there is no good, safe, reliable new antidepressant out there. do you guys think MAIOs while having to deal with restricted diet are probably much better choice than both classes mentioned previously ?

 

[asecin]

what about Tetracyclic antidepressants ? are they a class above TCAs ?

 

[sekio]

TeCAs are pretty closely related to TCAs.

yeh i have been reading quite a bit for while now about TCAs and it seems they are just horrible.

They work pretty well for many individuals due to their multispectrum nature. The side effect profile is pretty tolerable especially considering you can dose these things at night. Not everyone gets every side effect, and compared to crippling depression a little drowsiness and dry mouth is pretty minor.

do you guys think MAIOs while having to deal with restricted diet are probably much better choice than both classes mentioned previously ?

Most newer selective MAOIs don't need dietary restrictions. See for instance, moclobemide and selegiline, which don't carry the risk of "tyrosine syndrome". Older drugs like phenelzine do, though.

 

[asecin]

i was reading of deaths occurring with TCAs compared to none with SSRIs. but at the same time i read SSRIs do not even happen to be as effective as TCA when it comes to serious depressions. which is a risk to actually go for the TCAs knowing they might kill you compared to the SSRIs which are not even as effective.
i have checked moclobemide and selegiline information. i dunno what you refer to "tyrosine syndrome" do you mean serotonin syndrome ? moclobemide is reversible MAIO which can be reversed in instances and it has short half life anyway so it doesn't seem as dangerous. selegiline is irreversible but acts on MAO B specifically unless dosed higher than it affects MAO A as well and since its irreversible and has much longer half life than moclobemide, i assume it can probably cause bad reactions and needs restrictions in diets.

 

[pizzystrizzy]

The TCAs aren't so bad really if the dose isn't too high, the biggest issue is that they can be used for suicide in high doses which is a serious clinical concern with the population for whom they are designed. In general I think they are a bit more effective than the SSRIs, though the latter seem to be better for certain anxious depressions. They are especially effective in classic melancholic 'endogenous' depression.

The only tetracyclic available that I know of is mirtazapine, which is a kind of interesting drug with its own unique mechanism. It blocks some 5ht receptors kind of like a neuroleptic does, and also is a pretty potent antihistamine, one of the most potent mg per mg. It doesn't inhibit the reuptake of any of the monoamines, but it has indirect effects by blocking autoreceptors, and I believe it is more often prescribed as an add-on to another antidepressant even though it holds its own as a monotherapy in studies. It is kind of sedating esp at lower doses where the antihistamine effects are much larger than the adrenergic, and it makes people hungry, so it is great in cases where weight gain is desired, not so good when it isn't. It is closely related to mianserin, another tetracyclic that I don't believe is available any longer.

Some drugs that aren't classed as TCAs are structurally tricyclic -- the antipsychotic quetiapine is a good example. Tianeptine is another, a really interesting antidepressant that has a poorly understood mechanism of action but seems to enhance the reuptake of serotonin. It produces short-lived pleasant mild stimulation that is anxiolytic. It isn't available from US pharmacies though it is incredibly popular in France. The only real drawback to it is that it has a super short halflife and has to be dosed 3 times per day. I have no idea why they don't make an extended release variation.

The MAOIs are a good choice in certain kinds of depression. The dietary restrictions aren't really that big of a deal unless you really love cheese. And as Sekio said the newer ones don't have the same restrictions (though I don't know as much about their efficacy vs. the older ones -- phenelzine and tranylcypromine)

 

[sekio]

i dunno what you refer to "tyrosine syndrome" do you mean serotonin syndrome ?

I am talking about the fact that if you consume tyrosine or tyrosine-rich foods while on an unselecctive MAOI, you will get ewhat is essentiially a hyoertensive crisis, aka "cheese syndrome" or "tyrosine syndrome". This is the dietary restriction that you were concerned about.

 

[pizzystrizzy]

I am talking about the fact that if you consume tyrosine or tyrosine-rich foods while on an unselecctive MAOI, you will get ewhat is essentiially a hyoertensive crisis, aka "cheese syndrome" or "tyrosine syndrome". This is the dietary restriction that you were concerned about.

Tyrosine can be an issue (much like tryptophan), but the real concern is tyramine. Tyramine normally undergoes first pass metabolism and is deaminated in the liver by mao-a and mao-b, but when it doesn't, it competes with tyrosine for transport into the brain where it displaces norepinephrine from synaptic vesicles en masse, which can easily trigger a hypertensive crisis.

 

[sekio]

Whoopsy. Tyrosine is the carboxylated amino acid version of tyramine, easy to confuse.

 

[asecin]

I am talking about the fact that if you consume tyrosine or tyrosine-rich foods while on an unselecctive MAOI, you will get ewhat is essentiially a hyoertensive crisis, aka "cheese syndrome" or "tyrosine syndrome". This is the dietary restriction that you were concerned about.

its called serotonin syndrome. and you confused tyrosine for tyramine ? i dont think you are the best to give me advice on this

 

[ebola?]

its called serotonin syndrome.

No, it's not (tyramine doesn't even cause increases in intercellular serotonin downstream).

i dont think you are the best to give me advice on this

Someone makes a single 'conceptual typo', and you deem them unqualified to discuss things with you? This doesn't seem valid at all...

It doesn't inhibit the reuptake of any of the monoamines

Actually, mirtazapine has secondary (er...quaternary, maybe...) activity as an SRI, but this activity is not particularly relevant to experienced effects (binding is in the realm of an order of magnitude weaker than more relevant activities).

ebola

 

[AlphaMethylPhenyl]

Sekio is up there with the most knowledgeable on bluelight.

 

[pizzystrizzy]

MAO-Is can cause serotonin syndrome, but not with tyramine.