The therapeutic to lethal dose ratio can be as low as 5.0 in some people for TCAs.
Amitriptyline is in particular dangerous. a 70mg dose is not real safe for someone who has never taken the substance before... others have actually ended up in comas from, "my marmoset thinks" actual therapeutic doses and woke up in the hospitol and wondered what the $#)%$?
Barbiturates have a greater safety margin than TCA. Amitriptyline is metabolized into nortryptriptyne which is considered toxic. Or at least to a certain extent when it is metabolized.
SWIM's marmoset forgets the literature that listed the safety indexes, but barbiturates were 10.0 on average and amitriptyline fell into the "under 5.0 category" But, everyone's body is different so that is obviously an approximation and YMMV.
TCAs are far more effective in SWIM's case than any of the SSRIs or SNRIs... but the only other reason they seem to being phased out other than increased safety risk, is ISHO greedy pharma companies... TCAs are old, cheap, dangerous, but very effective in certain individuals.
The problem is that depressed individuals tend to be more likely to be suicidal and as Tricyclics are (from what SWIM has read) rather difficult to treat in an overdose they are not indicated for a patient who is has suicidal tendancies. But, TCAs in overdoses also can cause seizures and other unpleasant symptoms, not to mention death....
I think it has been mentioned by others, they can also put people at risk for increased complications with other meds. Please be careful with this one... it's pharmacologic profile is actually very interesting as it has side-effects that can actually be useful, such as increased appetite, and sedation when an illness or depression itself is causing loss of appetite and insomnia... Hepatitis C perhaps an example of such an illness, the
drugs used to treat it cause these symptoms, just as with chemo patients. So, in SWIM's opinion they are far from obselete, but must be treated with respect. OH and an accidental discovery by SWIM was as she mentioned below she just lost the desire to smoke after taking it, but she couldn't figure out why. Hell, it was really bugging SWIM so after 2 weeks of digging through books it suddenly was obvious as nortyptyline is it's major mebabolite as I described below. Not to be repeating myself but, this really caused SWIM to become quite intrigued in this
drug after realizing it was not FDA approved for smoking cessation, but it's metabolite was. It took her 2 weeks to figure this out, and felt rather silly when she realized that she had known the answer the whole time, just not bothered to take a few seconds to put the mystery together.
SWIM has not smoked a cigarette since, and never intended to quit. It worked when SWIM had no desire to discontinue smoking. SWIM is glad to have quit now, but was confused as hell til putting that together. The stuff was only taken for a brief period of time and still there is no desire to smoke a cigarette... This is something SWIM was excited about and wanted to do some research on and write up a paper, but alas life has been making it rather difficult lately to complete any compilations.
SWIM would be interested to here about more people who have had experience using that drug.
Imipramine was and still is "SWIM thinks, 99%" sure is the golden standard for TCAs and was not as helpful in SWIM's case as Amitriptyline... Errr actually Imipramine was the prototype for all TCAs that followed. In the 1960's perhaps it was first marketed??? Amitriptyline was not marketed in the US until 1983, shortly before the TCAs were considered by many to be obsolete as the SSRIs and SNRIs were introduced into the market.
Please be careful with this, or any other TCA as they are not very forgiving if someone were to attempt misuse them. Fortunately, SWIM has never had to experience this as some other posters have.
-Laud