Posted by Sunnely on June 28, 2001, at 0:09:24
In reply to TCAs do have their good points » Sunnely, posted by Elizabeth on June 27, 2001, at 12:19:27
> There are lots of different TCAs (about 10 of them in the US, if you count amoxapine and maprotiline), and some of them -- notably desipramine and nortriptyline -- have low binding affinity at cholinergic, adrenergic, and histaminic receptors, and unsurprisingly, these drugs have fewer side effects than other TCAs (amitriptyline, doxepin, and protriptyline are especially nasty).
I'm not sure I understand your logic here. I believe I was comparing SSRIs in general with TCAs in general and not subclasses of TCAs. I can't argue with you in the differences in receptor affinities you described above between tertiary amine TCAs and secondary amine TCAs. But as a class, SSRIs have less affinity to the receptors you described above than the TCAs, as a group.
>
> > The orthostatic hypotension (marked drop in blood pressure upon arising) can occur on TCAs may cause falls with resultant trauma.
>
> This is especially relevant in older adults (women in particular) who may have brittle bones. Serious injuries, such as hip fractures, can result.Again, can't argue with you on this. But again, as a class, SSRIs are less liable to cause orthostatic hypotension compared to the TCAs, when used in used in any group of age or gender population.
>
> Which is why I brought up the secondary amines (DMI and NOR).Both of which are also TCAs, metabolite of imipramine and amitriptyline (tertiary amine TCAs), respectively.
> Tricyclic serum levels should be monitored (although they often aren't), especially if a TCA-SSRI combination is going to be used. Also, one should have a cardiac workup because of the effects of TCAs on cardiac conduction.
Agree with you. Prolonged QTc and subsequent "torsades" and even sudden deaths can occur with SSRI-TCA combination. As you said TCA levels should be monitored, and IMHO, at least for a couple of reasons: 1. possible toxic levels, 2. "therapeutic levels," and 3. compliance. Desipramine which is mainly metabolized by CYP2D6 can lead to toxic blood levels when combined with Prozac and Paxil (both potent inhibitors of CYP2D6). Also, approximately 5-10% of Caucausians have polymorphism for CYP2D6 and can become markedly toxic even when given the "normal" recommended dose. Nortriptyline, believed to have a "therapeutic window" is one TCA that definitely requires periodic monitoring of blood levels, especially if it seems to be losing its antidepressant effect.
> I'm afraid it's not always that simple. Depression isn't a single disease: it's a syndrome that can have different causes and different effective treatments. SSRIs don't work for everyone, and they aren't the most tolerable drugs for everyone, either. (This is especially true of patients who have panic disorder; this group has a lower risk of suicide attempts, and panic patients frequently have a *very* hard time tolerating the activating effects of SSRIs.)
Again, I agree with you on this that SSRIs are not for everyone and not everyone who is depressed requires an SSRI (or an antidepressant). Indeed, depression is not uncommonly co-morbid with other conditions such as panic disorder, OCD, PTSD, schizophrenia, bipolar disorder, substance abuse, Parkinson's disease, dementing processes, etc. I guess I was mainly referring to the uncomplicated type of major depression. However, with the extra potentially serious baggage that TCAs carry with them, it has been relegated (per prescribers' choice) to second-line therapy when it comes to treating major depression (per se). This is not to imply that TCAs themselves are inferior to SSRIs when it comes to antidepressant efficacy. In fact, I believe in some studies, TCAs appear to be more efficacious than SSRIs in severe depression.
poster:Sunnely
thread:67742
URL: http://www.dr-bob.org/babble/20010625/msgs/68172.html