Posted by Elizabeth on June 27, 2001, at 12:19:27
In reply to Re: Maprotiline (Ludiomil): » Salilyn, posted by Sunnely on June 26, 2001, at 23:27:29
> The main reason as to why the newer generation of antidepressants (e.g., SSRIs) are now the first drugs of choice for depression over the TCAs is Safety, Tolerability, and Simplicity.
I don't agree about the tolerability -- that's a YMMV thing, and SSRIs, which were initially touted as free of side effects, turned out to be not so great in that department (sexual dysfunction (which seems to be almost universal with SSRIs), activation syndrome, sleep disruption, apathy, GI side effects, etc.).
Safety is the main issue. SSRIs are almost never lethal in overdose. Tricyclics can be, although I think you exaggerate a bit. People who don't metabolise tricyclics properly (due to genetic enzyme deficiencies or to interactions with other drugs) can kill themselves with a week's supply; normal metabolisers probably won't. SSRIs are also, as you say, safe for people with cardiac conduction defects (so are MAOIs, incidentally: they used to be the drugs of choice in these cases).
TCAs also carry an increased risk of mania and seizures, compared to SSRIs and MAOIs.
> SSRIs affect fewer sites of action and hence cause fewer types of adverse effects.
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).
> 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.
> The chronic anticholinergic effects can lead the patient to discontinue treatment during the maintenance phase of treatment and thus increase the risk of relapse.
They can also cause dental problems (due to dry mouth) and hemorrhoids (due to chronic constipation).
> In clinical studies, the discontinuation of tertiary amine TCAs such as imipramine (Tofranil) can be 3 times higher than the discontinuation rate on an SSRI (e.g., 22% versus 7%, respectively).
Which is why I brought up the secondary amines (DMI and NOR).
> E - Efficacy (overall response rate, unique spectrum of activity in subpopulations, rate of onset, maintenance, prophylactic)
This is important: certain types of depression tend to respond poorly to SSRIs and well to TCAs.
> S - Simplicity (ease of optimal dosing, drug administation schedule, need for blood levels, etc.)
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.
> Based on the above, it's a no brainer that the newer generation of antidepressants such as the SSRIs are clear choice.
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.)
-elizabeth
poster:Elizabeth
thread:67742
URL: http://www.dr-bob.org/babble/20010625/msgs/68092.html