PsychoTropicalResearch, serotonin and serotonin syndrome research.
Antidepressants - Choices; effectivness vs toxicity
Antidepressants - Choices; effectivness vs toxicity
Date Created: 20/06/1999 Last Modified: 02/01/2003 Last Checked: 03/01/2003
The view that one should not use the old TCAs because they are more toxic in overdose and also more likely to cause motor impairment and therefore be implicated in causing accidents of various sorts has been adduced to strongly promote newer drugs.
This point of view, as an unqualified generalisation, may have been overstated. This situation is partly the result of the high advertising profile now needed by most companies to market their new products. This results in the older drugs getting very little attention, indeed they are so cheap that advertising is uneconomical.
It is certainly the case that new is not automatically better. It is also worth appreciating that there are very considerable differences between the various old tricyclic antidepressants, so much so that lumping them all together (as is often done) is neither logical, nor scientific, nor helpful. For instance, lofepramine and clomipramine are probably much less toxic in overdose than the ‘average’ TCA -- their toxicity seems to be of the same order of magnitude as the SSRIs. On the other hand the new antidepressant venlafaxine is more toxic than most tricyclic antidepressants.
These statements are appropriately couched in cautious terms because the quality ‘toxico-epidemiological’ evidence from which we would be able to make definitive judgements is as yet incomplete.
Sedative potency (H1 blockade) is important for TCAs because it is the most prominent property that correlates with accident risk (see 'accidents') and potency for H1 blockade varies enormously between different tricyclic antidepressants, some being virtually devoid of this effect (see 'receptor affinities'). Of the new drugs mirtazapine is more potent as an anti-histamine than any tricyclic (see affinities-- it is nearly twice as potent as doxepin).
Falls in old people have not been shown definitively to be different between SSRIs and TCAs; indeed quite the contrary, a recent and very large study indicates that falls in the elderly are not any less common on SSRIs than they are with TCAs. This suggests that if one uses an appropriate TCA (a less sedative and less hypotensive one) then even in special at risk groups TCAs may be as good as, or better than, SSRIs (or other new drugs).
Even if some TCAs are significantly more toxic in over-dose than alternatives, this is a specific risk that may be satisfactorily managed in most patients by the simple expedient of giving out smaller numbers of tablets at a time; after all, if such patients are not in hospital then they are likely to require frequent visits. Suicide risk is certainly not, of itself, a reason to switch to more expensive drugs, most of which have modest evidence of equal efficacy (to amitriptyline) and certainly insignificant evidence of superior efficacy.
Suicide risk may in fact be a positive and strong indicator that:--
- A selective serotonin reuptake inhibitor should be avoided
- more potent antidepressant is required.
The evidence strongly suggests this means a tricyclic antidepressant, probably amitryptiline or clomipramine.
All text ©Dr Ken Gillman MRC Psych - PsychoTropical Research®
|Return to the menu at the top of this page|