PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Antidepressants - Pharmacology

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Antidepressants - Pharmacology

Antidepressants - Pharmacology

Date Created: 04/04/1999   Last Modified: 31/03/2002   Last Checked: 21/10/2002

It is not logical to consider the beneficial pharmacological properties of drugs without, at the same time, having some awareness of the methods of classifying and assessing illness and the rating scales used to do this, both of which have considerable limitations.

Most antidepressant rating scales assess measures of sleep / anxiety / sedation which will be affected by, for instance, the powerful H1 blockade of all the TCAs, which will tend to reduce the total depression score partly because of these sedative effects. This built in sedative action of TCAs could be proposed as an explanation for why they seem to be slightly more effective for ‘depression’ than the SSRIs. Whilst such an advantage might be of practical clinical utility, it could be considered artifactual from a theoretical standpoint.

The above illustrates a small part of the complexities that are relevant to an understanding of drug effects, benefits and side effects. What are called ‘side effects’ may be inevitable consequences of the therapeutic part of the drugs' action; since we do not always know for sure what that is, neither can we be sure what is really a side effect and what is not; eg delayed orgasm is probably an inevitable consequence of raised 5-HT levels and is thus an inescapable consequence of using SRIs.

We now have data indicating the potency of most drugs at various receptors (and other sites eg enzymes); this gives the best estimate we yet have of what to expect clinically. (see receptor affinities) It is incumbent on all practitioners to be cognisant of these developments because they underpin the rational, scientific and safe use of all of these drugs.

There are a number of intervening processes and we do not yet know what the actual concentration of any drug is at the effector site (usually a receptor) even for two structurally similar tricyclics. Nevertheless the figures in receptor affinities are an essential and helpful guide.