SSRI differentiation: Pharmacology and pharmacokinetics

Although the acute pharmacology properties of antidepressants is predominantly due to their presynaptic action, their therapeutic activity is believed to derive from adaptive post-synaptic changes in monoaminergic neurones. The selective serotonin reuptake inhibitors (SSRIs) exhibit differences in potency at inhibiting serotonin reuptake, although the differences do not correlate with clinical posology. There are also differences in their effects on neurotransmitter receptors; paroxetine has a slight affinity for muscarinic cholinergic receptors whilst citalopram has a slight affinity for histamine-H1 receptors. These properties may be related to clinical adverse effects. The pharmacokinetic profiles of the SSRIs show many differences. Whilst fluvoxamine, paroxetine and citalopram are metabolized to inactive products, fluoxetine is metabolized to norfluoxetine which is pharmacologically active and, like its parent compound, has a long half-life. Fluvoxamine is less protein-bound than the other SSRIs and sertraline is only well absorbed when taken with food. Differences are also apparent in the suitability of individual SSRIs in special patient groups. There has been considerable speculation over the inhibition of cytochrome P450 isoenzymes which are responsible for the metabolism of SSRIs and other drugs. In clinical practice, the differences between the SSRIs in this respect are probably of limited importance. However, it is worthwhile that clinicians be made aware of possible interactions between drugs that act as inhibitors or substrates of the hepatic cytochrome P450 system.