The development of a personalized psychopharmacotherapy could potentially reduce treatment failure
associated with drug intolerance or resistance, and therefore the burden and costs of affective disorders. An important
challenge in realising this potential will be to identify suitable markers of an individual’s metabolic response to
In the absence of suitable markers related directly to drug mechanism, the drug-metabolizing enzymes and transporters have emerged as
major determinants of variability in drug metabolism and response. In keeping with this emergent general pharmacological trend, numerous
studies concerning the relationship between antidepressants, their metabolism, transport, pharmacokinetic properties, efficacy and
tolerability have now been published. These studies are reviewed in this article.
The studies considered here frequently support a link between enzyme/transporter activity and/or the pharmacokinetic parameters of antidepressants.
However, the majority of studies explored the variability of tricyclic antidepressants, which are less often prescribed today.
Furthermore only a few studies have been conducted in naturalistic clinical conditions, seeking to determine whether the systematic assessment
of the variability may improve the management of ‘real-world’ patients.
Nonetheless recent studies have yielded promising results regarding the potential benefits of determining drug metabolism variability
which might encourage additional large-scale prospective systematic studies be set up to assess the relevance of this approach in everyday