The convergence of conventional therapeutic drug monitoring and pharmacogenetic testing in personalized medicine: focus on antidepressants.
The development and prospects of conventional therapeutic drug monitoring (TDM) and pharmacogenetic testing as aids in personalized treatment with antidepressants and antipsychotics are described. Our own experience is discussed in relation to international guidelines for rational TDM. Emphasis is put on the usefulness of TDM combined with genotyping of cytochrome P450 2D6 (CYP2D6), the key enzyme involved in the polymorphic metabolism of the majority of antidepressants (both tricyclics and selective serotonin reuptake inhibitors) and antipsychotic drugs. This combination of methods is particularly useful in verifying concentration-dependent adverse drug reactions (ADRs) due to poor metabolism, 'and diagnosing pharmacokinetic reasons (ultrarapid metabolism (UM)) for drug failure. This is because ADRs may mimic the psychiatric illness itself and therapeutic failure due to UM may be mistaken for poor compliance with the prescription.
Sjöqvist
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F
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. folke.sjoqvist@ki.se
Eliasson
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E
D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D012189:Retrospective Studies
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6