Pharmacopsychiatry 2005; 38 - 49
DOI: 10.1055/s-2005-862662

Follow-Up of a Pharmacovigilance Study in Psychiatry Involving TDM and Pharmacogenetic Testing

E Jaquenoud Sirot 1, CB Eap 2, P Baumann 2
  • 1Psychiatrische Dienste Aargau AG, Klinik Königsfelden, Brugg, Switzerland
  • 2Unité de Biochimie et Psychopharmacologie Clinique, DUPA, CNP, Prilly-Lausanne, Switzerland

The importance of genetic polymorphisms and drug drug interactions in relation to therapeutic response and susceptibility for adverse drug reactions (ADR) are increasingly recognized.

Objectives: Follow-up of a dynamic cohort study in psychiatric inpatients with ADRs (most of them being serious), with emphasis on plasma levels of the involved medication.

Methods: This study comprises data of an ongoing dynamic cohort study of in the meantime 250 psychiatric inpatients with ADRs: Within an ethically approved pharmacovigilance project (AMSP) in the clinic Königsfelden, we continuously and actively collect side effects meeting the criteria serious, unexpected or leading to stop of the medication. All adverse event cases are assessed for their causality in relation to disease and drug therapy. In order to better understand the impact of high plasma levels, we measure trough plasma levels during or immediately after the adverse event. If the plasma levels are at least 20% lower or higher than the expected reference plasma levels (Baumann et al. Therapeutic Monitoring of Psychotropic Drugs. AGNP-TDM Expert Group Consensus Guidelines, Pharmacopsychiatry (in press)), we also assess the pharmacogenetic status of the patient for the cytochrome P450 isozymes.

Results: In about 20–25% of the cases plasma levels of the medication lay at least 20% above the given reference ranges. In some drugs, we regularly find plasma levels of over 200% of the given upper reference value, hinting to a possible pharmacogenetic polymorphism for a metabolizing enzyme.

Conclusions: TDM and pharmacogenetic tests are useful for causality assessments of a number of ADR cases. It is too early to give a recommendation for routine TDM and pharmacogenetic testing, with the exception of drugs like clozapine with an established therapeutic index. To understand if high plasma levels and their cause really lead to more ADRs, more and controlled studies are needed.