Pharmacopsychiatry 2005; 38 - 48
DOI: 10.1055/s-2005-862661

TDM and Pharmacogenetic Tests as Tools in Pharmacovigilance: Case Reports

E Jaquenoud Sirot 1, P Stephan 1, B Knezevic 1, CB Eap 2, P Baumann 2
  • 1Psychiatrische Dienste des Kantons Aargau, Klinik Königsfelden, Brugg, Switzerland
  • 2Unité de Biochimie et Psychopharmacologie Clinique, Département Universitaire de Psychiatrie Adulte, Centre des Neurosciences Psychiatriques, Prilly, Switzerland

Our hypothesis is, that: 1) a relevant number of Adverse Drug Reactions are dose dependent side effects (e.g. extrapyramidal side effects correlate with Dopamin2 receptor occupancy which correlates with plasma levels of haloperidol), 2) plasma levels of a given drug reflect better than its dose brain concentrations, 3) plasma levels are, amongst other, dependent on the pharmacogenetic status of the patient.

Based on this hypothesis we perform an ethically approved dynamic cohort study in the psychiatric inpatient hospital Königsfelden (400 beds, 1800 patient entries). We continuously and actively collect adverse events meeting the AMSP-criteria: serious, leading to discontinuation of treatment and unexpected. All adverse event cases are assessed for their causality in relation to disease and drug therapy. 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 isoenzymes.

In 3 years time we have collected about 250 cases. TDM and pharmacogenetic tests helped us to elucidate difficult ADRs and to find for these patients better tolerated individualised drug treatment. Some of these cases will be presented and an algorithm for using TDM and pharmacogenetic tests in pharmacovigilance is proposed.