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Psychotropic Drug Treatment

OMIM numbers: 608902, 609535

Dipl.-Biol. Birgit Busse

Scientific Background

Side-effects or therapy resistance frequently complicates treatment with psychotropic drugs. Besides drug interactions, genetic disposition plays a major role. Genetic variants of the enzymes participating in the metabolism of the drug may be responsible for adverse drug reactions (ADR). The enzymes CYP2D6 and CYP2C19 are of special significance, since they are involved in the metabolism of many frequently prescribed psychotropic drugs (e.g. amitriptyline, fluoxetine, venlafaxine, escitalopram, risperidone). Side-effects may be caused by the variants CYP2D6*4 and *5 or CYP2C19*2 (poor metabolizer). In contrast, the CYP2D6*XN variant and the CYP2C19*17 allele are associated with an increased enzyme activity and increased metabolism of substrates (therapy resistance). Pharmacogenetic analysis can thus contribute to a) identify individuals who a priori carry an elevated risk for ADR due to their genetic disposition, b) better classify the individual efficacy and compatibility of a drug and c) adapt dose if necessary.

The enzymes CYP1A2 and CYP3A4 are frequently involved in the degradation of psychotropic drugs as well. However, interindividual differences in the metabolic capacity are mainly attributable to enzyme induction or inhibition by co-medication or food. Since the clinical relevance of the genetic variants in the CYP1A2 and CYP3A4 genes is not completely clarified yet, the analysis of these genes is conducted only after prior consultation.