TDM and Pharmacogenetics in Relation to Side Effect Monitoring in Psychiatry

Different strategies may be used to prevent or detect drug-related toxicity in psychiatry and, therefore, optimise psychotropic drug dosage. The first is based upon monitoring of the plasma drug levels. The second consists on evaluation of the metabolic capacity of an individual by pheno/genotyping. Therapeutic drug monitoring (TDM) may be useful for drugs with a narrow therapeutic index and with a large interindividual variability in pharmacokinetics. Several studies support the existence of a correlation between plasma concentrations of various psychotropic drugs, such as lithium, tricyclic antidepressants, traditional and newer antipsychotics (i.e., haloperidol, clozapine and risperidone), and toxic effects. When using these agents, TDM is indicated not only in clinical situations in which an expected therapeutic effect has not been observed, but also when concentration dependent toxicity is suspected, especially for drugs administered chronically. Conversely, genotyping for drug-metabolizing enzymes might help clinicians in selecting the right starting dose for an individual patient, thereby minimizing the risk of severe side effects. This might be an advantage in patients treated with antidepressants and antipsychotics predominantly metabolised by polymorphic enzymes. In fact, as a consequence of genetically impaired metabolism, plasma levels of a given substrate are more likely to reach toxic values. In accordance with this, some studies suggest that poor metabolizers of CYP2D6 are more prone to cardiovascular and central nervous system toxicity when treated with tricyclic antidepressants or venlafaxine and to extrapyramidal side effects during treatment with classical antipsychotics. Genotyping can today be recommended as a complement to plasma concentration determination when aberrant metabolic capacity of polymorphic enzymes substrates is suspected.