Therapeutic Drug Monitoring of Antidepressants and Cytochrome P450 Genotyping in General Practice

Abstract

In the psychiatric setting, therapeutic drug monitoring and genotyping for cytochrome P450 (CYP) polymorphisms help to ensure and maintain therapeutic drug levels. In this study, the authors extended the therapeutic drug monitoring and genotyping protocol routinely used in their psychiatric clinic to primary care patients treated with antidepressants. They examined the variation in serum concentrations and assessed the role of CYP polymorphisms, wrong dosing, and noncompliance in deviating serum concentrations. Of 227 serum concentrations obtained, 127 (56%) were more than 20% outside therapeutic ranges. Of these 127 cases, 64 (50%) were congruous with aberrant CYP2D6 or CYP2C19 genotypes, incorrect dosing, or a pharmacy record suggesting noncompliance. Prevalence of aberrant CYP2D6 and CYP2C19 genotypes did not differ significantly between the investigated primary care patients and 751 secondary care users of antidepressants. The therapeutic drug monitoring and the genotyping findings resulted in recommendations to physicians to alter the medication strategy of 146 (64%) patients. These results strongly suggest that the rationale for therapeutic drug monitoring and CYP genotyping when prescribing antidepressants in secondary care also applies to the primary care setting.

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

“…Co-prescription of psychotropic and other CNS-acting medications creates an especially high risk for drug-drug interactions in that these agents are often transported and metabolized by the same polymorphic enzymes. When antidepressant drug levels were measured in the blood of patients in a general practice setting, Kootstra et al found that 56% of patients were outside of the therapeutic range [26]. This suggests that variability in exposure may be driving the high degree of outcome variability with this class of medications.…”

“…However, although this may seem to be an infrequent event, this would represent nearly 200,000 patients over the age of 65 in the US alone based on 2012 census estimates. New practices are now available that target improved utilization of drug interaction data [4, 26]. …”

Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients

“…Furthermore, an optimal early antidepressant dosing strategy may have to comprise several endogenic and exogenic factors, possibly including age, body composition, concomitant medication, food components and/or smoking habit. 42 With regard to body composition, IMI doses applied by the physician are not generally based on the patient's sex, weight or body surface area. 7,43 In line with this, there was no significant contribution of body weight or sex to the prediction of IMI þ DESI plasma concentration, IMI dose at steady state or IMI dose requirement in our present multivariate linear regression model.…”

A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy

“…Indeed, in some secondary psychiatric care facilities in the Netherlands, genotyping is already implemented as care as usual [23]. However, no information concerning the cost-effectiveness of routine genotyping at the start of nortriptyline treatment among depressed hospitalized patients is available.…”