Onderzoek naar het DNA medicatie paspoort bij het starten van antidepressiva in de eerste lijn.

Anxiety disorders as a group are the most common mental health problems, occurring in 1/5 of the Dutch population. Whereas, depression is the most frequently occurring isolated psychiatric disorder, with an incidence of 135.600 newly diagnosed individuals per year in the Netherlands [www.trimbos.nl]. The pharmacological treatment of these psychiatric disorders is characterized by low efficacy and high incidence of side effects, both resulting in the need to switch from type of antidepressant in 30% of the patients [The Swedish Council]. Ineffectiveness and adverse drug reactions are partially caused by interindividual variation in drug metabolism. Pharmacogenetic (PGx) analysis can predict this variability in drug metabolism by analysing DNA of a patient. The Royal Dutch Pharmacogenetics Working Group (KNMP) has established evidence-based genotype-guided dosing advices for over 90 drugs, which are currently available in every pharmacy in the Netherlands and clinically used. This PGx diagnostic analysis can be used before start of antidepressant therapy, to maximally benefit from the genetic information in getting patients as quickly as possible on the right medication/dosage, and are currently used to adjust dosing of clinical patients. Erasmus MC received 14,000 PGx test requests (2018, prognosis 2019: 22,000), from which 9,000 in 2018 were related to psychiatric drugs. We see a trend in requesting a full DNA passport, making that an increasing number of patients will have DNA information prior to start of drug therapy. However, there is limited information on what the effects are of this knowledge implementation. The primary care setting is a suitable environment to monitor knowledge implementation, being the effects of using PGx information at start of antidepressant therapy. Important factors that will be addressed are evidence for improved treatment in the pre-emptive setting and cost-effectiveness.

Stepped wedge cluster randomized prospective implementation study

farmacogenetica bepaling voor aanvang behandeling met antidepressivum

Written informed consent will be asked from all participants. Collection of buccal swab material will be performed once in all participants at start of treatment, which poses no additional risk. For participants in the intervention group, PGx outcome and advice will be delivered prior to therapy. Material of patients in the control group will be stored at Erasmus MC and genotyped at the end of the study, so that both groups will have their DNA information (ethical aspect) and this retrospective analysis of endpoints in the control group will be possible. Participants in de intervention group will not have more visits compared to the individuals in the control group. Data will be extracted from the medical records of the patients. Information on quality of life will be collected in both allocation groups with the EQ-5d-5L questionnaire, which will performed at baseline (before start N06A drug) and 1 year after start treatment. The questionnaire will require 5 minutes per assessment (10 minutes total per participant).