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BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50-60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness. OBJECTIVES: To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients. To investigate the relationship between ABCB1 SNPs and clinical response. METHODS: Patients had MDD and received paroxetine 20 mg/day. We measured PSC after 6 weeks. We quantified SERT-occupancy with SPECT imaging (n = 38) and measured 17-item Hamilton Depression Rating Scale (HDRS17)-scores at baseline and after 6 week

Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual’s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy

Currently, there is a lack of international and national guidelines or consensus documents with specific recommendations for electrocardiogram (ECG) screening and monitoring during antidepressant treatment. To make a proper estimation of the risk of cardiac arrhythmias and sudden (cardiac) death during antidepressant use, both the drug and patient-specific factors should be taken into account; however, solid evidence on how this should be done in clinical practice is lacking. Available recommendations on the management of QT(c) prolongation (with antidepressant treatment) emphasize that special attention should be given to high-risk patients; however, clinicians are in need of more concrete suggestions about how to select patients for ECG screening and monitoring. Based on a review of the literature, a Dutch multidisciplinary expert panel aimed to formulate specific guidelines to identify patients at risk for cardiac arrhythmias and sudden death by developing a consensus statement regarding ECG screening before, and monitoring during, antidepressant use. We first reviewed the literature to identify the relative risks of various risk factors on cardiac arrhythmia and sudden (cardiac) death during antidepressant use. These relative contributions of risk factors could not be determined since no systematic reviews or meta-analyses quantitatively addressed this topic. Because evidence was insufficient, additional expert opinion was used to formulate recommendations. This resulted in readily applicable recommendations for clinical practice for selection of high-risk patients for ECG screening and monitoring. ECG screening and monitoring is recommended before and following the start of QTc-prolonging antidepressants in the presence of vulnerability to QTc prolongation or two or more risk factors (age > 65 years, female sex, concomitant use of a QTc-prolonging drug or concomitant use of a drug that influences the metabolism of a QTc-prolonging drug, cardiac disease, excessi