Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19.

Extensive migration has led to the necessity of knowledge regarding the treatment of migrants with different ethnical backgrounds. This is especially relevant for pharmacological treatment, because of the significant variation between migrant groups in their capacity to metabolize drugs. For psychiatric medications, CYP2D6 and CYP2C19 enzymes are clinically relevant. The aim of this meta-analysis was to analyze studies reporting clinically useful information regarding CYP2D6 and CYP2C19 genotype frequencies, across populations and ethnic groups worldwide. To that end, we conducted a comprehensive meta-analysis using Embase, PubMed, Web of Science, and PsycINFO (>336,000 subjects, 318 reports). A non-normal metabolizer (non-NM) probability estimate was introduced as the equivalent of the sum-prevalence of predicted poor, intermediate, and ultrarapid metabolizer CYP2D6 and CYP2C19 phenotypes. The probability of having a CYP2D6 non-NM predicted phenotype was highest in Algeria (61%) and lowest in Gambia (2.7%) while the probability for CYP2C19 was highest in India (80%) and lowest in countries in the Americas, particularly Mexico (32%). The mean total probability estimates of having a non-NM predicted phenotype worldwide were 36.4% and 61.9% for CYP2D6 and CYP2C19, respectively. We provide detailed tables and world maps summarizing clinically relevant data regarding the prevalence of CYP2D6 and CYP2C19 predicted phenotypes and demonstrating large inter-ethnic differences. Based on the documented probability estimates, pre-emptive pharmacogenetic testing is encouraged for every patient who will undergo therapy with a drug(s) that is metabolized by CYP2D6 and/or CYP2C19 pathways and should be considered in case of treatment resistance or serious side effects.

Proxy WHO Disability Assessment Schedule 2.0 Is Clinically Useful for Assessing Psychosocial Functioning in Severe Mental Illness.

AIMS: This study explores how well the World Health Organization Disability Assessment Schedule (WHODAS 2.0) assesses problems with psychosocial functioning in patients with severe mental illness (SMI). Further, we assessed the relationships between psychosocial functioning and psychopathology, medication side effects, treatment setting, and quality of life. METHODS: We performed an observational, cross-sectional study on the island of Curaçao to assess psychosocial functioning in 77 patients with SMI; they mainly had psychotic disorders. We interviewed their healthcare providers using the proxy version of the WHODAS 2.0. In addition, patients were examined for psychiatric symptoms, medication side effects (including drug-induced movement disorders), and quality of life. Associations were examined with Spearman's rank correlation (ρ). RESULTS: Difficulties in psychosocial functioning were reported by patients with SMI in the WHODAS 2.0 domains of understanding and communicating [mean (M)=34.5, standard deviation (SD)=18.6), participation in society (M=25.5, SD=15.6), and getting along with people (M=24.1, SD=16.1)]. Notably, outpatients had more problems participating in society than inpatients (M=33.6, SD=18.5 versus M=23.2, SD=14.1, p=0.03). A positive correlation was observed between drug-induced parkinsonism and the WHODAS 2.0 total score (ρ =0.30; p=0.02), as well as with various subscales, getting around, and household activities. CONCLUSION: The proxy version of the WHODAS 2.0 is clinically useful for patients with severe mental illness. The highest scores on the WHODAS 2.0 were found in domains related to interactions with other people and to participation in society. Inpatient status appeared to aid participation in society; this might be due to living in the sheltered clinic environment and its associated daily activities. We further found that drug-induced parkinsonism was associated with a broad spectrum of psychosocial disabilities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02713672; retrospectively registered in February 2016.

No Effect of Dose Adjustment to the CYP2D6 Genotype in Patients With Severe Mental Illness.

Background: The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the CYP2D6 genotype. Aims: To evaluate the effect of dose adjustment to the CYP2D6 genotype and phenotype, in patients with severe mental illness (SMI) already receiving psychopharmacological treatment. Methods: A total of 269 psychiatric patients (on the island Curaçao) receiving antipsychotic treatment were genotyped for CYP2D6. Of these, 45 patients were included for dose adjustment according to the clinical guideline of the Royal Dutch Association for the Advancement of Pharmacy, i.e., 17 CYP2D6 poor metabolizers, 26 intermediate metabolizers, and 2 ultrarapid metabolizers. These 45 patients were matched for age, gender, and type of medication with a control group of 41 patients who were CYP2D6 extensive metabolizers (i.e., with a normal CYP2D6 function). At baseline and at 4 months after dose adjustment, subjective experience, psychopathology, extrapyramidal side-effects, quality of life, and global functioning were assessed in these two groups. Results: At baseline, there were no differences between the groups regarding the prescribed dosage of antipsychotics, the number of side-effects, psychiatric symptoms, global functioning, or quality of life. After dose adjustment, no significant improvement in these parameters was reported. Conclusion: In psychiatric patients with SMI already receiving antipsychotic treatment, dose adjustment to the CYP2D6 genotype or phenotype according to the guidelines showed no beneficial effect. This suggests that dose adjustment guidelines are currently not applicable for patients already using antipsychotics. ClinicalTrials.gov: Cost-effectiveness of CYP2D6 and CYP2C19 Genotyping in Psychiatric Patients in Curacao; Identifier: NCT02713672; https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&rank=5.

CYP2D6 and CYP2C19 genotyping in psychiatric patients on psychotropic medication in the former Dutch Antilles.

AIM: This study was aimed to asses the prevalence of CYP2D6 and CYP2C19 polymorphisms in psychiatric patients and in volunteers from Dutch caribbean origin. METHODS: In total, 435 individuals were genotyped for CYP2D6 and CYP2C19. Of these, 269 were psychiatric patients on psychotropic medication, living in Curaçao and 166 were volunteers from the Dutch Caribbean population. RESULTS: No differences in prevalence of alleles were found. CONCLUSION: Although prevalence of alleles appeared to be very different from African and Caucasian populations, the distribution into predicted phenotypes shows an equal distribution as in Caucasians.