AUTHOR=Koopmans Anne B. , Vinkers David J. , Poulina Igmar T. , Gelan Petra J. A. , van Schaik Ron H. N. , Hoek Hans W. , van Harten Peter N. 

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

JOURNAL=Frontiers in Psychiatry

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00349

DOI=10.3389/fpsyt.2018.00349

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the <italic>CYP2D6</italic> genotype.</p><p><bold>Aims:</bold> To evaluate the effect of dose adjustment to the <italic>CYP2D6</italic> genotype and phenotype, in patients with severe mental illness (SMI) already receiving psychopharmacological treatment.</p><p><bold>Methods:</bold> A total of 269 psychiatric patients (on the island Curaçao) receiving antipsychotic treatment were genotyped for <italic>CYP2D6</italic>. 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> In psychiatric patients with SMI already receiving antipsychotic treatment, dose adjustment to the <italic>CYP2D6</italic> 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.</p><p>ClinicalTrials.gov: Cost-effectiveness of CYP2D6 and CYP2C19 Genotyping in Psychiatric Patients in Curacao; Identifier: NCT02713672; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&amp;rank=5" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&amp;rank=5</ext-link></p>