Genetic diversity of cytochrome P450 in patients receiving psychiatric care in Greece: a step towards clinical implementation.

Aim: We herein inferred the genetic diversity of CYP450 isoenzymes to predict the percentage of patients who need dose adjustment in drugs used in psychiatry. Materials & methods: Data of 784 Greek patients receiving psychiatric care who were genotyped for CYP2D6, CYP2C19, CYP1A2, CYP3A5 and CYP2C9 isoenzymes were inferred to gene-drug pairs according to the US FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group annotations and published literature. Results: Atypical metabolism was found for 36.8% of patients in CYP2D6, 49.2% in CYP2C19, 45% in CYP1A2, 16.7% in CYP3A5 and 41.8% in CYP2C9. Dosage adjustment need was estimated for 10.2% of venlafaxine, 10.0% of paroxetine, 6.4% of sertraline, 30.8% of citalopram, 52.1% of escitalopram, 18.2% of fluvoxamine, 54.1% of tricyclic antidepressants, 16.7% of zuclopenthixol, 10.6% of haloperidol and 13.3% of risperidone treated patients. Conclusion: Clinical psychiatric pharmacogenomic implementation holds promise to improve drug effectiveness and safety.

What is this summary about? Pharmacogenomic dosing guidelines exist for several antidepressant and antipsychotic drugs. However, psychiatric pharmacogenomics is not yet broadly applied in clinical practice. We herein examined the genetics of enzymes involved in the metabolism of psychiatric drugs to predict the percentage of patients who need dose adjustment. Gene­drug pairs were examined according to the US FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group annotations for CYP2D6 and CYP2C19, and according to existing literature for the other CYP450 isoenzymes.What were the results? In the total population consisting of 784 patients receiving psychiatric care, 36.8% of patients had atypical metabolism in CYP2D6, 49.2% in CYP2C19, 45% in CYP1A2, 16.7% in CYP3A5 and 41.8% in CYP2C9. Within cases that experienced adverse events, 35% had reduced metabolism in CYP2D6, 16.7% in CYP2C19, and 25% in CYP2C9. In cases showing lack of response, 5.8% were CYP2D6 ultra rapid metabolizers (UMs), 39.3% CYP2C19 UMs, 44.1% CYP1A2 fast metabolizers and 14.2% CYP3A5 expressors. Dosage adjustment need was estimated for 10.2% of venlafaxine, 10.0% of paroxetine, 6.4% of sertraline, 30.8% of citalopram, 52.1% of escitalopram, 18.2% of fluvoxamine, 54.1% of tricyclic antidepressants, 16.7% of zuclopenthixol, 10.6% of haloperidol and 13.3% of risperidone treated patients.What do the results mean? CYP450 genotyping can predict interindividual differences in drug response in the field of psychiatry. Clinical psychiatric pharmacogenomic implementation holds promise to improve drug effectiveness and safety.