Jose de Leon: Training psychiatrists to think like pharmacologts
28. Personalized medicine in psychiatry
Jose de Leon’s reply to Samuel Gershon’s commentary
I am very grateful that Dr. Gershon, one of the most important pioneers in psychopharmacology, had time to comment on my “Lecture 28. Personalized medicine in psychiatry.” A good part of my research in the last 20 years has been in pharmacokinetic studies and, in my view, one of Dr. Gershon’s articles is the first and most important proof that pharmacokinetics is crucial in psychiatry (Trautner et al., 1955). This classic article on lithium is described in slide 11 of my “Lecture 29. Pharmacokinetics of lithium.” When I present this lecture to my psychiatry residents, I encourage them to read this classic pharmacokinetics article.
I completely agree with Dr. Gershon on the limited application for tests recommending personalized prescription in psychiatry. Several commercial pharmacogenetic tests are being marketed in the US currently, but most of them are non-validated and should not be used. In my opinion, pharmacogenetic testing can help in a few psychiatric patients: 1) before starting: a) carbamazepine in patients of Asian ancestry (HLA-B*15:02 testing), or b) tricyclic antidepressants (CYP2D6 and CYP2C19 genotyping) and 2) occasionally when seeing lack of efficacy or adverse drug reactions: a) CYP2D6 and/or CYP2C19 genotyping for selective serotonin reuptake inhibitors (SSRIs), b) CYP2D6 genotyping for i) venlafaxine or vortioxetine, ii) pimozide, iii) CYP2D6-dependent second-generation antipsychotics (aripiprazole, brexpiprazole, iloperidone, or risperidone) and iv) atomoxetine and c) CYP2C19 genotyping for clozapine. Commercial tests 1) using CYP1A2, CYP2B6, CYP3A4 or CYP3A5 genotyping; 2) using brain neurotransmitter and/or transporter genotyping or 3) diagnosing schizophrenia, depression or bipolar disorder should not be ordered. My views are described in my “Lecture 6. Pharmacogenetic testing in psychiatry” and updated in a new editorial (de Leon, 2016) which is summarized in a PowerPoint lecture (Past, present and future of pharmacogenetics testing in psychiatry) that I hope to be able to post in the second version of this course in 2017.
Trautner EM, Morris R, Noack CH, Gershon S. The excretion and retention of ingested lithium and its effect on the ionic balance of man. Medical Journal of Australia 1955, 42: 280-291.
de Leon J. Pharmacogenetic tests in psychiatry: from fear to failure to hype. Journal of Clinical Psychopharmacology 2016; 36: 299-304.
Jose de Leon
December 15, 2016