Editorial
Pharmacogenetics in Psychiatry
Author
Daniel J. Müller1, 2, 3
Affiliations
1 Campbell Family Mental Health Research Institute, Centre for
Addiction and Mental Health, Toronto, ON, Canada
2 Department of Psychiatry, University of Toronto, Toronto, ON,
Canada
3 Department of Pharmacology, University of Toronto, Toronto,
ON, Canada
received 11.05.2020
revised 01.07.2020
accepted 02.07.2020
Bibliography
DOI https://doi.org/10.1055/a-1212-1101
Pharmacopsychiatry 2020; 53: 153–154
© Georg Thieme Verlag KG Stuttgart · New York
ISSN 0176-3679
This Special Issue on Pharmacogenetics in Psychiatry consists of
five selected articles which encompass the first concepts of phar-
macogenetics, to implementation strategies applyng pharmaco-
genetic testing into psychiatric clinical practice.
The first article by Müller & Rizhanovsky [1], illuminates how an-
cient scientists such as Pythagoras, already addressed challenges
of inter-individual variability observed in people who consumed
fava beans. While unaware of the molecular genetic causes, herit-
ability factors were long suspected and first proven for heritable
alkaptonuria by Garrod in the early 20th century. Unfortunately, the
first discoveries in genetics of such kind became systematically dis-
torted by the ill-informed eugenic movement which would facili-
tate the ignition of WWII. Following WWII, three clinical scientists
(Drs. Kalow, Motulsky, and Vogel) independently conceptualized
and greatly advanced modern pharmacogenetics, setting the foun-
dations for the new era of personalized (‘precision’) medicine.
The second article by Brown et al. [2] notes that at the time of
writing in 2019, there were 39 psychiatric drugs with pharmacog-
enomic language listed in their product labelling. Strikingly, 36 con-
tain information on CYP2C19 and CYP2D6 metabolizer status, mak-
ing both genes the primary targets in any implementation strate-
gy for pharmacogenetic testing. The article then illuminates the
perspectives from the views of important stakeholders in facilitat-
ing implementation, namely clinicians, pharmacists, implementa-
tion scientists, genetic counselors, and industry. While analytical
and clinical validity as well as clinical and economic utility analyses
are still underway, the article concludes that from a pragmatic point
of view, genetic information should be used if available (e.g., for
CYP metabolizer status) and might be most applicable in guiding
Müller DJ. Pharmacogenetics in Psychiatry. Pharmacopsychiatry 2020; 53: 153–154
Correspondence
Daniel J. Mueller, MD PhD
Professor Department of Psychiatry
University of Toronto
Centre for Addiction and Mental Health (CAMH)
250 College Street, R132
M5T 1R8 Toronto, Ontario
Canada
daniel.mueller@camh.ca
Downloaded by: Karolinska Institutet. Copyrighted material.
medication decisions for patients with depression after failing one
medication trial.
Fan & Bousman [3] investigated in their article whether com-
mercial pharmacogenetic testing kits are useful to facilitate imple-
mentation of medication dosing guidelines. The authors reviewed
22 commercial test panels and noted that six gene-drug pairs
(CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline,
CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline)
were included by all tests. This, along with other factors such as
types of alleles tested, demonstrated substantial variation among
the different test panels, raising the importance of choosing any
given test thoughtfully.
The article by Menke et al. [4] describes a new study protocol
developed at the University Clinic of Würzburg (Northern Bavaria;
Germany). This novel personalized medicine approach aims to in-
clude genetic data from CYP2C19 and CYP2D6 as well as addition-
al information such as clinical characteristics, history of childhood
trauma, biomarkers, therapeutic drug monitoring (TDM), epige-
netics, and polygenic risk scores to develop a machine learning
based, combinatorial algorithm. While such strategies will likely re-
quire large data sets, these efforts are important to explore addi-
tive and interactive effects of factors contributing to disease risk,
drug metabolism, treatment response, and adverse effects.
Bättig et al. [5] report on a naturalistic pharmacogenetic study
conducted in a psychiatric hospital with inpatients treated for de-
pression using a commercially available test panel. A prospective
pharmacogenetic-tested intervention cohort of n = 49 with geno-
type-guided treatment was compared retrospectively to a control
cohort of n = 94 patients for a variety of measures. The interven-
153
 Editorial
tion cohorts required significantly less hospitalization days than
the control group, with antidepressant naïve patients showing the
largest benefit. Notably, this hospital already developed close in-
terdisciplinary exchange between prescribing psychiatrists and the
onsite pharmacist (“Aichberger Modell”) in order to best possibly
account for phenoconversion and drug-drug interaction. It is plau-
sible that scrutinizing for both drug-drug interactions and gene-
drug interaction at the same time of antidepressant medication
prescription will lead to a significant treatment optimization.
In summary, propelled by recommendations from expert groups
and regulatory agencies, pharmacogenetic testing is becoming in-
creasingly implemented in clinical practice. However, test panels
must be evaluated and chosen thoughtfully, genetic information
to be interpreted as useful, and additional clinical information
weighed along with other factors which can also influence treat-
ment outcomes.
Conflict of Interest
The authors declare that they have no conflict of interest.
154
References
[1] Müller DJ, Rizhanovsky Z. From the Origins of Pharmacogenetics to
First Applications in Psychiatry. Pharmacopsychiatry 2020; 53: 155–161
[2] Brown L, Eum S, Haga SB et al. Clinical Utilization of Pharmacogenetics
in Psychiatry - Perspectives of Pharmacists, Genetic Counselors,
Implementation Science, Clinicians, and Industry. Pharmacopsychiatry
2020; 53: 162–173
[3] Fan M, Bousman CA. Commercial Pharmacogenetic Tests in Psychiatry:
Do they Facilitate the Implementation of Pharmacogenetic Dosing
Guidelines? Pharmacopsychiatry 2020; 53: 174–178
[4] Menke A, Weber H, Deckert J. Roadmap for Routine Pharmacogenetic
Testing in a Psychiatric University Hospital. Pharmacopsychiatry 2020;
53: 179–183
[5] Bättig VAD, Roll SC, Hahn M. Pharmacogenetic Testing in Depressed
Patients and Interdisciplinary Exchange between a Pharmacist and
Psychiatrists Results in Reduced Hospitalization Times. Pharmacopsychiatry
2020; 53: 185–192
Downloaded by: Karolinska Institutet. Copyrighted material.
Müller DJ. Pharmacogenetics in Psychiatry. Pharmacopsychiatry 2020; 53: 153–154