Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-16T11:27:09.206Z Has data issue: false hasContentIssue false

Chapter 24 - Pharmacogenomics and the Management of Mood Disorders

Published online by Cambridge University Press:  16 May 2024

By
Roos van Westrhenen
Edited by
Allan Young ,
Marsal Sanches ,
Jair C. Soares  and
Mario Juruena
Allan Young
Affiliation:
Institute of Psychiatry, King's College London
Marsal Sanches
Affiliation:
Baylor College of Medicine, Texas
Jair C. Soares
Affiliation:
McGovern Medical School, The University of Texas
Mario Juruena
Affiliation:
King's College London
Get access

Summary

Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase. Treatments for mental disorders are available, but their effect is limited due to patients’ (genetic) heterogeneity, low treatment compliance and frequent side effects. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience. Pharmacogenetic testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets .

Pharmacogenetics is a discipline that investigates genetic factors that affect the absorption, metabolism, and transport of drugs, thereby affecting therapy outcome. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recent studies in depressed patients show that genotyping of drug-metabolizing enzymes can increase the effectiveness of treatment, which could benefit millions of patients worldwide.

Keywords

pharmacogenomicspharmacogeneticsmetabolizer statusphenotypedosing guidelinespharmacogenomicspharmacogeneticsmetabolizer statusphenotypedosing guidelines
Type
Chapter
Information
Clinical Textbook of Mood Disorders , pp. 251 - 262
Publisher: Cambridge University Press
Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Vieta, E, Colom, F. Therapeutic options in treatment resistant depression. Ann Med 2011;43:7, 512–30. doi: 10.3109/07853890.2011.583675.CrossRefGoogle ScholarPubMed
Swedish Research Council on Health Technology Assessment (SBU). Treatment of Depression: A Systematic Review. 2004. ISBN 91-87890-87-9, 91–87890-887, 91–87890-94–12004.Google Scholar
Walker, E, Kestler, L, Bollini, A, Hochman, K. Schizophrenia: etiology and course. Annu Rev Psychol. 2004;55:410–30. doi.org/10.1146/annurev.psych.55.090902.141950.CrossRefGoogle Scholar
Altar, CA, Carhart, J, Allen, JD, et al. Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: evidence from three clinical studies. Mol Neuropsychiatry 2015;1(3):145–55. doi: 10.1159/000430915.Google ScholarPubMed
Porcelli, S, Drago, A, Fabbri, C, et al. Pharmacogenetics of antidepressant response. J Psychiatry Neurosci 2011.36(2):87–113.CrossRefGoogle ScholarPubMed
van Westrhenen, R, Aitchison, KJ, Ingelman-Sundberg, M, Jukic, MM. Pharmacogenomics of antidepressants and antipsychotic treatment: how far have we got and where are we going? Front Psych 2020;11:94 https://doi.10.3389/fpsyt.2020.00094CrossRefGoogle ScholarPubMed
Zhou, Y, Lauschke, VM. The genetic landscape of major drug metabolizing cytochrome P450 genes – an updated analysis of population-scale sequencing data. Pharmacogenomics J 2022;22:284–93. https://doi.org/10.1038/s41397-022-00288-2CrossRefGoogle ScholarPubMed
Ingelman-Sundberg, M, Persson, , Jukic, MM. Polymorphic expression of CYP2C19 and 2D6 in the developing and adult human brain causing variables in cognition, risk for depression and suicide: the search for endogenous substrates. Pharmacogenomics 2014:15(15):1841–4.CrossRefGoogle Scholar
Zackrinsson, AL, Lindblom, B, Ahler, J. High frequency of occurrence of CYP2D6 gene duplication/multiduplication in indicating ultrarapid metabolism among suicide cases. Clin Pharmacol Ther 2011;3:354-9.Google Scholar
Hall-Flavin, DK, Winner, JG, Allen, JD, et al. Using a pharmacogenomic algorithm to guide the treatment of depression. Transl Psychiatry 2012;2:e172. doi:10.1038/tp.2012.99.CrossRefGoogle ScholarPubMed
Hall-Flavin, DK, Winner, JG, Allen, JD, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics 2013;23(10):535–48. doi: 10.1097/FPC.0b013e3283649b9a. PubMed PMID: 24018772.CrossRefGoogle Scholar
Winner, JG, Carhart, JM, Altar, CA, et al. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med 2013;16(89):219–27. PubMed PMID: 24229738Google ScholarPubMed
Singh, AB. Improved antidepressant remission in major depression via a pharmacokinetic pathway polygene pharmacogenetic report. Clin Psychopharmacol Neurosci 2015;13(2):150–6. doi: 10.9758/cpn.2015.13.2.150.CrossRefGoogle Scholar
Perez, V, Salavert, A, Espadaler, J, et al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry 2017;14:17(1):250. doi: 10.1186/s12888-017-1412-1.CrossRefGoogle ScholarPubMed
Bradley, PJ, Shiekh, M, Mehra, V, et al. Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: randomized clinical trial demonstrating clinical utility. J Psych Res 2018;96:100–107. doi: 10.1016/.jpsychires.2017.09.024CrossRefGoogle ScholarPubMed
Greden, JF, Parikh, SV, Rothschild, AJ, et al. Impact of pharmacogenomics in major depressive disorder in the GUIDED trial: a large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res 2019;111:59–67 doi: 10.1038/tp.2012.99.CrossRefGoogle Scholar
Han, C, Wing, S-M, Bahk, W-M, et al. A pharmacogenomic-based antidepressant treatment for patients with major depressive disorder: results from an 8-week, randomized, single-blinded clinical trial. Clin Psychopharmacol Neurosci 2018;16:469–80.CrossRefGoogle ScholarPubMed
Tiwari, AK, Zai, CC, Altar, CA, et al. Clinical utility of combinatorial pharmacogenomic testing in depression: a Canadian patient- and rater-blinded, randomized, controlled trial. Transl Psychiatry 2022;12:101. https://doi.org/10.1038/s41398-022-01847-8CrossRefGoogle ScholarPubMed
Oslin, D.W, Lynch, KG, Shih, MC, et al. Effect of pharmacogenomic testing for drug-gene interactions on medication selection and remission of symptoms in major depressive disorder: the PRIME Care Randomized Clinical Trial. JAMA 2022;328(2):151–61. https://doi.org/10.1001/jama.2022.9805CrossRefGoogle ScholarPubMed
Shan, X, Zhao, W, Qiu, Y, et al. Preliminary clinical investigation of combinatorial pharmacogenomic testing for the optimized treatment of depression: a randomized single-blind study. Front Neurosci 2019;13:960. https://doi.org/10.3389/fnins.2019.00960CrossRefGoogle ScholarPubMed
McCarthy, MJ, Chen, Y, Demodena, A, et al. A prospective study to determine the clinical utility of pharmacogenetic testing of veterans with treatment-resistant depression. J Psychopharmacol 2021;35(8):992–1002. https://doi.org/10.1177/02698811211015224CrossRefGoogle ScholarPubMed
Perlis, RH, Dowd, D, Fava, M, Lencz, T, Krause, DS. Randomized, controlled, participant- and rater-blind trial of pharmacogenomic test-guided treatment versus treatment as usual for major depressive disorder. Depress Anxiety 2020;37(9):834–41. https://doi.org/10.1002/da.23029CrossRefGoogle ScholarPubMed
Vos, CF, ter Hark, SE, Schellekens, AFA, et al. Effectiveness of genotype-specific tricyclic antidepressant dosing in patients with major depressive disorder: a randomized clinical trial. JAMA Netw Open 2023;6(5):e2312443. doi:10.1001/jamanetworkopen.2023.12443Google ScholarPubMed
Hiemke, C, Bergemann, N, Clement, HW, et al. Consensus guidelines for therapeutic Drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018;51:9–62Google ScholarPubMed
van Westrhenen, R, van Schaik, RHN, van Gelder, T, et al. Policy and practice review: a first guideline on the use of pharmacogenetics in clinical psychiatric practice. Front Pharmacol 2021;12:640032. doi.org/10.3389/fphar.2021.640032Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×