Skip to main content
SpringerLink
Log in

Pharmacogenomics of Psychiatric Drugs

  • Chapter
  • First Online:
Pharmacogenomics in Precision Medicine

  • 680 Accesses

Abstract

Psychiatric pharmacogenomics combines the science of pharmacology and genetics to predict the interindividual outcomes (i.e., therapeutic response and adverse drug reactions) of psychiatric drug treatment. In the last decade, there has been an explosion in research examining the variation in therapeutic and adverse effects of antipsychotics (APs) across individuals. Current studies mainly focus on the identification of pharmacokinetic targets (e.g., cytochrome P450 superfamily) and pharmacodynamic targets (e.g., serotonin, dopamine, and norepinephrine). This chapter provides a review of relevant pharmacogenetic studies and treatments of psychiatric disorders in clinical practice. It also includes a brief discussion for future directions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Amare AT, Schubert KO, Baune BT (2017) Pharmacogenomics in the treatment of mood disorders: strategies and opportunities for personalized psychiatry. EPMA J 8(3):211–227

    Article  PubMed  PubMed Central  Google Scholar 

  2. Luck M, Turner M, Shad MU (2018) Effectiveness of genetically-guided treatment in first-episode schizophrenia. Schizophr Res 193:441–442

    Article  PubMed  Google Scholar 

  3. Zhou W, Xu Y, Lv QY, Sheng YH, Chen L, Li M et al (2019) Genetic association of olanzapine treatment response in Han Chinese schizophrenia patients. Front Pharmacol 10:177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Xu Q, Wu X, Li M, Huang H, Minica C, Yi Z et al (2016) Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population. Pharmacogenomics J 16(4):357–365

    Article  CAS  PubMed  Google Scholar 

  5. Shi Y, Li M, Song C, Xu Q, Huo R, Shen L et al (2017) Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients. Transl Psychiatry 7(7):e1170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tam V, Patel N, Turcotte M, Bosse Y, Pare G, Meyre D (2019) Benefits and limitations of genome-wide association studies. Nat Rev Genet 20(8):467–484

    Article  CAS  PubMed  Google Scholar 

  7. Cabaleiro T, Lopez-Rodriguez R, Roman M, Ochoa D, Novalbos J, Borobia A et al (2015) Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects. Int Clin Psychopharmacol 30(2):82–88

    Article  PubMed  Google Scholar 

  8. Yu H, Yan H, Wang L, Li J, Tan L, Deng W et al (2018) Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study. Lancet Psychiatry 5(4):327–338

    Article  PubMed  Google Scholar 

  9. Zhang JP, Robinson D, Yu J, Gallego J, Fleischhacker WW, Kahn RS et al (2019) Schizophrenia polygenic risk score as a predictor of antipsychotic efficacy in first-episode psychosis. Am J Psychiatry 176(1):21–28

    Article  PubMed  Google Scholar 

  10. Palk AC, Dalvie S, de Vries J, Martin AR, Stein DJ (2019) Potential use of clinical polygenic risk scores in psychiatry-ethical implications and communicating high polygenic risk. Philos Ethics Humanit Med 14(1):4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang Q, Wu HM, Yue WH, Yan H, Zhang YM, Tan LW et al (2018) Effect of damaging rare mutations in synapse-related gene sets on response to short-term antipsychotic medication in Chinese patients with schizophrenia a randomized clinical trial. JAMA Psychiat 75(12):1261–1269

    Article  Google Scholar 

  12. Manu P, Dima L, Shulman M, Vancampfort D, De Hert M, Correll CU (2015) Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management. Acta Psychiatr Scand 132(2):97–108

    Article  CAS  PubMed  Google Scholar 

  13. Whicher CA, Price HC, Holt RIG (2018) Mechanisms in endocrinology: antipsychotic medication and type 2 diabetes and impaired glucose regulation. Eur J Endocrinol 178(6):R245–R258

    Article  CAS  PubMed  Google Scholar 

  14. Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA (2017) Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat 13:2231–2241

    Article  PubMed  PubMed Central  Google Scholar 

  15. Musil R, Obermeier M, Russ P, Hamerle M (2015) Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf 14(1):73–96

    Article  CAS  PubMed  Google Scholar 

  16. Singh R, Bansal Y, Medhi B, Kuhad A (2019) Antipsychotics-induced metabolic alterations: recounting the mechanistic insights, therapeutic targets and pharmacological alternatives. Eur J Pharmacol 844:231–240

    Article  CAS  PubMed  Google Scholar 

  17. Malan-Müller S, Kilian S, van den Heuvel LL, Bardien S, Asmal L, Warnich L et al (2016) A systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia. Schizophr Res 170(1):1–17

    Article  PubMed  Google Scholar 

  18. Zhang JP, Malhotra AK (2018) Recent progress in pharmacogenomics of antipsychotic drug response. Curr Psychiatry Rep 20(4):24

    Article  PubMed  Google Scholar 

  19. El-Mallakh RS, Roberts RJ, El-Mallakh PL, Findlay LJ, Reynolds KK (2016) Pharmacogenomics in psychiatric practice. Clin Lab Med 36(3):507–523

    Article  PubMed  Google Scholar 

  20. Health Quality Ontario (2017) Pharmacogenomic testing for psychotropic medication selection: a systematic review of the Assurex Genesight Psychotropic test. Ont Health Technol Assess Ser 17(4):1–39

    Google Scholar 

  21. Ravyn D, Ravyn V, Lowney R, Nasrallah HA (2013) CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res 149(1–3):1–14

    Article  PubMed  Google Scholar 

  22. Zhang JP, Robinson DG, Gallego JA, John M, Yu J, Addington J et al (2015) Association of a schizophrenia risk variant at the DRD2 locus with antipsychotic treatment response in first-episode psychosis. Schizophr Bull 41(6):1248–1255

    Article  PubMed  PubMed Central  Google Scholar 

  23. Meltzer HY (2017) New trends in the treatment of schizophrenia. CNS Neurol Disord Drug Targets 16(8):900–906

    CAS  PubMed  Google Scholar 

  24. Siskind DJ, Lee M, Ravindran A, Zhang Q, Ma E, Motamarri B et al (2018) Augmentation strategies for clozapine refractory schizophrenia: a systematic review and meta-analysis. Aust N Z J Psychiatry 52(8):751–767

    Article  PubMed  Google Scholar 

  25. Vita A, Minelli A, Barlati S, Deste G, Giacopuzzi E, Valsecchi P et al (2019) Treatment-resistant schizophrenia: genetic and neuroimaging correlates. Front Pharmacol 10:402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Samanaite R, Gillespie A, Sendt KV, McQueen G, MacCabe JH, Egerton A (2018) Biological predictors of clozapine response: a systematic review. Front Psych 9:327

    Article  Google Scholar 

  27. Dougall N, Maayan N, Soares-Weiser K, McDermott LM, McIntosh A (2015) Transcranial magnetic stimulation for schizophrenia. Schizophr Bull 41(6):1220–1222

    Article  PubMed  PubMed Central  Google Scholar 

  28. WHO (2017) Depression and other common mental disorders. World Health Organization, Geneva

    Google Scholar 

  29. Fabbri C, Crisafulli C, Calabro M, Spina E, Serretti A (2016) Progress and prospects in pharmacogenetics of antidepressant drugs. Expert Opin Drug Metab Toxicol 12(10):1157–1168

    Article  CAS  PubMed  Google Scholar 

  30. Fabbri C, Serretti A (2015) Pharmacogenetics of major depressive disorder: top genes and pathways toward clinical applications. Curr Psychiatry Rep 17(7):50

    Article  PubMed  Google Scholar 

  31. Altar CA, Carhart J, Allen JD, Hall-Flavin D, Winner J, Dechairo B (2015) Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: evidence from three clinical studies. Mol Neuropsychiatry 1(3):145–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Torrellas C, Carril JC, Cacabelos R (2017) Optimization of antidepressant use with pharmacogenetic strategies. Curr Genomics 18(5):442–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Breitenstein B, Scheuer S, Holsboer F (2014) Are there meaningful biomarkers of treatment response for depression? Drug Discov Today 19(5):539–561

    Article  CAS  PubMed  Google Scholar 

  34. Manoharan A, Shewade DG, Rajkumar RP, Adithan S (2016) Serotonin transporter gene (SLC6A4) polymorphisms are associated with response to fluoxetine in south Indian major depressive disorder patients. Eur J Clin Pharmacol 72(10):1215–1220

    Article  CAS  PubMed  Google Scholar 

  35. Kautzky A, Baldinger P, Souery D, Montgomery S, Mendlewicz J, Zohar J et al (2015) The combined effect of genetic polymorphisms and clinical parameters on treatment outcome in treatment-resistant depression. Eur Neuropsychopharmacol 25(4):441–453

    Article  CAS  PubMed  Google Scholar 

  36. Yan TT, Wang LJ, Kuang WH, Xu JJ, Li SP, Chen J et al (2014) Brain-derived neurotrophic factor Val66Met polymorphism association with antidepressant efficacy: a systematic review and meta-analysis. Asia Pac Psychiatry 6(3):241–251

    Article  PubMed  Google Scholar 

  37. Colle R, Gressier F, Verstuyft C, Lepine JP, Ferreri F, Hardy P et al (2014) Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients. Eur Neuropsychopharmacol 24:S393

    Article  Google Scholar 

  38. Wang P, Zhang C, Lv Q, Bao C, Sun H, Ma G et al (2018) Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients. Eur J Clin Pharmacol 74(8):1011–1020

    Article  CAS  PubMed  Google Scholar 

  39. Hu Q, Zhang SY, Liu F, Zhang XJ, Cui GC, Yu EQ et al (2015) Influence of GNB3 C825T polymorphism on the efficacy of antidepressants in the treatment of major depressive disorder: a meta-analysis. J Affect Disord 172:103–109

    Article  CAS  PubMed  Google Scholar 

  40. Taranu A, El Asmar K, Colle R, Ferreri F, Polosan M, David D et al (2017) The Catechol-O-methyltransferase Val (108/158) Met genetic polymorphism cannot be recommended as a biomarker for the prediction of venlafaxine efficacy in patients treated in psychiatric settings. Basic Clin Pharmacol Toxicol 121(5):435–441

    Article  CAS  PubMed  Google Scholar 

  41. Qaseem A, Barry MJ, Kansagara D, Clinical Guidelines Committee of the American College of Physicians (2016) Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med 164(5):350–359

    Article  PubMed  Google Scholar 

  42. Lawton A, Moghraby OS (2016) Depression in children and young people: identification and management in primary, community and secondary care (NICE guideline CG28). Arch Dis Child Educ Pract Ed 101(4):206–209

    Article  PubMed  Google Scholar 

  43. Gartlehner G, Gaynes BN, Amick HR, Asher GN, Morgan LC, Coker-Schwimmer E et al (2016) Comparative benefits and harms of antidepressant, psychological, complementary, and exercise treatments for major depression: an evidence report for a clinical practice guideline from the American College of Physicians. Ann Intern Med 164(5):331–341

    Article  PubMed  Google Scholar 

  44. Cuijpers P (2018) The challenges of improving treatments for depression. JAMA 320(24):2529–2530

    Article  PubMed  Google Scholar 

  45. Lett TA, Walter H, Brandl EJ (2016) Pharmacogenetics and imaging-pharmacogenetics of antidepressant response: towards translational strategies. CNS Drugs 30(12):1169–1189

    Article  CAS  PubMed  Google Scholar 

  46. Rosenblat JD, Lee Y, McIntyre RS (2018) The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: a meta-analysis. J Affect Disord 241:484–491

    Article  PubMed  Google Scholar 

  47. Hornberger J, Li QY, Quinn B (2015) Cost-effectiveness of combinatorial pharmacogenomic testing for treatment-resistant major depressive disorder patients. Am J Manag Care 21(6):E357–E365

    PubMed  Google Scholar 

  48. Najafzadeh M, Garces JA, Maciel A (2017) Economic evaluation of implementing a novel pharmacogenomic test (IDgenetix®) to guide treatment of patients with depression and/or anxiety. PharmacoEconomics 35(12):1297–1310

    Article  PubMed  PubMed Central  Google Scholar 

  49. Peterson K, Dieperink E, Anderson J, Boundy E, Ferguson L, Helfand M (2017) Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. Psychopharmacology 234(11):1649–1661

    Article  CAS  PubMed  Google Scholar 

  50. Ramasubbu R, Burgess A, Gaxiola-Valdez I, Cortese F, Clark D, Kemp A et al (2016) Amygdala responses to quetiapine XR and citalopram treatment in major depression: the role of 5-HTTLPR-S/Lg polymorphisms. Hum Psychopharmacol 31(2):144–155

    Article  CAS  PubMed  Google Scholar 

  51. Outhred T, Das P, Dobson-Stone C, Felmingham KL, Bryant RA, Nathan PJ et al (2016) Impact of 5-HTTLPR on SSRI serotonin transporter blockade during emotion regulation: a preliminary fMRI study. J Affect Disord 196:11–19

    Article  CAS  PubMed  Google Scholar 

  52. Sanchez-Martin A, Sanchez-Iglesias S, Garcia-Berrocal B, Lorenzo C, Gaedigk A, Isidoro-Garcia M (2016) Pharmacogenetics to prevent maniac affective switching with treatment for bipolar disorder: CYP2D6. Pharmacogenomics 17(12):1291–1293

    Article  CAS  PubMed  Google Scholar 

  53. Yuodelis-Flores C, Ries RK (2015) Addiction and suicide: a review. Am J Addict 24(2):98–104

    Article  PubMed  Google Scholar 

  54. Esser MB, Guy GP, Zhang K, Brewer RD (2019) Binge drinking and prescription opioid misuse in the US, 2012-2014. Am J Prev Med 57(2):197–208

    Article  PubMed  PubMed Central  Google Scholar 

  55. Crist RC, Clarke TK, Berrettini WH (2018) Pharmacogenetics of opioid use disorder treatment. CNS Drugs 32(4):305–320

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zahari Z, Lee CS, Ibrahim MA, Musa N, Yasin MAM, Lee YY et al (2016) Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). Am J Drug Alcohol Abuse 42(5):587–596

    Article  PubMed  Google Scholar 

  57. Crist RC, Phillips KA, Furnari MA, Moran LM, Doyle GA, McNicholas LF et al (2019) Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African-Americans with opioid use disorder. Pharmacogenomics J 19(3):260–268

    Article  CAS  PubMed  Google Scholar 

  58. Zhou Y, Ingelman-Sundberg M, Lauschke VM (2017) Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharmacol Ther 102(4):688–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kringen MK, Chalabianloo F, Bernard JP, Bramness JG, Molden E, Hoiseth G (2017) Combined effect of CYP2B6 genotype and other candidate genes on a steady-state serum concentration of methadone in opioid maintenance treatment. Ther Drug Monit 39(5):550–555

    Article  CAS  PubMed  Google Scholar 

  60. Lee MR, Tapocik JD, Ghareeb M, Schwandt ML, Dias AA, Le AN et al (2020) The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study. Mol Psychiatry 25:461

    Article  CAS  PubMed  Google Scholar 

  61. Kose S, Cetin M (2018) Psychiatric pharmacogenomics in the age of neuroscience: promises and challenges. Psychiatr Clin Psychopharmacol 28(3):231–235

    Article  Google Scholar 

  62. FDA (2018) Table of pharmacogenomic biomarkers in drug labeling

    Google Scholar 

  63. Pisanu C, Heilbronner U, Squassina A (2018) The role of pharmacogenomics in bipolar disorder: moving towards precision medicine. Mol Diagn Ther 22(4):409–420

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Personalized Medicine Research Center, Bio-X Institutes of Shanghai Jiao Tong University, Shanghai, China

    Shengying Qin, Jingsong Ma, Cong Huai & Wei Zhou

Authors
  1. Shengying Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingsong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cong Huai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shengying Qin .

Editor information

Editors and Affiliations

  1. School of Pharmacy, Fudan University, Shanghai, Shanghai, China

    Weimin Cai

  2. Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhaoqian Liu

  3. School of Pharmacy, Suzhou University, Suzhou, Jiangsu, China

    Liyan Miao

  4. School of Pharmacy, Fudan University, Shanghai, Shanghai, China

    Xiaoqiang Xiang

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Qin, S., Ma, J., Huai, C., Zhou, W. (2020). Pharmacogenomics of Psychiatric Drugs. In: Cai, W., Liu, Z., Miao, L., Xiang, X. (eds) Pharmacogenomics in Precision Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-3895-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation