Skip to main content

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
Cancel
×
×
Home
  • Home
Article
  • Cited by 23
  • Cited by
    Crossref Citations
    Crossref logo
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.
    Corponi, Filippo Fabbri, Chiara and Serretti, Alessandro 2018. Pharmacogenetics. Vol. 83, Issue. , p. 297.
    Fabbri, Chiara and Serretti, Alessandro 2018. Understanding Depression. p. 3.
    Fabbri, Chiara Zohar, Joseph and Serretti, Alessandro 2018. Pharmacogenetic tests to guide drug treatment in depression: Comparison of the available testing kits and clinical trials. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 86, Issue. , p. 36.
    Fabbri, Chiara Hosak, Ladislav Mössner, Rainald Giegling, Ina Mandelli, Laura Bellivier, Frank Claes, Stephan Collier, David A. Corrales, Alejo Delisi, Lynn E. Gallo, Carla Gill, Michael Kennedy, James L. Leboyer, Marion Lisoway, Amanda Maier, Wolfgang Marquez, Miguel Massat, Isabelle Mors, Ole Muglia, Pierandrea Nöthen, Markus M. O’Donovan, Michael C. Ospina-Duque, Jorge Propping, Peter Shi, Yongyong St Clair, David Thibaut, Florence Cichon, Sven Mendlewicz, Julien Rujescu, Dan and Serretti, Alessandro 2017. Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response. The World Journal of Biological Psychiatry, Vol. 18, Issue. 1, p. 5.
    Peterson, Kimberly Dieperink, Eric Anderson, Johanna Boundy, Erin Ferguson, Lauren and Helfand, Mark 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, Vol. 234, Issue. 11, p. 1649.
    Pérez, Víctor Salavert, Ariana Espadaler, Jordi Tuson, Miquel Saiz-Ruiz, Jerónimo Sáez-Navarro, Cristina Bobes, Julio Baca-García, Enrique Vieta, Eduard Olivares, José M. Rodriguez-Jimenez, Roberto Villagrán, José M. Gascón, Josep Cañete-Crespillo, Josep Solé, Montse Saiz, Pilar A. Ibáñez, Ángela de Diego-Adeliño, Javier and Menchón, José M. 2017. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry, Vol. 17, Issue. 1,
    Bousman, Chad A. Forbes, Malcolm Jayaram, Mahesh Eyre, Harris Reynolds, Charles F. Berk, Michael Hopwood, Malcolm and Ng, Chee 2017. Antidepressant prescribing in the precision medicine era: a prescriber’s primer on pharmacogenetic tools. BMC Psychiatry, Vol. 17, Issue. 1,
    Amare, Azmeraw T. Schubert, Klaus Oliver and Baune, Bernhard T. 2017. Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry. EPMA Journal, Vol. 8, Issue. 3, p. 211.
    Bschor, T. Baethge, C. Hiemke, C. and Müller-Oerlinghausen, B. 2017. Genetische Tests zur Steuerung der Behandlung mit Antidepressiva. Der Nervenarzt, Vol. 88, Issue. 5, p. 495.
    Pereira, Cátia D. Martins, Filipa Wiltfang, Jens da Cruz e Silva, Odete A.B. and Rebelo, Sandra 2017. ABC Transporters Are Key Players in Alzheimer’s Disease. Journal of Alzheimer's Disease, Vol. 61, Issue. 2, p. 463.
    Espadaler, Jordi Tuson, Miquel Lopez-Ibor, Jose Miguel Lopez-Ibor, Franciso and Lopez-Ibor, Maria Ines 2017. Pharmacogenetic testing for the guidance of psychiatric treatment: a multicenter retrospective analysis. CNS Spectrums, Vol. 22, Issue. 04, p. 315.
    Najafzadeh, Mehdi Garces, Jorge A. and Maciel, Alejandra 2017. Economic Evaluation of Implementing a Novel Pharmacogenomic Test (IDgenetix®) to Guide Treatment of Patients with Depression and/or Anxiety. PharmacoEconomics, Vol. 35, Issue. 12, p. 1297.
    Fabbri, Chiara Crisafulli, Concetta Calabrò, Marco Spina, Edoardo and Serretti, Alessandro 2016. Progress and prospects in pharmacogenetics of antidepressant drugs. Expert Opinion on Drug Metabolism & Toxicology, Vol. 12, Issue. 10, p. 1157.
    El-Mallakh, Rif S. Roberts, R. Jeannie El-Mallakh, Peggy L. Findlay, Lillian Jan and Reynolds, Kristen K. 2016. Pharmacogenomics in Psychiatric Practice. Clinics in Laboratory Medicine, Vol. 36, Issue. 3, p. 507.
    Breitenstein, Barbara Scheuer, Sandra Brückl, Tanja Maria Meyer, Jobst Ising, Marcus Uhr, Manfred and Holsboer, Florian 2016. Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: Results from a randomized clinical study. Journal of Psychiatric Research, Vol. 73, Issue. , p. 86.
    Lett, Tristram A. Walter, Henrik and Brandl, Eva J. 2016. Pharmacogenetics and Imaging–Pharmacogenetics of Antidepressant Response: Towards Translational Strategies. CNS Drugs, Vol. 30, Issue. 12, p. 1169.
    Brückl, Tanja Maria and Uhr, Manfred 2016. ABCB1 genotyping in the treatment of depression. Pharmacogenomics, Vol. 17, Issue. 18, p. 2039.
    Mazerska, Zofia Mróz, Anna Pawłowska, Monika and Augustin, Ewa 2016. The role of glucuronidation in drug resistance. Pharmacology & Therapeutics, Vol. 159, Issue. , p. 35.
    Dubovsky, Steven L. and Dubovsky, Amelia N. 2015. The Role of Pharmacogenomics to Guide Treatment in Mood and Anxiety Disorders. Current Behavioral Neuroscience Reports, Vol. 2, Issue. 3, p. 154.
    Dubovsky, Steven L 2015. The usefulness of genotyping cytochrome P450 enzymes in the treatment of depression. Expert Opinion on Drug Metabolism & Toxicology, Vol. 11, Issue. 3, p. 369.
    Download full list
    ×
  • Get access
    Add to cart USD35.00
    Check if you have access via personal or institutional login
    Log in Register Recommend to librarian

The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study

  • Barbara Breitenstein (a1) (a2), Sandra Scheuer (a2), Hildegard Pfister (a2), Manfred Uhr (a2), Susanne Lucae (a2), Florian Holsboer (a1) (a2), Marcus Ising (a2) and Tanja M. Brückl (a2)...
Abstract
Background

The gene product of the ABCB1 gene, the P-glycoprotein, functions as a custodian molecule in the blood–brain barrier and regulates the access of most antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms predicted the response to antidepressants that are substrates of the P-gp, while the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim of the present study was to evaluate the clinical application of ABCB1 genotyping in antidepressant pharmacotherapy.

 Methods

Data came from 58 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project, whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton Depression Rating Scale (HAM-D) scores, remission rates, and duration of hospital stay were documented with dose and kind of antidepressant treatment.

 Results

Patients who received ABCB1 genotyping had higher remission rates [χ2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from hospital as compared to patients without ABCB1 testing. Among major allele homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter duration of hospital stay [rho(28) = –0.441, p = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome.

 Discussion

The implementation of ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to benefit from an increase in P-gp substrate dose.

 Conclusion

Results suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.
Copyright
COPYRIGHT: © Cambridge University Press 2013 
Corresponding author
*Address for correspondence: Dr. Tanja Brückl, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804 München, Germany. (Email brueckl@mpipsykl.mpg.de)
Footnotes
Hide All

Regardless of the order of the authors’ listed names, B. Breitenstein and S. Scheuer are joint first authors.

We thank Gertrud Ernst-Jansen, Karin Hofer, Elisabeth Kappelmann, Beate Siegel, Melanie Huber, Maik Ködel, and Susann Sauer for excellent technical assistance. Parts of the study were supported by a grant of the German Federal Ministry of Education and Research (BMBF), project no. 01KG0709.

Footnotes
References
Hide All
1. Rush, AJ, Trivedi, MH, Wisniewski, SR, etal. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 1905–1917.
2. Narasimhan, S, Lohoff, FW. Pharmacogenetics of antidepressant drugs: current clinical practice and future directions. Pharmacogenomics. 2012; 13(4): 441–464.
3. Horstmann, S, Binder, EB. Pharmacogenomics of antidepressant drugs. Pharmacol Ther. 2009; 124(1): 57–73.
4. Uhr, M, Grauer, MT, Holsboer, F. Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol Psychiatry. 2003; 54(8): 840–846.
5. Fukui, N, Suzuki, Y, Sawamura, K, etal. Dose-dependent effects of the 3435 C>T genotype of ABCB1 gene on the steady-state plasma concentration of fluvoxamine in psychiatric patients. Ther Drug Monit. 2007; 29(2): 185–189.
6. Uhr, M, Tontsch, A, Namendorf, C, etal. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008; 57(2): 203–209.
7. Gex-Fabry, M, Eap, CB, Oneda, B, etal. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit. 2008; 30: 474–482.
8. Kato, M, Fukuda, T, Serretti, A, etal. ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(2): 398–404.
9. Nikisch, G, Eap, CB, Baumann, P. Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacol Res. 2008; 58(5–6): 344–347.
10. Sarginson, JE, Lazzeroni, LC, Ryan, HS, etal. ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression. Pharmacogenet Genomics. 2010; 20(8): 467–475.
11. Lin, K-M, Chiu, Y-F, Tsai, I-J, etal. ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. Pharmacogenet Genomics. 2010; 21(4): 163–170.
12. Perroud, N, Bondolfi, G, Uher, R, etal. Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample. Pharmacogenomics. 2011; 12(3): 365–377.
13. De Klerk, OL, Nolte, IM, Bet, PM, etal. ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder. Pharmacogenomics J. 2012; 1–5.
14. Singh, AB, Bousman, CA, Ng, CH, Byron, K, Berk, M. ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression. Transl Psychiatry. In press. DOI: 10.1038/tp.2012.115.
15. Laika, B, Leucht, S, Steimer, W. ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack of association with side effects and therapeutic response in depressed inpatients treated with amitriptyline. Clin Chem. 2006; 52(5): 893–895.
16. Peters, EJ, Slager, SL, Kraft, JB, etal. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. Baune B, ed. PLoS One. 2008; 3(4): e1872.
17. Mihaljevic Peles, A, Bozina, N, Sagud, M, Rojnic Kuzman, M, Lovric, M. MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(6): 1439–1444.
18. Dong, C, Wong, M-L, Licinio, J. Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Mol Psychiatry. 2009; 14(12): 1105–1118.
19. Menu, P, Gressier, F, Verstuyft, C, etal. Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study. Neuropsychobiology. 2010; 62(3): 193–197.
20. Perlis, RH, Fijal, B, Dharia, S, Heinloth, AN, Houston, JP. Failure to replicate genetic associations with antidepressant treatment response in duloxetine-treated patients. Biol Psychiatry. 2010; 67(11): 1110–1113.
21. Uher, R, Perroud, N, Ng, MYM, etal. Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. Am J Psychiatry. 2010; 167(5): 555–564.
22. Holsboer, F. How can we realize the promise of personalized antidepressant medicines? Nat Rev Neurosci. 2008; 9(8): 638–646.
23. Hennings, JM, Owashi, T, Binder, EB, etal. Clinical characteristics and treatment outcome in a representative sample of depressed inpatients—findings from the Munich Antidepressant Response Signature (MARS) project. J Psychiatr Res. 2009; 43(3): 215–229.
24. Ising, M, Lucae, S, Binder, EB, etal. A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression. Arch Gen Psychiatry. 2009; 66(9): 966–975.
25. Wigginton, JE, Cutler, DJ, Abecasis, GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet. 2005; 76(5): 887–893.
26. Barrett, JC, Fry, B, Maller, J, Daly, MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005; 21(2): 263–265.
27. Uhr, M, Steckler, T, Yassouridis, A, Holsboer, F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology. 2000; 22(4): 380–387.
28. Uhr, M, Grauer, MT, Yassouridis, A, Ebinger, M. Blood-brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls. J Psychiatr Res. 2007; 41(1–2): 179–188.
29. Uhr, M, Grauer, MT. abcb1ab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice. J Psychiatr Res. 2003; 37(3): 179–185.
30. Wang, J-S, Zhu, H-J, Gibson, B-B, etal. Sertraline and its metabolite desmethylsertraline, but not bupropion or its three major metabolites, have high affinity for P-glycoprotein. Biol Pharm Bull. 2008; 31(2): 231–234.
31. Chiu, H-W, Li, T-C. Rapid weight gain during mirtazapine treatment. J Neuropsychiatry Clin Neurosci. 2011; 23: E7.
32. Roose, SP. Tolerability and patient compliance. J Clin Psychiatry. 1999; 60(suppl 17): 14–17; discussion 46–48.
33. Gury, C, Cousin, F. Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability. Encephale. 1999; 25(5): 470–476.
34. Jürgens, G, Jacobsen, CB, Rasmussen, HB, etal. Utility and adoption of CYP2D6 and CYP2C19 genotyping and its translation into psychiatric clinical practice. Acta Psychiatr Scand. 2012; 125(3): 228–237.
35. O'Brien, FE, Clarke, G, Fitzgerald, P, etal. Inhibition of P-glycoprotein enhances transport of imipramine across the blood-brain barrier: microdialysis studies in conscious freely moving rats. Br J Pharmacol. 2012; 166(4): 1333–1343.
36. Zhu, HJ, Wang, JS, Markowitz, JS, etal. Risperidone and paliperidone inhibit p-glycoprotein activity in vitro. Neuropsychopharmacology. 2007; 32(4): 757–764.
37. Feng, B, Mills, JB, Davidson, RE, etal. In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab Dispos. 2008; 36(2): 268–275.
38. Colabufo, NA, Berardi, F, Cantore, M, etal. Perspectives of P-glycoprotein modulating agents in oncology and neurodegenerative diseases: pharmaceutical, biological, and diagnostic potentials. J Med Chem. 2010; 53(5): 1883–1897.
39. Mrazek, DA, Biernacka, JM, O'Kane, DJ, etal. CYP2C19 variation and citalopram response. Pharmacogenet Genomics. 2011; 21(1): 1–9.
40. Horstmann, S, Lucae, S, Menke, A, etal. Association of GRIK4 and HTR2A genes with antidepressant treatment in the MARS cohort of depressed inpatients. Eur Neuropsychopharmacol. 2008; 18(suppl 4): 214–215.
41. Lucae, S, Ising, M, Horstmann, S, etal. HTR2A gene variation is involved in antidepressant treatment response. Eur Neuropsychopharmacol. 2010; 20(1): 65–68.
42. Porcelli, S, Fabbri, C, Serretti, A. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol. 2012; 22(4): 239–258.
43. Paddock, S, Laje, G, Charney, D, etal. Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry. 2007; 164(8): 1181–1188.
44. Binder, EB, Salyakina, D, Lichtner, P, etal. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 2004; 36(12): 1319–1325.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *

CAPTCHA *

Skip to the audio challenge
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 19
Total number of PDF views: 164 *
Loading metrics...

Abstract views

Total abstract views: 1321 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 12th June 2018. This data will be updated every 24 hours.

Cancel
Confirm
×