Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial

Céline K Stäuble, Markus L Lampert, Samuel Allemann, Martin Hatzinger, Kurt E Hersberger, Henriette E Meyer Zu Schwabedissen, Christian Imboden, Thorsten Mikoteit, Céline K Stäuble, Markus L Lampert, Samuel Allemann, Martin Hatzinger, Kurt E Hersberger, Henriette E Meyer Zu Schwabedissen, Christian Imboden, Thorsten Mikoteit

Abstract

Background: It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response.

Methods: This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm.

Discussion: The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice.

Trial registration: ClinicalTrials.gov NCT04507555 . Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015 . Registered August 18, 2020.

Keywords: Antidepressant; Depression; Pharmaceutical care; Pharmacogenomics; Psychiatry.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study procedures

References

    1. Zajecka JM. Treating depression to remission. J Clin Psychiatry. 2003;64(Suppl 15):7–12. doi: 10.4088/JCP.v64n1019b.
    1. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. doi: 10.1176/appi.ajp.163.1.28.
    1. Holsboer-Trachsler E, Hättenschwiler JA, Beck J, Brand S, Hemmeter UM, Keck ME, Rennhard S, Hatzinger M, Merlo M, Bondolfi G, Preisig M, Gehret A, Bielinski D, Seifritz E. Die Akutbehandlung depressiver Episoden. Swiss Medical Forum. 2016;16(35):716–724. doi: 10.4414/smf.2016.02704.
    1. Meyer Zu Schwabedissen HE. The role of pharmacogenomics in individualized medicine. In: Fischer T, Langanke M, Marschall P, Michl S, editors. Individualized medicine–ethical, economical and historical perspectives. Springer, Cham; 2014. P. 93-112.
    1. Owen RP, Sangkuhl K, Klein TE, Altman RB. Cytochrome P450 2D6. Pharmacogenet Genomics. 2009;19(7):559–562. doi: 10.1097/FPC.0b013e32832e0e97.
    1. Hicks J, Sangkuhl K, Swen J, Ellingrod V, Müller D, Shimoda K, Bishop JR, Kharasch ED, Skaar TC, Gaedigk A, Dunnenberger HM, Klein TE, Caudle KE, Stingl JC. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology Therapeutics. 2017;102(1):37–44. doi: 10.1002/cpt.597.
    1. Van Schaik RHN, Müller DJ, Serretti A, Ingelman-Sundberg M. Pharmacogenetics in psychiatry: an update on clinical usability. Front Pharmacol. 2020;11. 10.3389/fphar.2020.575540.
    1. Pawlowski MA, Gazea M, Wollweber B, Dresler M, Holsboer F, Keck ME, Steiger A, Adamczyk M, Mikoteit T. Heart rate variability and cordance in rapid eye movement sleep as biomarkers of depression and treatment response. J Psychiatr Res. 2017;92:64–73. doi: 10.1016/j.jpsychires.2017.03.026.
    1. Mikoteit T, Beck J, Eckert A, Hemmeter U, Brand S, Bischof R, Holsboer-Trachsler E, Delini-Stula A. High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression. Psychopharmacologyc (Berl) 2014;231(15):2955–2965. doi: 10.1007/s00213-014-3475-8.
    1. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clinical Pharmacology Therapeutics. 2012;92(4):414–417. doi: 10.1038/clpt.2012.96.
    1. Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M, Dose T, Ebinger M, Rosenhagen M, Kohli M, Kloiber S, Salyakina D, Bettecken T, Specht M, Pütz B, Binder EB, Müller-Myhsok B, Holsboer F. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008;57(2):203–209. doi: 10.1016/j.neuron.2007.11.017.
    1. Breitenstein B, Scheuer S, Brückl TM, Meyer J, Ising M, Uhr M, Holsboer F. Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: results from a randomized clinical study. J Psychiatr Res. 2016;73:86–95. doi: 10.1016/j.jpsychires.2015.11.010.
    1. Schatzberg AF, Debattista C, Lazzeroni LC, Etkin A, Murphy GM, Williams LM. ABCB1 Genetic effects on antidepressant outcomes: a report from the iSPOT-D trial. Am J Psychiatr. 2015;172(8):751–759. doi: 10.1176/appi.ajp.2015.14050680.
    1. Jeiziner C, Suter K, Wernli U, Barbarino JM, Gong L, Whirl-Carrillo M, Klein TE, Szucs TD, Hersberger KE, Meyer zu Schwabedissen HE. Pharmacogenetic information in Swiss drug labels - a systematic analysis. Pharm J. 2021;21(4):423–434. doi: 10.1038/s41397-020-00195-4.
    1. Pérez V, Salavert A, Espadaler J, Tuson M, Saiz-Ruiz J, Sáez-Navarro C, 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;17(1).
    1. Han C, Wang S-M, Bahk W-M, Lee S-J, Patkar AA, Masand PS, Mandelli L, Pae CU, Serretti A. A Pharmacogenomic-based antidepressant treatment for patients with major depressive disorder: results from an 8-week, randomized, single-blinded clinical trial. Clinical Psychopharmacology and Neuroscience. 2018;16(4):469–480. doi: 10.9758/cpn.2018.16.4.469.
    1. Bradley P, Shiekh M, Mehra V, Vrbicky K, Layle S, Olson MC, Maciel A, Cullors A, Garces JA, Lukowiak AA. Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility. J Psychiatr Res. 2018;96:100–107. doi: 10.1016/j.jpsychires.2017.09.024.
    1. Hamilton M. A RATING SCALE FOR DEPRESSION. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. doi: 10.1136/jnnp.23.1.56.
    1. Beck AT, Beamesderfer A. Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry 1974;7(0):151-169, doi: 10.1159/000395074.
    1. Wisniewski SR, Rush AJ, Balasubramani GK, Trivedi MH, Nierenberg AA. Self-rated global measure of the frequency, intensity, and burden of side effects. J Psychiatr Pract. 2006;12(2):71–79. doi: 10.1097/00131746-200603000-00002.
    1. U.S. Department of health and human services: common terminology criteria for adverse events (CTCAE) version 5.0, _v5_Quick_Reference_8.5x11.pdf (2017). Accessed 15 June 2020.
    1. Stäuble CK, Lampert ML, Mikoteit T, Hatzinger M, Hersberger KE, Meyer Zu Schwabedissen HE. Pharmacogenetic-guided antidepressant selection as an opportunity for interprofessional collaboration: a case report. Life. 2021;11(7):673. doi: 10.3390/life11070673.
    1. Wolf C, Pauly A, Mayr A, Grömer T, Lenz B, Kornhuber J, Friedland K. Pharmacist-led medication reviews to identify and collaboratively resolve drug-related problems in psychiatry – a controlled, clinical trial. PLoS One. 2015;10(11):e0142011. doi: 10.1371/journal.pone.0142011.
    1. Hahn M, Ritter C, Roll SC. Validation of pharmacist–physician collaboration in psychiatry: ‘the Eichberger-model’. Int J Clin Pharm. 2018;40(5):1001–1004. doi: 10.1007/s11096-018-0664-2.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere