Abstract
Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode.
Trial registration ClinicalTrials.gov NCT02529462.
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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. https://doi.org/10.1159/000430915
Bousman CA, Hopwood M (2016) Commercial pharmacogenetic-based decision-support tools in psychiatry. Lancet Psychiatry 3(6):585–590. https://doi.org/10.1016/S2215-0366(16)00017-1
Bradley P, Shiekh M, Mehra V, Vrbicky K, Layle S, Olson MC, Maciel A, Cullors A, Garces JA, Lukowiak AA (2018) Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: a randomized clinical trial demonstrating clinical utility. J Psychiatr Res 96:100–107. https://doi.org/10.1016/j.jpsychires.2017.09.024
Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C (2009) Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 373(9665):746–758. https://doi.org/10.1016/S0140-6736(09)60046-5
Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J (2010) Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA J Am Med Assoc 303(1):47–53. https://doi.org/10.1001/jama.2009.1943
Guy W (ed) (1976) EC-DEU assessment manual for psychopharmacology—Revised (DHEW Publ No ADM 76–338). Department of Health, Education, and Welfare Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, Rockville, MD, U.S. pp 218–222
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23(1):56
Perez V, Salavert A, Espadaler J, Tuson M, Saiz-Ruiz J, Saez-Navarro C, Bobes J, Baca-Garcia E, Vieta E, Olivares JM, Rodriguez-Jimenez R, Villagran JM, Gascon J, Canete-Crespillo J, Sole M, Saiz PA, Ibanez A, de Diego-Adelino J, Menchon JM (2017) Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry 17(1):250. https://doi.org/10.1186/s12888-017-1412-1
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163(11):1905–1917. https://doi.org/10.1176/appi.ajp.163.11.1905
Sheehan DV, Keene MS, Eaddy M, Krulewicz S, Kraus JE, Carpenter DJ (2008) Differences in medication adherence and healthcare resource utilization patterns: older versus newer antidepressant agents in patients with depression and/or anxiety disorders. CNS Drugs 22(11):963–973
Singh AB (2015) Improved antidepressant remission in major depression via a pharmacokinetic pathway polygene pharmacogenetic report. Clin Psychopharmacol Neurosci Off Sci J Korean Coll Neuropsychopharmacol 13(2):150–156. https://doi.org/10.9758/cpn.2015.13.2.150
Singh AB, Bousman CA, Ng C, Berk M (2014) Antidepressant pharmacogenetics. Curr Opin Psychiatry 27(1):43–51. https://doi.org/10.1097/YCO.0000000000000023
Tansey KE, Guipponi M, Hu X, Domenici E, Lewis G, Malafosse A, Wendland JR, Lewis CM, McGuffin P, Uher R (2013) Contribution of common genetic variants to antidepressant response. Biol Psychiatry 73(7):679–682. https://doi.org/10.1016/j.biopsych.2012.10.030
Tedeschini E, Levkovitz Y, Iovieno N, Ameral VE, Nelson JC, Papakostas GI (2011) Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. J Clin Psychiatry 72(12):1660–1668. https://doi.org/10.4088/JCP.10r06531
Tham A, Jonsson U, Andersson G, Soderlund A, Allard P, Bertilsson G (2016) Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder—a systematic review and a meta-analysis. J Affect Disord 205:1–12. https://doi.org/10.1016/j.jad.2016.06.013
Wisniewski SR, Rush AJ, Nierenberg AA, Gaynes BN, Warden D, Luther JF, McGrath PJ, Lavori PW, Thase ME, Fava M, Trivedi MH (2009) Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR*D report. Am J Psychiatry 166(5):599–607. https://doi.org/10.1176/appi.ajp.2008.08071027
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Authors wish to thank Trialance SCCP (Barcelona, Spain) for providing statistical services, and the AB-GEN Collaborative Group.
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JE and MT are full-time employees of AB-Biotics SA, the company that developed the Neuropharmagen test used in this study. VP, JM and EV have served as consultants for AB-Biotics SA.
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Menchón, J.M., Espadaler, J., Tuson, M. et al. Patient characteristics driving clinical utility in psychiatric pharmacogenetics: a reanalysis from the AB-GEN multicentric trial. J Neural Transm 126, 95–99 (2019). https://doi.org/10.1007/s00702-018-1879-z
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DOI: https://doi.org/10.1007/s00702-018-1879-z