Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-23T03:12:33.043Z Has data issue: false hasContentIssue false
  • English
  • Français

Influence of combinations of drugs that act on the CYP2D6 metabolic pathway in the treatment of major depressive disorder: A population-based study

Published online by Cambridge University Press:  15 April 2020

A. Sicras-Mainar ,
P. Guijarro ,
B. Armada ,
M. Blanca-Tamayo  and
R. Navarro-Artieda
A. Sicras-Mainar*
Affiliation:
Department of Planning, Badalona Serveis Assistencials SA, Badalona, Barcelona, Spain
P. Guijarro
Affiliation:
Health Economics & Outcomes Research Manager, Pfizer, Madrid, Spain
B. Armada
Affiliation:
Medical Advisor, Pfizer, Madrid, Spain
M. Blanca-Tamayo
Affiliation:
Department of Psychiatry, Badalona Serveis Assistencials SA, Badalona, Barcelona, Spain
R. Navarro-Artieda
Affiliation:
Medical Documentation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
*
*Corresponding author. Planning and Organizational Development, Badalona Serveis Assistencials SA, Calle Gaietà Soler, 6-8 entlo, 08911 Badalona, Barcelona, Spain. Tel.: +34 93 507 26 84. E-mail address:[email protected] (A. Sicras-Mainar).
Get access

Abstract

Objective

To describe the frequency of drug combinations (substrate-substrate or substrate-inhibitor) with the potential to interfere with the CYP2D6 metabolic pathway in patients receiving antidepressant medication for major depressive disorder.

Methods

We carried out an observational study using outpatient medical records. We included adult subjects who initiated antidepressant medication during 2008–2010. Patients were assigned to three study groups: no combination, substrate-substrate, and substrate-inhibitor. Follow-up period was 12 months. Main measures: demographics, comorbidity and medication persistence. Statistical analysis included a logistic regression model, P < 0.05.

Results

Five thousand six hundred and thirty patients were recruited (61.9 years, 76.9% female), 24.4% (CI: 23.8 – 26.0%) received some kind of drug combination (substrate-substrate: 15.4%, substrate-inhibitor: 9.0%). Variables significantly associated with drugs combinations that may act on the CYP2D6 metabolic pathway were: dementia (OR = 4.2), neuropathy (OR = 4.2) and stroke (OR = 1.9), P < 0.001. Medication persistence at 12 months was longer in patients with no combination (55.3%) than in patients receiving substrate-substrate (50.5%) or substrate-inhibitor (45.0%) combinations, P < 0.001.

Conclusions

Twenty-five percent of major depressive disorder patients received a combination of drugs with the potential to interfere with CYP2D6 metabolic pathway. These combinations increased with comorbidity and resulted in shorter medication persistence of antidepressant treatment.

Keywords

Major depressionCYP2D6Substrate-substrateSubstrate-inhibitorComorbidity
Type
Original article
Information
European Psychiatry , Volume 29 , Issue 6 , August 2014 , pp. 331 - 337
Copyright
Copyright © Elsevier Masson SAS 2014

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

Alfaro, C.L., Lam, Y.W., Simpson, J., Ereshefsky, L.CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: intraindividual variability and plasma concentration correlations. J Clin Pharmacol 2000;40:58–66.CrossRefGoogle Scholar
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders IV - Text Revision (DSM-IV-TR). Washington: American Psychiatric Association; 2008.Google Scholar
Anonymous Guidelines for ATC classification. Oslo: Nordic Collaborating Centre for Drug Statistics Methodology; 1991.Google Scholar
Beshai, S., Dobson, K.S., Bockting, C.L., Quigley, L.Relapse and recurrence prevention in depression: current research and future prospects. Clin Psychol Rev 2011;31:1349–1360.CrossRefGoogle ScholarPubMed
Campbell, L.C., Clauw, D.J., Keefe, F.J.Persistent pain and depression: a biopsychosocial perspective. Biol Psychiatry 2003;54:399–409.CrossRefGoogle ScholarPubMed
Charlson, M.E., Pompei, P., Ales, K.L., Mackenzie, C.R.A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–383.CrossRefGoogle ScholarPubMed
Clark, K., Weir, C.A review of depression prevention in primary care. W V Med J 2012;108:64–68.Google ScholarPubMed
Conde, V., Franch, J.L.Escalas de evaluación comportamental para la cuantificación de la sintomatología psicopatológica en los trastornos angustiosos y depresivos. Departamento de psicología médica y de psiquiatría del Hospital Clínico de la Facultad de Medicina de Valladolid; 1984.Google Scholar
Duhoux, A., Fournier, L., Nguyen, C.T., Roberge, P., Beveridge, R.Guideline concordance of treatment for depressive disorders in Canada. Soc Psychiatry Epidemiol 2009;44:385–392.CrossRefGoogle ScholarPubMed
Egberts, A.C.G., Borgh, J.T., Brodie-Meijer CCE:, Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol 1997;12:181–182.CrossRefGoogle ScholarPubMed
Elliot, V., Hersh, E.V., Pinto, A., Moore, P.A.Adverse drug interactions involving common prescription and over-the-counter analgesic agents. Clin Ther 2007;29:2477–2497.Google Scholar
Espen Molden, Æ., Beate Hennie Garcia, Æ., Pia Braathen Anne Elise Eggen Co-prescription of cytochrome P450 2D6/3A4 inhibitor-substrate pairs in clinical practice. A retrospective analysis of data from Norwegian primary pharmacies. Eur J Clin Pharmacol 2005;61:119–125.CrossRefGoogle Scholar
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Genet Med 2007;9:819–825.CrossRefGoogle Scholar
Evans, D.L., Charney, D.S., Lewis, L.et al.Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 2005;58:175–189.CrossRefGoogle ScholarPubMed
Gabilondo, A., Vilagut, G., Pinto-Meza, A., Haro, J.M., Alonso, J.Comorbidity of major depressive episode and chronic physical conditions in Spain, a country with low prevalence of depression. Gen Hosp Psychiatry 2012;34:510–517.CrossRefGoogle ScholarPubMed
Gerretsen, P., Pollock, B.G.Pharmacogenetics and the serotonin transporter in late-life depression. Expert Opin Drug Metab Toxicol 2008;4:1465–1478.CrossRefGoogle ScholarPubMed
Gili, M., Comas, A., Garcia, M., Monzon, S., Antoni, S.B., Roca, M.Comorbidity between common mental disorders and chronic somatic diseases in primary care patients. Gen Hosp Psychiatry 2010;32:240–245.CrossRefGoogle ScholarPubMed
Gili, M., Garcia-Toro, M., Vives, M., Armengol, S., Garcia-Campayo, J., Soriano, J.B.et al.Medical comorbidity in recurrent versus first episode depressive patients. Acta Psychiatr Scand 2011;123:220–227.CrossRefGoogle ScholarPubMed
Gołab-Janowska, M., Honczarenko, K., Gawrońska-Szklarz, B., Potemkowski, A.CYP2D6 gene polymorphism as a probable risk factor for Alzheimer's disease and Parkinson's disease with dementia. Neurol Neurochir Pol 2007;41:113–121.Google ScholarPubMed
Haro, J.M., Palacin, C., Vilagut, G.et al.[Prevalence of mental disorders and associated factors: results from the ESEMeD-Spain study]. Med Clin (Barc) 2006;126:445–451.CrossRefGoogle Scholar
Ingelman-Sundberg, M., Evans, W.E.Unravelling the functional genomics of the human CYP2D6 gene locus. Pharmacogenetics 2001;11:553–554.CrossRefGoogle ScholarPubMed
Janchawee, B., Wongpoowarak, W., Owatranporn, T., Chongsuvivatwong, V.Pharmacoepidemiologic study of potencial drug interaction in outpatients of a university hospital in Thailand. J Clin Pharm Ther 2005;30:13–20.CrossRefGoogle Scholar
Keller, M.B., Hirschfeld, R.M., Demyttenaere, K., Baldwin, D.S.Optimizing outcomes in depression: focus on antidepressant compliance. Int Clin Psychopharmacol 2002;17:265–271.CrossRefGoogle ScholarPubMed
Kennedy, S.H., Lam, R.W., Nutt, D.J., Me, T.Treating depression effectively: applying evidence based guidelines. 2nd ed. Informa UK Ltd; 2007.CrossRefGoogle Scholar
Kessler, R.C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K.R.et al.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095–3105.CrossRefGoogle Scholar
Kessler, R.C., Chiu, W.T., Demler, O., Merikangas, K.R., Walters, E.E.Prevalence, severity and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617–627.CrossRefGoogle ScholarPubMed
Lamberts, H., Wood, M., Hofmans-Okkes, I.M.The international classification of primary care in the European community. With a multi-language layer. Oxford: Oxford University Press; 1993.Google Scholar
Laugesen, S., Enggaard, T.P., Pedersen, R.S.et al.Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther 2005;77:312–323.CrossRefGoogle ScholarPubMed
Li, Z., Zhang, Y., Wang, Z., Chen, J., Fan, J., Guan, Y.et al.The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: Data from multicenter, prospective, longitudinal clinic practice. J Psychiatr Res 2013;47:8–14.CrossRefGoogle ScholarPubMed
Malhi, G.S., Adams, D., Porter, R., Wignall, A., Lampe, L., O’Connor, N.et al.Northern Sydney Central Coast Mental Health Drug & Alcohol; NSW Health Clinical Redesign Program; CADE Clinic, University of Sydney. Clinical practice recommendations for depression. Acta Psychiatr Scand Suppl 4392009 8–26.CrossRefGoogle Scholar
Malhotra, A.K.The pharmacogenetics of depression: enter the GWAS. Am J Psychiatry 2010;167:493–495.CrossRefGoogle ScholarPubMed
McAlpine, D.E., Biernacka, J.M., Mrazek, D.A., O’Kane, D.J., Stevens, S.R., Langman, L.J.et al.Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. Ther Drug Monit 2011;33:14–20.CrossRefGoogle ScholarPubMed
Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., Ustun, B.Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 2007;370:851–858.CrossRefGoogle ScholarPubMed
Nelson, E.M., Philbrick, A.M.Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother 2012;46:1712–1716.CrossRefGoogle ScholarPubMed
Nichols, A.I., Tourian, K.A., Tse, S.Y., Paul, J.Desvenlafaxine for major depressive disorders: incremental clinical benefits from a second-generation serotonin-norepinephrine reuptake inhibitor. Expert Opin Drug Metab Toxicol 2010;6:1565–1574.CrossRefGoogle ScholarPubMed
Olfson, M., Marcus, S.C., Tedeschi, M., Wan, G.J.Continuity of antidepressant medication for adults with depression in the United States. Am J Psychiatry 2006;163:101–108.CrossRefGoogle ScholarPubMed
Peng, C.C., Glassman, P.A., Marks, I.R., Fowler, C., Castiglione, B., Good, C.B.Retrospective drug utilization review: incidence of clinically relevant potential drug-drug interactions in a large ambulatory population. J Manag Care Pharm 2003;9:513–522.Google Scholar
Preskorn, S.H., Nichols, A.I., Paul, J., Patroneva, A.L., Helzner, E.C., Guico-Pabia, C.J.Effect of desvenlafaxine on the cytochrome P450 2D6 enzyme system. J Psychiatr Pract 2008;14:368–378.CrossRefGoogle ScholarPubMed
Prince, M., Patel, V., Saxena, S.et al.No health without mental health. Lancet 2007;370:859–877.CrossRefGoogle ScholarPubMed
Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder (3rd ed). Available at: http://psychiatryonline.org/.Google Scholar
Rau, T., Wohlleben, G., Wuttke, H., Thuerauf, N., Lunkenheimer, J., Lanczik, M.et al.CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants–a pilot study. Clin Pharmacol Ther 2004;75:386–393.CrossRefGoogle ScholarPubMed
Rojo Venegas, K., Aguilera Gómez, M., Cañada Garre, M., García Sánchez, A., Contreras-Ortega, C., Calleja Hernández, M.A.Pharmacogenetics of osteoporosis: towards novel theranostics for personalized medicine?. OMICS 2012;16:638–651.CrossRefGoogle ScholarPubMed
Rush, A.J., Warden, D., Wisniewski, S.R., Fava, M., Trivedi, M.H., Gaynes, B.N.et al.STAR*D. Revising conventional wisdom. CNS Drugs 2009;23:627–647.Google ScholarPubMed
Sareen, J., Cox, B.J., Afifi, T.O., De Graaf, R., Asmundson, G.J., Ten Have, M.et al.Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry 2005;62:1249–1257.CrossRefGoogle ScholarPubMed
Sawada, N., Uchida, H., Suzuki, T., Watanabe, K., Kikuchi, T., Handa, T.et al.Persistence and compliance to antidepressant medication in patients with depression: a chart review. BMC Psychiatry 2009;9:38.CrossRefGoogle ScholarPubMed
Scott, K.M., Von Korff, M., Alonso, J.Age patterns in the prevalence of DSM-IV depressive/anxiety disorders with and without physical co-morbidity. Psychol Med 2008;38:1659–1669.CrossRefGoogle ScholarPubMed
Shams, M.E., Arneth, B., Hiemke, C., Dragicevic, A., Müller, M.J., Kaiser, R.et al.CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther 2006;31:493–502.CrossRefGoogle ScholarPubMed
Stein, D.J.Comorbidity in generalized anxiety disorder: impact and implications. J Clin Psychiatry 2001;62(Suppl. 11):29–36.Google ScholarPubMed
Strandell, J., Wahlin, S.Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database. Eur J Clin Pharmacol 2011;67:633–641.CrossRefGoogle ScholarPubMed
Szymańska, E., Bouwman, J., Strassburg, K., Vervoort, J., Kangas, A.J., Soininen, P.et al.Gender-dependent associations of metabolite profiles and body fat distribution in a healthy population with central obesity: towards metabolomics diagnostics. OMICS 2012;16:652–667.CrossRefGoogle Scholar
Tavassoli, N., Sommet, A., Lapeyre-Mestre, M., Bagheri, H., Montrastruc, J.L.Drug interactions with cholinesterase inhibitors: an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (Vidal, British National Formulary). Drug Saf 2007;30:1063–1071.CrossRefGoogle Scholar
Thase, M.E.Evaluating antidepressant therapies: remission as the optimal outcome. J Clin Psychiatry 2003:64(Suppl.):18–25.Google ScholarPubMed
van der Merwe, N., Bouwens, C.S., Pienaar, R., Van der Merwe, L., Yako, Y.Y., Geiger, D.H.et al.CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application. Metab Brain Dis 2012;27:319–326.CrossRefGoogle ScholarPubMed
Weiner, J.P., Starfield, B.H., Steinwachs, D.M., Mumford, L.M.Development and application of a population-oriented measure of ambulatory care case-mix. Med Care 1991;29:452–472.CrossRefGoogle ScholarPubMed
Woo, S.I., Kim, J.W., Seo, H.G., Park, C.H., Han, S.H., Kim, S.H.et al.CYP2D6*4 polymorphism is not associated with Parkinson's disease and has no protective role against Alzheimer's disease in the Korean population. Psychiatry Clin Neurosci 2001;55:373–377.CrossRefGoogle Scholar
Zimmernan, M., McGlinchey, J.B., Posternak, M.A., Friedman, M., Attiullah, N., Boerescu, D.How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry 2006;163:148–150.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.