Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials
Abstract
Aim: To conducted a systematic review and meta-analysis of prospective, randomized controlled trials (RCTs) that examined pharmacogenetic-guided decision support tools (DSTs) relevant to depressive symptom remission in major depressive disorder (MDD). Patients & methods: Random-effects meta-analysis was performed on RCTs that examined the effect of DSTs on remission rates in MDD. RCT quality was assessed using the Cochrane Collaboration Criteria. Results & conclusion: A total of 1737 eligible subjects from five RCTs were examined. Individuals receiving pharmacogenetic-guided DST therapy (n = 887) were 1.71 (95% CI: 1.17–2.48; p = 0.005) times more likely to achieve symptom remission relative to individuals who received treatment as usual (n = 850). Pharmacogenetic-guided DSTs might improve symptom remission among those with MDD.
References
- 1 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust. N. Z. J. Psychiatry 49(12), 1087–1206 (2015).
- 2 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 (2006).
- 3 . Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int. Clin. Psychopharmacol. 25(4), 189–198 (2010).
- 4 Using a pharmacogenomic algorithm to guide the treatment of depression. Transl. Psychiatry 2, e172 (2012).
- 5 . Predictive socioeconomic and clinical profiles of antidepressant response and remission. Depress. Anxiety 30(7), 624–630 (2013).
- 6 Contribution of common genetic variants to antidepressant response. Biol. Psychiatr. 73(7), 679–682 (2013).
- 7 Pharmacogenetics of antidepressants. Front. Pharmacol. 2, 6 (2011).
- 8 . Commercial pharmacogenetic-based decision-support tools in psychiatry. Lancet Psychiatry 3(6), 585–590 (2016).
- 9 Antidepressant prescribing in the precision medicine era: a prescriber's primer on pharmacogenetic tools. BMC Psychiatry 17(1), 60 (2017).
- 10 . Combinatorial versus individual gene pharmacogenomic testing in mental health: a perspective on context and implications on clinical utility. Yale J. Biol. Med. 88(4), 375–382 (2015).
- 11 . The clinical validity and utility of combinatorial pharmacogenomics: enhancing patient outcomes. Appl. Transl. Genom. 5, 47–49 (2015).
- 12 . Cost–effectiveness of combinatorial pharmacogenomic testing for treatment-resistant major depressive disorder patients. Am. J. Manag. Care 21(6), e357–365 (2015).
- 13 a naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders. Prim. Care Companion CNS Disord. 17(2), (2015).
- 14 Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. Am. J. Psychiatry 175(9), 873–886 (2018).
- 15 . What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy? Expert Rev. Clin. Pharmacol. 9(3), 351–354 (2016).
- 16 . Antidepressant pharmacogenetics. Am. J. Psychiatry 174(5), 417–418 (2017).
- 17 . Pharmacogenetic tests in psychiatry. Am. J. Psychiatry 175(2), 189 (2018).
- 18 . Misleading guidance from pharmacogenomic testing. Am. J. Psychiatry 174(10), 922–924 (2017).
- 19 The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700 (2009).
- 20 . Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Hoboken, NJ, USA (2011).
- 21 . Meta-Analysis with R. Springer, Switzerland (2015).
- 22 . Conducting meta-analyses in R with the metafor package. J. Stat Softw. 36(3), 1–48 (2010).
- 23 . Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics. BMC Med. Res. Methodol. 11, 41 (2011).
- 24 . Estimation of between-trial variance in sequential meta-analyses: a simulation study. Contemp. Clin. Trials 37(1), 129–138 (2014).
- 25 . Random-effects model for meta-analysis of clinical trials: an update. Contemp. Clin. Trials 28(2), 105–114 (2007).
- 26 . Outlier and influence diagnostics for meta-analysis. Res. Synth. Methods 1(2), 112–125 (2010).
- 27 . Quantifying heterogeneity in a meta-analysis. Stats. Med. 21(11), 1539–1558 (2002).
- 28 . An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 85(3), 415–424 (2000).
- 29 . A re-evaluation of random-effects meta-analysis. J. Royal Stat. Soc. Ser. A 172(1), 137–159 (2009).
- 30 . The case of the misleading funnel plot. BMJ. 333(7568), 597–600 (2006).
- 31 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin. Pharmacol. Ther. 98(2), 127–134 (2015).
- 32 Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin. Pharmacol. Ther. 102(1), 37–44 (2016).
- 33 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 (2017).
- 34 . Improved antidepressant remission in major depression via a pharmacokinetic pathway polygene pharmacogenetic report. Clin. Psychopharmacol. Neurosci. 13(2), 150–156 (2015).
- 35 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 (2017).
- 36 . Commercial pharmacogenetic-based decision-support tools in psychiatry. Lancet Psychiatry 3(6), 585–590 (2016).
- 37 . Pharmacogenetic tests to guide drug treatment in depression: comparison of the available testing kits and clinical trials. Prog. Neuropsychopharmacol. Biol. Psychiatry 86, 36–44 (2018).
- 38 . Industry sponsorship and research outcome. Cochrane Database Syst. Rev. 2, MR000033 (2017).
- 39 . 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 (2017).
- 40 . Does pharmacogenomic testing improve clinical outcomes for major depressive disorder? A systematic review of clinical trials and cost–effectiveness studies. J. Clin. Psychiatry 78(6), 720–729 (2017).
- 41 Combinatorial pharmacogenetics significantly improves response and remission for major depressive disorder: a large, blinded, randomized controlled trail. In: American Psychiatric Association Annual Meeting. American Psychiatric Association, New York, NY, USA (2018).
- 42 . Use of combinatorial pharmacogenomic testing in two cases from community psychiatry. Pharmacogenom. Pers. Med. 9, 79–84 (2016).
- 43 . A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov. Med. 16(89), 219–227 (2013).
- 44 . Systematic evaluation of commercial pharmacogenetic testing in psychiatry: a focus on CYP2D6 and CYP2C19 allele coverage and results reporting. Pharmacogenet. Genomics 27(11), 387–393 (2017).
- 45 Economic evaluations of pharmacogenetic and pharmacogenomic screening tests: a systematic review. second update of the literature. PLoS ONE 11(1), e0146262 (2016).
- 46 . Economic utility: combinatorial pharmacogenomics and medication cost savings for mental health care in a primary care setting. Clin Ther. 39(3), 592–602 (2017).
- 47 . Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools. Pharmacogenomics J. In Press (2018).
- 48 . Survey of US public attitudes toward pharmacogenetic testing. Pharmacogenomics J. 12(3), 197–204 (2012).
- 49 Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clin. Pharmacol. Ther. 91(3), 450–458 (2012).
- 50 Physicians’ opinions following pharmacogenetic testing for psychotropic medication. Psychiatry Res. 229(3), 913–918 (2015).
- 51 Patient perceptions of care as influenced by a large institutional pharmacogenomic implementation program. Clin. Pharmacol. Ther. 102(1), 106–114 (2016).