Pharmacogenetic Approaches to Depression in Old Age

Year 2021, Volume: 7 Issue: 2, 173 - 179, 12.07.2021

Gül Özbey , Ceyda Özkoç Yunus Emre Özkan Kübra Koç Saka

https://doi.org/10.53394/akd.957675

Abstract

Late-life depression is a kind of major depressive disorder which depressive symptoms occurs
after the age of 50-65 years. Approximately one-third of patients with late-life depression do not
respond to current used antidepressants. Therefore, translation of pharmacogenetic knowledge into
clinical practice in late-life depression may provide improving efficacy and reducing side effects of
antidepressants. Although the majority of researchs on pharmacogenetics of antidepressants have
been reported for the younger adults, genetic variations that influence antidepressant treatment in
late-life depression should be elucidated for identification of pharmacogenetic testing strategies.
This review covers articles investigating the effects of genetic polymorphisms on pharmacokinetics,
therapeutic response and advers drug reactions of antidepressants in late-life depression.

Keywords

Antidepressant, Pharmacogenetics, Late-life depression

İleri Yaş Depresyonunda Farmakogenetik Yaklaşımlar

Abstract

Yaşlılık çağı depresyonu, depresif semptomların 50-65 yaştan sonra ortaya çıktığı bir majör depresif
bozukluk türüdür. Yaşlılık çağı depresyonu hastalarının yaklaşık olarak üçte biri günümüzde kullanılan
antidepresanlara yanıt vermemektedir. Farmakogenetik bilginin klinik pratiğe aktarılması yaşlılık çağı
depresyonu hastalarında antidepresanların etkinliğinin artırılmasını ve yan etkilerinin azaltılmasını
sağlayabilir. Antidepresanların farmakogenetiği ile ilgili çalışmaların birçoğu genç erişkinlerde
yapıldığından, farmakogenetik test stratejilerinin belirlenmesi için yaşlılık çağı depresyonunda
antidepresan tedaviyi etkileyen genetik varyasyonların aydınlatılması gerekmektedir. Bu derleme
yaşlılık çağı depresyonunda genetik polimorfizmlerin antidepresanların farmakokinetiği, terapötik
yanıt ve advers ilaç reaksiyonları üzerindeki etkilerini araştıran makaleleri kapsamaktadır.

Keywords

Antidepresan, Farmakogenetik, Yaşlılık-çağı depresyonu

References

• 1. Sachs-Ericsson N, Moxley JH, Corsentino E, Rushing NC, Sheffler J, Selby EA, Gotlib I, Steffens DC. Melancholia in later life: late and early onset differences in presentation, course, and dementia risk. Int J Geriatr Psychiatry 2014; 29:943-51.
• 2. Naismith SL, Norrie LM, Mowszowski L, Hickie IB. The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features. Prog Neurobiol 2012; 98:99-143.
• 3. Kok RM, Nolen WA, Heeren TJ. Efficacy of treatment in older depressed patients: a systematic review and meta-analysis of double-blind randomized controlled trials with antidepressants. J Affect Disord 2012; 141:103-15.
• 4. Bigos KL, Bies RR, Pollock BG. Population pharmacokinetics in geriatric psychiatry. Am J Geriatr Psychiatry 2006; 14:993-1003.
• 5. Mark TL, Joish VN, Hay JW, Sheehan DV, Johnston SS, Cao Z. Antidepressant use in geriatric populations: the burden of side effects and interactions and their impact on adherence and costs. Am J Geriatr Psychiatry 2011; 19:211-21.
• 6. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365:2002-12.
• 7. Marshe VS, Islam F, Maciukiewicz M, Bousman C, Eyre HA, Lavretsky H, Mulsant BH, Reynolds CF 3rd, Lenze EJ, Müller DJ. Pharmacogenetic Implications for Antidepressant Pharmacotherapy in Late-Life Depression: A Systematic Review of the Literature for Response, Pharmacokinetics and Adverse Drug Reactions. Am J Geriatr Psychiatry 2020; 28:609-29.
• 8. Abbott R, Chang DD, Eyre HA, Bousman CA, Merrill DA, Lavretsky H. Pharmacogenetic Decision Support Tools: A New Paradigm for Late-Life Depression? Am J Geriatr Psychiatry 2018; 26:125-33.
• 9. Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmöller J. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9:442-73.
• 10. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138:103-41.
• 11. Dücker CM, Brockmöller J. Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age- vs. Genotype-Related Differences. Clin Pharmacol Ther 2019; 105:625-40.
• 12. Ponticelli C, Sala G, Glassock RJ. Drug management in the elderly adult with chronic kidney disease: a review for the primary care physician. Mayo Clin Proc 2015; 90:633-45.
• 13. Waade RB, Hermann M, Moe HL, Molden E. Impact of age on serum concentrations of venlafaxine and escitalopram in different CYP2D6 and CYP2C19 genotype subgroups. Eur J Clin Pharmacol 2014; 70:933-40.
• 14. Murphy GM Jr, Pollock BG, Kirshner MA, Pascoe N, Cheuk W, Mulsant BH, Reynolds CF. CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression. Neuropsychopharmacology 2001; 25:737-43.
• 15. Bijl MJ, Visser LE, Hofman A, Vulto AG, van Gelder T, Stricker BH, van Schaik RH. Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants. Br J Clin Pharmacol 2008; 65:558-64.
• 16. Murphy GM, Kremer C, Rodrigues HE, Schatzberg AF. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 2003; 160:1830-35.
• 17. Feng Y, Pollock BG, Ferrell RE, Kimak MA, Reynolds CF, Bies RR. Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling. Br J Clin Pharmacol 2006; 61:558-69.
• 18. Whyte EM, Romkes M, Mulsant BH, Kirshne MA, Begley AE, Reynolds CF, Pollock BG. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry 2006; 21:542-49.
• 19. Sarginson JE, Lazzeroni LC, Ryan HS, Ershoff BD, Schatzberg AF, Murphy GM. ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression. Pharmacogenet Genomics 2010; 20:467-75.
• 20. Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK. Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. JAMA 2006; 296:1609-18.
• 21. Marshe VS, Maciukiewicz M, Rej S, Tiwari AK, Sibille E, Blumberger DM, Karp JF, Lenze EJ, Reynolds CF 3rd, Kennedy JL, Mulsant BH, Müller DJ. Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults. Am J Psychiatry 2017; 174:468-75.
• 22. Lavretsky H, Siddarth P, Kumar A, Reynolds CF. The effects of the dopamine and serotonin transporter polymorphisms on clinical features and treatment response in geriatric depression: a pilot study. Int J Geriatr Psychiatry 2008; 23:55-59.
• 23. Murphy GM, Hollander SB, Rodrigues HE, Kremer C, Schatzberg AF. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Arch Gen Psychiatry 2004; 61:1163-69.
• 24. Alexopoulos GS, Murphy CF, Gunning-Dixon FM, Glatt CE, Latoussakis V, Kelly RE Jr, Kanellopoulos D, Klimstra S, Lim KO, Young RC, Hoptman MJ. Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression. J Affect Disord 2009; 119:132-41.
• 25. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF, Kupfer DJ. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23:587-90.
• 26. Durham LK, Webb SM, Milos PM, Clary CM, Seymour AB. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl) 2004; 174:525-29.
• 27. Seripa D, Pilotto A, Paroni G, Fontana A, D'Onofrio G, Gravina C, Urbano M, Cascavilla L, Paris F, Panza F, Padovani A, Pilotto A. Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life. J Psychopharmacol 2015; 29:623-33.
• 28. Garfield LD, Müller DJ, Kennedy JL, Mulsant BH, Reynolds CF 3rd, Teitelbaum SL, Civitelli R, Dixon D, Todorov AA, Lenze EJ. Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults. World J Biol Psychiatry 2014; 15:404-10.
• 29. Yohn CN, Gergues MM, Samuels BA. The role of 5-HT receptors in depression. Mol Brain 2017; 10:28.
• 30. Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacol Ther 2013; 137:119-31.
• 31. Scutt G, Overall A, Scott R, Patel B, Hachoumi L, Yeoman M, Wright J. Does the 5-HT (1A) rs6295 polymorphism influence the safety and efficacy of citalopram therapy in the oldest old? Ther Adv Drug Saf 2018; 9:355-66.
• 32. Rawson KS, Dixon D, Civitelli R, Peterson TR, Mulsant BH, Reynolds CF, Lenze EJ. Bone Turnover with Venlafaxine Treatment in Older Adults with Depression. J Am Geriatr Soc 2017; 65:2057-63.
• 33. Antypa N, Drago A, Serretti A. The role of COMT gene variants in depression: Bridging neuropsychological, behavioral and clinical phenotypes. Neurosci Biobehav Rev 2013; 37:1597-610.
• 34. Zannas AS, McQuoid DR, Steffens DC, Chrousos GP, Taylor WD. Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms. Stress 2012; 15:425-34.
• 35. Björkholm C, Monteggia LM. BDNF- a key transducer of antidepressant effects. Neuropharmacology 2016; 102:72-79.
• 36. Ribeiro L, Busnello JV, Cantor RM, Whelan F, Whittaker P, Deloukas P, Wong ML, Licinio J. The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Neuroreport 2007; 18:1291-93.
• 37. Alexopoulos GS, Glatt CE, Hoptman MJ, Kanellopoulos D, Murphy CF, Kelly RE, Morimoto SS, Lim KO, Gunning FM. BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression. J Affect Disord 2010; 125:262-68.
• 38. Taylor WD, McQuoid DR, Ashley-Koch A, MacFall JR, Bridgers J, Krishnan RR, Steffens DC. BDNF Val66Met genotype and 6-month remission rates in late-life depression. Pharmacogenomics J 2011; 11:146-54.
• 39. Murphy GM, Sarginson JE, Ryan HS, O'Hara R, Schatzberg AF, Lazzeroni LC. BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression. Pharmacogenet Genomics 2013; 23:301-13.
• 40. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 2009; 34:86-95.
• 41. Sarginson JE, Lazzeroni LC, Ryan HS, Schatzberg AF, Murphy GM. FKBP5 polymorphisms and antidepressant response in geriatric depression. Am J Med Genet B Neuropsychiatr Genet 2010; 153:554-60.
• 42. Jamerson BD, Payne ME, Garrett ME, Ashley-Koch AE, Speer MC, Steffens DC. Folate metabolism genes, dietary folate and response to antidepressant medications in late-life depression. Int J Geriatr Psychiatry 2013; 28:925-32.
• 43. Diniz CRAF, Casarotto PC, Fred SM, Biojone C, Castrén E, Joca SRL. Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN. Neuropharmacology 2018; 135:163-71.
• 44. Kondo DG, Speer MC, Krishnan KR, McQuoid DR, Slifer SH, Pieper CF, Billups AV, Steffens DC. Association of AGTR1 with 18-month treatment outcome in late-life depression. Am J Geriatr Psychiatry 2007; 15:564-72.
• 45. Marshe VS, Gorbovskaya I, Kanji S, Kish M, Müller DJ. Clinical implications of APOE genotyping for late-onset Alzheimer's disease (LOAD) risk estimation: a review of the literature. J Neural Transm (Vienna) 2019; 126:65-85.
• 46. Murphy GM, Kremer C, Rodrigues H, Schatzberg AF, Group MvpS. The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients. Biol Psychiatry 2003; 54:665-73.
• 47. Finkelstein J, Friedman C, Hripcsak G, Cabrera M. Potential utility of precision medicine for older adults with polypharmacy: a case series study. Pharmgenomics Pers Med 2016; 9:31-45.
• 48. Bebia Z, Buch SC, Wilson JW, Frye RF, Romkes M, Cecchetti A, Chaves-Gnecco D, Branch RA. Bioequivalence revisited: influence of age and sex on CYP enzymes. Clin Pharmacol Ther 2004; 76:618-27.