Pharmacogenetic Implications for Antidepressant Pharmacotherapy in Late-Life Depression: A Systematic Review of the Literature for Response, Pharmacokinetics and Adverse Drug Reactions

Victoria S Marshe; Farhana Islam; Malgorzata Maciukiewicz; Chad Bousman; Harris A Eyre; Helen Lavretsky; Benoit H Mulsant; Charles F Reynolds 3rd; Eric J Lenze; Daniel J Müller

doi:10.1016/j.jagp.2020.01.007

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 Jun;28(6):609-629. doi: 10.1016/j.jagp.2020.01.007. Epub 2020 Feb 3.

Authors

Affiliations

¹ Institute of Medical Science, University of Toronto (VSM, BHM, DJM), Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada.
² Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada; Department of Pharmacology (FI, DJM), University of Toronto, Toronto, ON, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada.
⁴ Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology (CB), University of Calgary, Calgary, AB, Canada; Department of Psychiatry (CB), University of Melbourne, Melbourne, Victoria, Australia.
⁵ Innovation Institute, Texas Medical Center (HAE), Houston, TX; School of Medicine, IMPACT SRC, Deakin University (HAE), Geelong, Victoria, Australia; Brainstorm Lab, Department of Psychiatry and Behavioral Sciences (HAE), Stanford University, Palo Alto, CA; Discipline of Psychiatry (HAE), The University of Adelaide, Adelaide, South Australia, Australia.
⁶ Department of Psychiatry (HL), University of California, Los Angeles, CA.
⁷ Institute of Medical Science, University of Toronto (VSM, BHM, DJM), Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada; Department of Psychiatry (BHM, DJM), University of Toronto, Toronto, ON, Canada.
⁸ Department of Psychiatry (CFR), University of Pittsburgh, Pittsburgh, PA.
⁹ Healthy Mind Lab, Department of Psychiatry (EJL), Washington University, St. Louis, MO.
¹⁰ Institute of Medical Science, University of Toronto (VSM, BHM, DJM), Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada; Department of Pharmacology (FI, DJM), University of Toronto, Toronto, ON, Canada; Department of Psychiatry (BHM, DJM), University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.

PMID: 32122803
DOI: 10.1016/j.jagp.2020.01.007

Abstract

Affecting up to 15% of older adults, late-life depression (LLD) is characterized by the occurrence of depressive symptoms after the age of 50-65 years and maybe pathophysiologically distinct from depression in younger adults. Therefore, LLD is challenging to treat, and predictive genetic testing might be essential to improve treatment in this vulnerable population. The current review aims to provide a summary of the literature exploring genetic associations with antidepressant treatment outcomes in late-life. We conducted a systematic search of three integrated electronic databases. We identified 29 articles investigating genetic associations with antidepressant treatment outcomes, pharmacokinetic parameters, and adverse drug reactions in older adults. Given the small number of investigations conducted in older adults, it is difficult to conclude the presence or absence of genetic associations with the outcomes of interest. In sum, the most substantial amount of evidence exists for the CYP2D6 metabolizer status, SLC6A4 5-HTTLPR, and BDNF rs6265. These findings are consistent in the literature when not restricting to older adults, suggesting that similar treatment recommendations may be provided for older adults regarding genetic variation, such as those outlined for CYP2D6 by the Clinical Pharmacogenetics Implementation Consortium. Nonetheless, further studies are required in well-characterized samples, including genome-wide data, to validate if similar treatment adjustments are appropriate in older adults, given that there appear to be significant effects of genetic variation on antidepressant treatment factors.

Keywords: Late-life depression; antidepressant; pharmacogenetics; response; treatment outcomes.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Aged
Antidepressive Agents / adverse effects*
Antidepressive Agents / pharmacokinetics*
Brain-Derived Neurotrophic Factor / genetics
Cytochrome P-450 CYP2D6 / genetics
Depressive Disorder, Major / drug therapy*
Depressive Disorder, Major / etiology
Depressive Disorder, Major / genetics*
Humans
Pharmacogenetics*
Serotonin Plasma Membrane Transport Proteins / genetics
Treatment Outcome

Substances

Antidepressive Agents
Brain-Derived Neurotrophic Factor
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
BDNF protein, human
Cytochrome P-450 CYP2D6

Grants and funding

CIHR/Canada