TY - JOUR
T1 - Pharmacogenetic Implications for Antidepressant Pharmacotherapy in Late-Life Depression
T2 - A Systematic Review of the Literature for Response, Pharmacokinetics and Adverse Drug Reactions
AU - Marshe, Victoria S.
AU - Islam, Farhana
AU - Maciukiewicz, Malgorzata
AU - Bousman, Chad
AU - Eyre, Harris A.
AU - Lavretsky, Helen
AU - Mulsant, Benoit H.
AU - Reynolds, Charles F.
AU - Lenze, Eric J.
AU - Müller, Daniel J.
N1 - Funding Information:
Ms. Marshe is supported through the Frederick Banting and Charles Best Canada Graduate Doctoral Research Award from the Canadian Institute for Health Research (# 394160 ). Dr. Maciukiewicz is supported by the Postdoctoral Fellowship from the Canadian Institute of Health Research (# 81655 ). Dr. Lenze is supported by funding from NIH and from the Taylor Family Institute for Innovative Psychiatric Research and the Center for Brain Research in Mood Disorders at Washington University . Dr. Mulsant receives compensation from the Department of Psychiatry, University of Toronto, Toronto, Ontario; the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario; and the University of Pittsburgh, Pittsburgh, Pennsylvania. Dr. Mulsant belongs to the following Boards: Member, Board of Trustees, Centre for Addiction and Mental Health, Toronto, Ontario.
Funding Information:
Dr. Lenze has received funding from Takeda, Lundbeck, Janssen, Alkermes, Aptynx, and PCORI, and is a consultant for Janssen and Jazz Pharmaceuticals. Dr. Mulsant currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study funded by Brain Canada). He directly owns stocks of General Electric (less than $5,000). Within the past three years, he has also received research support from Eli Lilly (medications for an NIH-funded clinical trial) and Pfizer (medications for an NIH-funded clinical trial).
Funding Information:
Ms. Marshe is supported through the Frederick Banting and Charles Best Canada Graduate Doctoral Research Award from the Canadian Institute for Health Research (#394160). Dr. Maciukiewicz is supported by the Postdoctoral Fellowship from the Canadian Institute of Health Research (#81655). Dr. Lenze is supported by funding from NIH and from the Taylor Family Institute for Innovative Psychiatric Research and the Center for Brain Research in Mood Disorders at Washington University. Dr. Mulsant receives compensation from the Department of Psychiatry, University of Toronto, Toronto, Ontario; the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario; and the University of Pittsburgh, Pittsburgh, Pennsylvania. Dr. Mulsant belongs to the following Boards: Member, Board of Trustees, Centre for Addiction and Mental Health, Toronto, Ontario. Dr. Lenze has received funding from Takeda, Lundbeck, Janssen, Alkermes, Aptynx, and PCORI, and is a consultant for Janssen and Jazz Pharmaceuticals. Dr. Mulsant currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study funded by Brain Canada). He directly owns stocks of General Electric (less than $5,000). Within the past three years, he has also received research support from Eli Lilly (medications for an NIH-funded clinical trial) and Pfizer (medications for an NIH-funded clinical trial).
Publisher Copyright:
© 2020 American Association for Geriatric Psychiatry
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Late-life depression
KW - antidepressant
KW - pharmacogenetics
KW - response
KW - treatment outcomes
UR - http://www.scopus.com/inward/record.url?scp=85080084685&partnerID=8YFLogxK
U2 - 10.1016/j.jagp.2020.01.007
DO - 10.1016/j.jagp.2020.01.007
M3 - Review article
C2 - 32122803
AN - SCOPUS:85080084685
SN - 1064-7481
VL - 28
SP - 609
EP - 629
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 6
ER -