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Pharmacogenetics of Treating Anxiety & Depression
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Pharmacogenetics of Treating Anxiety & Depression

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Pharmacogenetics".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 22391

Special Issue Editor

Dr. Laura B. Ramsey

E-Mail Website
Guest Editor
1. Divisions of Clinical Pharmacology & Research in Patient Services, Cincinnati, OH 45229, USA
2. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
3. College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
Interests: pharmacogenetics of antidepressants; methotrexate pharmacogenetics & pharmacokinetics; pediatric pharmacogenetic implementation; model-informed precision dosing

Special Issue Information

Dear Colleagues,

Pharmacogenetics has the potential to improve the treatment of anxiety and depression. Though some institutions have been implementing pharmacogenetics in the clinical care of patients with anxiety and depression for many years, there is still much more research to be done. The aim of this Special Issue is to provide a comprehensive overview of how pharmacogenetics can influence the efficacy and tolerability of medications used to treat anxiety and depression, the current state of research in this area, and the challenges and opportunities for implementation in clinical care.

Articles may be in the areas of discovery, replication, trial design, position papers, meta-analyses, or a description of your implementation. Articles may be in the form of research article, review paper, or communication.

Dr. Laura B. Ramsey
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pharmacogenetics
  • Antidepressants
  • Anxiety disorders
  • Depressive disorders
  • Psychiatry
  • Implementation
  • Clinical trials
  • Pharmacokinetics
  • Pharmacodynamics

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Published Papers (6 papers)

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Research

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13 pages, 2582 KiB  
Article
Impact of Updating Pharmacogenetic Results: Lessons Learned from the PREDICT Program
by Michelle Liu, Sara L. Van Driest, Cindy L. Vnencak-Jones, Leigh Ann G. Saucier, Bartholomew P. Roland, Cheryl L. Gatto, Shari L. Just, Asli O. Weitkamp and Josh F. Peterson
J. Pers. Med. 2021, 11(11), 1051; https://doi.org/10.3390/jpm11111051 - 20 Oct 2021
Cited by 8 | Viewed by 2838
Abstract
Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical and technical challenges. Vanderbilt University Medical Center initiated panel testing in [...] Read more.
Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical and technical challenges. Vanderbilt University Medical Center initiated panel testing in 2010, added CYP2D6 testing in 2017, and released CDS for SSRIs in 2020. We systematically reinterpreted historic CYP2C19 and CYP2D6 genotypes to update phenotypes to current nomenclature and to launch provider CDS and patient-oriented content for SSRIs. Chart review was conducted to identify and recontact providers caring for patients with current SSRI therapy and new actionable recommendations. A total of 15,619 patients’ PGx results were reprocessed. Of the non-deceased patients reprocessed, 21% (n = 3278) resulted in CYP2C19*1/*17 reinterpretations. Among 289 patients with an actionable recommendation and SSRI medication prescription, 31.8% (n = 92) did not necessitate contact of a clinician, while 43.2% (n = 125) resulted in clinician contacted, and for 25% (n = 72) no appropriate clinician was able to be identified. Maintenance of up-to-date interpretations and recommendations for PGx results over the lifetime of a patient requires continuous effort. Reprocessing is a key strategy for maintenance and expansion of PGx content to be periodically considered and implemented. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)
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11 pages, 272 KiB  
Article
Associations of the SREBF2 Gene and INSIG2 Polymorphisms with Obesity and Dyslipidemia in Thai Psychotic Disorder Patients Treated with Risperidone
by Natchaya Vanwong, Chonlaphat Sukasem, Weerapon Unaharassamee, Napa Jiratjintana, Chalitpon Na Nakorn, Yaowaluck Hongkaew and Apichaya Puangpetch
J. Pers. Med. 2021, 11(10), 943; https://doi.org/10.3390/jpm11100943 - 22 Sep 2021
Cited by 2 | Viewed by 2244
Abstract
Background: Patients with psychotic disorders who receive atypical antipsychotic drugs often develop metabolic abnormalities. The sterol regulatory element-binding factor 2 (SREBF2) gene and insulin-induced gene (INSIG) have important roles in lipid metabolism. A previous study indicated that risperidone stimulated both lipogenesis and cholesterogenesis [...] Read more.
Background: Patients with psychotic disorders who receive atypical antipsychotic drugs often develop metabolic abnormalities. The sterol regulatory element-binding factor 2 (SREBF2) gene and insulin-induced gene (INSIG) have important roles in lipid metabolism. A previous study indicated that risperidone stimulated both lipogenesis and cholesterogenesis through activation of SREBP2 expression and inhibition of INSIG2. The SREBF2 gene and INSIG2 polymorphisms have been reported to be associated with metabolic abnormalities. Objective: To investigate the association of the SREBF2 gene (rs1052717, rs2267439, and rs2267443) and INSIG2 (rs7566605, rs11123469, and rs17587100) polymorphisms and the presence of obesity and dyslipidemia in Thai psychotic disorder patients treated with risperidone. Methods: All 113 psychiatric patients using risperidone were evaluated for their lipid profile and screened for obesity criteria. We genotyped the SREBF2 gene and INSIG2 polymorphisms using TaqMan real-time polymerase chain reaction. Results: None of the studied SREBF2 gene and INSIG2 SNPs were associated with obesity in Thai psychotic disorder patients receiving risperidone. Nonetheless, the SREBF2 rs2267443 (G/A) A-allele carriers were at a higher risk for hypertriglyceridemia, whereas the INSIG2 rs11123469 (T/C) C-allele carriers had a lower risk for hypertriglyceridemia, after being adjusted for clinical characteristics using multiple logistic regression. Conclusions: Our findings suggest that the SREBF2 gene rs2267443 (G/A) and the INSIG2 rs11123469 (T/C) polymorphisms are associated with dyslipidemia in Thai psychotic disorder patients treated with risperidone. Further studies with prospective designs and larger patient groups are needed. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)
10 pages, 951 KiB  
Article
Pharmacogenetic Testing in an Academic Psychiatric Clinic: A Retrospective Chart Review
by Lisa Brown, James Li, Naryan Katel, Kunbo Yu, Evangelia Fatourou, Brett Himmler and Angelos Halaris
J. Pers. Med. 2021, 11(9), 896; https://doi.org/10.3390/jpm11090896 - 8 Sep 2021
Cited by 4 | Viewed by 2723
Abstract
Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients [...] Read more.
Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients diagnosed with a psychiatric disorder at the Loyola University Medical Center, for whom PGx testing was performed. Information collected included demographics at the time of testing, psychiatric diagnosis, medical and psychiatric history and medications prior and after PGx testing. Of the 592 charts analyzed, the most common primary diagnoses were depression (52%) and anxiety (12%). Prior to PGx testing, 72% of patients were prescribed three or more medications, whereas, after testing, only 44% were prescribed three or more medications included in the test panel (p < 0.0001). The most common clinical consideration on the PGx reports was recommendation to reduce dosages (33%). After PGx testing, the proportion of patients taking incongruent medications decreased from 26% to 19% and that of patients taking congruent medications increased from 74% to 81% (p = 0.006). The results from this retrospective data analysis demonstrated a reduction in polypharmacy and an increase in recommendation-congruent medication prescribing resulting from implementation of PGx testing. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)
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8 pages, 253 KiB  
Article
Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action
by Taichi Ochi, Natalya M. Vyalova, Innokentiy S. Losenkov, Diana Z. Paderina, Ivan V. Pozhidaev, Anton J. M. Loonen, German G. Simutkin, Nikolay A. Bokhan, Bob Wilffert and Svetlana A. Ivanova
J. Pers. Med. 2021, 11(8), 731; https://doi.org/10.3390/jpm11080731 - 27 Jul 2021
Cited by 4 | Viewed by 2030
Abstract
Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used [...] Read more.
Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)

Review

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15 pages, 3995 KiB  
Review
Serotonin Transporter Genetic Variation and Antidepressant Response and Tolerability: A Systematic Review and Meta-Analysis
by Kiera Stein, Abdullah Al Maruf, Daniel J. Müller, Jeffrey R. Bishop and Chad A. Bousman
J. Pers. Med. 2021, 11(12), 1334; https://doi.org/10.3390/jpm11121334 - 9 Dec 2021
Cited by 19 | Viewed by 6921
Abstract
Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter ( [...] Read more.
Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)
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Other

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11 pages, 5916 KiB  
Study Protocol
Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial
by Jeffrey R. Strawn, Ethan A. Poweleit, Jeffrey A. Mills, Heidi K. Schroeder, Zoe A. Neptune, Ashley M. Specht, Jenni E. Farrow, Xue Zhang, Lisa J. Martin and Laura B. Ramsey
J. Pers. Med. 2021, 11(11), 1188; https://doi.org/10.3390/jpm11111188 - 12 Nov 2021
Cited by 7 | Viewed by 3984
Abstract
Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use “one size fits all” dosing strategies based on average responses in clinical trials. However, for some SSRIs, including escitalopram, variation in CYP2C19 activity produces substantial variation in medication [...] Read more.
Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use “one size fits all” dosing strategies based on average responses in clinical trials. However, for some SSRIs, including escitalopram, variation in CYP2C19 activity produces substantial variation in medication exposure (i.e., blood medication concentrations). This raises an important question: would refining current SSRI dosing strategies based on CYP2C19 phenotypes increase response and reduce side effect burden? To answer this question, we designed a randomized, double-blind trial of adolescents 12–17 years of age with generalized, separation, and/or social anxiety disorders (N = 132). Patients are randomized (1:1) to standard escitalopram dosing or dosing based on validated CYP2C19 phenotypes for escitalopram metabolism. Using this approach, we will determine whether pharmacogenetically-guided treatment—compared to standard dosing—produces faster and greater reduction in anxiety symptoms (i.e., response) and improves tolerability (e.g., decreased risk of treatment-related activation and weight gain). Secondarily, we will examine pharmacodynamic variants associated with treatment outcomes, thus enhancing clinicians’ ability to predict response and tolerability. Ultimately, developing a strategy to optimize dosing for individual patients could accelerate response while decreasing side effects—an immediate benefit to patients and their families. ClinicalTrials.gov Identifier: NCT04623099. Full article
(This article belongs to the Special Issue Pharmacogenetics of Treating Anxiety & Depression)
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