Genetic testing as a supporting tool in prescribing psychiatric medication: Design and protocol of the IMPACT study

Herbert, Deanna; Neves-Pereira, Maria; Baidya, Ruth; Cheema, Sheraz; Groleau, Sarah E.; Shahmirian, Anashe; Tiwari, Arun K.; Zai, Clement C.; King, Nicole; Müller, Daniel J.; Kennedy, James L.

doi:10.1016/j.jpsychires.2017.09.002

Cited by 35 publications

(30 citation statements)

References 23 publications

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“…in patients with MDD. [12][13][14] In addition, pharmacogenomic information about the medication dose adjustment, functional genomic information, relevant genomic markers, as well as drug interaction potential has been remarked in drug labels in western countries for some medications (i.e., tricyclic antidepressants, carbamazepine, and phenytoin, etc.). [15][16][17] In addition, pharmacogentic testing has been also beneficial in saving of medical costs.…”

Section: Introductionmentioning

confidence: 99%

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

Han

Wang

Bahk

et al. 2018

Clin Psychopharmacol Neurosci

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Objective: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≤7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by −4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by −2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

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Section: Introductionmentioning

confidence: 99%

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

Han

Wang

Bahk

et al. 2018

Clin Psychopharmacol Neurosci

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“…Our second dataset consisted of schizophrenia or schizoaffective disorder patients from a naturalistic pharmacogenetic study [The Individualized Medicine: Pharmacogenetics Assessment and Clinical Treatment (IMPACT, N = 20 TD cases and 41 TD-negative controls at baseline)] ( Herbert et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Investigation of the HSPG2 Gene in Tardive Dyskinesia – New Data and Meta-Analysis

et al. 2018

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Tardive dyskinesia (TD) is a movement disorder that may occur after extended use of antipsychotic medications. The etiopathophysiology is unclear; however, genetic factors play an important role. The Perlecan (HSPG2) gene was found to be significantly associated with TD in Japanese schizophrenia patients, and this association was subsequently replicated by an independent research group. To add to the evidence for this gene in TD, we conducted a meta-analysis specific to the relationship of HSPG2 rs2445142 with TD occurrence, while also adding our unpublished genotype data. Overall, we found a significant association of the G allele with TD occurrence (p = 0.0001); however, much of the effect appeared to originate from the discovery dataset. Nonetheless, most study samples exhibit the same trend of association with TD for the G allele. Our findings encourage further genetic and molecular studies of HSPG2 in TD.

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“…45,65 Recently, the Individualized Medicine: Pharmacogenetics Assessment and Clinical Treatment (IMPACT) study was launched to demonstrate the feasibility and utility of pharmacogenetic testing on a large scale and facilitate implementation of this testing in routine health care practice. 66 The implementation of pharmacogenomics in the clinic is supported by the establishment of comprehen-sive resources such as the Pharmacogenomic Knowledge Base (PharmGKB) (https://www.pharmgkb.org), and international expert groups that enable objective and transparent assessment of existing pharmacogenetic studies to derive clinical recommendations, such as the Clinical Pharmacogenomics Implementation Consortium (CPIC). Accordingly, CPIC performs a systematic review/evaluation of the comprehensive literature curated in PharmGKB to develop peer-reviewed gene-drug guidelines that are published and updated periodically (for further information on pharmacogenomics resources see Pouget et al 40 and Müller et al).…”

Section: Translating Pharmacogenomics To Clinical Practicementioning

confidence: 99%

The role of genetics and genomics in clinical psychiatry

Hoehe

Morris-Rosendahl

2018

Dialogues in Clinical Neuroscience

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The enormous successes in the genetics and genomics of many diseases have provided the basis for the advancement of precision medicine. Thus, the detection of genetic variants associated with neuropsychiatric disorders, as well as treatment outcome, has raised growing expectations that these findings could soon be translated into the clinic to improve diagnosis, the prediction of disease risk and individual response to drug therapy. In this article, we will provide an introduction to the search for genes involved in psychiatric illness and summarize the present findings in major psychiatric disorders. We will review the genetic variants in genes encoding drug metabolizing enzymes and specific drug targets which were found to be associated with variable drug response and severe side effects. We will evaluate the clinical translatability of these findings, whether there is currently any role for genetic testing and in this context, make valuable sources of information available to the clinician seeking guidance and advice in this rapidly developing field of psychiatric genetics.

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Genetic testing as a supporting tool in prescribing psychiatric medication: Design and protocol of the IMPACT study

Cited by 35 publications

References 23 publications

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

Investigation of the HSPG2 Gene in Tardive Dyskinesia – New Data and Meta-Analysis

The role of genetics and genomics in clinical psychiatry

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