TY  - JOUR
AU  - Milosavljević, Filip
AU  - Molden, Espen
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5593
AB  - The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.
PB  - Elsevier B.V.
T2  - European Neuropsychopharmacology
T1  - Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials
VL  - 81
SP  - 43
EP  - 52
DO  - 10.1016/j.euroneuro.2024.01.005
ER  - 

@article{
author = "Milosavljević, Filip and Molden, Espen and Ingelman-Sundberg, Magnus and Jukić, Marin",
year = "2024",
abstract = "The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.",
publisher = "Elsevier B.V.",
journal = "European Neuropsychopharmacology",
title = "Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials",
volume = "81",
pages = "43-52",
doi = "10.1016/j.euroneuro.2024.01.005"
}

Milosavljević, F., Molden, E., Ingelman-Sundberg, M.,& Jukić, M.. (2024). Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials. in European Neuropsychopharmacology
Elsevier B.V.., 81, 43-52.
https://doi.org/10.1016/j.euroneuro.2024.01.005

Milosavljević F, Molden E, Ingelman-Sundberg M, Jukić M. Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials. in European Neuropsychopharmacology. 2024;81:43-52.
doi:10.1016/j.euroneuro.2024.01.005 .

Milosavljević, Filip, Molden, Espen, Ingelman-Sundberg, Magnus, Jukić, Marin, "Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials" in European Neuropsychopharmacology, 81 (2024):43-52,
https://doi.org/10.1016/j.euroneuro.2024.01.005 . .