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
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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 corres...ponded 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.
Кључне речи:
Psychiatry / Antidepressant / CYP450 / Major depressive disorder / Meta-analysis / PharmacogenomicsИзвор:
European Neuropsychopharmacology, 2024, 81, 43-52Издавач:
- Elsevier B.V.
Финансирање / пројекти:
- The Swedish Research Council (grant 2021-02732)
- PsyCise - Utility of Plasma Drug Level Monitoring and Cyp2c19/Cyp2d6 Genotyping in Dose Personalization of Antidepressants and Antipsychotics (RS-ScienceFundRS-Promis-6066800)
- The Swedish Brain Foundation (grant FO2021-0314)
DOI: 10.1016/j.euroneuro.2024.01.005
ISSN: 1873-7862 0924-977X
PubMed: 38340605
WoS: 001183811200001
Scopus: 2-s2.0-85184919952
Институција/група
PharmacyTY - 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 . .