The role of pharmacogenetics in the treatment of major depressive disorder: a critical review

Barlati, Stefano; Minelli, Alessandra; Nibbio, Gabriele; Bertoni, Lorenzo; Necchini, Nicola; Paolini, Stefano; Muscarella, Alessia; Ubertino, Ughetta Bosco; Calzavara-Pinton, Irene; Vita, Antonio; Gennarelli, Massimo

doi:10.3389/fpsyt.2023.1307473

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…516G>T variant alone may be informative and clinically useful, for therapeutic benefit and potentially for .side effects, risks, and their mitigation (Barlati et al, 2023;Wang et al, 2023). 18 (0.90,1.77) 11.5 (7.6,25.1) 13.7 (5.9,15.7) 0.22 (0.12,0.32) 7.4 (5.6,9.1) NM 26 0.18 (0.09,0.24) 0.17 (0.10,0.30) 1.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion

Kharasch,

Lenze

2024

Drug Metabolism and Disposition

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Bupropion is used for treating depression, obesity, seasonal affective disorder, and for smoking cessation.Bupropion is commonly-prescribed, but has complex pharmacokinetics and interindividual variability in metabolism and bioactivation may influence therapeutic response, tolerability and safety. Bupropion is extensively and stereoselectively metabolized, the metabolites are pharmacologically active, and allelic variation in CYP2B6 affects clinical hydroxylation of single-dose bupropion. Genetic effects on stereoselective disposition of steady-state bupropion are not known. In this preplanned secondary analysis of a prospective, randomized, double-blinded, crossover study which compared brand and generic bupropion XL 300 mg drug products, we measured steady-state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations. This investigation evaluated the influence of genetic polymorphisms in CYP2B6, CYP2C19, and P450 oxidoreductase on the disposition of Valeant Pharmaceuticals Wellbutrin brand bupropion in 67 participants with major depressive disorder. We found that hydroxylation of both bupropion enantiomers was lower in carriers of the CYP2B6*6 allele and in carriers of the CYP2B6 516G>T variant, with correspondingly greater bupropion and lesser hydroxybupropion plasma concentrations. Hydroxylation was 25-50% lower in CYP2B6*6 carriers and one-third to one-half less in 516T carriers. Hydroxylation of the bupropion enantiomers was comparably affected by CYP2B6 variants. CYP2C19 polymorphisms did not influence bupropion plasma concentrations or hydroxybupropion formation but did influence the minor pathway of 4'-hydroxylation of bupropion and primary metabolites. P450 oxidoreductase variants did not influence bupropion disposition. Results show that CYP2B6 genetic variants affect steady-state metabolism and bioactivation of Valeant brand bupropion, which may influence therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion

Kharasch,

Lenze

2024

Drug Metabolism and Disposition

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“…In recent years, an increasing body of literature has emphasized the significance of personalized medicine in psychiatric care, highlighting the importance of tailoring treatments based on individual patient profiles [ 6 , 7 , 8 ]. The advent of precision psychiatry has underscored the need for robust analytical methods capable of delivering accurate and reliable data for informed decision-making in the clinical setting [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Towards Precision Medicine in Clinical Practice: Alinity C vs. UHPLC-MS/MS in Plasma Aripiprazole Determination

Toja-Camba,

Bandín-Vilar,

Hermelo-Vidal

et al. 2024

Pharmaceutics

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Therapeutic drug monitoring improves the benefit–risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) is considered the gold-standard method for measuring plasma drug concentrations; however, the Alinity C system has emerged as a promising alternative. This is the first study aimed at comparing UHPLC-MS/MS versus Alinity C in measuring plasma concentrations of aripiprazole and dehydroaripiprazole. A total of 86 plasma samples were analyzed. The active moiety of aripiprazole was measured in 60 samples using both systems and 26 samples were analyzed twice using Alinity C with an intermediate period of 6 months to assess its reproducibility. Spearman’s correlation revealed a good association between the two assays (rs = 0.96) and no significance differences were found by McNemar’s test when classifying samples between infra-, supra- and therapeutic ranges. Passing–Bablock regression showed a good correlation among methods (rs = 0.93) and a slope of 1.12 indicating a slight tendency of Alinity C to measure higher values than UHPLC-MS/MS. In addition, a good intra-method correlation across the two sequential analyses with Alinity C was obtained (rs = 0.99). Nonetheless, clinical decisions could be different in 15% of the cases depending on the chosen method. No differences were found in active moiety determination by Alinity C depending on the concentration of aripiprazole and dehydroaripiprazole of the samples.

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EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial

Ulke,

Kayser,

Tenke

et al. 2024

Psychiatry Research

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The role of pharmacogenetics in the treatment of major depressive disorder: a critical review

Cited by 4 publications

References 46 publications

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion

Towards Precision Medicine in Clinical Practice: Alinity C vs. UHPLC-MS/MS in Plasma Aripiprazole Determination

EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial

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