Correlation between pharmacokinetics and pharmacogenetics of Selective Serotonin Reuptake Inhibitors and Selective Serotonin and Noradrenaline Reuptake Inhibitors and maternal and neonatal outcomes: Results from a naturalistic study in patients with affective disorders

Colombo, Anna; Giordano, Francesca; Giorgetti, Federica; Bernardo, Ilaria Di; Bosi, M.; Varinelli, Alberto; Cafaro, Rita; Pileri, Paolo; Cetin, Irene; Clementi, Emilio; Viganò, Caterina; Dell’Osso, Bernardo

doi:10.1002/hup.2772

Cited by 7 publications

(22 citation statements)

References 49 publications

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“…The infant albumin level at birth is slightly higher than the maternal, whereas the level of AAP is only a third of the mothers [27]. In previous studies, the placental penetration of sertraline to infant serum has seemed low, with infantmother ratios at around 0.3-1.0 reported [25,[28][29][30][31][32]. Transient neonatal effects such as jitteriness, hypoglycemia, and respiratory disorders are described after intrauterine SSRI exposure [33,34].…”

Section: Introductionmentioning

confidence: 95%

Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

Heinonen

Blennow

Blomdahl-Wetterholm

et al. 2021

Eur J Clin Pharmacol

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Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

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Section: Introductionmentioning

confidence: 95%

Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

Heinonen

Blennow

Blomdahl-Wetterholm

et al. 2021

Eur J Clin Pharmacol

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“…Forty publications on 15 antidepressants studied in 961 pregnant women were identified (Tables S1 and S2). Seventeen manuscripts contained PK data for multiple drugs 26–42 . No information was found regarding PK of desvenlafaxine, milnacipran, viloxazine, levomilnacipran, nefazodone, desipramine, doxepin, amoxapine, maprotiline, protriptyline, trimipramine, vilazodone, esketamine, vortioxetine, isocarboxazid, phenelzine, and tranylcypromine in pregnancy.…”

Section: Resultsmentioning

confidence: 99%

“…Colombo reported the fluoxetine concentration following 30‐mg daily dosing in the third trimester in a patient genotyped as a CYP2D6 IM to 346.8 ng/mL 40 …”

Section: Resultsmentioning

confidence: 99%

“…Two studies evaluated concentrations of paroxetine in the third trimester. Colombo et al 40 . studied 11 women taking paroxetine with a median daily dose of 20 mg (10–25 mg).…”

Section: Resultsmentioning

confidence: 99%

“…Seven pregnant women taking extended‐release venlafaxine were included in the Colombo study 40 . The median (range) daily dose was 75 mg (37.5–150 mg) and the maternal plasma venlafaxine concentration was 86.1 (37.6–245) ng/mL at the third trimester.…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetics of Antidepressants in Pregnancy

Yue

Kus

Katta

et al. 2023

The Journal of Clinical Pharma

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Depression is common in pregnant women. However, the rate of antidepressant treatment in pregnancy is significantly lower than in nonpregnant women. Although some antidepressants may cause potential risks to the fetus, not treating or withdrawing the treatment is associated with relapsing and adverse pregnancy outcomes such as preterm birth. Pregnancy-associated physiologic changes can alter pharmacokinetics (PK) and may impact dosing requirements during pregnancy. However, pregnant women are largely excluded from PK studies. Dose extrapolation from the nonpregnant population could lead to ineffective doses or increased risk of adverse events. To better understand PK changes during pregnancy and guide dosing decisions, we conducted a literature review to catalog PK studies of antidepressants in pregnancy, with a focus on maternal PK differences from the nonpregnant population and fetal exposure. We identified 40 studies on 15 drugs, with most data from patients taking selective serotonin reuptake inhibitors and venlafaxine. Most of the studies have relatively poor quality, with small sample sizes, reporting concentrations at delivery only, a large amount of missing data, and not including times and adequate dose information. Only four studies collected multiple samples following a dose and reported PK parameters. In general, there are limited data available regarding PK of antidepressants in pregnancy and deficiencies in data reporting. Future studies should provide accurate information on drug dosing and timing of dose, PK sample collection, and individual-level PK data.

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Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology

Colombo,

Cafaro,

Di Bernardo

et al. 2023

International Clinical Psychopharmacology

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Objective Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants’ pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. Methods In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants’ blood concentrations and psychometric assessments were collected at five time points. Antidepressants’ cord blood concentrations were assessed at birth. Results Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants’ concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. Conclusions Pregnancy modulates cytochrome activity and drugs’ pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

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Correlation between pharmacokinetics and pharmacogenetics of Selective Serotonin Reuptake Inhibitors and Selective Serotonin and Noradrenaline Reuptake Inhibitors and maternal and neonatal outcomes: Results from a naturalistic study in patients with affective disorders

Cited by 7 publications

References 49 publications

Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

Pharmacokinetics of Antidepressants in Pregnancy

Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology

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