Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy

Horst, Peter G. J. ter; Larmené-Beld, Karin; Bosman, Judith; Veen, Elly L. van der; Wieringa, André; Smit, Jan Pieter

doi:10.1111/jcpt.12188

Cited by 10 publications

(12 citation statements)

References 15 publications

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“…Venlafaxine is metabolized by CYP2D6 to its equipotent metabolite O-desmethylvenlafaxine (ODVM) [24]. In a case report by Klier et al, a more than 50% reduction in venlafaxine plasma levels was observed in pregnancy compared to baseline [16].…”

Section: Discussionmentioning

confidence: 99%

“…In a case report by Klier et al, a more than 50% reduction in venlafaxine plasma levels was observed in pregnancy compared to baseline [16]. However, in a prospective study of seven pregnancies by ter Horst et al, only a 13% reduction in venlafaxine levels in pregnancy was found, with no change in ODMV levels [24]. Our study, with 33 pregnancies, confirms the latter observation; we found a trend towards a statistically significant decline in venlafaxine concentrations, but the metabolite concentrations did not change (Table 3), and the changes in total active moiety levels were not statistically significant (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…These results may reflect increased CYP2D6-induced bioconversion from venlafaxine to ODMV in pregnancy. This shift is expected to be of minor or no clinical relevance, since parent drug and metabolite share equal antidepressant potency [24]. We therefore suggest venlafaxine doses could be kept stable throughout pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition

et al. 2017

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BackgroundPregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women.MethodsUsing patient data from two routine therapeutic drug monitoring (TDM) services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women’s own baseline (non-pregnant) values, using a linear mixed model.FindingsOverall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only), we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (–51%; 95% confidence interval [CI], –66%, –30%; p<0.001), fluvoxamine (–56%; CI, –75%, –23%; p = 0.004) and citalopram (–24%; CI, –38%, –7%; p = 0,007), and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001). For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly.ConclusionsFor paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition

et al. 2017

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“…The PK of about half of the antidepressant drugs included in the search has been evaluated in pregnant women, although often a complete characterization of the PK profile is not available or data are not available for all gestational trimesters (e.g., citalopram, fluoxetine, sertraline, trazodone, lithium). Venlafaxine has been investigated in all trimesters of pregnancy, and decreased blood venlafaxine levels were observed in pregnancy compared to postpartum, although not all studies included postpartum measures or comparative data in non-pregnant individuals ( 24 – 26 ).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic data in pregnancy: A review of available literature data and important considerations in collecting clinical data

Coppola¹,

Kerwash²,

Nooney³

et al. 2022

Front. Med.

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Pregnancy-related physiological changes can alter the absorption, distribution, metabolism and excretion of medicines which may affect the safety and efficacy of the medicines administered in pregnancy. Pharmacokinetic data can thus be instrumental in supporting dose adjustments required in this population. This review considers the availability of published pharmacokinetic data for over 200 medicines of interest for use in pregnancy in the UK, to identify whether sufficient data currently exists, in principle, for any medicine or group of medicines to support dose adjustments to maintain maternal health through pregnancy. Very limited data was found for many of the medicines of interest. Nevertheless, well documented, large changes of exposure for some drugs, where data is available, highlights the urgent need to collect more data of good quality to inform appropriate doses, when needed, in this population. In addition, clinical study methodology can have an impact on the usefulness of the data and key clinical design aspects are highlighted for consideration in future clinical study design.

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“…Higher metabolic rate of most SRI in late pregnancy would lead to lower maternal serum concentrations, which could lead to decreased efficacy. For example, venlafaxine concentrations appear to significantly decrease during pregnancy when compared to the post-partum period [138]. The mean norfluoxetine/fluoxetine metabolic ratio increases over two folds late in pregnancy compared to two months postpartum, due to increased demethylation of fluoxetine by CYP2D6, decreasing the serum levels of the active metabolite and possibly leading to therapeutic failure [139].…”

Section: Pregnancy-induced Changes In Sri Metabolism Interaction mentioning

confidence: 99%

SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers?

Ornoy¹,

Koren

2019

IJMS

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Serotonin has important roles in the development of the brain and other organs. Manipulations of synaptic serotonin by drugs such as serotonin reuptake inhibitors (SRI) or serotonin norepinephrine reuptake inhibitors (SNRI) might alter their development and function. Of interest, most studies on the outcome of prenatal exposure to SRI in human have not found significant embryonic or fetal damage, except for a possible, slight increase in cardiac malformations. In up to a third of newborns exposed to SRI, exposure may induce transient neonatal behavioral changes (poor neonatal adaptation) and increased rate of persistent pulmonary hypertension. Prenatal SRI may also cause slight motor delay and language impairment but these are transient. The data on the possible association of prenatal SRIs with autism spectrum disorder (ASD) are inconsistent, and seem to be related to pre-pregnancy treatment or to maternal depression. Prenatal SRIs also appear to affect the hypothalamic hypophyseal adrenal (HPA) axis inducing epigenetic changes, but the long-term consequences of these effects on humans are as yet unknown. SRIs are metabolized in the liver by several cytochrome P450 (CYP) enzymes. Faster metabolism of most SRIs in late pregnancy leads to lower maternal concentrations, and thus potentially to decreased efficacy which is more prominent in women that are rapid metabolizers. Studies suggest that the serotonin transporter SLC6A4 promoter is associated with adverse neonatal outcomes after SRI exposure. Since maternal depression may adversely affect the child’s development, one has to consider the risk of SRI discontinuation on the fetus and the child. As with any drug treatment in pregnancy, the benefits to the mother should be considered versus the possible hazards to the developing embryo/fetus.

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Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy

Cited by 10 publications

References 15 publications

Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition

Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition

Pharmacokinetic data in pregnancy: A review of available literature data and important considerations in collecting clinical data

SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers?

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