Boucher Nina, Koren Gideon, Beaulac-Baillargeon Louise
Perinatalogy Unit, Saint-François d' Assise Hospital, CHUQ, Laval University, Quebec G1V 0A6, Canada.
Ther Drug Monit. 2009 Jun;31(3):404-9. doi: 10.1097/FTD.0b013e3181a58fb4.
The nature of neonatal adverse effects in the offspring after maternal use of venlafaxine at term is not fully understood. We correlated neonatal clinical signs over time with serum concentrations of venlafaxine and its active metabolite in the neonatal period. Women exposed to venlafaxine near term, and their neonates, were studied. Adverse neonatal signs and serum concentrations of venlafaxine and its active metabolite were assessed. Seven mother-child pairs were studied. Median maternal venlafaxine dose was 75 mg/d (37.5-300 mg/d). Five neonates presented with multiple clinical signs during their hospital stay, all including tachypnea and respiratory distress. Respiratory distress was present within the first hours after birth, with other symptoms appearing subsequently when the drug concentration declined. The elimination half-life, calculated for 3 neonates, ranged between 12 and 15 hours for venlafaxine and between 10 and 37 hours for O-desmethylvenlafaxine. Neonatal clinical signs emerged as drug concentrations declined, corroborating discontinuation as an etiology. Respiratory symptoms tended to occur earlier and, in one case, independently from the typical signs of abrupt cessation of venlafaxine. This suggests that it may be part of the wide range of respiratory problems reported in antidepressant-exposed neonates, including persistent pulmonary hypertension of the newborn reported with selective serotonin reuptake inhibitor. Neonatal clinical signs emerged with decreasing concentrations of venlafaxine, supporting that abrupt cessation of venlafaxine leads to discontinuation syndrome. Respiratory problems occurred earlier than typical discontinuation clinical signs. Larger studies are needed to confirm these findings.
母亲在足月时使用文拉法辛后子代新生儿不良反应的性质尚未完全明确。我们将新生儿期随时间变化的临床体征与文拉法辛及其活性代谢物的血清浓度进行了关联分析。对足月时接触文拉法辛的女性及其新生儿进行了研究。评估了新生儿的不良体征以及文拉法辛及其活性代谢物的血清浓度。研究了7对母婴。母亲文拉法辛的中位剂量为75毫克/天（37.5 - 300毫克/天）。5名新生儿在住院期间出现了多种临床体征，均包括呼吸急促和呼吸窘迫。呼吸窘迫在出生后的最初几个小时内出现，其他症状在药物浓度下降后随后出现。为3名新生儿计算的消除半衰期，文拉法辛在12至15小时之间，O - 去甲基文拉法辛在10至37小时之间。随着药物浓度下降出现新生儿临床体征，证实停药是病因。呼吸症状往往出现得更早，并且在1例中独立于文拉法辛突然停药的典型体征出现。这表明它可能是暴露于抗抑郁药的新生儿中报告的广泛呼吸问题的一部分，包括与选择性5 - 羟色胺再摄取抑制剂相关的新生儿持续性肺动脉高压。随着文拉法辛浓度降低出现新生儿临床体征，支持文拉法辛突然停药会导致停药综合征。呼吸问题比典型的停药临床体征出现得更早。需要更大规模的研究来证实这些发现。
