Antidepressant medication and the risk of pregnancy-induced hypertension

Background: Increased activity of the sympatic nervous system could possibly cause pregnancy-induced hypertension (PIH). Previous studies have suggested that antidepressants could contribute to this increased activity. Objectives: To examine whether the use of antidepressants during pregnancy increases the risk of developing pregnancy-induced hypertension. Methods: This retrospective cohort study was conducted using the prescription database IADB.nl among nulliparous women with singleton pregnancies between 1994 and 2014 in the Netherlands. Exposure was defined as at least one dispensing record of an antidepressant (AD; ATC-code N06A) during the first 20 weeks of gestation. Excluded were women using antithrombotic agents, antidiabetic drugs, antimigraine drugs, and antihypertensive drugs during six months before pregnancy till twenty weeks of gestation. The outcome, PIH, was defined as at least one dispensed record of an antihypertensive drug (methyldopa, nifedipine, labetalol, ketanserin, nicardipine) after 20 weeks of gestation till 14 days after delivery. Odds ratios (OR) and their corresponding 95% confidence intervals (95%CIs) were estimated using logistic regression analysis, adjusting for maternal age, benzodiazepine and antibiotic use. Subanalyses were conducted for class of AD, duration of use of AD (1-30, ≥ 31 Defined Daily Doses (DDD)), and maternal age. As the exact duration of gestation was unknown, all analysis were conducted for 3 theoretical gestational ages (35, 37, 39 weeks). Results: 28020 women were included, of which 539 (1,92%) used antidepressants (gestational age 39 weeks). The risk of pregnancy induced hypertension doubled for women using an antidepressant (aOR [95%CI] 2.00[1.30-3.18]). Significant associations (OR [95% CI]) were also found for the subgroup SSRI (2,12 [1.28-3,50]), ≥ 31 DDDs (2.53 [1.58-4.85]) and maternal age of 30-34 years (2,59 [1,35-4,98]). Decreasing the theoretical gestational age showed comparable results. Conclusions: Use of ADs during the first 20 weeks of gestations appeared to be associated with an increased risk of developing PIH. When balancing the benefit and risks of using these drugs during pregnancy, this should be taken into account.