Dispensing patterns of selective serotonin reuptake inhibitors before, during and after pregnancy: a 16-year population-based cohort study from the Netherlands

Abstract

Management of mental illness in the perinatal period with antidepressants is controversial, since evidence emerged on potential harmful effects to the unborn child. However, over time, the dispensing of antidepressants in the perinatal period has increased. We examined perinatal dispensing patterns over time and the role of a recently issued guideline in this regard. We identified a 16-year cohort of 153,952 Dutch pregnancies with a delivery date between January 1999 and December 2014. Data included exposure to selective serotonin reuptake inhibitors (SSRIs) related to phases of pregnancy (preconception, pregnancy and delivery, post-delivery). The chi-square test for trends was used. With standard logistic regression, we explored the influence of patient characteristics on continuation of SSRIs during pregnancy. A persistent significant rise of dispensing rates in all phases was observed, with the largest increase during pregnancy (from 0.8% in 1999/2000 to 2.1% in 2013/2014, chi-square for trend = 141.735, p < 0.001). A substantial change of practice in terms of the SSRI used (less paroxetine) and the policy towards continuation into pregnancy (more continuation over time) was visible. Concomitant use of psycholeptics halved the probability of continuation of SSRIs (OR 0.50, 95%CI 0.43-0.55, p < 0.01). Dispensing rates of SSRIs steadily increased last 16 years, especially during pregnancy, caused by an increase in the proportion of women continuing their medication during pregnancy. In view of the demonstrated impact of uncertainty regarding effectiveness and safety of SSRIs in pregnancy, future research should involve more detailed outcome research of SSRIs as it is, and research into viable alternatives.

Keywords: Antidepressants; Dispensing; Pharmacoepidemiology; Pregnancy; Serotonin.

Fig. 1

Selective serotonin reuptake inhibitors (SSRIs) perinatal dispensing rate per time period of interest per 100 pregnancies in the Netherlands, 1999–2014. 1 = the year before pregnancy, 2 = during pregnancy, 3 = the year after pregnancy. Complete data on all three phases was available for all women and thus the number of women at risk for each bar (1, 2 and 3) per 2 years is comparable. For example, a woman with a delivery date in 1999, who took SSRIs during all three phases (before, during, after) is represented in blue in all three bars (1, 2, 3) of the 1999 column. The dark blue bars represent the women that used their SSRI since the year before pregnancy. The pink and green bars represent the women that did not use SSRIs in the year before pregnancy but started using them during or after pregnancy respectively. The light blue bar represents those women that used SSRIs before pregnancy, discontinued during pregnancy, but restarted in the year after pregnancy

Fig. 2

Percentage of women with selective serotonin reuptake inhibitor (SSRI) dispensing in the year before pregnancy continuing during pregnancy in the Netherlands, 1999–2014. Dotted lines represent the 95% confidence intervals

Fig. 3

Relative and absolute dispensing rates per specific selective serotonin reuptake inhibitor (SSRI) before, during and after pregnancy in the Netherlands, 1999–2015. a Relative SSRI dispensing in the year before pregnancy. b Absolute SSRI dispensing in the year before pregnancy. c Relative SSRI dispensing during pregnancy. d Absolute SSRI dispensing during pregnancy. e Relative SSRI dispensing in the year after pregnancy. f Absolute SSRI dispensing in the year after pregnancy. Each year represents two calendar years