Trends in prescribing psychotropic drugs before and during pregnancy may have changed over the years, but actual information is lacking. We therefore compared and assessed the exposure and acceptance rates of classes of antipsychotic (+ lithium), anxiolytic, sedative/hypnotic, antidepressant, and psychostimulant before and during pregnancy in the past two decades. All singleton pregnancies with ≥1 prescription of psychotropic drug from six months before pregnancy until child’s birthdate were identified in the pregnancy subset of the IADB.nl prescription database. The prescription patterns of psychotropics were distinguished as continuation rate (CR), initiation rate (IR), discontinuation rate (DR), total exposure rate (TER), and acceptance rate. Singleton pregnancies exposed to psychotropic drugs before and during pregnancy increased from 118.4 to 136.5 (per 1000 singleton pregnancies) between decades. Changing trends were observed in decade 2, including a high increase in the TER of antipsychotic class (3.3 to 6.8) and antidepressant class (23.0 to 40.6). A marked increase for individual drugs was seen for sertraline (TER: 0.6 to 6.6 and PAT: 35.3% to 82.5%), citalopram (TER: 2.3 to 10.0 and PAT: 51.1% to 74.6%), and quetiapine (TER: 0.4 to 3.1 and PAT: 57.1% to 66.0%). Although the total exposure rates of five classes of psychotropics in singleton pregnancies increased in decade 2, only antidepressant class had a higher acceptance rate during pregnancy. Certain SSRI antidepressants and atypical antipsychotics were more frequently prescribed in decade 2 than in decade 1, reflecting that treatment options were preferred for safer treatment choices.

Introduction: Intraperitoneal tigecycline is a potential option for the treatment of peritoneal dialysis (PD)-associated peritonitis caused by microorganisms resistant to commonly used antibiotics. However, the stability of tigecycline must be assessed in the PD solution before evaluating its safety and therapeutic efficacy in PD-associated peritonitis. The objective of this study was to investigate the stability of tigecycline in 3 types of PD solutions at different temperatures for various time points. Methods: A total of 27 PD bags (9 PD bags for each type of PD solution; 1.5% glucose, 7.5% icodextrin, and 1.5% glucose pH neutral) containing 2 μg/mL of tigecycline were prepared and stored at either 4, 25, or 37°C. An aliquot was withdrawn immediately before (0 hour) and after pre-defined time points. Each sample was analyzed in duplicate for the concentration of tigecycline using a stability-indicating high-performance liquid chromatography (HPLC) technique. Samples were also assessed for pH, color changes, and evidence of precipitation immediately after preparation and on each day of analysis. Results: Tigecycline in all 3 types of PD solutions retained more than 90% of its initial concentration for at least 216, 72, and 8 hours at 4, 25, and 37°C, respectively. There was no evidence of precipitation at any time under the tested storage conditions. The pH and color of tigecycline admixed PD solutions stored at 4, 25, and 37°C remained essentially unchanged for 336, 96, and 48 hours respectively. Conclusion: The results obtained from the study provide a platform for future clinical studies aiming to determine the safety and therapeutic efficacy of intraperitoneally administered tigecycline for the treatment of PD-associated peritonitis.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39 weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67–1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

The purpose of the study is to examine the switching pattern and dose adjustment of antidepressants (ADs) prescribed to women from six months before to six months during pregnancy in the Netherlands. The recorded dispenses or refills were collected from the University of Groningen IADB.nl pregnancy subset for all singleton pregnancies in which the mother received ≥ 1 prescription of an AD dispensed before pregnancy and was present in the database at least six months after conception. The rates of continuation, discontinuation, and switching between 2001 and 2020 were assessed for the ADs studied. The mean number of Defined Daily Doses (DDDs) of the most frequently continued ADs used was calculated both before and during pregnancy, and a paired t-test was used to test for significant changes. The continuation rates for AD users, especially for SSRI and SNRI continued users, increased over time from 27% and 19% (2001–2005) to 65% and 65% (2016–2020). The switching rate between ADs remained consistently low from the start of the study (2001–2005) at 2.0% to the end of the study (2016–2020) at 2.3%. Most women who switched between antidepressants during pregnancy received a different SSRI monotherapy (85%), followed by an SNRI (6%), a TCA (4%), and an “other AD” (4%). In most cases observed, the dose adjustment for the mean DDDs during pregnancy compared to the mean DDDs before pregnancy only changed little (less than 10%). Continued use of SSRIs among singleton pregnancies doubled over the study period. The low rate of AD switching and little changes in the DDD adjustment for most AD continuers indicate that pregnant women prefer to continue their prepregnancy medication rather than switch it. Most observed findings cohere with the Dutch national guidelines for antidepressant use during pregnancy.

Adverse event reporting systems are an important source of safety signals for drug use in pregnancy, but their usefulness in the identification of potential drug-drug interactions (DDIs) remains unclear. Our objective was to explore the reliability of signal detection for pharmacokinetic DDIs during pregnancy in adverse event reporting systems, focusing on potential interactions between antipsychotics (APs) or antidepressants (ADs) and drugs modifying cytochrome P450 (CYP450) activity, increasing the occurrence of gestational diabetes mellitus (GDM). Reports related to the use of drugs during pregnancy were identified in VigiBase, the World Health Organization (WHO) global database of adverse event reports. Potential interacting drugs were selected based on WHO Drug Standardised Drug Groupings for CYP450 isoenzymes involved in the metabolic pathway of the AP or AD of interest. We conducted statistical interaction analysis using the omega disproportionality measure and including concomitant medication to identify potential DDIs, followed by a case series review for supporting evidence. Evaluation was subjective by author consensus. Of the 30 drug-drug-event combinations considered, statistical signals emerged for escitalopram, citalopram, and sertraline and the simultaneous use of CYP2D6 inhibitors with a higher relative reporting rate of GDM. However, case series review of reports did not support the existence of these DDIs because of uncertainties regarding the actual timing of medication use reported as concomitant. Statistical signals of DDIs between ADs and potential interacting drugs during pregnancy were identified but not pursued further after case reviews. Uncertainty around medication use and event timing affected the reliability of the outcomes. These findings highlight the need to validate signals using detailed report data and stress the importance of accurate medication reporting.