Lithium salts are the first-line prophylaxis treatment for bipolar disorder in most guidelines. The majority of bipolar women are treated with mood stabilizers at the time they wish to get pregnant. One reason for this is the rising average age at first childbirth, at least in the high-income countries, which increases in general the likelihood of a medication with psychotropic drugs. Previously, lithium exposition during pregnancy was thought to strongly increase the risk of severe cardiac malformation. However, recent studies only point to a low teratogenic risk, so nowadays an increasing number of women are getting pregnant with ongoing lithium treatment. Regarding lithium medication during breastfeeding, there is evidence that lithium transfers to the breastmilk and can also be detected in the infants’ serum. The influence on the infant is still a largely understudied topic. Regular monitoring of the infants’ renal clearance, thyroid function, and lithium levels is warranted when breastfeeding under lithium exposure. In this case series, we present three case reports of bipolar mothers who were treated with lithium during pregnancy and breastfeeding to add to the scarce literature on this important topic. In short, we strengthen the importance of therapeutic drug monitoring due to fluctuating plasma levels during pregnancy and after birth, and we can report the birth and development of three healthy infants despite lithium medication during pregnancy and breastfeeding.
Abstract Epigenetic signatures such as methylation of the monoamine oxidase A ( MAOA ) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N =28 female Caucasian PD patients (discovery sample) and N =28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients ( N =20). Patients exhibited lower MAOA methylation than healthy controls ( P <0.001), and baseline PD severity correlated negatively with MAOA methylation ( P =0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P =0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT ( P =0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
Introduction Even if an increasing number of women is treated with antidepressants during pregnancy, data about the phamacokinetics is still sparse and no guidelines exist that describe dosing strategies in this vulnerable period [1].
There is still limited knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breastmilk and the effects on exposed children. We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breastmilk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. High concentration‐by‐dose ratios in breastmilk were found for venlafaxine as well as lamotrigine, low for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed low milk/serum–penetration ratios. Regarding the birth outcome measures in children, we found no significant differences between in utero exposed compared to nonexposed newborns. There were no significant differences in the development in the first 12 months. Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy‐associated changes in pharmacokinetics. Accordingly, therapeutic drug monitoring can optimize a medication in pregnancy and lactation with the lowest effective dose.
Aim There is still only little knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breast-milk and the effects on exposed children. Methods We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breast milk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. Results We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. Highest concentration-by-dose-ratios in breast milk were found for venlafaxine as well as lamotrigine, lowest for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed lowest milk/serum-penetration-ratios. Regarding the birth outcome measures in children we found no significant differences between in utero exposed compared to non-exposed new-borns. There were no significant differences in the development in the first 12 months. Conclusion Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring (TDM) can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy-associated changes in pharmacokinetics. Accordingly, TDM can optimize a medication in pregnancy and lactation with the lowest but effective dose.
Abstract Background Perinatal depression affects 10–15% of mothers and approximately 5% of fathers. However, only a small number of affected individuals seek treatment. If left unrecognized and untreated, it can have negative long-term consequences for the family’s health, leading to subsequent high costs. Early treatment is crucial, yet there is a notable underdiagnosis and undertreatment. Affected individuals are often seen during this time, e.g. in paediatric practices, but not by specialists in mental health. Consequently, this study aims to increase detection and treatment rates of affected individuals by implementing a screening for depression and psychosocial stress in perinatal and postpartum parents within routine obstetric and paediatric care with subsequent advice and—if necessary—further referral to a mental health specialist. Methods UPlusE is a prospective, cluster-randomized controlled trial conducted in an outpatient setting. Obstetric and paediatric practices will be randomized into an intervention and control group (1:1 ratio). Practices and enrolling patients will be required to use specific smartphone apps (practice apps) for interaction. The screening will occur with the apps at each paediatric checkup up to the child’s age of 12 months, using the Edinburgh Postnatal Depression Scale (EPDS), KID-PROTEKT questionnaire, and the scale 1 (impaired bonding) of the Postpartum Bonding Questionnaire (PBQ-1). The goal is to screen 10,000 patients across Germany. Gynaecologists and paediatricians will receive certified training on peripartum depression. Participants in the intervention group with scores above cut-offs (EPDS ≥ 10, KID-PROTEKT ≥ 1, PBQ-1 ≥ 12) will receive counselling through their treating gynaecologists/paediatricians and will be provided with regional addresses for psychiatrists, psychotherapists, and “Frühe Hilfen” (early prevention) as well as family counselling centres, depending on symptom severity. At each screening, participants will be asked whether they sought support, where, and with whom (utilization). Utilization is the primary outcome. Discussion The screening is designed to reduce underdiagnosis to enable suitable support at an early stage (especially for those often overlooked, such as individuals with “high-functioning depression”) and hence to avoid manifestation of mental health problems in the whole family, especially infants who are exceptionally dependent on their parents and their well-being will benefit from this program. Trial registration German Clinical Trials Register, DRKS00033385. Registered on 15 January 2024.
