Model-based lamotrigine clearance changes during pregnancy: clinical implication

Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods: Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results: A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery

Mood disturbance and pregnancy: pros and cons of pharmacologic treatment

The management of psychiatric disturbances during pregnancy, particularly depression and bipolar disorders, is complex. This article reviews the existing data regarding the impact of an untreated psychiatric illness on the infant's development. In addition, the potential risks to the fetus due to prenatal exposure to different psychotropic agents, including antidepressants, mood stabilizers, antipsychotics, and benzodiazepines, are summarized. Moreover, this article emphasizes that no decision is risk-free, and the ultimate goal is to reduce the exposure to both the illness and the potential teratogenic effects of the treatment. Therefore, clinicians should seek a treatment strategy, which poses the least risk for both mother and infant

Primacy of (hypo) mania in the postpartum period: a concept worth considering

The traditional system of classifying postpartum psychiatric disorders into maternity blues, postpartum depression, and puerperal psychosis overlooks the clinical significance of hypomanic, manic, or mixed symptoms in the postpartum period. Although common after childbirth, episodes of hypomania or non‐psychotic mania, as well as mixed states, are generally not included in the traditional nomenclature. The Diagnostic and Statistical Manual of Mental Disorders (DSM) first acknowledged the role of childbirth in the triggering of manic episodes 25 years ago with the publication of its fourth edition. The official recognition that episodes of hypomania can occur during or after pregnancy came in 2013 with the publication of DSM‐5. Unfortunately, this endorsement by the DSM has not resulted in increased awareness of the common occurrence of hypomania or mania during the postpartum period

Primacy of (hypo) mania in the postpartum period: A concept worth considering

The traditional system of classifying postpartum psychiatric disorders into maternity blues, postpartum depression, and puerperal psychosis overlooks the clinical significance of hypomanic, manic, or mixed symptoms in the postpartum period. Although common after childbirth, episodes of hypomania or non‐psychotic mania, as well as mixed states, are generally not included in the traditional nomenclature. The Diagnostic and Statistical Manual of Mental Disorders (DSM) first acknowledged the role of childbirth in the triggering of manic episodes 25 years ago with the publication of its fourth edition. The official recognition that episodes of hypomania can occur during or after pregnancy came in 2013 with the publication of DSM‐5. Unfortunately, this endorsement by the DSM has not resulted in increased awareness of the common occurrence of hypomania or mania during the postpartum period