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Nader Rabie,1 Ronak Shah,2 Shona Ray-Griffith,3 Jessica L Coker,3 Everett F Magann,4 Zachary N Stowe5 1Tripler Army Medical Center, Department of Obstetrics and Gynecology, Honolulu, HI, USA; 2Our Lady of Angels, Department of Obstetrics and Gynecology, Bogalusa, LA, USA; 3University of Arkansas for Medical Sciences, Department of Psychiatry, Little Rock, AR, USA; 4University of Arkansas for Medical Sciences, Department of Obstetrics and Gynecology, Little Rock, AR, USA; 5University of Wisconsin School of Medicine and Public Health, Psychiatric Institute and Clinic, Madison, WI, USACorrespondence: Everett F MagannUniversity of Arkansas for Medical Sciences, Department of Obstetrics and Gynecology, Little Rock, AR, USAEmail efmagann@uams.eduObjective: The use of electroconvulsive therapy in pregnancy has been limited by concerns about its effects on fetal well-being, despite limited evidence that suggests it is safe and effective. No studies have utilized continuous fetal heart rate monitoring during electroconvulsive therapy sessions. We aimed to describe the fetal heart rate patterns of patients undergoing electroconvulsive therapy.Design: This study is a prospective case series of pregnant patients undergoing electroconvulsive therapy with continuous fetal heart rate monitoring.Setting: University-based hospital.Population: Pregnant patients with a psychiatric indication for electroconvulsive therapy.Methods: Patients underwent fetal heart rate monitoring immediately prior, during and immediately after ECT therapy.Main Outcome Measures: Characterization of the fetal heart rate tracing.Results: Five subjects underwent 44 electroconvulsive therapy sessions. Continuous fetal monitoring was performed on 34 of the sessions. Transient fetal heart rate decelerations occurred in 4 sessions, all self-resolved and none required intervention.Conclusion: This case series is the first to report the results of continuous FHR monitoring during electroconvulsive therapy. The most common finding was a transient, self-resolving bradycardia that was not associated with adverse perinatal outcomes. This supports the opinion that electroconvulsive therapy is a safe treatment option in pregnancy in women with severe mental disease.Keywords: pregnancy, electroconvulsive therapy, fetal monitoring, mental illness and pregnancy

Shona L Ray-Griffith,1,2 Michael P Wendel,2 Zachary N Stowe,3 Everett F Magann2 1Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 3Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA Background and purpose: The majority of the reviews and studies on chronic pain in pregnancy have primarily focused on the pharmacological and non-pharmacological treatment options. The purpose of our review was to identify evidence-based clinical research for the evaluation and management of preexisting chronic pain in pregnancy, chronic pain associated with pregnancy, and chronic pain in relation to mode of delivery. Methods: A literature search was undertaken using the search engines PubMed, CINAHL, EBSCOhost, and Web of Science. Search terms used included “chronic pain” AND “pregnant OR pregnancy” OR “pregnancy complications” from inception through August 2016. Results: The basis of this review was the 144 articles that met inclusion criteria for this review. Based on our review of the current literature, we recommend 7 guidelines for chronic pain management during and after pregnancy: 1) complete history and physical examination; 2) monitor patients for alcohol, nicotine, and substance use; 3) collaborate with patient to set treatment goals; 4) develop a management plan; 5) for opioids, use lowest effective dose; 6) formulate a pain management plan for labor and delivery; and 7) discuss reproductive health with women with chronic pain. Conclusion: The management of chronic pain associated with pregnancy is understudied. Obstetrical providers primarily manage chronic pain during pregnancy. Some general guidelines are provided for those health care providers until more information is available. Keywords: chronic pain, pregnancy, pregnancy complications, chronic pain in pregnancy, guidelines for pain in pregnancy, pain management in pregnancy

Generalised anxiety disorder (GAD) is defined as excessive and uncontrollable worry and anxiety about everyday life situations. It is a chronic disorder, and is associated with substantial somatisation, high rates of comorbid depression and other anxiety disorders, and significant disability. The evidence base for pharmacotherapy and psychotherapy has continued to grow, and a wide range of drug choices for GAD now exists. Current guidelines for GAD generally restrict themselves to presentation of the evidence for various treatments, which, as a result, generally do not offer detailed discussion or recommendation of strategies beyond the first level of treatment, or take into account the individual circumstances of the patient. Thus, there is a lack of algorithm-based treatment guidelines for GAD. Our aim is, therefore, to present an algorithm for the psychopharmacologic management of GAD, intended for all clinicians who treat patients with GAD, where issues of pharmacotherapy are under consideration. We also hope that these GAD algorithms and other guidelines can help to identify high-priority areas that need further study. In this algorithm, we provide a sequenced approach to the pharmacotherapy of GAD, taking into account salient symptomatology and comorbidity, levels of evidence and extent of response. Special issues, including comorbidity, insomnia, suicidality, substance abuse, treatment adherence, pregnancy and lactation, cross-cultural issues, use of medication in the elderly, psychosocial treatment and dosing issues are also addressed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Current practice guidelines discourage use of lithium during breast-feeding, despite limited data. This study aimed to quantify lithium exposure in nursing infants. METHOD: In 10 mother-infant pairs, the authors obtained assays of lithium in maternal serum, breast milk, and infant serum and indices of infant renal and thyroid function. RESULTS: Maternal serum, breast milk, and infant serum daily trough concentrations of lithium averaged 0.76, 0.35, and 0.16 meq/liter, respectively, each lithium level lower than the preceding level by approximately one-half. No serious adverse events were observed, and elevations of thyroid-stimulating hormone, blood urea nitrogen, and creatinine were few, minor, and transient. CONCLUSIONS: Serum lithium levels in nursing infants were low and well tolerated. No significant adverse clinical or behavioral effects in the infants were noted. These findings encourage reassessment of recommendations against lithium during breast-feeding and underscore the importance of close clinical monitoring of nursing infants. [ABSTRACT FROM AUTHOR]

Many real-world situations require navigating decisions for both reward and threat. While there has been significant progress in understanding mechanisms of decision-making and mediating neurocircuitry separately for reward and threat, there is limited understanding of situations where reward and threat contingencies compete to create approach-avoidance conflict (AAC). Here, we leverage computational learning models, independent component analysis (ICA), and multivariate pattern analysis (MVPA) approaches to understand decision-making during a novel task that embeds concurrent reward and threat learning and manipulates congruency between reward and threat probabilities. Computational modeling supported a modified reinforcement learning model where participants integrated reward and threat value into a combined total value according to an individually varying policy parameter, which was highly predictive of decisions to approach reward vs avoid threat during trials where the highest reward option was also the highest threat option (i.e., approach-avoidance conflict). ICA analyses demonstrated unique roles for salience, frontoparietal, medial prefrontal, and inferior frontal networks in differential encoding of reward vs threat prediction error and value signals. The left frontoparietal network uniquely encoded degree of conflict between reward and threat value at the time of choice. MVPA demonstrated that delivery of reward and threat could accurately be decoded within salience and inferior frontal networks, respectively, and that decisions to approach reward vs avoid threat were predicted by the relative degree to which these reward vs threat representations were active at the time of choice. This latter result suggests that navigating AAC decisions involves generating mental representations for possible decision outcomes, and relative activation of these representations may bias subsequent decision-making towards approaching reward or avoiding threat accordingly., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Maternal depression and anxiety may not only increase vulnerability for the development of postpartum depression and anxiety but may increase the perception of obstetric pain., Objective: This review focuses on the relationship among depression, anxiety, and pain during pregnancy and postpartum. We will first review common clinical screening tools for depression, anxiety, and pain. Then, the existing evidence describing the relationship of depression, anxiety, and pain will be covered., Evidence Acquisition: Queries for publications in PubMed, Google Scholar, and the CINAHL (Cumulative Index to Nursing and Allied Health Literature) were completed. Both searches were limited to publications within the last 20 years. Literatures on subtopics obtained from the references of publications identified in the initial search were not limited by publication year., Results: A total of 19 total publications were identified regarding postpartum depression and pain; 17 were identified in the initial search, and 2 related to postpartum depression, anxiety, and pain were found by reviewing references. Eleven studies were identified regarding postpartum anxiety and pain; 4 were found in the original search, and 7 were identified by reviewing the references., Conclusions and Relevance: The relationship between postpartum depression and pain is well characterized in the literature. However, the relationship between postpartum anxiety and pain is less well defined, and further research is needed. The interaction between maternal mental health and pain emphasizes the importance of screening for these conditions and also counseling and educating patients about expectations regarding intrapartum and postpartum pain.

Background: Current research suggests that there is a nuanced relationship between mental well-being and social media. Social media offers opportunities for empowerment, information, and connection while also showing links with depression, high-risk behavior, and harassment. As this medium rapidly integrates into interpersonal interactions, incorporation of social media assessment into the psychiatric evaluation warrants attention. Furthermore, the COVID-19 pandemic and containment measures (ie, social distancing) led to increased dependence on social media, allowing an opportunity to assess the adaptation of psychiatric interviews in response to sociocultural changes., Objective: The first aim of this study was to evaluate if general psychiatry residents and child and adolescent psychiatry fellows assessed social media use as part of the clinical interview. Second, the study examined whether changes were made to the social media assessment in response to known increase of social media use secondary to social distancing measures during the COVID-19 pandemic., Methods: As part of a quality improvement project, the authors surveyed general psychiatry residents and child psychiatry fellows in a university-based training program (n=21) about their assessment of social media use in patient evaluations. Soon after the survey closed, "stay-at-home" orders related to the COVID-19 pandemic began. A subsequent survey was sent out with the same questions to evaluate if residents and fellows altered their interview practices in response to the dramatic sociocultural changes (n=20)., Results: Pre-COVID-19 pandemic survey results found that 10% (2/21) of respondents incorporated social media questions in patient evaluations. In a follow-up survey after the onset of the pandemic, 20% (4/20) of respondents included any assessment of social media use. Among the 15 participants who completed both surveys, there was a nonsignificant increase in the likelihood of asking about social media use (2/15, 13% vs 4/15, 27%, for pre- and during COVID-19, respectively; McNemar χ 2 1 =0.25, P=.617, Cohen d=0.33)., Conclusions: These small survey results raise important questions relevant to the training of residents and fellows in psychiatry. The findings suggest that the assessment of social media use is a neglected component of the psychiatric interview by trainees. The burgeoning use and diversity of social media engagement warrant scrutiny with respect to how this is addressed in interview training. Additionally, given minimal adaptation of the interview in the midst of a pandemic, these findings imply an opportunity for improving psychiatric training that incorporates adapting clinical interviews to sociocultural change., (©Shiri Raphaely, Simon B Goldberg, Megan Moreno, Zachary Stowe. Originally published in JMIR Medical Education (https://mededu.jmir.org), 14.09.2021.)

Background: The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods., Methods: Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19-40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes., Findings: Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe., Interpretation: Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression., Funding: Janssen Research & Development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset., Method: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA., Results: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01)., Conclusions: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Objective  To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways. Design  Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use. Data sources  Data from the US National Birth Defects Prevention Study on 1180 liveborn infants with congenital heart defects and 1644 controls, born 1997-2008. Main outcome measures  Cases included infants with selected congenital heart defects and control infants had no major defects. SSRI use was obtained from telephone interviews with mothers. Results  For women who reported taking SSRIs periconceptionally, maternal SHMT1 (rs9909104) GG and AGgenotypes were associated with a 5.9 and 2.4 increased risk of select congenital heart defects in offspring, respectively, versus the AA genotype (BFDP=0.69). Compared with the AA genotype, BHMT (rs492842 and rs542852) GG and AG genotypes were associated with twice the riskof congenital heart defects (BFDP=0.74 and 0.79, respectively). MGST1 (rs2075237) CC and ACgenotypes were associated with an increased risk compared with the GG genotype (8.0 and 2.8, respectively; BFDP=0.79). Single nucleotide polymorphism in infant genes in the folate (MTHFS rs12438477), homocysteine (TRDMT1 rs6602178 and GNMT rs11752813) and transsulfuration (GSTP1 rs7941395 and MGST1 rs7294985) pathways were also associated with an increased risk of congenital heart defects. Conclusions  Common maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways are associated with an increased risk of certain congenital heart defects among children of women taking SSRIs during cardiogenesis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Bipolar disorder (BD) is highly familial, but studies have yet to examine preschoolers at risk for BD using standardized, developmentally appropriate clinical assessment tools. We used such methods to test whether preschoolers at familial risk for BD have more observed difficulty modulating emotions and behaviors than do low-risk preschoolers. Identification of emotional and behavioral difficulties in at-risk preschoolers is crucial for developing new approaches for early intervention and prevention of BD., Methods: Using the standardized disruptive behavior diagnostic observation schedule (DB-DOS) protocol for preschoolers, we compared 23 preschoolers (M(age): 4.53 ± 0.73 years; 18 males) with a first-degree relative with BD to 21 preschoolers (M(age): 4.65 ± 0.84 years; 11 males) without a family history of BD. We characterized psychopathology in this sample using the Preschool Aged Psychiatric Assessment and behavioral and emotional problems using the Child Behavior Checklist., Results: High-risk preschoolers demonstrated significantly more intense, pervasive, and clinically concerning problems in anger modulation and behavior dysregulation on the DB-DOS than the low-risk group. High-risk relative to low-risk preschoolers, were also more likely to have maternal-reported anxiety and oppositional defiant disorders and internalizing and externalizing problems., Conclusions: Clinically concerning problems in anger modulation and behavior regulation, measured during standardized laboratory observation, differentiate preschoolers at high familial risk for BD from those at low risk. Investigation in a large longitudinal sample is critical for replication and for determining whether these observed behavioral differences can be reliably used as prodromal indicators of mood disorders., (© 2015 Wiley Periodicals, Inc.)

Background: The current study examines the relationship between maternal depression and infant cortisol concentrations. The potential roles of comorbid maternal anxiety disorders, timing of maternal depression, and maternal treatment with psychotropic medications during pregnancy are addressed., Methods: Women with 6-month-old infants (105 boys and 84 girls) participated in a laboratory paradigm that included infant saliva collection at six points, noise burst and arm restraint stressor tasks, and a diagnostic interview of the mother., Results: Lifetime history of maternal depression was associated with increased baseline and mean (average) infant cortisol levels. Comorbidity with anxiety disorder was related to infant cortisol reactivity. Peripartum (prepartum and/or postpartum) maternal depression, rather than a pre-pregnancy history of disorder, was associated with higher infant cortisol reactivity. Prenatal and postnatal exposure to maternal disorder had similar effects, but prenatal maternal psychotropic medication treatment appeared to attenuate infant cortisol increases associated with prenatal maternal disorder exposure., Conclusions: These data suggest that exposure to maternal depression and anxiety during pregnancy and the postpartum period may increase infant salivary cortisol. This maternal depression-infant cortisol association is independent of the effects of delivery complications, and appears to be modulated by prenatal maternal psychotropic treatment.

Objective: Outcome investigations of prenatal maternal depression and psychotropic exposure rely extensively on maternal retrospective recall. This study compared postnatal recall to prospective documentation of illness and medication exposures., Design: Prospective cohort and retrospective case-control studies., Setting: Emory Women's Mental Health Program (prospective study) and Emory University Department of Psychology (retrospective study)., Sample: A total of 164 women who participated in both the prospective and retrospective studies., Methods: Women with a history of mental illness were followed during pregnancy for prospective prenatal assessments of depression and medication exposures. At 6 months postpartum, some of these women also participated in a retrospective study during which they were asked to recall prenatal depression and medication use. Agreement between prospective and retrospective documentation of exposures was analysed., Main Outcome Measures: Occurrence of maternal depression during pregnancy and maternal use of pharmacological agents during pregnancy., Results: There was only moderate agreement (k = 0.42) in prospective versus retrospective reporting of prenatal depression. Positive predictive value for recalling depression was 90.4%; however, negative predictive value for denying depression was only 53.8%. Participants accurately recalled psychotropic use but significantly underreported use of nonpsychotropic medications., Conclusions: Studies using retrospective data collection may be susceptible to systematic recall bias with underreporting of maternal depression and use of nonpsychotropic agents during pregnancy.

Objective: This study estimated the risk of recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued treatment with mood stabilizers during pregnancy., Method: In a prospective observational clinical cohort study, the authors determined recurrence risk and survival-analysis-based time to recurrence of a new episode in 89 pregnant women with DSM-IV bipolar disorder. Eligible subjects were euthymic at conception and continued mood stabilizer treatment or discontinued treatment proximate to conception., Results: The overall risk of at least one recurrence in pregnancy was 71%. Among women who discontinued versus continued mood stabilizer treatment, recurrence risk was twofold greater, median time to first recurrence was more than fourfold shorter, and the proportion of weeks ill during pregnancy was five times greater. Median recurrence latency was 11 times shorter after abrupt/rapid versus gradual discontinuation of mood stabilizer. Most recurrences were depressive or mixed (74%), and 47% occurred during the first trimester. Predictors of recurrence included bipolar II disorder diagnosis, earlier onset, more recurrences/year, recent illness, use of antidepressants, and use of anticonvulsants versus lithium., Conclusions: Discontinuation of mood stabilizer, particularly abruptly, during pregnancy carries a high risk for new morbidity in women with bipolar disorder, especially for early depressive and dysphoric states. However, this risk is reduced markedly by continued mood stabilizer treatment. Treatment planning for pregnant women with bipolar disorder should consider not only the relative risks of fetal exposure to mood stabilizers but also the high risk of recurrence and morbidity associated with stopping maintenance mood stabilizer treatment.

Objective: Bipolar disorder affects 0.5%-1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness., Method: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated., Results: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past., Conclusions: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.

Objective: The authors reviewed the risks and benefits regarding the use of psychiatric medications during breast-feeding as they relate to the health and well-being of mothers and their infants. Strategies are discussed to limit infant exposure to a medication while effectively treating the nursing mother., Method: A MEDLINE search of the literature since 1955 was conducted to determine the use of psychotropic medications in breast-feeding women. Search items included each of the categories of psychopharmacologic agents as well as each of the agents in association with nursing, breast-feeding, postpartum, lactation, and breast milk., Results: No controlled studies on the safety of psychotropic medications in nursing mothers were found. Case reports and small case series for each of the different psychotropic medications serve as the basis for suggested treatment guidelines for the management of psychiatric illnesses in breast-feeding women. Thus, each case needs to be considered on an individual basis, with a thoughtful analysis of the risks and benefits of nursing and exposure of the infant to medication. The baseline clinical status of the infant should also be reviewed., Conclusions: Women are vulnerable postpartum to psychiatric disorders and frequently face the need to decide whether to take psychotropic medications while breast-feeding. Should psychiatric medication be indicated, the parents should be provided with the available information regarding the effects of these medications on the neonate. In this way, an informed decision can be made. When psychotropic medication is used during breast-feeding, it is strongly recommended that the infant's pediatrician be involved in monitoring the infant.

The majority of psychiatric illness onsets early in an individual's life, typically before or during the reproductive years. The increased incidence of major depression, dysthymia, and panic disorder in women compared with men underscores the likelihood that the clinician will encounter the clinical dilemma of medication use during pregnancy and lactation. The emergence of specialized clinics at several academic centers specifically to investigate and address issues in Perinatal psychiatry illustrates this conundrum best. The extant literature derived from human studies suggests that maternal mental illness and stress may have an adverse impact on obstetrical outcome. These clinical investigations are complemented by a burgeoning series of laboratory studies in rodents and nonhuman primates, showing the profound deleterious impact of maternal stress during the perinatal and neonatal periods on the development of the offspring. Data obtained from pharmaceutical registries, cohort studies, toxicology centers, and case series have consistently failed to show an adverse effect associated with in utero antidepressant exposure. Despite these advances and treatment guidelines proposed by the various academic leaders, investigations describing the extent of fetal/neonatal exposure, clinical methods for minimizing such exposure, and clinical treatment guidelines that include the physiological impact of pregnancy are sparse. The available literature shows distinct pharmacokinetic profiles of the selective serotonin reuptake inhibitors in placental passage and breast milk. Preliminary animal studies have shown higher than expected central nervous system concentrations associated with exposure during pregnancy and mathematical modelling for calculating infant exposure when nursing. The clinical import of these data will require further investigations of central nervous system bioavailability in the fetus and neonate.

The use of antidepressants during pregnancy has undergone considerable scrutiny with respect to safety issues, though limited data with respect to dose management and symptom resolution is available. Previous reports on tricyclic antidepressants (TCAs) have demonstrated the need to adjust maternal dose later in pregnancy to maintain therapeutic serum concentrations. However, there is no data on the dosage of selective serotonin uptake inhibitors (SSRIs) required to maintain symptom resolution in women treated for major depression during pregnancy. The purpose of this study, then, was to assess the medication dosage requirements of SSRIs during this time. In this naturalistic study, pregnant women with a primary diagnosis of major depression were followed prospectively through pregnancy at monthly intervals with symptom assessment. Subjects were included in data analysis if they presented prior to 28 weeks gestation, were treated with SSRI monotherapy, received all psychiatric treatment during the pregnancy at the Emory Pregnancy and Postpartum Mood Disorders Program, and achieved euthymia after initial treatment intervention (CGI = 1 and Beck Depression Inventory (BDI) < 9) during pregnancy or failed to respond after eight weeks of treatment. Medication selection was based on personal treatment history or family treatment history (if any), and the published data on SSRIs in pregnancy. All medication dose adjustments were based on depressive symptoms as measured by the BDI and a psychiatric interview (ZNS). Thirty-four pregnant women were included in final analysis. Two thirds of the subjects (n = 22) required an increase in their daily dose of medication to maintain euthymia. The dose increases occurred at 27.1 +/- 7.1 weeks gestation, with mean BDI scores of 16.4 +/- 9.6, compared to a mean treatment response BDI of 6.9 +/- 5.4. Subject's age, education, past personal and familial psychiatric history were not significantly associated with dose adjustment. These novel data on SSRI daily dose in pregnancy parallels the extant literature with tricyclic antidepressants (TCA). Further work to determine the predictors of dose adjustments will provide guidelines for minimizing fetal exposure to both medication and maternal mental illness.

The lifetime incidence of mood disorders is twice as great in women compared with men, with the highest risk occurring during the childbearing years. The management of mental illness during pregnancy and lactation is a particularly complex clinical situation. The cornerstone of such a clinical decision is a completion of an assessment of the risks of the illness vs the risks of treatment. The following article reviews the factors influencing infant outcome and outlines the essential elements of the process of determining risk for the use of psychotropics in women during pregnancy and lactation. As the available data rapidly change, the facets of the risk benefit assessment are consistent and often the issue of specific medication is decided by prior history and exposure.

Objective: The relative risk of psychotropic medication use in women with puerperal psychiatric illness who are breastfeeding has yet to be quantified adequately. Although the emotional and medical benefits of breastfeeding and adverse effects of maternal depression on infant development are well described, how these absolute benefits weigh against the potential effects of psychotropic drug use during lactation to ultimately guide clinical decisions is still unclear. The objective of this report was to evaluate the extent that psychotropic medications were present in the serum of infants breastfed by mothers treated with antidepressants and benzodiazepines., Design: Serum samples were obtained from 35 nursing infants whose mothers were treated with psychotropic medications while breastfeeding. When a detectable concentration of medication was reported, information regarding infant behavior was obtained by maternal report., Setting: The Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital serves as a regional consultation center for the treatment of psychiatric disorders during pregnancy and the postpartum period., Patients: Subjects were mothers referred to the Perinatal Psychiatry Program for consultation regarding the relative safety of psychotropic medication use while breastfeeding., Primary Outcome Measures: Presence of detectable levels of medication in infants whose mothers breastfed while taking psychotropic medications during pregnancy and/or during the puerperium and the well-being (based on maternal report) of infants who had detectable serum concentrations of medication., Results: Seventy-four percent (n = 26) of infants had serum medication concentrations below the laboratory limit of detection (assay sensitivity 5-50 ng/mL). In the remaining 26% of the sample (n = 9), serum concentrations of psychotropic medications and/or active metabolites were detected. In each of these cases, infants had been exposed to the medication during pregnancy. Medications were not detected in infant serum when mothers had taken these agents solely during the postpartum period. No readily apparent difficulties with the infants were reported by mothers., Conclusions: These data support the low incidence of infant toxicity and adverse effects associated with antidepressant and benzodiazepine use during breastfeeding. These data also suggest that infant serum monitoring is helpful in the assessment of medication exposure in children of mothers who breastfeed while using psychotropic medications. Given the limited accumulated data regarding serum concentrations of psychotropic medications in breastfeeding infants, no single agent seems to be safer than another. Therefore, choice of pharmacologic treatment should be guided by the likelihood that it will result in restoration of maternal psychiatric well-being.

The use of psychotropic medications during lactation has not been investigated in a controlled and systematic fashion. The literature is laden with case reports and small case series containing numerous confounds that render the establishment of definitive treatment guidelines tenuous. The increasing number of women who plan to breast-feed and the high rate of psychiatric illness during the postpartum period underscore the need to develop such guidelines. A MEDLINE search was conducted for key words either in the titles or abstracts of publications citing the use of psychotropic medications in lactating women and describing the pharmacokinetics of medication excretion into breast milk. The publications identified span over three decades. The largest single study by one group of investigators examined 12 mother-infant pairs. The majority of studies report their results as a ratio of the breast milk concentration to the maternal serum concentration (milk/plasma [M/P]) ratio. Estimations that use the M/P ratio of the infant daily dose range from 0.1% to 6.2% of the maternal dose. Few studies attempt to account for the complex variations in the maternal, breast milk, and infant physiologic environments. The major confounds of the studies reviewed include (1) failure to document portion of breast milk assayed (foremilk versus hindmilk), (2) limited metabolite assay, (3) limited assay sensitivity (1-25 ng/mL), not of research quality, (4) concomitant maternal and/or infant medications, and (5) medication exposure during pregnancy. Despite these confounds, there are remarkably few reports of adverse effects on nursing infants exposed to psychotropic medications in breast milk. The limited data confirm that psychotropic medications are excreted into breast milk and that the infant is exposed to these medications. The ideal breast milk study that accounts for the confounds identified has not been completed. The complex matrix of breast milk and the changing infant metabolic capacity will require a more detailed analysis with assays of improved sensitivity. Despite the limited reports of adverse effects on nursing infants, the limitations of the available literature and minimal sample sizes make it premature to recommend specific medications from a given class. There is inadequate data on nursing infant exposure to multiple medications to support changing medication to a different agent in an otherwise stable patient. An individualized risk/benefit assessment with the empirical goal of minimizing infant exposure while maintaining maternal emotional health is the ideal approach.

The introduction of lithium salts almost a century ago and the subsequent approval of lithium carbonate for the treatment of patients with bipolar disorder represent one of the cornerstones of modern psychopharmacology. The onset of bipolar disorder in women often occurs during the childbearing years, which complicates the treatment decisions secondary to the possibility of conception while taking medication. The establishment of the lithium registry for fetal teratogenesis in the late 1960s ushered in a heightened level of concern for the use of lithium during the reproductive years; although, in the years to come, it has become apparent that alternative pharmacologic treatments for bipolar disorder may exceed the teratogenic risk of lithium monotherapy. In this paper, the available data on the use of antimanic medications during pregnancy and lactation are reviewed with an emphasis on providing a realistic risk/benefit assessment for medication selection and management of these patients. Treatment strategies are discussed for (1) women who are contemplating pregnancy (2) women who inadvertently conceive while taking medications (3) women who choose to become pregnant while taking medication, and (4) women who intend to breastfeed while taking medications.

Women in their reproductive years constitute the population at greatest risk for major depression. Consequently, many women will experience depression during the course of conception and pregnancy. Rates of major depression among pregnant women appear to be equivalent to those of nongravid women. The evaluation of depression during pregnancy, however, is confounded by the somatic experiences normative at this time. A small number of rating instruments have been validated among pregnant women and should take precedence in research studies until new instruments are developed specifically for this group. Other issues that require further exploration are risk factors for depression during pregnancy and the course of depression during pregnancy.

Objective: The purpose of this study was to determine the concentrations of sertraline and desmethylsertraline in both human breast milk and infant serum., Method: Breast milk samples from 12 women were collected at specific time intervals after oral doses of sertraline (25-200 mg once daily). For 11 mother-infant pairs, maternal serum levels 24 hours after a dose and their infants' serum levels 2-4 hours after nursing were ascertained by high-performance liquid chromatography., Results: Sertraline and desmethylsertraline were present in all breast milk samples, with a gradient from "fore" milk to "hind" milk. The highest concentrations of sertraline were observed in hind milk 7-10 hours after maternal dose. Increasing the maternal dose of sertraline resulted in increased breast milk concentrations of both sertraline and desmethylsertraline. Detectable concentrations of sertraline were found in three nursing infants and desmethylsertraline in six. No adverse effects of exposure were observed in any infant., Conclusions: Sertraline and desmethylsertraline were present in the breast milk of nursing women treated with sertraline. Concentrations were affected by aliquot of milk sampled, time after maternal dose, and maternal daily dose. The infants' serum concentrations detected were below the detection limit of most commercial laboratories. The presence of desmethylsertraline in six infants' samples underscores the importance of metabolite monitoring in determining infant exposure. Estimates of daily infant exposure can be determined after analysis of sertraline and desmethylsertraline concentrations from one full breast at maternal serum steady state. Future studies of breast milk and infant serum samples should address these issues.