Eydie L. Moses-Kolko, M.D. Crystal T. Clark, M.D., M.Sc. Sarah DeBrunner, M.D. Katherine L. Wisner, M.D., M.S. Although the prevalence of bipolar disorder is equal among men and women, the course of illness and clinical features differ across sexes. Women are more likely to have hypomanic episodes and carry a diagnosis of bipolar II disorder (BD II), whereas men are more likely to experience manic episodes (Baldassano et al. 2005; Schneck et al. 2008). Compared with men, women with BD II have more frequent depressive episodes. Women with bipolar I disorder (BD I) are more likely than men to rapidly cycle and have increased episode severity over time (Erol et al. 2015). Additionally, women with both BD I and II attempt suicide more often than men (Baldassano et al. 2005). These sex-related clinical differences most likely derive from neural impacts of sex steroid fluctuation during women’s reproductive years (Brunton and Russell 2008). In the sections that follow, we address what is known about the impact of female sex steroid fluctuations on the epidemiology, clinical presentation, and treatment of BD II in reproductive-aged women. There are inconsistent reports that earlier onset of menarche is associated with earlier onset and greater severity of mood disorder psychopathology. In the largest study to examine this association in bipolar disorder, this was confirmed for BD I but not BD II. Illness onset within 1 year before or after menarche accounted for 8.5% of women with BD I, but only 4.5% of women with BD II (Tondo et al. 2017). A smaller study (Freeman et al. 2002) found that bipolar disorder illness onset was more likely to occur before or within a year of menarche in 50% of affected women; however, these results might be influenced by the predominance of BD I in the sample (n=36, vs. BD II, n=13). Menstrual cycle dysfunction, present in 20% of the general population, is defined as unpredictable cycle length or cycle length <25 days or >35 days. The medical implications of menstrual cycle dysfunction include infertility, osteoporosis, and endometrial hyperplasia. Early-onset menstrual cycle dysfunction, occurring within the first 5 years postmenarche and prior to any long-term impact of psychotropics, was more prevalent in women with bipolar disorder (34.2%) relative to healthy control women (22%) and women with major depressive disorder (MDD; 25%) (OR=1.7; 95% CI, 1.1–2.4; Joffe et al. 2006b). Menstrual cycle dysfunction was threefold higher in BD I relative to BD II or bipolar disorder not otherwise specified (BD NOS). When incidence rate ratio (IRR) for first child was used as measure of fertility, women with bipolar disorder had reduced fertility (IRR=0.36) compared with women with MDD (IRR=0.57) and other nonpsychotic psychiatric disorders (IRR=0.70) that was not explained by increased rates of therapeutic abortion. This effect was accentuated within the 18-month period following initial psychiatric hospitalization and in more severe illness (i.e., schizophrenia), which suggests that illness severity might explain reduced fertility rates (Laursen and Munk-Olsen 2010). Several mood stabilizer agents, most notably valproic acid, first-generation antipsychotics (FGAs), and risperidone, further contribute to reduced fertility. Women exposed to valproic acid are at risk for developing polycystic ovarian syndrome either through direct effects on ovarian function or via weight gain and associated insulin resistance (Joffe et al. 2006a). Diminished fertility can also arise from FGA-mediated tuberoinfundibular dopamine2 receptor blockade, subsequent hyperprolactinemia, and ultimately suppression of ovulation. Second-generation antipsychotics (SGA) do not increase prolactin levels to the extent that FGAs do, with the exception of risperidone (Kinon et al. 2003). Because there is a limited role for valproic acid, FGAs, and risperidone in the treatment of BD II, it is conceivable that women with BD II have lower exposure to these medications and thus might be at lower risk for medication-induced infertility. Converging evidence points to a predilection for menstrual cycle–related mood worsening in BD II relative to BD I or other mood disorders. Premenstrual dysphoria was reported to be more frequent in women with BD II (70%) relative to BD I (44%) and MDD (42%) (Endicott et al. 1985). Perimenstrual mood worsening was also reported to be higher in women with BD II relative to those with BD I in a specialized bipolar disorders clinic (Perich et al. 2017). In the STEP-BD substudy (Dias et al. 2011), in which BD II represented 50% of the sample, premenstrual worsening in bipolar disorder was a predictor of more severe course of bipolar disorder illness, with more episodes per year, shorter time to subsyndromal relapse, and higher mood disorder severity. In a review of the case literature, authors described a heterogeneous temporal pattern of symptoms with respect to the menstrual cycle, with entrainment of either depressed or hypomanic mood not only to the premenstrual phase but also to the menstrual and periovulatory phases, as well as timing variability across cycles in the same woman (Teatero et al. 2014). Lamotrigine pharmacotherapy added to a baseline medication regimen, for menstrually entrained mood symptoms, was conducted in an open-label study of women with bipolar disorder (n=23 for BD I; 24 for BD II; 25 for BD NOS). Self-reported mood was most depressed during the menstrual phase of the cycle; the depressive symptoms attenuated with lamotrigine treatment. Additionally, within-phase mood variability diminished with lamotrigine augmentation (Robakis et al. 2015). Combined oral contraceptives (COCs) were also noted to attenuate premenstrual symptoms in bipolar disorder (Rasgon et al. 2003). Treatment recommendations for premenstrual mood symptoms occurring in the context of bipolar disorder endorsed by one group (Smith and Frey 2016) include optimization of mood stabilizer treatment followed by 2 months of prospective mood charting in order to confirm a premenstrual dysphoric disorder diagnosis. Hormonal agents, rather than antidepressants, are recommended as adjunctive treatment, in addition to lifestyle changes, psychoeducation, and cognitive-behavioral therapy, although behavioral trials for premenstrual dysphoric disorder in BD are lacking. Case Report: Role of Hormonal Agents in the Management of Mood Symptoms Related to the Menstrual Cycle in BD II Latasha is a 36-year-old woman with BD II who presents with premenstrual mood worsening despite treatment with quetiapine 200 mg nightly. In addition to irritable mood, her premenstrual symptoms include severe cramping, high levels of worry, irrational ideas about social rejection, and somatic symptoms of anxiety such as chest tightness, pit in stomach, and insomnia. She often misses work or incites conflict in relationships during the premenstrual period. Mood and functioning are better after onset of menses. Her psychiatrist discusses treatment options, including the addition of a selective serotonin reuptake inhibitor (SSRI), dosed premenstrually, or the addition of the COC levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg. Because Latasha is concerned that the SSRI will worsen her irritability, as has happened in the past, she opts for the COC. In addition, the psychiatrist recommends that she meet regularly with a therapist to develop skills to manage her premenstrual mood dysregulation. Latasha returns to the clinic 2 months after beginning the COC and engaging in regular psychotherapy. She reports a decrease in premenstrual anxiety, irritability, sleep problems, and cramps. Her boyfriend reports that she is less angry and that she has not missed any days of work. This case illustrates the role of COCs as part of the larger armamentarium for stabilization of mood symptoms across the menstrual cycle in BD II, in conjunction with a mood stabilizer and behavioral strategies for management of BD II. Several of the antiepileptic drug (AED) mood stabilizers interact bidirectionally with COCs and may result in the therapeutic failure of either drug (Reimers et al. 2015). The most common estrogen in COCs, 17α-ethinyl estradiol, lowers lamotrigine plasma concentrations via potent induction of uridine 5′-diphosphate-glucuronosyltransferase (Christensen et al. 2007). Therefore, in lamotrigine-treated women, hormonal contraception options are limited to progestogen-only contraceptives, the levonorgestrel-releasing intrauterine device (LNG-IUD), or the copper-bearing IUD. Carbamazepine and topiramate induce metabolism of estrogens and progestogens; therefore, women taking these AEDs can safely use depot medroxyprogesterone acetate, LNG-IUD, and the copper-bearing IUD, but risk reduced contraceptive effectiveness with COCs, combined transdermal patch, combined contraceptive vaginal ring, progestin-only pill, norethisterone enanthate injectable, levonorgestrel, and the etonogestrel implant (Reimers et al. 2015). Onset of bipolar disorder typically occurs during women’s reproductive years. The point prevalence of BD II or hypomania at 12-weeks gestation ranges from 0.3% to 1.4%, which mirrors the 0.8%, 12-month bipolar disorder prevalence in the general population (Sharma and Pope 2012). In naturalistic studies in pregnancy, women with BD II were less likely to 1) take psychotropics beyond the first trimester (Driscoll et al. 2017; Viguera et al. 2007b), 2) receive treatment that was evidence-based (Driscoll et al. 2017), and 3) remain euthymic (Viguera et al. 2007b). Women with BD II had an 89% rate of depression/mixed recurrence versus only a 4% rate of hypomanic recurrence, whereas the polarity of recurrence for women with BD I was 41% for depressed/mixed and 20% for hypomanic or manic (Viguera et al. 2007b). Recurrence was higher with discontinuation (86% vs. 37%), particularly with abrupt discontinuation in less than 2 weeks (Viguera et al. 2007b). Reduced psychotropic use in pregnancy (46%) and higher use postpartum (73%–86%) were reported in several studies of perinatal BD (Driscoll et al. 2017; Sharma et al. 2013). The first postpartum month is a period of high risk for BD I disorder relapse and hospitalization (Munk-Olsen et al. 2006), whereas BD II episodes were more widely distributed across the perinatal period (Di Florio et al. 2013) and not reported to be associated with hospitalization. Results from a meta-analysis yielded a postpartum bipolar disorder relapse rate of 37% that did not differ between BD I or BD II (Wesseloo et al. 2016). Although there were no results available for BD II, in BD I, prophylactic pharmacotherapy compared with no medications during late pregnancy/early postpartum was associated with a reduction in the postpartum relapse rate (23% vs. 65%, respectively) (Wesseloo et al. 2016). Recent studies have focused attention on the higher than expected prevalence of bipolar disorder in women with postpartum depression. Among 10,000 women recruited from an obstetric hospital, 22.6% of women with Edinburgh Postnatal Depression Scale (EPDS) scores of 10 or higher had a diagnosis of bipolar disorder; 50% of these women were diagnosed with BD II or BD NOS (Wisner et al. 2013). In another, small (n=56) study, 23% of women with postpartum depression were found to have lifetime BD II. Furthermore, among women unresponsive to antidepressants during postpartum depression, 54% were diagnosed with bipolar disorder, with nearly the whole group (52%) accounted for by BD NOS or BD II (Sharma et al. 2008). Several groups have examined the presence of hypomania in the first week postpartum by using the Highs Scale (Glover et al. 1994). The Highs Scale is a self-report scale based on DSM-III-R criteria for mania (American Psychiatric Association 1987), with a score of 2 (“Yes, a lot”) and 1 (“Yes, a little”) assigned to each of seven items (elated, more active, more talkative, thoughts raced, special talents, less sleep need, attention jumping). Using a threshold score of 8 or higher, Heron et al. (2009) reported that incidence of 1-week postpartum hypomania was approximately 12%, and surpassed the incidence of hypomania in pregnancy (1.4%) and 2 months postpartum (5%). Unlike the blues, which peak on day 3 or 4 postpartum, the highs can begin as early as day 1 postpartum. Prior to dissemination of this screening tool in the general population, further research is needed to confirm this finding in relation to standard instruments and to assess its clinical significance. Because BD II criteria exclude the presence of mixed or mania-associated psychosis, the BD II diagnosis is upheld only when psychotic symptoms accompany the depressive phase of bipolar disorder. Postpartum psychosis is rare, affecting approximately 0.1%–0.2% (1 in 1,000 to 1 in 500) of women in the postpartum period, and is considered by many to be a variant of BD I. A brief psychotic disorder phenotype may be evident, characterized by disorganized behavior and rapid shifts from excited to inhibited motoric states, from confusion to lucidity, and from anxiety/paranoia to happiness. Auditory or visual hallucinations, paranoid or grandiose delusions, and elements of delirium or disorientation are common, as are extreme deficits in judgment and high levels of impulsivity. Postpartum psychosis is a medical emergency because of the potential risk for infanticide or suicide; therefore, referral for immediate treatment in an intensive, structured setting, such as a day hospital or inpatient psychiatric unit, is indicated. Preventive and acute phase treatment strategies with lithium and antipsychotic medications were associated with favorable outcomes (Bergink et al. 2015). Although there are no validated screening instruments for BD II (see Chapter 3, “Interface Between Borderline Personality Disorder and Bipolar II Disorder”), a number of bipolar disorder screening tools have been applied to the perinatal population. The Mood Disorder Questionnaire (MDQ; Hirschfeld et al. 2003), a 15-item self-report instrument to screen for lifetime prevalence of bipolar disorder, has shown improved sensitivity and specificity for diagnosis of perinatal bipolar spectrum diagnoses by using a score threshold of 7 in Section 1 and when removing the functional impairment criterion in Section 3 (Chessick and Dimidjian 2010). Compared with DSM-IV based clinical diagnoses, MDQ sensitivity was improved from 40% to 89% and specificity remained high (91% to 84%) with the alternative scoring algorithm (Frey et al. 2012). Another study found that the alternative scoring algorithm increased identification of bipolar disorder diagnoses by nearly 20%, from 50% to 68% (Clark et al. 2015). In these studies of 100–150 women with affective disorders, BD II diagnoses represented only 6%–10% of the total sample, and larger samples are needed for confirmation for the alternative scoring algorithm’s utility in screening for BD II. Screening is best timed in early pregnancy, early postpartum, and at the time of a depression diagnosis. Exploring for clinical features associated with BD II has the potential to inform treatment selection and treatment course (Table 12–1). Although there is strong endorsement for perinatal depression screening in the United States (Committee on Obstetric Practice 2015; Siu et al. 2016), absence of similar directives for bipolar disorder threatens to result in high rates of undetected BD I and II. TABLE 12–1.History elements that increase suspicion for BD spectrum diagnosis in women with postpartum depression—WHIPLASHED mnemonic W Worse or wired when taking antidepressants H Hypomania I Irritability P Psychomotor retardation or agitation L Loaded family history of affective disorders (and/or postpartum mood disorder) A Abrupt onset and/or termination of depressive episodes or bursts of increased energy or subthreshold hypomanic symptoms S Seasonal or postpartum depressive episodes H Hyperphagia or hypersomnia E Early age at depression onset D Delusions or psychotic features during depressive episodes Comorbidity Anxiety disorders Substance use disorders Source.Adapted from Pies 2007. With 50% of pregnancies being unplanned, women often have not considered the impact of medication and other behaviors (e.g., tobacco, alcohol) on pregnancy (Finer and Zolna 2011). Family planning discussion should occur during pharmacotherapy initiation at the time of BD II diagnosis, and ideally while the patient is euthymic. With women who are pregnant, postpartum, or planning a pregnancy, a structured discussion (Wisner et al. 2000) should include patient education regarding the natural history of her psychiatric disorder, the risks associated both with the disorder and with available somatic treatments, and a discussion of available treatment options. Risks to mother and infant of BD II in pregnancy have not been specifically studied. In studies that did not discriminate among subtypes of bipolar disorder, both bipolar disorder (Bodén et al. 2012) and severe mental illness (Vigod et al. 2015) were associated with more adverse pregnancy outcomes relative to the general population. The most rigorous studies have methodologically adjusted for severity of illness and associated characteristics when examining impacts. Regardless of whether medication was taken in pregnancy, women with bipolar disorder were more commonly found to be smokers, to be overweight, to have misused alcohol or substances, and to have pregnancy induction, planned cesarean section, instrumental delivery, or preterm birth. Infants of women with bipolar disorder, regardless of medication exposure, were more likely to have microcephaly and neonatal hypoglycemia (Bodén et al. 2012) and tended to also be small for gestation age. Suboptimal maternal-infant interaction can adversely impact infant socioemotional, cognitive, and physical development. Mother-infant interactional style in women with severe mental illness is noted for reduced mind-mindedness and sensitivity to infant cues. Mother-infant synchrony was greater in bipolar disorder relative to schizophrenia (Rigby et al. 2016) and was not significantly different among women with bipolar disorder (50% BD II NOS), women with MDD, and healthy control women (Logsdon et al. 2015). Reports indicate reduced emotional regulation, reduced autonomic adaptation to stressors (Johnson et al. 2014), and lower motor attainment on the Bayley Scales of Infant Development (Santucci et al. 2017) in offspring of mothers with bipolar disorder who took psychotropics in pregnancy. The perinatal period is an ideal time to optimize nonpharmacological strategies to support mental health. Close clinical monitoring and enlisting supports to prevent sleep disruption and stabilize social rhythms in the new mother with bipolar disorder are particularly important. Psychotherapy treatment options should be determined based on review of patient history, current mood state, and reference to evidence-based treatments. Interpersonal and social rhythm therapy (IPSRT; see Chapter 10, “Psychosocial Interventions in Bipolar II Disorder”) is a compelling treatment approach given demonstrated benefit of interpersonal psychotherapy in mothers (Swartz et al. 2016) and of IPSRT in women with BD II (Swartz et al. 2018). In a small RCT, a midday dose of 7,000-lux bright white light was associated with a threefold higher depression remission rate compared with red placebo light by 6 weeks in adults with bipolar depression (30% of sample with BD II) who were taking mood stabilizer agents (Sit et al. 2018). These results await replication and delineation of maintenance strategies but show promise for use as an adjunct to mood stabilizer treatment in perinatal BD II depression. Psychotropic treatment options are determined on the basis of review of patient history, current mood state, and reference to evidence-based treatments described elsewhere in this book. A guiding principle is to optimize maternal disease management while minimizing offspring adverse effects posed by medications and maternal illness. The medication to which a mother has responded in the past is often the best choice even in the absence of substantial data, given the known risk of untreated illness. Psychotropics cross the placenta to varied extents, whereas transfer to the baby via lactation is much lower than placental transfer because of incomplete psychotropic absorption into breast milk as well as first-pass metabolism effects in the infant. If fetal exposure to a psychotropic has already occurred, this agent would be reasonable to continue during lactation rather than switching to one with theoretically lower exposure. The benefits of breastfeeding are well established. Irrespective of incremental benefits of breastfeeding for maternal and infant sleep quality (Cubero et al. 2005; Tobback et al. 2017), the demands of caring for and feeding a newborn result in interrupted sleep. Unlike women with BD I who have a greater risk for mania because of sleep disruption, women with BD II are less susceptible to the onset of hypomania (Lewis et al. 2017). Both women with BD I and women with BD II are at risk for depressive episodes because of sleep disruption and, when available, are advised to seek assistance with overnight feedings by using either expressed breast milk or formula. Medications pass into breast milk to varying degrees. A relative infant dose (the estimated infant dose divided by the mother’s dose in mg/kg/day) of less than 10% poses negligible risk to the infant (Newton and Hale 2015). Higher amounts of drug passage are not necessarily contraindicated, but precautions in following the infant closely should be applied. Up-to-date safety data on individual medications in lactation can be found at LactMed (http://toxnet.nlm.nih.gov). Since its first introduction for the treatment of mania in 1949, lithium has remained the gold standard for treatment of bipolar disorder because it is an effective prophylaxis and treatment for mania and postpartum psychosis, and it reduces the rate of rehospitalization and suicide (Bergink et al. 2016; Cade 1949; Lähteenvuo et al. 2018). For women with BD II, lithium is as effective as lamotrigine for the treatment of acute depressive episodes and is effective for maintenance therapy (Peselow et al. 1982; Suppes et al. 2008; Tondo et al. 1998). See Chapter 9, “Antidepressant Medications in Bipolar II Disorder,” for a discussion of the role of lithium in the treatment of BD II. In weighing risks and benefits of perinatal lithium treatment, women with BD II who are lithium responders must consider the risk that alternative treatments may be less effective or cause adverse effects. The association between in utero lithium exposure and congenital malformations is lower than described previously. In an investigation of cardiac malformations in 1,325,563 pregnancies (Patorno et al. 2017), Ebsteins’s anomaly (defined as right ventricular outflow tract obstruction defects) and overall cardiac malformations occurred at a rate of 0.6 and 1.7 versus 0.18 and 1.15 per 100 births, respectively, in lithium-exposed compared with nonexposed infants. Because of enhanced lithium clearance in pregnancy, increased serum level monitoring with appropriate dose adjustment is warranted to maintain the prepregnancy effective concentration and prevent recurrence of bipolar disorder episodes and illness exposure (Wesseloo et al. 2017). Pregnancy complications such as dehydration due to hyperemesis or preeclampsia require close lithium level monitoring because of the increased risk of toxicity. Some women taking lithium during pregnancy will develop polyhydramnios, which warrants close obstetrical evaluation but rarely requires intervention. The case literature describes an association between late-pregnancy fetal lithium exposure and poor neonatal outcomes including poor muscle tone, tachycardia, diabetes insipidus, transient hypothyroidism, and respiratory problems. Larger studies that control for confounding variables are needed to clarify the mechanisms underlying these outcomes. At birth, the rapid fluid shifts increase the risk for high or toxic maternal and newborn lithium concentrations. On the basis of an association between umbilical cord lithium concentrations >0.64 mEq/L and infant central nervous system, respiratory, and neuromuscular complications (Newport et al. 2005), women are advised to suspend dosing of lithium at the onset of labor or 24–48 hours prior to a scheduled delivery (i.e., cesarean section, induction) to reduce fetal passage of lithium. After delivery, the lithium dose is restarted at the prepregnancy dose to avoid large fluctuations in the serum level and to prevent toxicity in the postpartum period. Lithium has not been associated with long-term neurodevelopmental effects based on small studies and unpublished research. In a study of 15 mothers with bipolar disorder, rigorous tests of neurological and cognitive development determined that offspring ranging from 3 to 15 years of age had normative development (van der Lugt et al. 2012). Unpublished data from a study using an illness-matched comparison group confirm these findings (Viguera 2006). Complications such as cyanosis, hypothyroidism, and lithium toxicity have been reported in cases of infants exposed to lithium in breast milk; however, larger studies are needed to better understand the prevalence of these outcomes (Skausig and Schou 1977; Tunnessen and Hertz 1972). Case reports are confounded by the exposure to lithium during pregnancy, polypharmacy, and toxic maternal concentrations. Several studies dispel the notion that lithium should be contraindicated during breastfeeding. These studies report average infant lithium concentrations to be 20% relative to maternal lithium concentrations and provide recommendations for infant monitoring (Bogen et al. 2012; Viguera et al. 2007a). Formula supplementation should be considered in infants that are born prematurely, have an infection, or have difficulty feeding. Few studies have specifically examined antipsychotics in the treatment of perinatal BD II. A retrospective chart review of 18 women with postpartum BD I, BD II, or BD NOS treated with quetiapine (median dose 75 mg) found that at the end of 8 weeks of treatment, 83% were rated as “much” or “very much” improved (Sharma et al. 2015). In an open-label study of quetiapine extended-release for the treatment of BD II postpartum depression (n=26), 15 women completed the study, with depression remitting by week 12 at a mean total daily dose of 137.5 mg (Misri et al. 2015). Changes in the activity of the hepatic cytochrome P450 (CYP) enzyme system are prominent in pregnant women. The activity of CYP1A2 decreased, which resulted in reduced clearance of olanzapine or clozapine. Increased activity occurs for CYP2D6 (e.g., greater clearance of risperidone) and CYP3A4 (e.g., greater clearance of lurasidone) (Greenberg and Citrome 2017; Tsutsumi et al. 2001; Wadelius et al. 1997). Dosage adjustments are needed to maintain stability or to prevent emergent side effects. Because of lack of differentiation among bipolar disorder subtypes in the literature, guidance for women with BD II is extrapolated from the larger bipolar disorder literature. In a sample of 1,360,101 pregnant women, approximately 35% of whom had bipolar disorder, rigorous statistical methods were applied to examine risk of major congenital malformations and cardiac malformations associated with in utero antipsychotic exposure (Huybrechts et al. 2016). The authors reported no significant increase in risk of major malformations for SGAs (relative risk [RR]=1.05; 95% CI=0.96–1.16) or FGAs (RR=0.90; 95% CI=0.62–1.31) nor any significant increase in risk of cardiac malformations for SGAs (RR=1.06; 95% CI=0.9–1.24) or FGAs (RR=0.75; 95% CI=0.39–1.43). Analyses of specific medications within SGA and FGA classes revealed similar results, with the exception of risperidone, for which there was a small but significantly increased risk of major congenital malformations (RR=1.26; 95% CI=1.02–1.56) (Huybrechts et al. 2016). The efficacy of quetiapine for BD II depression provides a clinical rationale for this medication choice in some women, despite the association between SGAs and maternal weight gain, hyperlipidemia and increased insulin resistance, infant macrocephaly, and large-for-gestation-age infants (Bodén et al. 2012). Other risk considerations with the antipsychotic medication class include preterm birth, increased rate of higher level nursery admission, respiratory distress, and neonatal adaptation symptoms; however, larger studies are needed to disentangle effects of drug from those of illness (Kulkarni et al. 2014). Similarly, in small studies uncontrolled for diagnosis or focused on schizophrenia, gestational antipsychotic exposure was associated with lower neurodevelopmental ratings within 6 months following antipsychotic exposure (bipolar disorder was present in 32% of exposed pregnancies) (Johnson et al. 2012), with ratings recovering by 12 months of life (Peng et al. 2013). Lactational SGA relative infant dose levels below 10% make this group of medications increasingly acceptable during lactation; however, additional research is needed (Uguz 2016). The AEDs lamotrigine, valproic acid, and carbamazepine are U.S. Food and Drug Administration (FDA)–approved long-term maintenance options for treatment of bipolar disorder. Valproic acid is the AED associated with the highest risk of major congenital malformations (10.7%) and thus reserved for perinatal women with highly refractory bipolar disorder. Carbamazepine is also a less preferred option in pregnancy because of an increased risk of major congenital malformations (4.6%) (Meador et al. 2008). Late-gestational exposure to carbamazepine has been variably associated with reduced fetal head growth, hyperbilirubinemia, and intrauterine growth restriction, but these findings are inconsistent. Lamotrigine is a preferred option for women of childbearing age because of its favorable reproductive profile and its efficacy to prevent recurrent depressive episodes and the onset of postpartum depression in women with BD II (Campbell et al. 2014; Cunnington et al. 2011; Hernández-Díaz et al. 2012; Sharma and Sommerdyk 2016; Tomson et al. 2011). In 2008, the North American Lamotrigine Registry reported a relative risk of 10.4 for isolated cleft palate, isolated cleft lip, and combined cleft lip and palate for infants born to mothers who took lamotrigine monotherapy during pregnancy (Holmes et al. 2008); however, these findings were not reproduced in a population-based case-control study completed in 2016 (Dolk et al. 2016). Other lamotrigine registries report a rate of 2.0%–2.9% risk of cleft palate, which is consistent with the rate in the general population (Campbell et al. 2014). Lamotrigine has not been associated with other adverse effects related to pregnancy exposure. Off-label AEDs such as gabapentin and topiramate have not been shown to be effective antimanic agents or superior monotherapy options compared with FDA-approved options. Lamotrigine and carbamazepine are not associated with long-term neurodevelopmental abnormalities (Pariente et al. 2017). Although a delay in verbal ability has been reported for children exposed to carbamazepine during pregnancy, other investigations have concluded that children with carbamazepine exposure in utero do not differ in verbal IQ from those without exposure (Baker et al. 2015; Gaily et al. 2004). In contrast, children with in utero valproic acid exposure have significant language delays, and lower verbal IQ, and more often have clinical presentations that meet the criteria for intellectual disability (Bromley et al. 2009). The transfer of AED to breast milk is less than the transfer during gestation. Infant/maternal serum concentration ratios for carbamazepine range from 0.0 to 0.7 (Kacirova et al. 2011). Infant serum concentrations for valproic acid are reported as 0.9%–2.3% of maternal serum levels (Piontek et al. 2000), which is less than those for lamotrigine infant serum concentration, which vary from 6% to 50% of the maternal serum concentration (Clark et al. 2013; Newport et al. 2008). Breastfeeding is supported for women taking carbamazepine, valproic acid, and lamotrigine; however, concerns for difficulty feeding, lethargy, or slowed growth require assessment by a pediatrician and possible laboratory assessments to test for toxic effects. There have been no studies of antidepressant efficacy for BD II depression in perinatal women. As with other BD II depressed patient groups, this decision must be weighed carefully for the individual patient (see Chapter 9, “Antidepressant Medications in Bipolar II Disorder”). On the basis of recent evidence for equipoise between mood stabilizer monotherapy, SSRI monotherapy, or the combination thereof in BD II depression (Altshuler et al. 2017), some women may elect to continue or to initiate unopposed antidepressants during pregnancy or lactation. Several articles provide discussions of decision making regarding use of antidepressants in pregnancy and lactation (Byatt et al. 2013; Weissman et al. 2004). Although not a primary treatment for BD II, benzodiazepines are a common adjunct to bipolar disorder treatment; however, benzodiazepines are also abused more frequently in individuals with BD II relative to those with recurrent MDD and subthreshold mania (Merikangas et al. 2008). Therefore, the risk of benzodiazepine abuse must be considered when recommending this adjunctive treatment across the lifespan, and especially in the perinatal period. Early studies described an association between first trimester benzodiazepine exposure and an increased risk of oral clefts (Iqbal et al. 2002), whereas subsequent studies in larger samples and with more rigorous study methods have challenged this finding (Dolovich et al. 1998). A recent report of an association between gestational exposure to benzodiazepines and higher rates of cesarean section delivery, neonatal low birth weight, and newborn ventilatory support was published (Yonkers et al. 2017). Neonatal withdrawal from combination regimens that included benzodiazepines was more severe than from opioids alone (Huybrechts et al. 2017) or SSRIs alone (Salisbury et al. 2016). Additionally, in utero benzodiazepine exposure was associated with long-term behavioral problems in the offspring, including anxiety, emotional reactivity, somatic complaints (Brandlistuen et al. 2017), and aggressive behaviors (Radojčić et al. 2017). Additional research that controls for confounding variables will elucidate the association between adjunctive treatment with benzodiazepines and adverse perinatal outcomes. Higher prevalence of hypomania and BD II in women relative to men, as well as premenstrual symptom worsening in BD II, may be a function of heightened sex steroid hormone sensitivity in women’s reproductive years. Associations and interactions among bipolar disorder, mood stabilizer treatment, fertility (i.e., hyperprolactinemia and polycystic ovarian syndrome), hormonal contraception, and pregnancy must be understood in order to optimize family planning and mental and physical health in women with bipolar disorder. BD II episodes are more widely distributed across the antenatal and postpartum period, whereas BD I episodes more commonly cluster within the first 4 weeks postpartum. There is a high risk of perinatal BD II depressive/mixed polarity illness relapse that can be mitigated by maintaining pharmacotherapy in the perinatal period. Early discussions of family planning are imperative because of illness and mood stabilizer effects on infant outcomes, such as preterm birth, small for gestation age, microcephaly, hypoglycemia, and poor maternal sensitivity to infant cues described in bipolar disorder and in association with mood stabilizer medications. Prescription of mood stabilizer medication with which a woman can achieve symptom remission is the central component of perinatal treatment, along with the important adjunctive roles of social support and protection of sleep. Recent studies provide reassuring data on perinatal and lactational risks for lithium, SGA, and lamotrigine treatment. Ongoing studies of perinatal pharmacokinetics, treatment efficacy, and neurodevelopmental outcomes in exposed infants promise to further inform treatment decisions for perinatal women with BD II. Altshuler LL, Sugar CA, McElroy SL, et al: Switch rates during acute treatment for bipolar II depression with lithium, sertraline, or the two combined: a randomized double-blind comparison. Am J Psychiatry 174(3):266–276, 2017 28135846 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised. Washington, DC, American Psychiatric Association, 1987 Baker GA, Bromley RL, Briggs M, et al; Liverpool and Manchester Neurodevelopment Group: IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology 84(4):382–390, 2015 25540307 Baldassano CF, Marangell LB, Gyulai L, et al: Gender differences in bipolar disorder: retrospective data from the first 500 STEP-BD participants. Bipolar Disord 7(5):465–470, 2005 16176440 Bergink V, Burgerhout KM, Koorengevel KM, et al: Treatment of psychosis and mania in the postpartum period. Am J Psychiatry 172(2):115–123, 2015 25640930 Bergink V, Rasgon N, Wisner KL: Postpartum psychosis: madness, mania, and melancholia in motherhood. Am J Psychiatry 173(12):1179–1188, 2016 27609245 Bodén R, Lundgren M, Brandt L, et al: Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ 345:e7085, 2012 23137820 Bogen DL, Sit D, Genovese A, et al: Three cases of lithium exposure and exclusive breastfeeding. Arch Women Ment Health 15(1):69–72, 2012 22277970 Brandlistuen RE, Ystrom E, Hernandez-Diaz S, et al: Association of prenatal exposure to benzodiazepines and child internalizing problems: a sibling-controlled cohort study. PLoS One 12(7):e0181042, 2017 28746341 Bromley RL, Baker GA, Meador KJ: Cognitive abilities and behaviour of children exposed to antiepileptic drugs in utero. Curr Opin Neurol 22(2):162–166, 2009 19532040 Brunton PJ, Russell JA: The expectant brain: adapting for motherhood. Nat Rev Neurosci 9(1):11–25, 2008 18073776 Byatt N, Deligiannidis KM, Freeman MP: Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand 127(2):94–114, 2013 23240634 Cade JF: Lithium salts in the treatment of psychotic excitement. Med J Aust 2(10):349–352, 1949 18142718 Campbell E, Kennedy F, Russell A, et al: Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry 85(9):1029–1034, 2014 24444855 Chessick CA, Dimidjian S: Screening for bipolar disorder during pregnancy and the postpartum period. Arch Women Ment Health 13(3):233–248, 2010 20198393 Christensen J, Petrenaite V, Atterman J, et al: Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 48(3):484–489, 2007 17346247 Clark CT, Klein AM, Perel JM, et al: Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry 170(11):1240–1247, 2013 24185239 Clark CT, Sit DK, Driscoll K, et al: Does screening with the MDQ and EPDS improve identification of bipolar disorder in an obstetrical sample? Depress Anxiety 32(7):518–526, 2015 26059839 Committee on Obstetric Practice: The American College of Obstetricians and Gynecologists Committee Opinion no. 630. Screening for perinatal depression. Obstet Gynecol 125(5):1268–1271, 2015 25932866 Cubero J, Valero V, Sánchez J, et al: The circadian rhythm of tryptophan in breast milk affects the rhythms of 6-sulfatoxymelatonin and sleep in newborn. Neuroendocrinol Lett 26(6):657–661, 2005 16380706 Cunnington MC, Weil JG, Messenheimer JA, et al: Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology 76(21):1817–1823, 2011 21606453 Di Florio A, Forty L, Gordon-Smith K, et al: Perinatal episodes across the mood disorder spectrum. JAMA Psychiatry 70(2):168–175, 2013 23247604 Dias RS, Lafer B, Russo C, et al: Longitudinal follow-up of bipolar disorder in women with premenstrual exacerbation: findings from STEP-BD. Am J Psychiatry 168(4):386–394, 2011 21324951 Dolk H, Wang H, Loane M, et al: Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology 86(18):1716–1725, 2016 27053714 Dolovich LR, Addis A, Vaillancourt JM, et al: Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies. BMJ 317(7162):839–843, 1998 9748174 Driscoll KE, Sit DKY, Moses-Kolko EL, et al: Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study. Bipolar Disord 19(4):295–304, 2017 28665044 Endicott J, Nee J, Andreasen N, et al: Bipolar II. Combine or keep separate? J Affect Disord 8(1):17–28, 1985 3156908 Erol A, Winham SJ, McElroy SL, et al: Sex differences in the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I and II disorder. Bipolar Disord 17(6):670–676, 2015 26529373 Finer LB, Zolna MR: Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception 84(5):478–485, 2011 22018121 Freeman MP, Smith KW, Freeman SA, et al: The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 63(4):284–287, 2002 12004800 Frey BN, Simpson W, Wright L, et al: Sensitivity and specificity of the Mood Disorder Questionnaire as a screening tool for bipolar disorder during pregnancy and the postpartum period. J Clin Psychiatry 73(11):1456–1461, 2012 23146292 Gaily E, Kantola-Sorsa E, Hiilesmaa V, et al: Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 62(1):28–32, 2004 14718692 Glover V, Liddle P, Taylor A, et al: Mild hypomania (the highs) can be a feature of the first postpartum week. Association with later depression. Br J Psychiatry 164(4):517–521, 1994 8038942 Greenberg WM, Citrome L: Pharmacokinetics and pharmacodynamics of lurasidone hydrochloride, a second-generation antipsychotic: a systematic review of the published literature. Clin Pharmacokinet 56(5):493–503, 2017 27722855 Hernández-Díaz S, Smith CR, Shen A, et al; North American AED Pregnancy Registry; North American AED Pregnancy Registry: Comparative safety of antiepileptic drugs during pregnancy. Neurology 78(21):1692–1699, 2012 22551726 Heron J, Haque S, Oyebode F, et al: A longitudinal study of hypomania and depression symptoms in pregnancy and the postpartum period. Bipolar Disord 11(4):410–417, 2009 19500094 Hirschfeld RM, Holzer C, Calabrese JR, et al: Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry 160(1):178–180, 2003 12505821 Holmes LB, Baldwin EJ, Smith CR, et al: Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 70(22 Pt 2):2152–2158, 2008 18448870 Huybrechts KF, Hernández-Díaz S, Patorno E, et al: Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry 73(9):938–946, 2016 27540849 Huybrechts KF, Bateman BT, Desai RJ, et al: Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and psychotropic medications: cohort study. BMJ 358:j3326, 2017 28768628 Iqbal MM, Sobhan T, Ryals T: Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatr Serv 53(1):39–49, 2002 11773648 Joffe H, Cohen LS, Suppes T, et al: Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry 59(11):1078–1086, 2006a 16448626 Joffe H, Kim DR, Foris JM, et al: Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls. J Clin Psychiatry 67(2):297–304, 2006b 16566627 Johnson KC, LaPrairie JL, Brennan PA, et al: Prenatal antipsychotic exposure and neuromotor performance during infancy. Arch Gen Psychiatry 69(8):787–794, 2012 22474072 Johnson KC, Brennan PA, Stowe ZN, et al: Physiological regulation in infants of women with a mood disorder: examining associations with maternal symptoms and stress. J Child Psychol Psychiatry 55(2):191–198, 2014 23981139 Kacirova I, Grundmann M, Brozmanova H: Therapeutic monitoring of carbamazepine concentrations in breastfeeding mothers, maternal milk and nursed infants. Ther Drug Monit 33:503, 2011 Kinon BJ, Gilmore JA, Liu H, et al: Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology 28(Suppl 2):55–68, 2003 12650681 Kulkarni J, Worsley R, Gilbert H, et al: A prospective cohort study of antipsychotic medications in pregnancy: the first 147 pregnancies and 100 one year old babies. PLoS One 9(5):e94788, 2014 24787688 Lähteenvuo M, Tanskanen A, Taipale H, et al: Real-world effectiveness of pharmacologic treatments for the prevention of rehospitalization in a Finnish nationwide cohort of patients with bipolar disorder. JAMA Psychiatry 75(4):347–355, 2018 29490359 Laursen TM, Munk-Olsen T: Reproductive patterns in psychotic patients. Schizophr Res 121(1–3):234–240, 2010 20570491 Lewis KS, Gordon-Smith K, Forty L, et al: Sleep loss as a trigger of mood episodes in bipolar disorder: individual differences based on diagnostic subtype and gender. Br J Psychiatry 211(3):169–174, 2017 28684405 Logsdon MC, Mittelberg M, Jacob AE, et al: Maternal-infant interaction in women with unipolar and bipolar depression. Appl Nurs Res 28(4):381–383, 2015 26608442 Meador K, Reynolds MW, Crean S, et al: Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res 81(1):1–13, 2008 18565732 Merikangas KR, Herrell R, Swendsen J, et al: Specificity of bipolar spectrum conditions in the comorbidity of mood and substance use disorders: results from the Zurich cohort study. Arch Gen Psychiatry 65(1):47–52, 2008 18180428 Misri S, Abizadeh J, Eng AB, et al: An open-label study of quetiapine extended-release in a sample of postpartum women with bipolar II depressive episode. Curr Psychopharmacol 4:17–26, 2015 Munk-Olsen T, Laursen TM, Pedersen CB, et al: New parents and mental disorders: a population-based register study (see comment). JAMA 296(21):2582–2589, 2006 17148723 Newport DJ, Viguera AC, Beach AJ, et al: Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry 162(11):2162–2170, 2005 16263858 Newport DJ, Pennell PB, Calamaras MR, et al: Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics 122(1):e223–e231, 2008 18591203 Newton ER, Hale TW: Drugs in breast milk. Clin Obstet Gynecol 58(4):868–884, 2015 26457856 Pariente G, Leibson T, Shulman T, et al: Pregnancy outcomes following in utero exposure to lamotrigine: a systematic review and meta-analysis. CNS Drugs 31(6):439–450, 2017 28434134 Patorno E, Huybrechts KF, Hernandez-Diaz S: Lithium use in pregnancy and the risk of cardiac malformations. N Engl J Med 377(9):893–894, 2017 28854098 Peng M, Gao K, Ding Y, et al: Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study. Psychopharmacology (Berl) 228(4):577–584, 2013 23559219 Perich TA, Roberts G, Frankland A, et al: Clinical characteristics of women with reproductive cycle-associated bipolar disorder symptoms. Aust N Z J Psychiatry 51(2):161–167, 2017 27687774 Peselow ED, Dunner DL, Fieve RR, et al: Lithium prophylaxis of depression in unipolar, bipolar II, and cyclothymic patients. Am J Psychiatry 139(6):747–752, 1982 6805339 Pies RW: WHIPLASHED: a mnemonic for recognizing bipolar depression. Psychiatric Times, May 1, 2007 Piontek CM, Baab S, Peindl KS, et al: Serum valproate levels in 6 breastfeeding mother-infant pairs. J Clin Psychiatry 61(3):170–172, 2000 10817100 Radojčić MR, El Marroun H, Miljković B, et al: Prenatal exposure to anxiolytic and hypnotic medication in relation to behavioral problems in childhood: a population-based cohort study. Neurotoxicol Teratol 61:58–65, 2017 28259732 Rasgon N, Bauer M, Glenn T, et al: Menstrual cycle related mood changes in women with bipolar disorder. Bipolar Disord 5(1):48–52, 2003 12656938 Reimers A, Brodtkorb E, Sabers A: Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations. Seizure 28:66–70, 2015 25843765 Rigby J, Conroy S, Miele-Norton M, et al: Theory of mind as a predictor of maternal sensitivity in women with severe mental illness. Psychol Med 46(9):1853–1863, 2016 26979486 Robakis TK, Holtzman J, Stemmle PG, et al: Lamotrigine and GABAA receptor modulators interact with menstrual cycle phase and oral contraceptives to regulate mood in women with bipolar disorder. J Affect Disord 175:108–115, 2015 25601310 Salisbury AL, O’Grady KE, Battle CL, et al: The roles of maternal depression, serotonin reuptake inhibitor treatment, and concomitant benzodiazepine use on infant neurobehavioral functioning over the first postnatal month. Am J Psychiatry 173(2):147–157, 2016 26514656 Santucci AK, Singer LT, Wisniewski SR, et al: One-year developmental outcomes for infants of mothers with bipolar disorder. J Clin Psychiatry 78(8):1083–1090, 2017 28068465 Schneck CD, Miklowitz DJ, Miyahara S, et al: The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry 165(3):370–377, quiz 410, 2008 18198271 Sharma V, Pope CJ: Pregnancy and bipolar disorder: a systematic review. J Clin Psychiatry 73(11):1447–1455, 2012 22938889 Sharma V, Sommerdyk C: Lamotrigine in the prevention of bipolar II postpartum depression. Prim Care Companion CNS Disord 18(6), 2016 27907274 Sharma V, Khan M, Corpse C, et al: Missed bipolarity and psychiatric comorbidity in women with postpartum depression. Bipolar Disord 10(6):742–747, 2008 18837870 Sharma V, Sommerdyk C, Xie B, et al: Pharmacotherapy of bipolar II disorder during and after pregnancy. Curr Drug Saf 8(4):246–252, 2013 23859430 Sharma V, Khan M, Sommerdyk C: Quetiapine in the acute treatment of bipolar postpartum depression: a chart review. J Clin Psychopharmacol 35(6):733–735, 2015 26444950 Sit DK, McGowan J, Wiltrout C, et al: Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial. Am J Psychiatry 175(2):131–139, 2018 28969438 Siu AL, Bibbins-Domingo K, Grossman DC, et al; US Preventive Services Task Force (USPSTF): Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement. JAMA 315(4):380–387, 2016 26813211 Skausig OB, Schou M: [Breast feeding during lithium therapy] [in Danish]. Ugeskr Laeger 139(7):400–401, 1977 841726 Smith M, Frey BN: Treating comorbid premenstrual dysphoric disorder in women with bipolar disorder. J Psychiatry Neurosci 41(2):E22–E23, 2016 26898728 Suppes T, Marangell LB, Bernstein IH, et al: A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression. J Affect Disord 111(2–3):334–343, 2008 18358540 Swartz HA, Cyranowski JM, Cheng Y, et al: Brief psychotherapy for maternal depression: impact on mothers and children. J Am Acad Child Adolesc Psychiatry 55(6):495–503, 2016 27238068 Swartz HA, Rucci P, Thase ME, et al: Psychotherapy alone and combined with medication as treatments for bipolar II depression: a randomized controlled trial. J Clin Psychiatry 79(2):7–15, 2018 28703949 Teatero ML, Mazmanian D, Sharma V: Effects of the menstrual cycle on bipolar disorder. Bipolar Disord 16(1):22–36, 2014 24467469 Tobback E, Behaeghel K, Hanoulle I, et al: Comparison of subjective sleep and fatigue in breast- and bottle-feeding mothers. Midwifery 47:22–27, 2017 28232215 Tomson T, Battino D, Bonizzoni E, et al; EURAP study group: Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 10(7):609–617, 2011 21652013 Tondo L, Baldessarini RJ, Hennen J, et al: Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders. Am J Psychiatry 155(5):638–645, 1998 9585715 Tondo L, Pinna M, Serra G, et al: Age at menarche predicts age at onset of major affective and anxiety disorders. Eur Psychiatry 39:80–85, 2017 27992810 Tsutsumi K, Kotegawa T, Matsuki S, et al: The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans. Clin Pharmacol Ther 70(2):121–125, 2001 11503005 Tunnessen WW Jr, Hertz CG: Toxic effects of lithium in newborn infants: a commentary. J Pediatr 81(4):804–807, 1972 5074360 Uguz F: Second-generation antipsychotics during the lactation period: a comparative systematic review on infant safety. J Clin Psychopharmacol 36(3):244–252, 2016 27028982 van der Lugt NM, van de Maat JS, van Kamp IL, et al: Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies. Early Hum Dev 88(6):375–378, 2012 22000820 Vigod SN, Gomes T, Wilton AS, et al: Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population-based cohort study. BMJ 350:h2298, 2015 25972273 Viguera A: Neurobehavioral Outcomes in Children Exposed to Lithium in Utero. Toronto, ON, Society of Biological Psychiatry, 2006 Viguera AC, Newport DJ, Ritchie J, et al: Lithium in breast milk and nursing infants: clinical implications. Am J Psychiatry 164(2):342–345, 2007a 17267800 Viguera AC, Whitfield T, Baldessarini RJ, et al: Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry 164(12):1817–1824, quiz 1923, 2007b 18056236 Wadelius M, Darj E, Frenne G, et al: Induction of CYP2D6 in pregnancy. Clin Pharmacol Ther 62(4):400–407, 1997 9357391 Weissman AM, Levy BT, Hartz AJ, et al: Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 161(6):1066–1078, 2004 15169695 Wesseloo R, Kamperman AM, Munk-Olsen T, et al: Risk of postpartum relapse in bipolar disorder and postpartum psychosis: a systematic review and meta-analysis. Am J Psychiatry 173(2):117–127, 2016 26514657 Wesseloo R, Wierdsma AI, van Kamp IL, et al: Lithium dosing strategies during pregnancy and the postpartum period. Br J Psychiatry 211(1):31–36, 2017 28673946 Wisner KL, Zarin DA, Holmboe ES, et al: Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 157(12):1933–1940, 2000 11097953 Wisner KL, Sit DK, McShea MC, et al: Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry 70(5):490–498, 2013 23487258 Yonkers KA, Gilstad-Hayden K, Forray A, et al: Association of panic disorder, generalized anxiety disorder, and benzodiazepine treatment during pregnancy with risk of adverse birth outcomes. JAMA Psychiatry 74(11):1145–1152, 2017 28903165
12
Reproductive-Age Women With Bipolar II Disorder
Bidirectional Relationship of Bipolar Disorder and Menstrual Cycles
Menarche
Menstrual Cycle Dysfunction
Fertility
Menstrual Cycle Effects on Mood in Bipolar Disorder
Interaction of Mood Stabilizers With Hormonal Contraception
Perinatal Period
Antenatal Course of Bipolar II Disorder
Postpartum Course of Bipolar II Disorder
Postpartum Highs
Postpartum Psychosis
Screening Considerations
Perinatal Treatment Considerations
Nonmedication Therapy
Medications During Pregnancy and Lactation
Lithium
Antipsychotics
Antiepileptic Drugs
Antidepressants
Benzodiazepines
Conclusion
KEY POINTS
References
Related posts:
Mood Stabilizers and Antipsychotic Medications in Bipolar II Disorder
Antidepressant Medications in Bipolar II Disorder
Psychosocial Interventions in Bipolar II Disorder
Suicide and Bipolar II Disorder
Bipolar II Disorder in Childhood and Adolescence
Functional Brain Imaging and Neural Determinants in Bipolar II Disorder
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
