The comprehensive management of pregnant women with major mood disorders: a case study involving phenelzine, lithium, and quetiapine.

Pregnancy in women with severe mental illness (SMI) often bring added dimensions of complexity; considering that this group of women are choosing to have children at increasing rates, more highly complex cases will require management. A 31-year-old primigravida with a diagnosis of bipolar affective disorder was treated with an antidepressant, mood stabiliser and antipsychotic. This case discusses preconception counselling, pregnancy and labour management that resulted in the delivery of a 4,200 g baby at 39 weeks by emergency caesarian section. This case highlights the collaborative approach to care that is needed in this group of women and the need for increasing awareness and knowledge in health professionals. It follows the management from preconception through to the postpartum period.

Obstetric and neonatal outcomes of pregnant women with severe mental illness at a specialist antenatal clinic.

OBJECTIVE: To evaluate the obstetric and neonatal outcomes of pregnant women with severe mental illness (SMI) who attended a specialist multidisciplinary antenatal clinic in Perth, Western Australia. DESIGN, SETTING AND PARTICIPANTS: A retrospective case-note audit of outcomes from the Childbirth and Mental Illness Antenatal Clinic (CAMI clinic) at King Edward Memorial Hospital for pregnant women with severe mental illness (SMI), aged 18-41 years, who gave birth between December 2007 and April 2011, and their babies. MAIN OUTCOME MEASURES: Obstetric and neonatal outcomes for 138 women and newborns from singleton live births. Data were compared between three diagnostic groups (schizophrenia, bipolar and non-psychotic SMI), and with WA obstetric and perinatal statistics for 2008. RESULTS: 44 women with schizophrenia, 56 with bipolar disorder and 38 with non-psychotic SMI attended antenatal care for an average of 7.7 (SD, 3.3) visits. The proportion of women who smoked tobacco was significantly higher than that in the WA antenatal population (46% v 15%; P < 0.0001). Alcohol use, illicit substance use and psychotropic medication exposure during pregnancy were high. The women were at increased risk of developing gestational diabetes mellitus (15% v 4%; P < 0.0001) and pre-eclampsia (9% v 3%; P < 0.0001), and birth complications were more common. Babies born to CAMI clinic women were less likely to have Apgar scores ≥ 8 at 1 minute and 5 minutes. Pregnant women with schizophrenia had more psychiatric relapses during pregnancy, and had more statutory child welfare involvement. Gestational age at birth and infant birth weights were similar for the pregnant women with SMI and the WA population in 2008. CONCLUSIONS: Women attending our specialist clinic had increased rates of obstetric and neonatal complications compared with the general population, and were exposed to a cluster of risk factors. We report encouraging trends in antenatal attendance, gestational age at birth, and birth weights. Managing pregnant women with SMI will require a comprehensive approach aimed at early detection of obstetric complications and psychosocial difficulties, as well as neonatal monitoring. Optimising prepregnancy maternal health and welfare may also be of benefit.

Estimation of desvenlafaxine transfer into milk and infant exposure during its use in lactating women with postnatal depression.

This study characterises the extent of desvenlafaxine transfer into milk and provides data on infant exposure to desvenlafaxine via breast milk in ten women with postnatal depression and their breastfed infants. Desvenlafaxine concentration in milk and plasma was measured chromatographically in milk and in maternal and infant plasma collected at steady state. Theoretic and relative infant doses via milk were estimated and the per cent drug in infant versus mother's plasma was calculated. Theoretic infant dose via milk was 85 (53-117) µg kg(-1) day(-1) (mean and 95% confidence interval) and relative infant dose was 6.8% (5.5-8.1%). The ratio of drug in infant/maternal plasma also gave an infant exposure estimate of 4.8% (3.5-6.2%) for all ten infants and 5.3% (4.2-5.7%) in the eight infants who were exclusively breastfed. No adverse effects were seen in the infants. The relative infant dose was similar to that for previous studies using venlafaxine and was supported by a separate exposure measure using the ratio of drug in the infant's plasma relative to that in the mother's plasma. The theoretic infant dose of desvenlafaxine was 41-45% of that for venlafaxine and its metabolite desvenlafaxine in previous studies, reflecting the lower recommended maternal dose for desvenlafaxine. Although our data for desvenlafaxine use in lactation are encouraging and there are supporting data from venlafaxine studies, more patients and their infants need to be studied before the safety of desvenlafaxine as a single therapeutic agent can be fully assessed.

Managing pregnant women with serious mental illness: using the Edinburgh Postnatal Depression Scale as a marker of anxiety and depressive symptoms.

OBJECTIVE: To examine the course of depressive and anxiety symptoms using serial measurements of the Edinburgh Postnatal Depression Scale (EPDS) in pregnant women with serious mental illness (SMI) attending a specialist multi-disciplinary antenatal clinic in Perth, Western Australia. METHOD: A retrospective review of case notes was undertaken for 48 Western Australian pregnant women with schizophrenia and related psychoses and bipolar affective disorders who attended the Childbirth and Mental Illness (CAMI) antenatal clinic between December 2007 and November 2009. Of these patients, 27 completed the EPDS at booking (first appointment) and at 32 weeks gestation. Additional variables collected were demographic data, gestation at booking, and attendance rates for these 27 women, and for comparison another 21 women who did not complete the EPDS for one or both screening periods. RESULTS: Mean total EPDS score decreased from 12.2 (SD 7.6) at booking to 8.5 (SD 6.4) at 32 weeks gestation (p = 0.007). Overall mean attendance rates and number of appointments were similar to the non-SMI population and in keeping with standard guidelines. CONCLUSIONS: We speculate from these preliminary findings that being managed by a consistent small multi-disciplinary team and knowing that they will be supported throughout their pregnancy could lead to improvement of anxiety and depressive symptoms in pregnant women with SMI, and has the potential to increase their attendance for antenatal care.

Motherhood and mental illness: Part 1 - toward a general understanding.

BACKGROUND: Mental illness is common among women of childbearing age, and fertility rates of women with mental illness are close to those of the general population. General practitioners will see most of the women who may be seeking advice and management of their mental illnesses before, during or after a pregnancy. OBJECTIVE: This article reviews the current approaches to the management of mental illness in and around pregnancy, and provides practical advice regarding pregnancy related issues in women with mental health disorders. DISCUSSION: The GP is ideally placed to give information and encourage appropriate treatment choices in women with mental illness. Given the multifaceted complexities, the optimal approach is holistic and collaborative. Specialist opinion must be sought early and a multidisciplinary approach with access to specialist care offered if possible. Continuity of care, especially in the context of a trusting therapeutic relationship, is considered optimal.

Motherhood and mental illness--part 2--management and medications.

BACKGROUND: General practitioners see many women who may be on medication for the management of their mental illness before, during, or after a pregnancy. OBJECTIVE: This article reviews the current evidence and gives practical advice on management and use of psychotropic medication in women with mental health disorders in pregnancy. DISCUSSION: The general practitioner is often the first point of contact, and is vital in giving timely and accurate information and encouraging appropriate treatment choices in women with mental illness in our community. The risk-benefit analysis of treatment needs to be considered in light of the evidence at hand. Specialist opinion in complex cases must be sought early.

Early life origins of obesity.

There is increasing evidence that obesity has its origins in early life. Predisposition is based on interactions between the genome and environmental influences acting through epigenetic modifications. Individuals most at risk are those whose ancestral line has made a rapid transition from a traditional to a Westernized style of life. The process involves not only metabolism, but also behavior. As a result, those people who are most at risk of obesity may be those least likely to respond to educational programs based on lifestyle modification. Understanding the mechanisms and pathways that underpin the early origins of obesity is vital if we are to make progress in addressing this major problem of modern life.

Quetiapine and breast feeding.

OBJECTIVE: To quantify the relative infant dose of quetiapine during breast feeding, describe the milk:plasma (M:P) ratio, and determine the well-being of the exposed infant. CASE SUMMARY: A 26-year-old mother and her 3-month-old son were studied over a 24 hour quetiapine dose interval at steady-state. Quetiapine concentrations were quantified by high-performance liquid chromatography. Infant exposure was calculated as the concentration in milk multiplied by an estimated milk production of 0.15 L/kg/day and normalized to the weight-adjusted maternal dose. The average concentration in milk was 41 microg/L, the M:P ratio (measured using average concentrations in the elimination phase) was 0.29, and the relative infant dose was 0.09% of the maternal weight-adjusted dose (7273 microg/kg/day). The infant plasma concentration of 1.4 microg/L was some 6% of the corresponding maternal plasma concentration. No adverse effects were noted in the infant. DISCUSSION: Our findings of an infant exposure to quetiapine of less than 0.1% of the maternal dose and a lack of adverse effects confirm and extend the findings of 2 previous studies. CONCLUSIONS: Although limited, the data shown here support the prescription of quetiapine to a breast-feeding mother following a careful individual risk/benefit analysis. We suggest regular monitoring of infant progress and occasional measurement of quetiapine in the infant's plasma.

Transfer of the antidepressant mirtazapine into breast milk.

AIMS: To investigate the transfer of mirtazapine and desmethylmirtazapine into milk and to calculate dose to the infant via milk. METHODS: Plasma and milk samples were obtained from eight breast-feeding women who were taking a median dose of 38 mg mirtazapine per day. Milk/plasma ratio (M/P) and infant doses were estimated by standard methods. The infants were examined clinically and in four infants blood was taken for analysis. RESULTS: Mean (95% confidence interval) relative infant doses for mirtazapine and desmethylmirtazapine (n = 8) were 1.5% (0.8, 2.2) and 0.4% (0.2, 0.6) respectively. The mean M/P (area under curve n = 4, single or paired samples n = 3) was 1.1 (0.7,1.5) for mirtazapine and 0.6 (0.5, 0.7) for desmethylmirtazapine. No adverse effects were seen. Mirtazapine was detected (1.5 microg l(-1)) in only one of four infants tested. CONCLUSION: We suggest that mirtazapine use by lactating women is safe for the breast-fed infant. Nevertheless, each decision to breast feed should always be made on the basis of an individual risk/benefit analysis.

Transfer of escitalopram and its metabolite demethylescitalopram into breastmilk.

AIMS: To investigate the transfer of escitalopram and its demethyl metabolite into milk, the absolute and relative infant doses via milk and to assess any unwanted effects in the breastfed infant. METHODS: Multiple samples of blood and milk were obtained over a dose interval at steady state from eight women who were taking escitalopram for postnatal depression. Drug concentrations in plasma and milk were measured by high-performance liquid chromatography and milk/plasma ratio (M/P(AUC)), absolute infant dose and relative infant dose were estimated by standard methods. Their breastfed infants were also examined clinically and in five infants a blood sample was taken for drug analysis. RESULTS: The median dose taken by the women was 10 mg day(-1). The mean (95% confidence interval) M/P(AUC) was 2.2 (2.0, 2.4) for escitalopram and 2.2 (1.9, 2.5) for demethylescitalopram. Absolute infant doses were 7.6 microg kg(-1) day(-1) (5.2, 10.0) for escitalopram and 3.0 microg kg(-1) day(-1) (2.4, 3.6) for demethylescitalopram. The total relative infant dose for escitalopram plus its demethyl metabolite was 5.3% (4.2, 6.4) as escitalopram equivalents. All of the infants had met normal developmental milestones and no adverse effects were seen. Compared with average maternal plasma concentrations (24 microg l(-1)), the concentrations of the parent drug and its metabolite in plasma from five infants were most commonly below the limit of detection (

Transfer of reboxetine into breastmilk, its plasma concentrations and lack of adverse effects in the breastfed infant.

OBJECTIVE: To investigate the transfer of reboxetine into milk, the absolute and relative infant doses via milk and to assess plasma concentrations and adverse unwanted effects in the breastfed infant. METHODS: Multiple samples of blood and milk were obtained over a dose interval at steady-state from four women who were taking reboxetine for postnatal depression. Drug concentrations in plasma and milk were measured by high performance liquid chromatography and milk/plasma ratio (M/P), absolute infant dose and relative infant dose were estimated by standard methods. Their four, breastfed, infants were also examined clinically, and a blood sample was taken for drug analysis. RESULTS: The median (range) dose taken by the women was 6 (4-10) mg/day. There was no significant difference in reboxetine concentration between paired fore-and hind-milk samples. The mean (95% CI) M/P was 0.06 (0.03, 0.09). Absolute infant dose was 1.7 (0.7, 2.4) microg/kg/day for reboxetine while the relative infant dose was 2.0% (1.3, 2.7%). Three of the infants met normal developmental milestones and no adverse effects were seen in any infant. The fourth infant had developmental problems that were not associated with the maternal reboxetine therapy. The concentrations of reboxetine in plasma from the four infants were <4 microg/l, 2.6 microg/l, 2.3 microg/l and 5 microg/l, respectively. CONCLUSION: The study suggests that reboxetine use by lactating women is safe for the breastfed infant. Nevertheless, our study had only four mother/baby pairs, and each decision to breastfeed should always be made on the basis of an individual risk/benefit analysis.

A methodology for timing reviews of inpatient hospital stay.

OBJECTIVE: This paper aims to describe a methodology to inform decisions about the optimal time to schedule reviews of a patient's hospital stay and to provide an example of its implementation. METHOD: Length of hospital stay was assessed in 1227 consecutive inpatient admissions. Data were transformed to reflect the probability of discharge from hospital in the following 7 days. RESULTS: The resulting data reflected the points at which the conditional probability of being discharged were declining, revealing the potentially efficient times to conduct reviews of inpatient admissions. CONCLUSIONS: The methodology outlined appears useful in assisting psychiatrists responsible for inpatient care to decide upon optimal times to review a patient's stay in hospital.

A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate.

Antidepressants are often used antenatally, and placental transfer may lead to adverse effects (toxicity) in the neonate. Pregnant women taking fluoxetine (n=4), sertraline (n=4), paroxetine (n=2) or venlafaxine (n=1) in the last trimester were studied. Maternal and cord sera were collected at delivery and infant serum on day 5 after birth for measurement of antidepressant concentrations. Neonatal Abstinence Scores (NAS) were measured in the infants on days 13 after birth. In maternal serum, median drug concentrations were: fluoxetine (96 microg/l), norfluoxetine (110 microg/l), sertraline (11 microg/l), desmethylsertraline (38 microg/l), paroxetine (mean 12 microg/l), venlafaxine (220 microg/l), and O-desmethylvenlafaxine (392 microg/l). Corresponding median values in cord serum were: fluoxetine (65 microg/l), norfluoxetine (81 microg/l), sertraline (10 microg/l), desmethylsertraline (27 microg/l), paroxetine (mean 6 microg/l), venlafaxine (232 microg/l), and O-desmethylvenlafaxine (406 microg/l). Corresponding median cord:maternal concentration ratios were 0.67 for fluoxetine and 0.72 for norfluoxetine, 0.67 for sertraline and 0.63 for demethylsertraline, 0.52 (mean) for paroxetine, and 1.1 and 1.0 for venlafaxine and O-desmethylvenlafaxine respectively. The neonates of two patients taking fluoxetine had high NAS. Only fluoxetine and norfluoxetine were detected in infant serum. Our data show substantial placental transfer of antidepressants, but only fluoxetine persisted in the infants serum. Neonatal toxicity may be associated with serotonin uptake blockade, and also be influenced by neonatal clearance.

Transfer of olanzapine into breast milk, calculation of infant drug dose, and effect on breast-fed infants.

OBJECTIVE: This study characterized infant drug doses and breast-milk-to-plasma area-under-the-curve ratios for olanzapine and determined plasma concentrations and effects of this drug on breast-feeding infants. METHOD: Seven mother-infant nursing pairs were studied. Olanzapine was measured in plasma and milk with high-performance liquid chromatography over a dose interval (for six patients) or at a single time after dose ingestion (for one patient) at steady state. Infant drug exposure was estimated as the product of an assumed milk production rate and average drug concentration in milk, normalized to body weight, and expressed as a percentage of maternal drug dose, normalized to body weight. RESULTS: The median infant dose of olanzapine ingested through milk was 1.02% of the maternal dose; the median milk-to-plasma area-under-the-curve ratio was 0.38 for the six patients with data collected over the dose interval. Corresponding values in the patient with single-point data were 1.13% and 0.75. Olanzapine was not detected in the plasma of the six infants with an evaluable plasma sample. All of the infants were healthy and experienced no side effects. CONCLUSIONS: Breast-fed infants were exposed to a calculated olanzapine dose of approximately 1%-well below the 10% notional level of concern. In infant plasma, olanzapine was below the detection limit; there were no adverse effects on the infants. These data support the use of olanzapine during breast-feeding. However, the authors recommend that breast-fed infants be monitored closely and the decision to breast-feed be made after individual risk-benefit analysis.

Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants.

AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS: Six women (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high-performance liquid chromatography over a 12 h dose interval at steady-state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362, 1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 microg l(-1)), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day. CONCLUSIONS: The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5-7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.