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.

ncreased morbidity and mortality trends in patients with severe mental illness (SMI), coupled with suboptimal access to health provision, 1 highlights the need for comprehensive yet individualised care. Pregnant women with SMI and their babies appear to be a particularly vulnerable group, due to increased risks for obstetric and neonatal complications. 2-4 In a Western Australian population study, 3 women with schizophrenia and major affective disorders were more likely to experience placental abnormalities and fetal distress. Women with schizophrenia were also more likely to have newborns in the lowest weight/growth decile and have a neonatal narcotic antagonist administered. Pregnant women with bipolar disorder have been found to be at increased risk of preterm and low-birthweight infants. 5,6 Mothers with SMI present with poor maternal condition, 7 which is reflected by late presentation to obstetric services and fewer appointments, 8,9 poor nutrition, more likelihood of smoking, illicit substance use, and less support. 10,11 Additional concerns include antipsychotic exposure during pregnancy, which has been associated with fetal malformation; 12 infant growth disruption; increased or decreased birthweight; 12,13 and neonatal adjustment difficulties. 14 Pregnant women with SMI should be designated as a health disparity population, 15 and every effort should be made to improve their access to obstetric care. Within this context, the Childbirth and Mental Illness Antenatal Clinic (CAMI clinic) at King Edward Memorial Hospital (KEMH) was established in 2007. The weekly antenatal clinic comprises a multidisciplinary team of designated obstetrics, midwifery, psychiatry, mental health nursing and social work staff who provide care for pregnant women, in liaison with their treating psychiatrists. This approach has the potential to increase attendance at antenatal care for pregnant women with SMI. 16 We report on the obstetric and neonatal outcomes of pregnant women with SMI who attended the CAMI clinic between 2007 and 2011. Method A retrospective file audit was made of all pregnant women with SMI who attended the CAMI clinic and gave birth between December 2007 and April 2011. Psychiatric diagnoses were grouped into schizophrenia and related disorders, bipolar disorders, and non-psychotic disorders with significant functional impairment. Diagnoses were made by community mental health services, private psychiatrists or a consultant psychiatrist at KEMH using ICD-10 criteria. 17 Data audited from case notes were based on the Western Australian Midwives' Notification System. The purpose-designed database also included psychiatric diagnoses, detailed demographic information, attendance at the CAMI clinic (including the number of antenatal appointments), psychotropic medication use, and psychosocial outcomes, including psychiatric admissions and statutory welfare agency involvement. The KEMH Ethics Committee approved the study. Statistical analysis CAMI clinic data (summary data from all women combined) were compared wit...

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.

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 x1 , range 225±300 mg day x1 ) 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 x1 day x1) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. Results Mean M/P AUC 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) mg l x1 and 796 (362, 1230) mg l x1 . 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 mg l x1 ), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 mg l x1 . 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:bene®t analysis.

Aims To characterize milk/plasma (M/P) ratio and infant dose, for citalopram and demethylcitalopram, in breast-feeding women taking citalopram for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. Methods Seven women (mean age 30.6 years) taking citalopram (median dose 0.36 mg kg x1 day x1 ) and their infants (mean age 4.1 months) were studied. Citalopram and demethylcitalopram in plasma and milk were measured by highperformance liquid chromatography over a 24 h dose interval. Infant exposure was estimated (two separate methods) as the product of milk production rate and drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. ) was detected in three of the seven infants. Demethylcitalopram (2.2 and 2.2 mg l x1 ) was detected in plasma from two of the same infants. No adverse effects were seen in the infants, all were within appropriate percentile limits for weight and all had normal Denver developmental quotients. Conclusions The mean combined dose of citalopram and demethylcitalopram (4.4±5.1% as citalopram equivalents) transmitted to infants via breast milk is below the 10% notional level of concern. Plasma concentrations of these drugs in the infants were very low or absent and there were no adverse effects. These data support the safety of the use of citalopram in breast feeding women. Nevertheless, each decision to breast feed should always be made as an individual risk:bene®t analysis.