1. Jo Naidoo Dr Ramachandra 21/10/10

2.  Introduction  General principles of Mx of women with BAP  Medication in BAD  Women in pregnancy  Perinatal period  Breastfeeding

4.  Risk factor for relapse – as high as 50% (Jones 2005)  Viguera et al (2007) – small prospective Observational cohort of preg. BAD. Risk of recurrence in pregnancy was 71%.  27% of women with BAD, are admitted to psychiatric care in the first post partum year (Munk-Olsen 2009)  Risk of relapse after delivery – 8 fold in the first month post partum

5.  Majority of the episodes – depressive  Nearly half within the first trimester  Recurrence more likely if a woman :- -has discontinued medication -BAD II -had previously been treated with a mood stabiliser  These results emphasis the need to balance the risks of treatment to the fetus with those of a recurrence of an affective episode.

6. General Principles Of Women with BAD pregnancy plannedunplanned Perinatal Period Breast feeding

7.  The absolute and relative risks should be discussed with women.  contact by specialist mental health services, working closely with maternity services, should be considered for pregnant women with bipolar disorder, because of the increased risk of relapse during pregnancy and the postnatal period.  written plan for managing a woman’s bipolar disorder during the pregnancy, delivery and postnatal period should be developed as soon as possible.

8.  If stable on an antipsychotic - she should be maintained on the antipsychotic, and monitored for weight gain and diabetes.

9. What are some of the concerns?

10.  Risks of not treating incl.- -harm to the mother thru poor self-care, lack of obstetric care or self harm -harm to the fetus or neonate ( ranging from neglect to infanticide)  Mental health of the mother influences fetal well-being, obstetric outcome and child development

11.  Cardiac malformation, Ebsteins anomaly (AR 1:1000, RR 10-20 times more than control groups) (Cohen et al 2007)  Overall, recent evidence shows that the teratogenic risks are lower than originally believed  Max risk period is 2-6 weeks after conception  Preferred slow discontinuation before conception.

13.  Abrupt discontinuation – risk of relapse  Relapse rate postpartum – 70% in those who discontinued lithium before conception.  If discontinuation is unsuccessful during preg. – restart and continue  Li in preg – high resolution U/S, and echocardiography at 6 and 18 weeks of gestation  3 rd trimester – due to the changing pharmacokinetics, higher doses Li required

14.  Lithium equilibrates across the placenta  Effects on the neonate :- i. Neonatal Goitre ii. Hypotonia iii. Lethargy iv. Cardiac arrhythmia

15.  Well known teratogen, most teratogenic  7-10% risk of Neural Tube defects – esp Spina Bifida  Also assoc cardiac defects in the first trimester; craniofacial abnornalities  Adab and colleagues (2001) described a higher risk of additional educational needs amongst school-aged children exposed to valproate in utero compared to those exposed to carbemazepine or those not exposed to any ACD  Teratogenicity probably dose related

17.  1 % risk of neural tube defects, esp spina bifida in the first trimester  Also risk of craniofacial abnormalities and microcephaly in newborns  If using Carbamazepine in the third trimester – maternal and neonatal, Vit K may be necessary  Ideally all patients should be on folic acid a month before conception

18.  North American Antiepileptic Drug Registry suggested an increase risk of oral clefts associated with first trimester lamotrigine exposure (2006 /2007)  Increased risk of major malformations compared to unexposed

19.  Commonly used – mono or in combination  Relative safety – typical and atypical  Sparse data

20.  If on antidepressants – risk of relapse high  Older TCA safe  SSRI – no increased risk of major congenital defects  Paroxetine – cardiac defects (1.5-2 fold inc VSD & ASD)  Some studies show use of antidepressants in the last trimester – transient jitteriness, tremulousness, tachypnoea, hypotonia and pulmonary hypertension (?withdrawal/intoxication)

21.  Role of maternal depression on perinatal wellbeing not evaluated  If mod – severe depression develops use antidepressants if psychological management failed / not available  Risk of neonate having discontinuation symptoms – agitation, irritability, convulsions (switch to bottle feeds) – SSRI & Venlafaxine

22.  First trimester exposure associated with risk of oral clefts in newborns  Third trimester – neonatal difficulties including floppy baby syndrome  Best avoided in pregnancy

26.  stop taking AC, mood stab. and alternative prophylactic drugs (such as an antipsychotic) should be considered.  Antipsychotics - advised that the raised prolactin levels associated with some antipsychotics reduce the chances of conception. If prolactin levels are raised, an alternative drug should be considered.  If a woman who needs antimanic medication plans to become pregnant, a low-dose typical or atypical antipsychotic should be considered, because they are of least known risk

27.  If a woman taking lithium plans to become pregnant, the following options should be considered: if the patient is well and not at high risk of relapse – gradually stopping lithium if the patient is not well or is at high risk of relapse: − switching gradually to an antipsychotic, or − stopping lithium and restarting it in the second trimester if the woman is not planning to breastfeed and her symptoms have responded better to lithium than to other drugs in the past, or − continuing with lithium, after full discussion of the risks, while trying to conceive and throughout the pregnancy, if manic episodes have complicated the woman’s previous presentation

28.  If Mx lithium during pregnancy - serum lithium levels should be monitored every 4 weeks, then weekly from the 36th week, and less than 24 hours after childbirth. The dose should be adjusted to keep serum levels within the therapeutic range. The woman should maintain adequate fluid intake.  depression after stopping prophylactic medication, psychological therapy (CBT) should be offered in preference to an antidepressant.  If an antidepressant is used, it should usually be an SSRI (but not paroxetine because of the risk of cardiovascular malformations in the fetus) and the woman should be monitored closely.

30.  Confirm pregnancy  stop taking valproate, carbamazepine and lamotrigine  first trimester- stable, lithium should be stopped gradually over 4 weeks, and the woman informed that this may not remove the risk of cardiac defects in the fetus  if the woman remains on lithium during pregnancy serum lithium levels should be checked every 4 weeks, then weekly from the 36th week, and less than 24 hours after childbirth; the dose should be adjusted to keep serum levels within the therapeutic range, and the woman should maintain adequate fluid intake

31.  an antipsychotic should be offered as prophylactic medication  offer appropriate screening and counselling about the continuation of the pregnancy, the need for additional monitoring and the risks to the fetus if the woman stays on medication.

32.  not taking medication - an atypical or a typical antipsychotic should be considered.  taking prophylactic medication, prescribers should: check the dose of the prophylactic agent and adherence increase the dose if the woman is taking an antipsychotic, or consider changing to an atypical antipsychotic if she is not if there is no response to changes in dose or drug and the patient has severe mania, consider the use of ECT, lithium and, rarely, valproate.  If there is no alternative to valproate the woman should be informed of the increased risk to the fetus and the child's intellectual development. The lowest possible effective dose should be used and augmenting it with additional antimanic medication (but not carbamazepine) considered. The maximum dosage should be 1 gram per day, in divided doses and in the slow-release form, with 5 mg/day folic acid

33.  mild depressive symptoms :- self-help approaches such as guided self-help and computerised CBT brief psychological interventions antidepressant medication.  For moderate to severe depressive symptoms:- psychological treatment (CBT) for moderate depression combined medication and structured psychological interventions for severe depression.

34.  For moderate to severe depressive symptoms :- quetiapine alone, or SSRIs (but not paroxetine). Monitor closely for signs of switching and stop the SSRI if patients start to develop manic or hypomanic symptoms.  prescribed an antidepressants - potential, but predominantly short-lived, adverse effects of antidepressants on the neonate.

35.  Women taking lithium should deliver in hospital, and be monitored during labour by the obstetric medical team, in addition to usual midwife care. Monitoring should include fluid balance, because of the risk of dehydration and lithium toxicity.  After delivery, Patient is not on medication is at high risk of developing an acute episode, prescribers should consider establishing or reinstating medication as soon as medically stable (once the fluid balance is established).

36.  If maintained on lithium and is at high risk of a manic relapse in the immediate postnatal period, augmenting treatment with an antipsychotic should be considered.  If patient develops severe manic or psychotic symptoms and behavioural disturbance in the intrapartum period rapid tranquillisation with an antipsychotic should be considered in preference to a benzodiazepine because of the risk of floppy baby syndrome. Treatment should be in collaboration with an anaesthetist and obstetrician

38.  have advice on the risks and benefits of breastfeeding  be advised not to breastfeed if taking lithium, benzodiazepines or lamotrigine, and offered a prophylactic agent that can be used when breastfeeding – an antipsychotic should be the first choice  be prescribed an SSRI if an antidepressant is used (but not fluoxetine or citalopram).

40.  Symptoms including irritability, constant crying, shivering, tremor, restlessness, increased tone, feeding and sleeping difficulties and rarely seizures have been reported in neonates of mothers taking SSRIs.  Many of these symptoms are mild and self- limiting. In many cases these symptoms appear causally related to antidepressant exposure although there is debate about to what extent they represent serotonergic toxicity or a withdrawal reaction.