1. Psychotropic Medications in Pregnancy and Breastfeeding.
Presented by Dr Ian Harrison
Perinatal Psychiatrist
South Western Sydney Area Health Service

2. INTRODUCTION

3. The Perinatal Period. A uniquely stressful time.
Pre-existing psychological conditions can be exacerbated by the stresses of the period.
Many psychological illnesses have an increased risk of onset at this time.
Whether some psychological illnesses occur uniquely in this period is controversial.

4. Some Trends in the treatment of Maternal Psychological Illness (1).
maternal age means greater chance of prior treatment of a psychological illness.
treatment of depression generally in women of childbearing years.
detection of depression via screening programs (antenatally and postnatally).
recognition of “PND” beginning antenatally (ie antenatal depression).

5. More Trends in the treatment of Maternal Psychological Illness (2).
concern about the effects of maternal depression/anxiety on an infant’s psychological development.
use of a wider range of new medications, eg,
atypical antipsychotics
anticonvulsants
new antidepressants
use of medications in combination

6. Trends in treating Psychotic Illness.
successful therapies = social functioning =
rate of psychotic patients becoming pregnant.
New antipsychotics = no prolactin effect = reduced incidence of medication-induced birth control. proportion of patients with psychotic illness becoming pregnant.

7. Epidemiology of Psychiatric Illness in Pregnancy.
Pregnancy does not protect against mental illness as was previously thought.
5-10% of women have clinically significant psychological symptoms.
70% of women with a history of recurrent major depression will relapse during pregnancy.
50% of women with untreated Bipolar Disorder will develop an episode in Pregnancy.
Overall a large percentage of women, and their physicians will face this issue of relapse of illness during their pregnancy.

8. Epidemiology of Postnatal Psychiatric Illness.
2-3 x increased risk of onset of psychiatric illness in the first weeks postpartum.
Time of greatest risk of psych. hospitalisation for a woman cf any other time in her life.
The risk is as high as 20x
% of women will develop PND.
Risk higher if any previous history of illness.
Untreated Bipolar Disorder has a relapse rate of % (10-20% will experience a post partum psychosis).

9. Clinical Situations Involving Pregnancy and Psychotropics.
previous episode/s of Major Depression, Bipolar Disorder or psychotic illness and considering pregnancy
currently taking a psychotropic medication and considering pregnancy
currently taking a psychotropic medication and has become pregnant
first onset of depression or anxiety disorder during current pregnancy

10. Clinical Situations Involving Breastfeeding and Psychotropics.
previous history of postnatal depression or psychosis requiring prevention (prophylaxis) while breastfeeding
previous history of depressive illness where postnatal prophylaxis may be advisable
new onset of postnatal psychiatric illness requiring medication whilst breastfeeding

11. Potential Treatments for Maternal Psychiatric Illness.
No treatment
Psychotherapy
Supportive
Cognitive behavioural
Interpersonal
Psychodynamic
Medications
ECT

12. Supportive Psychotherapy.
has many helpful components.
information (education), and advice, which is especially relevant to new mothers
the ventilation of difficult thoughts and feelings,
support, praise, encouragement and reassurance
positive focussing,
all presented in the context of the therapist’s reliability, consistency and continuity of care.
Psychological therapies will most likely be used in the first instance. Supportive psychotherapy is a very powerful yet often underrated therapy.
The benefits of an empathic relationship with a therapist who exhibits genuine respect and interest while maintaining objectivity (and without overinvolvement) should not be underestimated. There are other helpful components including the ventilation of difficult thoughts and feelings, support and encouragement, praise and positive focussing, reassurance, advice and education, all presented in the context of the therapist’s reliability, consistency and continuity of care.
Cognitive-Behavioural Therapy (CBT) and Interpersonal Therapy (ITP) are more specialised forms of psychotherapy, which are especially useful for maternal depression and anxiety. They are however less widely available.
Some women, however, will require a combination of medication and psychotherapy to improve their mental state.

13. Psychotherapeutic Management (1).
Some women will only consider psychotherapy.
Some mild to moderate depression can be contained by this approach.
It is important to reassure the woman who is “phobic” about medication that you respect their position.
Ongoing intermittent psychotherapy allows for monitoring and re-evaluation.

14. Psychotherapeutic Management (2).
Supportive psychotherapy builds good will with the woman who is for the time being opposed to medication.
Helps to create a therapeutic alliance that will be needed if the depression worsens.
Avoid the dichotomy, “Well if you don’t want my medication I can’t help you”.
or “…. I don’t want to see you.”
Always keep the “door open”.

15. General Issues to Consider.
Mothers and babies elicit strong emotions.
We each bring our own attitudes and values into the situation - what are they? Be aware of them.
How many patients? One or two or more?
The mother,
the mother and foetus/baby
the parental couple,
the family

16. The Clinical Problem: Defining Exposure (1).
We focus on the issue of exposure.
There are 2 exposures:
1. What will the foetus/baby be exposed to in terms of medication? (in utero & breastfeeding)
2. What will the foetus/baby be exposed to in terms of maternal psychiatric illness? (in utero & breastfeeding)

17. The Clinical Problem: Defining Exposure (2).
The foetus/baby will be exposed to something. “There is no such thing as non-exposure.” Z. Stowe.
The foetus/baby will be exposed to medication or psychiatric illness or both.
Our role is to help the mother and her partner decide which path of exposure is best for them.

18. Two Basic Assumptions.
1. All medications cross the placenta and also enter breast milk.
2. We do not yet know all the potential risks from medication exposure.
We talk about the “Risk/Benefit ratio”.
Risks of treatment vs the benefits of treatment.
or risks of treatment vs risks of non-treatment.
Our knowledge about medication risks is increasing. We have more information about antidepressant medications in pregnancy and breastfeeding than any other class of drugs given to women in the whole pharmacopoeia.
Z Stowe has done most of the studies to do with blood levels in mothers and nursing infants.
We know that infants have very small, sometimes undetectable amounts of medication in their blood. What we don’t know is what this means in terms of its effects. Is their a long term effect or not? We still don’t know but the early studies are encouraging.
We have to presume that we don’t yet know all the potential risks. Hence we have two lists which are incomplete. A list for risks associated with treatment and a list for risks associated with non-treatment.
We don’t know how long each list will ultimately be.

19. The Risk/Benefit Ratio.
The risks associated with medication are fairly fixed even if some of them are as yet unknown.
The risks associated with maternal psychiatric illness varies enormously for each individual.
Hence we ask, “What is the risk-benefit ratio for this woman, given her current symptom pattern or what has happened in her previous episodes of illness?”
The risks of medication presumably vary somewhat according to time of initiation, dose and duration of exposure. etc,

20. Maternal Psychiatric Illness. What are the risks Prenatally? (1)
Effects on Mother and foetus and/or baby.
poor compliance with obstetric/medical care
poor maternal health/nutrition
abuse of alcohol and cigarettes
abuse of other substances including over the counter remedies
suicidality, self-harm, recklessness

21. Maternal Psychiatric Illness.What are the risks - Postnatally?
deficits in mother-infant attachment
neurobehavioural sequelae
increased failure to breastfeed
separations at home, possible psychiatric hospitalisation
abuse, neglect, self harm, recklessness
rarely, suicidality/infanticide

22. Maternal Psychiatric Illness. Further risks.
Effects on Family and Environment
reduced care of other children
emotional neglect of other children
marital disturbance
occupational deterioration
reduced social network
etc.

23. What about the direct effects of mat. psych. illness on the foetus?
These are potential effects on the foetus via changes in maternal blood chemistry, hormones, catecholamines, immune function etc,
What happens to the foetus in untreated maternal psychiatric illness?
What are the long term consequences of untreated maternal psychiatric illness (eg depression) for offspring into childhood, adolescence, etc.
The previous slides were all about indirect effects. But are there direct negative effects as a result of maternal psychiatric illness? Can the baby’s developing brain (in utero) and their later cognitive and emotional and social behaviour be affected by any physiological changes in the mother (during pregnancy) as a result of stress, anxiety, depression or psychosis (eg paranoia) etc
This is the big question. This is an important area of research.
We know that some woman need to be taking medication for the safety of themselves and their babies.
But what about the woman who can cope with depression? Does she have any reason to take medication?
She may be able to sit out her depression or sit through her panic attacks without treatment, for the benefit of the baby. But is the baby benefiting? This is the question we need to be able to answer.
What is the long term outcome for untreated depression or other psychiatric illness during pregnancy?

24. Potential direct effects of Maternal Depression/Stress.
Effects on foetus
changes in the HPA axis
lower birth weight
prematurity
behavioural teratogenicity
Information is lacking.
What are the long term neurobehavioural effects of medication in adolescence, young adulthood middle age and the elderly?
What are the long term consequences of untreated maternal psychiatric illness eg depression for offspring into adolescence, etc.
Changes to neuroendocrine and neurotransmitter activity in the infant.
The true extent of this list is as yet unknown.

25. What has been shown?
Deleterious effect on obstetric outcome and later infant development.
Severe Stress and Depression may:
impede foetal growth
smaller head circumference
increased rate of preterm delivery and other complications
long term behavioural problems in offspring

26. The Placenta as a Filter.
In an Ideal World:
the placenta would screen out any direct ill-effects from maternal psychiatric illness.
the placenta would block the medication from reaching the baby (or the medication would have no effect on the baby)

27. Does the placenta filter out direct effects of maternal psych. illness?
Research to date suggests No.
Cortisol (stress hormone) levels in the umbilical chord are typically higher than in the maternal serum.
There are also possible abnormalities in immune function across the placenta.
Research is difficult because of the obvious confounding effects of the postnatal period.
Animal data suggests that stress in pregnancy is detrimental to offspring. These negative effects in animals can be blocked by diazepam and antidepressants.
Medication may therefore be a protective factor.

28. Does the placenta filter out effects of medication?
Yes, to some extent.
the concentrations of antidepressant medications in the umbilical chord leading to the baby are less than in the maternal circulation
there is incomplete placental passage of antidepressants
“As a class of drug, antidepressants cross the placenta less that just about any other drug”.
Z Stowe.

29. The Placenta as a Filter. What Gets to the Baby?
Chord Samples: ratios 0.29 to 0.89
sertraline<paroxetine<fluoxetine<citalopram
Hendrick 2003
Blood samples:
maternal vs infant (breastfeeding) 1/50 to 1/200
Milk Samples:
concentrations in mother’s blood/in milk/ in babies blood

30. Pathways of Exposure in Pregnancy.

31. Pathways of Exposure in Pregnancy

32. Potential effects of exposure to illness and medications for the foetus/baby.
Miscarriage
Structural Malformations/Teratogenicity
Intra-uterine death
Growth Impairment (low birth wgt).
Prematurity
Neonatal toxicity and withdrawal
Behavioural teratogenicity
cognitive, emotional, social, behavioural.
The areas or domains headings under which we would need to look to determine how babies could be effected by medications or maternal mental illness.
We have to tick these domains off as we go through them to check if they are effected.
So miscarriage: does the baby get started. Growth retardation..etc.
Behavioural teratogenicity. Not something that can be “seen”. These are questions of degree. Not so much present or absent but “less” of something or “more” of something. As such they are difficult to investigate to explore to measure and to be conclusive about. These potential changes become mixed up with the potential changes resulting from maternal psychiatric illness.
Maternal morbidity. These issues are the same ones we would deal with if the woman was not pregnant. These risks are present none the less. They are risks for the woman but also for her family. If a woman with depression or psychosis suicides and leaves behind two small children and a husband. This is obviously a disaster irrespective of whether she is pregnant or not. We can’t expose women or families to these terrible outcomes just because the woman is pregnant. Yet in reality this is what sometimes happens
(Case example of patient with increased suicidality and Dr refusing to agree to increase in antidepressant medication).
Some of the most difficult management decisions occur when a partner doesn’t believe in depression they are less impressed with suicidality and don’t see it as reversible.

33. Effects of Antidepressants on Foetus.
Miscarriage possible slight increase
Malformations no increase
Intra-uterine deaths no increase
Low birth weight slight increase
Prematurity slight increase
Withdrawal syndromes can occur
Behavioural sequelae as yet unknown
As an example we can use antidepressants to discuss the direct effects on the foetus.
While the effects of antidepressants seem to be relatively benign. Other medications like mood stabilisers such as anticonvulsants or lithium are not so benign.

34. FDA: “Use in Pregnancy”- Drug categories.
Category A: Controlled studies show no risk
Category B: No evidence of risk in humans
Category C: Risk to humans cannot be ruled out
Category D: positive evidence of risk but it is possible in some situations the benefits may outweigh the risks
Category X: Contraindicated in pregnancy. Risks outweigh the benefits in almost every situation.
The difficulty is that none of the medications we use are rated A or X.
None of the psychotropic drugs are FDA approved in pregnancy or breastfeeding.
None of them have very comprehensive data in terms of safety.
However there has been more research on antidepressants than any other drug in the whole pharmacopoeia.

35. Risk Periods for Foetal Structural Malformations.
2-4 weeks neural tube closure
4-9 weeks heart is forming
6-9 weeks is when the oral cleft closes
by 12 weeks organogenesis is completed
These are the times when you are most worried about the potential teratogenic effects of medications. It is not thought that most psychotropic drugs increase the risks by much, but any increased risk is generally unacceptable.

36. Pathways of Exposure in Pregnancy

37. Psychotropics and Breastfeeding.
It is widely accepted that there are many benefits in breastfeeding both biologically and in terms of mother-baby attachment.
Do these benefits outweigh the potential risks of psychotropic ingestion?

38. Pathways of Exposures in Breastfeeding.

39. Pathways of Exposures in Breastfeeding.

40. Adverse Effects of Psychotropics on Breastfeeding. (1)
As with pregnancy, this depends on the class of medication.
All psychotropic drugs pass into the breast milk.
Antidepressants as an example:
various adverse effects reported
mostly non-specific
many studies show no ill effects
contraindicated in premature, low birth wgt, or medically ill babies.

41. Maternal SSRI use and Adverse reactions. (ADRAC, August 2003)

42. Adverse Effects of Psychotropics on Breastfeeding. (2)
Anti-anxiety (Anxiolytics)
various adverse effects reported mostly sedation, lethargy, sleep disturbance and in some instances respiratory depression.
The risk seems to diminish as the infant matures due to better metabolism gets older.
Long acting benzodiazepines (eg diazepam Valium) are more likely to build up in the infant.
Diazepam, lorazepam are secreted at higher levels in breast milk cf. oxazepam.

43. Adverse Effects of Psychotropics on Breastfeeding. (3)
Antipsychotics
generally OK to breastfeed
some adverse effects noted.

44. Adverse Effects of Psychotropics on Breastfeeding. (4)
Lithium:
contraindicated in most cases
if mother strongly desires can be done with very close monitoring
Anticonvulsants
Some adverse effects reported, some quite serious
again can be done if mother strongly desires this and is made aware of the risks.

45. Approach to Management
General Principles
Plan Ahead

46. Planning Ahead

47. Try to Pre-empt Difficulties.
Try to discuss the issues prior to pregnancy along with discussion of contraception.
Planning ahead is the key. This allows time for informed decisions. Have a plan in place based on the “risk-benefit ratio”.
Try to involve partners and families where appropriate.
The woman and her partner must ultimately decide what is best for them.
Inquire about any plans for pregnancy and discuss with partners where possible.
Emphasise the need for pre-pregnancy consultation.
50% of all pregnancies are unplanned.
Document the birth control method and any exposure to drugs and other substances.
Consider the risk of pregnancy even if not planned.

48. If Planning a Pregnancy.
Stop medications, if possible, while attempting conception.
This depends on the persons previous psychiatric history.
Stop medications on becoming pregnant
by testing each cycle.
again this depends on the history and should not be as a matter of routine.

49. Approach to Management: Early Pregnancy. (1)
Discuss the strengths and weaknesses of each treatment modality.
Discuss the risks and benefits of the various options - “Risk-Benefit ratio”.
No decision is risk free.
Try to minimise exposures.
Avoiding all drugs in the first trimester is the ideal, but this is not always possible.
Is this medication really necessary? ie Now? Given the current circumstances.
What is the risk for this woman it we stop medication?

50. Approach to Management: Early Pregnancy. (2)
Treat the mental illness as expertly as possible.
Avoid changing medications (this will add a new exposure).
Stick with medications with good body of information.
Avoid poly-pharmacy.
Avoid anticonvulsants unless absolutely necessary and monitor with ultrasound.
Dilemmas in early pregnancy:
Woman previously well on medication with limited safety data.
Woman refuses to take medication.

51. Approach to Management: Later in Pregnancy
Pharmacokinetics can change in pregnancy and doses may need to be changed.
Use lowest dose but be ready to increase dose or reintroduce a previous medication.
Discontinuation effects.(Neonatal Withdrawal). Consider gradual reduction of medication and ceasing prior to delivery (controversial).

52. How Are Decisions Made? A Question of Balance.
Decisions are rarely clear cut.
Usually there are two or more very reasonable options between which the mother and the physician have to chose.
Some factors lead to one decision, other factors lead to a different decision.
Weighing the risks is a colaborative process between parents and physician.
Decisions have to be made with often conflicting data. A clear cut decision is not always obvious.
Most cases fall in the broad middle range rather than at either extreme.
Previous decision making only considered the possible negative effects of medication vs the gross indirect effects of severe maternal illness. Now we have to consider the direct effects of maternal psychiatric illness on the foetus/baby.
Mothers with high, unrealistic or unreasonable expectations. They may want a 100% guarantee. Its easy and tempting to respond with reassurance because that it what we are trained to do. We may feel like we are being a spoil sport in pointing out all the risks rather than giving reassurance.
We have to present all the information that we can in such a way that mothers and fathers feel able to make an informed decision. We want to help them decide but we can’t be deciding for them or taking on responsibility that properly belongs to parents.
There are no 100% guarantees and we can’t be lulled into giving complete reassurance at a time of normal anxiety. We can’t give guarantees in order to encourage the woman to have treatment for her psychiatric illness. Fortunately the risks in many cases have been quantified. They tend to be small.
The problems that the woman faces are part of her the difficulty in having a psychiatric illness and part of her involvement in the real world.
There are potential medico legal issues for the future. Especially when we consider that babies/children possibly affected could sue 20 years later. We have to document that we discussed fully with the parents the risks and risk benefit ratio. And how the person came to their decision. What they took to be of most significance to them as to whether or not to take medication.
Although the FDA do not approve the use of these drugs in Pregnancy/lactation. That doesn’t mean they are not allowed to be used it just means that they are not willing to put their seal of approval on them.
In the end it has to depend on a woman’s values...

53. Who Decides and How?
Ultimately it must be a mother’s and partner’s decision.
This relies on the information we provide but also on her assessment based on:
her values and her choices
her desires for the future and how she gives weight and meaning to different risks and the different information presented
There is rarely a “right answer”.

54. External Considerations.
Family pressures
Partner pressures
doesn’t believe in depression as a diagnosis
doesn’t believe in medications
hasn’t seen an episode of depression yet
doesn’t want her to be like his mother/aunt etc

55. Individual Psychotropics.

56. Classes of psychotropics.
Antidepressants
SSRI’s
Tricyclics
MAOI’s
Mood Stabilisers
anticonvulsants
lithium
Antipsychotics

57. Antidepressant medications.
Tricyclics
SSRI’s (fluoxetine sertraline paroxetine citalopram fluvoxamine)
SNRI’s venlafaxine (Efexor-XR)
reboxetine (Edronax)
mirtazapine (Avanza)
MAOI’s

58. Tricyclic Antidepressants.
Extensive data that there are no structural abnormalities in the foetus
nortriptyline and desipramine have less anticholinergic side effects
low incidence of perinatal syndromes
Nulman (2002). No negative behavioural sequelae up to 6 years.
The data is reassuring
Self limited perinatal syndromes such as poor feeding, irritability. While these adverse effects do not appear to be serious or frequent it is important to note that there are obvious difficulties in determining the exact frequency of adverse effects in babies/infants exposed to medications. Because something is not visible does not mean it is not occurring.
Nulman study….

59. Fluoxetine (Prozac, Lovan)
Increased risk of:
miscarriage, 14% cf 7%
low birth weight
premature birth
decreased ARGAR Scores
minor anomalies
admission to NICU
poor neonatal adaptation
Baseline rate for miscarriage in the general population is considered to be up to 15%

60. Fluoxetine (Prozac, Lovan)
No increased malformations
some perinatal syndromes
Chambers study...
increased risk of minor malformations
increased risk of preterm labour
increased admission to special care
Extensive data which is mostly reassuring
Chambers study. Prospective Study. 228 women taking fluoxetine.
No major functional or cosmetic structural changes but suggestions that the medication is interfering with the foetus.
Higher rates of premature delivery
Higher rates of admission to special care
Poor neonatal adaptation including: respiratory difficulty, cyanosis on feeding,
jitteriness
Lower birth weight
Some problems with the study

61. Other SSRI’s (1) These have tended to be looked at as a group
No increase in
congenital malformations
miscarriage / stillbirth
increased preterm labour,
decreased APGAR scores
problems in “neonatal adaptation” (previously reported as withdrawal syndromes) especially paroxetine
Adriana Moldovan’s study 2002
55 women taking Paroxetine late in pregnancy (Cf exposure in early pregnancy)
12 had complications necessitating intensive treatment and prolonged hospitalization : respiratory distress (9) hypoglycemia (2) and jaundice (1)
Only 3rd trimester exposure to Paroxetine was associated wit neonatal distress.
Study in Finland K. Laine measured umbilical cord serotonin concentrations
proposed that a serotonergic overstimulation occurs in the neonate
agitation, myoclonus, hyperrflexia, sweating, shivering, tremor, diarrhea, incoordination, fever, confusion, seizures
The most common symptoms seen in the newborn were: tremor, restlessness, and rigidity typically seen in a serotinergic overstimulation in adults
The resolution of the symptoms corresponded with the fall in fetal concentrations of the SSRI which tends to be opposite what would be expected for a withdrawal syndrome.
withdrawal symptoms in adults are : dizziness, nausea, tremor, anxiety insomnia

62. Other SSRI’s (2)
problems in “neonatal adaptation” (previously reported as withdrawal syndromes) especially paroxetine
Casper J Pediatrics 2003
31 mother - baby pairs, various SSRI’s
found a negative effect on motor development and motor control
Regina Casper 2003
31 pairs
months follow up
Neurological examinations
Dysmorphology examinations
Bayley Behavioral Rating Scale ; 3 Scales
1. Mental development Index
2. Psychomotor Development Index
3. Behavioral Rating Scale
Medication exposed children were rated significantly lower for behavioral motor quality especially on : tremulousness and fine motor movements
Nulman did not find this in his studies but did not report data for the PDI or the BRS of the Bayley
Some problems with the study including the different ages of those tested.
Highlights the importance of motor testing in future studies

63. Venlafaxine Einarson Am J Psych. 2001
150 women all used venlafaxine during pregnancy and 34 used it throughout.
No increased risk of malformations but numbers small.
Small numbers
“Only 80% power to detect a 4 fold increase in the rate of malformations
Would need 800 subjects in each group to detect a 2 fold increase in risk of malformation

64. Other antidepressants
Bupropion/Mirtazapine/Reboxetine
No evidence yet that they are harmful but this could easily change
Not much data
We just don’t know

65. MAOI’s Not much data/studies Not used very often in pregnancy
What we know is concerning
We don’t know if they are dangerous though

66. Anxiety Disorders. High cortisol levels are problematic for the foetus
benzodiazepines are problematic
Try CBT
try SSRI’s as first line
use short acting drug
try to wean before delivery

67. Benzodiazepines (1). Neonatal sedation or withdrawal
Floppy baby syndrome (baby is not responsive and listless)
Oral Cleft Palate?
This is controversial 0.6% cf 0.06%
some studies dispute this
risk period is weeks hence avoid during

68. Benzodiazepines (2). animal data ...?behavioural teratogens
the data is confusing and not reassuring
Long acting agents can build up in the infant
SSRI’s are preferable

69. Bipolar Disorder - 3 problems.
1. Very high relapse rate.
2. When untreated it is a very dangerous condition for mother and baby.
3. The main treatments (except ECT) are all known teratogens.
Consider ECT. This is not always readily available and patients may not prefer it.

70. Anticonvulsants - Valproate.
The most dangerous psychotropic medication.
Discuss with any woman of reproductive age.
5 times higher rate of malformations or pregnancy complications.
Neural tube defects incr. from 0.3% to 1-5%
may be reduced by folate supplementation.
Increases defects in heart/limbs/genitals/CNS and face.
perinatal syndromes coagulopathy and liver dysfunction
behavioural sequelae
Category “D”

71. Using Valproate. Discuss ahead of time, before pregnancy.
Supplement with folate 4 mg per day from 4 weeks pre conception to 12 weeks gestation.
Check foetal alpha-fetoprotein.
Do high resolution ultrasound at weeks.
Give vitamin K in final month of pregnancy.
Keep serum level below 70 if possible.
Give in divided doses rather than once daily.

72. Valproate and Breastfeeding.
Valproate compatible with breastfeeding

73. Lithium.
increases Ebstein’s abnormality by times (1 in 1000 cf 1 in 20,000)
used to be thought to be 400 times
foetal diabetes insipidus can occur
floppy baby syndrome
has been around a long time
a lot of data, but the data is concerning.

74. Using Lithium in pregnancy.
High resolution foetal ultrasound at weeks to check for Ebstein’s abnormality.
Give in small divided doses if possible.
Monitor maternal serum levels which can change dramatically.
Taper dose by a half dose 2 weeks before delivery.
Hydrate the woman in labour.

75. Lithium in Breastfeeding.
Discourage breastfeeding.
Very high infant serum levels up to 50% of the maternal level.
High risk of toxicity in the infant, especially if dehydration in the infant. eg GIT virus with diarrhoea etc.
Many reports of infant toxicity.

76. Carbamazepine (Tegretol).
The data is quite concerning.
Associated with many different adverse outcomes in pregnancy.
It is however, like valproate, compatible with breastfeeding (levels 6% to 65% of maternal level).
Some case reports of adverse outcomes in breastfeeding.
Like valproate it increases the rate of neural tube defects but not as much as valproate. Overall malformation risk is doubled.
Deficiency in Vitamin K dependent clotting factors associated with foetal intra-cerebral haemorrhage.
Foetal hydantoin syndrome, and possibly developmental delays,
Breastfeeding adverse outcomes reported:
transient hepatotoxicity, seizure-like activity.

77. Lamotrigine.
A prospective trail did not show increased risk for major malformations but small sample size.
Supplement with folate through pregnancy.
Breastfeeding: infant serum levels 25% to 30% of maternal serum.
No reports of adverse outcomes thus far.
Theoretical risk for life threatening rash.

78. Olanzapine.
An atypical antipsychotic used increasingly in Bipolar Disorder.
One prospective study showed no increased risk in pregnancy but small sample size.
breastfeeding: Limited information.
Some case reports of adverse effects, but ?if related to the medication.

79. General guidelines for managing Bipolar Disorder in Pregnancy.
Plan ahead and discuss risks.
Abrupt discontinuation greatly increases relapse in Bipolar Disorder.
Reduce medications if possible.
Consider ECT (good safety data in pregnancy)
Monitor pregnancy closely with ultrasound.
Consider options for post partum prophylaxis.

80. Mild - Moderate Bipolar Disorder
Avoid medications in first trimester if possible.
Gradually taper medication before pregnancy or immediately on discovery of pregnancy.
Reintroduce mood stabiliser immediately if any deterioration in mood.
Strongly advise for post partum prophylaxis.

81. Severe Bipolar Disorder.
Maintain prophylaxis throughout the pregnancy despite dangerousness of medication.
Consider switching from an anticonvulsant to lithium prior to pregnancy or switching to olanzapine.

82. If Pregnancy occurs while on an anticonvulsant.
Foetus has possibly already been exposed at the high risk period for neural tube defects.
Switching to a different agent increases the number of drugs foetus is exposed to.
No good options.
Need full discussion with the woman about what she thinks is best for her. A balancing act depending on the woman’s history of illness.

83. Post Partum Management of Bipolar Disorder.
Prophylaxis is very important in this period.
Postpartum psychosis has a 4% risk of infanticide and 5% risk of suicide.
% of women with untreated Bipolar Disorder will have an episode of post partum psychosis.

84. Breastfeeding in Bipolar Disorder.
Breastfeeding is relatively contraindicated while taking lithium.
Consider using an anticonvulsant while breastfeeding. The woman would then need to weigh benefits of breastfeeding vs the unclear risks of breastfeeding with an anticonvulsant.
In this context being on a prophylactic medication should take precedence to breastfeeding.
The question is not “Should I breastfeed or should I take medication?” it is “Should I breastfeed while taking this medication?” some women will decide yes to the second question and some women no.

85. Antipsychotic drugs. High potency drugs: eg haloperidol
Neonatal extra pyramidal signs, are self limiting and resolve.
No known teratogenicity based on surveillance data.
Low potency drugs: eg chlorpromazine
Neonatal anticholinergic symptoms
?some teratogenicity not supported by surveillance data.
Err towards a high potency agent
Atypical agents: No data except for Olanzapine which has a small amount of data.

86. Approach To Management - Postnatal

87. Approach to Reducing exposures in Postnatal illness. (1) Newport (2002).
Document all psychiatric illness exposures (impaired maternal care, alcohol cigarettes drugs etc,)
If evidence of severe maternal impairment, err towards medication exposure.
Consider non-medication modalities according to their availability.

88. Approach to Reducing exposures in Postnatal illness. (2)
Exposure in breastfeeding is much less than the exposure in utero.
Hence stick to same medication that the infant has already been exposed to.
If infant has not yet been exposed, use a medication of previous response for the mother. i.e. Don’t experiment with new medications.
Use a medication with data.
If you change medications the infant is now exposed to two different medications rather than just one.

89. Approach to Reducing exposures in Postnatal illness. (3)
Avoid poly-pharmacy. Monotherapy at any dose is preferable to 2 or more medications.
Reduce infant exposure with pump and dump at hours.
Monitor the infant for side-effects.
discontinue breastfeeding or discontinue the medication depending on the circumstances.

90. Partners and others in family
Support partners as well, they are neither expendable or always durable.
Are they for or against management suggestions?
If against, find out why.
doesn’t believe in depression
has never experienced her depression
doesn’t want her “addicted” to medication

91. Summary.
Goal is to balance the reduction of exposures from both illness and medication
The severity of the illness tends to determine the options.
Use a medication of prior response and,
Use a medication of prior infant exposure.
Use a medication with data.
Try to use monotherapy.