Psychotropic Medications in Pregnancy and Breastfeeding.

1. Psychotropic Medications in Pregnancy and Breastfeeding.

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.

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 • 10 - 20% of women will develop PND. • Risk higher if any previous history of illness.

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.

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.

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?”

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.

24. Effects on foetus changes in the HPA axis lower birth weight prematurity behavioural teratogenicity Potential direct effects of Maternal Depression/Stress.

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.

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.

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

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.

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

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.

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.

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.