Perinatal Mental Health Angelika Wieck Consultant in Perinatal Psychiatry Manchester Mental Health Social Care TrustPerinatal Mental Illness
• Any mental health problem occurring in pregnancy or the first postnatal year
• All mental disorders of the age group
• How many women are affected ?
Perinatal Mental Illness
• About 1 in 5
• What are the consequences of maternal mental illness in the perinatal period ?
Maternal Mental Illness
Maternal mental illness
Pregnancy & Neonatal Outcomes
Bodén et al, BMJ. 2012;345:e7085. doi: 10.1136/bmj.e7085.
Lin et al, Schizophr Res. 2010;116:55-60.
Phys. illness
Total costs
Perinatal depression 1,688 2,831 20,672 48,631 73,822
Perinatal anxiety 4,320 4,475 16,474 9,542 34,811
Perinatal psychosis 24,302 347* 23,187 4,775* 52,611
Costs of perinatal mental illness, £ per case (Bauer et al, 20141)
*Little is as yet known about the costs in respect of the child.
Maternal Mental Illness
• Important to identify
• Important to include the wider family
Topics
• Psychotic disorders in the perinatal period
• Suicide
• Infanticide
• Perinatal services
Most disorders:
• Use codes from elsewhere in Chapter V (F) to classify mental disorder
• Add second code (F 99.3) – ‘mental diseases and diseases of the nervous system
complicating the puerperium’.
puerperium, not elsewhere classified’
This category should only be used if
• Onset is within 6 weeks of childbirth
• Insufficient information is available to make a diagnosis under another category
• Additional clinical features are present which make classification elsewhere
inappropriate.
• Includes postnatal depression NOS, puerperal psychosis NOS, other mental and
behavioural disorders associated with the puerperium, not elsewhere classified,
unspecified puerperal mental disorder
Question :
At what stage of the perinatal period is depression most common ?
Non-psychotic disorders in the perinatal period
• Point prevalence of major and minor depression in high income countries: 6.5 - 12.9 %
• Similar to non-perinatal women
• No qualitative differences in psychopathology
• Thought content coloured by themes of motherhood
Failure to bond
• Fetus or baby
• ‘He isn’t mine’, ‘it could be anybody’s child’, ‘I want her adopted’
• Extremely distressing
• Self blame, ‘what kind of person am I not to love my own child ?’
Mother – infant interaction
• Lower sensitivity of the mother towards the baby • Less interactive play • More negative comments
Risk factors
misuse, and neurotic personality traits
Psychosocial adversities • eg low socio-economic status -particularly in low and
middle income countries-, exposure to trauma, childhood sexual abuse, chronic and acute negative life stress, domestic violence, migration, relationship problems and low levels of social support
Course
• 40 % risk of recurrence after subsequent birth (Wisner et al, 2004)
• Increased risk of non-perinatal episodes (Cooper and Murray, 1995)
Anxiety disorders
• Period prevalence in pregnancy and postpartum no different (with exception of OCD) from non-childbearing women
• 12-13 % of women affected
• Commonly occur with other mental disorders, particularly other anxiety states, depression, bipolar disorder.
• Anxious thinking or ruminations often relate to serious harm coming to herself or the child, failing as a mother or being perceived by others as a poor mother
Obstetric PTSD (Andersen et al, 2012)
• In the postnatal period, the prevalence is about 1-2 %
• The most important risk factors are subjective distress in labour and obstetric emergencies.
• May lead to avoidance of future pregnancies, or vaginal deliveries
OCD (Russel and Mazamanian, 2013)
• Prevalence in perinatal period about 2 % (2 x increase)
• 1/3 OCD sufferers first become ill in pregnancy or after childbirth
• Thoughts - accidental or deliberate harm to the child – germs/knives/being a paedophile
• Resulting compulsive behaviour, avoidance
Eating Disorders (Easter et al, 2012, Micali, 2010)
• 2 % of pregnant women
• Often symptoms reduce but become more severe again after delivery
• Low birthweight
Personality Disorders
• EUPD most common
• Little research
• Previous traumatic delivery or nullipara
• Risk factors – other mental illness, history of sexual abuse, poor social support
• High level of subjective distress
• Requests for Caesarean Section
Valdimarsdóttir et al (2009) PLoS Med 6(2): e1000013. doi:10.1371/journal.pmed.1000013
http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1000013
days
Month
2
Month
3-6
Month
7-12
1. Munk-Olsen et al, JAMA 2006;296(21):2582-9 ; 2. Munk-Olsen et al, Arch Gen Psychiatry 2009; 66(2):189-95
Diagnosis and relative risk of admission
after childbirth in first time mothers
Presentation
• Abnormal thought content related to motherhood (eg baby still in
womb, woman is Virgin Mary, baby is Jesus Christ, baby can fly)
• High risks to mother and baby
Psychotic depression
dominated by motherhood themes, eg. unworthy mother,
baby is devil, baby needs to be protected from
persecutors
• No bonding: ‘He isnt mine, I want him adopted’, ‘she
could be anybody’s child’
• High risks to safety of infant and mother
Other common features of
Postpartum psychosis – a psychiatric emergency !!!
• Rapid onset
• Rapid escalation
• On call staff need to be very suspicious of incipient
mood symptoms and oddities in presentation – if
called to maternity ward assessment by experienced
psychiatrist within 4 hours ! (NICE, 2014)
Recurrence of puerperal affective psychosis
• 54.4 % of women with a past history of PPP experience
another severe episode after the next delivery
Perinatal course of bipolar disorder
• In pregnancy the course probably slightly improves but
high risk of relapse if medication is discontinued
Relapse of Bipolar Disorder during Pregnancy
in Dependence on Medication
Postpartum relapse in bipolar disorder
• About 1 in 2 develop a
recurrence in the early
severe
“My family has a grand tradition…… after a woman gives
birth, she goes mad."
postpartum trigger in bipolar
2001
• Only disorder where fertility is still reduced
• Higher rate of childhood abuse and domestic violence
• High rates of co-erced sex and sexual risk taking
• Less contraceptive use and more unwanted pregnancies
• Disorder with the highest involvement of social care
Schizophrenia
• if there is an admission in pregnancy
• where there is partner psychopathology
• Discontinuing medication in pregnancy
Pressures of becoming a mother, increased contact with health and social care professionals, disruption of routine, new cognitive demands
Causes of maternal death 2011-13
Dark bars show indirect causes, pale bars direct causes
Mental health-related deaths
100,000 maternities
Suicide Substance misuse
Late bookers (% > 12/40)* 30.0 59.3
Received minimal level of antenatal care (%)*
63.6 30.4
24.7 20.8
• 62% mental health female population violent suicide*
• Violent deaths more common in all time periods throughout
pregnancy and postnatal year
most commonly recurrent depressive disorder (45)
• 2 had prior bipolar diagnosis
• 2 had prior schizophrenia diagnosis
• 22 women had psychotic symptoms
• 14 women had additional substance misuse diagnosis
Red flag clinical features
• Feelings of incompetence as mother
• Feeling estranged from the child
Key recommendations to reduce suicide
• Improve the effectiveness of communication between health and other agencies
• Raise awareness of mental illnesses in the perinatal period
• Provide additional training to all involved health professionals
• Set up regional clinical networks for perinatal mental health with all stake holders
Questions
• What age group of children are most vulnerable to be killed or victim of abuse related serious harm ?
Vulnerability of children < 1 year old
Marks and Kumar, 1995
Age of victim in Serious Case Reviews in England
Sidebotham et al, 2011
0
20
40
60
0
10
20
30
40
50
Question
• What are the risk factors for infanticide and abuse related serious harm ?
Perpetrators of infanticide
• Half have lifetime diagnosis of severe mental illness – affective disorders, schizophrenia, personality disorder (Flynnn et al, 2007)
Serious Case Reviews in England: Background Factors ‘The Toxic Trio’
(Brandon et al, 2010)
Identification pregnancy and postnatal period:
All health professionals should consider asking the following depression identification questions as part of a general discussion about mental health and wellbeing:
During the past month have you often been bothered by :
• feeling down, depressed, or hopeless?
• having little interest or pleasure in doing things?
Also consider asking about anxiety using the GAD scale - 2:
during the past month have you been:
• feeling nervous, anxious, or on edge?
• unable to stop or control worrying?
Page 50
Further assessment
If the woman answers yes to any of the above questions, or where there is clinical concern, further assessment is needed :
As part of full assessment, consider using formal measures such as the patient health questionnaire (PHQ-9), the Edinburgh Postnatal Depression Scale (EPDS) or GAD-7 and referral to a general practitioner or mental health professional, depending on the severity of the presenting problem.
At all subsequent contacts during pregnancy and the first year after birth, the health visitor and other healthcare professionals who have regular contact with the woman should consider asking the two depression questions and using GAD-2 as well as the EPDS or the PHQ- 9 as part of monitoring
Page 51
Identification – severe mental illness
At a pregnant woman’s first contact with services, ask about
• any past or present severe mental illness
• previous or current treatment
• any severe postpartum mental illness in a first degree relative
If alcohol misuse is suspected, use the alcohol use disorders identification test (AUDIT) as an identification tool in line with the NICE guideline on alcohol use disorders.
If drug misuse is suspected, follow the recommendations on identification and assessment in the NICE guideline on drug misuse—psychosocial interventions.
Page 52
Referrals for psychological treatment
Assess all women with a known or suspected mental health problem who are referred in pregnancy or the postnatal period for psychological treatment within two weeks of referral
and provide psychological interventions within one month of initial assessment.
Page 53
Assessment and referral - severe
Refer all women who have, are suspected to have, or have a history of severe mental illness to a secondary mental health service (preferably a specialist perinatal mental health service) for assessment and treatment, and ensure that the woman’s GP knows about the referral.
Page 54
Assessment and referral – postpartum psychosis
If a woman has sudden onset of symptoms suggesting postpartum psychosis, refer her to a secondary mental health service (preferably a specialist perinatal mental health service) for immediate assessment (within four hours)
Page 55
• Referral to psychiatrist as soon as pregnancy is known
• Data on medication safety change all the time – perinatal psychiatrist would be ideal, if available.
• Prioritize appointment
• Detailed forensic style assessment, including assessments of risks and likely parenting competence
Principles of management in pregnancy (moderate – severe mental illness)
• Plan antenatal and postnatal care as early as possible
• Check woman has booked with antenatal clinic
• Be aware and discuss potential risks of comorbidities to pregnancy and child outcome
Overall management in pregnancy
• Identify risk factors for recurrence of mental illness, particularly for the postnatal period
• Optimize non-pharmacological treatments
• Talking therapy – to be provided within 1 month of assessment ! 1
• Discuss how to reduce postnatal stress, optimize sleep, and mobilize postnatal support
• Liaise with midwives, health visitors, child social workers
• Multi-disciplinary and multi-agency meetings
• Often > 1 planning appointment needed
• Write one multi-disciplinary care plan
• Care plan for intrapartum and postnatal period should be ready at least by 32 week gestation
• Distribute plan to all involved professionals
• Copy in handheld maternity notes
Management in pregnancy
• There are no risk-free management options !
• Discuss risks and benefits of medication options to mother and child : continuing
stopping
Also discuss risks of untreated illness !
• Avoid drugs with higher teratogenic risk
• Avoid drugs with the least safety data
• But !!! Important are … past response to treatment experience of side-effects woman’s preference
Prescribing in pregnancy
(unless it is valproate !)
Prescribing in pregnancy
• Record discussions in case notes
• Copy clinic letters to patient
• Advise on other resources for information on reproductive safety of psychotropic medication
• Inform obstetrician and midwife of medication
• Any changes to medication plan by other doctors or pharmacist should be discussed with psychiatrist beforehand
Prescribing in pregnancy
• Patient should bring psychotropic medication into hospital
• Withdrawal symptoms in neonate commences usually within 48 hours of delivery
• Offer 2-3 day stay on postnatal ward for paediatric observations
• Pre-discharge meeting on maternity ward
• Ensure community midwife and health visitor know about maternal psychotropic medication and possibility of neonatal withdrawal after early discharge
Management in pregnancy
• Approximately 50 % of cases are first episodes
• Incipient symptoms often missed: ‘Stressed and tired’ Fluctuating symptoms ‘The blues’ Woman conceals symptoms
• High level of awareness needed by maternity and on call mental health staff !
• If suspected, mental health team needs to assess within 4 hours1
Psychosis after delivery
1National Institute of Health and Care Excellence (2014). Clinical guideline 192
• Lower threshold for admission
• High risks – effective medication regime and frequent reviews essential
• Choice of medication less restricted
Postpartum psychosis
WHO, 2003 :
for the first six months of life.
Thereafter, to meet their evolving
nutritional requirements,
while breastfeeding continues for up to
two years of age or beyond.’
World Health Organization. Global strategy for infant and young child feeding. Geneva, 2003, World Health Organization. Available at: http://www.who.int/child_adolescent_health/documents/9241562218/en/index.html.
1
Breastfeeding
• All psychotropic drugs are transferred into breast milk
• Exposure of child during breastfeeding is usually much less than during pregnancy
• Few data for most psychotropic drugs
• Measure of exposure : relative infant dose (RID):
infant dose/kg bw : maternal dose/ kg bw
• RID < 10% regarded as ‘relatively safe’ (Bennett, 1996) 1
• Most psycho-tropics are well below 10 %, but some exceptions
1Bennett PN (1996) Use of monographs in drugs. In: Bennett PN (Editor), Drugs and Human Lactation (pp 67-74). Amsterdam: Elsevier Science Publishers
Psychotropic drugs and breastfeeding
• In general adult practice sexual health, fertility, planning for parenthood, and contraception should be discussed with all women of childbearing potential, aiming at once a year.
• Offer preconception counselling to women who plan a pregnancy
Women with childbearing potential
…….Contraception should be used
on every conceivable occasion……….
• The degree varies between drugs
Transfer of psychotropic medication to the fetus
Timing of exposure & adverse outcomes
Early pregnancy Major structural defects
Later pregnancy Minor structural defects Functional defects (eg valproate effects on brain development ! ) Premature delivery Abnormal fetal growth
Before delivery Neonatal toxicity Neonatal withdrawal
Longer-term outcomes Neurodevelopment
• Next best levels of evidence:
pregnancy registers, population studies, cohort studies,
case control studies
Investigating whether a drug is harmful to the developing child
• Depends on question and size of risk
• Major anomaly rate
1,000 exposed cases needed to test for doubling of risk1
Studies now can answer question for many psychotropic drugs as groups (antipsychotics) or individual agents (antidepressants and some antiepileptics)
• Specific anomalies
If anomaly has incidence of 0.1 % in general population (eg cleft palate): almost 11,000 exposed cases needed to test doubling of risk2. Studies on antidepressants can now answer question for some specific anomalies
Sample sizes needed to test for congenital anomalies
1European Medicines Agency (2008)
• No consistent approach to confounding factors
• Little known about untreated maternal illness
• Epidemiological studies – large numbers but lack of accuracy in neonatal diagnoses
• Diagnostic bias when assessing pregnancy and infant outcome
• Multiple statistical tests per study
• Research difficult to do !
Quality of current evidence
Outcome Odds ratio Comments
2.12 (CI – 1.25-3.57) Heart defects most common (often septal defects)
Preterm birth 1.86 (1.45-2.39) No difference between FGAs and SGAs
Small for gestational age 2.44 (1.22-4.86) No difference between FGAs and SGAs
Miscarriage No association -
Still birth No association -
Coughlin et al 1: Meta-analysis of 13 cohort studies (6,289 exposed, 1.6 million un-exposed)
1Obstetrics and Gynecology, Vol 125; 1224-1235
Adjustment for confounders Confounding factor How many of the 13 studies adjusted
Smoking 5
Obesity 2
Indication 0
• 1.3 million women enrolled in Medicaid, US
• 9,991 1st trimester exposures, large number of confounders accounted for
Any MCM Cardiovascular CM
No increased risks, except for risperidone:
small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81) - independent of measured confounders
1 other study - still-birth1
• Danish population study, 1997-2008
• Comparison with women who stopped medication before pregnancy
• Adjustment also made for age and history of drug misuse, but not other confounders
• Increased odds ratio for still-births:
2.27 (1.45-3.55) vs background population
2.06 (1.01-4.19) vs women who stopped antipsychotic medication some time before pregnancy
Sorensen et al (2015) Plos one, DOI:10.1371/journal.pone.0132280
1. Reis and Källen, J Clin Psychopharmacol.2008; 28(3):279-88;
2. Boden et al. Archives of General Psychiatry 2012, 69: 715-721.
Is there an increase of gestational diabetes ?
Two population-wide studies from Sweden1,2
• Incidence of GDM almost two-fold increased (odds ratios: 1.78, 1.77; 1.94)
• Effect of olanzapine/clozapine no greater than other antipsychotics taken together2
• In one study early pregnancy weight was accounted for and effect just dropped below significance level2
• No effect of antipsychotic exposure on fetal growth parameters,except for macrocephaly in olanzapine/clozapine group (OR: 3.02, CI: 1.60-5.71)2
Neurodevelopment
• Prospective study of 76 infants exposed to FGAs or SGAs
• 76 matched control children
• In early postnatal months, delay in several cognitive domains (Bayley Scales) in the early postnatal months
• By 12 months scores normalized
No difference at 12 months is consistent with findings in older children 2,3,4
1Peng et al. Psychopharmacology (Berl). 2013 Apr 5. [Epub ahead of print); 2Gentile S, Schizophr Bull 2010; 36: 518-44; 3Kris 1965, Curr Ther Res Clin Exp; 7: 785-9; 4Slone et al 1977, Am J Obstet Gynecol; 128: 486-8
Summary for antipsychotics
• Current evidence does not suggest that antipsychotics are major teratogens.
• Suggested increase of MCMs associated with risperidone is very small
• Association with a small increase in pre-term birth and babies small for gestational age. True effect or confounding factors ?
• Possibly small increase in still-births
• Uncertain association with gestational diabetes.
• There is no indication for any significant long-term neurodevelopmental effect
More research with larger samples and adequate control for confounding factors is needed !
Teratogenic effects of anti-epileptic drugs
• Evidence exclusively from studies of women with epilepsy
• Valproate is associated with a 3-fold increase of major congenital malformations – consistent finding1,2
• Carbamazepine has been associated with a 2-fold increased rate of major congenital anomalies3,4
• Malformations not due to seizure activity in pregnancy5
• Some dependence on dose, but reported critical thresholds vary widely6
• Lamotrigine – studies have not found teratogenic effect2,4,7 except for one8
• Little data on pregabalin
1Meador et al, Neurology 2008; 71(14):1109-17, 2 National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192, 3. National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192, 4Vajda et al, 2016. C Clin Neurosci 23:34-7, 5Fried et al, Drug Saf 2004; 27(3):197-202, 6Tomson T, Battino D, 2012. Lancet Neurol. 11(9):803- 13, 7. Dolk et al 2016; Neurology, 86, 1-10. Ban et al 2015; PLoS One, 10(7):e0131130.
Type of malformations
Valproate1 Spina bifida
Carbamazepine2 Spina bifida OR: 2.6 (CI : 1.2 to 5.3)
1. Jentink et al, N Engl J Med 2010 ; 362;23 2. Jentink et al, BMJ 2010;341:c6581; doi:10.1136/bmj.c6581
Cognitive development
1. Bromley et al, Epilepsia 2010; 51(10): 2058-2065 2. Meador et al, N Engl J Med 2009; 360(16):1597-605. 3. Adab et al, J Neurol Neurosurg Psychiatry 2004; 75(11):1575-83 4. Meador et al, The Lancet 2013 http://dx.doi.org/10.1016/S1474-4422(12)70323-X
80
90
100
110
Griffiths Mental
Development Score
*
Verbal IQ (Wechsler)
Estimated difference in IQ at school age: Approximately 8 points1
• Several earlier studies suggest association with autism spectrum disorders2
• Christensen et al (2013)3:
- Population study from Denmark
- Childhood autism : 2.50 %
- Autism spectrum disorder: 4.42 %
• Dose-relationships unclear4,5
1. Bromley et al 2014. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD010236. 2.Bromley et al, J Neurol Neurosurg Psychiatry, 2013: 1-7. 3. Christensen et al, JAMA, 2013: 309(16): 1696-1704. 4. Perucca et al, Neurobiol. Dis. ,2014, http://dx.doi.org/10.1016/j.nbd.2014.05.011; 5. Wood et al , Epilepsia, 2015: 58 (7): 1047- 55
• Evidence from general population studies and high risk families that folate (taken 3 months before and after conception) reduces incidence of congenital defects significantly.
• In women taking anti-epileptics (pregnancy registers and reviews)1,2,3,4,5
1. Wyszynski et al, Neurology 2005; 64(6):961-5 2. Morrow et al, J Neurol Neurosurg Psychiatry 2009; 80:506-511 3. Jentink et al, Pharmacoepidemiol Drug Saf 2010; 19: 803–807, 4. Bogdan et al, American Journal of Medical
Genetics 2012, Part A, 2071-2090
Effect at best uncertain. No protection seen in some studies.
Preventative effect of neurodevelopmental impairments unknown.
Summary for anti-epileptics
Valproate • Has widespread teratogenic and neurodevelopmental effects on offspring, • Harm throughout pregnancy • There is no safe time and no safe dose • Folate does not protect
Carbamazepine • General increase of malformations. Smaller risk of spina bifida than valproate
Lamotrigine • Current literature does not suggest that teratogenic effect is likely
• ‘Lithium baby register’ (N=225) 1
– 18 (8%) babies had cardiovascular defects compared to
1 % in general population
– 6 (2.7 %) had Ebstein anomaly compared to 1 : 20,000 in
general population
– Poor design
• Recent reviews 2,3 : – Original observations were most likely a significant
overestimation
– But actual risk remains uncertain
1 Weinstein ,1980, Handbook of lithium therapy, pp. 421-9. MTP Press, Lancaster. 2 Yacobi and Ornoy. Isr J Psychiatry Relat Sci 2008; 45: 95–106, 3McKnight et al, Lancet. 2012 Feb 25;379(9817):721-8
LITHIUM
Lithium
Recent prospective study with untreated bipolar control group1 :
• Risk of cv anomalies after 1st trim exposure 4.1% (5/123) vs non-exposure 0.6 % (4/711) (p<0.005)
• When spontaneously resolving anomalies excluded: no difference
• Higher rate of pre-term delivery (2-fold increase)
1Diav-Citrin et al (2014) Am J Psychiatry 171: 785-794
European lithium study
Case control study for Ebstein anomaly1 :
• Surveillance of 5.6 million births • 15 congenital anomaly registers in European countries • 264 Ebstein cases – none exposed to lithium • 9/264 exposed to maternal mental illness – Ebstein
associated with MI rather than lithium ?
Summary: It is unlikely that lithium causes Ebstein anomaly. A small effect on general cv anomalies cannot be excluded at present.
1Boyle et al (2016). Cardiology in the Young, 1-9.
• Cases of maternal lithium toxicity at delivery reported
• Fetal or neonatal symptoms reported in case reports 1
• Neurobehavioural consequences2
– 5 year prospective study of 60 children showed no adverse effects when compared with their unexposed siblings
1 American College of Obstetricians and Gynecologists 2007, Practice Bullletin Number 87 2 Schou, Acta Psychyiatr Scan 1976; 54: 193-7
LITHIUM
Antidepressants – first trimester exposure
Tricyclics Few and inconsistent data for whole group. Clomipramine has been associated with a small increase in cardiovascular defects
SSRIS Much more data, mostly from epidemiological studies
Cardiovascular anomalies: • Meta-analysis from 20131:
No association overall with congenital anomalies But small increase of cardiovascular anomalies (RR: 1.36, CI 1.08-1.71)
• Large recent study from US in 20142 : No increase of cardiovascular anomalies. Controlled for depression and depression severity and for a large number of other confounding factors
• Two other large studies with good control of confounders found no effect 3.4
1Grigoriadis et al (2013) J Clin Psychiatry 74: e293-308, 2Huybrechts et al (2014) NEJM 370: 2397-2407 3Furu et al (2015) BMJ;350:h1798, doi: 10.1136/bmj.h1798 4Petersen et al (2016) J Clin Psychiatry 77:1, e36-e42.
SSRIs – first trimester exposure
Differences between SSRIs Paroxetine has most consistently been associated with cardiovascular anomalies
Other antidepressants – first trimester exposure
Much less data
Venlafaxine Venlafaxine No increased risk of major congenital anomalies in two reviews1,2
More frequent withdrawal symptoms in neonates ?
Mirtazapine/trazodone/duloxetine Small body of data No definite conclusions can be drawn. Avoid, if possible
1. Bellantuono et al (2015) Hum Psychopharmacol. 2015, 30(3):143-51. doi: 10.1002/hup.2473.
2. Lassen et al (2016) Basic Clin Pharmacol Toxicol. ;118(1):32-6. doi: 10.1111/bcpt.12497.
Antidepressants – pregnancy outcomes
trimester (adjusted odds ratio 1.53, 1.40-1.66)1
• Depression is also associated with preterm delivery (odds ratio 1.37. CI 1.04-1.81)2
Other outcomes • Inconsistent results
1Huybrechts et al (2014) PLoS One, 9: e92778, 2Grigoriadis et al (2013) J Clin Psychiatry 74: e321-e341
Antidepressants – neonatal issues
• Odds ratio 2.50 (1.32 to 4.73) in meta-analysis1
• Effect seen after late pregnancy exposure only
• Base rate 1:2,000
• Number needed to harm : 286-351 for 1 additional case
• Much lower risk in a recent large study (adjusted odds ratio 1.10, 0.94-1.29) 2
1 Grigoriadis et al (2013), BMJ, doi: 10.1136/bmj.f6932 2 Huybrechts et al (2015) Jama 313: 2142-51
Antidepressants – poor neonatal adaptation
• Neonatal respiratory distress (OR 2.20)
• Neonatal tremors (OR 7.89)
• Affects 1:3 babies, but mild and transient, rarely needs more than monitoring
• Hypoglycaemia common (19%)2
1 Grigoriadis et al (2013) J Clin Psychiatry, 74(4): e309-e320 2Forsberg et al (2014) PLoS One, 9(11): 2111327
SSRIs – autism spectrum disorder
• Small increase (odds ratio 1.81, CI 1.47-2.24)
• Depression as confounding factor ? 1 study found higher rate in un-exposed siblings
• Role of other confounding factors ?
Issue remains controversial2,3
1 Man et al (2014) Neurosic Biobehav Rev 75: 1088-95, 2Sorensen et al (2013) Clinical Epidemiology, 5: 449-459 2Castro et al (2016) Psychiatry Jan 5;6:e708. doi: 10.1038/tp.2015.190.
.
Antidepressants – other neurobehavioural development
• No effects seen with tricyclic antidepressants, SSRIs and venlafaxine in early childhood1,2
• 1 study: weak association of SSRI exposure with delayed motor development at age 3 but not clinically significant3
1 Nulman et al (2012) Am J Psychiatry, 169: 1165-74 ,2Santucci et al (2014) J Clin Psychiatry 75(10):1088-95 3Handal et al (2015) BJOG, doi: 10.1111/1471-0528.13582
TCAs
with paroxetine
Summary of findings for antidepressants
Summary of findings for antidepressants
• Very small or no risk of congenital anomalies (except paroxetine – clomipramine)
• Increase of poor neonatal adapation but mild and transient
• Small increase in the rare persistent pulmonary hypertension of the newborn (only SSRIs)
• Currently controversial increased risk of ASD and language development (only SSRIs)
Anxiolytics and sleep-inducers
• Benzodiazepines Not teratogenic1,2
• Hypnotic benzodiazepine receptor agonists (Z – drugs) Not teratogenic2,3
Zolpidem: possibly some increased risk for preterm birth, small for gestational age, low birthweight but small effect (ORs1.5-1.7)4
• Trazodone, promazine, promethazine, pregabalin Very little known about 1st trimester exposure
1Enato et al (2011) J Obstet Gynaecol Can, 33: 46-48; 2Ban et al (2014) PLoS One, 9: 100996; 3Wikner and Källén (2011) J Clin Psychopharmacol 31: 356-9; 4Wang et al (2010) Clin Pharmacol Ther, 88: 369-74
• Avoid agents with few data, eg paliperidone , lurasidone
• ‘Do not offer depot antipsychotics to a woman who is planning a pregnancy, pregnant or considering breastfeeding, unless she is responding well to a depot and has a previous history of non-adherence with oral medication’ (NICE, 2014)1
Prescribing in preconception or pregnant patients : 1. Antipsychotics
1. National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
Antipsychotics and dysglycaemia
– Consider impact of anti-psychotic induced weight gain on pregnancy and infant outcome
– Consider other risk factors for gestational diabetes, (1st degree relative has type 2 DM, ethnicity, previous macrosomic baby, previous gestational diabetes) when choosing antipsychotic agents in pregnant women and women with childbearing potential
– Discuss weight management
(including oral glucose tolerance test at 24-28 weeks
of pregnancy2)
1. National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192 2. National Institute for Health and Care Excellence (2008) Diabetes in pregnancy. Clinical Guideline 63.
2. Prescribing anti-epileptic drugs :
Valproate:
NICE1
• Do not offer valproate for acute or long-term treatment of a mental health problem in women who
• are of childbearing potential • Plan a pregnancy • Are pregnant • Consider breastfeeding1.
MHRA (2015)2,3
• Can be prescribed to a woman of childbearing potential only in exceptional circumstances, if there is no alternative and if she is taking effective contraception
• She needs to be aware of the risks and be on effective contraception.
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192, 2 MHRA (2015) Medicines related to valproate: risk of abnormal pregnancy outcomes, MHRA (2016) Patient guide.
0
20
40
60
80
100
Harper et al, Annual Scientific Meeting (Poster), Perinatal Faculty, London, November 2015
Audits of Valproate Prescribing in Manchester1
• Women with childbearing potential • Evidence of clinicians discussing with patients ……
%
Carbamazepine:
• Do not offer carbamazepine to women who are planning a pregnancy or are already pregnant 1
Lamotrigine:
• Most studies find no increase in oral clefts. Use cautiously. • Serum levels decline in pregnancy • Monitor blood levels from early pregnancy into postnatal period • Mood diaries !!!
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
• The teratogenic risk of lithium is low but less researched than for antipsychotics.
• In a preconception or pregnant woman in the 1st trimester already taking lithium, a need to switch to an antipsychotic is less compelling. Patient can stay on lithium she needs a mood stabilizer and has responded to lithium.
• If the woman requires a second mood stabilizer in addition to an antipsychotic this should be either lithium or lamotrigine and not valproate or carbamazepine
3. Prescribing Lithium
• Measure frequently, particularly in month before expected delivery date1
• NICE (2014)1 recommends: 1 x / month up to week 36 of pregnancy
1 x / week in month before expected delivery date
Adjust lithium dose
Treatment with lithium
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
Delivery
• Measure level 12 hours after the last dose 1
• Monitor lithium level, fluid balance, and electrolytes during delivery 1
Postnatally
• Monitor baby for side-effects
• If lithium level in therapeutic range, continue with pre-pregnancy dose. Check level after one week
Treatment with lithium in pregnancy
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
Benzodiazepines
Z-Drugs
4. Treatment with anxiolytics and hypnotics
Breastfeeding
• Antipsychotics:
o NICE1 : do not offer depot antipsychotics unless the woman
is responding well to a depot and has a previous history of
non-adherence with oral medication.
o Don’t offer valproate and carbamazepine1
• Antidepressant
o In first onsets, prefer agents with more data
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
Breastfeeding
General advice to mother:
• Monitor baby for side effects (sedation, muscle tone, other side-
effects) – if in doubt discuss with community midwife/health visitor/ GP if in doubt
1National Institute of Health and Care Excellence (2014) Clinical Practice Guideline 192
Specilaist perinatal mental health services
Started in Britain, now in many other countries
For all stages of childbearing
• Specialist advice for preconception patients
• Management in community before and after birth
• Inpatient treatment in psychiatric mother and baby units
Hub and spokes • Mother and Baby Inpatient Units (often regional) • Community Teams • Antenatal Clinics • Obstetric Liaison Service
Collaborating with : • General adult services • Specialist Mental Health Midwives, Community Midwives • Obstetricians with a special interest in mental health • Health Visitors • Child Social Workers • NGOS
Funded by: • Specialised Commissioning + CCGs
Perinatal mental health services
Standards for inpatient units • Developed in 2007 • Annual review visits • Accreditation visits • 200 clearly defined criteria for
maternal management child care facilities staffing staff development and supervision
Standards for community services • Recently developed • First reviews being conducted
Quality network for perinatal mental health services
Mother and
Baby Units
• Poor provision in many parts of the country as yet
• Nationally strong drive to achieve equal access
• National funding made available
• All regions currently expanding / newly establishing community services and three more Mother and Baby Units
Current developments of perinatal services