Consultant Perinatal Psychiatrist Perinatal Psychiatry City CCG PLT 18th & 25th September 2018 Dr Zena Schofield Consultant Perinatal Psychiatrist

Show of hand please GPs- partners or salaried GPVTS Practice Nurses Non-medical prescribers FY1 and FY2 Who has done a perinatal psychiatry post?

Objectives Update your knowledge on prescribing in pregnancy and lactation in perinatal mental illnesses Reminder of why perinatal psychiatry is important Case Vignettes to apply knowledge

Presentation Quiz Medication in pregnancy & lactation Vignettes Nottinghamshire Perinatal Psychiatry Service including who to refer

Phone calls from GPs to our team Topic % of total GP calls about topic Anti-depressants in pregnancy 54% Anti-depressants postpartum 24% Other or multiple medications in pregnancy 14% Refer or not? 5% Urgent referral 3%

Quiz Most common mental health problem post-partum & incidence rate? Adjustment reaction 15-30% Incidence rates of: Mild-mod depression 10% Severe Depression 2-3%

Quiz % women with bipolar who have been well for 2(+) years who will relapse after delivery? 50%

Quiz Postpartum Psychosis: % of total cases onset by days 7, 16, 90 Incidence rate 2 in 1000 Recurrence rate for next pregnancy 1 in 2

Medication-Pregnancy Risk: benefit analysis Documentation British Association of Psychopharmacology perinatal guidelines 2017 NICE guidelines 2014

Anti-depressants in pregnancy Longer duration evidence base TCAs TCAs- most studies have not found statistically significant ↑ risk of congenital anomalies SSRIs- most recent data including meta-analyses has not demonstrated ↑ risk of congenital anomalies once confounders were removed (age, diabetes, obesity, alcohol use, illicit drug use) Paroxetine- small ↑ risk of cardiac defects BJOG 2015- antidepressants in late pregnancy ↑risk of PPH (aRR 1.5) SSRI use and ASD risk: case control study showed double risk of ASD but nested case control study showed increased risk with untreated maternal depression, mat. Dep & SSRI increased risk for ASD without ID. Also heritage component of ASD not controlled for in studies.

SSRIs in pregnancy neonatal outcomes Persistent Pulmonary Hypertension in neonate JAMA 2015- much lower risk than originally thought, OR=1.1 (not stat signif) when confounders removed Peds 2016 NNH=285 ↑ risk of admission to NICU which ↑ with antidepressant use in late pregnancy (aOR=1.6 CI=1.5-1.8) Peds 2016 (740,000 infants ‘06-’12)

SSRIs in pregnancy and ASD in offspring Autistic Spectrum Disorder Mixed evidence Meta-analysis in 2015 shows modest ↑ risk but many confounders Association, causality not demonstrated Swedish study (BMJ 2013) modest ↑ risk but not able to control for effects of maternal depression BMJ 2017 Rai et al- no pregnant woman took antidepressants then it might prevent 2% of all cases of ASD. Response from Dr Schendel

Antidepressants in pregnancy and offspring outcomes ADHD and Antidepressants- BMJ May 2017 Man et al- probably at least confounding factor, effect size smaller than previously estimated 2017 JAMA Sujan et al- antidepressants in 1st trimester- small ↑ risk of preterm birth but no increased risk of ASD or ADHD in offspring

SSRIs in pregnancy- long term outcomes Long term impact: 2015 BJOG-Danish pop. Cohort study- independent of maternal illness, prenatal antidepressant exposure is not associated with an increased risk of behavioural problems in children at 7 years of age (49,178 dyads) 2016 JClinPsych- language and behavioural differences but not cognitive (178 dyads)

Anti-depressants in pregnancy Venlafaxine (SNRI) and Duloxetine Far smaller evidence base than SSRIs Probably not teratogenic but not sure Poor Neonatal adaptation syndrome- SNRIs > SSRIs If can change to SSRI or TCA then do so Mirtazapine-limited data Buproprion-possible risk of cardiac defects but data is conflicting and limited

Antidepressants in pregnancy summary Tricyclics are generally OK unless OD risk Sertraline, fluoxetine and citalopram ok Limited data on other antidepressants so discuss with perinatal team and be cautious Stick with what works for the patient May be an opportunity to reduce and stop medication if she has been in recovery for awhile

Anti-psychotics in pregnancy Risks of relapse of psychotic illness if stopped GTT at 28/40 First generation anti-psychotics (FGA) Haloperidol, Trifluoperazine, Chlorpromazine Relatively safe in pregnancy No difference in development of children at 5 years Second generation anti-psychotics (SGA) Gestational diabetes

Anti-psychotics in pregnancy 2017 BMJ Grigoriadis- no significant ↑ risk of congenital anomalies with antipsychotics (SGA >9000, FGA 700 of 1.3 million births) 2015 O&G- meta-analysis of case controlled or cohort studies of antipsychotic use in pregnancy- ↑ risk of adverse obstetric and neonatal outcomes, inc small ↑ risk of congenital anomalies . No difference between FGA & SGA.

Anti-psychotics in pregnancy Aripiprazole-?? ↑ risk of miscarriage (2017) Clozapine- Very limited evidence Gestational diabetes rates x2 Monitor clozapine levels due to changes in pharmacodynamics in pregnancy Babies-floppy, ↓ pulse, seizures, ?agranulocytosis Crosses placenta, in breast milk, accumulates in baby

Mood Stabilisers in Pregnancy Valproate: AVOID in women of reproductive age- NICE Dec 2014 8-10% major congenital abnormalities particularly neural tube defects Up to 30% learning difficulties in 1 study Long term developmental delays continue Valproate syndrome Linked to autistic spectrum disorder

Mood stabilisers in pregnancy Lithium Increased risk of cardiac defects Epstein’s anomaly-1-2/1000 (gen. pop. 1/20,000) Floppy baby syndrome Careful monitoring of lithium levels in pregnancy No impact on child development at age 5 Carbamazepine- avoid due to neural tube defects

Mood stabilisers in pregnancy Lamotrigine Small ↑ risk of cleft lip & palate Safest of AEDs used as mood stabilisers Use of antipsychotics as mood stabilisers in pregnancy, especially first generation

Medications to avoid in pregnancy Valproate Lithium Carbamazepine Diazepam (?cleft lip & palate) Procyclidine Paroxetine

Psychotropic medications in lactation Antidepressants in low levels in breast milk: Tricyclic antidepressants e.g. imipramine Sertraline & paroxetine Antipsychotics: First generation antipsychotics e.g. haloperidol Starting to use some 2nd generation antipsychotics in breast feeding WITH CAUTION- specialist team

Medications in Lactation High levels in breast milk so DO NOT use: Lithium Benzos Lamotrigine-risk of SJ syndrome in baby Avoid meds with long half lives Avoid fluoxetine Insufficient data on other meds so avoid

M-BRRACE- UK Saving Lives, Improving Mothers’ Care The UK Confidential Enquiry into Maternal Deaths (CEMD) has represented a gold standard internationally for detailed investigation and improvement in maternity care for over 60 years. Reviewed maternal deaths in UK from 2009-2012 Death rate reduced from 11/100,000 (2006-2008) to 10/100,000 68% of deaths due to medical and mental health problems Key messages: Think sepsis Prevent influenza Mental health matters

‘Red Flags’ Recent significant change in mental state, new thoughts or acts of violent self-harm, new and persistent expressions of incompetency as a mother or estrangement from the infant

Classification of care received by women who died as a result of psychiatric causes and for whom case notes were available for a detailed review, UK and Ireland 2009-13 Care Classification Suicide n=93 (%) Substance misuse n=29 (%) Good Care 17 (18) 9 (32) Improvements to care were noted which would not have made a difference to outcome 10 (36) have made a difference to outcome 48 (51) 6 (21) Insufficient data to classify 12 (13) 3 (11)

Vignettes How would you manage this case? Would you refer to perinatal psychiatry?

Vignette 1 31, partner for 5 years, degree in biology, works as a commissioner for CCG, 2 previous admissions to hospital, 2 episodes with CRHT, on Quetiapine 300mg BD, wants to get pregnant, is currently using contraception but comes to you to discuss stopping it What would you advise her?

Vignette 2 27 female, G3 P1, 8/40 On citalopram 20mg daily for depressive episode, in recovery for 4 months No previous episodes Trigger- redundancy and loss of home

Vignette 3 Just moved into your area 3 older children not in her care, removed by social services Pregnant 34/40 She was fleeing DV but has allowed partner to know her new address Social care involved- she didn’t tell you No medication currently She is feeling a bit anxious

Notts Perinatal Team Whole county 1.7 WTE Consultants for MBU and community 1 WTE band 7 nurse- team leader 8 WTE band 6 CPNs Specialty Doctor, Mother-infant therapist (0.4), psychologist (0.8), OT, 2 nursery nurses, peer support workers 8 bed MBU- new, purpose built CT3 +/- ST OPCs throughout the county

Notts Perinatal Team 1,400 referrals per year, offer Ax to 700+ For serious SMI, 5% of live births=680 Birth rate 13,500 per year in Notts

Who to refer Serious mental illness-whether well or ill especially with an affective component PHx severe depression- esp post-partum Current symptoms of mod depression or mod-severe anxiety disorder Pre-conceptual counselling From 13/40 to max 12/12pp

Summary Anti-depressants in pregnancy- TCAs and SSRIs Anti-depressants in breast feeding- preference for SERTRALINE or Imipramine Anti-psychotics in pregnancy- get secondary MH services involved Active management of serious perinatal mental illnesses by our specialist team Milder perinatal MH difficulties are managed in primary care

Summary Good prognosis for perinatal illnesses Ask Perinatal Psychiatrists for advice Expansion in perinatal services ‘Red Flags’ Recent significant change in mental state, new thoughts or acts of violent self-harm, new and persistent expressions of incompetency as a mother or estrangement from the infant https://www.npeu.ox.ac.uk/mbrrace-uk

Any Questions?