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Perinatal psychiatry for the MRCPsych Course Dr David Middleton ST6 to Dr Fiona Blake 29th November 2011 Learning objectives • To be able to describe the most important perinatal psychiatric conditions • To list treatment principles during pregnancy and breastfeeding • To be able to state malformations associated with commonly used psychotropics • To state the recommended medications during pregnancy and breast-feeding for psychosis, depression, BPAD, anxiety and insomnia Psychiatric considerations • Classic triad -“Baby Blues” (50-75%) - Postnatal depression (10-15%) - Puerperal psychosis (0.1%) • Pre-existing active psychiatric disorder eg Schizophrenia, Bipolar disorder, Anxiety Disorder • New disorder in pregnancy • Substance/alcohol abuse, personality disorder • Disorder associated with childbirth eg PTSD, attachment disorder Postnatal depression • 10-15% pregnant women depressive episode • 16% self-limiting depressive reaction • Onset 2 weeks – 6 months • Previous depressive illness risk • Highest risk in women with BPAD • Other risks include lack of confidante, conflict with partner, life events, poor support network • Affective illness may risk of pre-term delivery Psychosis • Severe – usually a psychiatric emergency • Early onset –often within 2-4 days postpartum most within 1 month • Often begins with confusion, ‘perplexity’ • Later characteristics of mania, depression or schizophrenia symptoms evident • Resolves within weeks but recurs postnatally • Non puerperal and menstrual relapses also occur Case study – Dr Emson In October 2000 Dr Emson stabbed herself and her baby, set light to them both and died of extended suicide She had a h/o bipolar disorder – 5 hospital admissions, 3 courses of ECT, 1 serious suicide attempt, treatment with antidepressants and lithium prior to pregnancy Well during pregnancy CPN and consultant involved but no specific plan Prior to death consulted with poor sleep and low mood Treatment started days before death (3 months postpartum) Link to full report Medication in pregnancy ‘Normal’ pregnancy • Remember baseline complication rates! − spontaneous abortion 10-20% − spontaneous malformation rate 2-3% • Smoking/alcohol/diet affects on foetus • Caffeine low birth weight • Pre-pregnancy obesity neural tube defects Psychiatric considerations • Psychiatric illness in pregnancy is and independent risk factor for congenital malformation • Does not protect against mental illness: a myth! • Affective illness premature delivery • Medications account for only 5% abnormalities Categories of abnormality 1. Major malformations (1st trimester) 2. Neonatal toxicity (3rd trimester) 3. Longer term neurobehavioural effects • • • Medication safety cannot be assessed by RCTs, unethical Sometimes only data is from animal studies Therefore must weigh up risks/benefits All women of child bearing age • Always discuss possibility of pregnancy • Avoid prescribing contraindicated medications e.g. valproate • Consider prophylactic folate Mental illness newly diagnosed during pregnancy • Try to avoid all drugs in the 1st trimester unless benefits > risks • Use non-medication treatments e.g. CBT • If medication deemed necessary, use lowest effective dose and as monotherapy Planning pregnancy • Remember, 50% pregnancies unplanned… • Consider discontinuation of medication if − currently well − low risk of relapse • If high risk of relapse: − consider switch to low risk medication − NB risk of relapse during switch Pregnancy discovered whilst taking psychotropic medication • Do not abruptly stop medication! − high risk of relapse • Consider continuation of current treatment to avoid exposure to many drugs All pregnant women • • • • Involve patient and family in decisions Use lowest dose of lowest risk medication Aim for monotherapy Anticipate dose adjustment in 3rd trimester: − blood volume 30% − CYP2D6 activity 50%, therefore reduced levels of TCAs, SSRIs, FGAs etc − CYP1A2 activity 70&, therefore accumulation of olanzapine, haloperidol etc • Refer to specialist team and involve O&G • Consider foetal screening and withdrawal Depressive illness Depression - treatment • Use of antidepressants in pregnancy common (as high as 8% in USA) • Mostly SSRIs • High relapse rates if medication discontinued (68% vs 26%) Depression - treatment • Tricyclic antidepressants − high exposure to foetus but not apparently teratogenic − antidepressant of choice in pregnancy − risk of pre-term delivery − 3rd trimester use withdrawal symptoms including agitation, seizures, respiratory distress Usually mild and self-limiting Depression - treatment • SSRIs − sertraline least foetal exposure − do not appear to be teratogenic, fluoxetine seems safest − 1st trimester use of paroxetine cardiac malformations − pre-term delivery, spontaneous abortion, low birth weight, pulmonary hypertension − 3rd trimester use of SSRIs: 1. Serotonergic toxicity 2. Discontinuation (esp. paroxetine) 3. Pre-term delivery Depression - treatment • Others ‒ Moclobemide, reboxetine and venlafaxine do not appear to be teratogenic ‒ Trazodone, bupropion and mirtazapine little data ‒ MAOIs, avoid! Teratogenic and risk from hypertensive crisis ‒ ECT: ‒ no evidence of harm but usual anaesthetic risks. ‒ NICE recommends instead of antidepressant combinations Depression - treatment • Recommendations 1. On antidepressant and high risk of relapse maintain 2. Moderate/severe depressive illness during pregnancy antidepressant 3. Amitriptyline, imipramine and fluoxetine most data/experience of use 4. Avoid paroxetine and MAOIs 5. Reduce discontinuation by mixed breast and bottle feeding (especially venlafaxine and paroxetine, short t1/2 Psychotic illness Psychosis - incidence • Myth: pregnancy protects against relapse • Risk of post partum psychosis 0.1 – 0.25% but in BPAD 50% • In month after delivery relative risk of psychosis is 20x • Risk of recurrence of postpartum psychosis 50-90%: assume it will happen! Psychosis - treatment • Typical antipsychotics − minimal teratogenic risk − possible link between limb defects and haloperidol − neonatal dyskinesia reported − neonatal jaundice reported • Recommended typical antipsychotics 1. Chlorpromazine 2. Trifluoperazine 3. Haloperidol sedation/constipation Psychosis - treatment • Atypical antipsychotics − foetal exposure olanzapine > risperidone > quetiapine − most data for olanzapine low birth weight macrosmia gestational diabetes (increased birth weight!) few congenital malformations hip dysplasia, meningocele, anjyloblepharon and neural tube defects (? due to obesity) Psychosis - treatment • Atypical antipsychotics − risperidone/quetiapine, no evidence of teratogenicity − clozapine, no increased risk of malformations but: gestational diabetes neonatal seizures NICE recommend switch (but often on clozapine due to treatment resistence!) Psychosis - treatment • Recommended atypical antipsychotics 1. Olanzapine 2. Clozapine gestational diabetes • NICE states avoid depot and anticholinergics • Discontinuation syndrome: − − crying, agitation mixed bottle/breast feeding reduces severity Bipolar illness Bipolar affective disorder • Relapse rates high (2x) if medication discontinued during pregnancy • Post-partum relapse rates 8x in first month • Consider effects of relapse on foetus, obstetric outcomes and child development BPAD - treatment • Lithium ‒ Ebstein’s anomaly relative risk 10-20x (but incidence relatively low, 1 in 1000) ‒ Displacement of tricuspid valve towards apex of right ventricle ‒ Also ASD and VSD ‒ Highest risk is 2-6 weeks (often before pregnancy known) ‒ High resolution USS and echo at 6/52 and 18/52 BPAD - treatment • Lithium (continued) ‒ Crosses placenta, avoid if possible ‒ Consider gradual discontinuation before conception but 70% relapse post-partum ‒ Be aware of 3rd trimester pharmacokinetics total body water, so dose required But on delivery, dose required immediately Monthly serum lithium levels throughout Delivery in hospital ‒ goitre, hypotonia, lethargy and arrhythmias can occur BPAD - treatment • Carbamazapine and valproate ‒ Associated with neonatal malformations ‒ Spina bifida: Valproate 1-2%, Carbamazepine 0.5-1% (baseline 0.1%) ‒ Total malformations: Valproate 7.2% Carbamazepine 2.3% ‒ Dose-related, so lowest dose possible if essential ‒ Folate prescription pre-conception BPAD - treatment • Lamotrigine ‒ Low risk of malformations ‒ cleft palate ‒ Not recommended by NICE BPAD - treatment • Recommendations 1. If long period without relapse, consider switch or stop for at least 1st trimester 2. Abrupt discontinuation risk of relapse 3. Severe illness/high relpase risk, continue medication after discussion of risks 4. No mood stabiliser is safe but avoid valproate and combination therapy 5. NICE recommends considering atypical antipsychotic 6. Acute mania, use atypical antipsychotic or ECT 7. Acute depression: CBT if moderate, SSRI if severe Anxiety and insomnia Anxiety and insomnia • Anxiety disorders use CBT, insomnia use sleep hygiene advice where possible • Benzodiazepines: ‒ 1st trimester use oral clefts, pylorostenosis ‒ 3rd trimester use floppy baby syndrome ‒ Associated with low birth weight • Promethazine: ‒ Doesn’t appear teratogenic • NICE recommends low dose chlorpromazine or amitriptyline Breastfeeding and medication Breast feeding – drug choice • Benefits of breast feeding vs exposure • Little data on long term effects • Premature babies may be more vulnerable due to renal/hepatic/cardiac impairment • Close monitoring of baby for side effects, feeding, growth and development • Prioritise treatment of maternal illness • Low dose, monotherapy, timing of feeds/expressing Breastfeeding - antidepressants • Paroxetine excreted in milk but low/undetectable levels in newborn • Sertraline also excreted in milk but low levels, no known adverse effects Breastfeeding - antipsychotics • Sulpiride: low excretion in breast milk, may increase lactation, no adverse effects • Olanzapine: low-undetectable levels in breast milk • Avoid clozapine if possible (neutropenia and seizures) Breastfeeding – mood stabilisers • Antipsychotic e.g. Olanzapine • Valproate if contraception used • Not carbamazepine (hepatic problems), lamotrigine (rashes) or lithium (levels in newborn) Breastfeeding - sedatives • Benzodiazepines ‒ Anxiety: lorazepam (short t1/2). Avoid long t1/2 due to CNS depression/apnoea in newborn ‒ Insomnia: zolpidem Summary 1. Expect relapses in those with history and plan accordingly 2. Use lowest effective doses of low teratogenicity medications in pregnancy if relapse risk outweighs potential harm to the foetus 3. If breast feeding, consider effects on newborn of medication vs relapse risk 4. If in doubt, consult your local perinatal psychiatry lead (In CPFT this is Dr Fiona Blake) Learning objectives - recap • To be able to describe the most important perinatal psychiatric conditions • To list treatment principles during pregnancy and breastfeeding • To be able to state malformation rates for commonly used psychotropics • To state the recommended medications during pregnancy and breast-feeding for psychosis, depression, BPAD, anxiety and insomnia