Psychotropic Medications and...
Transcript of Psychotropic Medications and...
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Psychotropic Medications and Pregnancy
Renee M Bruno, MD (beginning shortly)
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Psychotropic Medications and Pregnancy
Renee M Bruno, MD
Medical Director, Selected Psychiatric Services Woman’s Hospital
Clinical Professor of Psychiatry & Behavioral Sciences, Tulane School of Medicine
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“Decisions about what constitutes reasonable risk during pregnancy requires shared responsibility but ultimately rests with the informed patient.” • Informed choices
• Close psychiatric follow up
• Coordinated care with OB
Cohen, Nonacs Mood and Anxiety Disorders in Pregnancy and Postpartum 2005; 24:54
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Outline • Background & Context
• Planning
• Guidelines (ACOG, APA)
• Effects of maternal illness
• Medications – Major Depression- antidepressants – Bipolar illness- mood stabilizers,
antipsychotics – Schizophrenia- antipsychotics – Anxiety Disorders-benzodiazepines
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Facts • Antidepressant discontinuation in pregnancy, relapse
common (75% in first trimester)
• Antenatal anxiety complicates depression
• Postpartum Mood and Anxiety disorders, intense and require aggressive treatment
• Bipolar Disorder may first present as Postpartum Psychosis
• Postpartum Psychosis is a Psychiatric Emergency
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Maximize maternal & fetal wellbeing while minimizing exposure to: • Medications • Maternal illness • Environmental toxins
Shared goal
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Planning
• Symptom free for 6 months minimum
• Slow taper 25% q 1-2 weeks
• Mild
• Moderate to severe
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Treatment Planning • Self care
• Vitamins
• Planned contraception, conception
• Planned delivery
• Breast feeding intent
• Illness history
• Medication risk; risk of untreated illness
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Bipolar Meds and Oral Contraceptives (OCP)
Carbamazepine > 1200mg
Oxcarbazepine > 1200mg
Topiramate > 200mg
Induce cytochrome P40 enzymes = ineffective OCP’s
OCP’s can decrease Lamotrigine levels
Am J Psychiatry 2004; 161: 608-620
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Folic Acid for ALL
• Antidepressants: Folic acid 1 mg daily
• Other (anticonvulsants) : Folic acid 2-4 mg daily
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Decision making
• Has the baby already been exposed?
• Has the medication been optimized?
• What trimester is she?
• What works?
• Will she breastfeed?
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Conundrums
• No decision is risk-free
• No psychotropic drugs approved for use during pregnancy
• Childbearing women & research studies
• Emphasis on error of commission rather than omission
• Risks more heavily weighted than benefits
• FDA labeling system inadequate
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Safety Ratings FDA Categories A no risk
B no evidence risk
C risk cannot be ruled
out
D positive evidence of
risk
X contraindicated
FDA Proposal Fetal Risk Summary
Clinical Considerations
Data
Breastfeeding section
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Resources • Developmental and Reproductive Toxicity: www.toxnet.nim.nih.gov
(DART database NLM)
• Organization of Teratology Information Specialists (OTI’s): www.otispregnancy.org (866)-626-OTIS
• Yonkers, Wisner et al (2009): The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians & Gynecologists. Obstetrics & Gynecology 114: 703-713
• MGH Center for Women’s Mental Health: www.womensmentalhealth.org
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Good Practice • Be familiar with risks of meds AND risks of
maternal illness
• Be familiar with guidelines
• Document
• Communicate
• Collaborate, refer
• Include spouse/support
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Guidelines for Antidepressant Use During Pregnancy
• Nonpharmacologic treatments ineffective • History of serious decompensation when antidepressants
discontinued • Suicidal ideation, past attempts • Psychosis • History of serious disabling depression during previous pregnancy • Inability to follow prenatal instructions (weight loss, missed visits) • Serious lapses in judgment • Severe and disabling anxiety • Family history; perinatal depression, suicide
Burt V Woman’s Health in Psych 2006; Vol. 2 No 5: 7 - 14
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ACOG Guidelines 1. Single medication in a higher dose favored over multiple
medications
2. Changing medications increases exposure
3. Selection of medication prior exposure during pregnancy
available reproductive safety data
history of effectiveness
higher protein binding = less placental passage
4. Abrupt discontinuation discouraged
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Untreated Perinatal Depression • Poor prenatal care • Cigarette/alcohol/drug abuse • Preeclampsia • Shorter gestation, motor maturity lower, cortisol higher • Lower birth weight • Suicide • Shorter periods of breastfeeding • More abusive • impaired attachment • Cognitive behavioral disturbances in children Orr ST et al. Pediatric and Perinatal Epidemiology 2000;14: 309-313
Young EA et al Biol Psychiatry 2006;60:831-836
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Stress/Anxiety in Pregnancy
• Spontaneous abortions
• Premature or prolonged labor
• Preterm delivery
• Fetal distress
• Forceps deliveries
Orr ST et al Psychosom Med 2007; 69 (6): 566 - 570
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Schizophrenia in Pregnancy • Placental abnormalities
• Antenatal hemorrhage
• Fetal distress/death
• LBW ≤ 10%
• Congenital anomalies 6%
• Feticide (delusional content)
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Risk Categories
• Pregnancy loss, miscarriage
• Major birth defects (@ 3% in general population)
• Growth effects, timing of delivery
• Neonatal syndrome
• Neurobehavioral effects, impact on development
These domains are impacted by BOTH psychiatric disorders AND antidepressants.
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Perinatal Antidepressant Use SSRI’s
• No loss, miscarriage
• Low birth weight
• Shorter gestation
• Paroxetine D
• PPHN */Autism
• NAS **
• No Neurobehavioral sequelae
TCA’s • No loss, miscarriage
• No major malformations
• + anticholinergic effects
• Nortriptyline favored in pregnancy
• No Neurobehavioral sequelae
* Persistent Pulmonary Hypertension
** Neonatal Adaptability Syndrome
Altshuler L et al Am J Psychiatry 1996; 153: 592- 606
Chambers et al N Eng J Medicine 2006; 354: 579-587
Bengt et al Pharmacoepid 2008; 17 (8): 801- 806
www.womansmentalhealth.org/newsletter/archives March 2008
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Prospective Studies Antidepressants and Major Malformations
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Antidepressants
• SSRI’s : Fluoxetine, citalopram, sertraline (escitalopram)
• TCA’s : nortriptyline, desipramine
• Buproprion
• Mirtazipine
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All Psychotropics Cross Placenta N=303 umbilical/maternal plasma
SSRI’s ESC > FLV > CIT@FLU > PAR@SER Lexapro Luvox Celexa Prozac Paxil Zoloft
TCA’s Nort > Clom Pamelor Anafranil
Other Ven ↑ > Bupr Effexor XR Wellbutrin
All are present in Amniotic Fluid
Case reports amniotic fluid/maternal serum
Ven>, Par,Ser < Kim J Br J Pharmacol 2006;61(2)15-163 Hendrick V et al Am J Psychiatry 2003;160:993-996
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Psychotropic medications and Breastfeeding
• All meds enter human breast milk
• Measuring serum blood levels in breast fed infants not recommended
• Meds with fewer metabolites favorable
• Shorter T ½ (half life) favorable
• Newborns ability to clear metabolically
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Lactation Safety Classification and Resources
American Academy of Pediatrics
Thomas Hale Medications and Mother’s Milk Laleche
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Bipolar Disorder in Pregnancy Treatment Planning
• Prepregnancy gradual discontinuation (gauge relapse)
• Resumption clinical judgment
• Benzodiazepines
• Risk of Postpartum Psychosis
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Bipolar Illness History
• Prior response to meds
• Illness severity
• Time to relapse after discontinuation
• Time to recovery when reintroduced
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Bipolar I
• Lithium responsive , no Li during pregnancy and well, protective until last 5 weeks
• Postpartum Psychosis risk
• Lithium Prophylaxis prior to delivery ( 36 weeks no later than 48 hrs postpartum)
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Psychiatric Hospitalization For Women During Postpartum Years
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Pharmacotherapy for Bipolar Disorder
• Mood stabilizers are essential • If patient wishes to avoid 1st trim Li, typical
antipsychotics preferred. May use benzos prn, Lorazepam preferred
• Additional medications OFTEN needed even with prophylaxis both during and after pregnancy
• ECT with medications • SLEEP and support may attenuate mood swings
Yonkers, 2004
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Antiepileptic Drugs (AEDS) Valproate
Carbamazepine Can breastfeed with infant monitoring
Gabapentin
Topiramate
Lithium
Lamotrigine
Neural tube defects major and minor malformations
Minimal data
Preferred over AEDS
Holds Promise
Oral clefts
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Bipolar treatment in pregnancy • Yonkers (psychosis)
If infant already exposed to atypical, patient tolerating and derives benefit continuing is preferable rather than switching to a typical which may not be beneficial ,patient may not tolerate or derive benefit and then you have exposed the fetus to two drugs
• Cohen
In severe bipolar, Lithium alone or in combination with an antipsychotic may be a safe alternative to valproate. For Lithium nonresponders consider lamotrigine monotherapy or treatment with lamotrigine and typical antipsychotic.
Inadequate response to typicals consider atypical antipsychotic monotherapy or atypical with Lithium or lamotrigine
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Clinical Considerations Perinatal Lithium Use
1. Gradual taper prior to conception
2. Taper before conception; reinstitute after organogenesis
3. Continue through gestation; counsel
4. Fetal assessment with fetal echocardiography
Viguera A et al Am J Psychiatry 2007; 164 : 342-345
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Lithium Use in Pregnancy
• Teratogenicity / Exposure
Ebstein’s Anomaly 1:1000
Fetal Goiter
Lethargy
Floppy baby syndrome
• Neurobehavioral Sequelae
None known Warner JP J Psychopharmacol 2000; 14: 77 – 80
Cohen et al JAMA 1994; 271: 146 – 50
Shoum Actapsychiatr Scand 1976; 54: 193 - 7
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Lithium Use in Pregnancy Late Exposure
1. Complete placental passage
2. Higher concentrations at delivery → ↑ adverse perinatal outcomes
3. Brief withholding (24 – 48hrs) prior to delivery does not compromise therapeutic outcome
Newport et al Am J Psychiatry 2005; 162: 2162-2170
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Perinatal use of Lamotrigine 1. Lamotrigine (Lamictal) inhibits folate formation
2. Potential maintenance therapy in pregnancy
3. Midline facial clefts (doses > 200)
4. Pregnancy increases clearance > 50%
5. Plasma concentration increases first 2 wks postpartum
6. Infants with slow elimination
7. Breastfeeding ??? Dolk H et al Neurology 2008 Sept vol 77
Tran T et al Neurology 2002 July 23; 59 (2): 251 – 5
Tennis P Epilepsia 2002 Oct; 43 (10): 1161 – 7
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Antipsychotics • FDA warning (2011) EPS, Neuromotor performance
(2012), Developmental effects (2013), Gestational Diabetes, SGA, head circumference (2012)
• First generation, typicals, high potency over low potency favored: Haloperidol, perphenazine, trifluoperazine
• Second Generation, atypicals, older drugs more data favored: Olanzapine, quetiapine
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Atypical Antipsychotics in Pregnancy Olanzapine, Risperidone, Quetiapine, Clozapine
N=151 + registries
No increase in rate of major malformations, spontaneous abortions or birth weight
Ziprasidone, Aripiprazole no data
Quetiapine
Least likely to elevate Prolactin and less placental passage
www.womansmentalhealth.org
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Placental Passage Antipsychotics
0
10
20
30
40
50
60
70
80
Olanz Haloper Risperi Quetia
Placental PassageUmbilical / MaternalPlasma
Newport et al Am J Psychiatry 2007; 164: 1214 - 1220
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• Not recommended due to minimal data • If a woman chooses to breastfeed Avoid polypharmacy Use lowest possible dose Monitor infant for side effects Coordinate with pediatrician
Antipsychotics in Breastfeeding Guidelines
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Perinatal Anxiety Disorders GAD, Panic Premature delivery
Preeclampsia
Postpartum panic within 12 wks
OCD SCARY; intrusive thoughts & images
of harm, sexual abuse, suicide
39% new onset in pregnancy
PTSD Chronic, multiple traumas, infertility,
pregnancy loss, birth trauma
Cohen L et al Biol Psych 1996; 39 (11): 950 – 954
Abramowitz J Anxiety Dis 2003; 17: 461 – 478
Loveland et al Obstet and Gynecol 2004; 103 (4): 710 - 714
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Benzodiazepines in Pregnancy Category D = Bad Wrap
C-Section
Induction of Labor
Premature Labor
Anxiety Disorders
Surgery
Placental Abruption
• Studies > 30 years – no increased risk of major malformations
• Case-control studies – increased risk for cleft palate (Diazepam)
• Occasional neonatal withdrawal symptoms minimized by slow tapering
• Long term studies show no adverse effects
• Very useful in pregnancy, postpartum, lactation
Lorazepam
Dolovich LR et al BMJ 1998; 317: 839 - 843
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Nontraditional Treatments • Light Therapy
• Massage
• Acupuncture
• Omega 3 fatty acids
• Mindfulness Based Stress Reduction
• Exercise
• Nutrition / Sleep
• rTMS
• Religiosity / Spirituality
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Questions Renee M. Bruno, MD, Presenter
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