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SUITABLE FOR PSYCHIATRISTS ,OBSETRICIANS AND OTHE HEALTH CARE PROVIDERS
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WALID SARHAN F.R.C.Psych
A -Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.
.
US FDA pregnancy drug labeling categories
B Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.OrAnimal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester
C Animal studies have shown an adverse
effect and there are no adequate and well-controlled studies in pregnant women.OrNo animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.
D Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.
X Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant.
Antidepressant medications SSRIs
Fluoxetine (Prozac)Sertraline (Zoloft)-solotikParoxetine (seroxat)Fluvoxamine (faverin)Citalopram (Cipram)Escitalopram (cipralex)-purlex
SNRIsVenlafaxine (Effexor)Duloxetine (Cymbalta)Desvenlafaxine (Pristiq)
Antidepressant medications Other
Wellbutrin (Bupropion)○ Norepinephrine and dopamine
TrazodoneMirtazapine (Remeron)
Tricyclic AntidepressantsAmitriptyline (tryptizol)Nortriptyline (nortrilene)Imipramine (Tofranil)Clomipramine (Anafranil)
MAOIsPhenylzine (Nardil)Tranylcypromine (Parnate)
Medication Choice
An individual decision that’s made on a case
by case basis!
Medication choices Pre-conception taper Stop medications entirely Stop and restart if symptoms Stop and restart after 1st trimester Continue through pregnancy Decrease dose Reduce or discontinue in late
pregnancy Transition to psychotherapy
General guidelines
Treat a woman as if she could become pregnant at any time…Up to 80% of pregnancies are unanticipatedDocument use of birth controlEncourage use of folic acid and multivitamin
FDA labels
Patients read them They will change They will be changing
Standard information on background ratesFetal risk dataClinical considerationsRegistry information
FDA Classifications Most psychotropics are C None are A No antidepressants are FDA approved for
pregnancyNo drug is “safe”No good randomized, placebo-
controlled studiesMost studies are retrospective, case
reports, and registry data
FDA categories of Antidepressants in Pregnancy as of 9/24/10
Medication Pregnancy Category Lactation Risk
Fluoxetine C Safety Unknown
Paroxetine D Safe
Sertraline C Safe
Citalopram C Safety Unknown
Escitalopram C Safety Unknown
Bupropion C Possibly Unsafe
Venlafaxine C Safety Unknown
Nortriptyline D Probably Safe
Amitriptyline C Probably Safe
Mirtazapine C Safety Unknown
Trazodone C Probably Safe
Pregnancy factors that may increase medication concentrations Reduced gastrointestinal motility
Absorption changes for some medicationsReduced fecal elimination
Serum proteins lowerMay result in higher ‘free’ drug concentrations
Pregnancy factors that may decrease medication concentration
Total blood volume increases 30 – 40%2nd and 3rd trimesters extravascular volume
increases○ Results in lower plasma levels of meds
Increased kidney plasma flow 30%GFR increased by 50%
○ Renal excreted drugs have faster elimination
Pregnancy factors that may decrease medication concentration
Nausea and vomitingReduced absorption
Increased liver metabolismMay result in increased elimination of certain
medications
Antidepressant Blood Levels and Pregnancy
Prepregnancy Conception 20 weeks Delivery Postpartum
Adapted from Sit et al 2008
What should we be concerned about?
1. Organ malformation (teratogenicity)○ Miscarriage is worst outcome of this
2. Neonatal Adaptation○ Physical and behavioral symptoms noted
shortly after birth Related to drug use near time of birth Limited duration
3. Long term behavioral abnormalities
Medication Background
Incidence of major birth defects in US is 2 to 4%65 – 70% of unknown cause2 – 4% medication related
Period of maximum vulnerability for birth defects of the nervous system is 14 – 35 days post conception
Medication Background
Women usually find out when already 5-7 weeks gestation
Therefore, may want to keep same medication if it’s working
Antidepressants During Pregnancy
SSRI complicationsCongenital anomaliesPersistent Pulmonary Hypertension of
the NewbornNeonatal adaptation syndrome
SSRIs DURING PREGNANCY AND RISK OF PERSISTENT PULMONARY HYPERTENSION IN THE NEWBORN: population based cohort study from the five Norodic countries
The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold .
The increase risk seems to be a class effect
BMJ .2011JAN 12,:d8012.doi:10.1136/bmj
Paroxetine Has FDA warning against using in first
trimester due to increased risk of cardiac defects
Neonatal Adaptation Syndrome
Cohort study (n = 120), included venlafaxineNeonatal abstinence syndrome
occurs in 30% of neonates exposed to SRIs in utero
Monitor for 48 hours after birth
Levinson-Castiel R (2006) Arch Pediatr Adolesc Med 160: 173-176.
Neonatal Adaptation Syndrome
Tremors Increased muscle tone Feeding difficulties Irritability Respiratory problems Increased reflexes Increased crying Sleep changes Seizures
Moses-Kolko EL et al (2005) JAMA 293: 2372-2382Moses-Kolko EL et al (2005) JAMA 293: 2372-2382
SSRIs and Persistent Pulmonary Hypertension N = 377 women with PPHN infants N = 836 matched controls
Blinded nurses interviews N = 14 PPHN infants exposed to SSRI
after 20 weeks gestation (n = 6 for controls)OR = 6.1 (95% CI: 2.2-16.8)
Use of SSRI before 20 weeks or use of non-SSRI at any time during pregnancynot associated with PPHN
Risk increases from 2/1000 to 6/1000
Chambers CD et al (2006). NEJM 354;6: 579-587.
SSRI Long Term Effects
Prospective cohort studyTCA (n = 46), FLX (n = 40), No MDD (n =
36) Children’s IQ, language, development,
temperament assessed and compared○ Ages 15 -71 months
No differences between groupsIQ negatively associated with duration of
depressionLanguage negative associated with # MDD
episodes after delivery
Nulman et al (2002) AJP 159: 1889-1895.
Tricyclics in pregnancy
The studies are conflicting Fetal tachycardia?
One case report Neonatal symptoms
TachypneaTachycardiaCyanosisIrritabilityHypertoniaClonusSpasm
ACOG 2007
Electroconvulsive Therapy Safe and effective treatment
70% of patients who have not responded to medications respond well to ECT
Effective for major depressive episode○ Especially with psychosis or melancholic
featuresEffective for manic episodeEffective for acute schizophrenia episode?
Non pharmacological treatments
Decrease caffeine, nicotine, alcohol Improve sleep Increase relaxation Psychotherapy
InterpersonalCognitive Behavioral
Support groups Education Marital counseling Decrease psychosocial stressors Communicate with obstetrical team
Breastfeeding Most medications excreted into breast milk
Amount infant receives is based on mother milk:plasma ratio and amount of breast milk received
Most important determinant of drug penetration is mother’s plasma levels
Drug levels in breastmilk are less than what crosses the placenta
Medications in breastfeeding Avoid long half life or sustained release
medications Schedule medication dosing
immediately after feeding or right before long rest period
Advise mother to monitor for oversedation, especially with cosleeping
Half Lives of AntidepressantsFluoxetine 2-3 days
Citalopram 34 hours
Escitalopram 30 hours
Sertraline 29 hours
Paroxetine 24 hours
Bupropion 12 hours
Duloxetine 12 hours
Venlafaxine 5 hours (metabolite = 11 hours)
Mood Stabilizer Medications Lithium (Lithobid) Valproic Acid (Valproate, Depakote,
Depakene) Carbamazepine (Tegretol, Equitro) Lamotrigine (Lamictal) Topiramate (Topamax) Atypical antipsychotics
Risperidone (Risperdal)Olanzapine (Zyprexa)Quetiapine (Seroquel)Ziprasidone (Geodon)Aripiprazole (Abilify)
Lithium and Breastfeeding Breast Feeding
Breast milk [Li] = 30-100% mother serum [Li]Cyanosis, muscle tone, T-wave changes
Not a good idea
Anticonvulsants
All studies done in women receiving anticonvulsants for epilepsyNone in women with primary psychiatric
disorderWomen with epilepsy bear more children
with malformations○ 3.5 %
Morrow J et al (2006) J Neurol Neurosurg Psychiatry 77: 193-198.
Valproic Acid
Intrauterine growth retardation Developmental delay Neonatal toxicity
HR decelerationsWithdrawal symptoms
○ Irritability, feeding problems, abnormal toneLiver toxicityHypoglycemia
Yonkers 2004
Valproic Acid
Increased glucoronidation in pregnancyLower VPA levels
In lactationBreast milk / infants
○ < 1% - 10% concentration○ Thrombocytopenic purpura○ Anemia○ Generally felt to be reasonable
Yonkers 2004, Gentile 2006
Carbamazepine in Breastfeeding “Probably safe” Possible effects
Transient cholestatic hepatitishyperbilirubinemia
Lamotrigine in Pregnancy N = 14 pregnant women
LTG monotherapyLTG metabolism increases during
pregnancy○ % in relative clearance (dose in mg/weight in
kg/serum conc in mg/L)1st trimester = 118% higher2nd trimester = 171% higher3rd trimester = 208% higherPostpartum = 4% higher
Pennell et al. Neurology; 62: 292-295, 2004
Benzodiazepines
Behavioral effectsImpaired learning and memory, absence of
startle reflexes, other sustained/subtle behavior
Data is conflicting
Benzodiazepines and PregnancyGenerally, if must use BZs in pregnancy,
stick with ones that are short acting and don’t have metabolites, e.g. lorazepam
NEROLEPTICS
Typical neuroleptics: Haldol ,clopixol atypical neuroleptics: Risperidone,
Olanzapine ,Seroquel Careful in choice in pregnancy and
lactation for the side effects. Sedation with Seroquel. Weight gain with olanzapine. Risperidone could be a good choice in
pregnancy and lactation.
Take Home Points Depression in pregnancy is common Untreated depression in pregnancy carries
risks for both the mother and the child No antidepressants are FDA approved in
pregnancyBut sertraline is generally agreed to be “safest”
Must weigh risks and benefits with the mother (and partner) on an individual basis
Take Home Points
SSRIs may be associated with septal defects, PPHN, and a neonatal syndrome.
SSRIs are “safe” in breastfeedingSertraline and paroxetine probably safest
ECT is safe with pregnancy and breastfeeding
Take Home Points
Lithium is moderately safe in pregnancy?? but not with breastfeeding
Carbamazapine and Valproic Acid are not safe in pregnancy but moderately safe with breastfeeding
Lamotrigine and the atypical antipsychotics seem to be relatively safe in pregnancy but need more data
Benzodiazepines are associated with clefting
Resources
www. Motherisk.org http://www.womensmentalhealth.org http://www.emorywomensprogram.org www.postpartumprogress.typepad.com Yonkers et al, 2009 APA and ACOG
Consensus Statement, General Hospital Psychiatry and Obstetrics and Gynecology
THANK YOU
www.walidsarhan.net
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