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WALID SARHAN F.R.C.Psych
US FDA pregnancy drug    labeling categoriesA -Adequate, well-controlled studies in pregnantwomen have not shown an increa...
B Animal studies have revealed no evidence ofharm to the fetus; however, there are no adequateand well-controlled studies ...
C Animal studies have shown an adverseeffect andthere are no adequate and well-controlledstudies in pregnant women.OrNo an...
D Adequate well-controlled or observational studiesin pregnant women have demonstrated a risk to thefetus. However, the be...
X Adequate well-controlled or observational studiesin animals or pregnant women have demonstratedpositive evidence of feta...
Antidepressant medications   SSRIs       Fluoxetine (Prozac)       Sertraline (Zoloft)-solotik       Paroxetine (serox...
Antidepressant medications   Other     Wellbutrin (Bupropion)        ○ Norepinephrine and dopamine     Trazodone     M...
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 ...
General guidelines   Treat a woman as if she could become    pregnant at any time…     Up to 80% of pregnancies are unan...
FDA labels Patients read them They will change They will be changing     Standard information on background rates    ...
FDA Classifications Most psychotropics are C None are A No antidepressants are FDA approved for  pregnancy   No drug i...
FDA categories of Antidepressants in Pregnancy as of9/24/10      Medication     Pregnancy Category          Lactation Risk...
Pregnancy factors that may increasemedication concentrations   Reduced gastrointestinal motility     Absorption changes ...
Pregnancy factors that may decreasemedication concentration      Total blood volume increases 30 – 40%        2nd and 3r...
Pregnancy factors that may decreasemedication concentration   Nausea and vomiting     Reduced absorption   Increased li...
Antidepressant Blood Levels and PregnancyPrepregnancy   Conception      20 weeks   Delivery   Postpartum Adapted from Sit ...
What should we be concerned about?  1. Organ malformation (teratogenicity)      ○   Miscarriage is worst outcome of this  ...
Medication Background   Incidence of major birth defects in US is    2 to 4%     65 – 70% of unknown cause     2 – 4% m...
Medication Background Women usually find out when already  5-7 weeks gestation Therefore, may want to keep same  medicat...
Antidepressants During Pregnancy SSRI   complications   Congenital anomalies   Persistent Pulmonary Hypertension of    ...
SSRIs DURING PREGNANCY AND RISK OFPERSISTENT PULMONARY HYPERTENSION INTHE NEWBORN: population based cohort studyfrom the f...
Paroxetine   Has FDA warning against using in first    trimester due to increased risk of cardiac    defects
Neonatal AdaptationSyndrome Cohort  study (n = 120), included   venlafaxine     Neonatal abstinence syndrome      occurs...
Neonatal Adaptation Syndrome   Tremors   Increased muscle tone   Feeding difficulties   Irritability   Respiratory pr...
SSRIs and Persistent PulmonaryHypertension   N = 377 women with PPHN infants   N = 836 matched controls     Blinded nur...
SSRI Long Term Effects    Prospective cohort study      TCA (n = 46), FLX (n = 40), No MDD (n =      36)    Children’s ...
Tricyclics in pregnancy   The studies are conflicting   Fetal tachycardia?     One case report   Neonatal symptoms    ...
Electroconvulsive Therapy   Safe and effective treatment     70% of patients who have not responded to      medications ...
Non pharmacologicaltreatments  Decrease caffeine, nicotine, alcohol  Improve sleep  Increase relaxation  Psychotherapy...
Breastfeeding   Most medications excreted into breast milk     Amount infant receives is based on mother      milk:plasm...
Medications inbreastfeeding Avoid long half life or sustained release  medications Schedule medication dosing  immediate...
Half Lives ofAntidepressantsFluoxetine     2-3 daysCitalopram     34 hoursEscitalopram   30 hoursSertraline     29 hoursPa...
Mood StabilizerMedications   Lithium (Lithobid)   Valproic Acid (Valproate, Depakote,    Depakene)   Carbamazepine (Teg...
Anticonvulsants – SummaryDrug          FDA   Fetal Risk SummaryLithium       D     Ebstein’s anomaly, “floppy baby” syndro...
Lithium andBreastfeeding   Breast Feeding     Breast milk [Li] = 30-100% mother serum [Li]     Cyanosis, ⇓ muscle tone,...
Anticonvulsants   All studies done in women receiving    anticonvulsants for epilepsy     None in women with primary psy...
Valproic Acid Intrauterine growth retardation Developmental delay Neonatal toxicity     HR decelerations     Withdraw...
Valproic Acid   Increased glucoronidation in pregnancy     Lower VPA levels   In lactation     Breast milk / infants  ...
Carbamazepine inBreastfeeding “Probably safe” Possible effects     Transient cholestatic hepatitis     hyperbilirubine...
Lamotrigine inPregnancy   N = 14 pregnant women     LTG monotherapy     LTG metabolism increases during     pregnancy  ...
Antipsychotics in PregnancyDrug             FDA Fetal risk summaryHaldol           CChlorpromazine   CAripiprazole     COl...
Benzodiazepines   Behavioral effects     Impaired learning and memory, absence of      startle reflexes, other sustained...
BZD and PregnancyDrug         FDA   Fetal risk summaryAlprazolam   D     Reports are conflicting. Cleft plate risk increas...
Benzodiazepines andPregnancyGenerally, if must use BZs in pregnancy, stick with ones that are short acting and don’t have ...
NEROLEPTICS Typical neuroleptics: Haldol ,clopixol atypical neuroleptics: Risperidone,  Olanzapine ,Seroquel Careful in...
Take Home Points   Depression in pregnancy is common   Untreated depression in pregnancy carries    risks for both the m...
Take Home Points SSRIs may be associated with septal  defects, PPHN, and a neonatal  syndrome. SSRIs are “safe” in breas...
Take Home Points   Lithium is moderately safe in pregnancy??    but not with breastfeeding   Carbamazapine and Valproic ...
Resources www. Motherisk.org http://www.womensmentalhealth.org http://www.emorywomensprogram.org www.postpartumprogres...
THANK YOU   www.walidsarhan.net
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Drugs in pregnancy&lactation

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  • (and eventually you may need to up the dose) Can alternative allow us to avoid med or use lower dose?
  • Why should you know this…your patients will read it..the good news? The FDA is going to change its labelling to include registry information, standard information on background rates
  • Paxil- OR 2.08 for congenital malformations – VSD – retrospective 3581 Swedish registry study – 4 % paxil major congenital anom vs 2 % with other AD 6.1 OR for PPH
  • Women get constipated, morning sickness
  • To appreciate some of the data that I’ll share on anti D in pg, some background info…
  • A couple of those helpful hints… It will be around for a while…though metabolism does change during pregnancy…
  • Transcript of "Drugs in pregnancy&lactation"

    1. 1. WALID SARHAN F.R.C.Psych
    2. 2. US FDA pregnancy drug labeling categoriesA -Adequate, well-controlled studies in pregnantwomen have not shown an increased risk of fetalabnormalities to the fetus in any trimester ofpregnancy..
    3. 3. B Animal studies have revealed no evidence ofharm to the fetus; however, there are no adequateand well-controlled studies in pregnant women.OrAnimal studies have shown an adverse effect, butadequate and well-controlled studies in pregnantwomen have failed to demonstrate a risk to the fetusin any trimester
    4. 4. C Animal studies have shown an adverseeffect andthere are no adequate and well-controlledstudies in pregnant women.OrNo animal studies have been conducted andthere are no adequate and well-controlledstudies in pregnant women.
    5. 5. D Adequate well-controlled or observational studiesin pregnant women have demonstrated a risk to thefetus. However, the benefits of therapy mayoutweigh the potential risk. For example, the drugmay be acceptable if needed in a life-threateningsituation or serious disease for which safer drugscannot be used or are ineffective.
    6. 6. X Adequate well-controlled or observational studiesin animals or pregnant women have demonstratedpositive evidence of fetal abnormalities or risks. Theuse of the product is contraindicated in women whoare or may become pregnant.
    7. 7. Antidepressant medications SSRIs  Fluoxetine (Prozac)  Sertraline (Zoloft)-solotik  Paroxetine (seroxat)  Fluvoxamine (faverin)  Citalopram (Cipram)  Escitalopram (cipralex)-purlex SNRIs  Venlafaxine (Effexor)  Duloxetine (Cymbalta)  Desvenlafaxine (Pristiq)
    8. 8. Antidepressant medications Other  Wellbutrin (Bupropion) ○ Norepinephrine and dopamine  Trazodone  Mirtazapine (Remeron) Tricyclic Antidepressants  Amitriptyline (tryptizol)  Nortriptyline (nortrilene)  Imipramine (Tofranil)  Clomipramine (Anafranil) MAOIs  Phenylzine (Nardil)  Tranylcypromine (Parnate)
    9. 9. Medication Choice An individual decision that’s made on a case by case basis!
    10. 10. 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
    11. 11. General guidelines Treat a woman as if she could become pregnant at any time…  Up to 80% of pregnancies are unanticipated  Document use of birth control  Encourage use of folic acid and multivitamin
    12. 12. FDA labels Patients read them They will change They will be changing  Standard information on background rates  Fetal risk data  Clinical considerations  Registry information
    13. 13. FDA Classifications Most psychotropics are C None are A No antidepressants are FDA approved for pregnancy  No drug is “safe”  No good randomized, placebo- controlled studies  Most studies are retrospective, case reports, and registry data
    14. 14. FDA categories of Antidepressants in Pregnancy as of9/24/10 Medication Pregnancy Category Lactation RiskFluoxetine C Safety UnknownParoxetine D SafeSertraline C SafeCitalopram C Safety UnknownEscitalopram C Safety UnknownBupropion C Possibly UnsafeVenlafaxine C Safety UnknownNortriptyline D Probably SafeAmitriptyline C Probably SafeMirtazapine C Safety UnknownTrazodone C Probably Safe
    15. 15. Pregnancy factors that may increasemedication concentrations Reduced gastrointestinal motility  Absorption changes for some medications  Reduced fecal elimination Serum proteins lower  May result in higher ‘free’ drug concentrations
    16. 16. Pregnancy factors that may decreasemedication 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
    17. 17. Pregnancy factors that may decreasemedication concentration Nausea and vomiting  Reduced absorption Increased liver metabolism  May result in increased elimination of certain medications
    18. 18. Antidepressant Blood Levels and PregnancyPrepregnancy Conception 20 weeks Delivery Postpartum Adapted from Sit et al 2008
    19. 19. 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 A Long term behavioral abnormalities
    20. 20. Medication Background Incidence of major birth defects in US is 2 to 4%  65 – 70% of unknown cause  2 – 4% medication related Period of maximum vulnerability for birth defects of the nervous system is 14 – 35 days post conception
    21. 21. Medication Background Women usually find out when already 5-7 weeks gestation Therefore, may want to keep same medication if it’s working
    22. 22. Antidepressants During Pregnancy SSRI complications  Congenital anomalies  Persistent Pulmonary Hypertension of the Newborn  Neonatal adaptation syndrome
    23. 23. SSRIs DURING PREGNANCY AND RISK OFPERSISTENT PULMONARY HYPERTENSION INTHE NEWBORN: population based cohort studyfrom 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
    24. 24. Paroxetine Has FDA warning against using in first trimester due to increased risk of cardiac defects
    25. 25. Neonatal AdaptationSyndrome Cohort study (n = 120), included venlafaxine  Neonatal abstinence syndrome occurs in 30% of neonates exposed to SRIs in utero  Monitor for 48 hours after birthLevinson-Castiel R (2006) Arch Pediatr Adolesc Med 160:173-176.
    26. 26. Neonatal Adaptation Syndrome Tremors Increased muscle tone Feeding difficulties Irritability Respiratory problems Increased reflexes Increased crying Sleep changes SeizuresMoses-Kolko EL et al (2005) JAMA 293: 2372-2382
    27. 27. SSRIs and Persistent PulmonaryHypertension 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 pregnancy  not associated with PPHN Risk increases from 2/1000 to 6/1000 Chambers CD et al (2006). NEJM 354;6: 579-587.
    28. 28. SSRI Long Term Effects  Prospective cohort study  TCA (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 groups  IQ negatively associated with duration of depression  Language negative associated with # MDD episodes after delivery Nulman et al (2002) AJP 159: 1889-1895.
    29. 29. Tricyclics in pregnancy The studies are conflicting Fetal tachycardia?  One case report Neonatal symptoms  Tachypnea  Tachycardia  Cyanosis  Irritability  Hypertonia  Clonus  Spasm ACOG 2007
    30. 30. 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 features  Effective for manic episode  Effective for acute schizophrenia episode?
    31. 31. Non pharmacologicaltreatments  Decrease caffeine, nicotine, alcohol  Improve sleep  Increase relaxation  Psychotherapy  Interpersonal  Cognitive Behavioral  Support groups  Education  Marital counseling  Decrease psychosocial stressors  Communicate with obstetrical team
    32. 32. 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
    33. 33. Medications inbreastfeeding 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
    34. 34. Half Lives ofAntidepressantsFluoxetine 2-3 daysCitalopram 34 hoursEscitalopram 30 hoursSertraline 29 hoursParoxetine 24 hoursBupropion 12 hoursDuloxetine 12 hoursVenlafaxine 5 hours (metabolite = 11 hours)
    35. 35. Mood StabilizerMedications 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)
    36. 36. Anticonvulsants – SummaryDrug FDA Fetal Risk SummaryLithium D Ebstein’s anomaly, “floppy baby” syndrome reportedCBZ D FHS, NTD, neurodevelopment effects?VPA D Major and minor congenital abnormalities, intrauterine growth retardation, hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, neural tube defects (day 17 – 30)Topiramate CLamotrigine C Unsafe with breastfeedingGabapentin C 4 reports of normal pregnancy, 1 report of respiratory distress
    37. 37. Lithium andBreastfeeding Breast Feeding  Breast milk [Li] = 30-100% mother serum [Li]  Cyanosis, ⇓ muscle tone, T-wave changes Not a good idea
    38. 38. Anticonvulsants All studies done in women receiving anticonvulsants for epilepsy  None in women with primary psychiatric disorder  Women with epilepsy bear more children with malformations ○ 3.5 % Morrow J et al (2006) J Neurol Neurosurg Psychiatry 77: 193-198.
    39. 39. Valproic Acid Intrauterine growth retardation Developmental delay Neonatal toxicity  HR decelerations  Withdrawal symptoms ○ Irritability, feeding problems, abnormal tone  Liver toxicity  Hypoglycemia Yonkers 2004
    40. 40. Valproic Acid Increased glucoronidation in pregnancy  Lower VPA levels In lactation  Breast milk / infants ○ < 1% - 10% concentration ○ Thrombocytopenic purpura ○ Anemia ○ Generally felt to be reasonable Yonkers 2004, Gentile 2006
    41. 41. Carbamazepine inBreastfeeding “Probably safe” Possible effects  Transient cholestatic hepatitis  hyperbilirubinemia
    42. 42. Lamotrigine inPregnancy N = 14 pregnant women  LTG monotherapy  LTG metabolism increases during pregnancy ○ % in relative clearance (dose in mg/weight in kg/serum conc in mg/L)  1st trimester = 118% higher  2nd trimester = 171% higher  3rd trimester = 208% higher  Postpartum = 4% higher Pennell et al. Neurology; 62: 292-295, 2004
    43. 43. Antipsychotics in PregnancyDrug FDA Fetal risk summaryHaldol CChlorpromazine CAripiprazole COlanzapine CSeroquel CRisperidone CClozapine BZELDOX C
    44. 44. Benzodiazepines Behavioral effects  Impaired learning and memory, absence of startle reflexes, other sustained/subtle behavior  Data is conflicting
    45. 45. BZD and PregnancyDrug FDA Fetal risk summaryAlprazolam D Reports are conflicting. Cleft plate risk increased to 7/1000. Withdrawal after in utero exposure reported (crying/restlessness)Clonazepam D Little data on teratogenicity. Newborn toxicity noted (apnea, cyanosis, lethargy, and hypotonia).Diazepam D Accumulates in fetus 1-3x mother. T1/2 prolonged. Increased risk of cleft palate. Floppy infant syndrome and withdrawal possibility.Triazolam X Little data available, but similar to other BDZ.
    46. 46. Benzodiazepines andPregnancyGenerally, if must use BZs in pregnancy, stick with ones that are short acting and don’t have metabolites, e.g. lorazepam
    47. 47. 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.
    48. 48. 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 pregnancy  But sertraline is generally agreed to be “safest” Must weigh risks and benefits with the mother (and partner) on an individual basis
    49. 49. Take Home Points SSRIs may be associated with septal defects, PPHN, and a neonatal syndrome. SSRIs are “safe” in breastfeeding  Sertraline and paroxetine probably safest ECT is safe with pregnancy and breastfeeding
    50. 50. 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
    51. 51. 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
    52. 52. THANK YOU www.walidsarhan.net
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