PERINATAL MOOD DISORDERS: Update on Psychotropic Prescribing
www. mainepsych. org Postpartum Depression Project
Disclosures and Thanks Disclosures: I do not have any conflicts of interest that may have any direct bearing on this CME presentation. I wish to thank Lee Cohen, M. D. Director of the Perinatal Psychiatry Clinical Research Program at MGH, for lending me the slides of some of the graphics in this presentation
DEPRESSION DURING PREGNANCY • Between 10 -20% of women will experience significant depression during pregnancy • This will be a first episode for one third
Course of Depression During Pregnancy Women from 3 specialty centers stable on antidepressants for at least 3 months prior to pregnancy : • 43% relapsed • 26% who continued meds relapsed (50% in first trimester) • 68% who discontinued meds relapsed (50 % In the 1 st trimester, 90% by the end of the 2 nd trimester) Cohen LS, et al. JAMA. 2006: 295; 499 -507.
Time to Relapse in Patients Who Maintained or Discontinued Antidepressant Percentage of Patients Remaining Well 1 0. 9 0. 8 0. 7 Maintained (N = 82) 0. 6 0. 5 0. 4 Discontinued (N = 65) 0. 3 0. 2 0. 1 0 0 12 24 Gestational Age Cohen LS, et al. JAMA. 2006: 295; 499 -507. 36
CONCLUSIONS: • Pregnancy puts women with a history of depression at higher risk of recurrence and is not protective. • Pregnant women stable on antidepressants need to be aware of the relapse risk with stopping meds • This should be discussed when weighing the risk/benefit ratio of using antidepressants during pregnancy Cohen LS, et al. JAMA. 2006: 295; 499 -507.
Relapse of Bipolar Disorder During Pregnancy • 89 women with BPD stable at least 1 month prior to conception, 62 continued treatment, 27 discontinued (treatment was mood stabilizer =/- antidepressant and/or antipsychotic) • 71% had at least one mood episode ( usually depressed) --47% of episodes occurred in the 1 st trimester --85. 5 % of those who discontinued treatment --37% of those who continued treatment • Those who discontinued spent 40% of their pregnancy in an illness state; those who continued only 8. 8% Viguera, et al , Am J Psychiatry, 2008
Relapse of Bipolar Disorder During Pregnancy Presented at NCDEU, Viguera et al, June 2006 Viguera, et al , Am J Psychiatry, 2008
RISKS OF UNTREATED DEPRESSION DURING PREGNANCY • Neonatal risks (low birth weight and small for gestational age infants • Obstetrical risks (higher rates of miscarriage, preterm labor, placental abruption, preeclampsia • Irritable babies (with high cortisol levels) • Lack of adequate prenatal care • Higher use of alcohol and drugs • SUBSEQUENT POSTPARTUM DEPRESSION • SUBSEQUENT RECURRENT EPISODES OF DEPRESSION • SUICIDE
GUIDELINES FOR TREATMENT OF DEPRESSION DURING PREGNANCY • Assess the overall risks through evaluation of the patient’s history, current risk factors and current presentation • For mild to moderate depression try non-pharmacologic intervention • Have an open discussion of the risks and benefits of treatment with medication • Consider the risks of inadequately treated depression
• For women who are stable on antidepressants who wish to discontinue antidepressants, inform them of the risks and monitor closely. Intervene early at signs of recurrence • When the decision is made to use medication, select medications with the best established safety profile. • Medication decisions should be guided by the patient’s history of prior medication treatment
• If a woman is already on an SSRI antidepressant that is working well, continue her on that one; pregnancy is not a time to change antidepressant s and risk relapse and exposure to two drugs. • TCA’s are safe, with nortriptyline being preferred • Use an adequate dosage, this often increases during the pregnancy because of the increase in blood volume • Consider ECT for severely depressed or psychotic women –it is safe and very effective
Regardless of circumstances, a woman with suicidal or psychotic symptoms should immediately see a mental health specialist for treatment.
APA/ACOG Guidelines “The Management of Depression During Pregnancy: A Report from the American Psychiatric Association and The American College of Obstetricians and Gynecologists, ” Obstetrics & Gynecology (September 2009) and General Hospital Psychiatry (September/October 2009).
FDA LABELING • FDA Category labeling is often misunderstood and interpreted to mean that the risk increases from A to B to C, etc That is NOT the case. • No distinction is made between human and animal data • Often is not updated • New FDA labeling will be released in 2013 and will eliminate the categories. • Pregnancy and lactation subsections would have three components: a risk summary, clinical considerations and a data section.
SSRI Use during Pregnancy • Recent findings and more data inform the pharmacologic treatment of depression during pregnancy – Consistent conclusions that the absolute risk of SSRI exposure in pregnancy is small 1 -3 – Recent case-control studies reveal inconsistent data regarding teratogenic risk of individual SSRIs 4 -9 • Reproductive safety data on SSRIs exceed what is known about most other medicines used in pregnancy Louik C, et al. N Engl J Med 2007; 2 Einarson TR, Einarson A. Pharmacoepidemiol Drug Saf 2005; 3 Einarson A, et al. Am J Psychiatry 2008; 4 Alwan S, et al. N Engl J Med 2007; 5 Greene MF. N Engl J Med 2007; 6 Hallberg P, Sjoblom V. J Clin Psychopharmacol 2005; 7 Wogelius P, et al. Epidemiology 2006; 8 www. gsk. ca/english/docs-pdf/PAXIL_Pregnancy. DHCPL_E-V 4. pdf Dear Healthcare Professional (3/17/08); 9 www. fda. gov/medwatch/safety/2005/Paxil_dearhcp_letter. pdf Dear Healthcare Professional (3/17/08) 1 17
Antidepressant Drug Treatment During Pregnancy • SSRI’s most commonly used • Largest sample size exists for Prozac and it is first line • Then Celexa/Lexapro, then Zoloft and TCA’s (favored are nortriptyline and desiprimine) • Accumulating safety data for Wellbutrin and Effexor
Non-SSRI’s During Pregnancy • More limited reproductive safety data available for SNRI’s compared to SSRI’s, i. e. . venlafaxine, duloxetine • Data on bupropion includes growing number of exposures supporting absence of increased risk for malformation Buproprion registry over 500 Retrospective analysis of 1200 exposed infants Prospective study of 105 infants http: //www. gsk. com/media/paroxetine/ingenix_study. pdf Chun-Fai-Chan B, Koren G, et al. Am J Obstet Gynecol, March 2005. 192(3). 19 Cole JA, Modell JG, Haight BR, et al Pharmacoepidemiol Drug Saf. 9 August 2006
Evidence for Increased Risk of Cardiac Malformations Following Paroxetine Exposure? • Some Epidemiologic data suggesting increased relative risk (1. 5) associated with first trimester exposure to paroxetine (VSD, ASD) • Absolute risk of 1/50 vs. background risk of 1/100 • Resulted in labeling change from category C to D • Recent data from global teratogen monitoring programs do no not support increased risks of overall cardiac malformations . Wogelius P, et al. Epidemiology. 2006; 17: 701 -704. Lennestål R, Källén. J Clin Psychopharmacol. 2007; 27: 607 -613. Cohen LS, Nonacs R. http: //www. womensmentalhealth. org/information/newsletter_2. 3. html. Accessed March 17, 2008. Einarson A, et al. Am J Psychiatry. 2008 Apr 1 [Epub ahead of print].
“Poor Neonatal Adaptation” and SSRI Use During Pregnancy • Consistent data: Late trimester exposure to SSRIs is associated with transient irritability, agitation, jitteriness, and tachypnea • Studies do not control for maternal mental health condition, blinding of exposure in neonatal assessments • Effectiveness of discontinuing or lowering the dose late in pregnancy aimed at reducing the risk of neonatal toxicity has not been prospectively studied
“Poor Neonatal Adaptation” and SSRI Use During Pregnancy • No correlation between measures of umbilical cord blood levels of SSRIS and the risk if developing neonatal symptoms • No difference in symptoms between two groups compared : infants born to mothers who had taken SSRIS but tapered 2 weeks prior to delivery vs. those who continued • Lowering the dose of antidepressants does, however, increase the risk for maternal postpartum depression Levinson-Castiel R, et al. Arch Pediatr Adolesc Med. 2006; 160: 173 -176. Chambers CD, et al. N Engl J Med. 2006; 354: 579 -587. Sit, D, et al. Pre-publication communication Warburton et al, Acta Psychiatr Scand 2010; 121(6): 471 -9.
Risk for PPHN Associated With Late Trimester Exposure to SSRI Inconsistent Findings: • One report showed increased risk by 6 -fold (Chambers 2006) (with this highest estimate of 6 -fold increase 1% of exposed infants would be affected) • Lower association seen with Källén and Olausson, 2008 • NO association seen by Andrade. et al. , 2009 Limitations: • Small number of SSRI exposures • Recall bias with respect to early versus late SSRI exposure • Recent data suggests lower risk than Chambers et al • PPHN correlated with cesarean section, race, body mass index, and other factors not related to SSRI use** ** Hernández-Díaz S, et al. Pediatrics. 2007; 120: e 272 -e 282. Kallen , August 2008 ; Pharmacoepidemiol Drug Safety Chambers CD, et al. N Engl J Med. 2006; 354: 579 -587. Hernández-Díaz S, et al. Pediatrics. 2007; 120: e 272 -e 282 23
SSRI Use vs. Untreated Depression • Both continuous untreated depression and continuous SSRI use associated with 20% increase risk preterm birth • Women taking SSRIs vs. those with psych histories vs. controls: those taking SSRI had higher risk of preterm birth (by only 5 days) • Depression, SSRI exposure and stopping SSRIs during pregnancy have been associated with increased spontaneous abortions Wisner at al Arch Pediatr Adolesc Med. 2009; 163: 949– 954. Lund N, Pedersen LH, Henriksen TB. Arch Pediatr Adolesc Med. 2009; 163: 949– 954. Rahimi R, Nikfar S, Abdollah M. Reprod Toxicol. 2006; 22: 571– 575. Hemels ME, Einarson A, Koren G, Lanctôt KL, Einarson TR. Ann Pharmacother. 2005; 39: 803– 809. Gavin AR, Chae DH, Mustillo S, Kiefe CI. J Womens Health (Larchmt). 2009; 18: 803– 811. Einerson et al, pre publication communication, Marce’ Sociaty Annual meeting, 2010
Zolpidem (Ambien) in Pregnancy • Evaluated 10, 343 women prescribed zolpidem • Included if prescribed for > 30 days in pregnancy • Excluded women with prior mental disorders, diabetes, hypertension coronary artery disease • Extracted 2497 zolpidem exposed and compared to matched control group of 12, 485 • Zolpidem exposed had higher rates of LBW, PTD, SGA , highest in those receiving Zolpidem > 90 days • No increase in fetal malformations • Recommend using alternatives to Ambien for insomnia during pregnancy
LONGTERM NEUROBEHAVIORAL EFFECTS • Two studies demonstrating absence of neurobehavioral differences with TCAs versus fluoxetine in exposed vs nonexposed children • Children ages 1 1/2 to 6 years exposed to antidepressants (Prozac or TCAs) in utero had similar IQ’s language development, behavioral development, temperament, mood, as those not exposed • No difference between those exposed during just the first trimester or throughout the pregnancy However, depression in the mother was associated with lower cognitive and language achievement Nulman I, et al. N Engl J Med. 1997; 336: 258 -262. Nulman I, et al. Am J Psychiatry. 2002; 159: 1889 -1895. Oberlander TF, et al. J Clin Psychiatry. 2004; 65: 230 -237. Oberlander TF, et al. Arch Pediatr Adolesc Med. 2007; 161: 22 -29. Misri S, et al. Am J Psychiatry. 2006; 163
Pharmacologic Treatment of Pregnant Women with Bipolar Disorder: Considering the Risks • Commonly used antimanic agents are either known teratogens or limited available reproductive safety data • Risks of untreated psychiatric illness • Risk of discontinuing maintenance psychotropic medications Cohen LS, et al. JAMA. 1994; 271: 146 -150. Steer RA, et al. J Clin Epidemiol. 1992; 45: 1093 -1099; Orr ST, et al. Am J Prev Med. 1996; 12: 459 -466; Suppes T, et al. Arch Gen Psychiatry. 1991; 48: 1082 -1088; Faedda GL, et al. Arch Gen Psychiatry. 1993; 50: 448 -55; Baldessarini RJ, et al. Clin Psychiatry. 1996; 57: 441 -448. 27
Lithium and Teratogenicity • 1970 s Lithium Baby Registry—risk for specific cardiovascular malformation high; Ebstein’s anomaly • Revised risk based on meta-analysis: 1/1000 to 1/2000 (0. 05%) • Relative risk 10 to 20 times the rate in general population (1/20, 000) • Absolute risk vs relative risk: absolute risk is small Cohen LS, et al. JAMA. 1994; 271: 146 -150. 28
Pregnancy Registries for Anticonvulsants: and Teratogenic Risk • North American Antiepileptic Pregnancy Registry • Lamotrigine Pregnancy Registry • United Kingdom Epilepsy and Pregnancy Register • Central Registry of Antiepileptic Drugs and Pregnancy (EURAP) • Australian Pregnancy Registry Holmes LB, et al. Arch Neurol. 2004; 61: 673 -678. Meador KJ, et al. Neurology. 2006; 67: 407 -412.
Summary of Findings Across Pregnancy Registries • Valproic acid (VPA) is associated with the highest risk for all major malformations – Risk estimates around 10% and higher 1 – Risk appears to be dose-dependent (>1000 mg/d); may be with LTG 2, 3 – Folic acid supplementation may not be protective against VPAassociated neural tube defects • Risk is highest with anticonvulsant polytherapy, specifically with VPA 4, 5, • Carbamazepine (CBZ) and LTG are associated with lower risk than VPA 1. Wyszynski DF, et al. Neurology. 2005; 64: 961 -965. 2. Morrow J, et al. J Neurol Neurosurg Psychiatry. 2006; 77: 193 -198. 3. Cunnington M, et al. Epilepsia. 2007; 48: 1207 -1210. 4. Meador KJ, et al. Neurology. 2006; 67: 407 -412. 5. Holmes LB, et al. Arch Neurol. 2004; 61: 673 -678. 30
Should Depakote (Valproate) be used in Pregnancy (or women of child bearing age)? • Three year old children of 309 women who took anticonvulsants studied: Valproate exposed had IQ’s 9 points lower than lamotrigine exposed Data from several studies suggest VPA exposure is associated with increased risk for adverse cognitive and neurodevelopmental effects compared with other anticonvulsants • 1565 pregnancies in which infants were exposed to valproic acid with 118 malformations – 14 malformations were more common in infants exposed to valproic acid in the 1 st trimester.
Should Depakote (Valproate) be used in Pregnancy (or women of child bearing age)? – spina bifida, microcephaly, ventricular and atrial septal defects, tetralogy of Fallot, cleft palate, hypospadias, club foot and craniosynostosis • Use of valproic acid monotherapy in 37, 154 women was associated with significantly increased risks for 6 of the 14 malformations: Spina bifida, Atrial septal defect , Cleft palate , Hypospadias , Polydactyly , Craniosynostosis AMERICAN ACADEMY OF NEUROLOGISTS RECOMMENDS AGAINST THE USE OF VALPROATE IN PREGNANCY • • Kimford, JM et al, Cognitive function at 3 years of age after fetal exposure to antepileptic drugs, NEJM; 2009 , 360 (16) 1597 -1605 Jentink, J. New England Journal of Medicine, 2010; vol 362: pp 2185 -2193. Adab N, et al. J Neurol Neurosurg Psychiatry. 2004; 75: 1575 -1583. Adab N, et al. J Neurol Neurosurg Psychiatry. 2001; 70: 15 -21. Vinten J, et al. Neurology. 2005; 64: 949 -954. Gaily E, et al. Neurology. 2004; 62: 28 -32
Lamotrigine (Lamictal) Monotherapy Exposure: Increased Risk for Oral Clefts • Overall risk for major malformations with lamotrigine approximately 2. 7% across several studies; no significant difference from the general population • North American Antiepileptic Pregnancy Registry showed an increased incidence of a specific malformation Oral clefts: 8. 9/1000 vs baseline 0. 37/1000 • Finding not found in the pooled analysis of 19 other registries • Absolute risk remains small Cunnington M, et al. Neurology March 22, 2005 64: 955 -960. Holmes LB, et al. Neurology 2008 70 (22 part 2) 2152 -8 Dolk, H et. ; Neurology 2008, 71 (10) 714 -22
Antipsychotic Use During Pregnancy Typical antipsychotics and teratogenic risk: Data support safety of typical antipsychotics with respect to teratogenicity Atypicals and teratogenic risk: • 151 subjects exposed to different atypicals-60 to olanzapine, 49 to risperidone, 36 to quetiapine, and 6 to clozapine-with non-exposed controls, major malformation rates were not significantly different between the two groups Altshuler LL, et al. Am J Psychiatry. 1996; 153: 592 -606 Yaeger D, et al. Am J Psychiatry. 2006; 163: 2064 -2070. . Mc. Kenna K, et al. J Clin psychiatry. 2005; 66: 444 -449. Kulkarni J, et al. Aust N Z J Psychiatry. 2008; 42: 38 -44 Newham, JJ et Br J Psych; 2008, 192(5) 333 -7 Mc. Kenna et al, J. Clin. Psychiatry 2005; 66: 444 -9
Antipsychotic Use During Pregnancy • Infants exposed to atypical antipsychotics are more likely to be large for gestational age Conclusions regarding reproductive safety of these agents are limited with currently available data, though no of teratogenicity is evident based on limited studies National Pregnancy Registry for Atypical Antipsychotics 1 -866 -961 -2388 Altshuler LL, et al. Am J Psychiatry. 1996; 153: 592 -606 Yaeger D, et al. Am J Psychiatry. 2006; 163: 2064 -2070. . Mc. Kenna K, et al. J Clin psychiatry. 2005; 66: 444 -449. Kulkarni J, et al. Aust N Z J Psychiatry. 2008; 42: 38 -44 Newham, JJ et Br J Psych; 2008, 192(5) 333 -7 Mc. Kenna et al, J. Clin. Psychiatry 2005; 66: 444 -9
Antipsychotic Use During Pregnancy New FDA Black Box warning: • All antipsychotics have been updated to have a black box warning about the use in pregnancy regarding abnormal movements (EPS) or withdrawal symptoms in infants exposed in the third trimester • Data from FDA adverse Event Reporting System • 69 cases of withdrawal or EPS with antipsychotics • Some resolved within hours without treatment; others required longer hospital stays
Antipsychotic Use During Pregnancy Pitfalls: • This data does not reveal anything about the incidence • Typical antipsychotics have been used during pregnancy since the 1950’s • FDA noted that these cases were confounded by other variables—other meds, other neonatal and obstetrical complications Bottom line: Be aware of the potential for adverse effects Balance the benefits and risks , especially that of relapse of a psychotic illness
Benzodiazepine Use during Pregnancy • Some evidence for a slight increase in oral clefts with first trimester exposure • Infants born to mothers taking high doses in late pregnancy may show signs of toxicity • Anxiety is a risk factor for preeclampsia, preterm labor, low birth weight, PPD; long term, behavioral, cognitive, developmental and medical problems in the exposed fetus
Treatment of Bipolar Disorder in Pregnancy Mild to moderate bipolar disorder: • Gradual taper and discontinuation of anti-manic prophylaxis (lithium, sodium valproate) prior to pregnancy can be considered • Reintroduce mood stabilizer as needed or during second trimester; except for sodium valproate given data for behavioral teratogenicity. Moderate to severe bipolar disorder: • Lithium may be the safest alternative for women dependent on mood stabilizers • For lithium nonresponders consider lamotrigine monotherapy • Consider lamotrigine and typical or atypical antipsychotic if lamotrigine monotherapy ineffective Cohen LS, J Clin Psychiatry 2007; 68 ( suppl 9).
ECT During Pregnancy l l Treatment of choice when urgent management is necessary or illness is life threatening Especially recommended in delusional depression, mania External fetal monitoring, ultrasonography increases safety Requires a comprehensive treatment team
Treatment of Mood Disorders during Pregnancy • Pregnancy is not protective with respect to new onset or recurrent mood disorders • Thoughtful consideration needs to be given to the risks of untreated psychiatric illness • Thoughtful treatment decisions can be made regarding the use of psychotropics during pregnancy • Weighing the relative risks of medication treatment should be done on an individualized case by case basis. • Maintaining euthymic mood during pregnancy is crucial • NO DECISION IS PERFECT; NO TREATMENT IS RISK FREE.
PPD as a Public Health Problem • Over 4 million women give birth in America • One of every 8 new mothers experience depression • Over half a million women will suffer postpartum depression each year • Most common complication of childbearing • Causes serious and lasting effects on child health and family functioning 1 Wisner K et al. N Engl J Med. 2002; 347: 194 -199; 2 Wisner K et al. J Clin Psychiatry. 2001; 62: 82 -86.
70 Epidemiology of Postpartum Episodes Admissions/Month 60 50 40 30 20 Pregnancy 10 0 – 2 Years – 1 Year Childbirth +1 Year +2 Years Kendell RE et al. Br J Psychiatry. 1987; 150: 662 -673.
Spectrum of Postpartum Mood Disorders Postpartum Psychosis(0. 10. 2%) Postpartum Depression(10 -15%) Postpartum Symptom Severity Postpartum Blues (50 -85%) None
Risks of Untreated PPD To mother: • Stressful impact on relationship with partner • Kindling phenomenon---development of a chronic low grade depression with more susceptibility to repeated episodes of MDD • Severe postpartum psychiatric disorder is associated with a high rate of death from natural and unnatural causes, particularly suicide • Suicide risk in the first postnatal year is increased 70 -fold
To child: Risks of Untreated PPD • Poor weight gain • Sleep problems • Less breastfeeding-depressed mothers more likely to discontinue breastfeeding • Impaired maternal health and safety practices • Disruption in the attuned infant-caregiver interactions which promote brain neurological “wiring”: – Future , hyperactivity, conduct disorders and school behavior problems – Delays in language and social development – Increased risk of depression – Maternal depression is an “Adverse childhood experience” ACE, often it is not the only adversity MATERNAL POST PARTUM MOOD IS ONE OF THE STRONGEST PREDICTORS OF NEUROCOGNITIVE DEVELOPMENT IN CHILDREN MEASURED UP TO AGE SIX
PRESENTATION OF PPD CLASSIC SYMPTOMS OF DEPRESSION WITH SOME FEATURES especially prominent with PPD: – Women are often unable to sleep even when given the opportunity to do so Anxiety symptoms are often a very prominent aspect of PPD – Frequently have intrusive, obsessional ruminations, or images, usually focused on the baby, often violent in nature, but they are egodystonic and there is not a problem with reality testing i. e. non-psychotic. One study showed 50% of women with PPD had these. Such obsessional thoughts do not increase the risk of harm to the baby and are important to distinguish from psychosis.
POST PARTUM PSYCHOSIS • Typical onset is within 2 weeks after delivery, first symptoms often within 48 -72 hours • Earliest signs are restlessness, irritability and insomnia • Often very labile in presentation • Often looks “organic” with a lot of confusion and disorientation • Most often consistent with mania or a mixed state
POST PARTUM PSYCHOSIS • Includes agitation, paranoia, delusions, disorganized thinking and impulsivity • Thoughts of harming the baby are frequently driven by delusions—Child must be saved from harm, child is malevolent, dangerous, has special powers, is Satan or God • Rates of infanticide associated with untreated postpartum psychosis have been estimated to be as high as 4% and of suicide as high as 5 %.
TREATMENT OF PPD Selection of treatment: • First requires good evaluation, review of prior history and assessment for suicidality/dangerousness • individual psychotherapy--CBT /IP Interpersonal and cognitive behavioral therapy very effective for mild to moderate PPD • support group • community support programs • Medication • ECT • hospitalization O'Hara MW, et al. Arch Gen Psych. 2000; 57: 1039 -1045. Stuart S, et al. J Psychother Pract Res. 1995; 4: 18 -29. Appleby L, et al. BMJ. 1997; 314: 932 -936.
Postpartum Depression: Pharmacologic Strategies • Data to support use of serotonergic agents (sertraline, fluoxetine, venlafaxine, fluvoxamine) and TCAs (nortriptyline) • Other antidepressants can also be effective • Adequate dosage need to be given • Adequate duration of treatment (>6 months) • TREAT ANXIETY: Adjunctive anxiolytic agents (lorazepam, clonazepam) are often needed Colombo, et al. 1999
Which Antidepressant is the Best ? The one that is most likely to be effective • Continue antidepressant used during pregnancy • Use agent to which patient has responded to in the past • All SSRIs are secreted into breast milk, but no serious adverse effects have been reported in association with this. There have been some anecdotal reports of mild adverse effects possibly associated with exposure to the drugs through breast milk • Caution may be needed with exposure in premature infants with hepatic immaturity
Use of SSRI’s During Lactation • Exposure for the infant is lowest for sertraline (Zoloft) and fluvoxamine (Luvox), somewhat higher for paroxetine (Paxil), highest with citalopram (Celexa) and fluoxetine (Prozac) • SSRI’s are present in the infant’s blood stream at very low levels, not detectable by usual methods. ACOG does not recommend checking infant serum levels. • With the current knowledge there is no strong evidence to recommend one drug over another or rationale to switch from one SSRI to another to promote safety during breastfeeding
Use of BZN’s/Hypnotics During Lactation • Data is somewhat limited • When measured, exposure through breast milk is extremely low • Some anecdotal reports of sedation, poor feeding, respiratory distress; pooled data show low incidence of adverse effects • Diazepam more likely to accumulate in breast feeding baby • Less likely to accumulate—lorazepam (Ativan) clonazepam (Klonopin) Birnbaum et al; Pediatrics, 1999, July 104 (1)e 11
Treatment of Postpartum Bipolar Disorder • PROTECT SLEEP! Sleep deprivation – similar to antidepressants regarding risk of induction of mania/hypomania (10%) • Despite theoretical risk of Stevens-Johnsons Syndrome with Lamictal, this has not been reported, Lamictal levels are significant in infant serum • Lithium is not generally recommended • Depakote and tegretol are approved for use during lactation by the AAP, but should be used with much caution
TREATMENT OF POSTPARTUM PSYCHOSIS • Psychiatric/obstetrical emergency • Treat as affective psychosis—i. e. as Bipolar disorder • Requires inpatient hospitalization • Medication treatment is necessary beginning with an antipsychotic/mood stabilizer such as Zyprexa, a traditional mood stabilizer like lithium or Lamictal, adjunctive bezodiazepines
TREATMENT OF POSTPARTUM PSYCHOSIS • ECT is very effective and rapid treatment • Then consider adding a mood stabilizer such as Lamictal or Lithium • As 70 -90% of women with a prior history of post partum psychosis relapse with subsequent pregnancies, prophylactic treatment either before delivery at 36 weeks or no later than 48 hours after delivery is recommended. Lithium has been best studied
Mood Stabilizers and Lactation • Lamictal present in breast milk at variable levels; infant serum levels 20 -50 % of maternal. Only one adverse event reported with daily maternal Lamictal dose of 850 mg. • Tegretol and Depakote are approved by the AAP for use in lactating infants. Need very close monitoring for drug levels and liver function • Lithium is excreted into breast milk at high levels – Breastfeeding generally avoided – Possible as monotherapy with close supervision at lowest possible dose with close clinical monitoring for signs of toxicity and checking Li levels, TSH, BUN, Cr Newport DJ, Pennell PB, Calamaras MR, et al. Pediatrics. 2008. 122(1): e 223 -e 231 Viguera AC, Newport DJ, Ritchie J et al. Am J Psychiatry. 2007: 164(2): 342 -345 Yonkers KA, Wisner KL, Stowe Z, et al. Am J Psychiatry. 2004: 161(4): 608 -620.
Antipsychotics and Lactation • Medium to high potency typical antipsychotics rarely have adverse effects • Thorazine associated with sedation and developmental delay • Clozapine may be concentrated in breast milk– requires infant blood monitoring • Atypicals: olanzapine, risperidone, and quetiapine– excretion into breast milk is low – adverse effects appear to be rare.
Effective treatment of maternal postpartum illness is an early intervention for a child
WEB RESOURCES • www. mainepsych. org MAPP’s website for the PPD Project • www. womensmentalhealth. org MGH Center for Women’s Mental Health • www. postpartum. net Postpartum Support International • www. mededppd. org NIMH supported website • Excellent resource, regularly updated • 9 educational modules aimed at different provider categories offering CME’s • www. motherisk. org Motherisk Program of Canada , clinical research and teaching program on drug and other exposure during pregnancy and lactation • www. marce
For more information or resources, or to get involved with the PPD project: Please contact me: P. Lynn Ouellette plopsymd@myfairpoint. net Subject line: MAPP PPD Project
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