Management of depression in pregnancy and the postpartum period

Educational Objectives

The goals of this program are to improve diagnosis and management of depression in pregnancy. After hearing and assimilating this program, the clinician will be better able to:

1. Weigh the arguments for and against treatment with antidepressants during pregnancy for patients with major depression.

2. Identify signs of suicidality and risk factors for postpartum psychosis.

3. Select the safest and most appropriate medications for patients with antepartum and postpartum psychiatric disorders.

Summary

Major depressive disorder (MDD): experienced by 1 in 5 people; most common perinatal disorder; ≈1 in 5 pregnant women meets criteria for MDD (depression severe enough to be disabling); another 70% meet criteria for depression not otherwise specified; diagnosis often missed; increases risk for postpartum depression

Pathophysiology: estrogen and progesterone target monoamine oxidase (MAO), which controls levels of serotonin, norepinephrine, and dopamine (govern sense of well-being); estrogen decreases MAO, which raises serotonin levels (improves mood); progesterone activates MAO with consequent lower serotonin (causes depressed mood); depression observed in patients on medroxyprogesterone acetate (Depo-Provera); 3-fold increase in symptoms and high risk for relapse observed when antidepressants stopped abruptly; psychiatric hospitalizations common during first postpartum year

Assessment: use Edinburgh Postnatal Depression Scale (EPDS) to assess perinatal and postpartum depression; sensitivity 86% and specificity 78%; test requires ≈1 min; score ≥10 requires evaluation or treatment; cultural background of patients may influence score; EPDS cannot detect comorbidities (eg, anxiety, personality disorders); assess psychiatric symptoms, history, past behavior, and ability to meet home and occupational responsibilities, including child care; infant may suffer if maternal needs not addressed; assess social support and availability of caregiver for child if mother needs hospitalization

Suicidality: relevant historical factors include frequency of psychiatric hospitalizations, overall stability, and suicide attempts or parasuicidal acts (eg, cutting); number of psychiatric medications used indicates refractoriness to treatment; patients commonly take 2 or 3 antidepressant medicines; current psychiatrist can assess stability

Antidepressants during pregnancy: arguments against — physical malformations; growth impairment; teratogenicity; neonatal toxicity; fetal death; perinatal issues; risks vary by drug; physical malformations multifactorial and influenced by genetic susceptibility, dose of drug, trimester, duration of use, and concomitant smoking; arguments in favor — long-term consequences of not treating illustrated by concept of intrauterine programming; in untreated mother, stress results in release of cortisol, which affects fetal hypothalamic-pituitary axis, DNA transcription, and protein synthesis; nutrition and other exposures influential, but cortisol primary factor; fetus under intrauterine stress (eg, untreated major depression in mother) at risk for cardiovascular disease, small for gestational age, chronic obstructive pulmonary disease, diabetes mellitus (DM), thyroid disease, fetal demise, admission to intensive care unit, low Apgar scores, and renal disease; Toronto Motherisk Program — followed normal and depressed mothers (through all trimesters) and their children; some mothers treated with antidepressive agents during pregnancy; children of mothers in treated group showed no effects on IQ, language, temperament, or behavior through 71 mo of age; duration and severity of depression in untreated mothers correlated with decreases in IQ of ≤30 points in child; lower childhood language scores correlate with severity of depression; early language development best predictor of academic success; uncontrolled depression presents greater developmental risk than antidepressants; longitudinal risk — study in low-birth-weight (LBW) children examined maternal risk factors for social stress during pregnancy (eg, teen pregnancy, physical abuse, drug abuse); more maternal risk factors increased odds of depression later in life after controlling for socioeconomic status and family history; LBW independently predicts outcomes; effects on functionality most pronounced in girls; LBW girls born to depressed women more likely to develop depression and give birth to LBW children; results in generational longitudinal risks; conclusion — stopping treatment or failing to treat more harmful than medication; choose best medication to minimize depression and fetal risk

Selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac) — well studied in pregnancy; no major malformations observed; increased spontaneous abortion and impaired growth noted with early use, but outcomes not confirmed in teratology registry; neonatal withdrawal (manifested by jitteriness, poor feeding, irritability, and difficulty sleeping) significant problem with all SSRIs; expect 7 to 10 days of symptoms with fluoxetine; paroxetine (eg, Paxil, Pexeva) — associated with cardiac defects (eg, right ventricular outflow tract obstruction, persistent pulmonary hypertension of newborn [PPHN]) more frequently than with other SSRIs; avoid paroxetine during pregnancy; citalopram (Celexa) — no difference noted in gestational age, fetal survival, or structural defects; Food and Drug Administration recommends maximum dose of 40 mg due to prolongation of QT interval; check electrocardiography and decrease dose in patients taking >40 mg; long-term dose >40 mg may be maintained after discussing risks and benefits with patient; sertraline (Zoloft) — delayed ossification observed in animal studies not found in birth registry or large cohort study; recommendation — sertraline and fluoxetine safest initial antidepressant choices

Controversies: gestational hypertension (HTN) — study finding higher incidence in SSRI-exposed patients flawed (patients had risk factors other than SSRI); data do not warrant warning patients; PPHN — study that found increased risk with third-trimester exposure did not control for specific drug; patients on paroxetine skewed results; rate of PPHN lower than in general population; no need to warn patients, but change medication for patients on paroxetine

Other antidepressants: tricyclics — not associated with anomalies; transient fetal anticholinergic toxicities include lethargy and constipation; has no effect on behavior of children up to 7 yr of age; nortriptyline and desipramine preferred because of fewer anticholinergic effects; venlafaxine (Effexor) — has no teratogenicity; similar to low-dose fluoxetine; has only serotonergic effects at doses <150 mg/day; duloxetine (Cymbalta) — few data; bupropion (Aplenzin, Budeprion, Wellbutrin) — use associated with malformation rate of 3.8%; transposition of great vessels (TGV) observed, but not clearly linked to drug; has activating effects in mother; associated with fetal agitation and irritability; useful in smokers; MAO inhibitors — avoid during pregnancy; outcomes include stillbirth, placental infarction, cleft palate, and agenesis of corpus callosum; trazodone and mirtazapine (Avanza, Remeron) — sedating and often used for sleep; neither drug clearly linked to defects; one case of Hirschsprung disease and one of TGV associated with trazodone; slight increase in preterm births seen with mirtazapine

Postpartum treatment: continue antidepressant; infant exposure less with breastfeeding than in utero

Postpartum “blues”: symptoms include mild dysphoria, tearfulness, and feeling overwhelmed; for symptoms lasting >2 wk, consider postpartum depression (PPD)

Postpartum depression: MDD linked to hormonal changes; PPD underrecognized and affects 1 in 10 women; risk factors include depression after previous pregnancy, family history of psychiatric illness, limited social support, domestic violence, and marital problems; affects bonding and attachment, feeding, bathing, and safety of child, emotional and language development, and attention and cognitive skills; American Journal of Psychiatry consensus panel statement — fetal risk from untreated PPD outweighs risks of short-term medication during breastfeeding; risk highest 1 to 3 mo postpartum; PPD associated with infanticide; diagnosis — rule out thyroid disease and anemia; assess severity of PPD and safety of infant; treatment — combine medications and therapy; same medications as during pregnancy; can use escitalopram (Lexapro), fluoxetine, or paroxetine during nursing; avoid doxepin (causes anticholinergic side effects of lethargy, constipation, and respiratory distress in infant)

Talk therapy: efficacy of interpersonal psychotherapy and cognitive behavioral therapy equal to that of medical therapy in mild to moderate disease; peer support improves EPDS scores and results in high patient satisfaction

Postpartum psychosis: psychiatric emergency with 4% risk for infanticide and 5% risk for suicide; occurs in 1 in 1000 births; usually due to bipolar disorder; schizophrenia less likely; risk factors include reduced sleep, psychiatric history, limited social support, and alcohol use; homicidal ideation greatest with perinatal symptom onset; onset abrupt, usually within 1 wk of birth; early behavioral signs — paranoia; shunning visitors; odd and unusual responses; auditory, tactile, and olfactory hallucinations; obtain psychiatric consultation and immediately separate mother from baby

Bipolar disorder: diagnosis — grandiosity or irritable mood; discrete manic and depressive episodes required for diagnosis, but any manic episode confirmatory; treatment — use monotherapy with safest effective mood stabilizer; carbamazepine (eg, Carbatrol, Equetro, Tegretol) — may lessen effectiveness of oral contraceptives; divalproex (Depakote) — may alter menstrual cycles; these drugs and lithium commonly used; maintain mood stabilizers during pregnancy; when changing medications, consider rapidity of mood shifts and length of maternal stability; divalproex — pregnancy risk factor D, with 6% to 13% risk for malformations; fetal valproate syndrome characterized by facial, skeletal, and limb anomalies, impaired IQ, and autism; carbamazepine — 2% to 5% risk for malformations, including neural tube, craniofacial, and cardiac defects (eg, TGV), absence of gallbladder or thyroid, and vitamin K deficiency; lithium (Li) — also risk factor D, but drug of choice for bipolar disorder in pregnancy; risk for malformations (eg, Ebstein anomaly, ventricular septal defect, aortic coarctation, and mitral atresia) 2.8%; management of Li — fetal birth complications due to fluid shifts (hydration important); check for fetal heart defects early with ultrasonography, follow Li levels, use minimal effective dose, check thyroid and renal function every 6 to 8 wk, use planned delivery, and suspend Li 48 to 72 hr before delivery; restart at previous dose; quetiapine (Seroquel) — risk factor C; does not cross placenta or into breast milk; associated with weight gain, diabetes, HTN, and large-for-gestational-age infants; lamotrigine (Lamictal) — risk factor C; second drug of choice for bipolar disease in pregnancy; rate of defects 3% (4.6% with polytherapy); has dose-dependent association with cleft lip and palate; use low dose

Anxiety: occurs in 50% to 60% of patients with depression; generalized anxiety disorder more common than panic attacks and hypochondriasis; assess using Generalized Anxiety Disorder 7 (GAD 7; available on internet); treatment — higher doses required for anxiety than for depression; for immediate relief, give propranolol (eg, Inderal, InnoPran), hydroxyzine, or benzodiazepines

Obsessive-compulsive disorder: obsessive thoughts and compulsive behaviors similar to postpartum psychosis, but with ego-dystonic thoughts (uncomfortable for patient); treat with high-dose SSRI

Electroconvulsive therapy: treatment of choice for severe depression or psychosis in pregnancy; has no effect on fetus; monitor fetus during administration; anesthetics and paralytics do not cross placenta

Readings

Agnafors S et al: Symptoms of depression postpartum and 12 years later-associations to child mental health at 12 years of age.

Matern Child Health J. 2012 Apr 1.[Epub ahead of print]; Amorim AR et al: Diet or exercise, or both, for weight reduction in women after childbirth. Cochrane Database Syst Rev. 2007;(3):CD005627; Barilla D et al: Postpartum follow-up: can psychosocial support reduce newborn readmissions? MCN Am J Matern Child Nurs. 2010;35:33-9; Bellamy L et al: Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773-9; Bergink V et al: Prevention of postpartum psychosis and mania in women at high risk. Am J Psychiatry. 2012 Mar 8.[Epub ahead of print]; Dennis CL and Allen K: Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression. Cochrane Database Syst Rev. 2008;(4):CD006795; Einarson A et al: Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study. Can J Psychiatry. 2009;54:242-6; Einarson A: Influence of the media on women taking antidepressants during pregnancy. J Clin Psychiatry. 2009;70:1313-4; Grace SL et al: The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health. 2003;6(4):263-74; Haga SM et al: A longitudinal study of postpartum depressive symptoms: multilevel growth curve analyses of emotion regulation strategies, breastfeeding self-efficacy, and social support. Arch Womens Ment Health. 2012 Mar 27.[Epub ahead of print]; Kingston D et al: Prenatal and postpartum maternal psychological distress and infant development: A systematic review. Child Psychiatry Hum Dev. 2012 Mar 10 [Epub ahead of print]; Koren G and Nordeng H: Antidepressant use during pregnancy: the benefit-risk ratio. Am J Obstet Gynecol. 2012 Feb 21 [Epub ahead of print]; Leeman LM and Rogers RG: Sex after childbirth: postpartum sexual function. Obstet Gynecol. 2012;119:647-55; Liberto TL: Screening for depression and help-seeking in postpartum women during well-baby pediatric visits: an integrated review. J Pediatr Health Care. 2012;26:109-17; Louik C et al: First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007;356:2675-83; Lu MC et al: Preconception care between pregnancies: the content of internatal care. Matern Child Health J. 2006;10(5 Suppl):S107-22; Nelson HD: Screening for domestic violence — bridging the evidence gaps. Lancet. 2004;364 Suppl 1:s22-3; Rahman A et al: Cognitive behaviour therapy-based intervention by community health workers for mothers with depression and their infants in rural Pakistan: a cluster-randomised controlled trial. Lancet. 2008;372(9642):902-9; Salim NR and Gualda DM: Sexuality in the puerperium: the experience of a group of women. Rev Esc Enferm USP. 2010;44:888-95; Toh S et al: Antidepressant use during pregnancy and the risk of preterm delivery and fetal growth restriction. J Clin Psychopharmacol. 2009;29:555-60; Toh S et al: Selective serotonin reuptake inhibitor use and risk of gestational hypertension. Am J Psychiatry. 2009;166:320-8; Viguera AC et al: Episodes of mood disorders in 2,252 pregnancies and postpartum periods. Am J Psychiatry. 2011;168:1179-85; Yonkers KA et al: Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obstet Gynecol. 2011;117:961-77.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Lang was recorded at Women’s Health Conference, held February 17, 2012, in Greenville, NC, and sponsored by East Carolina University Brody School of Medicine. 

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OB591101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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