Thorsness KR, Watson C, LaRusso EM. Perinatal anxiety: approach to diagnosis and management in the obstetric setting. Am J Obstet Gynecol. 2018 Oct;219(4):326-345. doi: 10.1016/j.ajog.2018.05.017. Epub 2018 May 24. Review. PubMed PMID: 29803818.
National Institute for Health and Care Excellence. Antenatal and postnatal mental health. Clinical management and service guidance. Updated edition. https://www.nice.org.uk/guidance/cg192. Published December 2014. Updated April 2018. Accessed October 22, 2019.
McAllister-Williams RH, Baldwin DS, Cantwell R, et al; endorsed by the British Association for Psychopharmacology. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 2017 May;31(5):519-552. doi: 10.1177/0269881117699361. Epub 2017 Apr 25. PubMed PMID: 28440103.
MacQueen GM, Frey BN, Ismail Z, et al; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Can J Psychiatry. 2016 Sep;61(9):588-603. doi: 10.1177/0706743716659276. Epub 2016 Aug 2. Review. Erratum in: Can J Psychiatry. 2017 May;62(5):356. PubMed PMID: 27486149; PubMed Central PMCID: PMC4994788.
Marchesi C, Ossola P, Amerio A, Daniel BD, Tonna M, De Panfilis C. Clinical management of perinatal anxiety disorders: A systematic review. J Affect Disord. 2016 Jan 15;190:543-550. doi: 10.1016/j.jad.2015.11.004. Epub 2015 Nov 4. Review. PubMed PMID: 26571104.
Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University, Antony MM, Bouchard S, Brunet A, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. doi: 10.1186/1471-244X-14-S1-S1. Epub 2014 Jul 2. Review. PubMed PMID: 25081580; PubMed Central PMCID: PMC4120194.
Pregnancy and the first year of the postpartum, commonly referred to as the perinatal period, are widely believed to be a time of bliss and joy. However, for many women the risk of depressive and/or anxiety disorders is elevated. These problems, if occur, are frequently not recognized or not managed appropriately. The lack of adequate treatment can increase the risk for obstetrical complications; negatively influence relationship with partners; impair maternal-infant attachment; result in poor breastfeeding outcomes; and result in behavioral, emotional, and cognitive problems in the offspring.
In this chapter we discuss the etiology of perinatal depressive and anxiety disorders as well as screening methods, outline recommended treatments, and discuss the consequences of untreated illness during this important period in life.
Epidemiology, Etiology, Clinical FeaturesTop
The prevalence of major depressive episodes during pregnancy has been estimated to vary between 4% to 13% and 6.5% to 16% during the first 3 months of the postpartum period.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1071-83. Review. PubMed PMID: 16260528. Gaynes BN, Gavin N, Meltzer-Brody S, et al. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ). 2005 Feb;(119):1-8. Review. PubMed PMID: 15760246; PubMed Central PMCID: PMC4780910. Marcus SM. Depression during pregnancy: rates, risks and consequences--Motherisk Update 2008. Can J Clin Pharmacol. 2009 Winter;16(1):e15-22. Epub 2009 Jan 22. Review. PubMed PMID: 19164843. Marchesi C, Ossola P, Amerio A, Daniel BD, Tonna M, De Panfilis C. Clinical management of perinatal anxiety disorders: A systematic review. J Affect Disord. 2016 Jan 15;190:543-550. doi: 10.1016/j.jad.2015.11.004. Epub 2015 Nov 4. Review. PubMed PMID: 26571104. Anxiety disorders are also very common during the perinatal period, with prevalence estimates ranging from 9% to 21% during pregnancy and 6% to 14% in the first 6 months postpartum. Of particular interest to women and clinicians is the fact that rates of generalized anxiety disorder and obsessive-compulsive disorder (OCD) are higher among pregnant and postpartum women relative to the general population.
Identifying a major depressive episode (symptoms: see Depressive Disorders) throughout pregnancy and the postpartum is complicated by the fact that physiologic changes commonly occurring during the perinatal period can produce physical complaints resembling somatic symptoms of a major depressive episode (eg, affecting appetite, weight, sleep, and energy). As a result, it is important to complement the use of screening instruments with a clinical interview and careful judgement. Of these instruments, the Edinburgh Postnatal Depression Scale (EPDS), which focuses more on the neurocognitive symptoms of depression (eg, low mood, anhedonia), has the most evidence to support its ability to reliably and accurately identify probable cases of perinatal depression. In general, a score ≥12 during pregnancy is suggestive of depression. A score ≥10 in the postpartum period has also been suggested to be consistent with an elevated risk of a depressive episode.
Significantly less evidence exists to support the widespread use of any specific screening instrument for perinatal anxiety. Some research has suggested that a score ≥6 on the anxiety subscale of the EPDS is suggestive of an anxiety disorder. The Generalized Anxiety Disorder-7 (GAD-7) (available at mdcalc.com) has been recommended as well, with a score ≥13 suggesting the presence of generalized anxiety disorder among perinatal women. The Perinatal Obsessive-Compulsive Scale (POCS) is a useful screening tool for perinatal OCD as it contains items that are specific to addressing obsessions and compulsions relating to the fetus/newborn baby. This is important given that perinatal OCD often presents with a distinctive clinical picture and course where obsessions and compulsions are focused on the fetus and/or newborn baby.
The severity of depressive and anxiety disorders is defined according to the fifth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
A complex interactive etiologic pathway involving psychosocial, clinical, and biologic factors contributes to the development of perinatal depressive and anxiety disorders.
Psychosocial risk factors for perinatal depression and anxiety include a lack of partner or social support, history of abuse (especially a history of childhood sexual abuse), domestic violence, unplanned or unwanted pregnancy, and experiencing adverse life events and/or high levels of perceived stress during pregnancy. Potent clinical risk factors include a past history of mental illness (most notably a mood or anxiety disorder), prepregnancy obesity, previous or current pregnancy complications, history of miscarriage, having an emergency caesarean section, chronic medical conditions (eg, diabetes mellitus or hypertension/heart disease), adolescence, and sleep deprivation.
In terms of biologic risk factors, genetics appears to play a role in the etiology of postpartum depression (PPD). A family history of PPD is higher among women who develop perinatal depression and women with PPD also report to have more than expected first-degree relatives with a major depressive disorder (MDD).
Major changes occur in the hypothalamic gonadal, adrenal, and thyroid axes as well as in the systems regulating prolactin and oxytocin throughout the perinatal period. However, for most of these hormones, it is not their absolute levels that are related to the development of perinatal anxiety or depression but rather the abrupt change seen in the hormonal milieu. Levels of estrogen and progesterone increase gradually during pregnancy with a rapid and abrupt drop to prepregnancy levels immediately in the postpartum period. It has been suggested that this rapid drop in these reproductive hormones contributes to the development of PPD. This notion is supported by the known interplay between reproductive hormones and neurotransmitters involved in mental health disorders (eg, serotonin and dopamine). Recent studies have shown that estrogen modulates changes in neurotransmitter systems which in turn may influence maternal sensitivity, behavior, and attitude in the postpartum. One notable exception is hypothyroidism, which can directly contribute to the development and presentation of a depressive disorder perinatally. Hypothyroidism often occurs in the setting of postpartum thyroiditis, a common complication affecting close to 5% of all women in the postpartum period.
Sleep is frequently disrupted during pregnancy as well as in the postpartum. Women experience dramatic changes in sleep patterns and quality throughout the perinatal period. This includes frequent awakenings, fewer hours of total sleep, reduced sleep efficiency, shorter rapid eye movement sleep latency, and circadian phase shifts, all of which may lead to changes in mood.
Treatment During Pregnancy
During pregnancy, women with depression and anxiety must make choices about treatment with psychotherapy and/or pharmacologic treatments in the absence of significant evidence and a complete lack of systematic studies comparing these interventions directly. Such decisions must take into account the risks associated with fetal exposure and those of untreated mental illness.
1. Mild to moderate MDD during pregnancy: Generally accepted first-line treatments for DSM-5–defined mild to moderate MDD during pregnancy include individual or group cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT) (definitions of MDD severity: see Depressive Disorders). In acknowledgement of the importance of the need for rapid treatment effects and risks associated with depressive symptoms during pregnancy, previously effective antidepressants for individual women may also be considered very early in treatment decision-making (assuming that women understand the risks and benefits and prefer it upon balancing these against the risks of other treatments and untreated depression). Since selective serotonin-reuptake inhibitors (SSRIs) are effective across the range of severity of MDD, despite a relative absence of randomized clinical trials during pregnancy sertraline, citalopram, and escitalopram are the top choices, given their effectiveness and relative lack of known teratogenic effects. However, these antidepressants should be considered second-line treatments, behind CBT and IPT.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). No experimental or directly comparative studies available. If patients are not able to tolerate antidepressant medications or are not willing to take them, referral to professionals able to deliver evidence-based psychotherapies is indicated. Before antidepressants are prescribed, bipolar disorder should be excluded by the clinician.
Based on the strength of evidence in the women’s general population, combination treatment with sertraline, citalopram, and escitalopram plus CBT or IPT are accepted as second-line treatments. The remainder of the SSRIs (except paroxetine) and newer antidepressants are generally viewed as third-line therapies, given relatively less reproductive data and more limited use in perinatal clinical practice. Tricyclic antidepressants (with the exception of clomipramine) are also considered third line, along with mindfulness-based, psychodynamic, and supportive psychotherapies, bright light therapy, transcranial magnetic stimulation, and complementary/alternative treatments (including structured exercise such as walking and depression-specific acupuncture).
Despite increased risks of cardiovascular malformations (see below), paroxetine and clomipramine can be used in pregnancy but should be reserved for cases with very strong indications (eg, previous good response, ongoing stability on the medication, preference after consideration of risks and benefits). Monoamine oxidase inhibitors (MAOIs) are not recommended during pregnancy given their propensity to interact with certain analgesic and anesthetic agents. Early consultation with an anesthetist is recommended if MAOIs are used.
2. Severe MDD during pregnancy: For severe major depressive episodes, sertraline, citalopram, and escitalopram, alone or in combination with CBT or IPT, should be considered as first-line treatments given their efficacy in nonperinatal populations. The remaining SSRIs (except paroxetine), newer antidepressants, and tricyclic antidepressants are generally considered second line. Electroconvulsive therapy (ECT) is recommended as third-line treatment given its superior effectiveness and relative safety and tolerability in pregnancy. Combination pharmacotherapy can also be considered, but since its use in pregnancy is limited to sparse case reports, very little is known about its short-term and long-term risks to the fetus (which are likely to be in excess of monotherapy) and it should be used only if absolutely necessary.
3. Anxiety during pregnancy: Although there is far less evidence examining the effectiveness of treatment options for anxiety disorders during pregnancy, it is generally recommended that the first-line treatment for DSM-5–defined mild to moderate anxiety disorders is either individual or group CBT. Pregnant women with mild anxiety may also benefit from low-intensity psychological therapies such as facilitated self-help. In the case of pregnant women exhibiting severe anxiety disorders or among those who are not responding to psychological interventions and require rapid relief of symptoms, SSRIs may be considered: sertraline, citalopram, and escitalopram. In general, benzodiazepines are not a widely considered treatment option for women who have a mild to moderate anxiety disorder during pregnancy. Pregnant women with a severe anxiety disorder and are not responding to the recommended SSRIs mentioned above may benefit from a short-term use of benzodiazepines. Among these medications, only lorazepam has been recommended for use in perinatal women. If the patient has a past history or current substance abuse/dependence disorder, a short-term use of a neuroleptic (eg, quetiapine) could be considered instead. However, the prescription of any medication for women in the perinatal period must be accompanied by a discussion of the benefits and drawbacks of treatment as well as the risks of untreated mental illness to the mother, fetus/infant, partner, and other children in the household.
4. Augmenting agents for depressive and anxiety disorders during pregnancy: Although very little research has been conducted with pregnant or lactating women, certain antipsychotics have been considered as augmenting agents for those with treatment-resistant depressive or anxiety disorders. Based on randomized controlled trials consisting of general population samples, aripiprazole, quetiapine, olanzapine, and risperidone seem to be effective as augmenting agents for depression. Furthermore, adding quetiapine or risperidone may also augment the effect of antidepressants among those with OCD. However, it is important to be cautious with these second-generation antipsychotics, as they may cause weight gain and increase the risk for metabolic complications (eg, gestational diabetes and/or obesity) during pregnancy. In addition, the use of these second-generation antipsychotics may also cause sedation and extrapyramidal symptoms in women. In general, clozapine should not be used during pregnancy, given that it can cross the placenta and possibly cause agranulocytosis in the fetus/newborn. Furthermore, gestational use of clozapine has also been associated with floppy infant syndrome (ie, signs of hypotonia) and seizures in the infant.
Research examining the risks associated with the use of psychotropic medications during pregnancy is limited by the fact that many variables that confound associations between medication exposure and offspring adverse effects (eg, maternal mental illness, substance misuse, poor prenatal care, maternal health problems) are not controlled for in observational studies of these links. As a result, in the absence of randomized controlled trials, the magnitude and nature of these risks are not completely understood.
1. Antidepressants during pregnancy: Among the evidence that does exist, there are suggestions that most antidepressant medications are not generally associated with an increased risk of major congenital malformations. A small increase in risk for cardiovascular malformations (odds ratio, ~1.5; not thought to be clinically relevant at the individual level) has been found with paroxetine.Evidence 3Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013 Apr;74(4):e321-41. doi: 10.4088/JCP.12r07968. Review. PubMed PMID: 23656857. Wurst KE, Poole C, Ephross SA, Olshan AF. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. Birth Defects Res A Clin Mol Teratol. 2010 Mar;88(3):159-70. doi: 10.1002/bdra.20627. PubMed PMID: 19739149. However, a number of these complications resolve spontaneously and do not pose significant functional impairment to the offspring. More recent work has linked fluoxetine to a small increase in cardiovascular malformations as well (relative risk, ~1.4). However, significant evidence has not accrued that supports increased risks with other SSRIs, bupropion, mirtazapine, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants except for clomipramine, which may be associated with an elevated risk of cardiovascular malformations. There may also be a modest link between gestational SSRI use and spontaneous abortion (odds ratio, ~1.5), but this may not be present for all agents.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Nikfar S, Rahimi R, Hendoiee N, Abdollahi M. Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis. Daru. 2012 Nov 1;20(1):75. doi: 10.1186/2008-2231-20-75. PubMed PMID: 23351929; PubMed Central PMCID: PMC3556001. Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 2013 Apr;70(4):436-43. doi: 10.1001/jamapsychiatry.2013.684. Review. PubMed PMID: 23446732. Furthermore, SSRI use may also slightly increase the risk of preterm birth (odds ratio, ~1.2). However, it is important to note that neither these risks nor that of congenital malformations are in excess of the 2-fold increase in risk that is traditionally accepted as clinically significant. It is also important to point out that studies that have linked SSRIs to shortened gestational age and reduced birth weight show that the magnitude of these findings are 4 days and 74 grams, respectively, and may not be greater than the risks associated with untreated depression during this time.
After delivery infants exposed previously to SSRIs in the third trimester are at an increased risk for a syndrome of poor neonatal adaptation marked by jitteriness, irritability, tremor, respiratory distress, and excessive crying. Occurring in up to 10% to 30% of infants, these symptoms are time limited (typically resolving in 2-14 days) and not associated with an increased risk of mortality or long-term neurodevelopmental problems (and resolve with supportive care). This risk may be highest with paroxetine, venlafaxine, and fluoxetine. Limited data also suggest that SSRIs taken late (but not early) in pregnancy may also be associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN). The absolute risk is about 3/1000 infants (the risk in the general population is 2/1000) and 339 additional infants need to be exposed to an SSRI in the third trimester in order to produce one additional case of PPHN.Evidence 5Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Grigoriadis S, Vonderporten EH, Mamisashvili L, et al. Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis. BMJ. 2014 Jan 14;348:f6932. doi: 10.1136/bmj.f6932. Review. PubMed PMID: 24429387; PubMed Central PMCID: PMC3898424.
The limited data that exist on the longer-term effects of fetal exposure to SSRIs report no lasting cognitive, emotional, or behavioral problems in the offspring. Finally, despite the fact that a small number of studies have suggested that fetal SSRI exposure may be associated with autism-spectrum disorder, these studies have significant methodological limitations (eg, lack of controlling for multiple confounds) and wide confidence intervals and require replication before they should be considered by patients and physicians.
2. Benzodiazepines during pregnancy: A past meta-analysis consisting of case-control studies has suggested that gestational use of benzodiazepines may increase the risk of the offspring in developing an oral cleft palate (odds ratio, ~1.8). In addition, the use of benzodiazepines during the third trimester and close to delivery may be associated with withdrawal symptoms (eg, irritability, restlessness, tremors) and signs of intoxication (eg, lethargy, respiratory distress, and hypothermia) in the neonate. Furthermore, gestational use of benzodiazepines has also been associated with floppy infant syndrome (ie, signs of hypotonia). Exposure to benzodiazepines during pregnancy may also be linked to other obstetrical complications including low birth weight, preterm birth, caesarean delivery, respiratory support for infants, and admission to neonatal intensive care units. Finally, there is a small number of studies suggesting that gestational exposure to benzodiazepines may be associated with delays in the infant during the postpartum period.
3. Antipsychotics during pregnancy: Two meta-analyses have suggested that antipsychotics may be associated with major congenital malformations including cardiovascular defects in the fetus/newborn. Exposure to antipsychotics during the third trimester may also increase the risk of extrapyramidal (eg, abnormal muscle movements) and withdrawal symptoms (eg, irritability, restlessness, and tremors) in the neonate. Additionally, gestational use of antipsychotics may also be associated with adverse obstetrical outcomes such as preterm birth, small for gestational age, and a decreased birth weight. Finally, a few prospective studies have suggested that there may also be a link between the use of antipsychotics during pregnancy and developmental delays in infants.
4. ECT during pregnancy: Like the studies examining the risks associated with psychotropic medications during gestation, those investigating adverse events from ECT use during pregnancy are small and methodologically limited. Indeed, most of these consist of case study designs with no control participants, small sample sizes, different ECT procedures, and varying periods of follow-up.
In addition to the general adverse effects that are commonly found in ECT treatment (eg, headaches, confusion, nausea), one systematic review of cases studies suggests that ECT use during the second or third trimester may lead to premature uterine contractions and preterm labor. Additionally, pregnant women undergoing ECT may frequently report vaginal bleeding as well as abdominal and pelvic pain. ECT use during pregnancy may also be linked with bradycardia and other cardiac arrhythmias in the fetus. Moreover, multiple reviews examining cases studies have noted that 3% to 8% of patients undergoing ECT during pregnancy report either abortions, stillbirths, or neonatal deaths.
Treatment During the Postpartum Period
1. Mild to moderate MDD in the postpartum period: This chapter outlines general treatment recommendations for women in the postpartum period who choose to breastfeed their infants. Those who do not should refer to general population guidelines for treating depressive disorders. For women with a DSM-5–defined mild to moderate major depressive episode who are breastfeeding, first-line treatments include CBT and IPT. As mentioned above, if these psychotherapies are not available in a given setting and women cannot or will not take an antidepressant, referral to other providers able to deliver CBT or IPT is warranted. Second-line agents include those for which data exist on the effectiveness during the postpartum period that minimize exposure during lactation and that poses the least known risk during the childbearing years (eg, sertraline, citalopram, and escitalopram).Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness. Molyneaux E, Howard LM, McGeown HR, Karia AM, Trevillion K. Antidepressant treatment for postnatal depression. Cochrane Database Syst Rev. 2014 Sep 11;(9):CD002018. doi: 10.1002/14651858.CD002018.pub2. Review. PubMed PMID: 25211400. Combination treatment with these agents plus CBT or IPT are also second line (owing mainly to the lack of studies examining their effectiveness). As in pregnancy, structured exercise (eg, walking) and depression-specific acupuncture are complementary and alternative therapies that have some evidence for efficacy and are accepted third-line treatments. Some evidence also supports the use of newer therapies like assisted internet behavioral activation and CBT as third-line options. While not extensively studied in the postpartum period, mindfulness-based, supportive, and psychodynamic psychotherapy have clinical support for their use.
Despite the presence of randomized controlled trial support for the efficacy in PPD, fluoxetine and paroxetine are third-line treatments. This is because fluoxetine has a long half-life and has been associated with higher rates of minor adverse reactions in breastfed infants, while paroxetine still poses a risk for cardiovascular malformations in potential subsequent pregnancies. The remainder of the new antidepressants are also third-line treatments for mild to moderate MDD because of the more limited clinical experience in lactating women. Tricyclic antidepressants, in particular nortriptyline, are also recommended at this level. Doxepin should be avoided if possible in the postpartum setting owing to reports of significant adverse reactions in breastfed infants. Finally, transcranial magnetic stimulation and bright light therapy may also be effective for the treatment of mild to moderate unipolar depressive episodes and are considered third line.
2. Severe MDD in the postpartum period: For severe PPD, sertraline, citalopram, and escitalopram are first-line choices, and third-line medications for mild to moderate depression (see above) are considered as second-line for women who are severely depressed. ECT is an extremely effective treatment that is listed as third line owing to its adverse-effect profile.
3. Postpartum anxiety: In terms of DSM-5–defined mild to moderate anxiety disorders in the postpartum period, first-line treatment is individual or group CBT. Facilitated self-help may also be useful in treating postpartum women with more mild anxiety. In postpartum women with severe anxiety or those who are not responding to psychological therapies, SSRIs may be considered as a treatment option: sertraline, citalopram, and escitalopram. As in during pregnancy, benzodiazepines should generally not be offered to lactating postpartum women with mild to moderate anxiety. A short-term use of lorazepam may be considered for those with severe levels of anxiety who are not responding to the SSRIs recommended above. If the patient has a history or current substance abuse/dependence disorder, a short-term use of a neuroleptic that has limited breastmilk passage like quetiapine might also be considered, although it is important to be aware that 2 breastfeeding patients using quetiapine reported mild delays in their infants.
4. Augmenting agents for postpartum depressive and anxiety disorders: Postnatal women with treatment-resistant depression may benefit from the following augmenting agents: aripiprazole, quetiapine, olanzapine, and risperidone. Quetiapine or risperidone may also enhance antidepressant therapy for postpartum OCD. In addition to being cognizant of the general adverse effects associated with antipsychotics (see above), clinicians should also monitor prolactin levels among women who choose to use antipsychotics as augmenting agents during the postpartum period. Clozapine should also not be used as an augmenting agent among lactating women because several adverse events have been reported among breastfed infants (more details on clozapine: see above).
Breastfeeding is an individual decision made by women and should be supported by physicians as the use of most psychotropic medications while nursing is not an absolute contraindication to breastfeeding. However, monitoring by women and clinicians is required when breastfeeding is undertaken while taking psychotropic medications. Concerns about breastfeeding while taking medications often regard short-term adverse reactions and longer-term neurodevelopmental effects.
1. Antidepressant risks in breastfeeding: Exposure to antidepressants in breastfed infants is 5 to 10 times lower than exposure in utero. Serum levels in infants born preterm or those with liver and/or kidney impairment can be higher and consultation with a pediatrician can help guide decisions in these infants. It is generally believed that relative infant doses (RIDs) of medication <10% are generally safe (RID estimates infant drug exposure through breast milk using a known milk concentration and comparing it to a weight-adjusted therapeutic dose); all of the SSRIs and SNRIs tested to date appear to produce exposures below this threshold. Of the SSRIs, sertraline, fluvoxamine, and paroxetine have the lowest RID and milk-to-plasma (M/P) ratios. Just 1 to 2 minor infant reactions have been noted in case studies of >200 infants breastfed by mothers treated with sertraline and paroxetine. Citalopram and fluoxetine have had higher rates of infant reactions (4%-5%) but these are reversible and generally limited to short-lived increases in irritability, restlessness, somnolence, or insomnia. Given its relatively low RID, nortriptyline can be a useful choice if women prefer or require treatment with a tricyclic antidepressant.
Next to no data exists on the MAOIs during lactation. There is also a paucity of data on the long-term neurodevelopmental outcomes associated with breastfeeding on antidepressants. However, the limited existing evidence fails to support an increased risk of adverse long-term neurodevelopmental effects. This should be considered given the known risks associated with untreated depression in new mothers.
2. Benzodiazepine risks in breastfeeding: Low levels of benzodiazepines can be found in the breast milk of mothers who are taking these medications during the postpartum period. In one study <2% of exposed infants reported adverse events. The most common adverse events seen among exposed infants is sedation followed by lethargy, poor weight gain, apnea, and irritability.
3. Antipsychotics risks in breastfeeding: Data on most second-generation antipsychotics indicate a RID <10% and a M/P ratio <1, suggesting that they are generally safe for short-term use while breastfeeding infants. However, use of olanzapine postnatally has led to reports of adverse events in exposed infants. The most frequent adverse event seen is sedation/lethargy followed by irritability, tremors, insomnia, diarrhea, poor suckling, and possibly jaundice. Amisulpride should be avoided in general given its RID ~11% and M/P ratio ranges from 11 to 20, suggesting that it may not be safe to use during breastfeeding. Also, clozapine exhibits a high M/P ratio of 2.8 and there was 1 case reported of agranulocytosis in the exposed infant. Other women using clozapine as they breastfeed have also reported sedation and irregular vocal development in their exposed infants.
4. ECT risks in the postpartum: ECT in the postpartum poses some risks to the mother. Common adverse effects include transient memory loss, confusion, anterograde amnesia, and prolonged seizures. Among postpartum women with venous thromboembolism, it is recommended that ECT should be avoided in the first 6 weeks of the postnatal period, given that the procedure can displace thrombi. Although it is suggested that anesthetic drugs may pose minimal risks to breastfed infants, clinicians should consult with anesthetists in determining whether ECT is a viable option for breastfeeding mothers.
Depression and anxiety disorders during pregnancy may not only cause impairment in functioning and affect interpersonal relationships but can increase the risk for adverse outcomes in the offspring. In its most severe form it can lead to suicide in mothers, one of the leading causes of maternal and neonatal mortality.
The mechanism for the association between mental distress during the perinatal period and adverse outcomes in the offspring is not fully understood. Dysregulation in the maternal-placental-fetal axis as well as irregular patterns of inflammation throughout pregnancy have been suggested to be common physiologic pathways. Environmental factors associated with depression and anxiety such as maternal smoking, drug or alcohol abuse, poor nutrition, and low socioeconomic status also play a role.
When untreated, MDD during pregnancy is associated with poorer nutrition and medical care as well as recreational substance misuse. In addition, it has been linked to an increased risk for poor obstetrical outcomes including preeclampsia, preterm delivery, low birth weight, poor head growth, low Apgar scores, smaller head circumference, and neonatal unit admission. Postnatally, depression during pregnancy is associated with increased rates of complications at delivery, decreased rates of breastfeeding, impaired mother-infant attachment, and cognitive, behavioral, and emotional problems in the offspring.
The deleterious effects of untreated PPD on women and their families are well known. PPD has been linked to impaired mother-infant attachment, negative parenting practices, poorer breastfeeding outcomes, relationship problems with their partner, paternal depression, as well as cognitive, emotional, and behavioral problems in the offspring. However, successful treatment of maternal depression during this period may reduce certain risks in the offspring.
As for untreated gestational anxiety, less is known, but it appears to be associated with several adverse obstetrical outcomes including preterm birth, low birth weight, small for gestational age, and a smaller head circumference for the neonate. Additionally, anxiety during pregnancy may increase the risk for a subsequent episode of PPD (odds ratio, ~2.5) and may also be associated with reduced rates of breastfeeding as well as behavioral, emotional, and cognitive problems in the offspring. In terms of postpartum anxiety, this may be linked with poorer breastfeeding outcomes as well as impaired bonding between the mother and the infant.