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org Reviews
OBSTETRICS
Postpartum depression
Teri Pearlstein, MD; Margaret Howard, PhD; Amy Salisbury, PhD; Caron Zlotnick, PhD
non-Western countries from 0.5-60%; bance may be both a risk factor for and and impaired child development.36,37
cultural factors can influence the devel- an outcome of PPD in the early postpar- Infant and child outcomes that are asso-
opment and reporting of PPD.13 tum period.26,27 Studies have suggested ciated with PPD include a higher inci-
Psychosocial risk factors for PPD in- that persistent infant and child sleep dence of excessive infant crying or colic,
clude MDD during pregnancy, anxiety problems are related to maternal depres- sleep problems, and temperamental dif-
during pregnancy, previous nonpuer- sion.28,29 Despite the consistent findings ficulties.34,38 Infant crying and sleeping
peral MDD, previous premenstrual dys- of a relationship between maternal de- problems may increase the risk for new
phoria, stressful life events during preg- pression and infant and child sleep prob- onset PPD but may also be reported
nancy or the early puerperium, poor lems, a causal pathway has not been de- more frequently by women with PPD. In
social support, marital conflict, low in- termined, and few studies have a study of ⬎ 600 infants, objective evi-
come, immigrant status, and young ma- measured infant sleep objectively. dence of infant regulation difficulties
ternal age.14,15 A recent study identified were found as early as 1 month after de-
previous depression, current depression Role of obstetricians livery, with infants of mothers with
and anxiety, and low partner support as and pediatricians PPD having poorer self-regulation,
key risk factors.16 Numerous studies have reported on the more stress signs, and heightened
PPD may be related to a differential low rates of screening, diagnosis, and arousal compared with infants of
sensitivity to hormonal fluctuations. Eu- treatment of perinatal depression in mothers without PPD.39 PPD is associ-
thymic women with previous PPD expe- medical settings. Clinician discomfort ated with negative mother-infant in-
rienced dysphoria after both the addi- with psychiatric disorders, time con- teractions that include maternal with-
tion and withdrawal of supraphysiologic straints, low belief in maternal mental drawal, disengagement, intrusion, and
doses of estradiol and progesterone, health having an important effect on hostility.40,41 Women with PPD may
compared with healthy control sub- child development, and lack of knowl- be less likely to initiate or maintain
jects.17 In addition to sensitivity to estro- edge about resources are some of the breastfeeding; depressive symptoms
gen and progesterone fluctuations, bio- barriers to clinician screening for psychi- commonly precede the early cessation
logic theories have included fluctuations atric disorders in medical settings.30-32 of breastfeeding.42,43
of other gonadal hormone and neuroac- However, the postpartum obstetric visit PPD is linked to poor cognitive func-
tive steroid levels after delivery, altered and pediatric well-baby visits are oppor- tioning, behavioral inhibition, and emo-
cytokines and HPA axis hormones, and tunities for the clinician to assess the tional maladjustment in infants and chil-
altered fatty acid, oxytocin, and arginine mother’s clinical status.31,33 Although dren.44-46 Persistent untreated maternal
vasopressin levels.18,19 Involvement of women with PPD are often hesitant to depression is associated with violent be-
the serotonin system has been suggested divulge their mood and anxiety symp- havior and externalizing disorders (eg,
by reports of altered platelet serotonin toms to their clinician because of guilt conduct disorders)47-49 and with psychi-
transporter binding20 and decreased about having symptoms when mother- atric and medical disorders in adoles-
postsynaptic serotonin-1A receptor hood is expected to be joyful, there may cence.50 The complex relationship be-
binding in the anterior cingulate and be indicators that further evaluation is tween maternal depression and child
mesiotemporal cortices.21 A recent study needed. For example, PPD may lead to behavioral-emotional development is
that used a functional magnetic reso- negative maternal perceptions of infant not yet understood but is likely to be a
nance imaging (fMRI) neuropsycho- temperament and behavioral patterns; multidimensional progression that may
logic activation paradigm suggested al- such complaints should be addressed in onset during pregnancy. Women with
tered neural processing in women with the context of the infant’s behavior and PPD often have been depressed during
PPD.22 how well the mother is coping with these pregnancy,5 which is a potential source
Normal fluctuations in hormonal lev- difficulties.34 PPD has been associated of exposure or influence on the fetus.
els during pregnancy and after delivery with frequent nonroutine visits to the The few published studies on the effects
result in changes in sleep patterns. De- pediatrician; such visits and telephone of antenatal depression on fetal out-
clining levels of progesterone in the early contacts may be warranted but could comes have not always used a diagnosis
postpartum period promote insomnia.23 also be an indicator for further assess- of MDD but have shown that higher lev-
In the first postpartum month, de- ment of maternal mood and family func- els of self-reported depressive symptoms
creased sleep efficiency and increased tioning.35 Follow-up with the woman during pregnancy were related to height-
slow wave sleep have been reported.23,24 who is referred for treatment within the ened fetal behavioral and physiologic re-
The changes in hormones and sleep dur- practice or to a mental health clinician activity.51 Alterations in fetal neurobe-
ing the early postpartum period may reinforces the importance of treatment havioral development are likely to
contribute major vulnerability to the on- recommendations. influence infant outcomes. The serious
set of PPD. A recent study identified dif- negative effects of PPD on the mother,
ficulty falling asleep in the first 3 months Risks to children of not treating PPD the infant, and the other family members
after delivery as a possible risk factor for There is a well-established relationship have made the recognition, prevention,
PPD.25 In addition, infant sleep distur- between untreated maternal depression and treatment of PPD a current area of
noted public health significance. Recent Postpartum psychosis to an infant or thoughts of infanticide
evidence suggests that successful treat- Postpartum psychosis occurs in 1 of rarely are acted upon.
ment of PPD may not be sufficient to im- 500 mothers, with rapid onset in the
prove attachment, temperament, and first 2-4 weeks after delivery.60 Post- Treatment of PPD
cognitive development in infants and partum psychosis includes confused Psychotherapy
toddlers,52,53 which indicates that efforts thinking, mood swings, delusions, Interpersonal psychotherapy (IPT), a
toward the prevention and treatment of paranoia, disorganized behavior, poor short-term efficacious treatment for
depression during pregnancy and after judgment, and impaired function- MDD that addresses interpersonal issues
delivery are critical. Additional focus on ing.61 Postpartum psychosis is consid- (such as role change, the marital rela-
mother-infant attachment and the needs ered a psychiatric emergency and usu- tionship, social support, and life stres-
of the family are also indicated. ally results in inpatient psychiatric sors) is highly pertinent to the needs of
hospitalization. Risk factors include a women during the postpartum period.69
Suicide during the postpartum period previous episode of postpartum psy- A randomized controlled trial (RCT) re-
chosis, previous hospitalization for a ported that 12 sessions of individual IPT
Completed suicide rates are lower dur-
manic or psychotic episode, recent dis- was superior in efficacy to a waitlist con-
ing the postpartum period compared
continuation of mood stabilizers, pri- trol in 120 women with PPD in reducing
with nonpuerperal time periods, al-
miparity, obstetric complications, depression and improving social adjust-
though rates in postpartum adolescents ment.70 A smaller RCT in women with
are higher than in older postpartum sleep deprivation, and a family history
of bipolar disorder or postpartum psy- PPD also reported that individual IPT
women.54 A study of perinatal maternal was superior to a wait-list condition.71
deaths in the United Kingdom from chosis.61-63 Longitudinal studies sug-
gest that most cases of postpartum psy- Additionally, 2 small open studies of
1997-1999 reported that suicide was the group IPT demonstrated significant re-
leading cause of maternal death, was in- chosis are related to bipolar disorder,
duction of depression in women with
creased in women with psychiatric and not schizophrenia.61
PPD.72,73
substance abuse disorders, and was more Systematic reviews of treatments for
Neonaticide and infanticide
likely to be a violent death compared PPD have suggested that individual IPT,
Infanticide is 1 of the most serious risks
with the suicides of men and nonpuer- cognitive-behavior therapy (CBT), and
of postpartum psychosis. The rate of ho-
peral women.55 Suicide may also be a psychodynamic therapy may be effective
micide of infants up to 1 year of age is 8
leading cause of maternal deaths in psychologic treatments for PPD.74 Over-
per 100,000 in the United States,64 but it
Australia.56 all, psychologic treatments for PPD
is unknown how many women with
A study of a United States popula- demonstrate moderate effect sizes75; an-
postpartum psychosis commit infanti- tidepressant medications demonstrate
tion sample reported that there was a 3
cide. Symptom exacerbation, command larger effect sizes.76 Methodologic flaws
times greater risk of a suicide attempt
hallucinations, and the stressor of new of studies of psychosocial treatments in-
and that inpatient psychiatric admis-
infant care can increase the risk of infan- clude small sample sizes, short-term
sions were increased after fetal death or ticide after delivery in a mother with psy-
infant death in the first postpartum treatments, lack of control groups,
chosis.65 Infanticide may also occur in poorly defined treatment interventions
year.57 In this study, labor and delivery the context of severe PPD, caused by ne-
complications, cesarean section, pre- and outcome measures, lack of partner
glect and abuse, because of the child be- participation, and lack of assessment of
term delivery, low birthweight, and ing unwanted or as revenge against the infant outcome.74 Although 1 study in-
congenital malformations were not as- infant’s father.65,66 Between 16% and cluded partners as 1 component of psy-
sociated with increased risk of suicide 29% of mothers who kill their children chologic treatments,77 there has not been
attempts. A review of studies that con- also kill themselves.64 Neonaticide is de- systematic study of couples therapy in
firmed that suicide rates are lower dur- fined as killing a newborn infant within women with PPD. Initial positive reports
ing pregnancy and the postpartum pe- 24 hours of birth and is associated with that deserve further study include tele-
riod emphasized that perinatal women denial of pregnancy, lack of prenatal phone support, lay peer support, indi-
complete suicide by more violent and care, dissociation, depersonalization, vidual counseling in the home, nurse-led
lethal means than do women who are and intermittent amnesia of deliv- or health visitor–led support groups, and
not perinatal.58 Assessment of suicid- ery.64,67 More study is needed of risk fac- group therapy led by mental health clini-
ality in the perinatal woman should in- tors for neonaticide and infanticide.64 cians.74,78 Women with mild PPD may
clude specific inquiry about depressed Intrusive thoughts of potential acciden- respond to treatment by nonmental
mood, substance abuse, previous sui- tal harm occurring to a newborn infant health professionals or to individual or
cide attempts, current or previous psy- are ubiquitous, and intrusive thoughts of group counseling with a mental health
chiatric illness, previous trauma, cur- intentionally harming an infant are also professional, although women with
rent intimate partner violence, and common.68 It is important to reassure more severe PPD may need IPT or CBT
access to firearms.58,59 women that intrusive thoughts of harm to be administered by trained profes-
sionals and/or antidepressant medica- placebo, and counseling (based loosely have reported that postpartum use of es-
tion.78 Women who are breastfeeding on CBT principles) in 87 women with trogen may have a role,94,95 although the
may prefer psychotherapy over medica- PPD.85 Women were assigned randomly postpartum use of progesterone has not
tion for the treatment of PPD.79-81 Bar- to 12 weeks of fluoxetine 20 mg daily and been promising.82 A small study re-
riers to participation in psychotherapy 6 counseling sessions, fluoxetine 20 mg ported that early morning bright light
include perceived negative stigma, lack daily and 1 counseling session, placebo therapy was not more effective than
of availability of a trained therapist in and 6 counseling sessions, or placebo sham dim red light in the reduction of
IPT or CBT, time commitment, child- and 1 counseling session. Fluoxetine was depressive symptoms.96 Two recent
care needs, and cost.82 significantly superior to placebo in re- RCTs failed to demonstrate superior ef-
ducing the severity of depressive symp- ficacy of omega-3 supplementation,
Mother-baby units toms. The combination of fluoxetine compared with placebo.97,98
The United States has lagged behind Eu- and 6 sessions of counseling were not su-
rope and Australia in the recognition perior to either treatment alone. Women Antidepressants and breastfeeding
and treatment of perinatal psychiatric who were breastfeeding were excluded The breastfeeding woman with PPD
disorders. The practice of joint admis- from this study; most of the women who must weigh the potential efficacy of an-
sion of mothers and infants was were enrolled had mild-to-moderate se- tidepressant medication for her depres-
prompted by concerns about disrupting verity of depressive symptoms. sion, the potential risks of exposure of
the mother-infant relationship during A comparator RCT randomly as- her infant to antidepressant medication
intensive psychiatric treatment. The first signed 109 women with PPD to sertra- through the breastfeeding, and the
joint mother-baby admission occurred line or nortriptyline, both of which were known negative effects of not treating
in the United Kingdom 60 years ago, and administered in an escalating dose regi- her depression on child development.
joint admission now takes place rou- men over 8 weeks.86 Almost one-half of Breastfeeding has multiple benefits for a
tinely in the United Kingdom, Australia, the subjects remitted by week 8 on either developing infant,42 and a woman with
France, Belgium, Germany, and the antidepressant. No adverse effects in PPD may believe that breastfeeding is an
Netherlands. Parent-infant units have breastfeeding infants were reported, and important positive experience that she is
been established in Australia. The only infant serum levels were near or below able to share with her infant in her de-
known current mother-baby unit in the quantifiable levels.86 Another compara- pressed state. There is a growing obser-
United States is conducted as a psychiat- tor RCT compared paroxetine with vational database of side-effects in in-
ric partial hospital.83 Advantages of combined paroxetine/CBT in 35 women fants who are exposed to antidepressants
mother-baby units include support, ab- with PPD and comorbid anxiety disor- through breast milk, and the choice of
sence of breastfeeding disruption or ces- ders.87 Paroxetine was flexibly dosed medication should be chosen after re-
sation, multidisciplinary treatment of over 12 weeks, and CBT was provided in view of these data.99 The Food and Drug
PPD, direct observation of mother-in- 12 individual sessions. Both treatments Administration has announced that, in
fant interaction, and the promotion and led to significant improvements on mea- the future, medications will be classified
modeling of a healthy maternal-child sures of depression, and there were no by their risk summary, clinical consider-
relationship. significant differences between treat- ations, and data in terms of lactation.100
ments. Approximately one-half of the Measurement of infant antidepressant
Antidepressant treatment subjects were breastfeeding, but antide- serum levels and breast milk analyses are
Four RCTs with antidepressant medica- pressant side-effects and serum levels in not obtained routinely in clinical care,101
tion have been conducted in women infants were not reported. The anxiety and milk-to-plasma ratios may not be
with PPD; 2 were placebo-controlled, comorbidity in the latter study and the relevant to adverse effects.102 When an
and 2 were active comparator studies. lack of a placebo control in both of these antidepressant is started in the woman
One placebo-controlled RCT compared comparator RCTs limits conclusions after delivery, it is recommended to start
immediate-release flexible-dosed parox- about the efficacy of these treatments for with low doses and to titrate the dose up
etine with placebo in 70 women with PPD. Notably, the remission rate with slowly while monitoring the infant for
postpartum onset of MDD.84 After 8 paroxetine was lower in the paroxetine adverse effects.82 Possible adverse effects
weeks of treatment, both groups im- study that included a placebo control.84 in the breastfeeding infants include irri-
proved significantly over time, but par- Small open trials and case reports have tability, sedation, poor weight gain, or a
oxetine was superior to placebo in terms also suggested efficacy of antidepressants change in feeding patterns.103,104 Ad-
of remission of depression (remission for the treatment of PPD.82,88 verse events are most likely to occur in
rates were 37% and 15%, respectively). newborn infants up to 8 weeks of age,
Approximately 40% of the subjects in Additional treatments and infants who are born prematurely or
this study were breastfeeding, but the ef- Studies have suggested a benefit with in- with medical problems may be at in-
fects in infants were not described in the fant massage,89 exercise,90 sleep depriva- creased risk.103 Infant exposure to anti-
published study.84 Another placebo- tion,91 infant sleep intervention,92 and depressant medication can be mini-
controlled RCT compared fluoxetine, electroconvulsive therapy.93 Studies mized by avoiding breastfeeding at the
time of peak antidepressant concentra- mended during breastfeeding because of medications, few studies have examined
tion in the breast milk.105 If adverse ef- reports of hypothermia, hypotonia, cya- long-term effects. Discussions of the
fects in the infant are noted, options in- nosis, T-wave inversion, and lethargy re- treatment options with the patient and
clude decreasing the dose, changing to ported in infants.61,101,111 There is a pau- her partner after delivery must include
partial or full bottlefeeding, or changing city of data about the safety of the newer the patient’s personal psychiatric history
the medication. Collaboration between antiepileptic drugs and atypical antipsy- and previous response to treatment, the
the pediatrician and mental health clini- chotics.105 Valproate and carbamaz- risks of no treatment, available data
cian is important. epine have been used safely during about the safety of medications with
Several reviews of the safety of breastfeeding. It was reported recently breastfeeding, and her individual expec-
selective serotonin reuptake inhibitors that infant serum levels of lamotrigine tations and treatment preferences.103
(SSRIs), tricyclic antidepressants (TCAs), are variable and sometimes high after Time constraints, financial restraints,
and newer antidepressants with breast- breastfeeding.112 Preliminary data have and perceived cultural dissonance can
feeding have been conducted.99,104,106,107 suggested that oxcarbazepine, topira- lead to poor treatment adherence. Even
A pooled analysis of antidepressant levels mate, gabapentin, and levetiracetam are with treatment adherence support in
in mother-infant dyads concluded that not associated with adverse ef- low-income mothers in Chile, the initial
sertraline, paroxetine, and nortriptyline fects.61,105,111 Sporadic adverse effects benefit of multicomponent care (includ-
usually yield undetectable infant serum have been reported with olanzapine, clo- ing psychosocial support and medica-
levels and that elevated infant levels are zapine, and traditional antipsychot- tion) for PPD, compared with usual care,
more likely with fluoxetine and citalo- ics.113 Infant monitoring should match was attenuated after 6 months.115
pram.107 Sertraline has been reported to the monitoring of potential adverse
have minimal or no effect on central se- events that is used in adults.105 Studies Comment
rotonin transport in the infant.108 Case that evaluate the long-term effect on Future efforts hopefully will improve the
reports of adverse effects in breastfeed- child development after breastfeeding screening and identification of psychiat-
ing infants have been reported with flu- exposure to anxiolytics, mood stabiliz- ric disorders in women at their postpar-
oxetine, citalopram, doxepin, bupro- ers, and antipsychotics are needed. tum visit with the obstetrician and at
pion, and nefazodone.82,88,101 If after well-baby visits with the pediatrician.
delivery, a woman is euthymic with an- Treatment dilemmas for Untreated depression and psychotropic
tidepressant therapy that is known to be women with PPD medications for the breastfeeding
associated potentially with mild adverse It can be argued that the risks of exposure woman each involve exposure of the
effects or high infant serum levels, it may to PPD outweigh at least the short-term child to potential short-term and long-
be more advisable to monitor the infant risks of infant exposure to antidepres- term negative effects. Psychotherapy is a
carefully rather than to switch the an- sants through breast milk, because the treatment option for women with PPD,
tidepressant.82,104 Even if there are no multiple negative effects of untreated with IPT being the most validated psy-
adverse effects and unquantifiable lev- PPD on short-term and long-term child chotherapy to be studied to date. Antide-
els in infants, the long-term effects of development are well-established. In ad- pressant medications are also efficacious
antidepressant exposure through breast dition to the multiple known benefits for for PPD. The critical goal of treatment is
milk on child cognitive, motor, neuro- infants with breastfeeding,42 a recent the resolution of the mother’s psychiat-
logic, and behavioral development are large sample study reported that pro- ric symptoms. Breastfeeding has multi-
unclear.109 longed and exclusive breastfeeding was ple known benefits for infant develop-
associated with improved cognitive de- ment, and a breastfeeding woman with
Other psychotropic medications velopment in 6-year-old children.114 PPD does not need necessarily to decline
and breastfeeding Women who are breastfeeding may pre- pharmacotherapy. Sertraline is the first-
Some women with PPD may be admin- fer psychotherapy over medication for line antidepressant used in PPD in
istered an adjunctive benzodiazepine for the treatment of PPD, but it may be less breastfeeding women because of the
anxiety or insomnia. Sedation and poor effective than pharmacotherapy for se- paucity of adverse effects that have been
feeding have been reported in breast- verely depressed women. For these reported in breastfeeding infants. Parox-
feeding infants who are exposed to ben- women and for women whose symp- etine or nortriptyline are second-line
zodiazepines, and divided low doses has toms are unresponsive to nonpharmaco- agents in women who are unable to tol-
been advised.101 Other psychotropic logic treatments, the consideration of erate or who do not respond to sertra-
medication may be used by breastfeed- antidepressant medication may be nec- line. Clinicians and patients can monitor
ing women with bipolar or psychotic ill- essary. All psychotropic medications current knowledge about breastfeeding
ness or severe depression. Even though it pass into breast milk, and the potential and medications through publica-
was reported recently that lithium could for infant exposure exists with each med- tions116 and websites that update and re-
be used during breastfeeding with care- ication. Although observational reports view published information frequently
ful infant serum level monitoring,110 suggest a lack of short-term adverse ef- (such as LactMed on http://toxnet.nlm.
lithium generally has not been recom- fects in infants with many psychotropic nih.gov, www.mededppd.org, www.
postpartum.net, www.womensmental- the postpartum period: a comparison of three models of mutual influence over time. Dev
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