J Clin Psychlopedia Main Page | Major Depressive Disorder in Women | CME Background

MDD in Women: Focus on Reproductive Events

Independently developed by the CME Institute of Physicians Postgraduate Press,
Inc., and the American Society of Clinical Psychopharmacology.
Managing Depression During Pregnancy
Marlene P. Freeman, MD
Center for Womens Mental !ealth" Massachusetts #eneral !ospital" Boston
Conclusive data a$out the effects of depression in pregnancy and
evidence for the efficacy and safety of antidepressant medications in
pregnancy are meager% &o pu$lished studies of antidepressant drug
efficacy in pregnancy are availa$le" and fe' 'ell(controlled studies
for antidepressant drug safety in pregnancy have $een undertaken%
!ealth and ethical considerations make it difficult to conduct
randomi)ed" controlled studies of depression in pregnant 'omen%
*lthough more evidence is needed" some data for the effects of $oth
maternal depression and antidepressant treatment on fetal
development and $irth outcomes are availa$le and provide clinicians
'ith some guidance%
Likelihood o Depression During Pregnancy
Women are at greatest risk of major depressive episodes during
the reproductive years"
+
and therefore" it is reasona$le to e,pect
that a 'oman may $ecome pregnant 'hile receiving antidepressant
treatment% -'o thirds of *merican 'omen 'ill have at least +
unplanned pregnancy"
.
and family planning decisions may also
change over the course of treatment/ so regardless of 'hat 'omen
report a$out family planning at the initiation of treatment" they may
very likely $ecome pregnant 'hile $eing treated for depression%
*$out 01 to +21 of 'omen e,perience depression during
pregnancy" thus depression is similarly common in pregnant 'omen
as in nonpregnant 'omen%
3
Risks o !ntreated Maternal Depression
4ntreated depression during pregnancy carries risks for $oth the
mother and $a$y% Depression may negatively affect maternal 'eight
gain and self care%
3
Depression" an,iety" and stress may also
contri$ute to preeclampsia%
5
6isks to the $a$y associated 'ith
untreated maternal depression include preterm delivery"
0
reduced
$irth 'eight"
5
and reduced head si)e%
5
&e'$orns cry more and are
harder to soothe if mothers 'ere an,ious or depressed during
pregnancy" and infants may have poorer psychomotor development
and adaptation to ne' environments%
5
7n addition" untreated
maternal depression can have psychosocial conse8uences that can
affect the 'hole family" for e,ample" hospitali)ation" relationship
pro$lems" ina$ility to care for other children" and loss of
employment%
9
:or more information on the effects of untreated
postnatal depression" see ;Postpartum Depression -reatment and
Breastfeeding%<
Risks to "a#y o Medications During Pregnancy
*= +% -eratogenic 6isks of Prescription Medications >22?35@
Aome medications taken during pregnancy carry risks for the
$a$y" and these teratogenic risks are currently rated $y the :D*
using letter grades >*= +@%
B
Clinicians must 'eigh the evidence and
$alance the risk of medication use to the $a$y against the risks of
the untreated maternal depression to the $a$y and mother% -he
system used $y the :D* is e,tremely limited" in that the risks of the
untreated maternal disorder are not taken into account" often there
is a paucity of human data that informs category assignment" and
ne' information is rarely used to update category assignment%
*lthough much of the older literature sho's a lack of association
$et'een -C*s or AA67s and major malformations or intrauterine
death" in some $ut not all studies" neonates 'hose mothers took
antidepressants in the third trimester had lo'er $irth 'eight than
controls and some had symptoms that are consistent 'ith side
effects or 'ithdra'al%
9
More recent studies
CD+3
have generated controversy a$out
'hether the teratogenic risks of antidepressant medications are
greater than once thought% :or e,ample" nonDpeer(revie'ed data
C

associated paro,etine use during the first trimester of pregnancy
'ith increased risk of cardiovascular malformations compared 'ith
first(trimester use of other antidepressants% Au$se8uent
analyses"
E"+5"+0
ho'ever" have not found an increased risk of major
cardiac malformations 'ith first(trimester use of paro,etine%
When taken in late pregnancy" AA67s have $een associated 'ith
PP!&" $ut the risk may $e lo'er than initially reported $y Cham$ers
and colleagues in .229%
+2
-his serious pulmonary condition is rare in
the general population >estimated at + or . infants per +222 live
$irths@" $ut" in Cham$ers and colleagues epidemiologic case(
controlled study"
+2
PP!& 'as found to $e 9%+ times more likely in
infants of 'omen 'ho used AA67s after 'eek .2 during pregnancy
than in controls >E01 C7F.%. to +9%C@% 7n a more recent A'edish
study"
++
the risk >3%9" E01 C7F+%. to C%3@ 'as lo'er than that
reported in the &orth *merican study%
+2
7n a$solute terms" the risk is
rare and needs to $e 'eighed against the untreated condition of the
mother% 7mportantly" in these studies"
+2"++
the underlying maternal
psychiatric symptoms 'ere not considered in the analyses" and it is
unkno'n 'hether maternal depression or an,iety could contri$ute
to an increased risk% * recent study $y *ndrade et al
+9
did not sho'
any increased risk of PP!& 'ith AA67 use in late pregnancy%
Gess
*= .% :re8uency of Aigns of &eonatal A67 Withdra'al Ayndrome >22?+5@
Aeveral other risks may $e associated 'ith prenatal AA67
e,posure% 6educed $irth 'eight for gestational age
+.
and increased
risk of preterm $irth
+3
have $een reported among $a$ies $orn to
mothers taking AA67s" although untreated maternal depression also
seems to result in prematurity%
+B
Go' $irth 'eight and premature
$irth may $e associated 'ith MDD"
5"0
$ut distinguishing 'hich factor
>depression or antidepressant use@ influences the outcome more is
challenging% 7n fact" 'omen 'ho continued to take AA67s during
pregnancy may have had more severe depression than 'omen 'ho
discontinued treatment during pregnancy" further clouding the
distinction $et'een medication effects and depression effects%
+.
Withdra'al or to,icity syndromes have also $een suspected in
$a$ies e,posed to AA67s late in gestation >*= .@%
9"+C
-hese effects
are transient and are reported to resolve $y . 'eeks of age" 'ithout
lasting effects" 'ith reported symptoms including jitteriness" trou$le
eating and sleeping" and fussiness%
+C
Risk o Relapse o Depression During Pregnancy
*= 3% -ime to 6elapse of Depression During Pregnancy *ccording to Medication Atatus >22?+9@
7n a recent" prospective study
+E
of 'omen 'ho 'ere follo'ed
during pregnancy and had histories of MDD" the rate of relapse of
depression 'as 9C1 among pregnant 'omen 'ho discontinued
medication compared 'ith .91 of those 'ho continued medication
at the same dose >*= 3@% Predictors of relapse include a longer
duration of MDD >H0 years@" more recurrent depression >H5
episodes@" $eing unmarried" and $eing younger than 3. years%
While treatment guidelines are generally lacking and care must
$e individuali)ed for each patient" in general" 'hen antidepressants
are used" the lo'est effective dose should $e prescri$ed% :or many
'omen" antidepressant use can $e avoided or minimi)ed $y
selecting nonmedication strategies%
$onpharmacologic %reatments
Data are availa$le for several nonpharmacologic treatments for
depression during pregnancy% Ine of the most important treatment
options includes psychotherapy%
.2
Bright light therapy has received
some study in pilot trials and appears promising for the treatment of
depression in pregnant 'omen"
.+
and omega(3 fatty acids may $e
advantageous as add(on therapy and are 'ell tolerated%
..
:or severe
cases of depression in pregnancy" EC- is thought to $e safe if
appropriate precautions are taken%
.3

&onclusion
Clinicians should routinely counsel 'omen 'ith depression 'ho
are of child$earing age a$out risks and $enefits of medications
during pregnancy" $ecause the likelihood of pregnancy is high
'hether or not it is planned% Clinicians and patients need to $alance
the risks of medication to the $a$y against the risks of depressive
relapse to $oth $a$y and mother" remem$ering that pregnancy is
not protective against depression% -reatment needs to $e tailored to
the individual patient" and nonpharmacologic options may $e
appropriate% More evidence($ased treatment information is needed%
Drug $ames
clo)apine >:a)aClo" Clo)aril" and others@" paro,etine >Pa,il"
Pe,eva" and others@
'##reviations
EC- F electroconvulsive therapy" EE# F electroencephalographic"
:D* F 4nited Atates :ood and Drug *dministration" MDD F major
depressive disorder" PP!& F persistent pulmonary hypertension of
the ne'$orn" A67 F serotonin reuptake inhi$itor" AA67 F selective
serotonin reuptake inhi$itor" -C* F tricyclic antidepressant
Take the online posttest.
Reerences
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+EE3/.E>.D3@?C0DE9%
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3% E$erhard(#ran M" Eskild *" Ipjordsmoen A% -reating mood disorders during
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5% Mulder EJ" 6o$les de Medina P#" !ui)ink *C" et al% Prenatal maternal stress? effects
on pregnancy and the >un$orn@ child% Early #um ev% .22./B2>+D.@?3D+5%
0% Gi D" Giu G" Idouli 6% Presence of depressive symptoms during early pregnancy and
the risk of preterm delivery? a prospective cohort study% #um (eprod% .22E/.5>+@?+59D+03%
9% Wisner JG" #elen$erg *J" Geonard !" et al% Pharmacologic treatment of depression
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.22E%
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.229/305>9@?0BED0CB%
++% JQllPn B" Ilausson PI% Maternal use of selective serotonin re(uptake inhi$itors and
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.22C/+B>C@?C2+DC29%
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.22C/+90>9@?B5EDB0.%
+0% #entile A" Bellantuono C% Aelective serotonin reuptake inhi$itor e,posure during early
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.22E/B2>3@?5+5D5..%
+9% *ndrade AE" McPhillips !" Goren D" et al% *ntidepressant medication use and risk of
persistent pulmonary hypertension of the ne'$orn% Pharmacoepidemiol rug Saf%
.22E/+C>3@?.59D.0.%
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pregnancy in 'omen 'ho maintain or discontinue antidepressant treatment% JAMA%
.229/.E0>0@?5EED02B%
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.+% Iren D*" Wisner JG" Apinelli M" et al% *n open trial of morning light therapy for
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