Depression during pregnancy.

Abstract

To review existing literature on depression during pregnancy and to provide information for family physicians in order to promote early detection and treatment.
MEDLINE was searched from January 1989 through August 2004 using the key words depression, pregnancy, prenatal, and antenatal. Articles focusing on depression during pregnancy were chosen for review; these articles were based on expert opinion (level III evidence) and prospective studies (level II evidence).
Pregnancy does not safeguard women against depressive illness. The Edinburgh Postnatal Depression Scale is an effective screening tool for identifying women with depressive symptoms during pregnancy. Once diagnosed with major depression, these patients need to be monitored closely for up to a year after delivery. Patients with mild-to-moderate illness should be referred for psychotherapy. More severely ill patients might require additional treatment with antidepressants. The most commonly used antidepressants are selective serotonin reuptake inhibitors and the serotonin and norepinephrine reuptake inhibitor, venlafaxine. For each patient, risk of treatment with an antidepressant needs to be compared with risk of not treating her depressive illness.
Early detection of depression during pregnancy is critical because depression can adversely affect birth outcomes and neonatal health and, if left untreated, can persist after the birth. Untreated postpartum depression can impair mother-infant attachments and have cognitive, emotional, and behavioural consequences for children.

Full text

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VOL 5: AUGUST • AOÛT 2005 d Canadian Family Physician • Le Médecin de famille canadien 1087
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Depression during pregnancy
Deirdre Ryan, MB, FRCPC Lisa Milis Nicholas Misri
ABSTRACT
OBJECTIVE To review existing literature on depression during pregnancy and to provide information for family physicians in
order to promote early detection and treatment.
QUALITY OF EVIDENCE MEDLINE was searched from January 1989 through August 2004 using the key words depression,
pregnancy, prenatal, and antenatal. Articles focusing on depression during pregnancy were chosen for review; these articles
were based on expert opinion (level III evidence) and prospective studies (level II evidence).
MAIN MESSAGE Pregnancy does not safeguard women against depressive illness. The Edinburgh Postnatal Depression Scale
is an eff ective screening tool for identifying women with depressive symptoms during pregnancy. Once diagnosed with major
depression, these patients need to be monitored closely for up to a year after delivery. Patients with mild-to-moderate illness
should be referred for psychotherapy. More severely ill patients might require additional treatment with antidepressants.
The most commonly used antidepressants are selective serotonin reuptake inhibitors and the serotonin and norepinephrine
reuptake inhibitor, venlafaxine. For each patient, risk of treatment with an antidepressant needs to be compared with risk of
not treating her depressive illness.
CONCLUSION Early detection of depression during pregnancy is critical because depression can adversely aff ect birth outcomes
and neonatal health and, if left untreated, can persist after the birth. Untreated postpartum depression can impair mother-
infant attachments and have cognitive, emotional, and behavioural consequences for children.
RÉSUMÉ
OBJECTIF Recenser les publications traitant de la dépression chez la femme enceinte et donner au médecin de famille
l’information nécessaire pour mieux déceler et traiter cette condition.
QUALITÉ DES PREUVES Une recherche a été eff ectuée dans MEDLINE entre janvier 1989 et août 2004 à l’aide des mots-clés
depression, pregnancy, prenatal, et antenatal. Les articles centrés sur la dépression durant la grossesse ont été retenus pour analyse;
ces articles reposaient sur l’opinion d’experts (preuves de niveau III) et sur des études prospectives (preuves de niveau II)
PRINCIPAL MESSAGE Les femmes enceintes ne sont pas à l’abri des troubles dépressifs. L’échelle de dépression postnatale
d’Édinbourg est un outil effi cace pour identifi er les femmes qui présentent des symptômes dépressifs durant la grossesse. En
cas de dépression sévère, la femme devra être suivie de près jusqu’à un an après l’accouchement. Les cas de dépression légère
à modérée devraient être dirigés en psychothérapie. Les dépressions plus graves pourraient exiger l’usage d’antidépresseurs.
Les plus couramment utilisés sont les inhibiteurs sélectifs du recaptage de la sérotonine et l’inhibiteur du recaptage de la
noradrénaline et de la sérotonine, la venlafaxine. Dans chaque cas, le risque lié à l’utilisation de l’antidépresseur doit être
comparé à celui de ne pas traiter la dépression.
CONCLUSION Il est crucial de déceler la dépression tôt durant la grossesse; en eff et, cette maladie peut aff ecter négativement
l’issue de la grossesse et la santé néonatale; non traitée, elle peut se prolonger au-delà de l’accouchement. Une dépression
postnatale peut interférer avec le développement des liens mère-enfant et avoir des conséquences cognitives, émotionnelles et
comportementales pour l’enfant.
This article has been peer reviewed
Cet article a fait l’objet d’une révision par des pairs.
Can Fam Physician 2005;51:1087-1093.

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T
Depression during pregnancy
here is growing evidence to challenge the
notion that pregnancy protects patients from
mental illness. Rates of depression during
pregnancy have been reported to be as high as 20%.1
Evidence suggests that postpartum depression (PPD)
can be part of a continuum, with onset of illness
during pregnancy.1-3 Family physicians are often the
fi rst caregivers to come into contact with pregnant
women; they, therefore, have a unique opportunity
to monitor women’s moods over several weeks. Early
detection of symptoms could facilitate timely treat-
ment and prevent ongoing depression. Th is article
was written to assist family physicians in recogniz-
ing prenatal depression and to aid their decision
making for managing this complex condition.
Quality of evidence
MEDLINE was searched from January 1989 through
August 2004 using the key words depression, preg-
nancy, prenatal, and antenatal. Articles were also
gathered from the references of papers generated
by the initial search. For this article, the search
was limited to English-language human studies;
articles focusing on depression during pregnancy
were chosen for review. Th e articles were based on
expert opinion (level III evidence) and prospec-
tive studies (level II evidence). Th ere are few trials
off ering level I evidence in this area due to ethical
restrictions on extracting data on pregnant popula-
tions. Available data have been incorporated into
this review.
Course of depression
during pregnancy
Diagnosis of major depression is often made by
mental health professionals during structured
clinical interviews using criteria described in
the Diagnostic and Statistical Manual of Mental
Disorders, fourth edition, text revision (DSM-IV-
TR).4 For family physicians facing time constraints,
one of the quickest ways to assess pregnant wom-
en’s moods is through responses to self-reported
questionnaires in conjunction with objective ques-
tions to assess mood.
Screening methods, such as the Edinburgh
Postnatal Depression Scale (EPDS) (Figure 1),5
have been developed for assessing postpartum
depression. As yet, no screening tools are specifi -
cally designed for assessing antenatal depression.
Murray and Cox6 investigated use of the EPDS dur-
ing pregnancy and found that it was eff ective at
identifying women with major depression (level II
evidence). Th e EPDS is commonly used in research
to detect perinatal mood disorders.7-9 Because the
EPDS is only a screening tool, high scores do not
in themselves confi rm diagnosis of depression. A
score above 12 indicates probable depressive disor-
der.6,7 Other self-rating screening tools, such as the
Beck Depression Inventory (BDI),10 tend to focus on
somatic symptoms and, therefore, make detection
of depression during pregnancy diffi cult. We need
screening tools that take into account the overlap
between symptoms of pregnancy and symptoms of
depression.
During the fi rst trimester, it can be particularly
difficult to diagnose depression because of this
overlap. Bennett et al9 reported a rate of depression
of 7.4% during the fi rst trimester. During the second
trimester, this fi gure rose to 12.8% and remained at
12% during the third trimester (level I evidence). In
a longitudinal study, Josefsson et al8 examined rates
of depression during late pregnancy and reported
Dr Ryan is a Clinical Assistant Professor in the
Department of Psychiatry at the University of British
Columbia and is a Psychiatrist with the Reproductive
Mental Health Program at St Paul’s Hospital and BC
Women’s Hospital and Health Centre in Vancouver.
Ms Milis and Mr Misri are researchers in the
Reproductive Mental Health Programs at St Paul’s
Hospital and BC Women’s Hospital and Health Centre.
here is growing evidence to challenge the
notion that pregnancy protects patients from
mental illness. Rates of depression during
pregnancy have been reported to be as high as 20%.
Levels of evidence
Level I: At least one properly conducted random-
ized controlled trial, systematic review, or meta-
analysis
Level II: Other comparison trials, non-randomized,
cohort, case-control, or epidemiologic studies,
and preferably more than one study
Level III: Expert opinion or consensus statements

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rates of 17%. When patients were followed into
the postpartum period, rates were found to have
decreased to 13% by 6 to 8 weeks after the birth
(level II evidence). Evans et al7 followed a group
of women through pregnancy to the postpartum
period and found that levels of depression during
pregnancy were comparable to those reported dur-
ing the postpartum period (level II evidence).
Gotlib and colleagues1 were among the fi rst to
point out a continuum of depression through preg-
nancy and into the postpartum period (level II
evidence). Despite their observation, research dur-
ing the past 25 years has focused on postpartum
depression, rendering pregnancy-related depres-
sion a secondary issue. While the DSM-IV-TR rec-
ognizes postpartum-onset mood disorders, it does
not make any reference to depression during preg-
nancy.
Only during the last 4 years have we seen depres-
sion during pregnancy resurface as an area of impor-
tance in the literature. This is due in part to the
increase in referrals of depressed pregnant patients
to reproductive psychiatry programs. Th is increase
might reflect patients’ increasing willingness to
report symptoms to their primary caregivers or a
heightened awareness among physicians of the onset
Figure 1. Edinburgh Postnatal Depression Scale
INSTRUCTIONS FOR USERS
1. The mother is asked to underline the response that comes closest to how she has been feeling in the previous 7 days.
2. All 10 items must be completed.
3. Care should be taken to avoid the possibility of the mother’s discussing her answers with others.
4. The mother should complete the scale herself, unless she has limited English or has diffi culty with reading.
Name: _______________________________ Baby’s age: ______
Address: ____________________________________________
Please UNDERLINE the answer that comes closest to how you have felt IN THE PAST 7 DAYS, not just how you feel today.
I have been able to laugh and see the funny side of things.
0 As much as I always could
1 Not quite so much now
2 Defi nitely not so much now
3 Not at all
I have looked forward with enjoyment to things.
0 As much as I ever did
1 Rather less than I used to
2 Defi nitely less than I used to
3 Hardly at all
*I have blamed myself unnecessarily when things went wrong.
3 Yes, most of the time
2 Yes, some of the time
1 Not very often
0 No, never
I have been anxious or worried for no good reason.
0 No, not at all
1 Hardly ever
2 Yes, sometimes
3 Yes, very often
*I have felt scared or panicky for no very good reason.
3 Yes, quite a lot
2 Yes, sometimes
1 No, not much
0 No, not at all
























*Items are reverse scored (ie, 3, 2, 1, 0). Responses are scored 0, 1, 2, and 3 according to increased severity of symptoms. Total score is calculated by adding the scores for each of the 10 items.
Scores >12 identify patients at risk for postpartum depression.
Figure reproduced from Cox et al.5 Users may reproduce the scale without further permission providing they respect copyright by quoting the names of the authors, the title, and the source of
the paper in all reproduced copies.
*Things have been getting on top of me.
3 Yes, most of the time I haven’t been able to cope at all
2 Yes, sometimes I haven’t been coping as well as usual
1 No, most of the time I have coped quite well
0 No, I have been coping as well as ever
*I have been so unhappy that I have had diffi culty sleeping.
3 Yes, most of the time
2 Yes, sometimes
1 Not very often
0 No, not at all
*I have felt sad or miserable.
3 Yes, most of the time
2 Yes, quite often
1 Not very often
0 No, not at all
*I have been so unhappy that I have been crying.
3 Yes, most of the time
2 Yes, quite often
1 Only occasionally
0 No, never
*The thought of harming myself has occurred to me.
3 Yes, quite often
2 Sometimes
1 Hardly ever
0 Never

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Depression during pregnancy
of illness during pregnancy. Th e fact that depression,
if left undiagnosed, can persist throughout preg-
nancy into the postpartum period is gaining wide-
spread recognition today (level II evidence).1,2,7,8
Risk factors
Many studies have delineated the risk factors associ-
ated with depression during pregnancy; risk factors are
summarized in Table 1. Personal and family history of
depression are substantial biologic risk factors (level II
evidence).11,12 Major psychosocial risk factors are his-
tory of childhood abuse, domestic violence or marital
confl ict, substance abuse or smoking, inadequate social
support, single motherhood, lower educational levels,
and unemployment (level II evidence).1,11,13-16
Once at-risk patients have been identified,
they can be monitored throughout pregnancy
for early signs of illness, whether it is new onset,
exacerbation, or relapse of an existing depression.
Treatment
Interventions for depression during pregnancy
most commonly include antidepressant medica-
tions; psychotherapy (individual or group); bright-
light therapy; and very rarely, electroconvulsive
therapy (ECT).
Th e two most commonly used psychotherapies
are interpersonal therapy (IPT), which focuses
on improving social interactions and coping with
life transitions, and cognitive behavioural therapy
(CBT), which aims to adjust patients’ self-defeating
thought patterns. Using IPT during pregnancy has
been shown to improve mood substantially after
16 weeks (level I evidence).17 Unfortunately, there
is little research on the eff ectiveness of other non-
pharmacologic treatments for prenatal depression.
Although the eff ectiveness of CBT for PPD has been
demonstrated (level I evidence),18 to date there is no
research on its use for depression during pregnancy.
The effectiveness of group therapy for depression
during pregnancy has not been reported, although
antenatal group therapy has been shown to be eff ec-
tive in preventing PPD (level II evidence).19
Pharmacologic treatment. Selective serotonin
reuptake inhibitors (SSRIs) and selective serotonin
and norepinephrine reuptake inhibitors (SNRIs), are
most commonly used today. Th e older antidepres-
sants, like the tricyclic antidepressants, are no lon-
ger used routinely as fi rst-line treatment for major
depression. Th e SSRIs include fl uoxetine (eg, Prozac),
paroxetine (Paxil), sertraline (eg, Zoloft), fl uvoxamine
(eg, Luvox), and citalopram (Celexa). Venlafaxine is
an example of a SNRI antidepressant. Bupropion (eg,
Wellbutrin) and mirtazapine (Remeron) are among
the newer dual-action antidepressants we are seeing
in pregnant women. All SSRIs, as well as venlafax-
ine (Eff exor), have been found to cross the placenta.
Paroxetine and sertraline pass through the placenta
more slowly than fluoxetine (level II evidence),20
but this fi nding must be interpreted with caution in
clinical practice. If a patient has responded best to
fl uoxetine, for example, it is recommended that she
continue taking fluoxetine throughout pregnancy.
Because every mother and baby metabolize medi-
cation diff erently, no universal statement about the
choice of a particular medication during pregnancy
can be made. Table 221-38 summarizes research fi nd-
ings on SSRI and SNRI exposure during pregnancy.
When a woman is treated with antidepressants
during pregnancy, both mother’s and doctor’s
concerns relate to the risk of teratogenesis, neonatal
Table 1. Summary of risk factors for developing depression during
pregnancy
BIOLOGIC
History of mood and anxiety disorders
History of postpartum depression
History of premenstrual dysphoric disorder
Family history of psychiatric illness
PSYCHOSOCIAL
History of childhood abuse
Younger age
Unplanned pregnancy
Ambivalence or negative feelings about the pregnancy
Single motherhood
Greater number of children
Limited social support
Domestic violence or marital confl ict
Low level of education and unemployment
Substance abuse and smoking

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toxicity, and long-term effects on child develop-
ment.39 During the first trimester, the main con-
cern is malformation of the fetus, although there is
no current evidence that SSRIs or venlafaxine cause
increased teratogenicity (level I evidence).28,40,41
Concerns in the third trimester focus on neona-
tal withdrawal because third-trimester exposure
to antidepressants has been correlated with higher
risk of adverse eff ects in neonates, such as respi-
ratory distress, feeding diffi culties, and low birth
weight. Th ese eff ects, however, have been shown to
be transient (level I evidence).23-25 Although there is
little evidence from research, no long-term adverse
eff ects from prenatal exposure to SSRIs or venla-
faxine have been reported (level II evidence).26,27,42
Th is area requires ongoing research.
A mother’s mood should be monitored very
closely throughout pregnancy, particularly in the
third trimester, where somatic changes might
lead to fl uctuating dose requirements (level II evi-
dence).43,44 In a recent study, pharmacologically
undertreated maternal mood disorders during the
third trimester were found to contribute to poor
neonatal adaptation (level II evidence).45
Health Canada recently issued a caution about
use of SSRIs during the third trimester. Although
mothers and doctors might be concerned about
exposure, rapid discontinuation of medications
is not recommended because it can substantially
increase risk of relapse (level II evidence).46 It is
always important to inform obstetricians and neo-
natologists about exposure to SSRIs in utero so that
babies can be closely monitored during delivery
and receive appropriate treatment, if necessary.
Among the more than 400 case reports on short-
and long-term eff ects of exposure to tricyclic medi-
cations during pregnancy, few major adverse eff ects
have been reported.47,48 In spite of this, because of
their side eff ect profi le, tricyclics are used less fre-
quently today. Monoamine oxidase inhibitors are
not recommended during pregnancy.
Nonpharmacologic biologic treatments. Bright-
light therapy could be an alternative to pharma-
cologic intervention and has been shown to be
effective for treating antenatal depression (level
II and III evidence).49,50 It is particularly helpful
for patients who report seasonal variation in their
moods and who do not want to use antidepressants
during pregnancy.
Several case reports have shown ECT to be
relatively safe and effective during pregnancy
(level II evidence).51-53 Th e American Psychiatric
Association, however, has strict guidelines for
administration of ECT54: it should be used only
when women are severely psychotic or acutely sui-
cidal and when other therapies or medications have
clearly failed.
Treatment of depression during pregnancy
requires patients and physicians to make collabora-
tive decisions. Each treatment needs to be chosen
on a case-by-case basis. For example, women with
Table 2. Summary of research fi ndings on the safety of taking
antidepressants during pregnancy: There was no increased risk of
teratogenicity with any of the medications.
MEDICATION
(NO. OF BABIES EXPOSED)
OBSTETRIC COMPLICATIONS
AND NEONATAL
WITHDRAWALLONG-TERM EFFECTS
Fluoxetine21-27 (1532)Third trimester:
premature delivery or
perinatal
complications; higher
doses might lead to low
birth weight; transient
withdrawal symptoms*
No long-term adverse
eff ects; children of
depressed mothers did
not have cognitive and
language diffi culties
Sertraline24,25,28-30 (234) Transient withdrawal
symptoms*
Further research
required
Paroxetine24,25,28,30,31
(313)
Transient withdrawal
symptoms*
Further research
required
Citalopram22-24,30,32,33
(318) Swedish birth
registry (375);
Lundbeck Safety
Database (100)
NoneFurther research
required
Fluvoxamine28-30 (30)None Further research
required
Venlafaxine24,29,34 (174) Transient withdrawal
symptoms*
Further research
required
Mirtazapine35,36 (9)None Further research
required
Bupropion37 (534)None Further research
required
Trazodone38 (58)
Nefazodone38 (89)
NoneFurther research
required
*Transient neonatal withdrawal symptoms include respiratory distress, jaundice, jitteri-
ness, increased fussing, tremors, and increased crying.