Antenatal Depression

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Mild to moderate antenatal unipolar depression:

Treatment
Author: Sophie Grigoriadis, MD, MA, PhD, FRCPC
Section Editors: Peter P Roy-Byrne, MD, Charles J Lockwood, MD, MHCM
Deputy Editor: David Solomon, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2020. | This topic last updated: Aug 09, 2019.
INTRODUCTION
Unipolar major depression is common in pregnant women and is often not treated [1,2]. In a
nationally representative survey in the United States that identified pregnant women with
major depression, only 50 percent received treatment [3]. Untreated disease causes
maternal suffering and is associated with poor nutrition, comorbid substance use disorders,
poor adherence with prenatal care, postpartum depression, impaired relationships between
the mother and her infant and other family members, and an increased risk of suicide [4,5].
Barriers to treatment of antenatal depression include cost, opposition to treatment (eg, fear
of exposing the fetus to antidepressant medication or lack of interest in psychotherapy),
unavailability of psychotherapy, and stigma [4,5]. In addition, many physicians are reluctant
to prescribe medications because they lack sufficient expertise [6], and the large literature is
often inconsistent [7].
This topic reviews choosing a specific treatment for mild to moderate episodes of antenatal
unipolar major depression. Other topics discuss the treatment of severe episodes of
antenatal unipolar major depression; general principles of treatment; risks of
https://www.uptodate.com/contents/mild-to-moderate-antenatal-unipolar-depression-treat... 8/11/2020
antidepressants during pregnancy; and the epidemiology, clinical features, assessment, and
diagnosis of antenatal depression.
● (See "Severe antenatal unipolar major depression: Choosing treatment".)
● (See "Unipolar major depression in pregnant women: General principles of treatment".)
● (See "Antenatal use of antidepressants and risk of teratogenicity and adverse

pregnancy outcomes: Selective serotonin reuptake inhibitors (SSRIs)".)
● (See "Antenatal use of antidepressants and risks of teratogenicity and adverse

pregnancy outcomes: Drugs other than selective serotonin reuptake inhibitors".)
● (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and

serotonin-norepinephrine reuptake inhibitors (SNRIs): Neonatal outcomes".)
● (See "Unipolar major depression during pregnancy: Epidemiology, clinical features,

assessment, and diagnosis".)
DEFINITIONS
Unipolar major depression — Unipolar major depression (major depressive disorder) is

diagnosed in patients who have suffered at least one major depressive episode and have
no history of mania or hypomania [8]. An episode of unipolar major depression is a period
lasting at least two weeks, with five or more of the following nine symptoms: depressed
mood, loss of interest or pleasure in most or all activities, insomnia or hypersomnia, change
in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration,
guilt or thoughts of worthlessness, and recurrent thoughts about death or suicide (table 1).
Additional information about the clinical presentation and diagnosis of unipolar major
depression is discussed separately. (See "Unipolar depression in adults: Clinical features"
and "Unipolar depression in adults: Assessment and diagnosis".)
Severity of illness — Selecting a treatment for antenatal major depression often depends
upon the severity of illness:
● Mild to moderate – Mild to moderate episodes of unipolar major depression are

generally characterized by five or six depressive symptoms (table 1), as indicated by a
score <20 points on the self-report Patient Health Questionnaire – Nine Item (PHQ-9)
(table 2). However, the instrument includes items about changes in appetite, energy,
and sleep, which may reflect the physical effects of pregnancy rather than depression.
Additional information about the PHQ-9 is discussed separately. (See "Using scales to
monitor symptoms and treat depression (measurement based care)".)
Patients with mild to moderate illness do not manifest suicidal behavior or obvious
impairment of functioning, and are less likely to develop complications such as
psychotic features and catatonic features, compared with patients who are severely ill.
Mild to moderate depression can typically be managed in outpatient or partial hospital
settings.
● Severe – Severe unipolar major depression is characterized by seven to nine

depressive symptoms (table 1), as indicated by a score ≥20 points on the Patient
Health Questionnaire – Nine Item (PHQ-9) (table 2). Severely ill patients often report
suicidal ideation and behavior, typically demonstrate obvious impairment of functioning,
and often manifest poor judgement that places the patient and others (including
children) at risk for imminent harm. In addition, patients with severe depression can
develop complications such as psychotic features and catatonic features, and often
have a history of severe or recurrent depressive episodes [8]. Patients with severe
major depression should be referred to a psychiatrist for management and often require
hospitalization [9,10].
Difficulties may arise in determining the number of depressive symptoms that are present
during pregnancy because changes in appetite, energy, and sleep may due to depression,
or may represent normal pregnancy-related changes. The presence of these somatic
symptoms should be evaluated in the context of normal expectations for pregnancy. As an
example, although food aversions can occur during pregnancy, patients with anorexia who
fail to gain weight may have mild to moderate depression, and pregnant patients with
anorexia who lose weight may have severe depression. In the same vein, pregnancy can
cause fatigue. However, lack of energy to the point that patients need to make a significant
effort to initiate or maintain usual daily activities can be a mild to moderate depressive
symptom, and anergia to the point that patients cannot get out of bed for hours is probably a
symptom of severe depression. Persistent uncertainty as to whether an episode of major
depression is mild to moderate or severe can be resolved by referral to a psychiatrist
(preferably one specializing in perinatal disorders).
GENERAL PRINCIPLES
The general principles and issues that are involved in treating unipolar major depression
during pregnancy include:
● Setting
● History of prior treatment
● Educating patients and families
● Adherence
● Monitoring symptoms
● Prescribing antidepressants
● Managing nonresponse
● Making referrals
These general principles are discussed in detail separately. (See "Unipolar major
depression in pregnant women: General principles of treatment".)
CHOOSING TREATMENT
Approach to treatment — We suggest that acute treatment of pregnant patients with mild
to moderate episodes of unipolar major depression proceed according to the sequence
described in the subsections below. Patients generally start with initial therapy and progress
through each step until they respond. The best evidence supports using a structured
psychotherapy such as cognitive-behavioral therapy (CBT) or interpersonal psychotherapy
as the primary treatment. However, many patients receive antidepressant medications. All
patients should receive psychoeducation about depression as part of treatment. (See
"Unipolar major depression in pregnant women: General principles of treatment", section on
'Educating patients and families'.)
It is important assess the benefit of previous treatment in order to guide treatment selection.
If psychotherapy is indicated and the patient was successfully treated with a particular
psychotherapy prior to pregnancy, the same therapy generally is used during pregnancy.
Similarly, if pharmacotherapy is indicated and the patient was successfully treated with a
particular antidepressant prior to pregnancy, the same drug is typically used during
pregnancy.
Continuation treatment is generally indicated for patients who respond to acute treatment of
unipolar major depression, and additional maintenance treatment is indicated for patients
with an increased risk of recurrence. (See "Unipolar depression in adults: Continuation and
maintenance treatment".)
Initial treatment — For mild to moderate episodes of antenatal unipolar major

depression, we recommend a structured psychotherapy (eg, CBT or interpersonal
psychotherapy) as first-line treatment [1,11-13]. Psychotherapies developed outside of the
antenatal context typically require modification for use in pregnant patients.
Administering structured psychotherapy as first-line treatment of mild to moderate antenatal

depression is consistent with multiple treatment guidelines, including those from the
American Psychiatric Association, American College of Obstetricians and Gynecologists,
and the United Kingdom National Institute for Health and Care Excellence [14-17]. In
addition, pregnant women typically prefer psychotherapy over pharmacotherapy [18,19].
Evidence supporting the use of psychotherapy includes numerous randomized trials that
found psychotherapy was efficacious in the general population of adults with depression.
(See "Unipolar major depression in adults: Choosing initial treatment", section on 'Efficacy
of psychotherapy'.)
In addition, randomized trials in patients with prenatal major depression support using
structured psychotherapies (see 'Cognitive-behavioral therapy' below and 'Interpersonal
psychotherapy' below). However, many of the studies have limitations, which include
diagnosing major depression with self-report questionnaires rather than clinical interviews,
and the failure to adequately blind outcome ratings. In addition, some trials lack active
comparators to control for the nonspecific aspects (eg, attention) of psychotherapy, and
instead use less rigorous comparators such as usual care or waiting lists.
Antidepressant medication is a reasonable alternative to structured psychotherapy for mild

to moderate episodes of antenatal unipolar major depression if [5,20]:
● Psychotherapy is not available or acceptable to patients
● Patients prefer pharmacotherapy (eg, they previously responded well to

antidepressants)
● Patients have a past history of severe depression (mild to moderate depression can
progress in severity) (see 'Severity of illness' above)
Choosing an antidepressant is discussed separately. (See "Severe antenatal unipolar major

depression: Choosing treatment", section on 'Initial treatment'.)
When treating mild to moderate antenatal depression with structured psychotherapy, we

typically choose either CBT or interpersonal psychotherapy. We use CBT in patients with
prominent symptoms of anxiety, and prefer interpersonal psychotherapy if the depressive
syndrome occurs in the context of role disputes, role transitions, or grief. Both therapies
have demonstrated efficacy in randomized trials in patients with perinatal depression
[1,11,21]. In addition, these two therapies have been more widely studied than other
psychotherapies in the general population of patients with depression. (See "Unipolar major
depression in adults: Choosing initial treatment", section on 'Selecting a specific
psychotherapy'.)
Structured psychotherapy for unipolar major depression is usually time limited (eg, 6 to 10
sessions); thus, patients treated with CBT or interpersonal psychotherapy generally receive
a full course of therapy, regardless if nonresponse persists through the middle phases of
treatment.
Mild episodes of antenatal major depression are characterized by only five depressive
symptoms, the absence of suicidal ideation, and minimal impairment of functioning. For
these patients, supportive psychotherapy is a reasonable alternative to CBT, interpersonal
psychotherapy, and antidepressants. Supportive psychotherapy treats depression by
improving self-esteem, psychological functioning, and adaptive skills; the therapy focuses
upon current, problematic relationships and maladaptive patterns of behavior and emotional
responses. Evidence supporting the use of supportive psychotherapy includes randomized
trials in the general population of patients with depression. In addition, an eight-week
randomized trial compared omega-3 fatty acids plus supportive psychotherapy (six
sessions, each lasting 30 minutes) with placebo plus supportive psychotherapy in women
with antenatal depression (n = 21) or postpartum depression (n = 30) [22,23]. The benefit of
omega-3 fatty acids and placebo were comparable; across both treatment groups (n = 51),
remission occurred in 31 percent. The administration and efficacy of supportive
psychotherapy in the general population of patients with depression are discussed
separately. (See "Unipolar depression in adults: Supportive psychotherapy".)
Other alternatives for patients with mild antenatal depression include low intensity
approaches such as bright light therapy, exercise/yoga, massage therapy, omega-3 fatty
acids, and peer support. (See 'Other options' below.)
In addition, reasonable alternatives to structured psychotherapy and antidepressants for

patients with mild episodes of major depression include clinician guided self-help
approaches. (See "Unipolar major depression in adults: Choosing initial treatment", section
on 'Clinician-guided self-help'.)
It is also reasonable to manage mild episodes of antenatal major depression with watchful
waiting and frequent monitoring (eg, weekly).
Cognitive-behavioral therapy — Cognitive-behavioral therapy (CBT) for major

depression combines cognitive therapy and behavioral therapy. Cognitive therapy attempts
to modify dysfunctional thoughts and illness beliefs; one technique is cognitive restructuring,
which involves reframing distorted thoughts (eg, “I’m no good”) by empirically testing them
and considering more benign explanations. Behavioral therapy aims to change problematic
behaviors that occur in response to dysfunctional thoughts, depressive symptoms, and
environmental stimuli; specific techniques include behavioral activation (counteracting
inertia and avoidance by assigning rewarding activities for patients to complete between
treatment sessions), problem solving (identifying the problem, generating multiple solutions,
considering the consequences of each solution, choosing one solution, and acting upon it),
progressive muscle relaxation, abdominal breathing exercises, and physical exercise.
The use of CBT is based upon many randomized trials in the general population of patients
with depression [24,25]. As an example,
● A meta-analysis of 115 trials (number of patients not reported) compared CBT with a
control condition (waiting list, usual care, or pill placebo) and found a significant,
clinically moderate to large effect favoring CBT [26].
● A pooled analysis of eight trials (number of patients not reported) compared CBT with a
control condition (eg, waiting list, usual care, or another active treatment), and found
that remission occurred in twice as many patients who received CBT than the control
condition (42 versus 21 percent) [27].
In addition, randomized trials and observational studies in patients with antenatal

depression have found that CBT is beneficial:
● A meta-analysis of seven studies (primarily randomized trials, sample size not reported)
compared CBT with a control condition and found a significant, clinically moderate
effect favoring CBT [28].
● A 15-week randomized trial not included in the meta-analysis compared CBT (12
individual sessions at the woman’s home) plus usual care with usual care alone in
pregnant patients who completed the study (n = 29) [29]. Symptomatic improvement
was greater in patients who received CBT than usual care alone.
Interpersonal psychotherapy — Interpersonal psychotherapy in pregnant women

with depression typically focuses upon role transitions (major changes in life roles or
circumstances) and role disputes (conflicts with others over different expectations about the
relationship). The administration of interpersonal psychotherapy for unipolar depression is
discussed separately. (See "Interpersonal Psychotherapy (IPT) for depressed adults:
Specific interventions and techniques".)
Evidence for the efficacy of interpersonal psychotherapy includes numerous randomized

trials in the general population of patients with unipolar major depression. (See
"Interpersonal Psychotherapy (IPT) for depressed adults: Indications, theoretical foundation,
general concepts, and efficacy", section on 'Evidence of efficacy'.)
Studies in patients with prenatal depression also suggest that interpersonal psychotherapy
is efficacious. A meta-analysis of 12 randomized trials and observational studies compared
interpersonal psychotherapy with a control condition in women with either prenatal
depression (n = 891) or postpartum depression (n = 112) [30]. The analysis found a
significant, clinically moderate effect favoring interpersonal psychotherapy over the control
conditions. Examples of randomized trials included in the meta-analysis are as follows:
● A three-month randomized trial compared interpersonal psychotherapy (nine sessions)

with treatment as usual in pregnant patients with depression (n = 53); both treatment
groups received case-management services [31]. Response (reduction of baseline
symptoms ≥50 percent) occurred in more women who received interpersonal
psychotherapy than controls (80 versus 25 percent).
● A 16-week randomized trial compared interpersonal psychotherapy with parenting

education in women with antenatal depression who completed the study (n = 38); both
interventions consisted of weekly sessions lasting 45 minutes [32]. Recovery occurred
in more patients who received interpersonal psychotherapy than the parenting program
(60 versus 15 percent). In addition, improved mood translated into better mother-infant
interactions.
Treatment resistant patients — Patients with antenatal major depression of mild to

moderate severity may not respond to initial treatment; response is typically defined as
reduction of baseline symptoms ≥50 percent. Next step treatment depends upon the degree
to which the initial treatment is beneficial:
● For patients who are treated with either CBT or interpersonal psychotherapy and
achieve a partial response (eg, reduction of baseline symptoms 25 to 49 percent), we
suggest increasing the total number of sessions (eg, providing 12 to 16 sessions rather
than 8), based upon our clinical experience. In addition, some clinicians increase the
frequency of treatment (eg, administering two sessions/week rather than one/week).
● For patients who are treated with either CBT or interpersonal psychotherapy and
achieve only a minimal response (eg, improvement <25 percent), we suggest switching
to the other psychotherapy, based upon our clinical experience.
In addition, we suggest that clinicians prescribe add-on treatments, depending upon

availability and patient preference. (See 'Other options' below.)
Treatment refractory patients — Patients with antenatal major depression of mild to

moderate severity may not respond to sequential courses of CBT and interpersonal
psychotherapy plus add-on treatments. For these treatment refractory patients, next step
treatment depends upon the degree of functional impairment:
● For patients with minimal impairment (eg, occupational functioning is intact) who want
to remain medication free, we suggest supportive psychotherapy.
● For patients with substantive impairment (eg, patients are skipping obstetric
appointments), we suggest pharmacotherapy, either alone or combined with supportive
psychotherapy. Choosing an antidepressant is discussed separately. (See "Severe
antenatal unipolar major depression: Choosing treatment", section on 'Initial treatment'.)
For all treatment refractory patients, we suggest using a different add-on treatment,
depending upon availability and patient preference. (See 'Other options' below.)
Other options — For patients with mild to moderate antenatal depression who do not
respond to initial and subsequent therapies, we suggest the following options as adjunctive
interventions [33]. In addition, these interventions can be used alone in patients with mild
episodes of major depression (see 'Initial treatment' above). In either case, the specific
choice depends upon patient preferences and availability.
● Acupuncture
● Bright light therapy
● Exercise/yoga
● Family/couples therapy
● Folic acid
● Massage therapy
● Omega-3 fatty acids
● Peer support
● S-adenosyl methionine
Evidence supporting the use of these treatments includes the following:
● Acupuncture – Although the evidence is insufficient to recommend the use of

acupuncture for the general population of patients with depression [34], randomized
trials have reported that acupuncture may be efficacious for antenatal depression:
• One eight-week trial compared acupuncture specific for depression (12 sessions)
with acupuncture not specific for depression in pregnant women with unipolar
major depression (n = 101) [35]. Response (reduction of baseline symptoms ≥50
percent) occurred in more patients who received active treatment than controls (63
versus 38 percent). The rate of adverse events (eg, feeling tired after treatment) for
the two groups was comparable.
• Another trial from the same research group compared acupuncture specific for
depression (12 sessions over eight weeks) with acupuncture not specific for
depression in pregnant women with unipolar major depression (n = 35) [36].
Response occurred in more patients who received active treatment than controls
(9 in 19 versus 11 in 16 [69 versus 47 percent]); although this difference was not
statistically significant, a difference of this magnitude, if real, would be clinically
meaningful.
General information about acupuncture is discussed separately. (See "Acupuncture".)
● Bright light therapy – Bright light therapy can be beneficial for seasonal affective
disorder as a stand-alone treatment, and can also help patients with nonseasonal
depressive syndromes [37-41]. As an example, randomized trials indicate that in the
general population of patients with nonseasonal, unipolar major depression, bright light
therapy can be efficacious as augmentation. (See "Unipolar depression in adults and
initial treatment: Investigational and nonstandard approaches", section on 'Bright light
therapy'.)
In addition, bright light therapy may be useful for antenatal depression. A small, five-
week randomized trial compared bright light therapy (7000 lux bright white light) with
placebo (70 lux dim red light) in pregnant patients with nonseasonal major depression
(n = 27) [42]. Each study treatment was administered for one hour/day. Most patients
received no other treatment, but four patients had initiated a selective serotonin
reuptake inhibitor prior to the study and continued the drug during the study. Remission
occurred in more patients who received bright light therapy than placebo (11 in 16
versus 4 in 11 [69 versus 36 percent]). No clinically meaningful side effects were
observed and all pregnancy deliveries occurred without complication. Information about
the administration, safety, and side effects of bright light therapy is discussed
separately. (See "Seasonal affective disorder: Treatment", section on 'Bright light
therapy'.)
● Exercise/yoga – In the absence of medical or obstetric complications, the general

population of pregnant women is typically encouraged to exercise. (See "Exercise
during pregnancy and the postpartum period".)
In addition, randomized trials suggest that exercise (eg, yoga) is beneficial for antenatal
depression. As an example, a meta-analysis of six randomized trials compared
exercise with a control condition in patients with antenatal depressive symptoms (n =
348) [43]. Five of the trials utilized yoga as the exercise intervention; one trial used
aerobic exercise. The control conditions included usual care, waiting list, social support
group, or parenting education. The analysis found a significant effect favoring exercise
over the comparators, and the clinical benefit was moderately large. However, the
quality of the trials was low to moderate, heterogeneity across studies was moderate to
large, and the safety and incidence of adverse events was not discussed in any of the
trials.
The efficacy and use of exercise in the general population of patients with depression is
discussed separately. (See "Unipolar major depression in adults: Choosing initial
treatment", section on 'Exercise'.)
● Family/couples therapy – For pregnant patients with mild to moderate depressive

disorders that stem from poor family functioning and marital problems, family therapy
may be used as a primary or adjunctive treatment, based upon randomized trials in
patients who usually were not pregnant. During evaluations for family therapy, women
should be assessed individually to assure privacy, particularly when screening for
intimate partner violence, and again with her partner to assess any relationship discord.
The assessment of families and efficacy and administration of family therapy are
discussed separately. (See "Unipolar depression in adults: Family and couples
therapy".)
● Folic acid – Folic acid is recommended for all pregnant women to prevent neural tube
defects. (See "Nutrition in pregnancy", section on 'Folic acid' and "Folic acid
supplementation in pregnancy".)
In addition, indirect evidence suggests that adjunctive folic acid may perhaps be
beneficial for antenatal depression:
• A randomized trial compared folic acid (500 micrograms/day) plus fluoxetine (20
mg/day) with placebo plus fluoxetine as initial treatment in patients with unipolar
major depression (n = 127; females who were pregnant were excluded) [44].
Response (reduction of baseline symptoms ≥50 percent) occurred in more patients
who received adjunctive folic acid than placebo (82 versus 62 percent). The benefit
appeared to be greater for women than men.
• An observational study of pregnant women (n = 709) included women with

clinically significant depressive symptoms (n = 51, 7 percent) [45]. Serum folate
concentrations were lower in the pregnant women with depressive symptoms than
the pregnant women without depressive symptoms.
However, randomized trials studying the use of folate in the general population of
patients with treatment resistant patients have found that the benefit is modest at best.
(See "Unipolar depression in adults: Management of highly resistant (refractory)

depression", section on 'Treatments with little to no benefit'.)
● Massage – Randomized trials in depressed patients who were not pregnant indicate
that massage therapy may be useful for antenatal depression. A meta-analysis of 17
trials compared massage therapy with control conditions (eg, progressive muscle
relaxation) in patients with depressive symptoms (n = 786; pregnant patients were
excluded); the study found a significant, clinically large effect favoring massage therapy
[46].
In addition, multiple randomized trials indicate that maternal massage can be helpful for
antenatal depression [47,48]:
• A six-week trial compared massage therapy plus group interpersonal

psychotherapy with group interpersonal psychotherapy alone in patients with
prenatal depression (n = 112); each treatment was administered once per week
[49]. Improvement of depression was greater in the group that received adjunctive
massage therapy; anxiety also improved more with massage therapy.
• A 16-week trial (n = 56 patients with depressive symptoms) compared massage

therapy with progressive muscle relaxation; each treatment was administered twice
per week [50]. Improvement of depression was greater with massage therapy than
muscle relaxation. In addition, anxiety and leg and back pain improved more with
massage therapy. The incidence of prematurity and low birthweight were each less
with massage therapy, and neonatal functioning was better in babies of mothers
treated with massage therapy.
• A 12-week trial compared massage therapy (two sessions per week) with usual
care in pregnant patients with major depression (n = 149) [51]. Improvement of
depressive symptoms was greater with massage therapy than usual care. In
addition, prematurity and low birth weight occurred in fewer babies of mothers
treated with massage therapy and neonatal functioning was better in babies of
mothers treated with massage therapy.
● Omega-3 fatty acids – Consumption of foods with omega-3 fatty acids is often
encouraged for the general population of pregnant patients. (See "Fish consumption
and marine omega-3 fatty acid supplementation in pregnancy".)
Randomized trials suggest that in the general population of patients with unipolar major
depression, omega-3 fatty acids may be efficacious as add-on therapy. (See "Unipolar
depression in adults and initial treatment: Investigational and nonstandard
approaches".)
In addition, an eight-week randomized trial compared omega-3 fatty acids

(eicosapentaenoic acid 2.2 grams/day and docosahexaenoic acid 1.2 grams/day) with
placebo (olive oil) in pregnant women with unipolar major depression (n= 33) [52].
Improvement was greater with omega-3 fatty acids than placebo. In addition, no
obstetric complications occurred in any of the study patients, and all of the newborns
were healthy.
● Peer support – Evidence supporting the effectiveness of peer support includes

randomized trials in the general population of patients with depression. (See "Unipolar
depression in adults and initial treatment: General principles and prognosis", section on
'Peer support'.)
In addition, a 12-week randomized trial compared peer support (weekly group sessions,
each lasting 20 minutes) with interpersonal psychotherapy (weekly group sessions,
each lasting 60 minutes) in pregnant patients with a depressive syndrome [53].
Compared with patients treated with interpersonal psychotherapy, patients assigned to
peer support had a lower socioeconomic status and a higher level of baseline
depression as assessed with a rating scale. Despite the differences in the intensity of
treatment and baseline treatment group differences, improvement of depression, as
well as anxiety symptoms, was comparable for the two treatments.
● S-adenosyl methionine – S-adenosyl methionine may be useful for patients with

prenatal depression, based upon studies in the general population of patients with
treatment resistant depression. (See "Unipolar depression in adults: Management of
highly resistant (refractory) depression", section on 'Treatments with potential benefit'.)
In addition, five randomized trials that evaluated S-adenosyl methionine for cholestasis
during pregnancy found no adverse effects in mothers or their infants [33,54].
A systematic review found that the evidence for treating antenatal depression with
acupuncture, bright light therapy, massage therapy, or omega-3 fatty acids was
inconclusive, because the randomized trials were too small and many trials lacked adequate
methodologic rigor [55]. However, the review did not perform a meta-analysis of the
treatments for which there are multiple trials, and did not include all of the trials discussed in
this section; thus, we view the evidence as sufficient to justify adjunctive acupuncture, bright
light therapy, massage therapy, or omega-3 fatty acids, particularly given the low risk of
harm.
SEVERE ANTENATAL UNIPOLAR MAJOR DEPRESSION
Treatment of severe antenatal unipolar major depression is discussed separately. (See

"Severe antenatal unipolar major depression: Choosing treatment".)
ANTIDEPERESSANTS PRIOR TO CONCEPTION
The use of antidepressant medications prior to conception is discussed separately. (See

"Severe antenatal unipolar major depression: Choosing treatment", section on
'Antidepressants prior to conception'.)
UNPLANNED PREGNANCIES AND DISCONTINUING

ANTIDEPRESSANTS DURING PREGNANCY
Unplanned pregnancies and discontinuing antidepressants during pregnancy are discussed

separately. (See "Severe antenatal unipolar major depression: Choosing treatment", section
on 'Unplanned pregnancies and discontinuing antidepressants during pregnancy'.)
MINOR DEPRESSION
Unipolar minor depression is diagnosed in patients with two to four depressive symptoms
lasting for a period of at least two weeks, and no history of mania or hypomania (table 3).
(See "Unipolar minor depression in adults: Epidemiology, clinical presentation, and
diagnosis", section on 'Diagnosis'.)
Management of minor depression is discussed separately. (See "Unipolar minor depression

in adults: Management".)
BIPOLAR DEPRESSION
Depression can occur in the context of bipolar disorder, which is marked by episodes of
hypomania (table 4) or mania (table 5). Distinguishing bipolar depression from unipolar
depression is discussed separately, as is treatment of bipolar major depression during
pregnancy. (See "Bipolar disorder in adults: Assessment and diagnosis", section on
'Unipolar major depression' and "Bipolar disorder in pregnant women: Treatment of major
depression".)
ANTIDEPRESSANTS AND BREASTFEEDING
The safety of antidepressants in lactating women is discussed separately. (See "Safety of

infant exposure to antidepressants and benzodiazepines through breastfeeding", section on
'Antidepressants'.)
POSTPARTUM DEPRESSION
Treatment of postpartum unipolar depression and postpartum bipolar depression are

discussed separately. (See "Severe postpartum unipolar major depression: Choosing
treatment" and "Bipolar disorder in postpartum women: Treatment", section on 'Bipolar
major depression'.)
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● Basics topics (see "Patient education: Depression (The Basics)" and "Patient
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SUMMARY AND RECOMMENDATIONS
● An episode of unipolar major depression is a period lasting at least two weeks, with five
or more of the following symptoms: depressed mood, loss of interest or pleasure in
most or all activities, insomnia or hypersomnia, change in appetite or weight,
psychomotor retardation or agitation, low energy, poor concentration, guilt or thoughts
of worthlessness, and recurrent thoughts about death or suicide (table 1). (See
'Unipolar major depression' above.)
● Mild to moderate episodes of unipolar major depression are generally characterized by

five or six depressive symptoms. Patients with mild to moderate illness do not manifest
suicidal behavior or obvious impairment of functioning, are less likely to develop
complications such as psychotic features, and can typically be managed in outpatient
or partial hospital settings.
Severe unipolar major depression is characterized by seven to nine depressive

symptoms. Severely ill patients often report suicidal ideation and behavior, typically
demonstrate obvious impairment of functioning, and often manifest poor judgement that
places the patient and others at risk for imminent harm. In addition, patients with severe
depression can develop complications such as psychotic features, and often have a
history of severe or recurrent depressive episodes. Patients with severe major
depression should be referred to a psychiatrist for management and often require
hospitalization. (See 'Severity of illness' above.)
● The general principles and issues involved in treating unipolar major depression during
pregnancy include setting, history of prior treatment, educating patients and families,
adherence, monitoring symptoms, prescribing antidepressants, managing

nonresponse, and making referrals. (See "Unipolar major depression in pregnant
women: General principles of treatment".)
● For patients with mild to moderate episodes of antenatal unipolar major depression, we
suggest structured psychotherapy as initial treatment rather than other treatments
(Grade 2B). We typically choose either cognitive-behavioral therapy (CBT) or
interpersonal psychotherapy. However, if psychotherapy is not available or acceptable,
or if patients prefer pharmacotherapy or have a past history of severe depression,
antidepressant medication is a reasonable alternative to psychotherapy.
Mild episodes of antenatal major depression are characterized by only five depressive
symptoms, the absence of suicidal ideation, and minimal impairment of functioning. For
these patients, supportive psychotherapy is a reasonable alternative to CBT,
interpersonal psychotherapy, and antidepressants. Other alternatives include bright
light therapy, exercise/yoga, massage therapy, omega-3 fatty acids, peer support, and
clinician guided self-help approaches, as well as watchful waiting with frequent
monitoring (eg, weekly). (See 'Initial treatment' above.)
● Patients with antenatal major depression of mild to moderate severity may not respond
to initial treatment with either CBT or interpersonal psychotherapy. For these treatment
resistant patients who achieve a partial response (eg, reduction of baseline symptoms
25 to 49 percent), we suggest increasing the total number of sessions (Grade 2C). For
patients who are treated with either CBT or interpersonal psychotherapy and achieve
only a minimal response (eg, improvement <25 percent), we suggest switching to the
other psychotherapy (Grade 2C). In addition, it may be helpful to administer adjunctive
interventions such as acupuncture, bright light therapy, exercise/yoga, massage
therapy, omega-3 fatty acids, peer support, and S-adenosyl methionine; the choice
depends upon availability and patient preference. (See 'Treatment resistant patients'
above and 'Other options' above.)
● Patients with mild to moderate episodes of antenatal major depression may not
respond to sequential courses of CBT and interpersonal psychotherapy plus adjunctive
interventions. If these treatment refractory patients have minimal impairment of
functioning, we administer supportive psychotherapy. If these patients have substantive
impairment, we use an antidepressant, either alone or combined with supportive
psychotherapy. For all treatment refractory patients, we also use a different adjunctive
intervention. (See 'Treatment refractory patients' above and 'Other options' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 108261 Version 4.0
GRAPHICS
DSM-5 diagnostic criteria for a major depressive episode
A. Five (or more) of the following symptoms have been present during the same two-week period and
represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood
or (2) loss of interest or pleasure.
NOTE: Do not include symptoms that are clearly attributable to another medical condition.
1) Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels
sad, empty, hopeless) or observations made by others (eg, appears tearful). (NOTE: In children and
adolescents, can be irritable mood.)
2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every
day (as indicated by either subjective account or observation)
3) Significant weight loss when not dieting or weight gain (eg, a change of more than 5% of body weight
in a month), or decrease or increase in appetite nearly every day. (NOTE: In children, consider failure to
make expected weight gain.)
4) Insomnia or hypersomnia nearly every day
5) Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective
feelings of restlessness or being slowed down)
6) Fatigue or loss of energy nearly every day
7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every
day (not merely self-reproach or guilt about being sick)
8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by their
subjective account or as observed by others)
9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan,
or a suicide attempt or a specific plan for committing suicide
B. The symptoms cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning.
C. The episode is not attributable to the direct physiological effects of a substance or to another medical
condition.
NOTE: Criteria A through C represent a major depressive episode.
NOTE: Responses to a significant loss (eg, bereavement, financial ruin, losses from a natural disaster, a
serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss,
insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode.
Although such symptoms may be understandable or considered appropriate to the loss, the presence of a
major depressive episode in addition to the normal response to a significant loss should also be carefully
considered. This decision inevitably requires the exercise of clinical judgement based on the individual's
history and the cultural norms for the expression of distress in the context of loss.
D. The occurence of the major depressive episode is not better explained by schizoaffective disorder,
schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified
schizophrenia spectrum and other psychotic disorders.
E. There has never been a manic or hypomanic episode.
NOTE: This exclusion does not apply if all of the manic-like or hypomanic-like epsidoes are substance-
induced or are attributable to the physiological effects of another medical condition.
Specify:
With anxious distress
With mixed features
With melancholic features
With atypical features
With psychotic features
With catatonia
With peripartum onset
With seasonal pattern
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright
© 2013). American Psychiatric Association. All Rights Reserved.
Graphic 89994 Version 12.0
PHQ-9 depression questionnaire
Name: Date:
Over the last 2 weeks, how often have you been Not at Several More Nearly
bothered by any of the following problems? all days than every
half day
the
days
Little interest or pleasure in doing things 0 1 2 3
Feeling down, depressed, or hopeless 0 1 2 3
Trouble falling or staying asleep, or sleeping too much 0 1 2 3
Feeling tired or having little energy 0 1 2 3
Poor appetite or overeating 0 1 2 3
Feeling bad about yourself, or that you are a failure, or that 0 1 2 3

you have let yourself or your family down
Trouble concentrating on things, such as reading the 0 1 2 3

newspaper or watching television
Moving or speaking so slowly that other people could have 0 1 2 3

noticed? Or the opposite, being so fidgety or restless that
you have been moving around a lot more than usual.
Thoughts that you would be better off dead, or of hurting 0 1 2 3

yourself in some way
Total ___ = ___ + ___ + ___ + ___
PHQ-9 score ≥10: Likely major depression
Depression score ranges:
5 to 9: mild
10 to 14: moderate
15 to 19: moderately severe
≥20: severe
If you checked off any problems, how difficult have Not Somewhat Very Extremely
these problems made it for you to do your work, take difficult difficult difficult difficult
care of things at home, or get along with other people? at all ___ ___ ___
___
PHQ: Patient Health Questionnaire.
Developed by Drs. Robert L Spitzer, Janet BW Williams, Kurt Kroenke, and colleagues, with an educational grant
from Pfizer, Inc. No permission required to reproduce, translate, display or distribute.
Diagnostic criteria for minor depression
We suggest diagnosing minor depressive episodes according to all of the

following criteria (A through F).
A. Two to four of the following symptoms have been present during the same two-week period:
1. Dysphoria – Depressed mood most of the day, nearly every day

2. Anhedonia – Markedly diminished interest or pleasure most of the day, nearly every day
3. Significant appetite or weight change
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation (observable by others)
6. Anergia – Fatigue nearly every day
7. Thoughts of worthlessness or inappropriate guilt nearly every day
8. Impaired concentration or memory nearly every day
9. Recurrent thoughts of death or suicide, or suicide attempt
B. At least one of the symptoms includes dysphoria or anhedonia
C. The symptoms cause clinically significant distress of psychosocial impairment
D. The symptoms are not due to the physiologic effects of a substance, medication, or general medical
condition
E. Persistent depressive disorder (dysthymia) and cyclothymic disorder are not present
F. The mood disturbance does not occur exclusively during a psychotic disorder
These criteria for minor depression are similar to the criteria that are used in the American Psychiatric
Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for the diagnosis,
"Other specified depressive disorder, depressive episode with insufficient symptoms" (ie, the depressive
episode is characterized by an insufficient number of symptoms to meet criteria for major depression).
Reference:
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
(DSM-5), American Psychiatric Association, Arlington 2013.
DSM-5 diagnostic criteria for hypomanic episode
A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally
and persistently increased activity or energy, lasting at least four consecutive days and present most of the
day, nearly every day.
B. During the period of mood disturbance and increased energy and activity, three (or more) of the
following symptoms (four if the mood is only irritable) have persisted, represent a noticeable change from
usual behavior, and have been present to a significant degree:
1) Inflated self-esteem or grandiosity.
2) Decreased need for sleep (eg, feels rested after only three hours of sleep).
3) More talkative than usual or pressure to keep talking.
4) Flight of ideas or subjective experience that thoughts are racing.
5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli), as reported
or observed.
6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor

agitation.
7) Excessive involvement in activities that have a high potential for painful consequences (eg, engaging
in unrestrained buying sprees, sexual indiscretions, or foolish business investments).
C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the
individual when not symptomatic.
D. The disturbance in mood and the change in functioning are observable by others.
E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to
necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic.
F. The episode is not attributable to the physiological effects of a substance (eg, a drug of abuse, a
medication, or other treatment).
NOTE: A full hypomanic episode that emerges during antidepressant treatment (eg, medication,
electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that
treatment is sufficient evidence for a hypomanic episode diagnosis. However, caution is indicated so that
one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant
use) are not taken as sufficient for a diagnosis of a hypomanic episode, nor necessarily indicative of a
bipolar diathesis.
NOTE: Criteria A through F constitute a hypomanic episode. Hypomanic episodes are common in bipolar I
disorder but are not required for the diagnosis of bipolar I disorder.
DSM-5 diagnostic criteria for manic episode
A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally
and persistently increased activity or energy, lasting at least one week and present most of the day, nearly
every day (or any duration if hospitalization is necessary).
B. During the period of mood disturbance and increased energy or activity, three (or more) of the following
symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable
change from usual behavior:
1) Inflated self-esteem or grandiosity.
2) Decreased need for sleep (eg, feels rested after only three hours of sleep).
3) More talkative than usual or pressure to keep talking.
4) Flight of ideas or subjective experience that thoughts are racing.
5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli), as reported
or observed.
6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor

agitation (ie, purposeless non-goal-directed activity).
7) Excessive involvement in activities that have a high potential for painful consequences (eg, engaging
in unrestrained buying sprees, sexual indiscretions, or foolish business investments).
C. The mood disturbance is sufficiently severe to cause marked impairment in social or occupational
functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic
features.
D. The episode is not attributable to the physiological effects of a substance (eg, a drug of abuse, a
medication, other treatment) or to another medical condition.
NOTE: A full manic episode that emerges during antidepressant treatment (eg, medication,
electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that
treatment is sufficient evidence for a manic episode and, therefore, a bipolar I diagnosis.
NOTE: Criteria A through D constitute a manic episode. At least one lifetime manic episode is required for
the diagnosis of bipolar I disorder.
Contributor Disclosures
Sophie Grigoriadis, MD, MA, PhD, FRCPC Consultant/Advisory Boards: Allergan [Depression
(Levomilnacipran)]; Sage [Postpartum depression]; Eli Lilly [Depression (Fluoxetine)]. Speaker's
Bureau: Pfizer [Depression]. Peter P Roy-Byrne, MD Employment: Mass Medical Society (Journal
Watch). Charles J Lockwood, MD, MHCM Nothing to disclose David Solomon, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Mild to moderate antenatal unipolar depression: Treatment - UpToDate Page 1 of 31

Official reprint from UpToDate®

Mild to moderate antenatal unipolar depression:

● (See "Severe antenatal unipolar major depression: Choosing treatment".)

● (See "Unipolar major depression in pregnant women: General principles of treatment".)

● (See "Antenatal use of antidepressants and risk of teratogenicity and adverse

● (See "Antenatal use of antidepressants and risks of teratogenicity and adverse

● (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and

● (See "Unipolar major depression during pregnancy: Epidemiology, clinical features,

Unipolar major depression — Unipolar major depression (major depressive disorder) is

● Mild to moderate – Mild to moderate episodes of unipolar major depression are

● Severe – Severe unipolar major depression is characterized by seven to nine

Initial treatment — For mild to moderate episodes of antenatal unipolar major

Administering structured psychotherapy as first-line treatment of mild to moderate antenatal

Antidepressant medication is a reasonable alternative to structured psychotherapy for mild

● Psychotherapy is not available or acceptable to patients

● Patients prefer pharmacotherapy (eg, they previously responded well to

Choosing an antidepressant is discussed separately. (See "Severe antenatal unipolar major

When treating mild to moderate antenatal depression with structured psychotherapy, we

In addition, reasonable alternatives to structured psychotherapy and antidepressants for

Cognitive-behavioral therapy — Cognitive-behavioral therapy (CBT) for major

In addition, randomized trials and observational studies in patients with antenatal

Interpersonal psychotherapy — Interpersonal psychotherapy in pregnant women

Evidence for the efficacy of interpersonal psychotherapy includes numerous randomized

● A three-month randomized trial compared interpersonal psychotherapy (nine sessions)

● A 16-week randomized trial compared interpersonal psychotherapy with parenting

Treatment resistant patients — Patients with antenatal major depression of mild to

In addition, we suggest that clinicians prescribe add-on treatments, depending upon

Treatment refractory patients — Patients with antenatal major depression of mild to

Evidence supporting the use of these treatments includes the following:

● Acupuncture – Although the evidence is insufficient to recommend the use of

General information about acupuncture is discussed separately. (See "Acupuncture".)

● Exercise/yoga – In the absence of medical or obstetric complications, the general

● Family/couples therapy – For pregnant patients with mild to moderate depressive

• An observational study of pregnant women (n = 709) included women with

(See "Unipolar depression in adults: Management of highly resistant (refractory)

• A six-week trial compared massage therapy plus group interpersonal

• A 16-week trial (n = 56 patients with depressive symptoms) compared massage

In addition, an eight-week randomized trial compared omega-3 fatty acids

● Peer support – Evidence supporting the effectiveness of peer support includes

● S-adenosyl methionine – S-adenosyl methionine may be useful for patients with

SEVERE ANTENATAL UNIPOLAR MAJOR DEPRESSION

Treatment of severe antenatal unipolar major depression is discussed separately. (See

ANTIDEPERESSANTS PRIOR TO CONCEPTION

The use of antidepressant medications prior to conception is discussed separately. (See

UNPLANNED PREGNANCIES AND DISCONTINUING

Unplanned pregnancies and discontinuing antidepressants during pregnancy are discussed

Management of minor depression is discussed separately. (See "Unipolar minor depression

ANTIDEPRESSANTS AND BREASTFEEDING

The safety of antidepressants in lactating women is discussed separately. (See "Safety of

Treatment of postpartum unipolar depression and postpartum bipolar depression are

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Mild to moderate episodes of unipolar major depression are generally characterized by

Severe unipolar major depression is characterized by seven to nine depressive

adherence, monitoring symptoms, prescribing antidepressants, managing

Use of UpToDate is subject to the Subscription and License Agreement.

4. ACOG Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin: Clinical

7. LaRusso EM, Freeman MP. Antidepressants in pregnancy. In: Clinical Pharmacology

8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorde

13. Boyce P, Galbally M, Snellen M, Buist A. Pharmacological management of major depr

19. Dimidjian S, Goodman SH. Preferences and attitudes toward approaches to

20. Chaudron LH. Complex challenges in treating depression during pregnancy. Am J

Total _ = _ + _ + _ + ___