Major depressive disorder in pregnancy

Interesting Facts of Major depressive disorder in pregnancy

  • Depressive disorders in pregnancy are characterized by sad, empty, or irritable mood and somatic and cognitive changes that affect functioning in a pregnant woman; these disorders differ in duration, timing, and cause
  • Diagnosis of major depressive disorder is based on DSM-5 criteria. Patient must have several specific symptoms including either depressed mood or anhedonia lasting at least 2 weeks
  • May be underdiagnosed and undertreated during pregnancy. Initial presentation may occur during pregnancy, or preexisting disease manifestations may change during pregnancy
  • Can initially use screening tools to help identify patients at risk for depression; most commonly used screening tools in perinatal populations include Edinburgh Postnatal Depression Scale, 1 Patient Health Questionnaire-9, 2 and Postpartum Depression Screening Scale 3
  • Confirm diagnosis by fulfilling DSM-5 criteria for major depressive disorder
  • Treatment decisions surrounding use of pharmacologic management must be weighed against risk of exposure to untreated depression and psychotropic medication, both of which may have potential adverse maternal and fetal effects 
  • Treatment strategy is often based on maternal symptom severity and functioning; primary treatment modalities include psychotherapy and pharmacologic treatment 
  • Preferred psychotherapeutic modalities include interpersonal therapy and cognitive behavioral therapy; selective serotonin reuptake inhibitors are the preferred pharmacotherapeutic option
  • Patients who are being treated for depression before pregnancy generally should continue taking the prescribed antidepressant that is successfully managing symptoms throughout pregnancy
  • Complications affecting pregnancy and fetal outcome can occur as a result of untreated or undertreated maternal depression and use of medication during pregnancy
  • Antidepressant medications used in pregnancy are not major teratogens (except paroxetine, which possibly increases risk of fetal cardiac septal defects with first trimester exposure)
  • Primary adverse affects related to selective serotonin reuptake inhibitor use in pregnancy include risk for poor neonatal adaptation syndrome and slight increased risk for persistent pulmonary hypertension of the newborn and preterm birth
  • Most guidelines endorse routine perinatal screening for depression


  • Diagnosis can be challenging during pregnancy because some somatic symptoms included in DSM-5 criteria for diagnosis of depression overlap with normal pregnancy-related symptoms (eg, sleep changes, appetite changes, fatigue)
  • Even if major depressive disorder is diagnosed correctly, bipolar disorder may be present. Treatment varies by disorder; careful differentiation is essential
  • Always consider substance use as a potential contributor to major depressive disorder and a potential consequence of it
  • Management must be individualized and must balance the risks of medication exposure during pregnancy against the risks of untreated maternal depression


Clinical Clarification

  • Depressive disorders in pregnancy are characterized by sad, empty, or irritable mood and somatic and cognitive changes that affect functioning in a pregnant woman; these disorders differ in duration, timing, and cause
  • Up to 15% of women meet criteria for depression at some point during pregnancy or postpartum period 
  • Diagnosis of major depressive disorder is based on DSM-5 criteria. Patient must have a minimum of 5 symptoms—listed here—and at least 1 needs to be either depressed mood or anhedonia lasting at least 2 weeks: 
    • Depressed mood present most of the day
    • Markedly reduced interest or pleasure in all or almost all activities for most of the day
    • Significant weight loss or gain or appetite increase or decrease
    • Psychomotor agitation or retardation (eg, slowed speech, thought, movement) nearly every day, observable by others
    • Insomnia or hypersomnia nearly every day
    • Fatigue or lack of energy nearly every day
    • Sense of worthlessness or guilt (which may be delusional)
    • Difficulty concentrating or making decisions
    • Recurrent thoughts of death, dying, or suicide
  • Depressive disorders may be underdiagnosed and undertreated during pregnancy; they may initially present during perinatal period, or preexisting disease manifestations may change during pregnancy 


  • Depressive disorders are all characterized by sad, empty, or irritable mood and somatic and cognitive changes that affect functioning; however, they differ in terms of duration, timing, and cause
  • DSM-5 classifies depressive disorders as follows: 
    • Major depressive disorder
    • Persistent depressive disorder (dysthymia)
    • Premenstrual dysphoric disorder
    • Substance/medication-induced depressive disorder
    • Disruptive mood dysregulation disorder
    • Depressive disorder related to another medical condition
    • Other specified and unspecified depressive disorders


Clinical Presentation


  • Disease onset
    • May occur for the first time during pregnancy, or patient may have history of depression
  • Symptoms may include: 
    • Dysphoria (feelings of sadness or hopelessness)
    • Anhedonia (loss of interest in pleasurable or usual activities)
    • Insomnia or hypersomnia
    • Sense of guilt or poor self-esteem
    • Difficulty concentrating and memory impairment
    • Negative thoughts about the future
    • Excessive weight loss or gain
    • Increased or decreased appetite
    • Preoccupation with physical complaints (eg, fatigue, headache, nausea, diarrhea, constipation) and pain
    • Disinterest in or excessive anxiety about pregnancy
    • Lack of adherence to prenatal care
    • Talk of suicide or death
    • Suicidal ideation or passive death wish
  • May be unclear whether some of the symptoms are due to depression or normal pregnancy-related symptoms 
    • Some somatic symptoms commonly associated with pregnancy overlap with symptoms of depression (eg, sleep and appetite disturbances, diminished energy, decreased libido) 
    • Attention to certain symptoms not common to pregnancy may be most helpful (eg, disinterest in pregnancy, excessive guilt, dysphoria, anhedonia, impaired concentration, suicidal ideation) 
    • Patients often present with anxiety (eg, excessive generalized worries, pervasive worries that are difficult to control, panic attacks)
  • Other important patient history factors: 
    • Suicidal ideation with or without plan
    • Patient medical history and/or family history may include depression diagnosis or other psychiatric diagnosis
    • Tobacco, alcohol, or other drug use
    • Social history may uncover current stressors (eg, marital discord, domestic violence, occupational stressors, limited social support)
    • Limitation or decline in social, occupational, or academic functioning
    • Limitation or decline in self-care may be present (eg, lack of adherence to prenatal care plan, poor nutrition)

Physical examination

  • General physical examination may demonstrate: 
    • Weight loss, weight gain, or evidence of poor nutrition
    • Evidence of self-harm (eg, healed lacerations, scars on trunk or extremities)
    • Stigmata of trauma, self-injury, or drug use
    • Evidence of self-neglect with poor personal hygiene 
  • Mental status findings may include: 
    • Poor to no eye contact
    • Speaking in low tones or slowly
    • Psychomotor retardation and flat affect
    • Depressed mood and crying
    • Sadness, hopelessness, preoccupation with death, and suicidal ideation

Causes and Risk Factors


  • Cause is unknown but is postulated to involve a combination of genetic susceptibility, structural and functional brain abnormalities, psychosocial adversity in childhood, and recent or ongoing psychological stress 

Risk factors and/or associations 

  • Adolescent and young adult pregnant patients are at higher risk for prenatal depression 
    • Up to a quarter of pregnant adolescents may develop major depression during pregnancy 
  • Major depressive disorder is a multifactorial disorder with genetic susceptibility
  • Greatest risk for major depressive disorder is observed in families with early age at onset 
  • In the United States, higher incidence in Black, Hispanic, and Asian American populations compared with White populations 
Other risk factors/associations
  • Pregnancy-related associations
    • Overall, pregnancy does not appear to be a distinct period when increased numbers of patients are depressed compared with the entire span of reproductive years; however, some women may be at increased risk of a major depressive episode during the perinatal period 
    • Pregnancy and the postpartum period are associated with risk for relapse in patients who previously experienced major depression
      • Discontinuing antidepressants during pregnancy is associated with greater risk for relapse in women with severe depression 
      • In women with milder forms of depression, risk for onset of a major depressive episode during pregnancy seems to be similar whether or not they continue antidepressant medication 
    • There is an increased prevalence of depressive disorders among women with high-risk pregnancies due to obstetric complications such as threatened preterm labor, preeclampsia, oligohydramnios, and gestational diabetes 
  • Risk factors for prenatal depression (in addition to adolescence and ethnicity)
    • Intimate partner violence 
    • Previous history of depression (eg, nonparental depression, postpartum depression) 
    • Anxiety during pregnancy 
    • Psychosocial stress and major/negative life events 
    • Low socioeconomic status 
    • Unstable housing and low resources 
    • Poor or absent social or relationship support; single marital status 
    • Unplanned pregnancy 
    • Substance use 
    • Comorbid medical problems or chronic medical illness 
    • Lower educational status 
    • Unfavorable obstetric/pregnancy outcomes; previous miscarriages 
    • Positive family history of depression 
  • Risk factors for depression relapse during pregnancy in patient with history of depression before conception 
    • Discontinuation of antidepressant medication during pregnancy
    • Longer duration of illness
    • Previous history of relapse
    • Relapse episode within 6 months before conception
    • Early age of onset of a mood disorder
    • Multiple past episodes of depression

Diagnostic Procedures

Primary diagnostic tools

  • Suspect diagnosis in pregnant patients presenting with manifestations of depression
  • Initially may use screening tools to identify patients at risk for depression
    • Edinburgh Postnatal Depression Scale, 1 Patient Health Questionnaire-9,  and Postpartum Depression Screening Scale are screening tools commonly used to assess patients during the perinatal period 
    • Patients who screen positive for possible depression require full diagnostic interview with focus on DSM-5 criteria and comprehensive psychosocial risk factor assessment 
    • Strongly consider psychiatric referral for patients with severe depressive symptoms, psychosis, suicidal and homicidal ideation or attempts, significant comorbidity (eg, substance use), and suspected bipolar disorder
  • Exclude alternative diagnoses
    • Consider laboratory testing (eg, thyroid function tests, CBC, biochemistry, urine or serum drug screen) to exclude conditions that may produce or exacerbate mood symptoms 
    • Assess for conditions that may initially mimic depression (eg, bipolar disorder, substance use) and comorbidities that affect treatment decisions (eg, anxiety disorders, substance use) (Related: Bipolar disorder in pregnancy)
  • Confirm diagnosis by fulfilling DSM-5 criteria for major depressive disorder 
    • Diagnosis can be challenging during pregnancy because some somatic symptoms associated with depression overlap with normal pregnancy-related symptoms (eg, sleep changes, appetite changes, fatigue) 
  • DSM-5 criteria for major depressive disorder 
    • At least 5 of the following symptoms are present nearly every day during the same 2-week period and represent a change from previous functioning; at least 1 symptom must be either depressed mood or loss of interest or pleasure
      • Depressed mood present most of the day, either subjectively or observed by others
      • Markedly reduced interest or pleasure in all or almost all activities for most of the day
      • Significant loss of weight or weight gain or increase or decrease in appetite
      • Psychomotor agitation or retardation (eg, slowed speech, thought, movement) nearly every day, observable by others
      • Insomnia or hypersomnia nearly every day
      • Fatigue or lack of energy nearly every day
      • Sense of worthlessness or guilt (which may be delusional)
      • Difficulty concentrating or making decisions
      • Recurrent thoughts of death, dying, or suicide
    • Symptoms cause clinically significant distress or impaired social, occupational, or other types of functioning
    • Not attributable to physiologic effects of a substance or medical disorder
    • Not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other psychotic disorders
    • Patient has never had a manic or hypomanic episode
  • Assessment of severity
    • Subjective assessment of severity is often based on frequency of symptoms and impact on functioning
    • Objective measures suggesting degrees of severity include:
      • Mild to moderate
        • 2 to 4 or more depressive symptoms 
        • Generally distressed but able to continue most activities (mild) or having great difficulty continuing activities (moderate) 
        • Score of less than 15 points on Patient Health Questionnaire-9 
        • Absence of suicidal behavior, psychotic features, or significantly impaired functioning
      • Moderate to severe
        • Score of 15 to 19 points on Patient Health Questionnaire-9 
      • Severe
        • At least 7 depressive symptoms 
        • Score of 20 or more on Patient Health Questionnaire-9 
        • Number of symptoms is substantially in excess of that required to make the diagnosis 
        • Presence of suicidal ideation or attempts, or psychotic features 
        • Intensity of symptoms is seriously distressing and unmanageable 
        • Symptoms markedly interfere with social and occupational functioning 
  • Screening tools for depression in pregnancy
    • Positive screening result is not diagnostic; screening tools are intended to identify women who warrant further evaluation 
      • Follow up a positive screening result with a detailed diagnostic interview with focus on DSM-5 criteria and assessment of psychosocial risk factors 
    • Most commonly used screening tools:
      • Edinburgh Postnatal Depression Scale 
        • Self-reported, 10-item questionnaire 
        • Validated for both prenatal and postnatal use; originally developed to screen for possible postnatal depression 
        • Excludes some nonspecific somatic symptoms common during the perinatal period even in the absence of depressive disorders 
        • Scores range from 0 to 30 
          • Score of 10 to 13 or higher suggests possible depressive or anxiety disorder 
        • Final item specifically addresses thoughts of self-harm and suicidal ideation; any score above 0 on this item warrants full risk assessment aimed at gaining better understanding of likelihood of self-harm 
        • Sensitivity ranges from 80% to 90% depending on threshold defined for positive score 
    • Australian guidelines 
      • Score of 10 to 12 (borderline high): repeat assessment in 2 to 4 weeks
      • Score of 13 or higher indicates possible depression warranting further assessment
      • Score of 15 or higher: urgent evaluation is recommended
    • Patient Health Questionnaire-9 
      • Self-report, 9-item questionnaire 
      • Validated for detection of possible prenatal depression 
      • Score of 10 or more suggests possible depression 
    • Postpartum Depression Screening Scale 
      • Self-report, more extensive inventory comprising 5 items in each of 7 dimensions: 
        • Sleeping and eating
        • Anxiety and insecurity
        • Emotional lability
        • Cognitive impairment
        • Loss of self
        • Guilt and shame
        • Self-harm thoughts
      • Validated for detection of possible perinatal depression 
      • Score of 60 or more identifies significant symptoms of depression; score of 80 or more is positive screening result for major depression 

Differential Diagnosis

Most common 

  • Normal pregnancy-related changes
    • Some somatic symptoms common during pregnancy overlap with those of major depressive disorder
    • Changes in sleep patterns, appetite, and energy level, as well as decrease in libido, are not uncommon during pregnancy
    • Changes associated with decline in function (eg, loss of energy resulting in inability to get out of bed or attend scheduled prenatal visits, lack of appetite resulting in poor weight gain) suggest major depressive disorder rather than normal pregnancy-related changes
    • Focus on evaluation of depression-related mood and cognitive symptoms (eg, dysphoria, anhedonia, excessive guilt, impaired concentration, suicidal ideation) may help differentiate normal pregnancy changes from depression
    • Differentiated by clinical history and DSM-5 criteria
  • Persistent depressive disorder (dysthymic disorder)
    • Mental disorder characterized by depressive symptoms that do not meet the DSM-5 criteria for major depressive disorder
    • Fewer symptoms than major depressive disorder, and symptoms are of variable duration
    • Episodes of major depressive disorder may be interspersed throughout patient’s lifetime
    • Differentiated by clinical history and DSM-5 criteria
  • Bipolar disorder (Related: ) Bipolar disorder in pregnancy
    • Mood disorder characterized by at least 1 lifetime episode of mania or hypomania and 1 major depressive episode
    • Carefully screen patients who have major depression for bipolar disorder 
      • 15% of patients with major depression have bipolar disorder
      • Bipolar disorder does not respond to antidepressants; therefore, differentiation is crucial
    • Family history of bipolar disorder may lead to heightened suspicion for illness
    • Presence of mania or hypomania is the cardinal feature that distinguishes bipolar disorder from major depressive disorder
      • May be critical to speak with family or significant other to obtain some insight into possible prior episodes of hypomania or mania; patient self-report of these episodes is often lacking
    • Differentiation can be challenging; diagnosis is based on clinical history and DSM-5 criteria
  • Adjustment disorder 
    • Temporary, short-term, nonpsychotic mental response to an event or situation, such as a divorce, a death in the family, a disappointment, or a failure
    • Symptoms can include sadness, anxiety, insomnia, poor concentration, or poor performance in school
    • Symptoms persist for no longer than 6 months after termination of stressor and do not meet criteria for another mental disorder
    • Differentiated by clinical history and DSM-5 criteria
  • Schizophrenia
    • Mental disorder characterized by significant distortion in thinking, perception, speech, and behavior
    • May cause altered mood and depression in addition to psychotic symptoms
      • Differentiating features are psychotic symptoms that occur in the absence of symptoms of a mood episode
    • Differentiated by clinical history and DSM-5 criteria
  • Borderline personality disorder
    • Personality disorder characterized by mood swings, recurrent suicidal ideation, and impulsive behaviors
    • Typically associated with affective instability, unstable personal relationships, and transient stress-related cognitive impairment
    • Differentiated by clinical history and DSM-5 criteria
  • Hypothyroidism
    • Clinical state induced by inadequate synthesis and secretion of thyroid hormone
    • May result in symptoms of major depressive disorder, in addition to signs and symptoms of slow metabolism (eg, dry skin, brittle hair, weight gain)
    • Differentiated by clinical findings and thyroid function test results
  • Substance- or medication-induced mood disorders (Related: )Alcohol use disorder
    • Characterized by significantly depressed mood that develops after use of medications or illicit substances (eg, stimulants, alcohol), resulting in psychosocial impairment (Related: Opioid use disorder)
    • Mood symptoms are typically confined to, and change in parallel with, periods of substance intoxication or withdrawal
    • Differentiated by clinical history and urine or serum toxicology results



  • If patient is suicidal, take steps to protect from self-harm as needed 
  • Stabilize mood and return patient to normal psychosocial functioning 
  • Encourage adherence to treatment to minimize relapse or recurrence 
  • Consider pharmacotherapy when risks of untreated illness are greater than risks of pharmacotherapy during pregnancy 
  • Address and minimize any complications such as malnutrition and substance use 


Admission criteria

  • Indications for admission include:
    • Suicidal or homicidal ideation with plan and intent or suicide attempts 
    • Substance withdrawal or intoxication 
    • Severe symptoms (eg, severe delusions, psychosis, catatonic behavior) 
    • Inability to care for self 
    • Undergoing electroconvulsive therapy 
    • Consider for patients at very high risk of relapse 
  • Partial hospital admission (intensive outpatient treatment) may be appropriate for some patients 

Recommendations for specialist referral

  • Optimal approach during pregnancy is multidisciplinary management involving mental health specialist, obstetrician, primary care provider, and social worker and/or case manager 
    • Integrated management is particularly ideal for patients who require both psychotherapy and pharmacotherapy 
  • Consult psychiatrist or mental health provider specializing in care of pregnant patients if patient exhibits any of the following:
    • Suicidal or homicidal ideation or attempts
    • Severe depression
    • Delusions or hallucinations
    • Catatonia
    • Substance use
    • Suspected bipolar disorder
    • Depression that has not responded to appropriate drug therapy

Treatment Options

Treatment is individualized and often based on severity of illness coupled with level of functioning

  • Little rigorous evidence is available to firmly direct treatment decisions
    • A systematic review of 2014 found a dearth of high-quality evidence; that review is now archived but not yet replaced, and the evidence base remains weak 
  • Balance clinical judgment regarding treatment decisions with risks of medication exposure during pregnancy and risks of untreated maternal depression 
  • Recommend treatment based on severity of depression
    • Mild to moderate depression (eg, absence of either suicidal behavior or significant impairments in functioning)
      • Guidelines recommend either psychotherapy or antidepressant medication as first line treatment 
    • Moderate to severe depression
      • Guidelines often recommend pharmacotherapy in addition to psychotherapy, particularly in presence of functional limitations and diminished ability for self-care 
  • Realize that peripartum depression is highly comorbid with anxiety disorders
    • Effective treatment involves treating both depression and anxiety

Primary modes of treatment include nonpharmacologic measures and pharmacologic treatment

  • Nonpharmacologic treatment measures
    • Psychotherapy is primary mode of nonpharmacologic treatment 
      • Preferred psychotherapeutic options include interpersonal therapy and cognitive behavioral therapy 
      • Psychotherapy is moderately effective and may reduce or obviate need for medications 
      • Psychotherapy may be effective as:
        • Single modality for mild to moderate depression 
        • Adjunct treatment of depression necessitating psychotropic medication 
    • Optimize other nonpharmacologic treatment options 
      • May include exercise, stress reduction techniques (eg, yoga, mindfulness), and optimization of general wellness measures (eg, nutrition, sleep) as well as social support structure
  • Pharmacologic treatment
    • General principles guiding psychotropic medication use during pregnancy:
      • Limit number of exposures
        • Primary goal is to achieve remission (euthymia) so that the fetus is not exposed to effects of both maternal depression and medication 
        • Preferred to maximize dose of a single drug over providing lower doses of multiple drugs 
      • Preferred medication profile includes the one with the best safety data, fewer metabolites, higher protein binding to decrease placental passage, and fewer interactions with other medications 
      • Consider patient history of medication response; preferentially prescribe medication that has proven effective in this patient in the past (eg, a particular selective serotonin reuptake inhibitor that has helped before) 
      • Use the lowest effective therapeutic dose 
      • Avoid discontinuing effective selective serotonin reuptake inhibitor antidepressant during pregnancy 
        • Tapering these medications during pregnancy puts patient at increased risk for prenatal relapse and postpartum depression and generally is not recommended outside of certain scenarios 
      • Adjust selective serotonin reuptake inhibitor dosing based on clinical symptoms; dose adjustments are frequently needed during the second and third trimesters 
        • Multiple pharmacokinetic changes in selective serotonin reuptake inhibitor metabolism occur in second and third trimesters, leading to lower serum drug concentrations 
        • Often need to increase dose in later stages of pregnancy to maintain therapeutic effect 
        • Serum drug concentrations return to prepregnancy levels after delivery; decrease in dose may be appropriate in postpartum period 
      • Experts usually recommend continuing medication used during pregnancy while breastfeeding; this continuation may minimize potential adverse manifestations in neonate and infant 
    • Preferred first line treatment is selective serotonin reuptake inhibitors for antidepressant-naive women 
      • Options include sertraline, fluoxetine, fluvoxamine, vilazodone, citalopram, and escitalopram 
        • Sertraline and citalopram are generally preferred owing to their favorable lactation profiles 
      • Overall, selective serotonin reuptake inhibitors are not considered to be major teratogens 
        • Exception is paroxetine, which is generally avoided owing to reports of cardiovascular malformations (ie, septal defects) with first-trimester exposure 
        • Where any associations between selective serotonin reuptake inhibitors and congenital abnormalities have been reported, the absolute magnitude of the risk is small and data are inconsistent owing to multiple confounding variables 
      • Use of selective serotonin reuptake inhibitors during the third trimester may be associated with the following: 
        • Poor neonatal adaptation syndrome 
          • Irritability
          • Insomnia
          • Rigidity or limpness
          • Tremors
          • Seizures
          • Respiratory distress
        • Small increased risk of persistent pulmonary hypertension of the newborn and preterm delivery
    • Alternative pharmacologic treatment of depression not responding to selective serotonin reuptake inhibitors 
      • Other options, for which there are more limited data about safety in pregnancy, include:
        • Serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine, duloxetine)
        • Bupropion
        • Mirtazapine 
        • Tricyclic antidepressants; nortriptyline is often preferred owing to lower tendency for anticholinergic adverse effects 

Considerations for patients who do not respond to initial management

  • Definitions of treatment-refractory depression vary 
    • Most experts agree that a patient has treatment-refractory depression when response has failed for at least 2 antidepressant regimens of adequate dose and duration
  • Assess for alternative explanation before considering alternative treatment
    • Verify correct diagnosis
    • Confirm adequate dose and duration of treatment (antidepressants may take 6-7 weeks to reach full benefit)
    • Verify treatment adherence
    • Reassess for comorbidity (eg, anxiety disorder, substance use)
    • Evaluate for worsening stress or new life stressor
  • Consult a mental health specialist to guide further treatment options; treatment decisions often depend on severity of depression and degree of response to prior treatment
    • Options include increasing frequency of psychotherapy sessions, changing type of psychotherapy, optimizing dose of medication, or adding or changing medications (eg, trial of different selective serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitors instead of selective serotonin reuptake inhibitor)

Treatment options for severe disease refractory to psychotherapy and pharmacologic interventions 

  • Electroconvulsive therapy
    • Approved and effective treatment modality during pregnancy; risks of therapy must be weighed against risks of untreated illness 
    • Consider in patients with severe depression, affective psychosis, and/or catatonia 
  • Repetitive transcranial magnetic stimulation
    • Emerging treatment option; data are limited 
    • May offer a medication-free treatment option for some women with severe disease refractory to other treatment

Maintenance pharmacotherapy for women treated for depression before pregnancy

  • No currently available antidepressants are absolutely contraindicated in pregnancy; however, no psychotropic medication is approved by the FDA for use during pregnancy 
    • Note: MAOIs are discouraged during pregnancy owing to risk of hypertensive crisis when combined with tocolytics
  • Continue current antidepressant that is successfully managing symptoms, particularly in women with history of severe or recurrent depression and history of relapse when discontinuing maintenance medication, even if asymptomatic at time of conception
  • Discontinuing antidepressants during pregnancy generally is not recommended 
    • Euthymic women who discontinue antidepressants may have an increased risk of depression relapse compared with women who continue antidepressant treatment; data are not straightforward or overwhelmingly conclusive 
    • May consider discontinuing ongoing pharmacologic therapy during pregnancy in select patients with mild depression. In these patients, gradually taper antidepressant over 1 to 2 weeks with close support and monitoring from psychotherapist or psychiatrist 
    • Before pregnancy is the ideal time to consider careful selective serotonin reuptake inhibitor taper in appropriate patients (ie, patients with mild and stable depression without history of recent relapse or several depressive episodes) with intent to avoid fetal medication exposure 

Drug therapy

  • Few prospective, well-controlled studies exist in pregnant women; psychotropic medication use during pregnancy must balance risk of adverse effects with risk of untreated illness 
  • If medication is required, consider enrolling a US patient in the National Pregnancy Registry for Antidepressants 
    • Information collected by registry can help improve safety information for medicines used during pregnancy; information collected may be used to update drug labeling
  • Selective serotonin reuptake inhibitors 
    • Sertraline 
      • Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily. A lower initial dose (25 mg PO once daily) may be used to minimize adverse effects. If necessary, increase at intervals of not less than 1 week. Max: 200 mg/day PO. The length of treatment should be determined on an individual basis. Periodically reassess the need for continued treatment.
        • Note: sertraline oral solution contains 12% alcohol and is not recommended during pregnancy because there is no known safe level of alcohol exposure during pregnancy. Use other sertraline formulations during pregnancy only if potential benefit to the mother outweighs potential risk to the fetus.
    • Fluoxetine
      • Fluoxetine Hydrochloride Oral tablet; Adults: 20 mg/day PO initially. May increase dose after several weeks by 10 to 20 mg as needed and tolerated. Doses above 20 mg/day may be given once daily or divided into 2 doses at morning and noon. Max: 80 mg/day PO. Periodically re-evaluate to determine the need for continued treatment.
    • Citalopram
      • Citalopram Hydrobromide Oral tablet; Adults: Initially, 20 mg PO once daily; may increase to 40 mg PO once daily after 1 week. Max: 40 mg/day. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 owing to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Escitalopram 
      • Escitalopram Oral tablet; Adults: 10 mg PO once daily is the initial and recommended dose. If needed, may increase to 20 mg once daily after a minimum of 1 week, but one trial suggested no additional benefit. Max: 20 mg/day PO. Periodically reassess the need for continued treatment.
  • Serotonin-norepinephrine reuptake inhibitors
    • Venlafaxine
      • Venlafaxine Hydrochloride Oral tablet, extended-release; Adults: Initially, 75 mg PO once daily. Alternatively, 37.5 mg PO once daily can be given for 4 to 7 days to allow for tolerability before increasing to 75 mg PO once daily. If needed, may increase further by 75 mg/day at intervals of no less than every 4 days. Recommended Max: 225 mg/day PO.
    • Duloxetine
      • Duloxetine Oral capsule, gastro-resistant pellets; Adults: Initially, give 20 mg PO twice daily or 60 mg/day PO as a single dose or in 2 divided doses (i.e., 30 mg PO twice daily). Alternatively, give 30 mg/day PO for 1 week, then increase to 60 mg/day. Target maintenance dose: 60 mg/day; dividing doses may increase tolerability. Max: 120 mg/day PO, but more than 60 mg/day has not been shown to have an additional benefit.
  • Noradrenergic and specific serotonin antidepressants
    • Mirtazapine 
      • Mirtazapine Oral tablet; Adults: Initially, 15 mg PO at bedtime. The effective dose range is 15 mg/day to 45 mg/day. The mean daily dose found in one study with pregnant women was 30 mg/day. Dosage adjustments should not be made more often than every 1 to 2 weeks. 
        • Safe use of mirtazapine during pregnancy has not been established. Therefore, it should not be administered to women of childbearing potential unless, in the opinion of the treating physician, the expected benefits to the patient outweigh the possible hazards to the fetus.
  • Noradrenergic and dopaminergic antidepressants
    • Bupropion
      • Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]; Adults: Initially, 150 mg PO each morning; titrate after 4 days to 150 mg PO twice daily if needed. After several weeks, titrate to 200 mg PO twice daily if needed; administer doses at least 8 hours apart.
  • Tricyclic antidepressants 
    • May be helpful in patients with concomitant agitation;  agents with least anticholinergic effects (ie, nortriptyline, desipramine) are preferred in pregnant patients 
    • Overall, tricyclic antidepressants are not associated with congenital anomalies, with possible exception of increased risk of congenital cardiac defects associated with clomipramine 
    • Nortriptyline
      • Nortriptyline Hydrochloride Oral capsule; Adults: Initially, 25 mg to 50 mg PO per day, given in divided doses or at bedtime. May increase as needed and tolerated. Max: 150 mg/day PO.
    • Desipramine
      • Desipramine Hydrochloride Oral tablet; Adults: 50 to 75 mg/day PO initially, in single or divided doses. Titrate by 25 to 50 mg at weekly intervals according to response and tolerance. Use the lowest effective dose. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance.

Nondrug and supportive care

Nonpharmacologic psychotherapeutic treatment modalities

  • First line modalities include:
    • Interpersonal therapy
      • Focus includes attention to role transition, interpersonal functioning, and building social rapport 
      • Structured, time-limited psychotherapy
    • Cognitive behavioral therapy
      • Focus involves correction of negative thinking and associated behaviors 
  • Other psychotherapeutic options include:
    • Perinatal period–specific treatments: mindfulness-based intervention and perinatal dyadic psychotherapy 
    • General treatment modalities for depression: behavioral activation therapy, problem-solving therapy, nondirective counseling, and psychodynamic therapy 

Anticipatory guidance and education

  • Educate patient and family about illness 
  • Anticipate potential problems that may arise in postpartum period and develop coping strategies (eg, based on cognitive behavioral therapy or behavioral strategies) 
  • Encourage open communication with medical provider(s): thoughts of self-harm, suicidal ideation, and homicidal ideation (eg, murder-suicide of mother and infant)
  • Maximize wellness strategies including: 
    • Engage in appropriate exercise
    • Optimize sleep, particularly consecutive hours of undisrupted sleep
    • Optimize nutrition
    • Strengthen family and social support networks
    • Use stress reduction techniques

Adjunct measures that may be effective include:

  • Routine exercise and sleep regimen 
  • Massage, yoga, and mindfulness techniques
  • Peer support and support groups for women who struggle with depression during pregnancy 
  • Data are mixed regarding efficacy of other complimentary treatments (eg, ω-3 fatty acids, folate, St John’s wort, bright light therapy, acupuncture) 
    • Bright light therapy may be helpful for patients with a seasonal component to their affective illness 
    • Acupuncture may be helpful in select patients 
Electroconvulsive therapy 

General explanation

  • Generalized seizures are intentionally induced using electrical impulses
  • Typically performed multiple times per week until clinical response is seen
  • Average course is 6 to 12 treatments, which are administered to patient who is under anesthesia and on muscle relaxants
  • Specific precautions for pregnant patients include: 
    • Some anesthesiologists recommend intubation to protect the airway after the first trimester because there is increased risk of gastric reflux and aspiration during second and third trimester 
    • Fetal heart rate monitoring before and after procedure is recommended 
    • Obstetrician should be readily available during procedure in the event of fetal compromise 


  • May be used as first line therapy for patients who have: 
    • Psychotic depression 
    • Catatonia 
    • Severe suicidality
    • Depression posing serious risk to health of patient or fetus 
    • Previous positive response to this treatment method 
    • Anorexia or rapidly deteriorating physical status
    • Treatment-resistant depression
    • Repeated medication intolerance


  • Relative contraindications include:
    • Younger than 18 years
    • Space-occupying brain lesions
    • Elevated intracranial pressure
    • Recent myocardial infarction
    • History of retinal detachment
    • Pheochromocytoma


  • Complications in the fetus include arrhythmia and demise; in the mother, vaginal bleeding, uterine contractions, and premature labor 
  • General adverse complications include:
    • Transient postictal confusion and period of antegrade and retrograde memory loss
    • Transient rise in heart rate, cardiac workload, and blood pressure
    • Aspiration 
    • Fractures
    • Dental and tongue injuries
Repetitive transcranial magnetic stimulation 

General explanation

  • Involves applying a strong, pulsed magnetic field to targeted brain region (often dorsolateral prefrontal cortex region when treating for depression) 
  • Electromagnetic coil is held against patient’s forehead, and short electromagnetic pulses are administered through the coil to generate electromagnetic field 
  • Electromagnetic field results in regional neuronal depolarization and generation of action potentials 
  • Data supports efficacy of various techniques (eg, high frequency, low frequency, theta burst pulse pattern) and application to various target areas for improvement in pharmacoresistant depression 
  • Treatments are repeated daily for 4 to 6 weeks; typical session lasts 30 to 60 minutes and does not require anesthesia 


  • Patients with major depression recalcitrant to antidepressant drug therapy 


  • Absolute and very strong contraindications include:
    • Ferromagnetic metal in the head (eg, plates, pins, bullets, shrapnel, aneurysm clips)
    • Microprocessor implants in the neck (eg, vagal nerve simulator, deep brain stimulator)
    • Life-sustaining microprocessor implants anywhere in body (eg, prosthetic cardiac valves)
  • Relative contraindications include:
    • Ferromagnetic material in neck and chest
    • Microprocessor implants below the neck (eg, spinal pumps, stimulators)
    • Conditions that may lower seizure threshold (eg, brain lesion, major head trauma, medications, recent withdrawal from alcohol or benzodiazepines)
    • Hearing loss and tinnitus


  • Tensionlike headache
  • Localized application site discomfort or pain
  • Seizure during treatment; approximately 0.1% risk over the full course of treatments


  • Substance or alcohol use disorders
    • Treat addiction while treating depression
  • Coexisting psychiatric conditions, such as anxiety, obsessive-compulsive disorder, and personality disorders
    • May impact the treatment of major depression and require additional treatment specific for comorbid disorder


  • All patients with depressive disorders in pregnancy
    • At every clinical encounter, screen for threat of harm to self or others
    • Monitor clinical symptoms and assess for decline in function throughout pregnancy and postpartum period
    • Frequency of monitoring varies
      • Base on depression severity, presence of suicidal ideation, adherence to treatment, strength of social supports, and presence of coexisting medical conditions
      • During the initial phase of treatment, monitoring can vary from once a week to multiple times a week, depending on depression severity
  • Patients requiring psychotropic medication
    • Frequently monitor symptom control, particularly during second and third trimester 
    • Patients often require their dosage of selective serotonin reuptake inhibitor to be increased during the latter stages of pregnancy owing to multiple pharmacologic changes in metabolism of the medication during second and third trimester 
    • Adjust selective serotonin reuptake inhibitor dosing based on clinical symptom control 
    • Consider fetal echocardiography with first trimester paroxetine exposure 
    • Venlafaxine is associated with dose-related increases in blood pressure; closely monitor blood pressure. Consider tapering and discontinuing if patient develops preeclampsia 
    • Therapeutic drug monitoring is recommended for certain psychotropic medications during both dose titration and maintenance therapy at least once per trimester and within 24 hours after delivery 
      • Monitoring of tricyclic antidepressants is strongly recommended 
  • Neonates exposed to selective serotonin reuptake inhibitor
    • Rigorous monitoring for poor neonatal adaptation syndrome is not standardized 
    • Absence of manifestations by 72 hours indicates that poor neonatal adaptation syndrome is unlikely to develop 

Complications and Prognosis


  • Complications secondary to untreated or undertreated prenatal depression include increased risk for the following:
    • Pregnancy-related complications and associations include:
      • Poor health behaviors leading to increased risk for obstetric complications and poor pregnancy outcomes 
        • Poor patient adherence to prenatal care, prenatal vitamins, and prescribed medications
        • Smoking, alcohol consumption, and substance use
        • Poor nutrition leading to poor weight gain
        • Lack of exercise
      • Ambivalence about the pregnancy and decreased intention to breastfeed 
      • Suicidal ideation 
      • Suicide
        • Absolute risk is low; however, suicide does represent a leading cause of death in depressed pregnant women, particularly in association with untreated depression 
      • Operative delivery requirement 
      • Intrauterine growth restriction 
      • Preterm birth 
      • Low birth weight and small-for-gestational-age neonate 
      • Postpartum depression 
    • Effects on infant and child
      • Outcome data are mixed and difficult to separate from multiple potential confounding variables (eg, continued postnatal maternal depression and anxiety, paternal mood symptoms, postpartum caregiving, other environmental factors) 
      • Potential complications include: 
        • Neonate and infant: lower neonatal behavioral scores, decreased vagal tone, diminished cortisol reactivity, reduced reactivity to pain or stress, depressed temperament, increased irritability, decreased attention, sleep problems, and delayed neuromotor and language development 
        • Young child: internalizing behaviors, externalizing behaviors, fearful temperament, anxiety, and delayed motor and cognitive development
        • Older child: altered stress response, attention-deficit/hyperactivity disorder, depression, and anxiety disorders
  • Complications secondary to prenatal exposure to antidepressant medications
    • Poor neonatal adaptation syndrome (also called neonatal toxicity, neonatal behavioral syndrome, and postnatal adaptation syndrome)
      • Occurs in up to one-third of neonates exposed to selective serotonin reuptake inhibitors and other psychotropic medications (eg, serotonin and norepinephrine reuptake inhibitors) late in third trimester 
      • Manifestations may include respiratory distress 
        • General: temperature instability, feeding difficulty, vomiting, sleep disturbance, jaundice, and hypoglycemia
        • Cardiovascular: prolonged QT and arrhythmias 
        • Respiratory: respiratory distress, apnea, and cyanosis
        • Central nervous system: tremor, jitteriness, hypotonia, hypertonia, hyperreflexia, irritability, persistent crying, lethargy, and seizures
      • Manifestations are usually mild and transient; age of onset is usually birth to 3 days and manifestations usually resolve within a few days. Less typically, manifestations may persist from 2 weeks to 1 month 
      • Most manifestations are mild and require only close observation and supportive care 
      • Dose-dependent relationship with syndrome severity has been observed 
    • Persistent pulmonary hypertension of the newborn
      • Failure of pulmonary vasculature to relax, which normally occurs during circulatory transition to postnatal life; results in extrapulmonary right to left shunting with potential cyanosis and respiratory distress 
      • Data are conflicting; there may be small increased risk with exposure after 20 weeks of gestation (odds ratio, 1.28; 95% CI, 1.01-1.64), but some studies have found no increased risk 
    • Postpartum maternal hemorrhage
      • Exposure to selective serotonin reuptake inhibitors late in pregnancy may increase risk of postpartum bleeding, particularly upper gastrointestinal bleeding 
      • Data are inconsistent and conflicting; reported relative risk is at best small (1.47; 95% confidence interval, 1.33-1.62) 
    • Validity of other possible suspected complications is unclear and debated
      • Data are conflicting and often inconclusive owing to inability to ethically conduct well-designed prospective studies. Available study designs are subject to multiple confounding variables (eg, uncontrolled underlying depression, poor prenatal health behaviors, concomitant medication, tobacco use, substance use, comorbid medical conditions [eg, obesity, diabetes, hypertension]) 
      • May include possible small but increased risk of the following:
        • Minor congenital cardiac malformations may occur with first trimester paroxetine exposure (eg, self-resolving septal defects) 
          • Risk is about 1% (risk among general population of newborns is about 0.7%) 
        • Preterm birth (modest effect, pregnancy shortened by 3-5 days) 
        • Delayed motor development (mild and transient) 
        • Lower birth weight (small effect, weight decreased by about −74 g) 
        • Lower 1- and 5-minute Apgar scores (small effect, largely undetermined clinical significance) 


  • Untreated major depressive disorder in pregnancy poses a risk to both mother and fetus (eg, malnutrition, poor prenatal care, substance use, suicide attempt, self-inflicted injury)
  • There is a high risk of relapse after a depressive episode, especially in the first 6 months; risk declines with time in remission 
    • Risk factors for relapse include:
      • Presence of residual symptoms
      • Higher number of previous episodes
      • Increasingly severe disease
      • Prolonged duration of disease
      • Higher degree of treatment resistance during the most recent episode

Screening and Prevention


At-risk populations

  • All pregnant patients are at risk
  • Higher risk occurs among certain patients including:
    • Patients with history of depression
    • Adolescent patients
    • Patients with risk factors for depression (eg, intimate partner violence, low socioeconomic status, poor or absent social or relationship support, psychosocial stress, anxiety)


  • US Preventive Services Task Force recommends screening all pregnant and postpartum adults and adolescents (aged 12 years and older) for depression 
    • Screening helps ensure accurate diagnosis, effective treatment, and appropriate follow-up 
  • Most guidelines endorse routine perinatal screening for depression 
    • Optimum timing for perinatal screening is not rigorously standardized 
  • American College of Obstetricians and Gynecologists recommends: 
    • Routine screening during the perinatal period with a validated, standardized tool
    • Heightened monitoring for women at increased risk for perinatal depression
  • Australian guidelines recommend screening for depression at least once during pregnancy and once in the postpartum period 
  • Other guidelines (eg, Canadian) do not endorse routine screening for depression in pregnancy 
  • Women’s Preventive Services Initiative recommends screening for anxiety in adolescent and adult women, including those who are pregnant or postpartum. Optimal screening intervals are unknown and clinical judgment should be used to determine screening frequency 

Screening tests

  • Standardized depression screening tools: 
    • Perinatal screening tools: Edinburgh Postnatal Depression Scale, 1 Patient Health Questionnaire-9, and Postpartum Depression Screening Scale 
    • General screening tools: Beck Depression Inventory,  Major Depression Inventory, and Hamilton Depression Rating Scale
  • Short case-finding questions (2 or 3 questions) are advocated by some guidelines to identify women who need to be monitored closely for depression and further assessed with standardized screening tools 
    • Questions are as follows
      • During the past month, have you often been bothered by feeling down, depressed, or hopeless?
      • During the past month, have you often been bothered by little interest in pleasure or doing things?
    • If either response is yes (affirmative) then follow with third question
      • Is this something you feel you need or want help with?
    • Rigorous validation is lacking; however, data show that negative predictive values for excluding depression approach 100% 


  • Data are scarce regarding prevention strategies for depressive disorders in pregnancy 
    • Psychosocial and psychological interventions (eg, intensive, professional-based postpartum home visits; telephone-based peer support; interpersonal psychotherapy) have been shown to result in fewer diagnoses of postpartum depression 
  • Effective preconception planning may diminish risk of active disease or relapse of known depression during pregnancy 
    • Encourage patient to review risks of untreated disease and medication use during pregnancy before conception
    • Establish appropriate psychotropic medication regimen in depressed women of childbearing age
    • Encourage clinically unstable patients to consider deferring pregnancy until clinical stability is achieved


Cox JL et al: Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 150:782-6, 1987 Reference


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