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    Major Depressive Disorder in Pregnancy

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    Jul.18.2024

    Major Depressive Disorder in Pregnancy

    Synopsis

    Key Points

    • Depressive disorders in pregnancy are characterized by sad, empty, or irritable mood and somatic and cognitive changes that affect functioning in a pregnant patient; these disorders differ in duration, timing, and cause
    • Diagnosis of major depressive disorder is based on DSM-5-TR 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,r1Patient Health Questionnaire-9,r2 and Postpartum Depression Screening Scaler3
    • Confirm diagnosis by fulfilling DSM-5-TR criteria for major depressive disorder
    • Treatment decisions surrounding the use of pharmacologic management must be weighed against the risk of exposure to untreated depression and psychotropic medication, both of which may have potential adverse maternal and fetal effects r4
    • Treatment strategy is often based on maternal symptom severity and functioning; primary treatment modalities include psychotherapy and pharmacologic treatment r4
    • 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 because 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 the risk of fetal cardiac septal defects with first-trimester exposure)
    • Primary adverse effects related to selective serotonin reuptake inhibitor use in pregnancy include risk for poor neonatal adaptation syndrome and slightly increased risk for persistent pulmonary hypertension of the newborn and preterm birth
    • Most guidelines endorse routine perinatal screening for depression

    Urgent Action

    • Urgent intervention and hospitalization are required for patients with severe depression symptoms, psychosis, or suicidal ideation or attempts

    Pitfalls

    • Diagnosis can be challenging during pregnancy because some somatic symptoms included in DSM-5-TR criteria for diagnosis of depression overlap with normal pregnancy-related changes (eg, sleep changes, appetite changes, fatigue)
    • Always exclude bipolar disorder before initiating any pharmacotherapy for depression, as treatment with antidepressant monotherapy may precipitate mania, rapid cycling, or psychosis in patients with bipolar disorder r5
    • 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
    • Financial concerns represent a significant barrier to adequate mental health treatment for a significant proportion of patients r6

    Terminology

    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 patient; these disorders differ in duration, timing, and cause
    • Up to 15% of females meet criteria for depression at some point during pregnancy or the postpartum period r7
    • Diagnosis of major depressive disorder is based on DSM-5-TR 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: r8
      • 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 the perinatal period, or preexisting disease manifestations may change during pregnancy r7r9

    Classification

    • Depressive disorders are all characterized by sad, empty, or irritable mood and somatic and cognitive changes that affect functioning; however, they differ in duration, timing, and cause
    • DSM-5-TR classifies depressive disorders as follows: r10
      • 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

    Diagnosis

    Clinical Presentation

    History

    • Disease onset
      • May occur for the first time during pregnancy, or patient may have history of depression c1
    • Symptoms may include: r11
      • Dysphoria (feelings of sadness or hopelessness) c2
      • Anhedonia (loss of interest in pleasurable or usual activities) c3
      • Insomnia or hypersomnia c4c5
      • Sense of guilt or poor self-esteem c6c7
      • Difficulty concentrating and memory impairment c8c9
      • Negative thoughts about the future c10c11
      • Excessive weight loss or gain c12c13
      • Increased or decreased appetite c14c15
      • Preoccupation with physical symptoms (eg, fatigue, headache, nausea, diarrhea, constipation)r12 and pain c16c17c18c19c20c21c22
      • Disinterest in or excessive anxiety about pregnancy c23c24
      • Lack of adherence to prenatal care c25
      • Talk of suicide or death c26c27
      • Suicidal ideation or passive death wish c28c29
    • May be unclear whether some of the symptoms are due to depression or normal pregnancy-related changes r11
      • Some somatic symptoms commonly associated with pregnancy overlap with symptoms of depression (eg, sleep and appetite disturbances, diminished energy, decreased libido) r13r14c30c31c32c33
      • Attention to certain symptoms not common to pregnancy may be most helpful (eg, disinterest in pregnancy, excessive guilt, dysphoria, anhedonia, impaired concentration, suicidal ideation) r13c34c35c36c37c38c39
      • Patients often present with anxiety (eg, excessive generalized worries, pervasive worries that are difficult to control, panic attacks) c40c41
    • Other important patient history factors: r12
      • Suicidal ideation with or without plan c42c43
      • Patient medical history and/or family history may include diagnosis of depression or other psychiatric disorder c44c45
      • Tobacco, alcohol, or other drug use c46c47c48c49
      • Social history may uncover current stressors (eg, marital discord, domestic violence, occupational stressors, limited social support) c50c51c52c53c54
      • Limitation or decline in social, occupational, or academic functioning c55c56c57
      • Limitation or decline in self-care may be present (eg, lack of adherence to prenatal care plan, poor nutrition) c58c59c60

    Physical examination

    • General physical examination may show: r12
      • Weight loss, weight gain, or evidence of poor nutrition c61c62c63
      • Evidence of self-harm (eg, healed lacerations, scars on trunk or extremities) c64c65c66
      • Stigmata of trauma, self-injury, or drug use c67c68c69
      • Evidence of self-neglect with poor personal hygiene r12c70c71
    • Mental status findings may include: r12
      • Poor or no eye contact c72
      • Speaking in low tones or slowly c73
      • Psychomotor retardation and flat affect c74
      • Depressed mood and crying c75c76
      • Sadness, hopelessness, preoccupation with death, suicidal ideation c77c78c79

    Causes and Risk Factors

    Causes

    • 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 r15c80c81c82c83

    Risk factors and/or associations r8

    Age
    • Adolescent and young adult pregnant patients are at higher risk for prenatal depression r4r16c84c85
      • Up to a quarter of pregnant adolescents may develop major depression during pregnancy r17
    Genetics
    • Major depressive disorder is a multifactorial disorder with genetic susceptibility c86
    • Greatest risk for major depressive disorder is observed in families with early age at onset r18c87
    Ethnicity/race
    • In the United States, higher incidence in Black, Hispanic, and Asian American populations compared with White populations r4c88c89c90c91
    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 females may be at increased risk for a major depressive episode during the perinatal period r4c92
      • Pregnancy and the postpartum period are associated with risk for relapse in patients who previously experienced major depression c93c94
        • Discontinuing antidepressants during pregnancy is associated with greater risk for relapse in females with severe depression r7
        • In females 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 r19
      • There is an increased prevalence of depressive disorders among females with high-risk pregnancies due to obstetric complications such as threatened preterm labor, preeclampsia, oligohydramnios, and gestational diabetes r20r21c95c96c97c98c99
    • Risk factors for prenatal depression (in addition to adolescence and ethnicity)
    • Risk factors for depression relapse during pregnancy in patient with history of depression before conception r4
      • Discontinuation of antidepressant medication during pregnancy c121
      • Longer duration of illness c122
      • Previous history of relapse c123
      • Relapse episode within 6 months before conception c124
      • Early age at onset of a mood disorder c125
      • Multiple past episodes of depression c126

    Diagnostic Procedures

    Primary diagnostic tools

    • Suspect diagnosis in pregnant patients presenting with manifestations of depression c127
    • Initially may use screening tools to identify patients at risk for depression
      • Edinburgh Postnatal Depression Scale,r1Patient Health Questionnaire-9,r2 and Postpartum Depression Screening Scaler3 are screening tools commonly used to assess patients during the perinatal period r25r26r27r28c128c129c130
      • Patients who screen positive for possible depression require full diagnostic interview with focus on DSM-5-TR criteria and comprehensive psychosocial risk factor assessment r4c131c132
      • Strongly consider referral to a psychiatrist 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 r29c133c134c135c136c137
      • Assess for conditions that may initially mimic depression (eg, bipolar disorder, substance use) and comorbidities that affect treatment decisions (eg, anxiety disorders, substance use) d1
        • Particularly important to screen for bipolar disorder before initiating any pharmacotherapy for depression, as treatment with antidepressant monotherapy may precipitate mania, rapid cycling, or psychosis in patients with bipolar disorder r5
    • Confirm diagnosis by fulfilling DSM-5-TR criteria for major depressive disorder r10c138
      • 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) r16
      • This can be done with either a self-administered or clinician-administered instrument such as the Mood Disorder Questionnaire or Composite International Diagnostic Interview, respectively. Because bipolar disorder and depression both include depressive symptomatology, and because hypomania or mania may have anxiety-like features, bipolar disorder diagnoses are often missed, with symptoms attributed to these more common diagnoses

    Procedures

    c139

    Other diagnostic tools

    • DSM-5-TR criteria for major depressive disorder r10c140
      • 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 reported by patient or observed by others
        • Markedly reduced interest or pleasure in all or almost all activities for most of the day
        • Significant weight loss or 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 c141
      • 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 r30
          • Generally distressed but able to continue most activities (mild) or having great difficulty continuing activities (moderate) r14r30
          • Score of less than 15 points on Patient Health Questionnaire-9 r2
          • Absence of suicidal behavior, psychotic features, or significantly impaired functioning
        • Moderate to severe
          • Score of 15 to 19 points on Patient Health Questionnaire-9 r2
        • Severe
          • At least 7 depressive symptoms r16r30
          • Score of 20 or more on Patient Health Questionnaire-9 r2
          • Number of symptoms is substantially in excess of that required to make the diagnosis r10
          • Intensity of symptoms is seriously distressing and unmanageable r10
          • Symptoms markedly interfere with social and occupational functioning r10
          • Presence of suicidal ideation or attempts or psychotic features
    • Screening tools for depression in pregnancy
      • Positive screening result is not diagnostic; screening tools are intended to identify females who warrant further evaluation r16c142
        • Follow up a positive screening result with a detailed diagnostic interview with focus on DSM-5-TR criteria and assessment of psychosocial risk factors r4
      • Most commonly used screening tools:
        • Edinburgh Postnatal Depression Scale r1c143
          • Self-reported, 10-item questionnaire r31
          • Validated for both prenatal and postnatal use;r16 originally developed to screen for possible postnatal depression r4
          • Excludes some nonspecific somatic symptoms common during the perinatal period even in the absence of depressive disorders r26
          • Scores range from 0 to 30 r31
            • Score of 10 to 13 or higher suggests possible depressive or anxiety disorder r4r31
          • 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 r26r32
          • Sensitivity ranges from 80% to 90%, depending on the threshold defined for positive score r26
          • Edinburgh Postnatal Depression Scale items and scoring.Begin screening with an introductory dialogue such as, "We would like to know how you are feeling during your pregnancy. Please underline the answer that comes closest to how you have felt in the past 7 days, not just how you feel today." Scores range from 0 to 30; a score of 10 to 13 or higher suggests possible depressive or anxiety disorder. Any score above 0 on the last item warrants full risk assessment.Adapted from Cox JL et al: Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 150:782-6, 1987.
            ItemAnswer (score 0)Answer (score 1)Answer (score 2)Answer (score 3)
            I have been able to laugh and see the funny side of thingsAs much as I always couldNot quite as much nowDefinitely not so much nowNot at all
            I have looked forward with enjoyment to thingsAs much as I ever didRather less than I used toDefinitely less than I used toHardly at all
            I have blamed myself unnecessarily when things went wrongNo, neverNot very oftenYes, some of the timeYes, most of the time
            I have been anxious or worried for no good reasonNo, not at allHardly everYes, sometimesYes, very often
            I have felt scared or panicky for no very good reasonNo, not at allNo, not muchYes, sometimesYes, quite a lot
            Things have been getting on top of meNo, I have been coping as well as everNo, most of the time I have coped quite wellYes, sometimes I have not been coping as well as usualYes, most of the time I have not been able to cope at all
            I have been so unhappy that I have had difficulty sleepingNo, not at allNot very oftenYes, sometimesYes, most of the time
            I have felt sad or miserableNo, not at allNot very oftenYes, quite oftenYes, most of the time
            I have been so unhappy that I have been cryingNo, neverOnly occasionallyYes, quite oftenYes, most of the time
            The thought of harming myself has occurred to meNeverHardly everSometimesYes, quite often
        • Australian guidelines r33
          • 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 r2c144
          • Self-report, 9-item questionnaire r2r34
          • Validated for detection of possible prenatal depression r4
          • Score of 10 or higher suggests possible depression r4
        • Postpartum Depression Screening Scale r3c145
          • Self-report, more extensive inventory comprising 5 items in each of 7 dimensions: r26
            • 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 r26
          • Score of 60 or higher identifies significant symptoms of depression; score of 80 or higher is a positive screening result for major depression r26
      • Other available tools:
        • Beck Depression Inventoryr35c146
          • Self-rated questionnaire; measures intensity, severity, and depth of common depression symptoms r27
          • Standard test has 21 questions; a shorter 7-question version is optimized for office screening use r27
        • Hamilton Depression Rating Scale c147
          • Observer-rated scale designed to be administered by health care professionals r27
        • Major Depression Inventory c148
          • Self-rated questionnaire; incorporates both the ICD‐10 symptoms of depression and the DSM-IV symptoms of major depression r28

    Differential Diagnosis

    Most common r36

    • Normal pregnancy-related changes c149c150
      • 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 symptoms of depression
      • Differentiated by clinical history and DSM-5-TR criteria
    • Persistent depressive disorder (dysthymic disorder) c151
      • Mental disorder characterized by depressive symptoms that do not meet the DSM-5-TR 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-TR criteria
    • Bipolar disorder r37c152d1
      • 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 r38
        • 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-TR criteria
    • Adjustment disorder r39c153
      • 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-TR criteria
    • Schizophrenia c154d2
      • 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-TR criteria
    • Borderline personality disorder c155d3
      • Personality disorder characterized by mood swings, recurrent suicidal ideation, and impulsive behavior
      • Typically associated with affective instability, unstable personal relationships, and transient stress-related cognitive impairment
      • Differentiated by clinical history and DSM-5-TR criteria
    • Hypothyroidism r40c156d4
      • 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 c157d5
      • Characterized by significantly depressed mood that develops after use of medications or illicit substances (eg, stimulants, alcohol), resulting in psychosocial impairment d6
      • 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

    Treatment

    Goals

    • If patient is suicidal, take steps to protect from self-harm as needed r34
    • Stabilize mood and return patient to normal psychosocial functioning r34
    • Encourage adherence to treatment to minimize relapse or recurrence r34
    • Consider pharmacotherapy when risks of untreated illness are greater than risks of pharmacotherapy during pregnancy r41
    • Address and minimize any complications such as malnutrition and substance use r34

    Disposition

    Admission criteria

    • Indications for admission include:
      • Suicidal or homicidal ideation with plan and intent or suicide attempts r42
      • Substance withdrawal or intoxication r42
      • Severe symptoms (eg, severe delusions, psychosis, catatonic behavior) r42
      • Inability to care for self r42
      • Undergoing electroconvulsive therapy r42
      • Consider for patients at very high risk for relapse r22
    • Partial hospital admission (intensive outpatient treatment) may be appropriate for some patients r42

    Recommendations for specialist referral

    • Optimal approach during pregnancy is multidisciplinary management involving mental health specialist, obstetrician, primary care clinician, and social worker and/or case manager r4
      • Integrated management is particularly ideal for patients who require both psychotherapy and pharmacotherapy r9
    • Consult a psychiatrist or mental health professional specializing in care of pregnant patients if a 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 done in 2014 found a dearth of high-quality evidence; that review is now archived but not yet replaced, and the evidence base remains weak r43
    • Balance clinical judgment regarding treatment decisions with risks of medication exposure during pregnancy and risks of untreated maternal depression r4r44
    • 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 r9r45r46r47
      • Moderate to severe depression
        • Guidelines often recommend pharmacotherapy in addition to psychotherapy, particularly in the presence of functional limitations and diminished ability for self-care r9r13

    Primary modes of treatment include nonpharmacologic measures and pharmacologic treatment

    • Nonpharmacologic treatment measures
      • Psychotherapy is a first line treatment for patients with mild to moderate major depressive disorder during pregnancy r46r47r48
        • Preferred psychotherapeutic options include interpersonal therapy and cognitive behavioral therapy r4r9r49
        • Psychotherapy is moderately effective and may reduce or obviate need for medications r4
        • Psychotherapy may be effective as:
          • Single modality for mild to moderate depression r4r50
          • Adjunct treatment of depression necessitating psychotropic medication r4
      • Optimize other nonpharmacologic treatment options r4
        • 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
      • No randomized trials have evaluated the efficacy or safety of pharmacotherapy for depression during pregnancy r47
      • If medication is required, consider enrolling a US patient in the National Pregnancy Registry for Antidepressants r51
        • Information collected by registry can help improve safety information for medicines used during pregnancy; information collected may be used to update drug labeling
      • Multiple observational studies support a favorable safety profile for selective serotonin reuptake inhibitors r47
      • Preferred first line treatment for antidepressant-naive patients is a selective serotonin reuptake inhibitor r19r22r41r44r47
        • Options include sertraline, fluoxetine, fluvoxamine, vilazodone, citalopram, and escitalopram r19r41
          • Sertraline and citalopram are generally preferred owing to their favorable lactation profiles r52
          • Overall, selective serotonin reuptake inhibitors are not considered to be major teratogens r4r7r41
            • Exception is paroxetine, which is generally avoided owing to reports of cardiovascular malformations (ie, septal defects) with first-trimester exposure r53
            • 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 r7
        • Serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine, duloxetine) are reasonable alternatives
      • Preferred treatment for patients who have been effectively treated with an antidepressant of any class in the past is the effective medication r47
      • Other options (with more limited data about safety in pregnancy) for depression not responding to selective serotonin reuptake inhibitors, include: r9r41
        • Bupropion
        • Mirtazapine r54
        • Tricyclic antidepressants; nortriptyline is often preferred owing to lower tendency for anticholinergic adverse effects r53
          • Tricyclic antidepressants may be helpful for patients with concomitant agitation; agents with the fewest anticholinergic effects (ie, nortriptyline, desipramine) are preferred for pregnant patients
          • Overall, tricyclic antidepressants are not associated with congenital anomalies, with the possible exception of increased risk of congenital cardiac defects associated with clomipramine r4
      • 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 r44
          • Preference is to maximize dose of a single drug rather than provide lower doses of multiple drugs r44
        • Preferred medication profile includes the one with the best safety data, few metabolites, higher protein binding to decrease placental passage, and few interactions with other medications r4
        • Consider patient history of medication response; preferentially prescribe medication that has proven effective for this patient in the past (eg, a particular selective serotonin reuptake inhibitor that has helped before) r44
        • Use the lowest effective therapeutic dose r9r44
        • Avoid discontinuing an effective selective serotonin reuptake inhibitor antidepressant during pregnancy r44
          • Tapering these medications during pregnancy puts patient at increased risk for prenatal relapse and postpartum depression and generally is not recommended outside certain scenarios r44
        • Adjust selective serotonin reuptake inhibitor dosing based on clinical symptoms; dose adjustments are frequently needed during the second and third trimesters r44
          • Multiple pharmacokinetic changes in selective serotonin reuptake inhibitor metabolism occur in the second and third trimesters, leading to lower serum drug concentrations r44
          • Often need to increase dose in later stages of pregnancy to maintain therapeutic effect r4
          • Serum drug concentrations return to prepregnancy levels after delivery; decrease in dose may be appropriate in postpartum period r44
        • Use of selective serotonin reuptake inhibitors during the third trimester may be associated with the following: r4
          • Poor neonatal adaptation syndrome r55
            • Irritability
            • Insomnia
            • Rigidity or limpness
            • Tremors
            • Seizures
            • Respiratory distress
          • Small increased risk of persistent pulmonary hypertension of the newborn and preterm deliveryr56r57
          • Newborns exposed to selective serotonin reuptake inhibitors have also been shown to have lower birth weights and Apgar scores at delivery r58
        • Experts usually recommend continuing medication used during pregnancy while breastfeeding; this continuation may minimize potential adverse manifestations in neonates and infants r9r16

    Considerations for patients who do not respond to initial management

    • Definitions of treatment-refractory depression vary r59
      • Most experts agree that a patient has treatment-refractory depression when a response has not been observed with 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, and 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: r19
      • Electroconvulsive therapy
        • Approved and effective treatment modality during pregnancy; risks of therapy must be weighed against risks of untreated illness r60
        • Consider for patients with severe depression, affective psychosis, and/or catatonia r13
      • Repetitive transcranial magnetic stimulation
        • Emerging treatment option; data on pregnant patients are limited r61
        • May offer a medication-free treatment option for some females with severe disease refractory to other treatment

    Maintenance pharmacotherapy for females treated for depression before pregnancy

    • Management of psychotropic medication use during pregnancy must balance the risk of adverse effects with the risk of untreated illnessr44
    • No currently available antidepressants are absolutely contraindicated during pregnancy;r19 however, no psychotropic medication is approved by FDA for use during pregnancy r9
      • Note: MAOIs are discouraged during pregnancy owing to risk of hypertensive crisis when combined with tocolytics
      • Atypical antipsychotic medications are associated with heart and gastrointestinal defects, cleft palate when used in early pregnancy r62
    • Continue current antidepressant that is successfully managing symptoms, particularly for females with a history of severe or recurrent depression and history of relapse when discontinuing maintenance medication, even if asymptomatic at the time of conception r4
    • Discontinuing antidepressants during pregnancy is generally not recommended r19
      • Euthymic females who discontinue antidepressants may have an increased risk for depression relapse compared with females who continue antidepressant treatment; data are not straightforward or overwhelmingly conclusive r4r16
      • May consider discontinuing ongoing pharmacologic therapy during pregnancy for select patients with mild depression. For these patients, gradually taper antidepressant over 1 to 2 weeks with close support and monitoring from a psychotherapist or psychiatrist r53
      • Before pregnancy is the ideal time to consider careful selective serotonin reuptake inhibitor taper for appropriate patients (ie, patients with mild and stable depression without a history of recent relapse or several depressive episodesr16) with the intent to avoid fetal medication exposure r44

    Drug therapy

    • Selective serotonin reuptake inhibitors r63c158
      • Citalopram c159
        • Citalopram Hydrobromide Oral tablet; Adults 18 to 60 years: 20 mg PO once daily, initially. May increase the dose at intervals of at least 1 week if inadequate response and depending on tolerability. Max: 40 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Sertraline r64c160
        • Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily, initially. May increase the dose by 25 to 50 mg/day at intervals of at least 1 week if inadequate response and depending on tolerability. Usual dose: 50 to 200 mg/day. Max: 200 mg/day.
          • 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 the potential benefit to the mother outweighs the potential risk to the fetus
      • Escitalopram r65c161c162
        • Escitalopram Oral tablet; Adults: 10 mg PO once daily, initially. May increase the dose to 20 mg/day after at least 1 week if inadequate response and depending on tolerability. Usual dose: 10 mg/day. Max: 20 mg/day.
      • Fluoxetine c163
        • Fluoxetine Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: 20 mg PO once daily, initially. May increase the dose after several weeks if inadequate response and depending on tolerability. May divide doses of 20 mg/day or more in 2 doses. Max: 80 mg/day.
    • Serotonin-norepinephrine reuptake inhibitors c164
      • Duloxetine c165
        • Duloxetine Oral capsule, gastro-resistant pellets; Adults: 20 or 30 mg PO twice daily or 60 mg PO once daily, initially. Alternatively, 30 mg PO once daily for 1 week, then 60 mg PO once daily. Usual Max: 60 mg/day. Max: 120 mg/day.
      • Venlafaxine c166
        • Venlafaxine Hydrochloride Oral tablet, extended-release; Adults: 75 mg PO once daily, or alternatively, 37.5 mg PO once daily for 4 to 7 days, then 75 mg PO once daily, initially. May increase the dose by 75 mg/day at intervals of at least every 4 days if inadequate response and depending on tolerability. Max: 225 mg/day.
    • Noradrenergic and specific serotonin antidepressants c167
      • Mirtazapine r65c168
        • Mirtazapine Oral tablet; Adults: 15 mg PO once daily at bedtime, initially. May increase the dose up to 45 mg/day at intervals of at least 1 to 2 weeks if inadequate response. Max: 45 mg/day.
          • Safe use of mirtazapine during pregnancy has not been established. Therefore, it should not be administered to females 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 c169
      • Bupropion c170
        • Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]; Adults: 150 mg PO once daily, initially. May increase the dose to 150 mg PO twice daily after 3 days, and then 200 mg PO twice daily after several weeks if inadequate response. Max: 400 mg/day.
    • Tricyclic antidepressants r63c171
      • Desipramine c172
        • Desipramine Hydrochloride Oral tablet; Adults: 100 to 200 mg/day PO once daily or in divided doses; start at lower dose and increase dose gradually as needed and tolerated. Max: 300 mg/day. Reduce dose to the lowest dose that will maintain remission after satisfactory improvement has occurred.
      • Nortriptyline c173
        • Nortriptyline Hydrochloride Oral capsule; Adults: 25 mg PO 3 or 4 times daily, or alternately, 75 to 100 mg PO once daily, initially; start at lower dose and increase dose gradually as needed and tolerated. Max: 150 mg/day. Reduce dose to the lowest dose that will maintain remission after satisfactory improvement has occurred.

    Nondrug and supportive care

    Nonpharmacologic psychotherapeutic treatment modalities

    • First line modalitiesr66 include:
      • Interpersonal therapy c174
        • Focus includes attention to role transition, interpersonal functioning, and building social rapport r4r9
        • Structured, time-limited psychotherapy
      • Cognitive behavioral therapy c175
        • Focus involves correction of negative thinking and associated behaviors r24
    • Other psychotherapeutic options include:
      • Perinatal period–specific treatments: mindfulness-based intervention and perinatal dyadic psychotherapy r44c176c177
      • General treatment modalities for depression: behavioral activation therapy, problem-solving therapy, nondirective counseling, and psychodynamic therapy r34r67c178c179c180c181

    Anticipatory guidance and education c182c183

    • Educate patient and family about illness r4r13c184
    • Anticipate potential problems that may arise in postpartum period and develop coping strategies (eg, based on cognitive behavioral therapy or behavioral strategies) r34c185
    • Encourage open communication with medical professional(s): thoughts of self-harm, suicidal ideation, and homicidal ideation (eg, murder-suicide of mother and infant) c186c187
    • Maximize wellness strategies including: r44
      • 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 r68c188c189c190c191
    • Massage, yoga, and mindfulness techniques r4c192c193c194
    • Peer support and support groups for females who struggle with depression during pregnancy r13c195c196
    • Data are mixed regarding efficacy of other complementary treatments (eg, ω-3 fatty acids, folate, St John's wort, bright light therapy, acupuncture) r4r69c197
      • Bright light therapy may be helpful for patients with a seasonal component to their affective disorder r13r44c198
      • Acupuncture may be helpful for select patients r44c199
    Procedures
    Electroconvulsive therapy r70c200
    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: r4r50r71
      • Some anesthesiologists recommend intubation to protect the airway after the first trimester because there is increased risk of gastric reflux and aspiration during the second and third trimesters r13
      • Fetal heart rate monitoring before and after procedure is recommended r13
      • Obstetrician should be readily available during procedure in the event of fetal compromise r13
    Indication
    • May be used as first line therapy for patients who have: r50r71
      • Psychotic depression r13
      • Catatonia r13
      • Severe suicidality
      • Depression posing serious risk to health of the patient or fetus r13
      • Previous positive response to this treatment method r13
      • Anorexia or rapidly deteriorating physical status
      • Treatment-resistant depression
      • Repeated medication intolerance
    Contraindications
    • Relative contraindications include:
      • Younger than 18 years
      • Space-occupying brain lesions
      • Elevated intracranial pressure
      • Recent myocardial infarction
      • History of retinal detachment
      • Pheochromocytoma
    Complications
    • Complications in the fetus include arrhythmia and demise; in the mother, vaginal bleeding, uterine contractions, and premature labor r4r19
    • 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 r13
      • Fractures
      • Dental and tongue injuries
    Repetitive transcranial magnetic stimulation r72c201
    General explanation
    • Involves applying a strong, pulsed magnetic field to targeted brain region (often dorsolateral prefrontal cortex region when treating for depression) r73
    • Electromagnetic coil is held against patient's forehead, and short electromagnetic pulses are administered through the coil to generate electromagnetic field r73
    • Electromagnetic field results in regional neuronal depolarization and generation of action potentials r73
    • Data support efficacy of various techniques (eg, high-frequency, low-frequency, theta burst pulse pattern) and application to various target areas for improvement in patients with pharmacoresistant depression r73
    • Treatments are repeated daily for 4 to 6 weeks; a typical session lasts 30 to 60 minutes and does not require anesthesia r74r75
    Indication
    • Patients with major depression recalcitrant to antidepressant drug therapy r46r71
    Contraindications
    • 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 the body (eg, prosthetic cardiac valves)
    • Relative contraindications include:
      • Ferromagnetic material in the 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
    Complications r76
    • Tension-like headache
    • Localized application site discomfort or pain
    • Seizure during treatment; approximately 0.1% risk over the full course of treatments

    Comorbidities

    • Substance or alcohol use disorders c202c203
      • A significant proportion of pregnant females with a major depressive episode report either misusing opioids, using marijuana, or drinking alcohol r6
      • Treat substance use disorder while treating depression
    • Coexisting psychiatric conditions, such as anxiety, obsessive-compulsive disorder, and personality disorders c204c205c206c207
      • May affect the treatment of major depression and require additional treatment specific for comorbid disorder
      • Peripartum depression is comorbid with anxiety in approximately 28% of patients, and effective treatment involves treating both depression and anxiety r5
      • Approximately 22% of patients with a positive perinatal depression screen will be found to have bipolar disorder if further evaluated; treatment with a mood stabilizer is usually indicated, and antidepressant monotherapy is contraindicated r5

    Monitoring

    • All patients with depressive disorders during pregnancy
      • At every clinical encounter, screen for threat of harm to self or others c208c209
      • Monitor clinical symptoms and assess for decline in function throughout pregnancy and postpartum period c210
      • Frequency of monitoring varies
        • Determine based on depression severity, presence of suicidal ideation, adherence to treatment, strength of social supports, and presence of coexisting medical conditions c211c212c213c214c215
        • During the initial phase of treatment, monitoring can vary from once a week to multiple times a week, depending on depression severity c216c217
    • Patients requiring psychotropic medication
      • Frequently monitor symptom control, particularly during the second and third trimesters r44c218
      • 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 the second and third trimesters r44c219c220c221
      • Adjust selective serotonin reuptake inhibitor dosing based on clinical symptom control r44c222
      • Consider fetal echocardiography with first-trimester paroxetine exposure r4r44c223
      • Venlafaxine is associated with dose-related increases in blood pressure; closely monitor blood pressure. Consider tapering and discontinuing if the patient develops preeclampsia r13c224
      • 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 r77c225
        • Monitoring of tricyclic antidepressants is strongly recommended r77
    • Neonates exposed to selective serotonin reuptake inhibitor
      • Rigorous monitoring for poor neonatal adaptation syndrome is not standardized r16
      • Absence of manifestations by 72 hours indicates that poor neonatal adaptation syndrome is unlikely to develop r16c226

    Complications and Prognosis

    Complications

    • Complications secondary to untreated or undertreated prenatal depression include increased risk for the following:
      • Pregnancy-related complications and associations including: c227
        • Poor health behaviors leading to increased risk for obstetric complications and poor pregnancy outcomes r4c228c229
          • Poor patient adherence to prenatal care, prenatal vitamins, and prescribed medications c230
          • Smoking, alcohol consumption, and substance use
          • Poor nutrition leading to poor weight gain c231
          • Lack of exercise
        • Ambivalence about the pregnancy and decreased intention to breastfeed r4c232c233
        • Suicidal ideation r4c234
        • Suicide c235
          • Absolute risk is low; however, suicide does represent a leading cause of death in depressed pregnant females, particularly in association with untreated depression r78r79
        • Operative delivery requirement r80c236
        • Intrauterine growth restriction r80c237
        • Preterm birth r4r80r81c238
        • Low-birthweight and small-for-gestational-age neonate r4r80c239c240
        • Postpartum depression r41c241
      • 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) r4
        • Potential complications include: r4c242
          • Neonate and infant: lower neonatal behavioral scores,r82 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 developmentr44c243c244c245c246c247c248c249
          • Young child: internalizing behaviors, externalizing behaviors, fearful temperament, anxiety, and delayed motor and cognitive development c250c251c252c253c254c255
          • Older child: altered stress response, attention-deficit/hyperactivity disorder, depression, and anxiety disorders c256c257c258
    • Complications secondary to prenatal exposure to antidepressant medications include:
      • Poor neonatal adaptation syndrome (also called neonatal toxicity, neonatal behavioral syndrome,r4 postnatal adaptation syndrome) c259
        • 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 the third trimester r4
        • Manifestations may include respiratory distress r4r41r80
          • General: temperature instability, feeding difficulty, vomiting, sleep disturbance, jaundice, and hypoglycemia
          • Cardiovascular: prolonged QT interval and arrhythmias r9
          • 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 at 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 r44r80
        • Most manifestations are mild and require only close observation and supportive care r41
        • Dose-dependent relationship with syndrome severity has been observed r80
      • Persistent pulmonary hypertension of the newborn c260
        • 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 r80
        • Data are conflicting; there may be small increased risk with exposure after 20 weeks of gestation (odds ratio, 1.28; 95% confidence interval, 1.01-1.64),r83 but some studies have found no increased riskr41
      • Postpartum maternal hemorrhage c261
        • Exposure to selective serotonin reuptake inhibitors late in pregnancy may increase risk of postpartum bleeding, particularly upper gastrointestinal bleeding r44
        • Data are inconsistent and conflicting; reported relative risk is at best small (1.47; 95% confidence interval, 1.33-1.62)r84
      • 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]) r4
        • 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) r4c262
            • Risk is about 1% (risk among general population of newborns is about 0.7%) r80
          • Preterm birth (modest effect, pregnancy shortened by 3-5 days) r4c263
          • Delayed motor development (mild and transientr44) r4r9c264c265
          • Lower birth weight (small effect, weight decreased by about 74 g) r4c266
          • Lower 1- and 5-minute Apgar scores (small effect, largely undetermined clinical significance) r4r16

    Prognosis

    • 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)
      • It has been found that more than half of pregnant patients with a major depressive episode did not receive any mental health treatment, with financial concerns being the primary reason r6
    • There is a high risk of relapse after a depressive episode, especially in the first 6 months; risk declines with time in remission r50
      • 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

    Screening

    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)

    Guidelines

    • US Preventive Services Task Force recommends screening all pregnant and postpartum adults and adolescents (aged 12 years and older) for depression r25r85c267
      • Screening helps ensure accurate diagnosis, effective treatment, and appropriate follow-up r25
    • Most guidelines endorse routine perinatal screening for depression r26
      • Optimum timing for perinatal screening is not rigorously standardized r86
    • American College of Obstetricians and Gynecologists recommends all pregnant patients be screened for depression at the initial prenatal visit, again later in pregnancy, and at postpartum visits using a validated, standardized tool r5
    • Australian guidelines recommend screening for depression at least once during pregnancy and once in the postpartum period r33
    • Canadian guidelines do not endorse routine questionnaire-based screening for depression for all patients during pregnancy and in the postpartum period r87r88r89

    Screening tests

    • Standardized depression screening tools: r25r26r27r34r85
      • Perinatal screening tools: Edinburgh Postnatal Depression Scale,r1Patient Health Questionnaire-9,r2 and Postpartum Depression Screening Scaler3c268c269c270
      • General screening tools: Beck Depression Inventory, Major Depression Inventory, and Hamilton Depression Rating Scale c271c272c273
    • Short case-finding questions (2 or 3 questions) are advocated by some guidelines to identify females who need to be monitored closely for depression and further assessed with standardized screening tools r26r90
      • 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 the following 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% r26

    Prevention

    • Data are scarce regarding prevention strategies for depressive disorders in pregnancy r16r32r91
      • 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 r92
    • Effective preconception planning may diminish risk of active disease or relapse of known depression during pregnancy r13
      • Encourage the patient to review risks of untreated disease and medication use during pregnancy before conception
      • Establish an appropriate psychotropic medication regimen for depressed females 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, 19873651732Spitzer RL et al: Patient Health Questionnaire-9 (PHQ-9). PHQ Screeners website. Accessed August 24, 2023. https://www.phqscreeners.com/images/sites/g/files/g10060481/f/201412/PHQ-9_English.pdfhttps://www.phqscreeners.com/images/sites/g/files/g10060481/f/201412/PHQ-9_English.pdfTatano Beck C et al: Postpartum Depression Screening Scale. WPS Publishing website. Published 2002. Accessed April 20, 2021. https://www.wpspublish.com/pdss-postpartum-depression-screening-scalehttps://www.wpspublish.com/pdss-postpartum-depression-screening-scalePearlstein T: Depression during pregnancy. Best Pract Res Clin Obstet Gynaecol. 29(5):754-64, 201525976080Screening and diagnosis of mental health conditions during pregnancy and postpartum: ACOG Clinical Practice Guideline No. 4. Obstet Gynecol. 141(6):1232-1261, 202337486660Sanmartin MX et al: Mental health treatment and unmet mental health care need among pregnant women with major depressive episode in the United States. Psychiatr Serv. 70(6):503-6, 201930966943Aftab A et al: Behavioral emergencies: special considerations in the pregnant patient. Psychiatr Clin North Am. 40(3):435-48, 201728800800González HM et al: The epidemiology of major depression and ethnicity in the United States. J Psychiatr Res. 44(15):1043-51, 201020537350Kimmel MC et al: Pharmacologic treatment of perinatal depression. Obstet Gynecol Clin North Am. 45(3):419-40, 201830092919American Psychiatric Association: Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed., Text Revision. American Psychiatric Association; 2022:178-215Romera I et al: Individual residual symptoms and functional impairment in patients with depression. Psychiatry Res. 220(1-2):258-62, 201425149132Silverman JJ et al: The American Psychiatric Association practice guidelines for the psychiatric evaluation of adults. Am J Psychiatry. 172(8):798-802, 201526234607Wichman CL et al: Diagnosing and treating depression during pregnancy. Prim Care Companion CNS Disord. 17(2), 201526445696Kirby N et al: Assessing low mood during pregnancy. BMJ. 366:l4584, 201931358493aan het Rot M et al: Neurobiological mechanisms in major depressive disorder. CMAJ. 180(3):305-13, 200919188629Howard LM et al: Non-psychotic mental disorders in the perinatal period. Lancet. 384(9956):1775-88, 201425455248Dietz PM et al: Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 164(10):1515-20, 200717898342Singh MK et al: The neuroscience of depression: implications for assessment and intervention. Behav Res Ther. 62:60-73, 201425239242McAllister-Williams RH et al: British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 31(5):519-52, 201728440103Tsakiridis I et al: Epidemiology of antenatal depression among women with high-risk pregnancies due to obstetric complications: a scoping review. Arch Gynecol Obstet. 300(4):849-59, 201931422459Wilson CA et al: Is there an increased risk of perinatal mental disorder in women with gestational diabetes? A systematic review and meta-analysis. Diabet Med. ePub, 201931693201Paschetta E et al: Perinatal psychiatric disorders: an overview. Am J Obstet Gynecol. 210(6):501-9.e6, 201424113256Ogbo FA et al: Determinants of antenatal depression and postnatal depression in Australia. BMC Psychiatry. 18(1):49, 201829463221Marcus SM et al: Depression in childbearing women: when depression complicates pregnancy. Prim Care. 36(1):151-65, ix, 200919231607Siu AL et al: Screening for depression in adults: US Preventive Services Task Force recommendation statement. JAMA. 315(4):380-7, 201626813211Milgrom J et al: Screening for perinatal depression. Best Pract Res Clin Obstet Gynaecol. 28(1):13-23, 201424095728Schneibel R et al: Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients. Psychiatry Res. 198(1):62-7, 201222445070Bech P et al: The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity. J Affect Disord. 66(2-3):159-64, 200111578668Glover J et al: Assessment of the person with late-life depression. Psychiatr Clin North Am. 36(4):545-60, 201324229656WHO: ICD-10: International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Version 2019. WHO website. Published 2019. Accessed August 24, 2023. https://icd.who.int/browse10/2019/enhttps://icd.who.int/browse10/2019/enO'Hara MW et al: Perinatal mental illness: definition, description and aetiology. Best Pract Res Clin Obstet Gynaecol. 28(1):3-12, 201424140480Austin MP et al: Antenatal psychosocial assessment for reducing perinatal mental health morbidity. Cochrane Database Syst Rev. 4:CD005124, 200818843682Austin MP et al: Detection and management of mood disorders in the maternity setting: the Australian clinical practice guidelines. Women Birth. 26(1):2-9, 201322217978Bentley SM et al: Major depression. Med Clin North Am. 98(5):981-1005, 201425134869Beck Institute: Beck Depression Inventory. Beck Institute website. Accessed August 24, 2023. https://beckinstitute.org/cbt-resources/resources-for-professionals-and-students/assesment-tools/https://beckinstitute.org/cbt-resources/resources-for-professionals-and-students/assesment-tools/Andriopoulos P et al: Depression, quality of life and primary care: a cross-sectional study. J Epidemiol Glob Health. 3(4):245-52, 201324206795Woo YS et al: A diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: a 5-year retrospective study. J Affect Disord. 174:83-8, 201525486276Zimmermann P et al: Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry. 66(12):1341-52, 200919996039Wakefield JC et al: Validity of the bereavement exclusion to major depression: does the empirical evidence support the proposal to eliminate the exclusion in DSM-5? World Psychiatry. 11(1):3-10, 201222294996Wu EL et al: Increased risk of hypothyroidism and hyperthyroidism in patients with major depressive disorder: a population-based study. J Psychosom Res. 74(3):233-7, 201323438714Payne JL: Psychopharmacology in pregnancy and breastfeeding. Med Clin North Am. 103(4):629-50, 201931078197Schoepf D et al: Comorbidity and its relevance on general hospital based mortality in major depressive disorder: a naturalistic 12-year follow-up in general hospital admissions. J Psychiatr Res. 52:28-35, 201424513499McDonagh M et al: Antidepressant Treatment of Depression During Pregnancy and the Postpartum Period. Evidence Report/Technology Assessment No. 216. (Prepared by the Pacific Northwest Evidence-Based Practice Center under Contract No. 290-2007-10057-I.) AHRQ Publication No. 14-E003-EF. Agency for Healthcare Research and Quality website. Published July 2014. Accessed August 24, 2023. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/depression-pregnancy-postpartum_research.pdfhttps://effectivehealthcare.ahrq.gov/sites/default/files/pdf/depression-pregnancy-postpartum_research.pdfSusser LC et al: Selective serotonin reuptake inhibitors for depression in pregnancy. Am J Obstet Gynecol. 215(6):722-30, 201627430585Yonkers KA et al: The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 31(5):403-13, 200919703633US Department of Veteran Affairs et al: VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder. Version 4.0. VA website. Published April 2022. Accessed August 24, 2023. https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPG_ProviderSummary_Final_508_updated.pdfhttps://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPG_ProviderSummary_Final_508_updated.pdfTreatment and management of mental health conditions during pregnancy and postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 141(6):1262-1288, 202337486661Genovez M et al: Psychotherapeutic treatments for depression during pregnancy. Clin Obstet Gynecol. 61(3):562-72, 201829965823van Ravesteyn LM et al: Interventions to treat mental disorders during pregnancy: a systematic review and multiple treatment meta-analysis. PLoS One. 12(3):e0173397, 201728358808Cleare A et al: Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 29(5):459-525, 201525969470MGH Center for Women's Mental Health: National Pregnancy Registry for Antidepressants. MGH Center website. Accessed August 24, 2023. https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/Molenaar NM et al: Guidelines on treatment of perinatal depression with antidepressants: an international review. Aust N Z J Psychiatry. 52(4):320-7, 201829506399Cohen LS et al: Treatment of mood disorders during pregnancy and postpartum. Psychiatr Clin North Am. 33(2):273-93, 201020385337Djulus J et al: Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes. J Clin Psychiatry. 67(8):1280-4, 200616965209Koren G et al: Diagnosis and management of poor neonatal adaptation syndrome in newborns exposed in utero to selective seretonin/norepinephrine reuptake inhibitors. J Obstet Gynaecol Can. 31(4):348-50, 200919497154Yang A et al: Neonatal discontinuation syndrome in serotonergic antidepressant-exposed neonates. J Clin Psychiatry. 78(5):605-11, 201728570796Ross LE et al: Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 70(4):436-43, 201323446732Corti S et al: Neonatal outcomes in maternal depression in relation to intrauterine drug exposure. Front Pediatr. 7:309, 201931403037Berlim MT et al: Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 52(1):46-54, 200717444078Ray-Griffith SL et al: Pregnancy and electroconvulsive therapy: a multidisciplinary approach. J ECT. 32(2):104-12, 201626796501Felipe RM et al: Transcranial magnetic stimulation for treatment of major depression during pregnancy: a review. Trends Psychiatry Psychother. 38(4):190-7, 201628076639Anderson KN et al: Atypical antipsychotic use during pregnancy and birth defect risk: National Birth Defects Prevention Study, 1997-2011. Schizophr Res. 215:81-8, 202031761471von Wolff A et al: Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis. J Affect Disord. 144(1-2):7-15, 201322963896Cipriani A et al: Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev. 4:CD006117, 200919370626Cipriani A et al: Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2:CD006532, 200919370639Parikh SV et al: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. Can J Psychiatry. 61(9):524-39, 201627486150Driessen E et al: The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis update. Clin Psychol Rev. 42:1-15, 201526281018Schuch FB et al: Exercise as a treatment for depression: a meta-analysis adjusting for publication bias. J Psychiatr Res. 77:42-51, 201626978184Dennis CL et al: Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression. Cochrane Database Syst Rev. 7:CD006795, 201323904069Charlson F et al: ECT efficacy and treatment course: a systematic review and meta-analysis of twice vs thrice weekly schedules. J Affect Disord. 138(1-2):1-8, 201221501875Milev RV et al: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Neurostimulation treatments. Can J Psychiatry. 61(9):561-75, 201627486154Fitzgerald PB et al: Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 60(10):1002-8, 200314557145Garnaat SL et al: Updates on transcranial magnetic stimulation therapy for major depressive disorder. Psychiatr Clin North Am. 41(3):419-31, 201830098655McClintock SM et al: Consensus recommendations for the clinical application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. J Clin Psychiatry. 79(1):pii:16cs10905, 201828541649Perera T et al: The Clinical TMS Society consensus review and treatment recommendations for TMS therapy for major depressive disorder. Brain Stimul. 9(3):336-46, 201627090022Janicak PG et al: Transcranial magnetic stimulation for the treatment of major depression. Neuropsychiatr Dis Treat. 11:1549-60, 201526170668Hiemke C et al: Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 51(1-02):9-62, 201828910830Palladino CL et al: Homicide and suicide during the perinatal period: findings from the National Violent Death Reporting System. Obstet Gynecol. 118(5):1056-63, 201122015873Khalifeh H et al: Suicide in perinatal and non-perinatal women in contact with psychiatric services: 15 year findings from a UK national inquiry. Lancet Psychiatry. 3(3):233-42, 201626781366Hanley GE et al: The effect of perinatal exposures on the infant: antidepressants and depression. Best Pract Res Clin Obstet Gynaecol. 28(1):37-48, 201424100223Grote NK et al: A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 67(10):1012-24, 201020921117Gressier F et al: Negative impact of maternal antenatal depressive symptoms on neonate's behavioral characteristics. Eur Child Adolesc Psychiatry. ePub, 201931297657Huybrechts KF et al: Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA. 313(21):2142-51, 201526034955Palmsten K et al: Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States. BMJ. 347:f4877, 201323965506US Preventive Services Task Force et al: Screening for depression and suicide risk in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA. 328(15):1534-42, 202236219440Reynolds CF 3rd et al: US Preventive Services Task Force recommendation statement on screening for depression in adults: not good enough. JAMA Psychiatry. 73(3):189-90, 201626815331Joffres M et al: Recommendations on screening for depression in adults. CMAJ. 185(9):775-82, 201323670157Lang E et al: Recommendation on instrument-based screening for depression during pregnancy and the postpartum period. CMAJ. 194(28):E981-E989, 202235878894Screening for perinatal depression: a missed opportunity. Lancet. 387(10018):505, 201626867429National Institute for Health and Care Excellence: Antenatal and Postnatal Mental Health: Clinical Management and Service Guidance. Clinical guideline CG192. NICE website. Published December 17, 2014. Updated February 11, 2020. Accessed August 24, 2023. https://www.nice.org.uk/guidance/cg192https://www.nice.org.uk/guidance/cg192Mahdi A et al: Approaches to the prevention of postnatal depression and anxiety--a review of the literature. J Psychosom Obstet Gynaecol. ePub, 201830204522Dennis CL et al: Psychosocial and psychological interventions for preventing postpartum depression. Cochrane Database Syst Rev. 2:CD001134, 201323450532
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