INTRODUCTION — Although delivering a baby is typically a happy event, some postpartum women become depressed. Patients may manifest postpartum blues consisting of mild depressive symptoms that are self-limited, or more severe syndromes such as unipolar major depression. Untreated postpartum major depression can result in both short- and long-term negative consequences for the mother and infant [1-4].
This topic reviews choosing a specific treatment for severe postpartum unipolar major depression. Other topics discuss treatment of mild to moderate episodes of postpartum unipolar major depression, the clinical features and diagnosis of postpartum major depression, safety of infant exposure to psychotropic drugs through breastfeeding, the postpartum blues, and the diagnosis and treatment of antepartum unipolar major depression and postpartum bipolar mood episodes.
●(See "Mild to moderate postpartum unipolar major depression: Treatment".)
●(See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis".)
●(See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding".)
●(See "Postpartum blues".)
●(See "Mild to moderate episodes of antenatal unipolar major depression: Choosing treatment".)
●(See "Severe antenatal unipolar major depression: Choosing treatment".)
●(See "Bipolar disorder in postpartum women: Epidemiology, clinical features, assessment, and diagnosis".)
●(See "Bipolar disorder in postpartum women: Treatment".)
DEFINITIONS
Postpartum period and disorders
●Postpartum period – We define the postpartum period as the first 12 months after birth. Definitions of the puerperium range from the first 1 to 12 months following a live birth. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Definition of postpartum period'.)
●Postpartum blues – During the puerperium, mild, transient depressive symptoms such as dysphoria, insomnia, emotional lability, and decreased concentration occur in many women. (See "Postpartum blues".)
●Postpartum depression – The diagnostic criteria for postpartum depression are the same criteria that are used to diagnose nonpuerperal major depression (table 1). (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Diagnosis' and "Unipolar depression in adults: Assessment and diagnosis", section on 'Unipolar major depression'.)
Severity of illness — Factors involved in choosing a treatment for postpartum unipolar major depression include the severity of illness:
●Mild to moderate – Mild to moderate episodes of major depression are generally characterized by five or six depressive symptoms (table 1), as indicated by a score <20 points on the Patient Health Questionnaire – Nine Item (PHQ-9) (table 2). Alternatively, a study of patients with postpartum unipolar major depression (n >4000) empirically defined relatively mild episodes as an average score of 11 on the Edinburgh Postnatal Depression Scale (figure 1A-B), and moderate episodes as an average score of 15 [5]. The PHQ-9 and the Edinburgh Postnatal Depression Scale are discussed separately. (See "Using scales to monitor symptoms and treat depression (measurement based care)", section on 'Patient Health Questionnaire - Nine Item' and "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening'.)
Patients with mild to moderate illness generally do not manifest suicidal behavior or obvious impairment of functioning and are less likely to develop complications such as psychotic and catatonic features. Mild to moderate depression can typically be managed in outpatient or partial (day) hospital settings.
●Severe – Severe major depression is characterized by seven to nine depressive symptoms (table 1) that occur nearly every day, as indicated by a score ≥20 points on the self-report Patient Health Questionnaire – Nine Item (PHQ-9) (table 2). Alternatively, a study of patients with postpartum unipolar major depression (n >4000) empirically defined relatively severe episodes as an average score of 20 on the Edinburgh Postnatal Depression Scale (figure 1A-B) [5].
Severely ill patients often report suicidal ideation and behavior, typically demonstrate obvious impairment of functioning, and often manifest poor judgement that places the patient and others (including children) at risk for imminent harm. In addition, patients are more likely to develop complications such as psychotic and catatonic features and have a history of severe or recurrent episodes. Patients with severe major depression should be referred to a psychiatrist for management and often require hospitalization [6,7]. Treating major depression with psychotic features or catatonia is discussed separately. (See "Unipolar major depression with psychotic features: Acute treatment" and "Catatonia: Treatment and prognosis".)
Difficulties may arise in determining the number of depressive symptoms that are present during the puerperium because changes in appetite, energy, and sleep may be due to depression or may represent normal postnatal-related changes. The presence of these somatic symptoms should be evaluated in the context of normal expectations for the postpartum period. As an example, postpartum patients frequently lack energy due to sleep deprivation and caring for an infant. However, lack of energy to the point that patients need to make a significant effort to initiate or maintain usual daily activities can be a mild to moderate depressive symptom, and anergia to the point that patients cannot get out of bed for hours is probably a symptom of severe depression. Persistent uncertainty as to whether an episode of major depression is mild to moderate or severe can be resolved by referral to a psychiatrist (preferably one specializing in perinatal disorders).
GENERAL PRINCIPLES — The general principles and issues that are involved in treating postpartum unipolar major depression include:
●Setting (eg, outpatient or inpatient)
●History of prior treatment
●Educating patients and families
●Adherence to treatment
●Monitoring symptoms
●Prescribing antidepressants
●Managing nonresponse
●Making referrals
These general principles are discussed in detail separately. (See "Postpartum unipolar major depression: General principles of treatment".)
CHOOSING TREATMENT FOR BREASTFEEDING PATIENTS
Overview — For patients with severe, postpartum unipolar major depression who are breastfeeding, acute treatment proceeds according to the sequence described in the sections below. Patients receive initial treatment and progress through each step until they respond. The primary treatments are antidepressant medications [8]. In addition, psychotherapy is nearly always indicated as an adjuvant to pharmacotherapy, unless symptoms render the patient incapable of participating.
The duration of an adequate trial with antidepressant medications is discussed separately. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Duration of an adequate trial'.)
Continuation treatment is generally indicated for patients who respond to acute treatment of unipolar major depression, and additional maintenance treatment is indicated for patients with an increased risk of recurrence. (See "Unipolar depression in adults: Continuation and maintenance treatment".)
Many women with severe postpartum depression are likely to breastfeed their infants. One review estimated that among all women who deliver, breastfeeding is initiated by approximately 80 percent [9].
Initial treatment — For patients with severe, postpartum unipolar major depression who are breastfeeding, we suggest antidepressant medications [9-11]. Multiple randomized trials indicate that antidepressants are efficacious for postpartum depression (see 'Choosing an antidepressant' below). In addition, the potential risks of most antidepressants to the infant are typically regarded as low, and there is a general consensus that the benefits of antidepressants outweigh the risks [8,10,12]. Antidepressants are more available than structured, evidence-based psychotherapy, and using antidepressants is consistent with multiple practice guidelines, including the National Institute for Health and Care Excellence and the Canadian Network for Mood and Anxiety Treatments [6,7,13-18]. The potential risks of antidepressants to breastfeeding infants are discussed separately. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding".)
Choosing a specific antidepressant depends primarily upon the prior treatment history. (See 'Choosing an antidepressant' below.)
Indirect evidence supporting the use of antidepressants for severe postpartum major depression includes several randomized trials that excluded patients who were breastfeeding; these trials have demonstrated that numerous antidepressants (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors, and mirtazapine) can efficaciously treat the general population of patients with major depression. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Efficacy of antidepressants'.)
Patients receiving pharmacotherapy for postpartum unipolar major depression typically receive psychotherapy as an adjuvant if they are not too ill to participate in therapy. Most patients prefer combination therapy; a study of women with perinatal unipolar major depression (n = 100, including 73 postpartum patients) found that pharmacotherapy plus psychotherapy was preferred by 55 percent, whereas medication monotherapy was preferred by only 8 percent [19].
Indirect evidence supporting the use of add-on psychotherapy includes numerous, relatively large randomized trials that excluded breastfeeding patients; these trials found that combination therapy is more efficacious than pharmacotherapy alone. Although several randomized trials in patients with postnatal depression have failed to show that combination therapy is superior to monotherapy, each study was small and underpowered, and many of the patients had mild to moderate episodes of major depression, rather than severe depression [20-23]. The efficacy of antidepressants plus psychotherapy for treating the general population of patients with severe unipolar major depression is discussed separately. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Choosing a treatment regimen'.)
Using psychotherapy alone is a reasonable alternative to antidepressants for severe postpartum depression in patients with a prior history of poor response to multiple antidepressants, or if patients decline pharmacotherapy after weighing the risks (see 'Discussing the risks' below) [13]. Psychotherapy alone is appropriate provided that the depressive syndrome does not include suicidal ideation or obvious impairment of function. Evidence supporting the use of psychotherapy for treating patients with postpartum depression as well as the general population of patients with major depression is discussed separately. (See "Mild to moderate postpartum unipolar major depression: Treatment", section on 'Evidence of efficacy' and "Unipolar major depression in adults: Choosing initial treatment", section on 'Efficacy of psychotherapy'.)
Patients with severe, postpartum unipolar major depression may present with symptoms such as unrelenting intent to commit suicide or infanticide. For these patients, we suggest initial treatment with electroconvulsive therapy (ECT) because it often has a relatively rapid onset of action. The use of ECT for postpartum depression is discussed elsewhere in this topic. (See 'Treatment-refractory patients' below.)
Discussing the risks — Postpartum patients with severe major depression who are breastfeeding need to understand and weigh various risks when deciding whether to use an antidepressant [3,8,13,15,24,25]:
●Untreated depression poses risks to the mother and infant, such as nonadherence with postnatal care, poor self-care, neglect of the infant (and other children), disrupted maternal-infant bonding, family dysfunction, child abuse, and suicidal behavior. Also, complications of depression may ensue, including psychotic features, catatonia, and comorbid substance use disorders. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Adverse consequences'.)
In addition, postnatal depression is associated with:
•Abnormal child development (see "Postpartum depression: Risks of abnormal child development")
•Cognitive impairment and psychopathology in the children (see "Postpartum depression: Risks of cognitive impairment and psychopathology in the children")
●Maternal use of antidepressants poses risks to breastfeeding infants. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding".)
●Antidepressants carry the risk of maternal side effects (table 3). As an example, antidepressant-induced sedation can interfere with the mother’s ability to care for her baby.
The discussion of these risks should emphasize that the benefits and harms of treatment are uncertain [13].
Choosing an antidepressant — The choice of antidepressant for severe postpartum unipolar major depression in patients who are breastfeeding depends primarily upon the prior treatment history and potential adverse effects for the mother and nursing infant. There is no compelling evidence that among commonly used antidepressants, specific drugs differ in their safety [17].
Patients treated prior to their pregnancies with pharmacotherapy that was effective and well tolerated should generally resume the same regimen, provided it is compatible with breastfeeding [3,12,13,17,26]. This includes drug regimens that consisted of an antidepressant plus add-on treatment with drugs such as second-generation antipsychotics, lithium, or triiodothyronine. The safety of using psychotropic drugs during breastfeeding is discussed separately. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding" and "Breastfeeding infants: Safety of exposure to antipsychotics, lithium, stimulants, and medications for substance use disorders".)
For patients treated with antidepressants during pregnancy, it is preferable to use the same medication while breastfeeding, even if there are better lactation safety data for other drugs, because switching increases the risk of relapse and number of drug exposures [3,10,11,26,27]. The evidence regarding the use of antidepressants during breastfeeding does not clearly demonstrate that one drug is safer than another. In addition, exposure to antidepressants that has already occurred in utero is substantially greater than exposure through breast milk.
For patients with severe major depression who are breastfeeding and have not been treated with antidepressants in the past, we suggest initial treatment with SSRIs because of their efficacy and tolerability for postpartum depression [9-12,28,29]. SSRIs have been used and more widely studied in breastfeeding patients than other antidepressant classes; as an example, a retrospective study of women (n = 459) who were treated for postpartum depression with antidepressants found that SSRIs were used in 90 percent [30]. Nevertheless, reasonable alternatives to SSRIs include serotonin-norepinephrine reuptake inhibitors, mirtazapine, and nortriptyline.
Among SSRIs, we generally choose paroxetine or sertraline for initial treatment because adverse effects in infants appear to be low, and studies suggest that paroxetine and sertraline are usually undetectable in the sera of infants who are exposed through breast milk [8,10,11,17,31]. However, citalopram is a reasonable alternative [10,16].
Escitalopram, fluoxetine, and fluvoxamine are used less often for initial treatment of postpartum depression in patients who are breastfeeding. Escitalopram and fluvoxamine have been studied in fewer nursing infants than other SSRIs [9,15,29].
Evidence supporting the efficacy of SSRIs for severe, postpartum unipolar major depression includes randomized trials [32]:
●A meta-analysis of three trials lasting six or eight weeks compared paroxetine (10 to 40 mg/day) or sertraline (50 to 200 mg/day) with placebo in 146 patients with postpartum unipolar major depression, some of whom were breastfeeding [33,34]. Remission occurred in more patients who were treated with SSRIs than placebo (relative risk 1.8, 95% CI 1.1-3.0), and in each of the studies, the incidence of adverse effects was comparable for active drug and placebo. However, the patients generally had mild to moderate depression, sample sizes were small, and attrition was high [3].
●A four-week trial compared antidepressants (primarily SSRIs) with usual care in 254 patients with postpartum unipolar major depression (n = 254) [35]. More than 40 percent of the patients were breastfeeding their infants. Improvement (Edinburgh Postnatal Depression Scale (figure 1A-B) score <13) occurred in more patients who received antidepressants than usual care (45 versus 20 percent).
In addition, randomized trials in the general population of patients with severe major depression support using SSRIs for severe postpartum depression. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Choosing an antidepressant'.)
Few head-to-head randomized trials have compared different antidepressants for treating postpartum depression. A 16-week trial (n = 109 patients, including 29 who breastfed) compared sertraline (50 to 200 mg/day) with nortriptyline (25 to 150 mg/day) and found that improvement was comparable [36,37].
Treatment-resistant patients — Patients with severe postpartum unipolar major depression often do not respond to initial treatment with an antidepressant [38]. As an example, a pooled analysis of three randomized trials found that among patients (n = 72) who were treated with SSRIs, response occurred in only 54 percent [33,34].
For lactating women who are resistant to initial treatment and show minimal response (eg, improvement <25 percent), we suggest switching antidepressants rather than augmentation with a second drug [10,11]. Options include switching to another SSRI, a serotonin-norepinephrine reuptake inhibitor (eg, desvenlafaxine, duloxetine, or venlafaxine), an atypical antidepressant such as bupropion or mirtazapine, or a tricyclic such as nortriptyline [29]. The specific choice depends upon prior treatment history, side effects, and patient preference. Choosing next-step treatment and the process of switching antidepressants are discussed separately in the context of the general treatment of resistant depression. (See "Unipolar depression in adults: Choosing treatment for resistant depression", section on 'Switching to a different treatment'.)
For patients who are switching to another antidepressant, some drugs (eg, bupropion and doxepin) are typically avoided due to concerns about their safety in breastfeeding infants [10,11]. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding", section on 'Antidepressants'.)
For lactating women with a partial response (eg, reduction of baseline symptoms by 25 to 49 percent) to initial treatment, we add a second drug that is compatible with breastfeeding, rather than switch antidepressants [11,12]. Options for add-on pharmacotherapy include second-generation antipsychotics (eg, aripiprazole, risperidone, or olanzapine), lithium, and triiodothyronine. A small retrospective study found that among postpartum patients treated with antidepressants (n = 26), medication combinations were required for 60 percent [39]. The safety of these add-on psychotropic drugs in breastfeeding infants is discussed separately. (See "Breastfeeding infants: Safety of exposure to antipsychotics, lithium, stimulants, and medications for substance use disorders".)
If patients with severe postpartum unipolar major depression receive psychotherapy as initial treatment and do not respond after several sessions (eg, eight), we switch patients to antidepressants. (See 'Choosing an antidepressant' above.)
Treatment-refractory patients — Severe postpartum unipolar major depression may not respond to pharmacotherapy. For patients refractory to multiple (eg, four) sequential medication trials, we suggest ECT. ECT is particularly useful when a rapidly acting treatment is imperative; specific indications include psychotic depression, plans and intent to commit suicide or infanticide, and fluid and food refusal leading to dehydration and malnutrition [10,11,40].
There are few studies in breastfeeding mothers who were exposed to ECT anesthetic drugs, such as glycopyrrolate, methohexital, propofol, and succinylcholine [17]. Nevertheless, the risk of these drugs passing into breast milk appears low; after each ECT treatment, breastfeeding can be resumed when the patient recovers from anesthesia. Using ECT in patients who are breastfeeding is consistent with multiple practice guidelines, including those from the United Kingdom National Institute for Health and Care Excellence and the Canadian Network for Mood and Anxiety Treatments [13,15-17,41].
Evidence supporting the use of ECT for severe postpartum major depression includes randomized trials that excluded lactating patients [10]. (See "Unipolar major depression in adults: Indications for and efficacy of electroconvulsive therapy (ECT)", section on 'Acute ECT'.)
In addition, observational studies suggest that ECT is beneficial for postpartum major depression, and is a safe option for breastfeeding mothers because there appear to be few if any adverse effects upon lactation [17,38], as well as few adverse effects for either the mother or infant [42]:
●In one review of retrospective studies (total n = 87 postpartum patients), the authors concluded that ECT was effective and well tolerated [43].
●A subsequent retrospective study used a national registry to identify patients with postpartum depression (n = 99) who were treated with ECT, and found that response occurred in 81 percent [44].
Additional information about ECT is discussed separately. (See "Unipolar major depression in adults: Indications for and efficacy of electroconvulsive therapy (ECT)" and "Overview of electroconvulsive therapy (ECT) for adults" and "Medical evaluation for electroconvulsive therapy" and "Technique for performing electroconvulsive therapy (ECT) in adults".)
Patients with severe postpartum major depression may decline or not respond to ECT. For these patients, we suggest intravenous brexanolone, which is a derivative of the progesterone metabolite allopregnanolone. Although randomized trials indicate that brexanolone can rapidly improve symptoms, we recommend the drug only for patients who do not improve with antidepressants and ECT because of the limited clinical experience with brexanolone, as well its restricted availability.
In the United States, brexanolone is dispensed only to certified health care facilities and patients who enroll in a Risk Evaluation and Mitigation Strategy program [45-47]. The program requires on site clinicians to monitor patients for excessive sedation and sudden loss of consciousness during the intravenous infusion, and also requires continuous pulse oximetry to monitor for hypoxia.
Brexanolone is administered continuously as a single intravenous infusion for 60 hours in an inpatient facility [45]. The dosing schedule is as follows:
●0 to 4 hours – 30 mcg/kg/hour
●4 to 24 hours – 60 mcg/kg/hour
●24 to 52 hours – 90 mcg/kg/hour (however, 60 mcg/kg/hour is a reasonable alternative for patients who cannot tolerate the higher dose)
●52 to 56 hours – 60 mcg/kg/hour
●56 to 60 hours – 30 mcg/kg/hour
Infusions should be immediately terminated in patients who develop excessive sedation or sudden loss of consciousness [45]. After the drug is stopped, clinicians can expect the adverse effect to remit within 15 to 60 minutes. Following resolution of the sedation/loss of consciousness, brexanolone can be resumed at the same or lower dose.
In addition, clinicians should immediately stop the infusion if pulse oximetry indicates that the patient is hypoxic [45]. After hypoxia resolves, the infusion should NOT be resumed.
Additional information about administering brexanolone is available through the US Food and Drug Administration approved labeling [45].
Multiple randomized trials, in which a minority of patients received concomitant antidepressants, suggest that brexanolone can provide a rapid, beneficial response for women hospitalized with moderate to severe postpartum unipolar major depression, and that the drug is usually well tolerated:
●A trial compared brexanolone with placebo in 21 patients; study drugs were administered as a single, continuous intravenous infusion for 60 hours [48]. The dose of brexanolone was initiated at 30 mcg/kg per hour, titrated up to 90 mcg/kg per hour, tapered back down to 30 mcg/kg per hour, and then discontinued. Remission occurred in more patients who received active drug than placebo (7/10 versus 1/11 patients [70 versus 9 percent]). In addition, the benefit of treatment persisted at the 30-day follow-up assessment and brexanolone was generally well tolerated.
●Another trial randomly assigned 122 patients to one of three groups: brexanolone titrated up to 90 mcg/kg per hour, brexanolone titrated up to 60 mcg/kg per hour, or placebo [49]. Study drugs were administered as a single, continuous intravenous infusion for 60 hours. Improvement was greater with each dose of active drug than placebo. In addition, the benefit of treatment persisted at the 30-day follow-up assessment, and brexanolone was generally well tolerated. (The study did not report whether efficacy differed between the two doses of brexanolone.)
●A third trial compared brexanolone titrated up to 90 mcg/kg per hour with placebo in 104 patients; study drugs were administered as a single, continuous intravenous infusion for 60 hours [49]. Improvement was greater with active drug than placebo and the benefit of treatment persisted at the 7-day follow-up assessment; however, outcomes were comparable at the 30-day follow-up assessment. Brexanolone was generally well tolerated.
In results pooled from randomized trials, discontinuation of treatment with brexanolone and placebo was 2 and 1 percent [45]. The incidence of the following adverse effects in patients treated with brexanolone was at least 5 percent and at least two times greater than the rate with placebo:
●Dry mouth
●Flushing/hot flash
●Loss of consciousness
●Sedation/somnolence
Among patients who received brexanolone or placebo, excessive sedation/somnolence that caused a dose interruption or reduction occurred in 5 and 0 percent [45]. Sedation/somnolence may occur more frequently in patients treated with brexanolone plus antidepressants, compared with patients who receive brexanolone monotherapy. Loss of consciousness or altered state of consciousness with either brexanolone or placebo occurred in 4 and 0 percent of patients. Patients who interact with their children during the infusion with brexanolone must be accompanied, due to the risk of sedation/somnolence and loss of consciousness.
For patients who are breastfeeding, we suggest that they temporarily cease nursing during treatment with brexanolone and wait until four days have elapsed before they resume breastfeeding; these were the procedures followed in the two larger randomized trials described above [49]. Based upon low-quality evidence, it appears that brexanolone quickly disappears from breast milk [47]. In one small study, the drug was administered intravenously to healthy women for 60 hours according to the recommended dosing schedule, with a maximum dose of 90 mcg/kg/hour [45]. Thirty-six hours after the infusion was completed, the concentration of brexanolone in breast milk was low. In addition, the drug has low bioavailability, and it is thus expected that infant exposure would be low.
Psychotic depression — Treatment of unipolar psychotic major depression in breastfeeding patients is similar to treatment of non-postpartum patients. Psychotic depression is generally treated with an antidepressant plus an antipsychotic; however, ECT is a reasonable alternative [10,11,13,16,50]. The choice between pharmacotherapy and ECT depends upon several factors that are discussed separately, as is the administration of treatment and evidence of efficacy (in randomized trials that excluded breastfeeding patients). (See "Unipolar major depression with psychotic features: Acute treatment", section on 'First line'.)
The safety of infant exposure to antipsychotics through breast milk is also discussed separately. (See "Breastfeeding infants: Safety of exposure to antipsychotics, lithium, stimulants, and medications for substance use disorders", section on 'Antipsychotics'.)
Anxiety or insomnia — For breastfeeding patients with postpartum major depression that includes significant anxiety or insomnia, monotherapy with an antidepressant drug is usually preferred over the combination of an antidepressant and a benzodiazepine [13]. However, an antidepressant plus a benzodiazepine at initiation of treatment is reasonable for severe anxiety or insomnia [10,11]. Benzodiazepines are often added at the beginning of pharmacotherapy, using standard doses, and then gradually discontinued once the antidepressant begins to take effect. Given the risk of dependence and possibly increased risks of neonatal complications, we suggest not using benzodiazepines for more than two weeks. However, longer use may be necessary to achieve remission of anxiety and/or insomnia. The general efficacy and use of adjunctive benzodiazepines for the general treatment of anxious depression are discussed separately. (See "Unipolar depression in adults: Treatment with anxiolytics", section on 'Benzodiazepines'.)
Clonazepam and lorazepam are generally preferred for anxious depression; benzodiazepines with shorter half-lives (eg, alprazolam) can result in maternal rebound anxiety. However, the intermediate length half-lives of clonazepam and lorazepam may predispose to accumulation in the infant, and benzodiazepines can cause a withdrawal syndrome; lorazepam is preferred over clonazepam because of its shorter half-life.
The safety of infant exposure to benzodiazepines through breast milk is discussed separately. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding", section on 'Benzodiazepines'.)
Agitation — Severe unipolar major depression may include episodes of agitation, which is defined as nonproductive, excess motor activity in conjunction with inner tension [51,52]. The initial assessment of agitation in patients with a known diagnosis of unipolar major depression should focus upon determining whether the agitation is due to causes beyond depression, such as a general medical disorder, or intoxication or withdrawal from alcohol or other substances such as cocaine or methamphetamines [53]. In addition, clinicians should assess safety, including risk for suicide, and develop a treatment plan.
Hospitalized postnatal patients with severe major depression who are acutely agitated often require oral, inhaled, or intramuscular medications to manage threatening or aggressive behavior, and may also require seclusion from other patients and physical restraints [17]. Patients placed in seclusion should be constantly observed by clinical staff. In addition, the patient should be kept hydrated and vital signs should be regularly monitored.
The goal of pharmacologic tranquilization is to rapidly eliminate the need for seclusion and restraints, and to prevent or reduce self-harm and harm to others. We suggest a second-generation antipsychotic, such as aripiprazole or olanzapine; however, first-generation antipsychotics, such as haloperidol, are reasonable alternatives. Doses are shown in a table (table 4). Another alternative for managing acute behavioral disturbances is a benzodiazepine such as lorazepam, using a dose of 0.5 to 2 mg. Intramuscular medications are typically administered in the gluteal muscle or lateral thigh. Oral rapidly dissolving formulations and short-acting intramuscular formulations generally have a calming effect within minutes.
SELECTING TREATMENT FOR PATIENTS NOT BREASTFEEDING — Initial and next step treatment of severe unipolar major depression in postpartum patients who are not breastfeeding is similar to treatment in the general population of patients with severe depression. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Severe major depression' and "Unipolar depression in adults: Choosing treatment for resistant depression".)
TREATMENTS WITH LITTLE OR NO BENEFIT — The hormones progestin and estrogen are generally not used for treating postpartum depression due to the lack of supporting evidence [3,12]. A systematic review found that in one randomized trial (n = 168 patients), the benefits of progestin (single norethisterone 200 mg injection) and placebo were comparable [54]. In addition, the review identified one small randomized trial (n = 61) that compared estrogen (transdermal 17 beta-estrogen 200 mg/day plus cyclical dydrogesterone) with placebo; improvement was greater with estrogen than placebo.
SAFETY OF INFANT EXPOSURE TO PSYCHOTROPIC DRUGS THROUGH BREASTFEEDING — The safety of infant exposure to psychotropic medications through breastfeeding is discussed separately. (See "Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding" and "Breastfeeding infants: Safety of exposure to antipsychotics, lithium, stimulants, and medications for substance use disorders".)
ANTENATAL UNIPOLAR MAJOR DEPRESSION — Treatment of severe unipolar depression during pregnancy is discussed separately. (See "Severe antenatal unipolar major depression: Choosing treatment".)
POSTPARTUM BIPOLAR MAJOR DEPRESSION — Treatment of postpartum patients with bipolar major depression is discussed separately. (See "Bipolar disorder in postpartum women: Treatment", section on 'Bipolar major depression'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Depressive disorders" and "Society guideline links: Postpartum care".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Coping with high drug prices (The Basics)" and "Patient education: Depression during and after pregnancy (The Basics)")
●Beyond the Basics topics (see "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)")
In addition, several lay groups offer support and education to women with postpartum mood disorders and to family members. One such group is Postpartum Support International (www.postpartum.net/ or call 1-805-967-7636), which holds local, state, national, and international meetings. Educational information is also available at the National Women's Health Information Center (www.womenshealth.gov).
SUMMARY AND RECOMMENDATIONS
●Definitions – An episode of unipolar major depression is a period lasting at least two weeks, with five or more of the following symptoms: depressed mood, loss of interest or pleasure in most or all activities, insomnia or hypersomnia, change in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration, guilt or thoughts of worthlessness, and recurrent thoughts about death or suicide (table 1).
Severe unipolar major depression is characterized by seven to nine depressive symptoms. Severely ill patients often report suicidal ideation and behavior, typically demonstrate obvious impairment of functioning, and often manifest poor judgement that places the patient and others at risk for imminent harm. Patients with severe major depression should be referred to a psychiatrist for management and often require hospitalization. (See 'Definitions' above.)
●General principles of treatment – The general principles and issues involved in treating postpartum unipolar major depression include setting (eg, outpatient or inpatient), history of prior treatment, educating patients and families, adherence, monitoring symptoms, prescribing antidepressants, managing nonresponse, and making referrals. (See "Postpartum unipolar major depression: General principles of treatment".)
●Patients who are breastfeeding
•Initial treatment – For patients with severe, postpartum unipolar major depression who are breastfeeding, we suggest antidepressant medications rather than other treatments (Grade 2B). There is a general consensus that the benefits of antidepressants outweigh the potential risks to the infant. Patients receiving pharmacotherapy typically receive psychotherapy as an adjuvant.
However, psychotherapy alone is a reasonable alternative in patients with a prior history of poor response to multiple antidepressants, or if patients decline pharmacotherapy after weighing the risks. Using psychotherapy alone is appropriate provided that the depressive syndrome does not include suicidal ideation or obvious impairment of function. (See 'Initial treatment' above and 'Discussing the risks' above.)
•Choosing an antidepressant
-For postpartum patients treated with antidepressants during pregnancy, it is preferable to use the same medication while breastfeeding, even if there are better lactation safety data for other drugs, because switching increases the risk of relapse and number of drug exposures. The evidence regarding the use of antidepressants during breastfeeding does not clearly demonstrate that one drug is safer than another. In addition, exposure to antidepressants that has already occurred in utero is substantially greater than exposure through breast milk. (See 'Choosing an antidepressant' above.)
-For patients who have not been treated with antidepressants in the past, we suggest selective serotonin reuptake inhibitors (SSRIs) as initial treatment, rather than other antidepressants (Grade 2B). We typically select paroxetine or sertraline. However, reasonable alternatives to SSRIs include serotonin-norepinephrine reuptake inhibitors, mirtazapine, and nortriptyline. (See 'Choosing an antidepressant' above.)
•Treatment-resistant patients – Patients with severe postpartum unipolar major depression who are breastfeeding often do not respond to initial treatment with an antidepressant. For patients showing a minimal response (eg, improvement <25 percent), we suggest switching to a different antidepressant (Grade 2C). For patients showing a partial response (eg, reduction of baseline symptoms by 25 to 49 percent), we suggest augmentation with a drug that is compatible with breastfeeding, such as a second-generation antipsychotic, lithium, and triiodothyronine (Grade 2C). (See 'Treatment-resistant patients' above.)
•Treatment-refractory patients – Postpartum patients with unipolar major depression who are breastfeeding may not respond to multiple (eg, four) sequential medication trials; for these refractory patients, we suggest electroconvulsive therapy (ECT) (Grade 2B). An option for patients who do not respond to or who decline ECT is intravenous brexanolone. (See 'Treatment-refractory patients' above.)
•Patients with agitation – Treatment options for acute behavioral disturbances in patients with postpartum major depression who are breastfeeding include an antipsychotic or a benzodiazepine. (See 'Agitation' above.)
●Patients who are not breastfeeding – In postpartum patients who are not breastfeeding, initial and next step treatment of severe unipolar major depression is similar to treatment in the general population of patients with severe depression. (See "Unipolar major depression in adults: Choosing initial treatment", section on 'Severe major depression' and "Unipolar depression in adults: Choosing treatment for resistant depression".)
