Perinatal Depression

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), the criteria for major depressive disorder (MDD) remain the same (5 of 9 symptoms over at least 2 weeks), but the term “with peripartum onset” versus “postpartum” is used as a qualifier. The diagnosis requires its occurrence during pregnancy or within 4 weeks postpartum. However, many specialists (and ACOG) continue to define perinatal and postpartum depression as occurring anytime during pregnancy or within the first year postpartum, as this period is notable for ongoing stressors unique to maternal recovery and infant care.

Other important definitions in the perinatal period include those for postpartum blues and postpartum psychosis. Postpartum blues is very common, with a global prevalence of 39%, ranging from 14% to 76% in a meta-analysis. Postpartum blues is characterized by tearfulness, increased emotional reactivity, irritability, fatigue, and a depressed affect, starting a few days after delivery and resolving within approximately 10 days postpartum. Postpartum blues is not considered a psychiatric diagnosis, but rather a normal response to the hormonal postpartum changes. Postpartum psychosis is rare, ranging from 0.9% to 2.6%. It is characterized by delusions, hallucinations, and thoughts of harming oneself or the infant, with onset within the first 4 months postpartum. Many birthing persons with postpartum psychosis will eventually be diagnosed with bipolar 1 disorder.

Perinatal Anxiety Disorders

Perinatal anxiety disorders (PADs) are less well understood and often underdiagnosed versus major depressive disorders. The most common anxiety spectrum disorders in the perinatal period include generalized anxiety disorder (GAD), panic attacks and panic disorders, and obsessive-compulsive disorder (OCD). Perinatal anxiety disorders occur in 13% to 21% of pregnant persons, and in 11% to 17% of postpartum persons.

The diagnosis of PAD is complicated by the prevalence of normal pregnancy anxiety, which may impact 6% to 10% of women. PAD includes concerns about finances, miscarriage, the baby’s health, and caring for the infant after delivery. Just as postpartum blues are a common—even physiologic—response in the early days and weeks postpartum, normal maternal anxiety can facilitate pregnancy and postnatal care, resulting in attentiveness to the infant and desire to protect them. PADs differ from normal anxiety in their intensity, persistence, and negative impact on functioning.

There is a high rate of comorbid depression and other anxiety disorders in birthing persons with GAD. The rate of comorbid depression was 49.5% in a Canadian sample, which also reported comorbid rates for the following disorders: OCD (4.4%), agoraphobia (8.8%), and panic disorder (9.9%). A systematic review and meta-analysis of 13 studies found a 2-fold higher risk of postpartum depression within 6 months for those with anxiety during pregnancy, even when controlling for the risk of depression during pregnancy.

Though GAD is common in the perinatal period, there is not a specific perinatal specifier in the DSM-V entry for this diagnosis. The qualifier “with peripartum onset” is used only for major depressive disorder. The DSM-V criteria for GAD require presence of symptoms for at least 6 months to qualify for diagnosis. Some providers may therefore use a shorter time course for diagnosis in the perinatal period.

Panic attacks, panic disorder, and OCD are less common than GAD, and are likely also under-recognized and under-reported in the perinatal period. A panic attack is defined by the DSM-V as a discrete period of intense fear or discomfort that reaches a peak within 10 minutes, and must include 4 of 13 symptoms including palpitations, chest pain, shortness of breath, dizziness, and fear of dying. Panic attacks may be confined to the perinatal period and happen only once or more frequently. Panic disorder is characterized by recurrent, unpredictable attacks leading to persistent worry about recurrent attacks and/or to behavior changes to avoid attacks. Panic disorders affect 1.3% to 2.0% of birthing persons in the perinatal period. Certain physiologic changes in pregnancy, such as tachycardia and increased awareness of breathing, can cause concern and precipitate these attacks.

A person with OCD can have obsessions, compulsions, or both to meet diagnostic criteria. Obsessions are recurrent or persistent thoughts that the individual attempts to ignore or suppress. Compulsions are repetitive behaviors aimed at preventing distress or a feared scenario. In the perinatal period, these thoughts and behaviors are often focused on the pregnancy, including obsessions with the baby’s health or fears of hurting the baby. The prevalence of OCD in pregnant persons is 3.5%. The postpartum prevalence is up to 9%. For those with pre-existing OCD, 8% experienced worsening in pregnancy, and 50% experienced worsening postpartum.

Perinatal Mood and Psychotic Disorders

Though depression and anxiety disorders are commonly encountered in birthing persons, they are not the only type of mental health conditions occurring during pregnancy and postpartum. The authors provide a brief discussion of perinatal issues specific to bipolar disorder and schizophrenia spectrum disorders (SSD).

If a history of a less common mood or psychotic disorder is identified, the provider should obtain as much information as possible about previous and current treatment and medication use and refer to Reproductive Psychiatry for assistance. Table 1 provides a guide to safe and contraindicated medications. Patients commonly present to obstetric care having discontinued psychotropic medications out of concern for the pregnancy. In these cases, it is important to assess their mood and functioning and secure an expedited referral, if indicated.

Table 1

Psychotropic medications in pregnancy ^,

Medication Class	Drug Name	Starting Dosage	Dosage Range	Side Effects (Mother)	Pregnancy Complications	Fetal Malformations	Neonatal Effects	Breastfeeding Concerns	Pregnancy Recommendations	Breast-Feeding Recommendations	Pregnancy Summary
Alpha-1 Antagonist	Prazosin	1–2 mg q hs	1–15 mg qd	Dizziness, drowsiness, headache, weakness	Limited data	No increased risk	No significant risks	Limited data; probably compatible	Limited human data/animal data suggest low risk	Limited human data/potential toxicity/consider risk/benefit discussion	Animal reproduction data suggest low embryo/fetal risk
Other Antidepressant	Bupropion	150 mg qd	150–450 mg qd	Dry mouth, nausea, insomnia, agitation	Possible increased risk of spontaneous abortion	Likely low risk	No significant risks	Limited data; use with caution	Human data suggest possible low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Small increases in heart defects reported but confounding by indication. Possible attention-deficit/hyperactivity disorder in offspring
Other Antidepressant	Trazodone	50–100 mg q hs	50–400 mg qd	Sedation, dizziness, dry mouth	Limited data	No increased risk	No significant risks	Limited data; probably compatible	Limited human data/animal data suggest low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Animal and limited human data suggest low risk for major malformations in embryo
Other Antidepressant	Mirtazapine	15 mg q hs	15–45 mg qd	Sedation, increased appetite, weight gain	Limited data	No increased risk, limited data	No significant risks	Limited data; probably compatible	Limited human data/animal data suggest possible risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Limited human/animal data suggest possible risk
Other Antidepressant	Buspirone	7.5 mg BID	15–60 mg qd	Dizziness, nausea, headache	Limited data	No increased risk	No significant risks	Limited data; probably compatible	Limited human/animal data suggest low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No drug-induced congenital malformations observed. Limited data prevent assessing human safety
Tricyclic antidepressants (TCAs)	Amitriptyline	25–50 mg q hs	25–300 mg qd	Dry mouth, constipation, blurred vision	Possible increased preterm delivery risk	No consistent pattern of malformations	Neonatal adaptation syndrome	Limited data; use with caution	Human data suggest low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Occasional reports of congenital malformations, relatively low risk in pregnancy
TCAs	Nortriptyline	25 mg q hs	25–150 mg qd	Similar to amitriptyline	Similar to amitriptyline	Similar to amitriptyline	Similar to amitriptyline	Limited data; probably compatible	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Limited human data. No major association with congenital defects.
Mood Stabilizer	Lithium	300 mg BID	600–1800 qd	Tremor, thirst, weight gain	Increased risk of preterm birth	Increased risk of cardiac malformations (Ebstein’s anomaly)	Neonatal adaptation syndrome, hypotonia	Avoid, high levels in breast milk	Human data suggest risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	If possible. avoid during pregnancy, especially during organogenesis.
Mood Stabilizer	Lamotrigine	25 mg qd	25–400 mg qd	Rash, dizziness, headache	Limited data	Possible increased risk of oral clefts	No significant risks	Limited data; probably compatible	Compatible. Maternal benefits outweigh embryo/fetal risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Increased risk for oral clefts following first trimester exposure. The absolute risk of lamotrigine- induced cleft lip/palate or cleft palate alone was 0.1%–0.4%
Mood Stabilizer	Valproate	250 mg BID	500–3000 mg qd	Nausea, sedation, weight gain	Increased risk of preterm birth	High risk of neural tube and cardiac defects	Neonatal adaptation syndrome	Limited data; use with caution	Human data suggest risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	The absolute risk of neural tube defects with use between 17 and 30 d after fertilization is 1%–2%. Distinct constellation of defects including fetal growth restriction. Correlation with dosage and timing.
Atypical Antipsychotic	Quetiapine	25–50 mg q hs	50–800 mg qd	Sedation, dizziness, weight gain	Gestational diabetes risk	No clear increased risk	Possible extrapyramidal symptoms	Limited data; probably compatible	Compatible. Maternal benefits outweigh embryo/fetal risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No structural malformations with quetiapine or other agents in the subclass. Limited data regarding the embryo/fetal risk.
Atypical Antipsychotic	Risperidone	0.5–1 mg qhs	0.5–6 mg qd	Weight gain, elevate prolactin	Gestational diabetes	No clear increased risk	Possible extrapyramidal symptoms	Limited data; use with caution	Maternal benefits outweigh embryo/fetal risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No structural malformations reporter. Limited data regarding embryo/fetal risk.
Atypical Antipsychotic	Aripiprazole	2–5 mg qd	2–30 mg qd	Akathisia, nausea, weight gain	Gestational diabetes	No increased risk	Possible extrapyramidal symptoms	Limited data; probably compatible	Human data suggest low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No developmental human toxicity. Animal data suggest risk.
Atypical Antipsychotic	Olanzapine	2.5–5 mg q hs	2.5–20 mg qd	Weight gain, sedation, metabolic changes	gestational diabetes	No clear increased risk	Possible extrapyramidal symptoms	Limited data; probably compatible	Compatible. Maternal benefits outweigh embryo/fetal risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No attributable structural malformations. Limited data for embryo/fetal risk.
Typical Antipsychotic	Haloperidol	0.5–2 mg BID	1–20 mg qd	Extrapyramidal symptoms, sedation	Limited data	No clear increased risk	Possible extrapyramidal symptoms	Limited data; probably compatible	Limited human data/animal data suggest moderate risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Minimal data suggest moderate risk. Limited human pregnancy data of embryo/fetal risk. Three case reports of limb defects
Typical Antipsychotic	Perphenazine	4–8 mg BID	8–64 mg qd	Similar to haloperidol	Limited data	No clear increased risk	Similar to haloperidol	Limited data; use with caution	Human data suggest low risk		Low risk for birth defects
Benzodiazepine	Lorazepam	0.5–1 mg prn	0.5–6 mg qd	Sedation, dizziness, cognitive impairment	Limited data	Possible increased risk of anal atresia	mild floppy infant syndrome	Limited data; short-term use probably compatible	Human data suggest some risk in first and third trimesters	Limited human data probably compatible	Possible anal atresia. When used close to delivery, floppy infant syndrome, neonatal withdrawal
Benzodiazepine	Clonazepam	0.25–0.5 mg BID	0.5–4 mg qd	Similar to lorazepam	Limited data	Similar to lorazepam	Similar to lorazepam	Limited data; short-term use probably compatible	Human data suggest low risk	Compatible	Limited human pregnancy data. Possible major congenital defect. Risk of adverse pregnancy outcome low.
Benzodiazepine	Alprazolam	0.25–0.5 mg TID	0.5–4 mg qd	Similar to lorazepam	Limited data	Similar to lorazepam	Similar to lorazepam	Limited data; short-term use probably compatible	Human and animal data suggest risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No congenital anomalies; limited follow-up.
Benzodiazepine	Diazepam	2–5 mg BID	4–40 mg qd	Similar to lorazepam	Limited data	Similar to lorazepam	Similar to lorazepam	Not recommended; accumulates in breast milk	Human data suggest risk in first and third trimesters	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Effects on human embryo/fetus controversial.
selective serotonin reuptake inhibitor (SSRI)	Fluoxetine	20 mg qd	20–80 mg qd	Nausea, insomnia, sexual dysfunction	Possible increased risk of preterm birth	No consistent pattern of malformations	Neonatal adaptation syndrome, possible pulmonary hypertension of the newborn (PPHN)	Limited data; probably compatible	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Not a major teratogen. Possible increased risk of birth defects. But the absolute risks are small
SSRI	Sertraline	25–50 mg qd	50–200 mg qd	Similar to fluoxetine	Similar to fluoxetine	No consistent pattern of malformations	Similar to fluoxetine	Limited data; preferred SSRI during breastfeeding	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Not a major teratogen. Possible increased risk for some birth defects; absolute risk is small.
SSRI	Paroxetine	20 mg qd	20–50 mg qd	Similar to fluoxetine	Similar to fluoxetine	Possible increased risk of cardiac defects	Similar to fluoxetine	Limited data; use with caution	Human data suggest risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Increased risk of cardiac defects. Dose related
SSRI	Fluvoxamine	50 mg qd	50–300 mg qd	Similar to fluoxetine	Limited data	No clear increased risk	Similar to fluoxetine	Limited data; probably compatible	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Limited animal and human data, not a major teratogen.
SSRI	Citalopram	20 mg qd	20–40 mg qd	Similar to fluoxetine	Similar to fluoxetine	No consistent pattern of malformations	Similar to fluoxetine	Limited data; probably compatible	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	not a major human teratogen
SSRI	Escitalopram	10 mg qd	10–20 mg qd	Similar to fluoxetine	Similar to fluoxetine	No consistent pattern of malformations	Similar to fluoxetine	Limited data; probably compatible	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Limited experience. Animal data suggest embryo/fetus risk is low.
Selective norepinephrine reuptake inhibitors (SNRI)	Venlafaxine	37.5 mg qd	75–225 mg qd	Nausea, dizziness, sweating	Possible increased risk of preterm birth	No consistent pattern of malformations	Neonatal adaptation syndrome, possible PPHN	Limited data; use with caution	Human data suggest risk in third trimester	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	No major risk for structural anomalies.
SNRI	Duloxetine	30 mg qd	30–120 mg qd	Similar to venlafaxine	Limited data	No clear increased risk	Similar to venlafaxine	Limited data; use with caution	Human data suggest low risk	Limited human data/potential toxicity toxicity/consider risk/benefit discussion	Limited human pregnancy data. No increased risk of birth defects.

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