PERINATAL DEPRESSION

Introduction:

-Depression is twice as common in women than in men

-1 in 7 women experience perinatal depression that occurs during pregnancy or in the first 12 months after delivery (range is 14-23%)

-Maternal suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality

-Less than 20% of women in whom postpartum depression was diagnosed had reported their symptoms to a health care provider

-Untreated perinatal depression can have devastating effects on women, infants, and families

-In spite of the high risk of this illness in women, it is often not recognized and diagnosed, and women are not offered appropriate treatment for depression during pregnancy likely due to the fact that somatic symptoms of depression such as changes in sleep and appetite may be attributed to normal pregnancy related changes

-ACOG recommends that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized, validated tool such as the Edinburgh Postnatal Depression Scale

-Clinicians should be prepared to initiate medical therapy, refer patients to appropriate behavioral health resources, or both

-In 2003, 13% of women took an antidepressant at some point in pregnancy

-Postpartum blues generally start 2-3 days after birth and resolve within 1-2 weeks, where some women feel depressed, anxious, or angry which can affect their ability to care for their baby. Postpartum depression starts about 1-3 weeks after delivery and is marked by intense feelings of sadness, anxiety, or despair that affects daily functioning and can last up to 1 year.

-Up to 60% of women with postpartum major depression have obsessive thoughts focusing on aggression toward the infant

Epidemiology:

-Studies have shown that depression is more common in the second and third trimester than the first trimester (12-13% vs 7 %)

Etiology:

-Hormonal changes, neuroendocrine changes, genetics, and psychosocial adjustments (major life events)

Risk Factors:

Postpartum Blues

- Antepartum depressive symptoms, stress around child care, psychosocial impairment, hx of PMS or oral contraceptives associated with mood changes, depressive symptoms predating pregnancy, family hx of depression

Depression during pregnancy

- Hx of depression, maternal anxiety, life stress, lack of social support, unintended pregnancy, domestic violence, lower income, lower education, smoking, single, poor relationship quality

Postpartum Depression

- Previous hx of depression, Depression and anxiety during pregnancy, experiencing stressful life events during pregnancy and postpartum period, traumatic birth experience, preterm birth/infant admission to NICU, low levels of social support, breastfeeding problems, hx of physical or sexual abuse, positive family psychiatric hx, young age, marital conflict, gestational diabetes, congenital malformation in the infant, stillbirth, and neonatal death

Clinical Manifestations

Symptoms

-Changes in somatic functions such as sleep, energy, appetite, weight, and libido

-Insomnia associated with depression usually manifests as not being able to sleep even when their babies sleep

-Fatigue is usually in the form of not being able to get out of bed for hours

-Anxiety and panic attacks

-Irritability and anger

-Feeling inadequate, overwhelmed, or unable to care for the baby

-Feelings of shame, guilt, and having failed as a mother

-Rumination about harming oneself or the baby can occur in postpartum depression, with 3% of women having suicidal ideation

-66% of women have comorbid anxiety disorders

Course of Illness

826 women with postnatal depression declared the onset was as follows:

Prepregnancy – 27%

Antepartum – 33%

Postpartum – 40%

* Postpartum depression increases risk for future episodes of major depression. Untreated postpartum depression will resolve spontaneously or develop into a chronic depressive disorder

Consequences

Antepartum

Maternal: Nonadherence to prenatal care, substance use, poor appetite and weight gain, insomnia, not initiating breastfeeding, worsening of depression, impaired maternal-infant bonding, postpartum depression, suicidal ideation and behavior

*One study found that the rate of attempted suicide during pregnancy was 0.4 in 1000 pregnancies (risk factors were young age, multiparity, African-American race, low socioeconomic status, and history of substance abuse)

Data neither support nor refute a link between depression and Miscarriage, LBW, and preterm delivery

Fetal: Data does support that neonates born to mothers with a depressive disorder have increased risk for irritability, less activity and attentiveness, and fewer facial expressions and altered infant language acquisition

-Several studies have suggested that risk of anxiety, ADHD, Conduct, Depression, and ODD are in increased in offspring of depressed mothers (suggesting genetics and environment)

Postpartum

Impaired bonding – postpartum depression can interfere with maternal-infant bonding

Impaired infant and child development – Problems with emotional regulation and social behavior and increased risk of psychiatric diagnosis of the above

Marital discord – Strain in the marital relationship is both a risk factor and consequence of postpartum depression and the two often exacerbate each other

Suicide – Suicide is among the leading causes of death in postpartum women, estimated rate is 3-11 per 100,000 births (however a similar number to the rate of suicide in the general female population)

Screening

*Women should be screened for and counseled about their risk of developing a mood disorder

*Questions such as “How have you been feeling?” and “Are you able to enjoy your usual activities?” followed by “Do you feel overwhelmed? Sad? Depressed? Hopeless or helpless?”

*If depression is suspected, the assessment should address suicidality and possible psychosis

Edinburgh Postnatal Depression scale – 10 self-reported items which take less than 5 minutes to complete

-includes anxiety symptoms and excludes constitutional symptoms of depression such as changes in sleeping patterns that are common in pregnancy and the postpartum period thereby increasing the specificity of the test

-Sensitivity and specificity 80-90%

-can be used prenatally as well

-includes a question on suicidal ideation

-scaled from 0-3

-available in many languages

-Scores 12 identify most women with depression, however some studies use a cutoff of 10

-Scores 5-9 should be re-evaluated in one month to determine clinical status

-Postpartum Depression in one study at 6 weeks PP was detected in more women with the screening tool than routine assessment (35% vs 6%)

Diagnosis

*A diagnosis of major depressive disorder requires the presence of five key symptoms that last at least 2 weeks and impair normal function. Depressed mood or anhedonia must be present.

Symptoms: Depressed mood, decreased interest in pleasurable activities (anhedonia), decreased energy, changes in sleep pattern (insomnia or hypersomnia), weight change (gain or loss), decreased concentration or indecisiveness, feelings of guilt or worthlessness, psychomotor retardation or agitation, suicidal ideation (passive or active)

*The diagnosis of postpartum major depression should also include asking patients about past manic episodes and positive answers require a referral to a psychiatrist:

1) “Have you ever had four continuous days when you were feeling so good, high, excited, or hyper that other people thought you were not your normal self or you got into trouble?”

2) “Have you experienced four continuous days when you were so irritable that you found yourself shouting at people or starting fights or arguments?”

Workup

A medical evaluation for mood and anxiety disorders in pregnancy should include an appropriate medical work-up including CBC, TSH, Renal, and LFTs. Urine toxicology can screen for comorbid substance use.

Treatment Scenarios

Women thinking about getting pregnant

  • For women on medication with mild or no symptoms for six months or longer, it may be appropriate to taper and discontinue medication before becoming pregnant and offer psychotherapy (if unsure if trial is reasonable, may consult psychiatrist)
  • Reduce anti-depressant by 25% every 1-2 weeks
  • For women on medication for less than 6 months OR pts with moderate to severe symptoms, a reasonable period of stability should be considered prior to conceiving. Psychotherapy may also be helpful.
  • Medication discontinuation may not be appropriate in women with a history of severe, recurrent depression, those with psychosis, bipolar, or a history of suicide attempts and psychotherapy should be offered to these patients
  • One study showed a 68% relapse of depression in those women taking antidepressants before conception who discontinued medication during pregnancy vs 25% who continued antidepressants

Pregnant and not currently on medication for depression

  • Psychotherapy may be beneficial in women who prefer to avoid antidepressant medication
  • For women who prefer taking medication, risks and benefits of treatment choices should be evaluated and discussed including stage of gestation, the patient’s symptoms, history and therapeutic preferences
  • The dose of agents metabolized primarily by cyt P450 may require an increase in the second half of pregnancy
  • Psychotherapy should also be offered

Pregnant women currently on medication for depression

  • Stable women who prefer to stay on medication may be able to do so after discussing risks and benefits
  • Women willing to consider discontinuation of medication may attempt medication tapering and discontinuation if they are not experiencing symptoms, have not relapsed after stopping antidepressants, and have not relapsed or failed to respond to psychotherapy
  • Women with symptoms despite medication, or those who taper off medication should be offered psychotherapy
  • Women with severe, recurrent depression (suicide attempts, functional incapacitation, aggression, psychosis, or impaired judgement) should remain on medication with psychotherapy

Postpartum patients at risk of developing major depression

  • Patients at risk due to a history of depression and were successfully treated with antidepressants in the past, prophylaxis with the previously used antidepressant is suggested
  • Alternatives are psychotherapy or watchful waiting are reasonable alternatives with close follow up

All patients

  • Women with suicidal or acute psychotic symptoms should be referred to a psychiatrist

Treatment

Psychotherapy – considered for patients with mild to moderate depression

  • Randomized trials have found that Cognitive behavioral therapy and interpersonal psychotherapy are effective for treating pregnant patients
  • Typically at least 8-12 weekly sessions

Pharmacotherapy– a reasonable alternative for pregnant women with mild to moderate depression if psychotherapy is not successful

  • typically used for patients who responded to pharmacotherapy for prior episodes of depression
  • used for patients who have failed psychotherapy
  • patients with a past history of severe depression

Light Therapy– one randomized trial compared 7000 lux fluorescent bright white light with placebo and remission occurred in more patients who received bright light (69% vs 36%)

Family Therapy – used when depression may stem from marital problems and poor family functioning

Pharmacotherapy

Pregnant patients

  • The current data on SSRI exposure during early pregnancy provide conflicting data on the risk for both overall and specific malformations. Some investigators have found a small increased risk of cardiac defects with paxil exposure. The risk is not greater than 2 per 1,000 births; hence these agents are not major teratogens
  • Paxil use in pregnant women and preconception should be avoided, if possible BUT if used, a fetal echo should be considered
  • Sertraline, citalopram, escitalopram, fluoxetine
  • Bupropion may be helpful if a smoker (C/I in eating and seizure disorder)

Risks to Infant:

  • There have been no randomized trials of antenatal antidepressant exposure, all consist of observational studies.
  • The rate of adverse events is less than 1%
  • PPHN – 3-12 in 1000 infants
  • Poor neonatal adjustment syndrome: associated with exposure to SSRIs during 3rd trimester
  • Agitation, restlessness, irritability, crying, insomnia, poor feeding, hypoglycemia, hypothermia, respiratory distress, altered muscle tone, tremors, seizures
  • Range of incidence – 5-85%
  • Etiology is either withdrawal or effects of SSRI
  • Usually self-resolving within 2 weeks
  • Observational studies of pregnant women have consistently found that exposure to SSRIs is associated with preterm birth and a small reduction in gestational age at birth particularly in 3rd trimester exposure (however, the difference was only by 3 days and heterogeneity across the studies was significant)
  • It is not clear if use of SSRIs is associated with low birth weights (the largest difference found was 74 g difference)
  • Although some data suggest that paroxetine may be associated with a small absolute increase in congenital heart defects, several studies have found no such association

Pregnancy complications:

  • SSRIs do not appear to be associated with increased risk for SAB or hypertensive disorders of pregnancy
  • Multiple observational studies indicate that SSRIs are associated with bleeding, including postpartum hemorrhage (one study did not control for confounders and the study that did, the difference was 4% vs 3% postpartum hemorrhage)

Patients not breastfeeding - the choice of antidepressant is similar to the choice in non-postpartum patients

Breastfeeding patient

  • Prior treatment history – patients previously treated with an antidepressant that was effective should generally be resumed if compatible with breastfeeding
  • Paroxetine and sertraline are first line
  • Other SSRIs and Bupropion and nortriptyline are reasonable alternatives

RISKS to Infant: Drug toxicity (especially in preterm infants), undetermined long-term effects on neurobehavioral development

Resistant patients

  • If not lactating, may augment therapy with risperidone and olanzapine
  • Lactating women, change antidepressant

Refractory patients

  • If at least 3 medication trials have failed, ECT is particularly useful with a rapid response
  • Other candidates are those who are psychotically suicidal or severely disabled

REFERENCES:

The American College of Obstetricians and Gynecologists. Screening for Perinatal Depression. Committee Opinion, Number 630, May 2015.

The American College of Obstetricians and Gynecologists. Use of Psychiatric Medications during Pregnancy and Lactation. ACOG Practice Bulletin, Number 92, April 2008.

Hirst, K., MD & Moutier, C., MD. Postpartum Major Depression. Am Fam Physician. 2010 Oct 15;82(8):926-933.

Roy-Byrne, P., MD. Postpartum blues and unipolar depression: Epidemiology, clinical features, assessment, and diagnosis. UptoDate, November 24, 2014.

Roy-Byrne, P., MD. Postpartum blues and unipolar depression: Prevention and Treatment. UptoDate, August 5, 2014.

Roy-Byrne, P., MD. Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding. UptoDate,October 28, 2014.

Roy-Byrne, P., MD. Unipolar major depression in pregnant women: Clinical Features, consequences, assessment, and diagnosis. UptoDate, February 10, 2015.

Roy-Byrne, P., MD. Unipolar major depression in pregnant women:Treatment. UptoDate, March 26, 2015.

Stewart, D., CM,MD,FRCPC & Vigod, S., MD,MSc,FRCPC. Infants with antenatal exposure to SSRIs and SNRIs. UptoDate, February 26, 2015.

Stewart, D., CM,MD,FRCPC & Vigod, S., MD,MSc,FRCPC. Risks of antidepressants during pregnancy: Drugs other than SSRIs. UptoDate, April 27, 2015.

Stewart, D., CM,MD,FRCPC & Vigod, S., MD,MSc,FRCPC. Risks of antidepressants during pregnancy: SSRIs. UptoDate, May 26, 2015.

Yonkers, K, MD et al. The Management of depression during pregnancy: a report from the APA and ACOG. Obstetrics and Gynecology, 2009 September;114(3):703-713.