Antidepressant Treatment in Pregnancy

  • Treatment of depressed pregnant women requires skilled management by a psychiatrist, working collaboratively with the woman and her obstetric team.0002
  • Medication should be used with caution and only after careful analysis of the associated risks and benefits.
  • Many women are reluctant to take medication during pregnancy and feel the need to make a choice ‘between the drug and the baby’.
  • Every woman is individual and each management plan should reflect this.
  • There are several factors to be taken into account:
    • Potential adverse outcomes include fetal toxicity, intrauterine death and major physical malformations, fetal growth restriction, behavioural teratogenicity and neonatal toxicity, all of which are discussed below by individual drug type.
  • Women should be fully counselled about these risks and informed consent sought.0002

Tricyclic antidepressants

Tricyclic antidepressants, such as amitriptyline and imipramine, have lower known risks in pregnancy than other antidepressants.

The risks associated with overdose of tricyclic antidepressants remain, however, as does the issue of tolerability. As tricyclicantidepressant usage during pregnancy has been associated with a neonatal withdrawal syndrome consideration should be given to a dose reduction 3–4 weeks prior to delivery.9101

Monoamine-oxidase inhibitors

  • Fetal growth restriction and fetal toxicity are the main problems associated with the use of monoamine-oxidase inhibitors in pregancy.
  • No neonatal effects have been reported.
  • There is limited data available on the use of many newer antidepressants and they are not, therefore, recommended for treatment.


Benzodiazepines are used in pregnancy for the treatment of seizuresand other conditions such as anxiety disorders and panic attacks.

Their use in the first trimester has been associated with orofacialclefts.

Selective serotonin re-uptake inhibitors

Prozac (Fluoxetine) is the best-documented selective serotonin re-uptake inhibitor (SSRI) used in pregnancy. Information on the safety of other SSRIs in pregnancy is limited, but the US Food and Drug Administration issued a warning in December 2005FDA advising that the use of paroxetine  in the first trimester of pregnancy was associated with an increased risk of birth defects, in particular cardiac defects, compared with other SSRIs.

There is reassurance that the use of Prozac in the first trimester of pregnancy is not associated with teratogenic effects.0003 There is, however, increasing recognition of an association between SSRI use in pregnancy and a neonatal withdrawal syndrome characterised by convulsions, irritability and feeding problems.

Prozac (Fluoxetine hydrochloride) (other trade names , Fontex, Ladose, Sarafem) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) group. Prozac is approved for the treatment of major depression - including pediatric depression, obsessive-compulsive disorder , bulimia nervosa, anorexia nervosa, panic disorder and premenstrual dysphoric disorder. Despite the availability of newer agents, it remains extremely popular. Over 22.2 million prescriptions for generic formulations of Prozac were filled in the United States in 2007, making it the third most prescribed antidepressant. Prozac was developed by Eli Lilly and Company, who also markets it for use with pets under the Reconcile brand name.

Depression During Pregnancy - Introduction

Women experience major depression twice as often as men.0401 This increased incidence occurs mainly during the reproductive years0201 and is unrelated to culture, race or class.9601 Antenatal depression is prevalent - in one study 37% of women were affected.0701 Until fairly recently, it was beleived that pregnancy and the postpartum period exerted a protective effect against suicide and that the maternal suicide rate was lower than would be expected. However, the 1997–1999 and 2000–2002 reports on the Confidential Enquiry into Maternal Deaths changed this misconception.

The fifth report described 42 psychiatric deaths, 68% of which resulted from suicide—the leading cause of indirect death and the second leading cause of maternal death overall. Subsequently, the sixth report described similar statistics, with suicide the second leading cause of maternal death. Both reports revealed that half of women who committed suicide had a previous history of serious mental illness, which was related to their last childbirth in a quarter of cases. In most cases, the risk of recurrence was neither identified nor managed in the index pregnancy.

The method of suicide in both reports was predominantly violent, including hanging, jumping, throat cutting, self-immolation, drowning and intentional road traffic accidents. The majority of women were aged 30 years or over and white.

These reports provided recommendations that should be followed in an attempt to reduce these harrowing statistics. The seventh report showed a decrease in the rate of suicide which may indicate that pthese recommendations are having a beneficial effect. It is advised that all women with a history of serious psychiatric illness, peripartum or otherwise, should be assessed by a psychiatrist in the antenatal period, to ensure that a management plan can be drawn up involving all disciplines relevant to their care.

Although pregnancy is often a time of great happiness, that's not the reality for all women. At least one in ten pregnant women suffers from bouts of depression.

Hormonal changes can make you feel more anxious than usual. Anxiety is a condition that can require careful management during pregnancy.

Depression and anxiety may go unnoticed as women often dismiss their feelings, that often accompanies pregnancy. So don't be shy about letting your doctor or midwife know if you feel low. Your emotional health is every bit as important as your physical health.

Research has shown, for instance, that depression and anxiety can increase your risk for preterm labor.2000-01 These conditions can reduce your ability to care for yourself and your developing baby.

Women with a history of major depression are at high risk of recurrent depression during pregnancy, especially if antidepressant therapy has been discontinued.0601 For one-third of women, however, this can be their first episode of major depression. Other risk factors for antenatal depression include: 

  • lack of psychosocial support
  • difficulty coping with changes in body image
  • hyperemesis gravidarum
  • relationship problems
  • unplanned or unwanted pregnancy.

Depression in pregnancy creates several challenges. Maternal depression can itself adversely affect the developing fetus: a number of studies have suggested an association between maternal depression and factors that predict poor neonatal outcome including:

  • preterm birth
  • low birthweight
  • smaller head circumference
  • low Apgar scores

The physical condition of the mother can also be affected.8901

  • Poor attendance for antenatal care, together with poor personal care, diet and decreased weight gain are associated with negative pregnancy outcomes.
  • Pregnant women with depression are more likely to smoke and to take alcohol or illicit drugs.
  • Self-harm is also more common in pregnant women with severe depression.
  • Maternal depression has effects on the rest of the family.
  • Interpersonal relationships are strained and mother–baby bonding can be disrupted, which can be detrimental to the development of the infant.
  • Studies have also shown that children born to depressed mothers are more likely to have behavioural problems and/or disruptions in cognitive and emotional development.
  • Lastly, untreated antenatal depression significantly increases the risk of subsequent postnatal depression.8601


The recently published National Institute for Health and Clinical Excellence (NICE) guidelinesNICE suggest that for women developing mild or moderate depressive illness during pregnancy, psychotherapeutic interventions such as brief cognitive behavioural therapy (CBT) or interpersonal psychotherapy should be considered. Self-help strategies and nondirective counselling delivered at home can also be useful. They advise that there should be a lower threshold for access to psychological therapies during pregnancy because of the changing risk–benefit ratio for psychotropic medication.  

Guidelines for the treatment of psychiatric illness during pregnancy.

The American College of Obstetricians and Gynecologists (ACOG) has issued updated guidelines for the treatment of certain psychiatric illnesses during pregnancy and breast-feeding. The April 2008 Practice Bulletin updates the previous November 2007 bulletin and is based on current evidence of risks and benefits of treatment of psychiatric illnesses during pregnancy. The guidelines are designed to aid clinicians in providing appropriate care.

"The bulletin acknowledges that there's good evidence that untreated or inadequately treated mental illness is unhealthy, which is probably one of the first times it's ever been pointed out so definitively," Zachary N. Stowe, MD, from Emory University in Atlanta, Georgia, who contributed to the development of these guidelines, toldMedscape Psychiatry.

The committee that developed the practice bulletin sought to evaluate all available information and provide a critical appraisal of whether particular studies should influence treatment paths, he added.

The study is published in the April issue ofObstetrics and Gynecology.

Risks of Fetal Exposure vs Untreated Maternal Illness

It is estimated that each year in the United States, more than 500,000 women have psychiatric illnesses before or during pregnancy, and one third of all pregnant women are exposed to psychiatric medication during their pregnancy, the bulletin authors write.

"Advising a pregnant or breastfeeding woman to discontinue medication exchanges the fetal or neonatal risks of medication exposure for the risk of untreated mental illness," they note. Untreated or inadequately treated maternal mental illness "may result in poor compliance with prenatal care, inadequate nutrition, exposure to additional medications or herbal medicines, increased alcohol and tobacco use, deficits in mother-infant bonding, and disruptions within the family environment," they add.

"All psychotropic medications studied to date cross the placenta, are present in amniotic fluid and can also enter human breast milk," the authors write.

They summarized their findings in the following 15 recommendations and conclusions stratified according to the strength of the evidence supporting them:

  • Level A evidence (from good and consistent scientific evidence):

    • Lithium exposure in pregnancy may be associated with a small increase in congenital cardiac malformations, with a risk ratio of 1.2 to 7.7.

    • Valproate exposure in pregnancy is associated with an increased risk for fetal abnormalities and should be avoided if possible, especially during the first trimester.

    • Carbamazepine exposure during pregnancy is associated with fetal carbamazepine syndrome and should be avoided if possible, especially during the first trimester.

    • Maternal benzodiazepine use shortly before delivery is associated with floppy infant syndrome.

  • Level B evidence (from limited or inconsistent scientific evidence):
    • Paroxetine use in pregnant women and women who are planning to become pregnant should be avoided, if possible, and fetal echocardiography should be considered when fetuses are exposed to paroxetine in early pregnancy.
    • Prenatal benzodiazepine exposure increased the risk for oral cleft (absolute risk increased by 0.01%).
    • Lamotrigine is a potential maintenance therapy option for pregnant women with bipolar disorder and has a growing reproductive safety profile relative to alternative mood stabilizers.
    • Untreated or inadequately treated maternal psychiatric illness may have various negative consequences.
  • Level C evidence (primarily from consensus and expert opinion):
    • Multidisciplinary care management involving the patient's obstetrician, mental health clinician, primary health care provider, and pediatrician is recommended whenever possible.
    • Use of a single medication at a higher dose is favored vs the use of multiple medications to treat psychiatric illness during pregnancy.
    • Close monitoring of lithium during pregnancy and postpartum is recommended.
    • Measuring serum drug levels in breast-fed neonates is not recommended.
    • Treatment with selective serotonin-reuptake inhibitors, selective norepinephrine reuptake inhibitors, or both during pregnancy should be individualized.
    • A fetal echocardiogram examination should be considered when the fetus is exposed to lithium during the first trimester of pregnancy.

Clinical Context

Psychiatric illness can promote multiple negative effects on pregnancy outcomes. Anxiety disorders are associated with an increased risk for forceps deliveries, prolonged labor, fetal distress, and preterm delivery. Maternal depression increases the risk for low birth weight delivery, as does schizophrenia. Schizophrenia is also associated with placental abnormalities and antenatal hemorrhage.

Despite these negative effects of psychiatric illnesses on pregnancy, there are also significant concerns with the safety of psychotropic medications during gestation. All psychotropic medications cross the placenta and are present in amniotic fluid. The current review examines the safety of these medications.

Study Highlights

  • Psychiatric illness during pregnancy is best managed with a multidisciplinary approach involving the obstetrician, mental health clinician, and primary care provider.
  • A single medication at a higher dose is preferred vs multidrug therapy for psychiatric illness during pregnancy.
  • Of women receiving medications for depression at conception, more than 60% will have symptoms of depression during pregnancy. The risks for negative pregnancy outcomes are higher when depression occurs in the late second to early third trimester.
  • Women with depression may be considered for medical therapy during pregnancy on an individual basis, depending primarily on the severity of the illness. However, paroxetine should be avoided because of evidence of congenital cardiac malformations, anencephaly, and omphalocele with the use of this medication during pregnancy.
  • Other selective serotonin-reuptake inhibitors are not considered major teratogens. Limited data from studies of antidepressants other than selective serotonin-reuptake inhibitors have failed to demonstrate any significant fetal anomalies associated with their use.
  • Prenatal use of benzodiazepines increases the risk for oral cleft by 0.01%, and maternal benzodiazepine use immediately before delivery can result in floppy infant syndrome. It remains unclear whether there are any long-term neurobehavioral consequences of maternal benzodiazepine use on children.
  • Lithium can increase the risk for cardiac malformations by a factor of 1.2 to 7.7 and the risk for overall congenital malformations by a factor of 1.5 to 3. Neonatal lithium toxicity can result in flaccidity, lethargy, and poor suck reflexes.
  • Echocardiogram examination of the fetus should be considered for women exposed to lithium during the first trimester.
  • Women using lithium for mild bipolar disorder should be considered for tapering of the medication before conception, whereas women at moderate risk for relapse of bipolar disorder may stop lithium until organogenesis is complete. Women at a high risk for relapse of bipolar disorder may continue lithium throughout gestation.
  • Valproate and carbamazepine should be avoided in pregnancy, if possible, because each is associated with a higher risk for fetal anomalies. Lamotrigine appears to be a safer choice as a treatment of bipolar disorder.
  • Typical antipsychotic drugs have a more extensive reproductive safety profile vs second-generation antipsychotic medications. No significant teratogenic effects have been documented with the use of chlorpromazine, haloperidol, and perphenazine. Nonetheless, second-generation antipsychotic drugs have not been associated with a significant risk for neonatal toxicity or somatic teratogenesis.
  • Exposure to selective serotonin-reuptake inhibitors in breast milk is lower than during fetal growth, and tricyclic antidepressants (except doxepin) are also generally safe during breast-feeding. The use of lithium during breast-feeding is discouraged, but valproate and carbamazepine are most likely safe.

Women's Health

This is the personal website of David A Viniker MD FRCOG, retired Consultant Obstetrician and Gynaecologist - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.
I do hope that you find the answers to your women's health questions in the patient information and medical advice provided.

I do hope that you find the answers to your women's health questions in the patient information and medical advice provided.

The aim of this web site is to provide a general guide and it is not intended as a substitute for a consultation with an appropriate specialist in respect of individual care and treatment.

David Viniker retired from active clinical practice in 2012.
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