Women have a lifetime risk of depression of about 1 in 4 and it is most prevalent during their reproductive years. Much emphasis has been placed on the detection and treatment of postnatal depression (due to its morbidity in mother and child), but antenatal depression is actually more frequent, and about half of postnatal depression appears to start antenatally.

Pregnancy and depression inevitably interact:¹

• Pregnancy is a major psychological as well as physiological event:
  • With an excess of chronic life stressors, women may find themselves unable to cope with the additional demands of pregnancy.
  • Many women, particularly those living in poverty or already with many dependent children, will view pregnancy with ambivalence or negative feelings.
  • Issues or memories, surrounding poor parenting or abuse women have suffered, may reassert themselves and cause distress.
  • Relationships are often under pressure - domestic violence increases during pregnancy.
• Pregnancy-related sex steroids increase activation of the hypothalamic-pituitary-adrenal axis (the cortisol stress system) which is associated with depression. Some investigators have suggested that high levels of cortisol may effect fetal growth and development and be associated with altered temperament and behaviour.²
• Many women stop antidepressant medication due to concerns about potential harm to their developing fetus - this underlies high rates of relapse in pregnancy.³
• Depressed women are more likely to smoke and drink alcohol and less likely to attend for antenatal care - one behavioural pathway mediating poorer obstetric and neonatal outcomes.

Epidemiology¹

Estimates suggest:

• 7% women are depressed outside the perinatal period.
• 7-15% of women in developed countries are depressed in pregnancy compared to 19-25% in economically poorer countries.
• 10% of women are depressed postnatally.
• Rates of relapse in pregnant women with a history of recurrent mood disorder may be up to 50%.

Risk factors^4,5

Women experiencing social or economic adversity are most likely to experience antenatal depression. Risk factors include:

• History of mood and anxiety disorders
• History of postnatal depression
• History of premenstrual dysphoric disorder
• Family history of perinatal psychiatric illness
• History of childhood abuse
• Low income
• Poor social support
• Unplanned pregnancy
• Single motherhood
• Large number of existing children
• Domestic violence or relationship conflict
• Young age

The National Institute for Health and Clinical Excellence (NICE)⁶ advises against using single risk factors to predict individuals at risk of antenatal mental illness. A Cochrane review concluded that there was insufficient evidence to suggest that the use of psychosocial risk assessments improves perinatal mental health outcomes.⁷

Vigorous exercise may have a protective effect.⁸

Presentation

The signs and symptoms of antenatal depression are as for depression in general. See separate article on Depression. However, if one focuses on somatic symptoms (e.g. fatigue, insomnia, appetite changes), pregnancy symptoms may mask those of depression, particularly in the first trimester. Thus, the psychological symptoms (e.g. anhedonia, hopelessness, guilt) may be more reliable during pregnancy.

The Diagnostic and Statistical Manual of Mental Disorders - fourth edition (DSM-IV) recognises postpartum-onset mood disorders but does not refer specifically to depression during pregnancy.

Screening

Identifying antenatal depression is potentially difficult - women are reluctant to acknowledge 'difficult' emotions rather than the 'bloom' expected in pregnancy and many of the biological symptoms of depression can also be attributed to the pregnancy itself. NICE guidelines⁶ suggest that health professionals (whether midwives, GPs, health visitors or obstetricians) should screen pregnant women at first contact and at booking with 2 questions:

• During the past month, have you often felt bothered by feeling low, depressed or hopeless?
• During the past month, have you often been bothered by having little interest or pleasure in doing things?

If the woman answers 'yes' to either of the above, then a third question should be asked:

• Is this something you need or want help with?

Use of other self-report measurement tools such as the Edinburgh Postnatal Depression Scale (EPDS)⁹, Hospital Anxiety and Depression (HAD) Scale^10,11 and the Patient Health Questionnaire (PHQ-9) may be helpful in further assessment or for monitoring of response to treatment.

Management^1,12

Women with depression and those caring for them need to balance risks to the woman's health and a potential fetus' development:

• The risk to fetus and neonate posed by medication. There is conflicting evidence regarding the risk of congenital malformations associated with some psychotropic medications. Since these are such rare events, it is often difficult confidently to quantify the risk or establish causation.
• The risk of untreated mental illness.
• The risk of abrupt cessation of current medication.

Guidelines⁶ recommend treatment options dependent on severity of depression, past history of affective disorder and maternal preference. As there has been concern about the risk associated with antidepressant use during pregnancy, the threshold for use of psychological treatments is much lower at this time but the availability of psychological treatments has obvious implications.

Watchful waiting

Where an individual has had mild depression treated with antidepressants and is pregnant/intends to become pregnant, withdraw the drugs gradually and monitor regularly.

Self-help

This is suggested where intervention is required for mild-to-moderate depression without a previous history of depression. Possibilities include:

• Guided self-help
• Computerised cognitive behavioural therapy (C-CBT)
• Exercise¹³

Alternatives, where available, would be nondirective counselling ('listening visits') or brief psychological treatment (usually 4-6 sessions of CBT or interpersonal psychotherapy (IPT)).
Other approaches such as massage and acupuncture have not been shown to be beneficial.¹⁴

IPT and CBT

These therapies have been shown to be effective for milder cases in one small trial, but evidence is extremely limited.¹⁵ Also, the time to response is longer than with medication. Psychological treatments may be considered for moderate or severe depression where a woman opts for this in preference to drug treatment or in combination with antidepressant medication. They should also be considered with mild depression with episodes of more severe depression in the past.

Antidepressants

Discussion of the potential risks of antidepressants in pregnancy should occur prior to prescribing them to women of child-bearing age. However, when prescribing antidepressants to pregnant women or women who intend or may become pregnant, consider:

• Tricyclics are considered lower risk than newer antidepressants during pregnancy but have a higher fatal toxicity index than selective serotonin reuptake inhibitors (SSRIs).
• SSRIs:
  • It is estimated that about 2-3% of current pregnancies are exposed to SSRIs.¹⁶
  • Fluoxetine had previously been considered the SSRI with the lowest risk in pregnancy. However, recent advice from the Medicines and Healthcare products Regulatory Agency (MHRA), based on meta-analysis of existing epidemiological data, suggests that fluoxetine has a similar risk to paroxetine (previously considered the most risky SSRI in pregnancy) and that a class effect of SSRIs in general cannot be excluded on existing data.¹⁶ Fluoxetine may cause a small increase in congenital cardiac abnormalities but does not appear to be associated with an excess of non-cardiac congenital abnormalities. The background risk for congenital cardiac abnormalities is approximately 1 in 100 births; taking fluoxetine in pregnancy raises this to less than 2 in 100 births.
  • Other studies have found similar increased risk of congenital cardiac abnormalities with sertraline (septal defects), paroxetine (right ventricular outflow tract obstruction) and citalopram (septal defects) but again the absolute risk of these defects remained small.^17,18
  • An increased risk of omphalocele with the use of sertraline has been suggested.¹⁷
  • Exposure to SSRIs during the third trimester may be associated with persistent pulmonary hypertension of the newborn.
  • MHRA advice is to consider potential risks in the context of the benefits of treatment when making prescribing decisions concerning SSRIs in pregnant women or women who may become pregnant.
• Imipramine, nortriptyline and sertraline are present in breast milk at relatively low levels whilst citalopram and fluoxetine are present at much higher levels.
• Venlafaxine increases blood pressure during pregnancy and has a higher toxicity in overdose compared with SSRIs and some tricyclics. In general, the advice is to avoid mirtazapine, reboxetine, moclobemide or venlafaxine.
• Avoid St John's wort in pregnancy.
• All antidepressants carry the risk of withdrawal or toxicity in the neonate. Normally this is mild and self-limiting. Serotonin withdrawal syndrome is a self-limiting condition with usual neonatal symptoms including hypotonia, irritability, excessive crying, sleeping difficulties and mild respiratory distress. It is more likely to occur with paroxetine. Some centres try to prevent it by gradually discontinuing medication in the third trimester but this carries a high risk of relapse. Note, serotonin toxicity may give very similar symptoms to its withdrawal syndrome.¹⁹

Antidepressant use is an option in:⁶

• Moderate or severe depression dependent on patient preference.
• Mild depression that has failed to respond to other measures or when associated with a past history of severe depression.

Electroconvulsive therapy (ECT)⁶

Where depression is severe and treatment resistant, strategies include a trial of a different single drug or ECT. There is limited available evidence but it appears effective for severe mental depression in pregnancy and that the risks to fetus and mother are low.²⁰ Lithium augmentation should be avoided.

Referral¹²

Refer to perinatal psychiatric services (or general psychiatric services where not available):

• Women with recurring depression or bipolar disorder at the outset of their pregnancy.
• Women with new onset depression in pregnancy when:
  • The woman is severely depressed and at risk of self-harm or suicide.
  • There is evidence of severe self-neglect.
  • There are psychotic or manic features.
  • The woman may have undiagnosed bipolar disorder or has a history of other severe mental illness.
  • There is a family history of severe depression, puerperal psychosis, suicide, or bipolar illness.
• Consider referral or seek advice when:
  • Antidepressant treatment is under consideration.
  • There is uncertainty regarding diagnosis.
  • The woman has recurrent depression.
  • The depression is poorly responsive to treatment.
• Other factors, including level of functional impairment and comorbidities, should also be considered.

Complications

Antenatal stress or depression is associated with increased risk of:

• Miscarriage - this may be mediated by antenatal exposure to antidepressants
• Preterm delivery
• Increased pregnancy symptoms, pain relief in labour and worse obstetric outcome²¹
• Low birthweight - may be due to confounding variables²²
• Poor infant growth
• Attempted/completed suicide
• Possible longer-term cognitive, emotional and behavioural difficulties in offspring
• Relationship and family break-up

Prognosis

Early detection of depression during pregnancy and its adequate treatment are critical to avoid its persistence into the postpartum period and sequelae such as impaired mother-infant attachments and the consequences this has for children. Exposure to tricyclic antidepressants or fluoxetine in pregnancy does not appear to affect cognition, language development, or the temperament of preschool and early-school children adversely, whilst maternal depression is associated with less cognitive and language achievement by their children.²³ There is no current evidence to suggest that treatment of antenatal depression alters obstetric and neonatal outcome, however.

Whilst women are at generally low risk of suicide during pregnancy,²⁴ it is a significant cause of maternal death in the year following birth in the UK²⁵ so improving awareness of perinatal mental health problems, in all their diversity, is important.

Prevention

Women with pre-existing affective disorder

• All women with affective disorders, of reproductive age and potential, should have family planning discussed as part of their routine care. Where women with a past history of severe or resistant depression are planning to become pregnant, referral to specialist psychiatric services for preconceptual advice is appropriate.
• The decision to stop or continue medication should be an informed decision made by the woman, with access to available evidence and risk assessment.

Women with depressive symptoms⁶

Where a woman experiences depressive symptoms that do not meet diagnostic criteria but do significantly interfere with her personal or social functioning:

• If she has not had a previous episode of depression, consider increasing social support during pregnancy and the postnatal period with regular informal individual or group based sessions.
• If she has had a previous episode of depression, consider offering brief psychological treatment (4-6 sessions) such as interpersonal psychotherapy (IPT) or cognitive behavioural therapy (CBT).

Document references

1. O'Keane V, Marsh MS; Depression during pregnancy. BMJ. 2007 May 12;334(7601):1003-5.
2. Davis EP, Glynn LM, Schetter CD, et al; Prenatal exposure to maternal depression and cortisol influences infant temperament. J Am Acad Child Adolesc Psychiatry. 2007 Jun;46(6):737-46. [abstract]
3. Cohen LS, Altshuler LL, Harlow BL, et al; Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006 Feb 1;295(5):499-507. [abstract]
4. Lancaster CA, Gold KJ, Flynn HA, et al; Risk factors for depressive symptoms during pregnancy: a systematic review. Am J Obstet Gynecol. 2010 Jan;202(1):5-14. [abstract]
5. Ryan D, Milis L, Misri N; Depression during pregnancy. Can Fam Physician. 2005 Aug;51:1087-93. [abstract]
6. Antenatal and postnatal mental health: clinical management and service guidance, NICE Clinical Guideline (February 2007); (amended April 2007)
7. Austin MP, Priest SR, Sullivan EA; Antenatal psychosocial assessment for reducing perinatal mental health morbidity. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD005124. [abstract]
8. Strom M, Mortensen EL, Halldorson TI, et al; Leisure-time physical activity in pregnancy and risk of postpartum depression: a J Clin Psychiatry. 2009 Dec;70(12):1707-14. [abstract]
9. Edinburgh Postnatal Depression Scale, University of California, San Francisco
10. Hospital Anxiety and Depression (HAD) Scale, NHS Specialist Libraries; MS Word document
11. Hospital Anxiety and Depression (HAD) Scale, GL Assessments; for purchase of questionnaire from copyright owners
12. Depression - antenatal and postnatal, Clinical Knowledge Summaries (March 2008)
13. Polman R, Kaiseler M, Borkoles E; Effect of a single bout of exercise on the mood of pregnant women. J Sports Med Phys Fitness. 2007 Mar;47(1):103-11. [abstract]
14. Dennis CL, Allen K; Interventions (other than pharmacological, psychosocial or psychological) for Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006795. [abstract]
15. Dennis CL, Ross L, Grigoriadis S; Psychosocial and psychological interventions for treating antenatal depression. Cochrane Database Syst Rev. 2007 Jul 18;3:CD006309. [abstract]
16. MHRA Drug Safety Update: volume 3, issue 8, March 2010.
17. Louik C, Lin AE, Werler MM, et al; First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2675-83. [abstract]
18. Pedersen LH, Henriksen TB, Vestergaard M, et al; Selective serotonin reuptake inhibitors in pregnancy and congenital BMJ. 2009 Sep 23;339:b3569. doi: 10.1136/bmj.b3569. [abstract]
19. Haddad PM, Pal BR, Clarke P, et al; Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome? J Psychopharmacol. 2005 Sep;19(5):554-7. [abstract]
20. Anderson EL, Reti IM; ECT in pregnancy: a review of the literature from 1941 to 2007. Psychosom Med. 2009 Feb;71(2):235-42. Epub 2008 Dec 10. [abstract]
21. Alder J, Fink N, Bitzer J, et al; Depression and anxiety during pregnancy: a risk factor for obstetric, fetal and neonatal outcome? A critical review of the literature. J Matern Fetal Neonatal Med. 2007 Mar;20(3):189-209. [abstract]
22. Evans J, Heron J, Patel RR, et al; Depressive symptoms during pregnancy and low birth weight at term: longitudinal study. Br J Psychiatry. 2007 Jul;191:84-5. [abstract]
23. Nulman I, Rovet J, Stewart DE, et al; Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002 Nov;159(11):1889-95. [abstract]
24. Lindahl V, Pearson JL, Colpe L; Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health. 2005 Jun;8(2):77-87. Epub 2005 May 11. [abstract]
25. CEMACH; Confidential Enquiry into Maternal and Child Health. Why Mothers Die 2000 - 2002: The Sixth Report of the Confidential Enquiries into Maternal Death in the United Kingdom. London: RCOG Press, 2004

Internet and further reading

• Antenatal care: routine care for the healthy pregnant woman, NICE Clinical Guideline (March 2008)
• Depression in adults, NICE Clinical Guideline (October 2009); Depression: the treatment and management of depression in adults
• Yonkers KA, Wisner KL, Stewart DE, et al; The management of depression during pregnancy: a report from the American Obstet Gynecol. 2009 Sep;114(3):703-13. [abstract]
• National Teratology Information Service
• Frayne J, Nguyen T, Allen S, et al; Motherhood and mental illness--part 2--management and medications. Aust Fam Physician. 2009 Sep;38(9):688-92. [abstract]

Acknowledgements