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 because of the morbidity in mother and child. However, antenatal depression is actually more frequent and about half of postnatal depression appears to start antenatally.
Pregnancy and depression affect each other:
- 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, may 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 affect fetal growth and development and be associated with altered temperament and behaviour.
- Many women stop antidepressant medication due to concerns about potential harm to their developing fetus - this underlies high rates of relapse in pregnancy.
- 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.
- 7% of women are depressed outside the perinatal period.
- 10-15% of women in developed countries are depressed in pregnancy.
- 19-25% of women are depressed 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%.
- 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.
A Cochrane review concluded that there was insufficient evidence to suggest that the use of psychosocial risk assessments improves perinatal mental health outcomes.
The signs and symptoms of antenatal depression are as for depression in general. See separate Depression article. However, if one focuses on somatic symptoms (eg, fatigue, insomnia, appetite changes), pregnancy symptoms may mask those of depression, particularly in the first trimester. Thus, the psychological symptoms (eg, anhedonia, hopelessness, guilt) may be more reliable during pregnancy.
The 2016 edition of the International Classification of Diseases 10th edition (ICD-10) system classifies depression in pregnancy under the code O99.340 (other mental disorders complicating pregnancy, unspecified trimester). There are sub-codes according to the trimester in which the condition presents.
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. National Institute for Health and Care Excellence (NICE) guidelines suggest that health professionals (whether midwives, GPs, health visitors or obstetricians) should screen pregnant women at first contact and at booking with two 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 self-report measurement tools may be helpful in further assessment or for monitoring of response to treatment but should not be used for diagnosis.
There have been increasing concerns about the effects on fetal development of antidepressants taken during pregnancy. The threshold for use of non-medication options such as psychological treatments is much lower at this time but the availability of such options has obvious implications.
Each case has to be taken on its own merits. A discussion should be held with each patient and, if appropriate, with her family, which should address:
- Non-medication options.
- The risks associated with any normal pregnancy.
- The risks and benefits of antidepressants - the possibility of overdose, abrupt cessation of medication, and safer choices for breast-feeding.
Having had this discussion, the patient's view should then be obtained. Other considerations will include the stage of pregnancy, the severity of the depression, any previous treatment (if applicable) and the need for referral (see below).
Where an individual has had mild depression treated with antidepressants and is pregnant/intends to become pregnant, withdraw the drugs gradually and monitor regularly.
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).
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.
One study reported that aerobic exercise improved depressive symptoms in nulliparous patients with mild-to-moderate depression.
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.
IPT and CBT
These therapies (also known as structured psychological treatments) are useful for moderate- to-severe depression. They should also be considered with mild depression with episodes of more severe depression in the past. They are sometimes combined with antidepressant medication.
No antidepressant is considered completely safe in pregnancy, if for no other reason that marketing trials on pregnant women are eschewed by pharmaceutical companies on ethical grounds. The information base is therefore limited.
Moreover, a recent meta-analysis found that antidepressants may significantly increase the risk for preterm birth and low birth weight.However, this has to be balanced against the risks of untreated depression. Psychiatric illness during pregnancy is in itself an independent risk factor for preterm delivery and perinatal mortality, as well as congenital malformations,
NICE recommends antidepressant medication for a woman with moderate-to-severe depression who:
- Has not responded to high intensity psychological treatment (eg, CBT).
- Declines psychological treatment.
- Has expressed a preference for medication.
- Understands the risks and benefits of the proposed medication.
Before starting antidepressant treatment during pregnancy, consider seeking advice from the UK Teratology Information Service (UKTIS) on 0844 892 0909; a specialist perinatal mental health team, where available; or from secondary psychiatric care.
Inevitably, there is more safety information about older antidepressants than newer medication. On this basis, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and in some circumstances serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered the safest options. Even then, the following should be borne in mind:
- TCAs - amitriptyline has the most supportive information and suggests no risks of congenital abnormalities or adverse fetal outcome. Similarly, the literature that is available has supported the use of trazadone and dosulepin, but there are fewer data available.
- SSRIs - there is an increased risk of congenital malformations in the first trimester, most consistently reported with paroxetine. After 20 weeks, SSRIs have been associated with persistent pulmonary hypertension of the newborn (PPHN). 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. NB: serotonin toxicity may give very similar symptoms to its withdrawal syndrome.
- SNRIs - they are not routinely used as there is even less safety information available than other options but are useful in some circumstances on specialist advice.
- Avoid St John's wort and monoamine-oxidase inhibitors (MAOIs) in pregnancy.
- All antidepressants carry the risk of withdrawal or toxicity in the neonate. Normally this is mild and self-limiting.
For patients who become pregnant whilst taking antidepressants:
- Consider seeking specialist advice before stopping or switching medication.
- Avoid abrupt withdrawal.
- Cover all the relevant issues that would be discussed with a patient who was taking an antidepressant for the first time.
- Consider (with specialist advice) the range of options available and discuss with the patient. This may include gradual withdrawal of medication, instituting psychological therapy and/or switching to a drug with fewer adverse effects.
Any woman taking lithium in pregnancy needs an individualised psychiatric care plan, involving maternity services and the woman herself, for lithium management throughout pregnancy and the peripartum. This needs to include:
- Frequency of monitoring and dose adjustment.
- Potential for interaction with other medications used in pregnancy.
- Preparation for and mode of delivery.
- Risks to the neonate.
There are potential risks to the infant when a breast-feeding mother takes lithium, so mothers should be discouraged from breast-feeding. If they decide to breast-feed, the infant needs close monitoring including serum lithium levels, thyroid and renal monitoring.
Electroconvulsive therapy (ECT)
Where depression is severe and treatment resistant, ECT may be considered, especially if the physical health of the mother or fetus is at serious risk.
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.
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 outcome.
- Higher incidence of lower birth weight, caesarean section but not infant mortality.
- Attempted/completed suicide.
- Possible longer-term cognitive, emotional and behavioural difficulties in offspring.
- Relationship and family break-up.
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. However, maternal depression is associated with less cognitive and language achievement by their children.This is not universal but tends to occur when the mother is unable to actively engage with the infant.
Whilst women are at generally low risk of suicide during pregnancy, it is a significant cause of maternal death in the year following birth in the UK.Improving awareness of perinatal mental health problems, in all their diversity, is important.
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 symptoms
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 IPT or CBT.
Vigorous exercise (3-5 times a week, raising the heart rate to 70-80% of maximum) may have a protective effect.
Further reading and references
Antenatal and postnatal mental health; NICE Quality Standard, February 2016
Edinburgh Postnatal Depression Scale; University of California, San Francisco
Frayne J, Nguyen T, Allen S, et al; Motherhood and mental illness--part 2--management and medications. Aust Fam Physician. 2009 Sep38(9):688-92.
UK Teratology Information Service; Regional Drug and Therapeutics Centre (RDTC)
O'Keane V, Marsh MS; Depression during pregnancy. BMJ. 2007 May 12334(7601):1003-5.
Baibazarova E, van de Beek C, Cohen-Kettenis PT, et al; Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amniotic fluid on birth outcomes and child temperament at 3 months. Psychoneuroendocrinology. 2013 Jun38(6):907-15. doi: 10.1016/j.psyneuen.2012.09.015. Epub 2012 Oct 7.
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 1295(5):499-507.
Management of perinatal mood disorders; Scottish Intercollegiate Guidelines Network - SIGN (March 2012)
Lancaster CA, Gold KJ, Flynn HA, et al; Risk factors for depressive symptoms during pregnancy: a systematic review. Am J Obstet Gynecol. 2010 Jan202(1):5-14.
Austin MP, Priest SR, Sullivan EA; Antenatal psychosocial assessment for reducing perinatal mental health morbidity. Cochrane Database Syst Rev. 2008 Oct 8(4):CD005124.
Antenatal and postnatal mental health: clinical management and service guidance; NICE Clinical Guideline (December 2014)
Depression - antenatal and postnatal; NICE CKS, September 2015 (UK access only)
Dennis CL, Allen K; Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression. Cochrane Database Syst Rev. 2008 Oct 8(4):CD006795.
Robledo-Colonia AF, Sandoval-Restrepo N, Mosquera-Valderrama YF, et al; Aerobic exercise training during pregnancy reduces depressive symptoms in nulliparous women: a randomised trial. J Physiother. 201258(1):9-15. doi: 10.1016/S1836-9553(12)70067-X.
Huang H, Coleman S, Bridge JA, et al; A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry. 2014 Jan-Feb36(1):13-8. doi: 10.1016/j.genhosppsych.2013.08.002. Epub 2013 Oct 2.
Pogliani L, Schneider L, Dilillo D, et al; Paroxetine and neonatal withdrawal syndrome. BMJ Case Rep. 2010 Apr 292010. pii: bcr1220092528. doi: 10.1136/bcr.12.2009.2528.
Haddad PM, Pal BR, Clarke P, et al; Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome? J Psychopharmacol. 2005 Sep19(5):554-7.
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 Mar20(3):189-209.
Yedid Sion M, Harlev A, Weintraub AY, et al; Is antenatal depression associated with adverse obstetric and perinatal outcomes? J Matern Fetal Neonatal Med. 2016 Mar29(6):863-7. doi: 10.3109/14767058.2015.1023708. Epub 2015 Apr 9.
Saving Mothers' Lives. Reviewing maternal deaths to make motherhood safer: 2006-2008; Centre for Maternal and Child Enquiries (CMACE), BJOG, Mar 2011
Strom M, Mortensen EL, Halldorson TI, et al; Leisure-time physical activity in pregnancy and risk of postpartum depression: a prospective study in a large national birth cohort. J Clin Psychiatry. 2009 Dec70(12):1707-14.
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