Assessing low mood during pregnancyBMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4584 (Published 29 July 2019) Cite this as: BMJ 2019;366:l4584
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This excellent review will be widely read and used by practising clinicians . Prescribing antidepressants in pregnancy is a familiar dilemma, but, at ~5%, the prevalence of antidepressant prescribing in trimester 1 is high enough to make this a public health concern. We identified a dose-response association between selective serotonin reuptake inhibitor (SSRI) exposure and major congenital anomalies or stillbirth and, most specifically, severe congenital heart defects . Without SSRIs, 6 infants in 200 were born with a major anomaly or stillborn: SSRI exposure raised this to 7 in 200. A posteriori subgroup analysis highlighted increased risks to those exposed to substance misuse or heavy alcohol use.
Balancing the number needed to harm from first trimester prescribing, 192, with the severity of potential adverse effects (stillbirth or major anomaly) might entail taking records of SSRI prescriptions as indicating need for additional preconception care. Suggestions include:
o Using electronic health records to identify women of childbearing age prescribed antidepressants.
o Contacting all women prescribed antidepressants, not just those identifying themselves as planning pregnancy, since ~43% UK pregnancies are unplanned.
o Regarding substance misuse or heavy drinking as possible indicators of high risk from SSRI prescribing (6.3%).
o Expanding pre-conception care to include: reviewing therapeutic regimens, particularly high doses of SSRIs; reflecting that ~40% women discontinuing SSRIs after conception do not restart within a year of childbirth , and cognitive behavioural therapy may be equally effective .
o Prescribing folic acid, which may reduce the prevalence of CHD .
o Consider offering women prescribed SSRIs in pregnancy 24-26 week and third trimester scans or alternative continuous monitoring technology to:
• take advantage of advances in monitoring and surgery in utero
• ensure appropriate levels of neonatal care are available at birth.
o Consider offering a modified care pathway to include detailed ultrasound scans with views of the 4 cardiac chambers, outflow tracts and aortic arch plus Doppler investigation of blood flow.
Many of these suggestions, which are offered to supplement the current review , could be embraced by nurse or midwives and the wider multidisciplinary team.
1. Kirby Natalie, Kilsby Anna, Walker Ruth. Assessing low mood during pregnancy BMJ 2019; 366 :l4584
2. Jordan S , Morris JK , Davies GI, Tucker D, Thayer DS, Luteijn JM, Morgan M, Garne E, Hansen AV, Klungsøyr K, Engeland A, Boyle B, Dolk H (2016) Article Source: Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark Plos One 11(12): e0165122. doi: 10.1371/journal.pone.0165122
3. Charlton RA, Jordan S, Pierini A, Garne E, Neville AJ, Hansen AV, et al. Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions. BJOG. 2015;122(7):1010-20. doi: 10.1111/1471-0528.13143.
4. Amick HR, Gartlehner G, Gaynes BN, Forneris C, Asher GN, Morgan LC, et al. Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis. BMJ. 2015;351:h6019. PubMed PMID: 26645251; PubMed Central PMCID: PMCPMC4673103.
5. Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L. Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. BMJ. 2009;338:b1673. PubMed PMID: 19436079; PubMed Central PMCID: PMCPMC2682153.
6. Li Y, Hua Y, Fang J, Wang C, Qiao L, Wan C, et al. Performance of different scan protocols of fetal echocardiography in the diagnosis of fetal congenital heart disease: a systematic review and meta-analysis. PLoS One. 2013;8(6):e65484. doi: 10.1371/journal.pone.0065484. PubMed PMID: 23750263; PubMed Central PMCID: PMCPMC3672155.
Competing interests: No competing interests
Is any ECT is unacceptable in pregnancy?
A 2003 UK ECT Review Group concluded that ECT is an effective short-term treatment for depression. In contrast, a 2015 systematic review by Leikenes and colleagues of the effects on the child recommended an urgent update of international guidelines.
The Leikenes case studies involved 69 pregnant women who were given a mean number of 9.4 ECTs, at a mean age of 29 years. Most women received ECT during the 2nd trimester and many were primigravida. Main diagnostic indication in the years 1970 to 2013 was depression/bipolar disorder (including psychotic depression). Missing data on foetus/child was 12%. ECT parameter report was often sparse. Both bilateral and unilateral electrode placement was used and thiopental was the main anaesthetic agent. Adverse events such as foetal heart rate reduction, uterine contractions, and premature labour (29 to 37 weeks gestation) occurred in nearly one third (29%). The overall child mortality was 7.1% overall. Lethal outcomes for the foetus and/or baby had diverse associations. They advised that ECT during pregnancy is should only be considered as last resort treatment under very stringent diagnostic and clinical indications
There is also evidence linking antidepressant medications with increases in autism. Of 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). 
Zinc, magnesium, B vitamins and omega-3 and omega-6 polyunsaturated fatty acids levels are commonly deficient in depression. In 1988 we found that dyslexic children were zinc deficient and low maternal zinc in early pregnancy may adversely affect the development of stress coping mechanisms.  THINK ZINC! Monitored repletion of deficiencies is vital for the physical and mental health of both mother and child both before and during pregnancy and lactation. 
It is alarming that psychiatrists would choose to give depressed pregnant women potentially dangerous antidepressants or electroconvulsive therapy (ECT) rather than investigate and correct very common essential nutrient deficiencies.
1 UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003 Mar 8;361(9360):799-808.
2 Leikenes KA Cooke MJ, von Schweder J, Harboe I, Hoie B. Electroconvulsive therapy during pregnancy: a systematic review of case studies. Arch Womens Ment Health. 2015; 18: 1–39.
3 Rai D, Lee B K, et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ 2017;358:j2811.
4 Grant ECG, Howard JM, et al. Zinc deficiency in children with dyslexia: concentrations of zinc and other minerals in sweat and hair. BMJ 1989;296:607-609.
5 Barnes B, Grant ECG et al. Nutrition and preconception care. Lancet 1985;2:1297.
Competing interests: No competing interests
Kirby et al suggest general practitioners (GPs) should initiate antidepressant therapy for pregnant women with moderate to severe depressive illness, whilst they await psychiatric assessment (1). This is potentially harmful advice.
Most people diagnosed with depressive illness in primary care do not, in fact, have the disease at all (2) and do not require medication. Sadly, clinical accuracy will not be improved by the authors’ failure to state properly the cardinal diagnostic symptom: depressive episode is not characterised by “persistent low mood”(1), but by “depressed mood, to a degree that is definitely abnormal for the individual, present for most of the day and almost every day, largely uninfluenced by circumstances, and sustained for at least two weeks.”(3) In my experience, widespread use in primary care of diagnostic tools that largely ignore the various aspects of this clear description is the biggest reason for misdiagnosis.
The authors correctly identify the myriad potential risks to mother and child associated with antidepressant use in pregnancy. Consequently, their initiation should only be considered by a specialist, after a clear diagnosis has been reached by taking a careful history. With the best will in the world, a comprehensive discussion with the patient and her family on the possible risks and benefits of pharmacotherapy during pregnancy, weighed up alongside those of delaying treatment and of the faster-acting, more effective electroconvulsive therapy (4), cannot be adequately conducted by a GP during a ten-minute consultation.
A pregnant woman with a provisional diagnosis of moderate to severe depressive illness should be urgently referred for a psychiatric opinion, followed by active treatment within secondary care if indicated.
I beg to remain, Madam, your most obedient servant,
Dr Richard Braithwaite
1. Kirby N, Kilsby A, Walker R. Assessing low mood during pregnancy. BMJ 2019;366:l4584
2. Mitchell AJ, Vaze A, Rao S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet 2009;374:589-99.
3. World Health Organisation (1993) The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. WHO.
4. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003;361:799-808.
Competing interests: No competing interests
Depression in pregnancy, previous progestogen use, and nutritional deficiencies Re: Assessing low mood during pregnancy
The high incidence of depression, of up to 10% during pregnancy with higher risks for the children, makes depressing reading. Vigod and colleagues recommended (side-effect) prone selective serotonin reuptake inhibitor antidepressant drugs or psychological therapies but they do however refer to one trial of omega-3 supplementation.
A search of PubMed brings up -
171 results for zinc deficiency and depression
141 results for magnesium deficiency and depression
100 results for vitamin B6 deficiency and depression
229 results for vitamin B12 deficiency and depression
462 results for copper and depression
77 results for omega-3 deficiencies and depression
1133 results for progestins and mental depression
Clearly major causes of depression in pregnancy include essential nutrient deficiencies and previous use of progestins which increase depressive mood changes and increase monoamine activity in the brain, blood and endometrium.[2-4] In developed countries most women are given progestogenic hormonal contraceptives from young ages, usually without being monitored for increasingly prevalent essential nutrient deficiencies. Progestogens and oestrogens can lower zinc and increase copper levels (but can lower copper stores) and increase adverse reactions to common food and chemicals, impair liver and pancreatic function, and prevent absorption of essential nutrients during before or pregnancy.
The epidemiology of single drug therapy is fraught with mistakes but it is a mistake to ignore the importance of previous progestogen use and residual multiple essential nutrient imbalances or deficiencies. I spent decades correcting these before conception in couples with histories of "unexplained" infertility or recurrent miscarriages.
1. Vigod SN, Brown LM, Howard LM. Depression in pregnancy. BMJ 2016;352:i1547.
2 Grant EC, Pryse-Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. Br Med J 1968 Sep 28;3(5621):777-80.
3 Robinson DS, Davies JM, Nies A, Ravaris CL, Sylwester D. Relation of Sex and Aging to Monoamine Oxidase Activity of Human Brain, Plasma, and Platelets. Arch Gen Psychiatry 1971;24(6):536-539.
4 Kolla NJ, Chiuccariello L, Wilson AA, Houle S, Links P, Michael Bagby R, McMain S, Kellow C, Patel J, Rekkas PV, Pasricha S, Meyer J. Elevated Monoamine Oxidase-A Distribution Volume in Borderline Personality Disorder Is Associated With Severity Across Mood Symptoms, Suicidality, and Cognition. Biological Psychiatry 2016;79:117-126.
5 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity, and mineral imbalance. J Nutr Environ Med 1998;8(2):105-116.
Competing interests: No competing interests
Depression is two to three times more frequent in women than men. The highest prevalence figures are reached during the years of fertile life, so that women may be depressed before conception or depressed during pregnancy.
Some countries report depressive illness during pregnancy represents a public health problem. It is estimated that in 2020 depression will be the second leading cause of disability worldwide.
In recent years there has been notable progress in the field of perinatal psychiatry, a discipline that deals with psychopathological aspects related to pregnancy and postpartum. In light of this fact, it is essential that gyneco-obstetrics and pediatrics professionals become familiar with these advances, since the close contact they have with pregnant or puerperal women provides a unique opportunity to diagnose and treat depression early. maternal pre and postpartum. This can make it possible to avoid or minimize numerous negative consequences that perinatal depression can cause to the mother, the family environment and in particular, to the offspring, at the stage of the fetus or infant and at later times of life.
The clinical picture of pregnancy depression is similar to that presented in depressive episodes at other times of life. In addition to the cardinal symptoms of depression - such as discouragement, disinterest in activities that were previously attractive, deterioration in self-esteem, emotional lability - symptoms such as distress, irritability and deconcentration usually occur.
There may be rejection or ambivalence in relation to pregnancy, especially if it is not planned. Likewise, the woman may experience anguish over the responsibility of assuming the role of mother or feeling guilty for believing that she is not contributing to the well-being of her baby.
It is essential to diagnose episodes of major depression. In this sense, the persistence of discouragement as a diagnostic requirement is particularly important. To diagnose a major depression it is required, among other clinical characteristics, that the discouragement be prolonged for at least two weeks.
Depressed pregnant women have a higher risk of neglecting their pregnancy, of abandoning prenatal check-ups, or of not following or erroneously following medical indications, compared to non-depressed pregnant women. In addition, they are more likely to abuse tobacco, alcohol and drugs; all of which can affect the obstetric outcome. In turn, some symptoms of depression such as anorexia, can alter some aspects of pregnancy - such as weight gain - and thus contribute to adverse outcomes.
Some discomforts typical of gravity, such as fatigue, emotional lability and sleep and appetite disorders, are usually found during depression. It is also pertinent to remember that pregnant women may suffer from certain medical conditions such as anemia, gestational diabetes and thyroid dysfunction, which are often associated with depressive symptoms. For this reason to minimize the risk of false positives, it is recommended to systematically explore the psychic symptoms of major depression, feelings of guilt, hopelessness and suicidal ideation.
Acute major depressive disorders of pregnancy are often not treated or treated insufficiently. Moreover, it is known that even having made the diagnosis of a psychiatric disorder during pregnancy, it is often not treated.
The purpose of a treatment for depression in a pregnant woman is to improve her mood, minimizing the risks to the developing fetus. You should start with general strategies such as recommending to stop the consumption of caffeine, nicotine and alcohol, or try to maximize the chances of rest. It may be beneficial to resort to relaxation techniques and also to environmental management measures.
In general, its use is considered in pregnant women with moderate to severe depression, pregnant women who have not responded to other treatments or when there is a high probability of recurrence. Due to obvious ethical reasons, there are no studies on the efficacy of antidepressants in the treatment of depression in pregnant women. However, there is no reason to think that the therapeutic response of gravid women should be different from that observed in non-pregnant women. Moreover, there are guidelines for the treatment of depression during pregnancy.
1. American Psychiatric AssociationDiagnostic and Statistical Manual for Mental Disorders (5th), American Psychiatric Association, Washington, DC (2013).
2. C. Rubertsson, K. Börjesson, A. Berglund, A. Josefsson, G. SydsjöThe Swedish validation of the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy Nord J Psychiatry, 65 (6) (2011), pp. 414-8.
3. C. Castañon, J. Pinto. Mejorando la pesquisa de depresión postparto a través de un instrumento de tamizaje, la escala de depresión postparto de Edimburgo Rev Méd Chile, 136 (2008), pp. 851-858.
4. Antenatal and Posnatal Mental HealthClinical management and service guidance. Clinical Guideline 45 National Institute for Clinical Excellence (NICE), London (2007).
5. D.J. Newport, M.M. Wilcot, Z.N. StoveMaternal depression: A child's first adverse life event. Semin Clin Neuropsychiatry, 7 (2) (2002), pp. 113-119
6. T. Deave, J. Heron, J. Evans, A. EmondThe impact of maternal depression in pregnancy on early child development. BJOG, 115 (8) (2008), pp. 1043-1051.
7. S. Pawlby, D.F. Hay, D. Sharp, C.S. Waters, V. O’KeaneAntenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based studyJ Affect Disord, 113 (3) (2009), pp. 236-243.
8. A. Daley, L. Foster, G. Long, C. Palmer, O. Robinson, H. Walmsley, et al.The effectiveness of exercise for the prevention and treatment of antenatal depression: systematic review with meta-analysis. BJOG (2014) Jun 17.
9. M. Ellfolk, H. MalmRisks associated with in utero and lactation exposure to selective reuptake inhibitors (SSRIs) Reprod Toxicol, 30 (2) (2010), pp. 249-260
10. S.D. Sie, J.M. Wennink, J.J. van Driel, A.G. Te Winkel, K. Boer, G. Casteelen, M.M. van WeissenbruchMaternal use of SSRIs, SNRIs and NaSSAs: practical recommendations during pregnancy and lactation.Arch Dis Child Fetal Neonatal Ed., 97 (6) (2012), pp. 472-476.
11. K.F. Huybrechts, K. Palmsten, J. Avorn, L.S. Cohen, L.B. Holmes, J.M. Franklin, et al.Antidepressant use in pregnancy and the risk of cardiac defects N Engl J Med, 370 (25) (2014), pp. 2397-2407.
12. M. Soufia, J. Aoun, M.A. Gorsane, M.G. KrebsSSRIs and pregnancy: a review of the literature. Encephale 2010, 36 (6) (2010), pp. 513-516.
13. L. Hantsoo, D. Ward-O’Brien, K.A. Czarkowski, R. Gueorguieva, L.H. Price, C.N. EppersonA randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression Psychopharmacology (Berl), 231 (5) (2014), pp. 939-948.
Competing interests: No competing interests