- Email: [email protected]
The obstetrician and depression during pregnancy
European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 125–130
Review
The obstetrician and depression during pregnancy Daniel M. Campagnea,b a
Department of Personality, Evaluation and Psychological Treatments, Facultad de Psicologı´a, Universidad Nacional de Educacio´n a Distancia, Madrid, Spain b Clinica Bella Medica, Partida Cap Negret 18, 03590 Altea, Spain
Received 8 October 2002; received in revised form 30 May 2003; accepted 25 November 2003
Abstract The objective of this article is to review the literature as to the presence of depression during and after pregnancy and some of its clinical implications; and to present a simple statistical aide for screening purposes. Clinical depression affects at least one in five women of childbearing age. During pregnancy, this figure does not diminish and not only signals problems for the pregnant woman but also for the child, measurably so into adolescence. Postpartum depression, but even more so antepartum depression, are medical conditions that negatively affect mother and child, and need to be detected as early as possible to avoid or limit the use of pharmacological treatments with possible side effects. The obstetrician should regularly test for depression from the very first moments of planning for a child, and use the test results for a ‘‘pregnancy mood profile’’. This profile requires only a few minutes and is very simple to complex. It could serve for early control of depression during pregnancy as well as determine the risk for postpartum depression and thus serve as a pre-alert for postpartum suicide. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Pregnancy mood profile; Antepartum depression; Postpartum depression; Suicide
Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Serious effects of depression on pregnancy. . . . . . . 2. Antepartum depression . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Alternative, non-pharmacological treatments. . . . . . 2.2. Imperative: early detection . . . . . . . . . . . . . . . . . . 3. Postpartum depression: screening for suicidal tendencies 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction When the World Health Organization (WHO) estimates that 22% of women of childbearing age suffer from depression at one time or another, this should be taken as a very cautious estimate. The tendency in Europe and the United States, but also increasingly in other parts of the industrialized world, is that clinical depression affects more adults, more adolescents and more children every year. If other related mood disorders are included, the numbers increase dramatically. Thus, depression has become the primary cause of incapacity in the world, according to the WHO.
E-mail address: [email protected] (D.M. Campagne).
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Pregnancy is a time when women are specially vulnerable to the negative consequences of depression. The hormonal changes in their bodies can aggravate the condition, or make it more difficult to control. There is also the concern for the wellbeing of the child. Recent longitudinal and large-number investigations are showing that this concern is justified. Depression can have negative consequences by itself, but anti-depressant medication too can have negative consequences for the child, in the short and in the long-term. Not treating depression adequately with proper medication may result in loss of life, because the risk of suicide in postpartum depression is all too real. In May 2002 the US authorities, through the US Preventive Services Task Force, Agency for Healthcare Research and Quality, made public a rather dramatic change
0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.11.028
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D.M. Campagne / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 125–130
in the official recommendations for screening for depression. Before this date the official standpoint considered insufficient evidence available to support a recommendation to use standardized screening tests to detect depression in primary care patients. This evidence now is considered to exist, and routine screening for depression in all adults is recommended [1]. Special risk-groups such as women between 20 and 50 should be screened for depression, and because of the prevailing clinical evidence that the consequences of depression for mother and child can amount to changes in fetal development, miscarriage, and suicide, screening for depression during pregnancy should become a matter or priority. 1.1. Serious effects of depression on pregnancy Depression, like anxiety and stress, is a psychopathological condition that even at subclinical levels affects many aspects of pregnancy, both in the mother and in the fetus, both in the short and in the long-term [2–5]. Many physicians, however, underestimate the severity of the effects of depression on health and well-being, and obstetricians are no exception to this rule [6].
2. Antepartum depression The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association specifies a number of mood disorders, together commonly called depression, and specifically refers to postpartum onset, within 4 weeks postpartum [7]. There is no similar reference to the depression that manifests itself just before or during pregnancy. However, clinical data indicate that both the interaction of depression and pregnancy and the interaction of depression and infertility, could be considered pathologies with specific parameters and etiology and with an important epidemiology. Postpartum depression is common, affecting as many as one in every eight women [8]. However, the Avon cohort longitudinal study in the United Kingdom verified that depression during pregnancy is more common than postpartum depression. Of the 9028 women evaluated nearly 14% had probable depression at 32 weeks of pregnancy compared with 9.1% of women at 8 weeks postpartum [9]. When referring to antepartum depression we should not limit the scope to severe major depressive disorder according to DSM-IV standards, but should include all clinical negative mood disorders, be they mild, moderate or severe, if related to and/or concurring with pregnancy. Depressive mood disorders during pregnancy can cause negative effects: in the pregnant woman, through insufficient self care, or physical abandonment (alcohol, smoking, other drugs including cannabis [10], personal hygiene, suicidal
tendencies, self medication, inadequate alimentation, amongst others [11]; in the fetus, as a consequence of the lack of control as to the physical and psychological well-being of the mother, as well as the possible direct influence of negative mood conditions in the mother on fetal cerebral development [12,13]. 2.1. Alternative, non-pharmacological treatments Pharmacological treatment for depression, although highly successful in normal conditions, encounters problems during pregnancy on account of possible side effects of antidepressants on mother and fetus. Although no links have been established between the use of some antidepressants and birth defects, significant influence on gestational age, birth weight and Apgar scores was found for infants exposed to selective serotonine reuptake inhibitors (SSRI), the most widely used class of antidepressants [14,15]. One of these effects is an increase in stress caused by antidepressants that increment serotonine and noradrenaline levels (SSNRI). Higher stress levels in the mother do negatively affect fetal development. Moreover, although several studies consider antidepressants safe during pregnancy [16,17], SSRI’s have shown to cause withdrawal symptoms in the fetus and the newborn child [18] and may cause transitory but significant effects of fetal hypoxemia, with its possible consequences for fetal development [19]. The Policy Statement of the American Academy of Pediatrics urges the physician to minimize the risk of fetal and neonatal toxicity, including the possibility of an abstinence syndrome, and prescribe the lowest dosage that provides adequate control of the woman’s illness. Even so, it considers psychotherapy a first option, and drug treatment only indicated if psychotherapy is inadequate or inappropriate for the patient’s severity of illness [14]. Although antidepressants remain a first option in major depressive disorder, and as such should not be discarded in the treatment of depression during pregnancy, more investigation is needed before they can be considered safe. The US Federal Drug Agency has assigned risk categories B, C, D, and X to different psychotropic medications. Category A indicates no risk, category B indicates an absence of human risk with the caveat of limited data. SSRIs (fluoxetine, sertraline, paroxetine), desipramine, venlafaxine, mirtazapine, nefazodone, clonazepam, and most conventional and atypical antipsychotics have received the C designation. This denotes than human risk cannot be entirely eliminated because of inadequate human clinical trials and either no animal studies or, in some, evidence of risk in animals. The D designation has been assigned to lithium, carbamazepine, sodium valproate, most tricyclic antidepressants, and other benzodiazepines (other than clonazepam), indicating evidence of fetal risk but not an across-the-board contraindication during pregnancy. Benzodiazepines, including triazolam, temazepam, flurazepam, and quazepam have received the X (completely contraindicated) designation [6].
D.M. Campagne / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 125–130
In mild forms of depression, the alternatives [20–22] are not limited to individual or group psychotherapy, and some are more effective than others. Recent but limited-scale investigations consider the following to be effective: morning light [23] or photo therapy, dietary changes and/or supplements [24], increase of physical activity [25] (but criticized [26]), chiromassage, and repetitive transcranial magnetic stimulation [27]. A word of caution as to ‘‘natural’’ remedies for depression such as St John’s wort: although considered effective for mild to moderate depression in a number of randomized, double-blind clinical trials [28] including a long-term study [29], but found ineffective for major depressive disorder in other investigations [30], are now known to produce several kinds of possibly serious side effects [31], as well as changes in the functioning of certain drugs and substances, including contraceptives [32,33]. In March 2003, the US National Institute of Health started a 4-year study (N ¼ 300) that will compare St.John’s wort, citalopram and placebo in patients with mild depression. 2.2. Imperative: early detection There is an across-the-board consensus that depression is best handled when detected early. Handbooks on gynecological endocrinology [34] or psychiatry emphasize that 50% of patients with major depressive disorder have significant depressive symptoms before the first identified episode [35], making early detection feasible and early treatment possible. Mood disorders at mild and moderate levels can normally be effectively treated with behavioral remedies or psychotherapy, but major depression generally requires concurrent pharmacotherapy. Thus, early detection aims to (1) limit the direct negative effects of depression on the pregnant woman and the fetus and to (2) limit the negative side effects of antidepressant medication. A simple screening procedure that monitors for depression would help to comply with these aims and should be included in routine gynecological check-ups or consultations. The screening results would result in a ‘‘pregnancy mood profile’’ that would reflect elementary mood data from the very moment pregnancy is considered [36]. Fig. 1. This profile is not a test for depression, but a simple screening instrument that helps to systematically monitor for depression during pregnancy. The mood profile indicates early symptoms and reflects mood swings during the stages of pregnancy, and monitors the effectiveness of therapies that are applied once depressive symptoms have been detected. Depression is not difficult to detect, although more difficult to fathom. For screening purposes it is not necessary to use long or complicated tests. The detection capacity of very simple tests is comparable to that of sophisticated ones, according to the US Agency for Healthcare Research and Quality. This agency considers that two simple questions based upon DSM-IV criteria would be enough for detection
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purposes: ‘‘over the past 2 weeks, have you ever felt down, depressed, or hopeless?’’ and ‘‘have you felt little interest or pleasure in doing things?’’ [37]. Although similar questions form part of other more elaborate tests, in this case they are merely used as a first screening instrument. If the reply to both questions is positive, more in-depth diagnostic tools should be used. A recent study confirms that these two questions would detect most cases of depression in general practice [49]. Several modern standardized tests for depression, though psychological tools, need no psychologist. The physician or auxiliary personnel could apply them, some are auto-administered, and many are computer-applied. Complete interpretation of the results may need training. The earlier the obstetrician and/or clinician starts screening for depression as a routine part of any consultation related to pregnancy, both when already existing or merely planned, the better the chance of preventive and effective damage control, should depression occur. A recent study found that postpartum depression could not be prevented by preventive measures during pregnancy [38]. However, postpartum depression has a different ethiology from antepartum depression and there is no reason to believe that early measures to counter the development of a full depressive period during pregnancy are less efficient than they have proven to be outside of pregnancy [39]. Although a variety of validated tests for depression are at hand, no specific tests for depression during pregnancy are available. These tests should be developed urgently, and should preferably be self-administered, free of cultural influences, resistant to habituation (as they will be applied several times with relatively short intervals), and with a standardized or computerized interpretation of the results. The tests should measure mood ‘‘downs’’ but could also monitor out-of-proportion mood ‘‘ups’’, to include screening for bipolar disorder. In the meantime and for lack of such a specific test, several other short tests including the Edinburgh Postnatal Depression Scale [40], although developed for postpartum depression, can be used for antepartum depression [41].
3. Postpartum depression: screening for suicidal tendencies? About half of all women suffer from a postpartum depression period that can vary from a few days to several months [37], and that qualifies as a mood disorder in between 10 (overall) and 22% (inner city) [42] of cases. Hormonal changes and psychosocial factors combine to produce mood changes in the mother and, to a much lesser extent, in the father. Mood disorders at moderate to severe levels are not infrequent and at least two of every 1000 new mothers suffer from major postpartum depression with suicidal tendencies. In 20–30% of the cases a serious suicide attempt follows.
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Fig. 1. Example of the Pregnancy Mood Profile reflecting conception on October 16, 2001 and birth on July 17, 2002, where the first double sign of depression was recorded on November 28. No action was taken until the second double sign was registered on December 11, when was referred for therapy, initially 3 times weekly, later 2 and finally once a week. Patient responded well to behavioural therapy, but needed some more counselling in the first weeks after birth. No medication was needed.
In several countries the consensus is that screening for postpartum depression is always indicated. The vigilance should be maintained throughout the first three months, which is considered the high-risk period for psychiatric disorders [43,44], with testing intervals of no longer than 2 weeks.
Major postpartum depression needs medication. However, antidepressant medication when breast-feeding remains a controversial issue for the reasons indicated before, and prescription of an antidepressant for a breastfeeding woman is a ‘‘case-specific risk-benefit decision’’ [45–47]. Therefore, just as in the antepartum period it
D.M. Campagne / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 125–130
remains important to early detect signs of postpartum mood disorders so as to prevent major postpartum depression from developing with the help of alternative remedies and limiting the use of pharmacotherapy. Several self-administered tests such as the EPDS and the CES-D are available and help to early identify this particularly morbid form of depression early [48].
4. Discussion Depression and pregnancy are a dangerous combination. The pregnant or puerperal woman is at considerable risk of this all-too-underestimated pathology. Depression has direct negative consequences on mother and child, and indirectly causes possible side effects through medication. Depression during pregnancy and in nursing mothers is therefore more complicated to (effectively and safely) treat, thus making early detection imperative in order to apply early and adequate multi-disciplinary treatment. A standardized check at regular intervals as to the patient’s mood condition should be done by the obstetrician, and the results used to make a pregnancy mood profile, serving as an early alert to depression. Specific tests for antepartum depression should be developed that are free of cultural influences, self-administered, insensitive to habituation and with a standardized or computerized interpretation of calibrated results. More investigation is needed as to the relationship between depression and pregnancy.
References [1] US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Int Med 2002;136(10):760–4. [2] Campagne DM. Psiconeuroendocrinologı´a de la infertilidad. Boletin de la SEF Madrid 2002;11(2):9–18. [3] Guerra D, Golombok S, Brewaeys A, et al. Estudio europeo de familias de reproduccio´ n asistida. Progrde Obstretricia y Ginecologı´a (Barcelona) 1998;41(5):283–93. [4] Rainey Ch. In: Proceedings of the APA 52nd Conference on Sexual Dysfunction in People being Treated for Depression; 2000, Philadelphia. [5] Girdler SS, Straneva PA, Light KC, Pedersen CA, Morrow AL. Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol Psychiatry 2001;49(9): 788–97. [6] Marcus SM, Barry KL, Flynn HA, Tandon R, Greden JF. Treatment guidelines for depression in pregnancy. Int J Gynecol Obstet 2001; 72(1):61–70. [7] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-IV). APA Washington; 1994. [8] Wisner KL, Parry BL, Piontek CM. Clinical practice. Postpartum depression. N Engl J Med 2002;347(3):194–9. [9] Evans J, Heron J, Francomb H, Oke S, Golding J. Cohort Study of depressed mood during pregnancy and after childbirth. BMJ 2001;323(7037):257–60. [10] Bovasso GB. Cannabis abuse as a risk factor for depressive symptoms. Am J Psychiatry 2001;158(12).
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[11] Cunningham M, Zayas LH. Reducing depression in pregnancy: designing multimodal interventions. Soc Work 2002;47(2):114–23. [12] O’Connor TG, Heron J, Golding J, Beveridge M, Glover V. Maternal antenatal anxiety and children’s behavioural/emotional problems at 4 years: report from the Avon Longitudinal Study of Parents and Children. Br J Psychiatry 2002;180(6):502–8. [13] Allister L, Lestem BM, Carr S, Liu J. The effects of maternal depression on fetal heart rate response to vibroacoustic stimulation. Dev Neuropsychol 2001;20(3):639–51. [14] Policy statement: use of psychoactive medication during pregnancy and possible effects on the fetus and newborn (RE9866). American Academy of Pediatrics. Pediatrics 2000;105(4):880–7. [15] Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002;159:2055–61. [16] Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K. Citalopram in pregnancy and lactation. Clin Pharmacol Ther 2002;72(2): 184–91. [17] Ericson A, Ka¨ lle´ n B, Wiholm B-E. Pharmacodynamics: delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol 1999;55(7) 503–8. [18] Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr 2001;90(3):288–91. [19] Morrison JL, Chien C, Riggs KW, Gruber N, Rurak D. Effect of maternal fluoxetine administration on uterine blood flow, fetal blood gas status, and growth. Pediatr Res 2002;51(4):433–42. [20] Chilvers C, Dewey M, Fielding K, et al. Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. BMJ 2001;322:772. [21] Ward E, King M, Lloyd M, et al. Randomised controlled trial of nondirective counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I Clinical effectiveness. BMJ 2000;321:1383–8. [22] Nonacs R, Cohen LS. Depression during pregnancy: diagnosis and treatment options. J Clin Psychiatry 2002;63(7):24–30. [23] Oren DA, Wisner KL, Spinelli M, et al. An open trial of morning light therapy for treatment of antepartum depression. Am J Psychiatry 2002;159(4):666–9. [24] Tiemeier H, Ruud van Tuijl H, Hofman A, Meijer J, Kiliaan AJ, Breteler MMB. Vitamin B12, folate and homocysteine in depression: the Rotterdam study. Am J Psychiatry 2002;159:2099–101. [25] Dimeo F, Bauer M, Varahram I, Præst G, Halter U. Br J Sports Med 2001;35:114–7. [26] Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomized controlled trials. BMJ 2001;322:763–6. [27] Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 2003;60(10):1002–8. [28] Ernst E. The risk-benefit profile of commonly used herbal therapies. Ann Int Med 2002;136(1):44–6. [29] Woelk H, Beneke M, Gebert I, Rappard F, Rechziegler H. Hypericum extract ZE 117: an open long-term study in patients with mildmoderate depression. Phytomedicine 2000;109(suppl 2):115. [30] Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John’s Wort in major depression. JAMA 2001;285(15):1978–86. [31] Turton-Weeks SM, Barone GW, Gurley BJ, et al. St John’s Wort: a hidden risk for transplant patients. Prog Transplant 2001;11(2):116– 20. [32] St. John’s Wort may weaken effectiveness of oral contraceptives. Reuters Health Information; 7 February 2002. [33] Dresser GK. Chairman’s Introduction. In: Proceedings of the Annual Meeting of the American Society of Clinical Pharmacology and Therapeutics; Orlando, Florida, 2001.
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[34] Speroff L, Glass RH, Kase NG. Clinical gynecologic endocrinology and infertility. 1st ed. (Spanish). Madrid: Waverly; 2000. p. 468. [35] Kaplan HI, Sadock BJ, Grebb JA. Synopsis of Psychiatry. 7th Ed. Baltimore: Williams & Wilkins; 1994. p. 538. [36] Campagne DM. Screening depressive patients in pregnancy with the pregnancy mood profile. J Reprod Med 2003;48(10):813–8. [37] Agency for Healthcare Research and Quality (Chairman’s statements). Mental Health Weekly 2002;12(29):5. [38] Webster J, Linnane J, Roberts J, Starrenburg S, Hinson J, Dibley L. Identify, educate and alert (IDEA) trial: an intervention to reduce postnatal depression. BJOG 2003;110:842–6. [39] Jane´ -Llopis E, Hosman C, Jenkins R, Anderson P. Predictors of efficacy in depression prevention programmes. Br J Psychiatry 2003;183:384–97. [40] Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry 1987;150:782–876. [41] Fergerson SS, Jamieson DJ, Lindsay M. Diagnosing postpartum depression: can we do better? Am J Obstet Gynecol 2002;186(5 Pt 1): 899–902.
[42] Morris-Rush JK, Freda MC, Bernstein PS. Screening for postpartum depression in an inner-city population. Am J Obstet Gynecol 2003;188(5):1217–9. [43] Newport DJ, Hostetter A, Arnold A, Stowe ZN. The treatment of postpartum depression: minimizing infant exposures. J Clin Psychiatry 2002;63(Suppl 7):31–44. [44] Beck CT. Postpartum depression: a metasynthesis. Qual Health Res 2002;12(4):453–72. [45] Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996;153(9):1132–7. [46] Misri S, Kostaras X. Benefits and risks to mother and infant of drug treatment for postnatal depression. Drug Saf 2002;25(13):903–11. [47] Young SA, Campbell N, Harper A. Depression in women of reproductive age, considerations in selecting safe, effective therapy. Postgrad Med 2002;112(3):45–50 [quiz 2]. [48] Houston TK, Cooper LA, Vu HT, Kahn J, Toser J, Ford DE. Screening the public for depression through the Internet. Psychiatr Serv 2001;52(3):362–7. [49] Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ 2003;327:1144–6.
Review
The obstetrician and depression during pregnancy Daniel M. Campagnea,b a
Department of Personality, Evaluation and Psychological Treatments, Facultad de Psicologı´a, Universidad Nacional de Educacio´n a Distancia, Madrid, Spain b Clinica Bella Medica, Partida Cap Negret 18, 03590 Altea, Spain
Received 8 October 2002; received in revised form 30 May 2003; accepted 25 November 2003
Abstract The objective of this article is to review the literature as to the presence of depression during and after pregnancy and some of its clinical implications; and to present a simple statistical aide for screening purposes. Clinical depression affects at least one in five women of childbearing age. During pregnancy, this figure does not diminish and not only signals problems for the pregnant woman but also for the child, measurably so into adolescence. Postpartum depression, but even more so antepartum depression, are medical conditions that negatively affect mother and child, and need to be detected as early as possible to avoid or limit the use of pharmacological treatments with possible side effects. The obstetrician should regularly test for depression from the very first moments of planning for a child, and use the test results for a ‘‘pregnancy mood profile’’. This profile requires only a few minutes and is very simple to complex. It could serve for early control of depression during pregnancy as well as determine the risk for postpartum depression and thus serve as a pre-alert for postpartum suicide. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Pregnancy mood profile; Antepartum depression; Postpartum depression; Suicide
Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Serious effects of depression on pregnancy. . . . . . . 2. Antepartum depression . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Alternative, non-pharmacological treatments. . . . . . 2.2. Imperative: early detection . . . . . . . . . . . . . . . . . . 3. Postpartum depression: screening for suicidal tendencies 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction When the World Health Organization (WHO) estimates that 22% of women of childbearing age suffer from depression at one time or another, this should be taken as a very cautious estimate. The tendency in Europe and the United States, but also increasingly in other parts of the industrialized world, is that clinical depression affects more adults, more adolescents and more children every year. If other related mood disorders are included, the numbers increase dramatically. Thus, depression has become the primary cause of incapacity in the world, according to the WHO.
E-mail address: [email protected] (D.M. Campagne).
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125 126 126 126 127 127 129 129
Pregnancy is a time when women are specially vulnerable to the negative consequences of depression. The hormonal changes in their bodies can aggravate the condition, or make it more difficult to control. There is also the concern for the wellbeing of the child. Recent longitudinal and large-number investigations are showing that this concern is justified. Depression can have negative consequences by itself, but anti-depressant medication too can have negative consequences for the child, in the short and in the long-term. Not treating depression adequately with proper medication may result in loss of life, because the risk of suicide in postpartum depression is all too real. In May 2002 the US authorities, through the US Preventive Services Task Force, Agency for Healthcare Research and Quality, made public a rather dramatic change
0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.11.028
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D.M. Campagne / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 125–130
in the official recommendations for screening for depression. Before this date the official standpoint considered insufficient evidence available to support a recommendation to use standardized screening tests to detect depression in primary care patients. This evidence now is considered to exist, and routine screening for depression in all adults is recommended [1]. Special risk-groups such as women between 20 and 50 should be screened for depression, and because of the prevailing clinical evidence that the consequences of depression for mother and child can amount to changes in fetal development, miscarriage, and suicide, screening for depression during pregnancy should become a matter or priority. 1.1. Serious effects of depression on pregnancy Depression, like anxiety and stress, is a psychopathological condition that even at subclinical levels affects many aspects of pregnancy, both in the mother and in the fetus, both in the short and in the long-term [2–5]. Many physicians, however, underestimate the severity of the effects of depression on health and well-being, and obstetricians are no exception to this rule [6].
2. Antepartum depression The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association specifies a number of mood disorders, together commonly called depression, and specifically refers to postpartum onset, within 4 weeks postpartum [7]. There is no similar reference to the depression that manifests itself just before or during pregnancy. However, clinical data indicate that both the interaction of depression and pregnancy and the interaction of depression and infertility, could be considered pathologies with specific parameters and etiology and with an important epidemiology. Postpartum depression is common, affecting as many as one in every eight women [8]. However, the Avon cohort longitudinal study in the United Kingdom verified that depression during pregnancy is more common than postpartum depression. Of the 9028 women evaluated nearly 14% had probable depression at 32 weeks of pregnancy compared with 9.1% of women at 8 weeks postpartum [9]. When referring to antepartum depression we should not limit the scope to severe major depressive disorder according to DSM-IV standards, but should include all clinical negative mood disorders, be they mild, moderate or severe, if related to and/or concurring with pregnancy. Depressive mood disorders during pregnancy can cause negative effects: in the pregnant woman, through insufficient self care, or physical abandonment (alcohol, smoking, other drugs including cannabis [10], personal hygiene, suicidal
tendencies, self medication, inadequate alimentation, amongst others [11]; in the fetus, as a consequence of the lack of control as to the physical and psychological well-being of the mother, as well as the possible direct influence of negative mood conditions in the mother on fetal cerebral development [12,13]. 2.1. Alternative, non-pharmacological treatments Pharmacological treatment for depression, although highly successful in normal conditions, encounters problems during pregnancy on account of possible side effects of antidepressants on mother and fetus. Although no links have been established between the use of some antidepressants and birth defects, significant influence on gestational age, birth weight and Apgar scores was found for infants exposed to selective serotonine reuptake inhibitors (SSRI), the most widely used class of antidepressants [14,15]. One of these effects is an increase in stress caused by antidepressants that increment serotonine and noradrenaline levels (SSNRI). Higher stress levels in the mother do negatively affect fetal development. Moreover, although several studies consider antidepressants safe during pregnancy [16,17], SSRI’s have shown to cause withdrawal symptoms in the fetus and the newborn child [18] and may cause transitory but significant effects of fetal hypoxemia, with its possible consequences for fetal development [19]. The Policy Statement of the American Academy of Pediatrics urges the physician to minimize the risk of fetal and neonatal toxicity, including the possibility of an abstinence syndrome, and prescribe the lowest dosage that provides adequate control of the woman’s illness. Even so, it considers psychotherapy a first option, and drug treatment only indicated if psychotherapy is inadequate or inappropriate for the patient’s severity of illness [14]. Although antidepressants remain a first option in major depressive disorder, and as such should not be discarded in the treatment of depression during pregnancy, more investigation is needed before they can be considered safe. The US Federal Drug Agency has assigned risk categories B, C, D, and X to different psychotropic medications. Category A indicates no risk, category B indicates an absence of human risk with the caveat of limited data. SSRIs (fluoxetine, sertraline, paroxetine), desipramine, venlafaxine, mirtazapine, nefazodone, clonazepam, and most conventional and atypical antipsychotics have received the C designation. This denotes than human risk cannot be entirely eliminated because of inadequate human clinical trials and either no animal studies or, in some, evidence of risk in animals. The D designation has been assigned to lithium, carbamazepine, sodium valproate, most tricyclic antidepressants, and other benzodiazepines (other than clonazepam), indicating evidence of fetal risk but not an across-the-board contraindication during pregnancy. Benzodiazepines, including triazolam, temazepam, flurazepam, and quazepam have received the X (completely contraindicated) designation [6].
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In mild forms of depression, the alternatives [20–22] are not limited to individual or group psychotherapy, and some are more effective than others. Recent but limited-scale investigations consider the following to be effective: morning light [23] or photo therapy, dietary changes and/or supplements [24], increase of physical activity [25] (but criticized [26]), chiromassage, and repetitive transcranial magnetic stimulation [27]. A word of caution as to ‘‘natural’’ remedies for depression such as St John’s wort: although considered effective for mild to moderate depression in a number of randomized, double-blind clinical trials [28] including a long-term study [29], but found ineffective for major depressive disorder in other investigations [30], are now known to produce several kinds of possibly serious side effects [31], as well as changes in the functioning of certain drugs and substances, including contraceptives [32,33]. In March 2003, the US National Institute of Health started a 4-year study (N ¼ 300) that will compare St.John’s wort, citalopram and placebo in patients with mild depression. 2.2. Imperative: early detection There is an across-the-board consensus that depression is best handled when detected early. Handbooks on gynecological endocrinology [34] or psychiatry emphasize that 50% of patients with major depressive disorder have significant depressive symptoms before the first identified episode [35], making early detection feasible and early treatment possible. Mood disorders at mild and moderate levels can normally be effectively treated with behavioral remedies or psychotherapy, but major depression generally requires concurrent pharmacotherapy. Thus, early detection aims to (1) limit the direct negative effects of depression on the pregnant woman and the fetus and to (2) limit the negative side effects of antidepressant medication. A simple screening procedure that monitors for depression would help to comply with these aims and should be included in routine gynecological check-ups or consultations. The screening results would result in a ‘‘pregnancy mood profile’’ that would reflect elementary mood data from the very moment pregnancy is considered [36]. Fig. 1. This profile is not a test for depression, but a simple screening instrument that helps to systematically monitor for depression during pregnancy. The mood profile indicates early symptoms and reflects mood swings during the stages of pregnancy, and monitors the effectiveness of therapies that are applied once depressive symptoms have been detected. Depression is not difficult to detect, although more difficult to fathom. For screening purposes it is not necessary to use long or complicated tests. The detection capacity of very simple tests is comparable to that of sophisticated ones, according to the US Agency for Healthcare Research and Quality. This agency considers that two simple questions based upon DSM-IV criteria would be enough for detection
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purposes: ‘‘over the past 2 weeks, have you ever felt down, depressed, or hopeless?’’ and ‘‘have you felt little interest or pleasure in doing things?’’ [37]. Although similar questions form part of other more elaborate tests, in this case they are merely used as a first screening instrument. If the reply to both questions is positive, more in-depth diagnostic tools should be used. A recent study confirms that these two questions would detect most cases of depression in general practice [49]. Several modern standardized tests for depression, though psychological tools, need no psychologist. The physician or auxiliary personnel could apply them, some are auto-administered, and many are computer-applied. Complete interpretation of the results may need training. The earlier the obstetrician and/or clinician starts screening for depression as a routine part of any consultation related to pregnancy, both when already existing or merely planned, the better the chance of preventive and effective damage control, should depression occur. A recent study found that postpartum depression could not be prevented by preventive measures during pregnancy [38]. However, postpartum depression has a different ethiology from antepartum depression and there is no reason to believe that early measures to counter the development of a full depressive period during pregnancy are less efficient than they have proven to be outside of pregnancy [39]. Although a variety of validated tests for depression are at hand, no specific tests for depression during pregnancy are available. These tests should be developed urgently, and should preferably be self-administered, free of cultural influences, resistant to habituation (as they will be applied several times with relatively short intervals), and with a standardized or computerized interpretation of the results. The tests should measure mood ‘‘downs’’ but could also monitor out-of-proportion mood ‘‘ups’’, to include screening for bipolar disorder. In the meantime and for lack of such a specific test, several other short tests including the Edinburgh Postnatal Depression Scale [40], although developed for postpartum depression, can be used for antepartum depression [41].
3. Postpartum depression: screening for suicidal tendencies? About half of all women suffer from a postpartum depression period that can vary from a few days to several months [37], and that qualifies as a mood disorder in between 10 (overall) and 22% (inner city) [42] of cases. Hormonal changes and psychosocial factors combine to produce mood changes in the mother and, to a much lesser extent, in the father. Mood disorders at moderate to severe levels are not infrequent and at least two of every 1000 new mothers suffer from major postpartum depression with suicidal tendencies. In 20–30% of the cases a serious suicide attempt follows.
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Fig. 1. Example of the Pregnancy Mood Profile reflecting conception on October 16, 2001 and birth on July 17, 2002, where the first double sign of depression was recorded on November 28. No action was taken until the second double sign was registered on December 11, when was referred for therapy, initially 3 times weekly, later 2 and finally once a week. Patient responded well to behavioural therapy, but needed some more counselling in the first weeks after birth. No medication was needed.
In several countries the consensus is that screening for postpartum depression is always indicated. The vigilance should be maintained throughout the first three months, which is considered the high-risk period for psychiatric disorders [43,44], with testing intervals of no longer than 2 weeks.
Major postpartum depression needs medication. However, antidepressant medication when breast-feeding remains a controversial issue for the reasons indicated before, and prescription of an antidepressant for a breastfeeding woman is a ‘‘case-specific risk-benefit decision’’ [45–47]. Therefore, just as in the antepartum period it
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remains important to early detect signs of postpartum mood disorders so as to prevent major postpartum depression from developing with the help of alternative remedies and limiting the use of pharmacotherapy. Several self-administered tests such as the EPDS and the CES-D are available and help to early identify this particularly morbid form of depression early [48].
4. Discussion Depression and pregnancy are a dangerous combination. The pregnant or puerperal woman is at considerable risk of this all-too-underestimated pathology. Depression has direct negative consequences on mother and child, and indirectly causes possible side effects through medication. Depression during pregnancy and in nursing mothers is therefore more complicated to (effectively and safely) treat, thus making early detection imperative in order to apply early and adequate multi-disciplinary treatment. A standardized check at regular intervals as to the patient’s mood condition should be done by the obstetrician, and the results used to make a pregnancy mood profile, serving as an early alert to depression. Specific tests for antepartum depression should be developed that are free of cultural influences, self-administered, insensitive to habituation and with a standardized or computerized interpretation of calibrated results. More investigation is needed as to the relationship between depression and pregnancy.
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