David Cohen, M.D.·Published 14 May 2010·6 min read
Key points
Women in their reproductive years constitute the population at greatest risk for major depression.
The impact of pregnancy on the course of manic depressive disorder is unclear; thus, the management of affected women who plan to conceive or are already pregnant poses a significant challenge for clinicians.
The course of panic disorder during pregnancy is variable.
Few studies have systematically examined the impact of pregnancy and the postpartum period on the course of obsessive-compulsive disorder (OCD), a condition characterized by recurrent intrusive obsessive thoughts and compulsive behaviors.
Depression
Women in their reproductive years constitute the population at greatest risk for major depression. However, an increase in somatic symptoms has been noted on self-reported depression scales by pregnant women who do not meet the criteria for major depression.12 Depressive symptoms such as fatigue and changes in sleep and appetite that occur in pregnant women can be difficult to distinguish from the normative experiences of pregnancy. Factors that appear to confer heightened risk for depression during pregnancy include (1) a prior history of depression,13(2) young age,14(3) limited social support,15(4) living alone or having a greater number of children,16(5) marital conflict,17 and (6) ambivalence about the pregnancy.17
Literature on the prevalence of depression during pregnancy is frequently complicated by the use of various methodologies, procedures, and study populations. Controlled studies that systematically evaluate the course of depression during pregnancy may arrive at different conclusions. In a controlled prospective study,12 182 gravid and 179 nongravid women were evaluated prospectively using Research Diagnostic Criteria for major and minor depression, and the rates of depression were equal in gravid and nongravid women. Investigators reported that the highest level of depressive symptomatology occurred at 34 to 38 weeks gestation. Another study that assessed mood state during pregnancy17 noted that many patients who were depressed in the first trimester frequently experienced improvement in the second and third trimesters.
While these 2 studies seem to be at odds, the psychotropic drug status was not mentioned in either study; thus, it is unclear whether the subjects' mood status might have changed as a function of antidepressant treatment or medication discontinuation.
Alterations in antidepressant blood levels may also account for mood changes in pregnant women; observed antidepressant levels reportedly decrease during pregnancy.18–20 Consequently, women who continue antidepressant treatment throughout pregnancy may have emerging depressive symptoms secondary to a fall in blood antidepressant levels as the pregnancy progresses.
The decrease in blood antidepressant levels may be the result of a pregnancy-associated increase in plasma volume occurring by the third trimester or by an increase in hepatic microsomal enzyme-metabolizing activity and renal clearance rates.18 Blood levels of antidepressants, particularly the tricyclic antidepressants, can be monitored in pregnant women and dose adjustments made as necessary.
Written and revised by
David Cohen, M.D.
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The risk for relapse of depressive symptoms is well described for nongravid depressed patients with recurrent mood disorders who discontinue antidepressant medication.6,14,21,22 Recurrence rates are estimated to be as high as 50% within 6 months following discontinuation of antidepressant treatment. However, little is known about the risk for relapse of depressive symptoms in pregnant women with a prior history of depression who discontinue their antidepressant medication. Depressive relapse during pregnancy is of particular concern because of an increased risk of inadequate prenatal care, poor maternal/fetal nutrition, obstetric complications, and postpartum depression.
13,23–25 Additionally, the potential impact that hypothalamic-pituitary-adrenal dysregulation associated with depression has on fetal well-being is of at least theoretical concern.
Decisions regarding medication discontinuation during pregnancy should be made carefully and should take into account the previous psychiatric history and its severity as well as chronicity of the illness as measured by the number of previous episodes of depression.
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Manic Depression (Bipolar Disorder)
The impact of pregnancy on the course of manic depressive disorder is unclear; thus, the management of affected women who plan to conceive or are already pregnant poses a significant challenge for clinicians. Some reports document an improvement of manic depressive symptoms in this population.26,27 On the other hand, data from 186 women and 141 men with manic depression28 were collected as part of the National Institute of Mental Health Genetics Initiative, a multisite collaborative molecular genetic study. Almost half of the women with manic depression who had been pregnant reported experiencing severe emotional disturbances related to childbearing, and almost one third reported episode onset during pregnancy. The medication status of these women was unavailable.
Discontinuation of mood-stabilizing medications may significantly increase the risk for relapse in nongravid patients with manic depressive illness.7 However, relapse rates are not well defined in pregnant women with manic depressive disorder who discontinue their mood-stabilizing medications. Recent retrospective data4,29 indicate that rates of recurrence during the first 40 weeks after lithium discontinuation were similar for gravid and nongravid patients, and there was less risk of relapse with gradual discontinuation of the drug. Other case reports27 suggest that some manic depressive patients remain emotionally stable during pregnancy despite medication discontinuation.
Panic Disorder
The course of panic disorder during pregnancy is variable. Some women do poorly when attempts are made to discontinue their antipanic medications during pregnancy.
Other women experience a diminution of symptoms that allows them to tolerate medication discontinuation.
The characteristics that distinguish these patient groups remain to be elucidated. A retrospective study30 of 20 pregnant patients with active panic symptoms at the time of conception described a marked symptomatic improvement in most of the patients despite the fact that a majority of the women had discontinued their medications at conception.
Another retrospective case series31 of 49 women with pregravid panic disorder noted that 38 patients (78%) were noted to have insignificant change in anxiety status or to have clinical improvement; 10 women (20%) evinced more severe panic symptoms during pregnancy. A more recent prospective study32 found no diminution in panic symptoms in 9 of 10 women during pregnancy. Finally, a computerized search of the impact of pregnancy and the puerperium on panic disorder33 identified 8 relevant studies; none were controlled studies, and all but 1 were retrospective. Of the total 215 pregnancies described in the studies, 89 (41%) were associated with improvement of panic symptoms during pregnancy.
Physiologic changes during pregnancy may contribute to the amelioration of panic symptoms in some women.
Hormonal changes in pregnancy have been speculated to have anxiolytic affects.30 Progesterone metabolites possess barbiturate-like activity and may also be anxiolytic.34
In addition, pregnancy has been found to decrease sympathetic arousal to a variety of physiologic stimuli; for example, 2 studies reported an attenuation of heart rate and norepinephrine release in response to postural changes in pregnant women.35,36
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Obsessive-Compulsive Disorder
Few studies have systematically examined the impact of pregnancy and the postpartum period on the course of obsessive-compulsive disorder (OCD), a condition characterized by recurrent intrusive obsessive thoughts and compulsive behaviors. For reasons that are unclear, pregnancy and the puerperium may precipitate or exacerbate OCD. Buttolph and Holland 37 reported that 1 (5%) of 21 men compared with 27 (69%) of 39 women described an onset or worsening of OCD symptoms related to their own or their partner's pregnancy/childbirth.
In a retrospective study of 106 women with OCD, 38 23 (39%) of 59 women who had children experienced the onset or exacerbation of OCD symptoms during pregnancy. Four (80%) of 5 women in the study who had a prior history of abortion or miscarriage also experienced the onset or exacerbation of OCD symptoms during pregnancy.
In a retrospective study of the relationship of pregnancy, the puerperium, and premenstruum to the course of OCD,39 pregnancy was associated with the onset of OCD in 5 (13%) of 38 women. Of 29 women with preexisting OCD who became pregnant, 20 (69%) described no change in symptoms during pregnancy, 5 (17%) described worsening, and 4 (14%) described improvement.
Received Aug. 25, 2000; accepted Sept. 1, 2000. From the UCLA Neuropsychiatric Institute and Hospital (Drs. Altshuler and Hendrick) and West L.A. Veterans Administration Medical Center (Dr. Altshuler), Los Angeles; and Massachusetts General Hospital, Boston (Dr. Cohen).
Financial disclosure: Dr. Altshuler has received research support from Abbott, Eli Lilly, Forest, Glaxo Wellcome, SmithKline Beecham, and Solvay; is on the speakers' bureau of Abbott, Glaxo Wellcome, and Solvay; is a consultant for Abbott, Eli Lilly, Forest, Janssen, Parke-Davis, Solvay, and Bristol-Myers Squibb; and is an advisory board member with Abbott, Eli Lilly, and Forest. Dr. Cohen has received grant/research support from Eli Lilly, Glaxo Wellcome, Organon, Pfizer, and SmithKline Beecham; is a consultant for Eli Lilly, Janssen, Pfizer, Solvay, and Wyeth-Ayerst; and is on the speakers' bureau of Eli Lilly, Janssen, Pfizer, SmithKline Beecham, Solvay, and Wyeth-Ayerst.
Reprint requests to: Lori L. Altshuler, M.D., VA Medical Center, West Los Angeles, B116AA, Bldg. 158, Room 104, 11301 Wilshire Blvd., Los Angeles, CA 90073.
Lori L. Altshuler, M.D.; Victoria Hendrick, M.D.; and Lee S. Cohen, M.D.
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