To screen or not to screen: Are we asking the right question? In response to considering de-implementation of universal perinatal depression screening.

This Editorial is a response to the Canadian Task Force on Preventive Health Care's recent recommendation "against instrument-based depression screening using a questionnaire with cut-off score to distinguish 'screen positive' and 'screen negative' administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth)." While we acknowledge the gaps and limitations in research on perinatal mental health screening, we have concerns regarding the potential impact of a recommendation against screening and for "de-implementation" of existing perinatal depression screening practices, particularly if there is not careful attention to the specificity as well as limitations of the recommendation, or if there are not clear alternative systems put in place to support the detection of perinatal depression. In this manuscript, we highlight some of our key concerns and suggest considerations for perinatal mental health practitioners and researchers.

Safety of Psychotropic Medications During Pregnancy.

Risks, benefits, alternatives, and appropriateness of psychotropic medications, including risks of no treatment, are discussed for antidepressants, mood-stabilizing medications, anxiolytic/sedative hypnotic medications, stimulants, and medication-assisted treatment of substance use disorders. Early screening, diagnosis, and intervention prior to and/or during pregnancy often reduce morbidity and mortality of mental health disorders for mothers and infants.

Psychiatric Medications and Reproductive Safety: Scientific and Clinical Perspectives Pertaining to the US FDA Pregnancy and Lactation Labeling Rule.

Pregnancy labeling of prescription medications in the US is in the midst of a major transformation. The FDA's previous system, which used letter ratings to convey drug safety, was simple but led to misunderstandings-both faulty assurances and undue concerns. The new system, established under the Pregnancy and Lactation Labeling Rule, aims for more descriptive and up-to-date explanations of risk as well as context needed for informed decision-making based on available data. In April 2017, a conference titled "Pharmacovigilance, Reproductive Safety, and the Pregnancy and Lactation Labeling Rule" brought together clinicians and researchers, FDA officials, and representatives of the public and industry to discuss a host of questions relating to the new system. This Academic Highlights article summarizes their discussions, which included topics such as how the new system came about and how the new labeling can be used effectively to inform physician-patient conversations about use of medications during pregnancy and ultimately the clinical decisions that follow.​​.

Increased estradiol and improved sleep, but not hot flashes, predict enhanced mood during the menopausal transition.

BACKGROUND: The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. METHODS: Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17ß-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. RESULTS: Seventy-two peri/postmenopausal women with depression disorders were randomized to 17ß-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. CONCLUSIONS: For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

Treatment of mood disorders during pregnancy and postpartum.

Studies suggest that pregnancy does not protect women from the emergence or persistence of mood disorders. Mood and anxiety disorders are prevalent in women during the childbearing years and, for many women, these mood disorders are chronic or recurrent. Maintenance antidepressant therapy is often indicated during the reproductive years and women face difficult treatment decisions regarding psychotropic medications and pregnancy. Treatment of psychiatric disorders during pregnancy involves a thoughtful weighing of the risks and benefits of proposed interventions and the documented and theoretical risks associated with untreated psychiatric disorders such as depression. Collaborative decision-making that incorporates patient treatment preferences is optimal for women trying to conceive or who are pregnant. This article reviews the diagnosis and treatment guidelines of mood disorders during pregnancy and postpartum, with specific reference to the use of psychotropic medications during this critical time.

Birth outcomes following prenatal exposure to antidepressants.

BACKGROUND: Antidepressant use during pregnancy and the peripartum period is common despite the absence of clear evidence-based guidelines to direct clinical use of these compounds. METHOD: We compared obstetrical and neonatal outcomes as recorded in medical records among 84 pregnant women with major depressive or anxiety disorders (DSM-IV criteria) who took antidepressants during pregnancy (cases) versus a 2:1 age- and parity-matched control group of 168 unexposed women. Women in the case group had sought psychiatric consultation regarding the use of medication from the Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital between 1996 and 2000. RESULTS: There were no significant differences among cases versus controls and their offspring, with respect to various neonatal and obstetrical outcomes, including gestational age and weight, although 1-minute Apgar scores were slightly lower in exposed infants. Admissions to the special care nursery were more frequent, but briefer and based on relatively minor indications, among case newborns. There were no significant differences in neonatal outcomes between exposures to serotonin reuptake inhibitor (SRI) and tricyclic (TCA) antidepressants. CONCLUSION: This retrospective cohort study found no evidence of major increases in risk of adverse obstetrical or neonatal outcomes following prenatal exposure to antidepressants, nor between SRIs and TCAs. Larger, prospective studies with specific neurobehavioral measures are required to resolve current uncertainties about safe and effective use of antidepressants by pregnant women.

Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.

CONTEXT: Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary. OBJECTIVE: To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications. DESIGN, SETTING, AND PATIENTS: A prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (<12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study. MAIN OUTCOME MEASURE: Relapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria. RESULTS: Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001). CONCLUSIONS: Pregnancy is not "protective" with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.

Bupropion SR for the treatment of postpartum depression: a pilot study.

Despite the prevalence of postpartum depression, few studies have assessed the efficacy of antidepressants for the treatment of this disorder. Failure to treat postpartum depression (PPD) places the woman at risk for chronic depression and may have adverse effects on child wellbeing and development. Eight female outpatients aged 18-45 yr were enrolled in an 8-wk open-label trial of bupropion SR for PPD. All patients met DSM-IV criteria for major depression with onset within 3 months of delivery and scored 17 or greater on the Hamilton Depression Rating Scale (HAMD) at baseline. Those with onset of depressive symptoms during pregnancy, psychotic symptoms, or significant medical illness were excluded. Median scores on the HAMD declined from 20.5 (range 15-38) at baseline to 10.0 (range 1-20) at end-point (p<0.05, Wilcoxon signed-ranks test; LOCF). Six out of the eight subjects demonstrated a > or =50% decrease in HAMD scores from baseline; three subjects achieved remission (HAMD score of < or =7) at week 8. Median final dosage of bupropion SR was 262.5 (range 37.5-300). Bupropion SR was well tolerated, and no subjects discontinued treatment as a result of medication side-effects. Bupropion SR represents an effective and well-tolerated antidepressant for the treatment of PPD.

Diagnosis and treatment of depression during pregnancy.

Pregnancy has frequently been described as a time of affective well-being. However, a growing literature suggests that women are neither "protected" against new-onset or recurrence of depression during this time. Diagnosis and effective treatment of depression during pregnancy requires a careful weighing of risk of treatment which may include psychotropic medications against the risks associated with failure to adequately manage affective distress and its potential impact of maternal and fetal well-being. Treatment options during pregnancy are reviewed in the context of developing the most appropriate risk/benefit decision for individual patients with past or current depression who either anticipate pregnancy or who become pregnant.

Assessment and treatment of depression during pregnancy: an update.

Depression occurs commonly during pregnancy, and women with recurrent depression are at particularly high risk for depressive illness in this setting. Though the use of psychotropic medications during pregnancy raises concerns, there are data to support the use of certain antidepressants, including fluoxetine and the tricyclic antidepressants. Data on the newer SSRI antidepressants is gradually accumulating and is encouraging. None of the SSRIS or TCAs have been associated with an increased risk of congenital malformation. However, information on the long-term neurobehavioral effects of these medications still remains limited. As depression during pregnancy carries risk for both the mother and child, it is crucial to diagnose depression in this setting and to provide appropriate treatment strategies. Further data on nonpharmacologic and pharmacologic strategies is needed to aid in the treatment of this challenging clinical population. The clinician must weigh the relative risks of various treatment options and take into account individual patient wishes. Such a process will lead to thoughtful treatment choices, which with close clinical follow-up can minimize the risk for maternal morbidity.

Managing bipolar disorder during pregnancy: weighing the risks and benefits.

BACKGROUND: Challenges for the clinical management of bipolar disorder (BD) during pregnancy are multiple and complex and include competing risks to mother and offspring. METHOD: We reviewed recent research findings on the course of BD during pregnancy and postpartum, as well as reproductive safety data on the major mood stabilizers. RESULTS: Pregnancy, and especially the postpartum period, are associated with a high risk for recurrence of BD. This risk appears to be limited by mood-stabilizing treatments and markedly increased by the abrupt discontinuation of such treatments. However, drugs used to treat or protect against recurrences of BD vary markedly in teratogenic potential: there are low risks with typical neuroleptics, moderate risks with lithium, higher risks with older anticonvulsants such as valproic acid and carbamazepine, and virtually unknown risks with other newer-generation anticonvulsants and atypical antipsychotics (ATPs). CONCLUSIONS: Clinical management of BD through pregnancy and postpartum calls for balanced assessments of maternal and fetal risks and benefits.

Depression during pregnancy: diagnosis and treatment options.

Women often seek clinical consultation for antidepressant use both prior to conception and during pregnancy. Some women experience a new onset of symptoms during pregnancy, while those with a history of depressive symptoms are at increased risk. Nevertheless, clinicians are faced with the challenge of treating the mother without posing risks to the fetus. This review discusses risk factors for depression during pregnancy and the consequences of untreated depression. Nonpharmacologic and pharmacologic treatment options are reviewed, and guidelines for treating depression during pregnancy are presented.