Perinatal Psychiatry: What We Still Don't Know

November 1, 2005

A number of highly publicized cases in the lay press have underscored the significance of, and dangers associated with, perinatal psychiatric illness. Unfortunately, the field of psychiatry has failed to use these tragic cases to disseminate accurate information and educate the public about the high frequency of perinatal depression and anxiety, as well as the relative rarity of postpartum psychosis and infanticide. Moreover, psychiatrists continue to have difficulty in educating their medical colleagues about the need to screen for these illnesses, so most obstetricians and pediatricians still do not screen for perinatal depression and anxiety, much less manage it effectively. Decisions about appropriate treatment are further complicated by a lack of empiric outcome data.

The article by Dr Chaudron and accompanying case reports provide important information for psychiatrists and emergency medicine clinicians who encounter perinatal women in emergency department (ED) and other acute care settings. As the authors note, the epidemiology of depression during pregnancy and the postpartum period, as well as of postpartum psychosis, is well known and should assist clinicians in making differential diagnoses and planning treatment. The high incidence of postpartum depression, coupled with the fact that more than 50% of cases are not recognized, should be a clarion call for routine screening of perinatal women. The profound effects of depression on the developing fetus and infant, as well as on perinatal women, demand greater vigilance.

Empiric Data: What We Still Don't Know About Treatment Efficacy

There is much that is not covered in the review article and the case presentations. This is no fault of the authors--we simply lack even the most basic data for many perinatal mental illnesses. The incidence of anxiety disorders, for instance, is unknown both during pregnancy and postpartum. Little is known about the natural course of these disorders, although most experts agree that they may be exacerbated during the puerperium. The perinatal course of women with more severe mental illnesses, such as schizophrenia, is also unknown. Treating these women tends to be even more complicated than treating women who have affective disorders.

More striking still is the paucity of solid empiric treatment data, which are lacking for all mental disorders that occur during pregnancy and postpartum. Given the widespread use of antidepressants, the lack of data is particularly concerning: clinicians may be exposing pregnant and breast-feeding women to medications that may be ineffective. Risk-benefit assessment is extremely difficult.

This problem is highlighted by a brief review of the perinatal treatment literature. There is only one treatment trial for depression during pregnancy; in the study, interpersonal psychotherapy (IPT) was shown to be only marginally more effective for treating indigent women than was a parenting education group.1 There are no medication trials. No data exist on either medication or psychotherapeutic treatment of anxiety during pregnancy.

The situation regarding the acute treatment of depression during the postpartum period is only slightly less dismal. There is a single placebo-controlled study of antidepressant medication,2 but it involved fluoxetine, a drug that most experts suggest not be taken during breast-feeding because of its long half-life and potential for accumulation.3 There are several open trials of antidepressants, but the study population totals only about 80 women.

A number of studies have investigated the effectiveness of psychotherapeutic treatments during the puerperium.4,5 Many of the interventions are based on the British Health Visitor model and appear to be helpful for women with mild depressive symptoms.6 Unfortunately, this model is not in use in the United States and would take a massive public health initiative to implement universally as has been done in the United Kingdom. IPT has been shown to benefit women with severe depression as well as those with more mild symptoms,7,8 but this intervention, like cognitive-behavioral therapy, requires the ready availability of a highly trained therapist who is well versed in both IPT and perinatal psychopathology.

The situation regarding perinatal anxiety is even more dire. There are no efficacy studies of interventions with either medications or psychotherapy during the perinatal period. While most experts recommend the use of selective serotonin reuptake inhibitors (SSRIs) to manage perinatal anxiety (despite the lack of efficacy and safety data supporting their use), Dr Chaudron points out that the use of benzodiazepines during pregnancy and breast-feeding may be more problematic.

The title "Pregnancy and Bipolar Disorder: Treatment Dilemmas" aptly describes the state of empiric research on the management of bipolar disorder during the perinatal period. The case illustrates that there are no definitive empiric data on treatment efficacy; moreover, other data unequivocally show that many of the commonly used mood stabilizers are teratogenic. Thus, without solid data, the clinician responsible for management of bipolar disorder is faced with the unpleasant task of attempting to minimize risk in a situation in which the seriousness of the illness dictates that treatment be provided.

Empiric Data: What We Still Don't Know About Safety

The articles note that treatment decisions must be made by using a careful risk-benefit evaluation, with sensitivity to the values of individual women and their families.9 The efficacy data needed for risk-benefit analyses are missing, as are data on the safety of medications during pregnancy and breast-feeding. Although several large registries of exposed women and children exist, all are fraught with reporting bias.3 Moreover, because duration of exposure to antidepressants is not constant (women start and stop medications at various times during pregnancy and the postpartum period), naturalistic comparison of exposure is problematic. Assessment of more subtle effects, such as changes in behavior, is often crude or absent, and there are no long-term follow-up data after exposure; thus, the distant effects of exposure are unknown. One can best summarize the existing data by stating that there is no evidence that treatment with the tricyclic antidepressants and SSRIs is harmful, but there is no definitive evidence that they are completely safe either.

What is clear, as noted by the authors, is that untreated perinatal depression and anxiety carry substantial risks. The deleterious effects of postpartum depression on attachment and child behavior have been clear for some time,10-12 and there is emerging evidence that maternal anxiety during the prenatal period may have even more profound neurobiologic effects on exposed infants.13

The balance weighs heavily in favor of treating patients who have perinatal anxiety and depression; management of postpartum psychosis is absolutely necessary. Experts agree that the SSRIs and tricyclic antidepressants are relatively safe. While psychotherapy does not confer risks of exposure, it is not clear whether counseling works as rapidly as medication, nor whether it is as effective as medication to manage more severe anxiety and depression. Additional research is desperately needed to make more empirically informed treatment decisions.

Public Health: What We Are Still Failing to Provide

The case of postpartum anxiety described by Drs Patel and Chaudron highlights additional missing pieces in the optimal management of perinatal psychiatric disorders. For many postpartum women and their clinicians, treatment options are limited, because mothers do not want to be hospitalized and separated from their infants. This is a serious concern, and although no data confirm the benefits of mother-infant inpatient units over outpatient treatment, there are valid reasons to believe that such units are of great benefit. At the very least, mother-infant units allow for a wider and more appropriate range of treatment options that are acceptable to a greater number of women.

In addition to providing more intensive care and observation, the mother-infant inpatient setting allows clinicians to assist women with mother-crafting skills. Support groups, which many postpartum women find helpful, can also be conducted in such units. These units are quite common in Europe and Australia; there are no dedicated mother- infant inpatient units in the United States, however, and very few perinatal day hospital programs. In addition to the lack of routine screening for perinatal depression and anxiety, we have failed to provide a public health system to address these disorders. Consequently, clinicians in ED settings are likely to see women who are further along in the progression of their illness and who are more functionally impaired.

Drs Chaudron and Robertson-Blackmore's description of a patient with postpartum psychosis is a prime example of this public health failure. Although postpartum psychosis, as they note, is frequently of very rapid onset, some women at risk for such episodes could be identified with adequate screening and could be monitored closely during the puerperium. The case also highlights the need to ask every pregnant and postpartum woman about suicidal thoughts and homicidal ideation, particularly toward her infant. It may be uncomfortable initially for clinicians to do so, but the potential lethality dictates that such questions be asked of all women.

Another public health failure is highlighted in the case of bipolar disorder during pregnancy discussed by Dr Freeman. In her example, a woman with a history of bipolar disorder presented to the ED with manic symptoms at 18 weeks' gestation. The patient was already taking several medications and apparently had not discussed with her primary care physician the risk and benefits of taking these medications during pregnancy. The ED psychiatrist was therefore left with the difficult task of managing medications after a lengthy exposure during pregnancy had already taken place.

Best medical practice mandates that every woman of childbearing age for whom medication is prescribed be engaged in a discussion of what to do should she become pregnant. This is unfortunately not the norm, because physicians assume (incorrectly) that women who are taking birth control medication or who are not currently in relationships are not at risk for becoming pregnant. Even more important, physicians and patients must discuss treatment options if patients who are receiving psychotropic medications wish to become pregnant. In such cases, it is incumbent on the physician to help the patient plan--before the fact--a reasonable approach to medication so that risk of exposure and illness exacerbation may be minimized.

The lack of mother-infant inpatient units; the lack of screening for depression, anxiety, and lethality; and the lack of proactive planning for psychopharmacologic management during pregnancy and the postpartum period are but 3 of the public health issues that might be described currently as failures. They can be addressed only by a concerted effort to better educate physicians, patients, and stakeholders in patient care.

Conclusion

Until screening and public health measures are improved, physicians in psychiatric emergency settings and EDs undoubtedly will continue to provide acute care to many perinatal women. While risk-benefit evaluations of treatment should always be conducted with these women, evaluations will continue to be difficult because there are few data to guide most treatment decisions.

Despite these problems, the cases in this series lead to 3 specific recommendations:

•All cases of postpartum psychosis require aggressive and immediate inpatient treatment.

•All women in the perinatal period should be asked directly about suicidality and homicidality, particularly toward their infant.

•Physicians in the emergency care setting should be aware of the empiric data that do exist to optimize their treatment decisions. *

References:

REFERENCES

1. Spinelli MG, Endicott J. Controlled clinical trial of interpersonal psychotherapy versus parenting education program for depressed pregnant women.

Am J Psychiatry.

2003;160:555-562. 2. Appleby L, Warner R, Whitton A, Faragher B. A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression.

BMJ.

1997;314:932-9366.3. Abreu A, Stuart S. Medical treatments for postpartum depression.

Psychiatr Ann.

2005;35:568-575.4. Kopelman R, Stuart S. Psychological treatment of postpartum depression.

Psychiatr Ann

. 2005;35:556-565.5. Dennis CL. Treatment of postpartum depression, part 2: a critical review of nonbiological interventions.

J Clin Psychiatry.

2004;65:1252-1265.6. Stuart S, O'Hara MW, Gorman LL. The prevention and psychotherapeutic treatment of postpartum depression.

Arch Women Ment Health.

2003;6(suppl 2):S57-S69.7. O'Hara MW, Stuart S, Gorman LL, Wenzel A. Efficacy of interpersonal psychotherapy for postpartum depression.

Arch Gen Psychiatry.

2000;57:1039-1045.8. Zlotnick C, Johnson SL, Miller IW, et al. Postpartum depression in women receiving public assistance: pilot study of an interpersonal-therapy-oriented group intervention.

Am J Psychiatry.

2001;158:638-640. 9. Wisner KL, Zarin DA, Holmboe ES, et al. Risk-benefit decision making for treatment of depression during pregnancy.

Am J Psychiatry.

2000;157:1933-1940.10. Field T. Maternal depression effects on infants and early interventions.

Prev Med.

1998;27:200-203.11. Murray L. The impact of postnatal depression on infant development.

J Child Psychol Psychiatry

.

1992;33:543-561.12. Murray L, Cooper P. Effects of postnatal depression on infant development.

Arch Dis Child

. 1997;77:99-101.13. O'Connor TG, Ben-Shlomo Y, Heron J, et al. Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children.

Biol Psychiatry.

2005;58: 211-217.