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Barbara L. Parry, MD

Primary Psychiatry. 2004;11(3):48-51

Focus Points

Postpartum depression (PPD) is often underrecognized and undertreated.

 

Untreated PPD in the mother can impair the neurocognitive development of the child.

 

Pharmacologic treatments and other forms of therapy showing reasonable efficacy and safety profiles can be administered to breast-feeding women with PPD.


Abstract

Postpartum mood disorders are often underrecognized and undertreated. They can present as maternity blues or baby blues, a major depressive episode with features of melancholia, or postpartum psychoses. Untreated postpartum depression in the mother is particularly distressing, as it can impair the neurocognitive development of the child. However, a range of therapeutic modalities are available that have reasonable safety and efficacy in breast-feeding women. New nonpharmacologic treatment strategies include sleep and light therapies that potentially offer benefit within days and do not have the potential adverse effects that are of concern with some pharmacologic interventions.

Introduction

The recognition and management of major depressive disorder (MDD) with postpartum onset is critically important to women’s health. While the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,1 terms the disorder “MDD with postpartum onset,” the disorder will be referred to as postpartum depression (PPD) for this article. Particularly in the United States, these postpartum depressive disorders are often underrecognized and undertreated, potentially contributing to devastating effects on the child, the mother, the family, and society. This article reviews the clinical phenomenology and pharmacologic and nonpharmacologic intervention strategies for improving the health of postpartum women.

Clinical Phenomenology

Postpartum psychiatric conditions are characterized by three primary syndromes: “maternity blues” or “baby blues,” psychosis, and MDD.2 Maternity blues is characterized by mood lability, tearfulness, crying, and even euphoria. Its usual onset occurs >3 days postpartum and it generally resolves within 7–10 days postpartum. As 20% to 30% of women will develop a depressive disorder further along in the postpartum course, a thorough evaluation for MDD is warranted if blues symptoms persist for >2 weeks. However, maternity blues is not considered a disorder, as it occurs in 50% to 80% of women.3

 

Postpartum psychosis is characterized by an acute onset of sleep disturbance, depersonalization, and hallucinations and delusions within the first 2 weeks postpartum, which may occur in women with bipolar illness.4 It is considered a medical emergency, given the risk of infanticide in 4% of women. Treatment, including inpatient hospitalization, should be instituted immediately.

 

Postpartum MDD, in contrast, generally has a more insidious onset within the first 4–6 weeks postpartum, though it may not reach peak intensity until 3–5 months postpartum. It may present with anxious agitated features associated with thyrotoxicosis in 5% to 9% of cases, but may change course with prominent features of melancholia by 3–5 months postpartum, and is associated with hypothyroidism in 10% to 15% of women. This article specifically focuses on treatment of postpartum MDD.

 

General Principles of Treatment

 

Pharmacologic, hormonal, psychotherapeutic, and chronobiological interventions will herein be addressed for MDD in postpartum women who are breast feeding. Treatment for these disorders requires the clinician to weigh the benefits of treatment against many unknown potential risks.5,6 Unfortunatly, information is often scarce, as double-blind, placebo-controlled trials of medication in women who are lactating are not feasible. However, an increasing database supports replicated observations that untreated depression in the mother can impair neurocognitive development of the child.7,8 Animal studies substantiate this finding.9 For example, Weissman and colleagues10,11 reported that children of depressed parents were not only at higher risk for early-onset MDD, but also were at greater risk for anxiety disorders, alcohol abuse, social impairment, and medical problems.

 

Studies to date indicate that most psychotropic medications in dosages commonly used today do not have major teratogenic effects, although long-term behavioral effects of these medications are unknown. However, in many instances, the benefit of a mother’s well-being (resulting from greater mother-child interaction and bonding) outweighs the potential adverse effects of psychotropics. As such, the lowest possible dosage of medication should be used whenever possible and alternative nonpharmacologic interventions, such as outpatient psychotherapy, hospitalization, or milieu therapy, should always be considered as alternative or adjunctive treatments. For example, with maternity blues, treatment with education and reassurance generally is sufficient and does not require routine use of psychotropics. With more severe or worsening illness, however, maintenance or altered dosing of psychotropics may be required to prevent exacerbations of the illness. In addition, it is important that the clinician discuss the option of refraining from breast feeding, which may be a relief to some depressed patients who are feeling overwhelmed. Treatment should be based on the particular individual’s history and clinical assessment. A referral to social services should be considered if concerns arise about the care of the infant and other children at home.

 

The importance of a close rapport between the treating physician and the breast-feeding patient cannot be overstated and will obviate or decrease reliance on psychotropics in many cases. Women with previous episodes of depression or psychoses occurring during the puerperium may develop
significant anticipatory anxiety about suffering from the potentially devastating effects of these illnesses again, which can be dramatically mitigated by ongoing care and effective management by the healthcare provider. In the United Kingdom, Australia, and certain European countries, for example, the existence of mother-baby units and home healthcare providers has had a major impact on improving recognition and management and reducing the adverse consequences of these disorders. Whether treatment interventions are psychosocial or pharmacologic, early intervention with close follow-up and maintenance throughout the puerperium have the best prognosis and can prevent the untoward consequences and refractory course that may otherwise develop.

Pharmacologic Treatment

While maternity blues should be managed by education and reassurance, MDD warrants treatment with antidepressant medication. Only one placebo-controlled trial12 and three open trials13-15 that specifically address PPD have been published. In the controlled trial, fluoxetine was compared with psychotherapy and both treatments were similarly effective. Fluoxetine was significantly more effective than placebo.12 In open trials, sertraline,13 venlafaxine,14 and medication grouped according to class (selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs])15 were effective in the treatment of PPD.

 

In general, women who have given birth recently are often sensitive to the side effects of medications.16 Treatment should therefore be initiated at half the recommended starting dose (eg, sertraline 25 mg/day or paroxetine 10 mg/day) for 4 days and doses should be increased by small increments (eg, sertraline 25 mg/week or paroxetine 10 mg/week) as tolerated until full remission is achieved. If the patient has a response to an initial trial of medication lasting 6–8 weeks, the same dose should be continued for ?6 months after a full remission has been achieved, in order to prevent a relapse.17 If there is no improvement in >6 weeks of drug therapy, or if the patient has a response but then has a relapse, referral to a psychiatrist should be considered. Long-term treatment for the prevention of recurrence should be considered for women who have had three or more episodes of severe depression. As depressive symptoms often present with anxious, agitated features early in the postpartum course, antidepressant treatment for these symptoms is superior to use of benzodiazepines, given their high excretion in breast milk and propensity to induce respiratory depression.

Breast-Feeding Mothers

All antidepressants are excreted into the breast milk18 but sufficient information is not available to classify them differently on this basis. Therefore, the lowest effective dose of antidepressants should be used in a lactating mother. Observation of the infant’s behavior before the mother is treated permits clinicians to avoid misinterpreting typical behavior as potentially drug-related.

Tricyclic Antidepressants

TCAs are not typically found in measurable amounts in nursing infants.18 Of the TCAs, nortriptyline and desipramine have few side effects. However, respiratory depression and sedation, the only adverse outcomes reported with any TCA, occurred in one infant whose mother was taking doxepin.18

 

Of the drugs in this class, nortriptyline has been studied the most as a treatment for breast-feeding women. Children who were exposed to TCAs through breast milk have been followed through preschool and compared with children who were not exposed to these drugs, and no developmental problems were found.19 Nonetheless, TCAs are not first-line medications for depression for most patients because of the cardiovascular risks and other side effects.

 

Selective Serotonin Reuptake Inhibitors

 

Altshuler and colleagues20 recommend that sertraline be used as a first-line treatment for breast-feeding mothers because of its relatively low risk. Sporadic high levels, though, have been observed in some infants.21,22 Epperson and colleagues23 also observed minimal change in infants who were exposed to small amounts of sertraline through breast milk by assessing platelet serotonin level, reflective of central neuronal serotonin transporters. Other investigators have not observed adverse effects in breast-fed infants whose mothers were treated with sertraline, paroxetine, or fluvoxamine.24-26 In one report, though, citalopram, with a relatively short half-life, was associated with “uneasy sleep” in an infant with a measurable serum level.27

 

Fluoxetine may have adverse effects in the breast-fed infant. Breast-fed infants of fluoxetine-treated mothers tend to gain less weight after birth, although unusual behavior has not been observed in these infants.28 Colic has been reported in three infants who were breast-fed by mothers taking fluoxetine. The infants had serum levels of fluoxetine and the active metabolite norfluoxetine that were in the therapeutic range for adults.29,30 As both fluoxetine and norfluoxetine have long half-lives (84 and 146 hours, respectively), continuous exposure to fluoxetine through breast milk is more likely to lead to measurable serum levels compared with other SSRIs.18

 

There are no published long-term evaluations of infants exposed to SSRIs through breast-milk. Exposure to antidepressants through breast milk does not appear to affect infants’ weight. Infants exposed to maternal depression lasting >2 months, however, appear to experience significantly less weight gain than infants of euthymic mothers or mothers who experience brief (<2 months) MDD episodes.31 As most of the published studies on antidepressant levels in infants exposed through breast milk are in full-term infants, close clinical monitoring and measurement of serum levels are warranted for premature or sick newborns.

 

It should be noted that the full-term neonatal cytochrome P450 activity is approximately 50% of that found in adults.32 Also, the collective data on serum levels suggest that infants >10 weeks of age are at low risk for adverse effects from TCAs. Furthermore, the higher lipid content of hindmilk makes it likely that the second half of feeding will have a higher concentration of maternal medication than the foremilk of the first half. Thus, taking medication immediately after breast-feeding minimizes the amount of medication present in milk and maximizes clearance before the next feeding.33

Other Forms of Treatment

Hormonal Treatment

Estrogen and progesterone have been used to treat PPD. Gregoire and colleagues34 compared 17-b-estradiol (200 µg/day) with placebo. The estradiol-treated group had a significant reduction in depression scores during the first month. Half of the women, however, were on antidepressant treatment.

 

Transdermal estradiol may be used with antidepressants for women with PPD without interfering significantly with lactation. At higher doses, however, steroids in milk have been suspected of contributing to neonatal jaundice and of causing vaginal epithelial changes indicative of estrogenic influence.35 Given the lack of controlled randomized trials, use of progesterone as a treatment or prophylaxis in the management of postpartum mood disorders is not advised.36 Prophylactic administration of a progestogen after delivery increased the risk of PPD compared with placebo.37

 

To investigate the hormonal basis of PPD, Bloch and colleagues38 simulated the decline in reproductive hormones after delivery in nonpregnant women with the use of leuprolide to induce a hypogonadal state. The women were then treated with supraphysiological doses of estradiol and progesterone and then both steroids were withdrawn under double-blind conditions. Five of the eight women with a history of PPD, but none of the eight women without previous depression, had mood changes. Thus, women with PPD appear to be differentially sensitive to the effects of the withdrawal of gonadal steroids on mood.

Psychotherapeutic Treatment

In a study of 35 economically-disadvantaged women, Zlotnick and colleagues39 administered a group intervention based on interpersonal psychotherapy during pregnancy, which successfully prevented PPD. In addition, O’Hara and colleagues40 studied 120 postpartum women who were given either a 12-session treatment with interpersonal psychotherapy that focused on changing roles and important relationships or were put on a waiting list for therapy (control condition). The active therapy was effective in relieving depressive symptoms and improving psychosocial functioning. In a study by Appleby and colleagues,12 psychotherapy, in addition to fluoxetine, did not improve outcomes more than fluoxetine or psychotherapy alone in women with PPD.

Electroconvulsive Therapy

Electroconvulsive therapy is an effective treatment for PPD and psychosis. It is also effective for nonpuerperal MDD refractory to pharmacologic interventions, although its implementation requires referral to a psychiatrist.2

 

Postpartum Prophylactic Treatment

 

Preventive therapy after delivery should be considered for women with any previous history of depression. The drug to which the patient previously responded, including any SSRIs, is a reasonable choice. However, it should be noted that the TCA nortriptyline did not confer protection compared with placebo.41 Stewart and colleagues42 instead found that lithium carbonate served as an effective prophylactic agent. An international trial is underway to investigate this work further by testing the efficacy of the neuroleptic haloperidol versus lithium carbonate in the prevention of recurrent postpartum psychosis.

Chronobiological Treatment

One theory for the basis of depression includes desynchronization of circadian rhythms.43 Treatment implications include resynchronizing the biological rhythms of sleep and activity with those of other underlying circadian rhythms such as melatonin, cortisol, thyroid-stimulating hormone, or prolactin. This end may be achieved by administration of bright light (>2500 lux) or wake therapy (sleep deprivation) at critical times of the day. Although still in its experimental stages, the use of bright light or wake therapy in women with pregnancy or PPD has had promising results in pilot studies.44-46 Further studies in this area would be worthwhile given the relatively short onset of action of these treatments and the avoidance of risks associated with pharmacologic interventions.

Conclusion

Recognizing the symptoms of PPD is critical. The earlier the symptoms are recognized, the earlier they can be treated, which dramatically improves the prognosis of the patient and prevents otherwise potentially devastating effects of these illnesses on the child, the mother, the family, and society. Both pharmacologic and nonpharmacologic treatment strategies need to be tailored to the individual needs of the patient. PP

References

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44. Parry BL, Curran ML, Stuenkel CA, et al. Can critically timed sleep deprivation be useful in pregnancy and postpartum depressions? J Affect Disord. 2000;60(3):201-212.

 

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Dr. Parry is professor of psychiatry in the Department of Psychiatry at the University of California in San Diego.

 

Disclosure: Dr. Parry is a consultant to Wyeth; has received honoraria for speaking engagements from Eli Lilly, Pfizer, and Wyeth; and has received grant/research support from Pfizer.

 

Funding/support: This work was supported in part by a grant from the National Institute of Health Clinical Research Center (grant #M01 RR00827) awarded to Dr. Parry.

 

Please direct all correspondence to: Barbara L. Parry, MD, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0804; Tel: 619-543-5592; Fax: 619-543-7519; E-mail: bparry@ucsd.edu.