The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Pilot validation of blood-based biomarkers during pregnancy and postpartum in women with prior or current depression.

Major depressive disorder (MDD) is more common in women than in men, and evidence of gender-related subtypes of depression is emerging. Previously identified blood-based transcriptomic biomarkers distinguished male and female subjects with MDD from those without the disorder. In the present pilot study, we investigated the performance of these biomarkers in pregnant and postpartum women with prior major depressive episodes, some of whom had current symptomatology. The symptom scores of 13 pregnant and 15 postpartum women were identified by the Inventory of Depressive Symptoms (IDS-SR-30) at the time of blood sampling. Blood levels of the 20 transcriptomic biomarkers and that of estrogen receptor 2 (ESR2), membrane progesterone receptor alpha and beta (mPRα, mPRß) were measured. In pregnant women, transcript levels of ADCY3, ASAH1, ATP11C, CDR2, ESR2, FAM46A, mPRß, NAGA, RAPH1, TLR7, and ZNF291/SCAPER showed significant association with IDS-SR-30 scores, of which ADCY3, FAM46A, RAPH1, and TLR7 were identified in previous studies for their diagnostic potential for major depression. ASAH1 and ATP11C were previously also identified as potential markers of treatment efficacy. In postpartum women, transcript levels of CAT, CD59, and RAPH1 demonstrated a trend of association with IDS-SR-30 scores. Transcript levels of ADCY3, ATP11C, FAM46A, RAPH1, and ZNF291/SCAPER correlated with ESR2 and mPRß expressions in pregnant women, whereas these associations only existed for mPRß in postpartum women. These results suggest that a blood biomarker panel can identify depression symptomatology in pregnant women and that expression of these biomarker genes are affected by estrogen and/or progesterone binding differently during pregnancy and postpartum.

Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression.

The physiological changes of pregnancy can affect the pharmacokinetics of a drug, thereby affecting its dose requirements. Because pharmacokinetic (PK) studies in pregnant women have rarely been conducted, evidence-based dosing adjustments are seldom available. In particular, despite the fact that the use of antidepressants has become increasingly common, pregnancy-associated PK changes of the selective serotonin reuptake inhibitors (SSRIs) are largely unknown.

Serum nortriptyline levels in nursing mothers and their infants.

The nortriptyline levels of seven depressed mothers and their breast-fed infants were obtained. Nortriptyline was not detected in the infants' sera. However, two of four infants evaluated developed low concentrations of 10-hydroxynortriptyline. No adverse effects were observed.

Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs.

OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. METHOD: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.

Tricyclic dose requirements across pregnancy.

In a series of eight pregnant women, the authors found that the doses of tricyclic antidepressants required to achieve remission of symptoms and adequate serum levels increased during the second half of pregnancy. During the final trimester, the mean dose required was 1.6 times the mean dose required when the patients were not pregnant.

Antidepressant treatment during breast-feeding.

OBJECTIVE: The primary purpose of this article is to review critically the literature about use of antidepressants during lactation. Strategies for the clinical management of depressed breast-feeding mothers are also suggested. METHOD: The authors conducted a computerized search of MEDLINE for articles. The review includes studies in which serum levels of drugs were obtained from nursing infants. RESULTS: Fifteen published reports were located that provided information for the following nine antidepressants: amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, dothiepin, fluoxetine, sertraline, and bupropion. CONCLUSIONS: Amitriptyline, nortriptyline, desipramine, clomipramine, dothiepin, and sertraline were not found in quantifiable amounts in nurslings, and no adverse effects were reported. Therefore, these are the drugs of choice for breast-feeding women. Adverse effects were described in some young infants whose mothers had been treated with doxepin or fluoxetine during breast-feeding. The collective serum level data suggest that infants older than 10 weeks are at low risk for adverse effects of tricyclics, and there is no evidence of accumulation. Research needs include an expanded database of mother-baby serum levels, behavioral assessments of infants during nursing, and longitudinal developmental evaluation of nurslings. Prescription of an antidepressant for a breast-feeding woman is a case-specific risk-benefit decision.

Risk-benefit decision making for treatment of depression during pregnancy.

OBJECTIVE: The Committee on Research on Psychiatric Treatments of the American Psychiatric Association identified treatment of major depression during pregnancy as a priority area for improvement in clinical management. The goal of this article was to assist physicians in optimizing treatment plans for childbearing women. METHOD: The authors' work group developed a decision-making model designed to structure the information delivered to pregnant women in the context of the risk-benefit discussion. Perspectives of forensic and decision-making experts were incorporated. RESULTS: The model directs the psychiatrist to structure the problem through diagnostic formulation and identification of treatment options for depression. Reproductive toxicity in five domains (intrauterine fetal death, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity) is reviewed for the potential somatic treatments. The illness (depression) also is characterized by symptoms of somatic dysregulation that compromise health during pregnancy. The patient actively participates and provides her evaluation of the acceptability of the various treatments and outcomes. Her capacity to participate in this process provides evidence of competence to consent. Included in the decision-making process are the patient's significant others and obstetrical physician. The process is ongoing, with the need for incorporation of additional data as the pregnancy and treatment response progress. CONCLUSIONS: The conceptual model provides structure to a process that is frequently stressful for both patients and psychiatrists. By applying the model, clinicians will ensure that critical aspects of the risk-benefit discussion are included in their care of pregnant women.

Serum valproate levels in 6 breastfeeding mother-infant pairs.

BACKGROUND: Women with bipolar disorder are at high risk for recurrence of an affective episode in the postpartum period, and treatment with a mood stabilizer may be indicated. Few data are available to inform the risk-benefit decision regarding the use of valproate for women with bipolar disorder who elect to breast-feed. METHOD: Serum valproate levels were obtained from 6 breastfeeding mother-infant pairs. All mothers had a diagnosis of bipolar disorder (Research Diagnostic Criteria) and were taking divalproex sodium as prophylaxis for or treatment of a recurrent affective episode. None of the mothers received valproate during pregnancy. RESULTS: The mothers had serum valproate levels near or within the therapeutic range (39.4 to 79.0 microg/mL). Infant serum levels were low, ranging from 0.7 to 1.5 microg/mL (0.9%-2.3% of maternal serum levels). No adverse clinical effects were observed in the infants. CONCLUSION: Serum valproate levels were low in nurslings of mothers treated with valproate. These data can be used to inform clinical decisions regarding the use of valproate during breastfeeding.

Serum clomipramine and metabolite levels in four nursing mother-infant pairs.

BACKGROUND: Women with postpartum-onset obsessive compulsive disorder may elect treatment with clomipramine. There is minimal information to guide the clinician who must advise breastfeeding women about clomipramine therapy. METHOD: Four clomipramine-treated breastfeeding mother-infant pairs were assessed for serum concentrations of clomipramine, N-desmethylclomipramine, and corresponding 8-hydroxymetabolites. RESULTS: Although the mothers exhibited a wide range of serum concentrations, the parent drug and metabolites were either nondetectable or below the quantifiable limit in the sera of all infants. No adverse clinical effects were observed. CONCLUSION: This report adds to the growing literature that suggests that tricyclic use during breastfeeding rarely results in measurable drug levels in infant sera.

Obsessions and compulsions in women with postpartum depression.

OBJECTIVE: The quantity, content, and intensity of the obsessions and compulsions of women with postpartum onset major depressive disorder were compared with those of women with major depressive disorder with non-postpartum onset. METHOD: Sequential cases of women with postpartum onset major depression (N = 37) and major depression (N = 28) who presented to our Women's Mood Disorders program were included. Psychiatric examination using DSM-IV criteria and the Inventory to Diagnose Depression established the diagnosis of major depression. Obsessive thoughts and compulsions were reported on the Yale-Brown Obsessive Compulsive Scale and reviewed during the psychiatric examination. Comparisons between groups were performed with chi-square statistics, Fisher exact test and its extensions, and Mann-Whitney U test. RESULTS: Although more women with postpartum onset major depression (N = 21, 57%) than major depression (N = 10, 36%) reported obsessional thoughts, the difference between the groups was not significant (p = .13). However, for women who endorsed obsessions, those with postpartum onset had a higher median number (median = 7) than women without postpartum onset (median = 2, p = .00). Most of the difference in frequency of thoughts was owing to more women with postpartum onset major depression having aggressive thoughts (N = 20, 95%) than women with major depression (N = 6, 60%, Fisher exact p = .03). The most frequent content of the aggressive thoughts for women with postpartum onset major depression was causing harm to their newborns or infants. The presence or number of obsessional thoughts or compulsions was not related to severity of the depressive episode. CONCLUSION: Childbearing-aged women commonly experience obsessional thoughts or compulsions in the context of major depressive episodes. Women with postpartum onset major depression experience disturbing aggressive obsessional thoughts more frequently than women with non-postpartum major depression.

Serum fluvoxamine levels in breastfed infants.

BACKGROUND: Between 10% and 15% of new mothers will experience an episode of postpartum depression. Although antidepressants are effective agents for the treatment of postpartum depression, minimal data are available to support their safety in infants of breastfeeding mothers. METHOD: In this article, we present 2 cases of nursing mother-infant pairs in which the mother was treated with fluvoxamine and in which infant serum fluvoxamine levels were obtained. Both mothers began the fluvoxamine treatment postpartum, and serum levels were obtained from mothers and infants after a minimum of 7 days on a stable maternal dose. One level was obtained from the infant in case 1, and 2 levels were obtained from the infant in case 2. RESULTS: Each of the infant serum fluvoxamine levels obtained was too low to quantify (at a limit of detection of 2.5 ng/mL). Neither of the infants experienced adverse events related to the mother's treatment with fluvoxamine. Each of the infants is reportedly healthy 2 to 3 years after the exposure. CONCLUSION: While these results are encouraging, they are limited and cannot be generalized to all cases of infants exposed to fluvoxamine. Additional mother-infant serum fluvoxamine levels and infant behavioral observations will facilitate the risk-benefit decision-making process for women who choose to breast-feed while taking fluvoxamine.

Prevention of recurrent postpartum depression: a randomized clinical trial.

BACKGROUND: Women who have suffered one episode of postpartum-onset major depression (PPMD) comprise a high-risk group for subsequent episodes. We conducted a double-blind, randomized clinical trial to test the efficacy of nortriptyline in the prevention of recurrent PPMD. METHOD: Nondepressed women who had at least one past episode of PPMD (Research Diagnostic Criteria) were recruited during pregnancy. Subjects were randomly assigned to nortriptyline or placebo. Treatment began immediately postpartum. Each subject was assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression and Research Diagnostic Criteria for recurrence of major depression. RESULTS: No difference was found in the rate of recurrence in women treated with nortriptyline compared with those treated with placebo. Of 26 subjects who took nortriptyline preventively, 6 (0.23, 95% exact confidence interval [CI] = 0.09 to 0.44) suffered recurrences. Of 25 subjects who took placebo, 6 (0.24, 95% exact CI = 0.09 to 0.45) suffered recurrence (Fisher exact p = 1.00). CONCLUSION: Nortriptyline did not confer additional preventive efficacy beyond that of placebo. The rate of recurrence of PPMD (one fourth of women) was unacceptably high.

Diminished response to pleasant stimuli by depressed women.

This study examined the self-report and facial expressions of emotional response to pictorial stimuli and the incidental learning of pleasant and unpleasant words by depressed (n = 20) and nondepressed (n = 20) women. Depression was associated with reports of diminished emotional response and reduced frequency and intensity of facial expressions only to pleasant stimuli. The 2 groups did not differ in response to hedonically unpleasant stimuli, even those specifically relevant to the emotion of sadness. In a similar vein, depressed and nondepressed participants showed differences in incidental recall for only pleasant self-referential terms. There was no difference in recall of unpleasant words. These findings suggest the importance of hedonic deficits on psychological processes in clinical depression.

Relationship of psychiatric illness to childbearing status: a hospital-based epidemiologic study.

Women who presented to a University psychiatric hospital were categorized into those with childbearing-related onset illness (CBROI, n = 168) and compared to those with non-childbearing-related onset illness (NCBROI, n = 1004). Women with CBROI were an average of five years younger. The two groups did not differ in membership across five major psychiatric diagnostic categories. However, women with CBROI were given the specific diagnosis adjustment disorder with depressed mood more frequently. Anxiety disorders were also common in women with CBROI. Most women with CBROI had the onset of illness during the postpartum period compared to during pregnancy or after pregnancy loss.

Symptomatology of affective and psychotic illnesses related to childbearing.

Symptom patterns in women with childbearing-related onset illnesses (CBROI) and nonchildbearing-related onset illnesses (NCBROI) were compared. Women with diagnoses of Affective Disorders and Psychoses (n = 762) were divided into four groups: CBROI with psychosis, CBROI with non-psychotic affective illnesses, NCBROI with psychosis, and NCBROI with non-psychotic affective illness. Principal components analysis of 64 symptoms revealed 9 factors. The most dramatic result was the high score for psychotic women with CBROI on the factor cognitive disorganization/psychosis. Psychotic women with CBROI also reported homicidal ideation more frequently. Symptoms of non-psychotic women with CBROI and NCBROI did not differ.

Effects of childbearing on the natural history of panic disorder with comorbid mood disorder.

This historical prospective study included 22 women with panic disorder. They experienced 45 pregnancies associated with or after their first lifetime episode of panic disorder. Mood disorder predated or was associated with 32 of these pregnancies. The most common effect of pregnancy was No Change in symptoms from baseline during pregnancy and continued No Change postnatally for both panic attacks (n = 22; 49%) and depression (n = 19; 59%). The pattern of panic attack across gestations was consistent for only 5 of 14 multiparae. An interesting observation was that first lifetime onset of panic disorder was common postpartum (n = 4) or post-miscarriage (n = 2). First-onset depression was also common postpartum (n = 4).

Psychiatric episodes in women with young children.

An historical cohort study was performed. Subjects were 118 pregnant women or mothers of children of < 3 years who were assessed at presentation to a psychiatric hospital and 5 years later. The relationship of episode onset to childbearing (during pregnancy or within 3 months of birth) was derived from psychiatric records at presentation and retrospectively determined by interview and life-event charting at follow-up. Determining childbearing status from records yielded an error rate of 30% compared with the status derived from direct interview. A change in diagnosis in the ChildBearing-Related Onset Illness (CBROI) category occurred in 50% of subjects. When Research Diagnostic Criteria were applied retrospectively to the presenting episodes, 95% of women with CBROI had affective disorder diagnoses. Clinicians in our intake setting often missed episodes of mania or hypomania in our subjects' histories.

Treatment of phobias in a hospitalized child.

A 12-year-old girl, hospitalized on a psychiatric intensive care unit, was treated for phobias of school and unfamiliar males. Treatment focused on decreasing several avoidance responses and increasing prosocial approach responses. Treatment consisted of instruction, performance feedback, participant modeling and social reinforcement. Marked changes were evident when treatment was introduced in a multiple-baseline design across several phobic and prosocial behaviors. Treatment effects generalized beyond the persons and situation included in training, were reflected in overall global ratings by persons unfamiliar with the treatment, and were maintained up to a 7-week follow-up when the child returned to the hospital for reassessment. Contact with the child 21 weeks after discharge indicated that the gains were reflected in school attendance and social interaction in everyday situations.

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.

RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D. METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n = 25) followed prospectively from third trimester of pregnancy to 3 months postpartum. RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase = 23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase = 19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.