Predictors of Recovery from Depression and Anxiety in Women: A Longitudinal Study from Childbirth to 6 Years.

OBJECTIVE: This study prospectively examined maternal biopsychosocial predictors of recovery from comorbid depression and anxiety from 25 weeks' gestation to 6 years postbirth. Specifically, the study investigated the influence of 1) maternal factors and 2) the child's behaviours and physical health on the course of the mother's depressed mood and anxiety. METHODS: Eighty-six women diagnosed with antenatal depression/anxiety were recruited through the Reproductive Mental Health Program and family practices in Vancouver. Based on the trajectory and status of their symptom remission, participants were categorised into 3 groups: full recovery, partial recovery, and no recovery. The following measures were completed over 6 years: Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) at baseline; Parental Stress Index (PSI) added at 6 months postpartum; Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI-II), and Child Behavior Checklist (CBCL) at 3 years postbirth; and HAM-A, HAM-D, MacArthur Health and Behavior Questionnaire (HBQ-P), and PSI at 6 years postbirth. RESULTS: Factors that predicted full recovery from depression included the absence of maternal health concerns, low total parental stress, and few child behavioural issues, whereas low levels of spousal stress were a significant factor in achieving full recovery from anxiety. CONCLUSION: A variety of maternal and child-related factors govern full recovery or sustained remission of depression/anxiety in the postpartum up to 6 years postbirth. Early awareness of these predictors could lead to timely interventions, ensuring long-term maternal-child well-being.

Generalized Anxiety Disorder and Major Depressive Disorder in Pregnant and Postpartum Women: Maternal Quality of Life and Treatment Outcomes.

OBJECTIVES: Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) in perinatal women is often under-diagnosed, resulting in suboptimal treatment and leading to significant maternal dysfunction. We describe a prospective, longitudinal study of the course, treatment outcomes, and quality of life (QoL) in pregnant and postpartum women with MDD and anxiety disorders. METHODS: Two separate cohorts of women were recruited through the Reproductive Mental Health Program, Women's and Children's Hospital, Vancouver, British Columbia, for pharmacotherapy of depressed mood. One cohort was recruited during pregnancy and followed to one month postpartum; the other cohort was recruited postpartum and followed for 12 weeks. All women met the DSM-5 criteria for MDD and anxiety disorders. This non-lactating perinatal population completed measures of depression, anxiety, worry symptoms, and QoL at multiple study visits. Depressed women with GAD or excessive worry were compared to those without GAD in each cohort. RESULTS: Analysis revealed that despite the majority of women with MDD having remission of symptoms with treatment, those with postpartum GAD displayed a poorer quality of life, with persistent worry symptoms, and their illness was slower to remit. Pregnant depressed women with uncontrollable worry (a GAD indicator) showed a lower probability of achieving remission of symptoms with treatment than those without uncontrollable worry. CONCLUSION: All pregnant and postpartum women with GAD and MDD responded to pharmacotherapy, and the majority attained complete remission of MDD. However, their GAD symptoms persisted, and their QoL was compromised. Given the chronic debilitating course of concomitant MDD and GAD in the perinatal population, it is essential to focus on adjunctive therapies to aim for full recovery.

Objectifs : La présence comorbide d'un trouble d'anxiété généralisée (TAG) et d'un trouble dépressif majeur (TDM) pendant la période périnatale est souvent sous-diagnostiquée, ce qui se traduit en un traitement sous-optimal et qui mène à un dysfonctionnement maternel important. Nous décrivons une étude longitudinale prospective de l'évolution, des résultats du traitement et de la qualité de vie (QdV) chez des femmes enceintes et en postpartum qui présentent un TDM et des troubles anxieux. Méthodes : Deux cohortes distinctes de femmes ont été recrutées par l'intermédiaire du Reproductive Mental Health Program du Women's and Children's Hospital de Vancouver, en Colombie-Britannique, aux fins de la mise en œuvre d'une pharmacothérapie visant l'humeur dépressive : une cohorte a été recrutée pendant la grossesse et a fait l'objet d'un suivi postpartum d'un mois, tandis que l'autre cohorte a été recrutée pendant la période postpartum et a fait l'objet d'un suivi de 12 semaines. Toutes les femmes répondaient aux critères du DSM-5 pour ce qui est du TDM et des troubles anxieux. Les femmes de cette population périnatale n'étant pas en lactation ont rempli des mesures de la dépression, de l'anxiété, des symptômes d'inquiétude et de la QdV dans le cadre de multiples consultations menées aux fins de l'étude. Les femmes déprimées qui connaissaient un TAG ou des inquiétudes excessives ont été comparées aux femmes ne connaissant pas un TAG au sein de chacune des cohortes. Résultats : L'analyse a révélé que malgré le fait que le traitement ait donné lieu à une rémission des symptômes chez la majorité des femmes connaissant un TDM, les femmes connaissant un TAG postpartum présentaient une qualité de vie moindre, s'accompagnant de symptômes d'inquiétude persistants, et la rémission de leur maladie était plus lente. Les femmes enceintes déprimées qui connaissaient des inquiétudes incontrôlables (un indicateur de TAG) ont présenté une probabilité moindre d'obtenir la rémission de leurs symptômes à la suite de la mise en œuvre d'un traitement, par comparaison avec les femmes qui ne connaissaient pas d'inquiétudes incontrôlables. Conclusion : Toutes les femmes enceintes et en postpartum qui présentaient un TAG et un TDM ont réagi à la pharmacothérapie, et la majorité d'entre elles ont obtenu la rémission complète du TDM. Toutefois, leurs symptômes TAG ont persisté et leur QdV a été compromise. Compte de l'évolution débilitante chronique de la présence concomitante d'un TDM et d'un TAG au sein de la population périnatale, il s'avère essentiel de centrer les traitements adjuvants sur l'obtention d'une récupération complète.

Factors impacting decisions to decline or adhere to antidepressant medication in perinatal women with mood and anxiety disorders.

PURPOSE: To identify specific quantitative and qualitative factors that govern the decision to adhere or decline antidepressant medication in antenatal women with moderate-to-severe mood and anxiety disorders. METHODS: Fifty women (30 adherers, 20 decliners) were recruited between 18 and 34 weeks gestation in a tertiary care clinic for perinatal mothers. They were prospectively monitored 4 weeks apart up to 1-month postpartum on the: Hamilton Anxiety Scale, Hamilton Depression Scale, Mood Disorders Insight Scale, Antidepressant Compliance Questionnaire, Penn State Worry Questionnaire, and NEO Personality Inventory. Qualitative interviews were conducted at baseline. Hierarchical linear modeling determined illness trajectories of the two groups. RESULTS: Significantly different course of illness was observed in adherers versus decliners. Adherers had healthier attitudes toward depression and compliance with medication (P < .005). Decliners had less illness insight (P < .001) and cited fear of fetal exposure, and thought medication was unwarranted. CONCLUSIONS: Pregnant women experienced significantly divergent illness trajectories depending on if they accepted antidepressant medication therapy for their illness. Risk perception, attitudes, and illness insight impacted decisions surrounding adherence and decline.

Biopsychosocial determinants of treatment outcome for mood and anxiety disorders up to 8 months postpartum.

Little is known about the biopsychosocial determinants that predict postpartum treatment outcome for mood and anxiety disorders. Postpartum mood and anxiety symptoms and psychosocial/biological variables were recorded for 8 months of 22 women treated with antidepressants during pregnancy. Depression scores decreased by 58%, whereas anxiety scores decreased by 35%. Family history of psychiatric illness and prior psychiatric illness unrelated to pregnancy predicted depressive treatment outcome, and sexual abuse history and prior psychiatric illness unrelated to pregnancy predicted anxiety outcome. Biological and psychosocial variables predicted pharmacological treatment outcome in postpartum-depressed and anxious women.

Antenatal depression and anxiety affect postpartum parenting stress: a longitudinal, prospective study.

OBJECTIVE: Postpartum depression has been associated with parenting stress, impacting attachment and child development. However, the relation between antenatal depression or anxiety and postpartum parenting stress has not been investigated. We studied the effect of antenatal depression and anxiety and treatment with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (antidepressants [ADs]) on postpartum parenting stress. METHOD: Ninety-four pregnant women (part of a larger study examining prenatal AD exposure on infants) were prospectively monitored for depression and anxiety during the third trimester and 3- and 6-months postpartum using the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale. Parenting stress was assessed using the Parenting Stress Index-Short Form at 3- and 6-months postpartum. RESULTS: Both antenatal third trimester depression and anxiety were significant predictors of 3- and 6-month postpartum parenting stress, after controlling for maternal age, number of children, and exposure to prenatal ADs (all Ps < 0.001). Third trimester depression accounted for 13% to 22% of the variance in postpartum stress at 3 and 6 months. Prenatal AD use was not a significant predictor in any of the models (all Ps > 0.2). Twenty of 41 mothers on ADs achieved remission (HDRS = 7) in pregnancy and had average parenting stress scores of about 1 standard deviation lower than those who did not at 3- and 6-months postpartum (t = 3.32, df = 32, P = 0.002 and t = 2.52, df = 32, P = 0.02, respectively). CONCLUSIONS: Our findings indicate that antenatal depression and anxiety directly impact postpartum parenting stress, regardless of antenatal AD treatment. Ongoing maternal mental illness in pregnancy is an important predictor of postpartum parenting stress. Early recognition and treatment to remission is key.

Caregiving behavior and interactions of prenatally depressed mothers (antidepressant-treated and non-antidepressant-treated) during newborn acute pain.

This exploratory study aimed to examine time-based measures of the behaviors and interactions of prenatally depressed serotonin reuptake inhibitors (SRI)-medicated mothers to their infant's pain (n = 10) by comparing them with similar measures obtained from prenatally depressed nonmedicated mothers and their infants (n = 10), and nondepressed mothers and their infants (n = 10). During the second trimester of their pregnancy, the 30 study mothers were assessed for depression and anxiety, with no further measures of maternal mood taken. Maternal and infant interactions were continuously videorecorded while the infant underwent a scheduled heel lance for routine blood screening that occurred when study infants were between the ages of 24 and 60 hr. Maternal behavior and infant cry, for all 30 cases, were coded second-by-second for the full duration of each infant's heel lance using a reliable coding system and analyzed using odds ratio and regression analyses. Infants exposed to prenatal SRIs and depressed maternal mood were more likely to have lower Apgar scores and to exhibit weak and absent cry. Even when duration of the heel lance was controlled for, women with depression during the second trimester were more likely to exhibit depressed behavior at 2 days' postpartum despite sustained SRI antidepressant treatment. Both groups of prenatally depressed mothers were more likely to exhibit diminished response to their infants' pain cue although nonmedicated mothers' expressions of depressed behavior were more similar to healthy controls. Comprehensive understanding is essential to optimize the clinical care of mothers and their infants in this complex setting. This study contributes preliminary new findings that warrant prospective and longitudinal studies to clarify further the impacts of prenatal SRI and maternal mental mood (e.g., chronic depression and anxiety) effects on the mother-infant interaction and infant pain and stress reactivity.

Hypothalamic-pituitary-adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure.

BACKGROUND: Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic-pituitary-adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown. OBJECTIVE: To examine HPA basal levels and stress responsiveness in 3-month olds with prenatal exposure to SSRIs. METHODS: Salivary cortisol levels in infants of SSRI treated mothers (n=31, mean exposure 230.2+/-72.2 days) were compared with non-SSRI exposed (n=45) infants in response to a challenge (infant-controlled habituation task) and under basal conditions in the late afternoon/early evening. Mode of feeding, to account for possible postnatal drug exposure via breast milk, as well as measures of pre and postnatal maternal mood, were included as covariates. RESULTS: Lower post-stress cortisol levels were observed in non-SSRI exposed/non-breastfed infants compared with non-SSRI exposed infants who were breastfed at 3 months of age. Stress reactivity patterns among SSRI exposed infants did not differ with mode of feeding. The cortisol reactivity slope (CRS) was significantly lower among non-SSRI exposed non-breastfed infants compared with non-SSRI exposed breastfed infants. Early evening basal cortisol levels were lower in SSRI exposed infants than in non-SSRI exposed infants, controlling for maternal mood and mode of feeding. Postnatal SSRI exposure (infant SSRI drug levels) via breast milk was not associated with stress or basal cortisol levels. Total cortisol, reflected by the AUC measure, did not differ significantly between exposure groups. CONCLUSIONS: Prenatal SSRI exposure altered HPA stress response patterns and reduced early evening basal cortisol levels. Stress challenge HPA response differences only became apparent when the moderating effect of method of feeding was accounted for. These findings suggest an early "programming" effect of antenatal maternal mood, prenatal SSRI exposure and postnatal maternal care giving on the HPA system.

Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data.

BACKGROUND: To determine a population-based incidence of congenital anomalies following prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants used alone and in combination with a benzodiazepines (BZ). METHODS: Population health data, maternal health, and prenatal prescription records were linked to neonatal records, representing all live births (British Columbia, Canada, N=119,547) during a 39-month period (1998-2001). The incidence and risk differences (RD) for major congenital anomalies (CA) and congenital heart disease (CHD), including ventricular and atrial septal defects (VSD, ASD), from infants of mothers treated with an SRI alone, a benzodiazepine (BZ) alone, or SRI+BZ in combinationcompared to outcomesno exposure. RESULTS: Risk for a CA or CHD did increase following combined SRI+BZ exposure compared with no exposure. However, using a weighted regression model, controlling for maternal illness characteristics, combination therapy risk remained significantly associated only with CHD. The risk for an ASD was higher following SRI monotherapy compared with no exposure, after adjustment for maternal covariates. Dose/day was not associated with increased risk. CONCLUSIONS: Infants exposed to prenatal SRIs in combination with BZs had a higher a incidence of CHD compared to no exposure, even after controlling for maternal illness characteristics. SRI monotherapy was not associated with an increased risk for major CA, but was associated with an increased incidence of ASD. Risk was not associated with first trimester medication dose/day.

Feasibility of a mindfulness-based cognitive therapy group intervention as an adjunctive treatment for postpartum depression and anxiety.

BACKGROUND: Many women experience moderate-to-severe depression and anxiety in the postpartum period for which pharmacotherapy is often the first-line treatment. Many breastfeeding mothers are reticent to increase their dose or consider additional medication, despite incomplete response, due to potential adverse effects on their newborn. These mothers are amenable to non-pharmacological intervention for complete symptom remission. The current study evaluated the feasibility of an eight-week mindfulness-based cognitive therapy (MBCT) intervention as an adjunctive treatment for postpartum depression and anxiety. METHODS: Women were recruited at an outpatient reproductive mental health clinic based at a maternity hospital. Participants had a diagnosis of postpartum depression/anxiety within the first year following childbirth. They were enrolled in either the MBCT intervention group (n = 14) or the treatment-as-usual control group (n = 16), and completed the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and the Mindful Attention Awareness Scale (MAAS) at baseline and at 4 weeks, 8 weeks, and 3 months following baseline. RESULTS: Multivariate analyses demonstrated that depression and anxiety levels decreased, and mindfulness levels increased, in the MBCT group, but not in the control group. Many of the between-group and over time comparisons displayed trends towards significance, although these differences were not always statistically significant. Additionally, the effect sizes for anxiety, depression, and mindfulness were frequently large, indicating that the MBCT intervention may have had a clinically significant effect on participants. LIMITATIONS: Limitations include small sample size and the non-equivalent control group design. CONCLUSIONS: We demonstrated that MBCT has potential as an adjunctive, non-pharmacological treatment for postpartum depression/anxiety that does not wholly remit with pharmacotherapy. (249 words).

Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy.

OBJECTIVE: To evaluate attentional and activity behaviors in 4-year-olds following prenatal selective serotonin reuptake inhibitor (SSRI) exposure. DESIGN: Prospective cohort design. SETTING: Tertiary care center. PARTICIPANTS: Twenty-two 4-year-olds with prolonged prenatal SSRI medication exposure and 14 children without prenatal exposure. MAIN EXPOSURE: Prenatal SSRI exposure. MAIN OUTCOME MEASURES: Group differences in externalizing behaviors (according to the Child Behavior Checklist) and direct observations of child attention, activity, and impulsiveness in a laboratory setting using the procedure by Crowell and colleagues were compared, including measures of the duration of prenatal SSRI exposure, umbilical cord drug levels, a history of poor neonatal adaptation, and maternal mood. RESULTS: Externalizing behaviors did not differ between groups. Maternal depression and anxiety at the 4-year follow-up were associated with increased reports of externalizing behaviors. Increased externalizing behaviors were associated with increased umbilical cord drug levels (F(1,34) = 6.3; P = .02), but when controlling for maternal depressed mood at the 4-year follow-up, such levels only accounted for 11.2% of the behavioral outcomes (P>.05). On direct observation, the persistence score for child behavior was significantly lower in the exposed group. Increased aggressiveness scores were associated with a history of poor neonatal adaptation, even when parental report of stress was added to the model (F(1,34) = 4.0; P = .03); however, neither parental report of stress nor poor neonatal adaptation were significant (both P = .09), suggesting that both are important, if not unique, predictors of child behavior. CONCLUSIONS: These findings suggest that the best predictors of externalizing behaviors at age 4 years are current maternal mood and parental stress, regardless of prenatal depressed mood and SSRI treatment during pregnancy. It remains uncertain whether poor neonatal adaptation can be excluded as a possible predictor of externalizing behaviors.

Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data.

CONTEXT: Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression both alter neonatal health, and distinguishing the effects of each influence remains challenging. OBJECTIVE: To determine whether exposure to SSRIs and depression differs from exposure to maternal depression alone. DESIGN: Using population health data, records of neonatal birth outcomes were linked to records of maternal health and prenatal maternal prescriptions for SSRIs. SETTING: Population of British Columbia, Canada. PARTICIPANTS: Mothers and their infants, representing all live births during a 39-month period (N = 119,547) (1998-2001). MAIN OUTCOME MEASURES: Outcomes from infants of depressed mothers treated with SSRIs (SE-D) were compared with outcomes from infants of depressed mothers not treated with medication (DE) and nonexposed controls. To control for maternal mental illness severity, propensity score matching was used to identify a comparison group of DE mothers who were similar to the SE-D mothers in characteristics in the year preceding and during pregnancy. RESULTS: Fourteen percent of mothers were diagnosed as having depression during their pregnancy, and the incidence of prenatal SSRI exposure increased from 2.3% to 5.0% during a 39-month period. Birth weight and gestational age for SE-D infants were significantly less than for DE infants, as was the proportion of infants born at less than 37 weeks (95% confidence interval [CI], -1 to -64, -0.25 to -0.45, and -0.009 to -0.04, respectively), although differences in the incidence of birth weight less than the 10th percentile for gestational age were not significant. An increased proportion of SE-D infants had neonatal respiratory distress (13.9% vs 7.8%), jaundice (9.4% vs 7.5%), and feeding problems (3.9% vs 2.4%) compared with DE infants (95% CI of difference, 0.042-0.079, 0.003-0.334, and 0.005-0.025, respectively). When outcomes were compared between SE-D and propensity score-matched DE neonates, SE-D was associated with increased incidence of birth weight below the 10th percentile and rates of respiratory distress. CONCLUSION: With linked population health data and propensity score matching, prenatal SE-D exposure was associated with an increased risk of low birth weight and respiratory distress, even when maternal illness severity was accounted for.

Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications.

OBJECTIVE: Internalizing behaviors in children between 4 and 5 years of age who had been prenatally exposed to psychotropic medications were investigated. The authors had previously reported the effects of prenatal medication exposure in this same cohort when they were newborns and infants at 3 and 8 months of age. METHOD: Parental/teacher reports and a clinical measure of mother and child interactions were used to assess levels of internalizing behaviors (e.g., depression, anxiety, withdrawal). Outcomes were compared between children with prenatal selective serotonin reuptake inhibitor (SSRI) exposure (N=22) and nonexposed children of healthy, nondepressed, nonmedicated mothers (N=14). Measures of maternal mood were obtained. Ordered logistic regressions, independent-sample t tests, and univariate ANOVAs were used to compare outcomes between groups. Pearson correlations were used to determine associations between maternal mood and child behaviors. RESULTS: Levels of internalizing behaviors did not differ significantly between children with prenatal psychotropic medication exposure and those not exposed. However, as symptoms of maternal anxiety and depression increased, so did reported internalizing behaviors in their children. CONCLUSIONS: Prenatal exposure to psychotropic medications was not associated with increased reports of internalizing behaviors at 4 years of age, whereas impaired maternal mood did have an identified impact on child behavior. Further study of complex associations between maternal psychiatric disorders, prenatal SSRI exposure, and childhood internalizing behaviors is required to understand if the child outcome is affected by the illness, medications, or a combination of both.

The impact of treatment intervention on parenting stress in postpartum depressed mothers: a prospective study.

The aim of this study was to evaluate whether treatment intervention for postpartum depression impacted maternal parenting stress levels. Twenty-three mothers referred for postpartum mood and anxiety disorder to an outpatient program were included in the study. Statistically and clinically significant decreases in levels of parenting stress were evident at the end of the treatment. Subjects' perceptions of their parenting characteristics were found to be a major contributor to stress levels. In addition to monitoring of depressive symptoms, routine assessment of maternal parenting qualities is recommended to ensure healthy child outcomes.

Overcoming functional impairment in postpartum depressed or anxious women: a pilot trial of desvenlafaxine with flexible dosing.

OBJECTIVES: Antidepressants are the first line treatment for moderate to severe major depressive disorder (MDD) in perinatal and general populations. However, there appears to be paucity of evidence around antidepressant use in women with postpartum depression or anxiety. Selection of an appropriate antidepressant is crucial in promoting efficacy, optimizing tolerability, and managing comorbid anxiety or depression. Our aim was to investigate the treatment effect and tolerability profile of desvenlafaxine, and to examine the functionality of women with postpartum depression or anxiety after desvenlafaxine treatment. METHODS: Fifteen postpartum women with depression or anxiety completed this 12-week prospective pilot study with a flexible dose of desvenlafaxine (50-100 mg). Participants were recruited at a tertiary care level program. Measures of depression (Montgomery-Åsberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAM-A), worry (Penn State Worry Questionnaire, PSWQ) and functional impairment (Sheehan Disability Scale, SDS) were completed at baseline, 8 weeks, and 12 weeks. RESULTS: In the intention-to-treat analysis (n = 17), the majority of women responded to medication (88.2%, n = 15), and reached remission of depressive (82.4%, n = 14) and anxiety symptoms (82.4%, n = 14). Remission of depression was achieved in a mean of 6.9 weeks [standard deviation (SD) = 3.01] at a mean dose of 71 mg/day (SD = 25.7). Significant decreases were observed on PSWQ worry scores (p < 0.0001) and SDS scores for social (p < 0.0001) and family life impairment (p < 0.0001). The medication was generally well tolerated. CONCLUSION: The results of our prospective pilot study suggest that treatment with desvenlafaxine of postpartum mothers with depression or anxiety can lead to symptom remission and restoration of functionality.

Perinatal Generalized Anxiety Disorder: Assessment and Treatment.

Perinatal generalized anxiety disorder (GAD) has a high prevalence of 8.5%-10.5% during pregnancy and 4.4%-10.8% postpartum. Despite its attendant dysfunction in the patient, this potentially debilitating mental health condition is often underdiagnosed. This overview will provide guidance for clinicians in making timely diagnosis and managing symptoms appropriately. A significant barrier to the diagnosis of GAD in the perinatal population is difficulty in distinguishing normal versus pathological worry. Because a perinatal-specific screening tool for GAD is nonexistent, early identification, diagnosis and treatment is often compromised. The resultant maternal dysfunction can potentially impact mother-infant bonding and influence neurodevelopmental outcomes in the children. Comorbid occurrence of GAD and major depressive disorder changes the illness course and its treatment outcome. Psychoeducation is a key component in overcoming denial/stigma and facilitating successful intervention. Treatment strategies are contingent upon illness severity. Cognitive behavior therapy (CBT), relaxation, and mindfulness therapy are indicated for mild GAD. Moderate/severe illness requires pharmacotherapy and CBT, individually or in combination. No psychotropic medications are approved by the FDA or Health Canada in pregnancy or the postpartum; off-label pharmacological treatment is instituted only if the benefit of therapy outweighs its risk. SSRIs/SNRIs are the first-line treatment for anxiety disorders due to data supporting their efficacy and overall favorable side effect profile. Benzodiazepines are an option for short-term treatment. While research on atypical antipsychotics is evolving, some can be considered for severe manifestations where the response to antidepressants or benzodiazepines has been insufficient. A case example will illustrate the onset, clinical course, and treatment strategies of GAD through pregnancy and the postpartum.

The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial.

BACKGROUND: Approximately 10% to 16% of women experience a major depressive episode after childbirth. A significant proportion of these women also suffer from comorbid anxiety disorders. The purpose of this study was to evaluate whether the addition of cognitive-behavioral therapy (CBT) to standard antidepressant therapy offers additional benefits in the treatment of post-partum depression with comorbid anxiety disorders. METHOD: Thirty-five women referred to a tertiary care hospital outpatient program with a DSM-IV diagnosis of postpartum depression with comorbid anxiety disorder were randomly assigned to 1 of 2 treatment groups-paroxetine-only monotherapy group (N = 16) or paroxetine plus 12 sessions of CBT combination therapy group (N = 19)-for a 12-week trial. Progress was monitored by a psychiatrist blinded to treatment group, using the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Yale-Brown Obsessive Compulsive Scale, Clinical Global Impressions scale, and Edinburgh Postnatal Depression Scale. Data were analyzed using 2-tailed statistical tests at an alpha level of.05. The study was conducted from April 1, 2002, to June 30, 2003. RESULTS: Both treatment groups showed a highly significant improvement (p <.01) in mood and anxiety symptoms. Groups did not differ significantly in week of recovery, dose of paroxetine at remission, or measures of depression, anxiety, and obsessive-compulsive symptoms at outcome. CONCLUSION: Antidepressant monotherapy and combination therapy with antidepressants and CBT were both efficacious in reducing depression and anxiety symptoms. However, in this sample of acutely depressed/anxious postpartum women, there were no additional benefits from combining the 2 treatment modalities. Further research into the efficacy of combination therapy in the treatment of moderate-to-severe depression with comorbid disorders in postpartum women is recommended.

Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure.

BACKGROUND: Selective serotonin reuptake inhibitor antidepressants (SSRIs) and benzodiazepines are frequently used to treat maternal depression and anxiety disorders during pregnancy. Recent reports suggest that prenatal SSRI exposure is associated with a neonatal discontinuation syndrome. It remains unclear whether these symptoms are directly related to SSRI exposure alone or are due to concurrent pharmacologic factors. Also, this study explores relationships between neonatal outcomes and medication levels during pregnancy, at delivery, and in the newborn period. METHOD: This study sought to compare newborn behavior following second and third trimester exposure to either single-agent SSRIs (group 1) or SSRIs combined with clonazepam (group 2). A prospective cohort of mothers and their infants (N = 46) who had received SSRI medication alone or in combination with clonazepam were studied from June 1996 through June 2000 and compared with a nonexposed control group (N = 23). Infants were assessed in the newborn period for signs suggestive of a "discontinuation syndrome." Maternal drug levels were measured during the pregnancy and at delivery. Infant drug levels from cord blood and at day 2 of life were also obtained. RESULTS: Overall, 30% of the exposed infants (groups 1 and 2, N = 14) showed symptoms of transient poor neonatal adaptation compared with 9% (N = 2) of control infants. In group 1, 25% had symptoms (fluoxetine N = 3; paroxetine N = 3; sertraline N = 1) and in group 2, 39% of infants had symptoms (paroxetine with clonazepam, N = 7). Symptoms were typically mild respiratory distress and, less commonly, hypotonia. Symptoms were self limited and not associated with other neonatal conditions. When paroxetine was combined with clonazepam, infants with symptoms had significantly elevated paroxetine levels when compared with similarly exposed infants without symptoms (p <.05). Among single-agent paroxetine-exposed infants, drug levels did not differ significantly between those with and without symptoms. Maternal dose of clonazepam was significantly higher (p <.05) during pregnancy and at delivery among symptomatic infants compared with nonsymptomatic infants. Developmental outcomes at 2 and 8 months of age did not differ between symptomatic and nonsymptomatic infants. CONCLUSION: While transient neonatal symptoms were found in infants after single-agent prenatal exposure to SSRIs and when paroxetine was combined with clonazepam, the addition of clonazepam appeared to alter paroxetine metabolism, leading to increased drug levels and risk for transient neonatal symptoms. These data highlight the importance of accounting for a variety of pharmacologic factors beyond single-agent SSRI exposure that may lead to poor neonatal adaptation. Further studies are needed with a larger sample of infants to determine the role of clonazepam and whether similar outcomes occur when exposure includes other SSRIs in combination with clonazepam.

Benefits and risks to mother and infant of drug treatment for postnatal depression.

The postnatal period presents a special problem to healthcare providers treating psychiatric disorders in women. Many new mothers who need antidepressant treatment may wish to breastfeed their infants, but are hesitant to do so for fear of passing on possible harmful effects of the medication through their milk. The focus of this article will be on highlighting and interpreting the existing literature on the benefits and risks to mother and infant of drug treatment for postnatal depression, as well as outlining treatment guidelines for the use of antidepressants in breastfeeding mothers. The article will specifically focus on the use of fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram, which are more commonly used and belong to the selective serotonin reuptake inhibitor group of antidepressants. The tricyclic and other newer antidepressant medications will also be discussed. As there are no published controlled studies on the use of antidepressants by breastfeeding women, publications of individual case reports, case series, and pharmacokinetic investigations serve as the basis for the development of treatment guidelines. Results from this growing body of literature are promising in that, with the exception of a few cases, no serious adverse events have been reported in infants exposed to antidepressant medications through breast milk. In addition nonpharmacological treatments consisting of different types of psychotherapies will be discussed. It is critical that healthcare providers evaluate each mother-infant dyad on an individual basis when faced with the decision to prescribe antidepressant medications during the postnatal period.

Affect Expression and Self-Regulation Capacities of Infants Exposed in utero to Psychotropics.

This study explored the affect expression and self-regulation capacities of 8-month-old infants exposed in utero to psychotropic medications. This was a continuation of our previous study conducted on the same cohort when the infants were 3 months old. Psychotropics implicated included selective serotonin reuptake inhibitors (SSRIs), and a benzodiazepine derivative anxiolytic (clonazepam). The three comparison groups were: control (n = 23; infants not exposed to psychotropics in utero), SSRI-alone (n = 22; infants exposed to SSRIs only and having mothers who had a primary diagnosis of depressive disorder without having comorbid anxiety disorder), and SSRI+ group (n = 15; infants gestationally exposed to SSRIs and clonazepam and having mothers that had both clinical depression and anxiety disorder). Using the Parent-Child Early Relational Assessment Scale, infants were assessed in a dyadic context during free play and a structured task. There were significant differences in psychotropic exposed and non-exposed dyads regarding infant negative affect management. There were significant associations between the SSRI+ group of mothers and infant negative affect. This group of mothers also showed significant associations with infants' averting and avoiding behaviors in both play situations. The SSRI-alone group was similar to the control group and showed variable associations with infant's positive, negative, and sober moods unlike the SSRI+ group. There were no differences in infants' capacity for self-regulation in psychotropic exposed and non-exposed groups. Increased awareness of these vulnerable subgroups (SSRI-alone and SSRI+) is needed, in order to safeguard these dyads through better support systems and improved management.