The efficacy of antidepressant medication and interpersonal psychotherapy for adult acute-phase depression: study protocol of a systematic review and meta-analysis of individual participant data.

BACKGROUND: Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, 'conventional' meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis. AIMS: We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891). METHOD: We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies. CONCLUSIONS: This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

Delayed sleep timing and circadian rhythms in pregnancy and transdiagnostic symptoms associated with postpartum depression.

Later sleep timing, circadian preference, and circadian rhythm timing predict worse outcomes across multiple domains, including mood disorders, substance use, impulse control, and cognitive function. Disturbed sleep is common among pregnant and postpartum women. We examined whether sleep timing during third trimester of pregnancy predicted postpartum symptoms of mania, depression, and obsessive-compulsive disorder (OCD). Fifty-one women with a previous, but not active, episode of unipolar or bipolar depression had symptoms evaluated and sleep recorded with wrist actigraphy at 33 weeks of gestation and 2, 6, and 16 weeks postpartum. Circadian phase was measured in a subset of women using salivary dim light melatonin onset (DLMO). We divided the sample into "early sleep" and "late sleep" groups using average sleep onset time at 33 weeks of gestation, defined by the median-split time of 11:27 p.m. The "late sleep" group reported significantly more manic and depressive symptoms at postpartum week 2. Longer phase angle between DLMO and sleep onset at 33 weeks was associated with more manic symptoms at postpartum week 2 and more obsessive-compulsive symptoms at week 6. Delayed sleep timing in this sample of at-risk women was associated with more symptoms of mania, depression, and OCD in the postpartum period. Sleep timing may be a modifiable risk factor for postpartum depression.

Premenstrual Dysphoric Disorder.

Premenstrual dysphoric disorder (PMDD) comprises emotional and physical symptoms and functional impairment that lie on the severe end of the continuum of premenstrual symptoms. Women with PMDD have a differential response to normal hormonal fluctuations. This susceptibility may involve the serotonin system, altered sensitivity of the GABAA receptor to the neurosteroid allopregnanalone, and altered brain circuitry involving emotional and cognitive functions. Serotonin reuptake inhibitors are considered the first-line treatment. Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.

A placebo controlled treatment trial of sertraline and interpersonal psychotherapy for postpartum depression.

BACKGROUND: The purpose of the present study was to test the efficacy of sertraline and Interpersonal Psychotherapy (IPT) relative to pill placebo in a two site randomized controlled trial over a period of 12 weeks. It was hypothesized that sertraline and IPT would be more efficacious than pill placebo with respect to depression and social adjustment. METHODS: 162 breastfeeding and non-breastfeeding women experiencing a major depressive episode in the first year postpartum from two sites in Iowa and Rhode Island were randomly assigned to IPT, sertraline-clinical management (CM), or pill placebo-CM. CM included infant-focused psychoeducation. Interview-based and self-report measures of depression and social adjustment were obtained at baseline, 4-weeks, 8-weeks, and 12-weeks of treatment. Linear mixed effects regression (LMER) was used for the longitudinal data analysis. RESULTS: There was no significant effect for treatment condition associated with the primary outcome measure, the HamD-17, but there was a significant effect for sertraline-CM relative to the IPT and placebo conditions over the duration of the trial based on the General Depression scale of the Inventory of Depression and Anxiety Symptoms. There was a main effect for time in that study subjects across all three conditions showed significant improvement for the duration of the trial. LIMITATIONS: Limitations of the present study included significant non-engagement with assigned condition and differential effects of IPT across the two study sites. CONCLUSIONS: There was improvement for all postpartum women in all conditions. The results do suggest that active interventions with or without medication delivered over a period of twelve weeks can lead to significant improvement in depression and social adjustment among postpartum women. ClinicalTrials.gov identifier: NCT00602355.

Premenstrual Dysphoric Disorder.

Premenstrual dysphoric disorder (PMDD) comprises emotional and physical symptoms and functional impairment that lie on the severe end of the continuum of premenstrual symptoms. Women with PMDD have a differential response to normal hormonal fluctuations. This susceptibility may involve the serotonin system, altered sensitivity of the GABAA receptor to the neurosteroid allopregnanalone, and altered brain circuitry involving emotional and cognitive functions. Serotonin reuptake inhibitors are considered the first-line treatment. Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Infant sleep and feeding patterns are associated with maternal sleep, stress, and depressed mood in women with a history of major depressive disorder (MDD).

Our goal was to examine associations of infant sleep and feeding patterns with maternal sleep and mood among women at risk for postpartum depression. Participants were 30 women (age ± SD = 28.3 ± 5.1 years) with a history of MDD (but not in a mood episode at enrollment) who completed daily sleep diaries, wore wrist actigraphs to estimate sleep, and had their mood assessed with the Hamilton Depression Rating Scale (HAM-D-17) during four separate weeks of the perinatal period (33 weeks pregnancy and weeks 2, 6, and 16 postpartum). They logged their infants' sleep and feeding behaviors daily and reported postnatal stress on the Childcare Stress Inventory (CSI) at week 16. Mothers' actigraphically estimated sleep showed associations with infant sleep and feeding patterns only at postpartum week 2. Shorter duration of the longest infant-sleep bout was associated with shorter maternal sleep duration (p = .02) and lower sleep efficiency (p = .04), and maternal sleep efficiency was negatively associated with the number of infant-sleep bouts (p = .008) and duration of infant feeding (p = .008). Neither infant sleep nor feeding was associated with maternal sleep at 6 or 16 weeks, but more disturbed infant sleep and more frequent feeding at 6 weeks were associated with higher HAM-D scores at 6 and 16 weeks and higher CSI scores. Sleep in the mother-infant dyad is most tightly linked in the early postpartum weeks, but mothers continue to experience disturbed sleep and infant sleep and feeding behaviors continue to be associated with mothers' depressive symptoms and stress ratings as long as 16 weeks postpartum. These data imply that interventions designed to improve maternal sleep and postpartum mood should include both mothers and infants because improving infant sleep alone is not likely to improve maternal sleep, and poor infant sleep is linked to postpartum depression and stress.

Depression during Pregnancy.

A proportion of women enter pregnancy with active psychiatric symptoms or disorders, with or without concomitant psychotropic medication. Studies report that exposure to untreated depression and stress during pregnancy may have negative consequences for birth outcome and child development. Studies also report that antenatal exposure to antidepressant medications may have adverse consequences for birth outcome and child development. Antidepressant medication use during pregnancy leads to a small increased risk of miscarriage, a possible small increased risk of congenital cardiac malformations, a small increased risk of preterm birth, a small increased risk of persistent pulmonary hypertension of the newborn (PPHN), and transient neonatal symptoms in up to one-third of neonates. In addition, there is a possible increased risk of delayed motor development in children. Several recent systematic reviews and meta-analyses of the existent literature emphasize that there are minimal definitive conclusions to guide treatment recommendations. This review describes best practices for the management of depression in pregnancy, and it provides suggestions for future research.

Use of psychotropic medication during pregnancy and the postpartum period.

Women with active psychiatric disorders who become pregnant face treatment dilemmas. Although results from studies are inconsistent, small but significant, risks on birth outcomes occur with exposure to untreated disorders, as well as to psychotropic medications. Prenatal antidepressant medication exposure may increase the risk for spontaneous miscarriage, preterm birth, cardiac malformations, persistent pulmonary hypertension of the newborn and postnatal adaptation syndrome. The use of valproate is contraindicated during pregnancy due to teratogenicity and neurocognitive delay and deficits. This review of selected studies will highlight some of the current issues with the use of psychotropic medications during pregnancy and the postpartum period.

A pilot study to compare fluoxetine, calcium, and placebo in the treatment of premenstrual syndrome.

Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of premenstrual syndrome. A comparison of these agents to placebo may guide treatment selection. The goal of this pilot study was to compare fluoxetine and calcium to placebo.We enrolled 39 women with at least 3 moderate to severe premenstrual symptoms and functional impairment. The trial compared fluoxetine (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the course of 4 menstrual cycles. The Inventory of Depressive Symptomatology, Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement scales, and Daily Record of Severity of Problems were used to measure symptoms.Symptom improvement was greatest for the fluoxetine group, although significance was achieved only for the Daily Record of Severity of Problems (ß = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical Global Impression-Improvement (ß = -1.03; 95% confidence interval= -1.70 to -0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were between 0.80 and 2.08, whereas the effect sizes for calcium were only between 0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome, whereas the effect of calcium was much smaller. Results of this pilot do not support the need for a larger study that would compare these compounds.

Circadian phase shifts and mood across the perinatal period in women with a history of major depressive disorder: a preliminary communication.

BACKGROUND: Perinatal changes in maternal sleep patterns may modify circadian phase. Our objectives were to (a) measure changes in circadian phase and phase angle between salivary dim light melatonin onset (DLMO) and sleep onset across the perinatal period; and (b) prospectively examine associations between circadian measures and depressed mood in women with a history of major depressive disorder (MDD). METHODS: Twelve women (age±SD=26.9±5 years) who fulfilled DSM-IV criteria for history of MDD (but not in a mood episode at enrollment) were studied from third trimester of pregnancy through postpartum week 6. Participants completed sleep diaries, wore wrist actigraphs and light sensors, and had mood assessed with the Hamilton Depression Rating Scale (HAMD-17) during 3 separate weeks of the perinatal period; they gave saliva samples at 33 weeks gestation and 6 weeks postpartum to determine DLMO phase. RESULTS: Nine women had DLMO phase shifts ≥30 min. On average±SD, new mothers phase delayed 42±80 min (range=163 min phase delay to 144 min phase advance). The time interval between average actigraphic sleep onset and DLMO was shorter at 6 weeks postpartum compared to 3rd trimester in 9 of 12 women, indicating that most new mothers were going to bed closer to the onset of endogenous melatonin secretion. Circadian measures were associated with depressed mood at postpartum weeks 2 and 6. LIMITATIONS: These data are preliminary findings from a small sample and require replication. CONCLUSIONS: We observed individual differences in magnitude and direction of circadian phase shifts and their timing relative to sleep across the perinatal period. These measures were correlated with postpartum depressive symptoms. These preliminary data indicate that changes in perinatal circadian rhythms may contribute to the development of postpartum mood disorders.

ISPMD consensus on the management of premenstrual disorders.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

Analysis of brief screening tools for the detection of postpartum depression: comparisons of the PRAMS 6-item instrument, PHQ-9, and structured interviews.

Postpartum depression (PPD) is an important mental health issue affecting approximately 10 % of women. Self-report screening measures represent utility for detecting PPD in both clinical and research settings. The current study sought to inspect the accuracy of two screening measures compared to clinical interviews. As part of an ongoing clinical trial, 1,392 women between the ages of 18 and 45 were screened for PPD using the Patient Health Questionnaire-9 (PHQ-9) and a six-item scale developed from CDC Pregnancy Risk Assessment questions (PRAMS-6). Three item subscales of the PRAMS-6 were also inspected-three depression (PRAMS-3D) and three anxiety items (PRAMS-3A). Receiver operating characteristics compared the diagnostic accuracy of the PHQ-9, PRAMS-6, PRAMS-3D, and PRAMS-3A to both the Structured Clinical Interview for the DSM-IV (SCID) and the Hamilton Rating Scale for Depression. The PHQ-9, PRAMS-6, and PRAMS-3D all showed moderate accuracy at diagnosing PPD. Diagnostic cut points are provided. The PRAMS-6 instrument is a brief and effective screening tool for PPD. The time frame of symptom assessment may account for some variability in accuracy between the PHQ-9 and PRAMS screening instruments.

Clinical subtypes of core premenstrual disorders: a Delphi survey.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

Examination of premenstrual symptoms as a risk factor for depression in postpartum women.

Postpartum depression (PPD) is a significant public health concern with prevalence of major and minor depressions reaching 20 % in the first three postpartum months. Sociodemographic and psychopathology correlates of PPD are well established; however, information on the relationship between premenstrual disorders and the development of PPD is less well established. Thus, the aim of this study was to examine the role of premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) as a risk factor for PPD. Premenstrual symptoms were assessed retrospectively using the premenstrual symptoms screening tool (PSST) and depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and assessed using the Hamilton Depression Rating Scale (HDRS). A two-stage screening procedure was applied. In the first stage, the Patient Health Questionnaire (PHQ-9) was employed. In the second stage, women endorsing ≥5 symptoms on the PHQ-9 were administered the Structured Clinical Interview for DSM-IV, HDRS, and PSST. Hierarchical linear regression showed that history of depression and PMS/PMDD contributed an additional 2 % of the variance (p < 0.001), beyond that of sociodemographic factor effects. The full model accounted for 13 % of the variance in postpartum depressive symptoms. Using logistic regression, a significant association also emerged between PMS/PMDD and PPD (OR = 1.97). The findings of this study suggest that PMS/PMDD is an important risk factor for PPD. Women endorsing a history of PMS/PMDD should be monitored during the perinatal period.

Psychological/verbal abuse and utilization of mental health care in perinatal women seeking treatment for depression.

Research on psychological violence has suggested it is common among perinatal women and is predictive of later physical violence. Psychological violence is also a strong correlate of negative mental and physical health outcomes and may influence engagement in health services. Both physical and mental health care are of critical importance for perinatal women who may be especially vulnerable to psychological violence and its deleterious effects. This study examined the clinical records of 299 perinatal patients who received treatment in a psychiatric partial hospital program to determine whether there were differences in utilization of care between those women with and without current interpersonal psychological abuse. More women than expected who reported current psychological abuse left treatment early compared to those without such reports.

Psychotropic medications and other non-hormonal treatments for premenstrual disorders.

Selective serotonin re-uptake inhibitors have well-established efficacy for severe premenstrual syndrome and premenstrual dysphoric disorder. Efficacy has been reported with both continuous dosing (all cycle) and intermittent or luteal phase dosing (from ovulation to menses). Efficacy may be less with intermittent dosing, particularly for premenstrual physical symptoms. The efficacy of symptom-onset dosing (medication taken only on luteal days when symptoms occur) needs further systematic study. Women going through the menopausal transition may need to adjust their antidepressant dosing regimen due to the change in frequency of menstruation. Anxiolytics, calcium, chasteberry and cognitive-behaviour therapy may also have a role in the treatment of premenstrual symptoms.

Newborn neurobehavioral patterns are differentially related to prenatal maternal major depressive disorder and serotonin reuptake inhibitor treatment.

BACKGROUND: Prenatal serotonin reuptake inhibitor (SRI) exposure has been related to adverse newborn neurobehavioral outcomes; however, these effects have not been compared to those that may arise from prenatal exposure to maternal major depressive disorder (MDD) without SRI treatment. This study examined potential effects of MDD with and without SRI treatment on newborn neurobehavior. METHODS: This was a prospective, naturalistic study. Women were seen at an outpatient research center twice during pregnancy (26-28 and 36-38 weeks gestational age (GA)). Psychiatric diagnoses were assessed using the Structured Clinical Interview for the DSM-IV; medication use was measured with the Timeline Follow-Back instrument. Three groups were established based upon MDD diagnosis and SRI use: Control (N = 56), MDD (N = 20), or MDD + SRI (N = 36). Infants were assessed on a single occasion within 3 weeks of birth with the NICU Network Neurobehavioral Assessment Scale. Generalized Linear Modeling was used to examine neurobehavioral outcomes by exposure group and infant age at assessment. RESULTS: Full-term infants exposed to MDD + SRIs had a lower GA than CON or MDD-exposed infants and, controlling for GA, had lower quality of movement and more central nervous system stress signs. In contrast, MDD-exposed infants had the highest quality of movement scores while having lower attention scores than CON and MDD + SRI-exposed infants. CONCLUSION: MDD + SRI-exposed infants seem to have a different neurobehavioral profile than MDD-exposed infants in the first 3 weeks after delivery; both groups may have different neurobehavioral profiles with increasing age from birth.