Perinatal depression: The use of the Edinburgh Postnatal Depression Scale to derive clinical subtypes.

BACKGROUND: Predicting the course and complications of perinatal depression through the identification of clinical subtypes has been previously undertaken using the Edinburgh Postnatal Depression Scale and has the potential to improve the precision of care and improve outcomes for women and their children. METHODS: Edinburgh Postnatal Depression Scale scores were collected twice in pregnancy and twice in the postpartum in a sample of 360 women who met diagnostic criteria for perinatal depression using the Structured Clinical Interview for DSM disorder. These data were used to compare with previous, though conflicting, evidence from cross-sectional studies and extend this by undertaking longitudinal measurement invariance modelling to test the structural validity across the perinatal period. Latent profile and transition modelling was used to identify distinct subtypes of women and assess the utility of these subtypes and transition profiles to predict clinically meaningful outcomes. RESULTS: Although our data supported one of the previously reported three-factor Edinburgh Postnatal Depression Scale structures used to compute subfactor totals for depressed mood, anxiety and anhedonia at both early pregnancy and 6 months postpartum, there was little value in using these Edinburgh Postnatal Depression Scale subfactor scores to identify subtypes predictive of clinically meaningful postpartum symptom subtypes, or of general health, pregnancy and neonatal outcomes. CONCLUSION: Our study does not support the use of the Edinburgh Postnatal Depression Scale to distinguish perinatal depressive subtypes for the purposes of predicting course and complications associated with perinatal depression. However, the results give guidance on alternative ways to study the value of personalised management in improved outcomes for women living with or at risk for perinatal depression.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Prophylactic Management of Women With Bipolar Disorder During Pregnancy and the Perinatal Period: Clinical Scenario-Based Practical Recommendations From A Group of Perinatal Psychiatry Authors.

ABSTRACT: Many women with bipolar disorder experience episodes of illness or relapses over the perinatal period, especially in the immediate postpartum period. Risks associated with treated/untreated psychopathologies and fetal exposure to bipolar medications make the management of bipolar disorder during these periods challenging for clinicians and patients. In light of the available effectiveness and reproductive safety data, the current clinical update based on the opinions of a group of international perinatal psychiatry authors recommends general considerations and specific management strategies for each possible clinical scenario, including mixed features, predominant polarity, diagnosis of subtypes of bipolar disorder, severity of previous episodes, and risk of recurrence of mood episodes.

Fetal SSRI antidepressant exposure and infant sleep: Findings from the MPEWS pregnancy cohort study.

This longitudinal study examines the association between fetal Selective Serotonergic Reuptake Inhibitor antidepressant exposure and infant sleep behaviours at six and 12 months of age and focus on three of the most commonly prescribed antidepressants in pregnancy. This study utilises data on 698 women recruited at less than 20 weeks of pregnancy and are followed up at six and 12 months postpartum. Women were recruited into one of three groups: those taking either sertraline, citalopram or escitalopram antidepressants in pregnancy (n = 85); women with a depressive disorder who were not taking antidepressants (non-medicated depressed, NMD; n = 82); and, and a control group of women (n = 531). At six and 12 months, data were collected on breastfeeding and sleep location and infant sleep was measured using the Brief Infant Sleep Questionnaire. Antidepressants sertraline, escitalopram and citalopram were not associated with increased infant waking or time awake. However, sertraline was associated with longer time for an infant to go to sleep. This study provides reassurance that SSRI antidepressants and, in particular, sertraline, escitalopram and citalopram are not associated with infant sleep behaviours that are commonly regarded as problematic including night waking. Further replication of these findings, including with direct measures of infant sleep, are recommended.

Difficult decision-making in major depressive disorder: Practical guidance based on clinical research and experience.

OBJECTIVES: To extend current published guidance regarding the management of major depression in clinical practice, by examining complex cases that reflect real-world patients, and to integrate evidence and experience into recommendations. METHODS: The authors who contributed to recently published clinical practice guidelines were invited to identify important gaps in extant guidance. Drawing on clinical experience and shared knowledge, they then generated four fictional case studies to illustrate the real-world complexities of managing mood disorders. The cases focussed specifically on issues that are not usually addressed in clinical practice guidelines. RESULTS: The four cases are discussed in detail and each case is summarised using a life chart and accompanying information. The four cases reflect important real-world challenges that clinicians face when managing mood disorders in day-to-day clinical practice. To partly standardise the presentation of each case and for ease of reference we provide a Time Line, History Box and Management Chart, along with a synopsis where relevant. Discussion and formulation of the cases illustrate how to manage the complexities of each case and provide one possible pathway to achieving functional recovery. CONCLUSION: These cases draw on the combined clinical experience of the authors and illustrate how to approach diagnostic decision-making when treating major depressive disorder and having to contend with complex presentations. The cases are designed to stimulate discussion and provide a real-world context for the formulation of mood disorders.

Positioning of psychodynamic psychotherapy in the treatment of depression: A comparison of the RANZCP 2020 and NICE 2022 guidelines.

OBJECTIVE: To compare the 2022 NICE guidelines (NG222) and 2020 RANZCP clinical practice guidelines (MDcpg2020) recommendations for the treatment of depression using psychodynamic psychotherapy. CONCLUSIONS: Both guidelines recommend psychological interventions first-line. However, only short-term psychodynamic psychotherapy (STPP) is recommended, and in the NG222 it is ranked last for less severe depression and 7th for more severe depression. In contrast, cognitive behavioural therapy and behavioural activation are deemed the more clinically effective and cost-effective psychological therapies. And antidepressants play a significant role - largely in more severe depression.

A novel exploration of irritability in adolescent males: A preliminary study.

OBJECTIVE: Irritability is a key symptom of mood disorders and is common in adolescence; nevertheless, it is poorly understood and assessed. Research examining irritability and its relationship to mood and anxiety disorders risk factors in adolescent males is lacking. Therefore, the current study aimed to address this gap. METHOD: An online survey designed to interrogate the relationship between irritability and other risk factor variables was administered to 627 adolescent males (ages 12-17). Findings were analysed statistically using MANOVAs. RESULTS: When divided into high and low irritability groups, higher irritability scores were significantly correlated with higher scores on all risk factor variables. Further, higher irritability scores were associated with higher scores on all variables that indicate an increased risk for development of psychological disorders, such as depression and anxiety. CONCLUSION: This study is the first to focus on subjective irritability. In adolescent males, it identifies a potentially novel model of irritability's involvement in maladaptive processes relating to emotional dysregulation, behavioural difficulties and anxiety.

The management of depression: the evidence speaks for itself.

Comparing the recommendations of two recently published national clinical practice guidelines for depression, this editorial highlights the concordance of advice concerning the selection and sequencing of therapies. Lifestyle and psychological interventions feature prominently and there is broad agreement regarding medication choice and optimisation strategies. The guidelines are therefore a useful resource.

Common and differential neural mechanisms underlying mood disorders.

BACKGROUND: Despite homogenous clinical presentations between bipolar and unipolar disorders, there are distinct neurobiological differences. Chronicity of illness may be a factor impacting and sustaining certain neural features. The goal of this study was to investigate common and shared neural mechanisms underlying mood disorders, and possible sustained neural changes relating to illness chronicity by investigating a cohort of euthymic patients with bipolar disorder (BD), unipolar depression who had responded to treatment (treatment-sensitive depression, TSD), and a chronically treatment-resistant depressed (TRD) group. METHODS: One hundred and seventy-two participants (40 BD, 39 TSD, 40 TRD, and 53 age-gender-matched healthy controls) underwent resting-state fMRI scans. Seed-based and independent component analyses were performed to investigate group differences in resting-state connectivity between the four groups. RESULTS: All three clinical groups had significantly lower connectivity within the frontoparietal network (FPN) relative to controls. TRD and BD were significantly different from TSD (TRD, BD > TSD) but were not significantly different from each other. TRDs were also significantly different from both BD and TSD for salience network connectivity with the posterior cingulate (DMN) and the FPN with frontal pole (DMN). Additionally, the BD group exhibited greater DMN-FPN (sgACC-RDLPFC) connectivity relative to TRD, TSD, and controls, which was correlated with a previous number of depressive episodes, in the BD group only. CONCLUSIONS: BD demonstrated shared and differential connectivity features relative to symptomatic TRD and euthymic TSD groups. The increased sgACC-RDLPFC connectivity in BD and its correlation with a number of depressive episodes could be a neural feature associated with illness chronicity.

Perinatal depression screening: a systematic review of recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD).

Perinatal depression (PND) screening recommendations are made by national, state-based and professional organisations; however, there is disagreement regarding screening timing, provider responsible, screening setting, screening tool as well as the follow-up and referral pathways required post-screening. This systematic review aimed to identify, describe and compare PND screening recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD). Publications were identified through systematically searching PubMed, Google and the Guidelines International Network (GIN). Recommendations regarding PND screening endorsement, timing, frequency, responsible provider, tools/assessments and follow-up and referral were extracted. Twenty-one publications, including guidelines, from five countries were included. Most made recommendations in support of PND screening using the Edinburgh Postnatal Depression Scale. Details differed regarding terminology used, as well as frequency of screening, follow-up mechanisms and referral pathways. A broad range of health providers were considered to be responsible for screening. This is the first review to identify and compare PND screening recommendations from OECD member countries; however, only online publications published in English, from five countries were included. Heterogeneity of publication types and inconsistency in definitions rendered quality assessment inappropriate. While most publications generally endorsed PND screening, there are exceptions and the associated details pertaining to the actual conduct of screening vary between and within countries. Developing clear, standardised recommendations based on current evidence is necessary to ensure clarity amongst healthcare providers and a comprehensive approach for the early detection of PND.

An Evidence-Based Perspective on The 2020 Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines.

OBJECTIVE: To rebut the claims made in an opinion piece by Anaf and colleagues regarding the recommendations for psychotherapy within the 2020 RANZCP Mood Disorders Clinical Practice Guidelines (CPG). CONCLUSIONS: The CPG attaches importance to psychological interventions and recommends their administration as first-line in the treatment of depression. The concerns raised by Anaf and colleagues have no basis and are readily dismissed by referring to the guidelines. Therefore, we strongly encourage clinicians to formulate their own views by reading the guidelines for themselves.

Abnormal habenula functional connectivity characterizes treatment-resistant depression.

BACKGROUND: A significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of treatment-resistant depression (TRD) is anhedonia, or the inability to feel pleasure, which has been attributed to disrupted habenula function - a component of the reward network. This study aimed to map detailed neural circuitry architecture related to the habenula to identify neural mechanisms of TRD. METHODS: 35 TRD patients, 35 patients with treatment-sensitive depression (TSD), and 38 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were performed using the left and right habenula as seed regions of interest, and the three groups were compared using whole-brain voxel-wise comparisons. RESULTS: The TRD group demonstrated hyperconnectivity of the left habenula to the left precuneus cortex and the right precentral gyrus, compared to the TSD group, and to the right precuneus cortex, compared to the TSD and HC groups. In contrast, TSD demonstrated hypoconnectivity than HC for both connectivity measures. These connectivity values were significantly higher in patients with a history of suicidal ideation. CONCLUSIONS: This study provides evidence that, unlike TSD, TRD is characterized by hyperconnectivity of the left habenula particularly with regions of the default mode network. An increased interplay between reward and default mode networks is linked to suicidality and could be a possible mechanism for anhedonia in hard to treat depression.

Guidelines for the management of psychosis in the context of mood disorders.

Psychotic episodes occur in a substantial proportion of patients suffering from major mood disorders (both unipolar and bipolar) at some point in their lives. The nature of these episodes is less well understood than the more common, non-psychotic periods of illness and hence their management is also less sophisticated. This is a concern because the risk of suicide is particularly high in this subtype of mood disorder and comorbidity is far more common. In some cases psychotic symptoms may be signs of a comorbid illness but the relationship of psychotic mood to other forms of psychosis and in particular its interactions with schizophrenia is poorly understood. Therefore, our targeted review draws upon extant research and our combined experience to provide clinical context and a framework for the management of these disorders in real-world practice - taking into consideration both biological and psychological interventions.