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Background: Medication is commonly used to treat youth depression, but whether medication should be added to cognitive behavioural therapy (CBT) as first-line treatment is unclear. We aimed to examine whether combined treatment with CBT and fluoxetine was more effective than CBT and placebo in youth with moderate-to-severe major depressive disorder., Methods: The Youth Depression Alleviation-Combined Treatment (YoDA-C) trial was a randomised, double-blind, placebo-controlled, multicentre clinical trial. Participants were aged 15-25 years with moderate-to-severe MDD and had sought care at one of four clinical centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive CBT for 12 weeks, plus either fluoxetine or placebo. Participants began on one 20 mg capsule of fluoxetine or one placebo pill per day. All participants received CBT, delivered by therapists in weekly 50-minute sessions and attended interviews at baseline, and at weeks 4, 8, and 12, during which they completed assessments with research assistants. Participants saw a psychiatrist or psychiatry trainee to complete medical assessments at the same timepoints. The primary outcome was change in the interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001281886)., Findings: 153 participants (mean age 19·6 years [SD 2·7]) were enrolled from Feb 20, 2013, to Dec 13, 2016. 77 (50%) patients were allocated to CBT and placebo and 76 (50%) to CBT and fluoxetine. Participants had severe depression at baseline (mean MADRS score 33·6 [SD 5·1] in the CBT and placebo group and 32·2 [5·6] in the CBT and fluoxetine group), with high proportions of participants with anxiety disorder comorbidity (47 [61%] in the CBT and placebo group and 49 [64%] in the CBT and fluoxetine group) and past-month suicidal ideation (55 [71%] in the CBT and placebo group and 59 [78%] in the CBT and fluoxetine group). 59 (77%) participants in the CBT and placebo group and 64 (84%) in the CBT and fluoxetine group completed follow-up at week 12. After 12 weeks of treatment both groups showed a reduction in MADRS scores (-13·7, 95% CI -16·0 to -11·4, in the CBT and placebo group and -15·1, -17·4 to -12·9, in the CBT and fluoxetine group). There was no significant between-group difference in MADRS scores (-1·4, -4·7 to 1·8; p=0·39). There were five suicide attempts in the CBT and placebo group and one suicide attempt in the CBT and fluoxetine group (odds ratio 0·2, 0·0-1·8; p=0·21), and no significant between-group differences for other suicidal behaviours., Interpretation: We did not find evidence that the addition of fluoxetine (rather than placebo) to CBT further reduced depressive symptoms in young people with moderate-to-severe MDD. Exploratory analyses showed that the addition of medication might be helpful for patients with comorbid anxiety symptoms and for older youth., Funding: Australian National Health and Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. Methods: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15–25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. Results: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. Conclusions: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression. [ABSTRACT FROM AUTHOR]

Introduction: Borderline personality disorder (BPD) is common among people diagnosed with first episode of psychosis (FEP), but is often under‐recognized and under‐researched. This study aimed to determine: (i) the prevalence of borderline personality pathology (subthreshold features and categorical disorder) in a FEP cohort (termed FEP + BPP); (ii) demographic and clinical factors associated with FEP + BPP; (iii) the symptomatic and functional outcomes. Methods: This study was conducted within the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen over the 30‐month period between 2014 and 2016. BPP was evaluated by using the Structured Clinical Interview for DSM‐IV Axis II Personality Questionnaire BPD criteria. Results: In a cohort of 457 young people with a FEP (mean age 19.5 years, 56% male), 18.4% had borderline personality pathology (BPP). Compared with FEP alone, young people with FEP + BPP were more likely to be female, younger, Australian‐born. In addition, young people with FEP + BPP were more likely to be diagnosed with Psychosis NOS, present with more severe hallucinations, and have alcohol abuse. Young people with FEP + BPP had more relationship difficulties at presentation and they were more likely to suffer of depression and to engage in self‐harm throughout the follow‐up. In relation to outcome, FEP + BPP was not associated with different rates of remission or relapse, however they were less likely to be admitted to hospital at presentation or involuntarily during their episode of care. Conclusion: BPP is a common occurrence in psychotic disorders and is associated with more severe hallucinations and depression with higher risks of self‐harm. Specific interventions need to be developed. [ABSTRACT FROM AUTHOR]

Aim: Personality disorder is a common co‐occurrence ('comorbidity') among patients with bipolar disorder and appears to affect outcome negatively. However, there is little knowledge about the impact of this comorbidity in the early phases of bipolar disorder. We examined the prevalence and effect of personality disorder co‐occurrence on outcome in a cohort of youth with first episode mania with psychotic features. Methods: Seventy‐one first episode mania patients, aged 15–29, were assessed at baseline, 6, 12, and 18 months as part of a randomized controlled trial of olanzapine and chlorpromazine as add‐on to lithium in first episode mania with psychotic features. The current study involved secondary analysis of trial data. Results: A co‐occurring clinical personality disorder diagnosis was present in 16.9% of patients. Antisocial and narcissistic personality disorders were the most common diagnoses. Patients with co‐occurring personality disorder had higher rates of readmission to hospital, lower rates of symptomatic recovery and poorer functional levels at 6 months, but these differences disappeared after 12 and 18 months. Conclusions: In the early phase of bipolar disorder, patients with personality disorder comorbidity display delayed symptomatic and functional recovery and increased likelihood to need hospital readmissions. These observations suggest that routine assessment for personality disorder and specific interventions are important in order to improve short‐term treatment efficacy in this subgroup. [ABSTRACT FROM AUTHOR]

Abstract: Aim: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well‐documented, anti‐inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti‐inflammatory agent (YoDA‐A) study is to determine whether individuals receiving adjunctive anti‐inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. Methods: YoDA‐A is a 12‐week triple‐blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15–25, with moderate‐to‐severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to week 12. Results: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. Conclusion: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and ‘real‐world’, but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD. [ABSTRACT FROM AUTHOR]

Borderline personality disorder (BPD) has been demonstrated to be a reliable and valid construct in young people (adolescents and young adults). Both borderline- and mood-related psychopathology become clinically apparent from puberty through to young adulthood, frequently co-occur, can reinforce one another, and can be difficult to differentiate clinically. This Gordian knot of overlapping clinical features, common risk factors, and precursors to both BPD andmood disorders complicates clinical assessment, prevention, and treatment. Regardless of whether an individual crosses an arbitrary diagnostic threshold, a considerable proportion of young people with borderline- and moodrelated psychopathology will develop significant and persistent functional, vocational, and interpersonal impairment and disability during this critical risk and developmental period. There is a clear need for early intervention, but spurious diagnostic certainty risks stigma, misapplication of diagnostic labels, inappropriate treatment, and unfavorable outcomes. This article aims to integrate early intervention for BPD and mood disorders in the clinical context of developmental and phenomenological change and evolution. "Clinical staging," similar to disease staging in general medicine, is presented as a pragmatic, heuristic, and trans-diagnostic framework to guide prevention and intervention. It acknowledges that the early stages of these disorders cannot be disentangled sufficiently to allow for disorder-specific preventive measures and early interventions. Clinical staging defines an individual's location along the continuum of the evolving temporal course of a disorder. Such staging aids differentiation of early or milder clinical phenomena from those that accompany illness progression and chronicity, and suggests the application of appropriate and proportionate intervention strategies. [ABSTRACT FROM AUTHOR]

Objectives There are no established tools to identify individuals at risk for developing bipolar disorder. We developed a set of ultra-high-risk criteria for bipolar disorder [bipolar at-risk ( BAR)]. The primary aim of the present study was to determine the predictive validity of the BAR criteria. Methods This was a 12-month prospective study that was conducted at Orygen Youth Health Clinical Program, a public mental health program for young people aged 15-24 years in metropolitan Melbourne, Australia. At intake, BAR screen-positive individuals and a matched group of individuals who did not meet BAR criteria were observed over a period of 12 months. The BAR criteria include general criteria such as being in the peak age range for the onset of the disorder, as well as sub-threshold mania, depression plus cyclothymic features, and depression plus genetic risk. Conversion to first-episode mania/hypomania was defined by the presence of DSM- IV manic symptoms for more than four days, in line with the DSM- IV definition of hypomania/mania. Results A total of 559 help-seeking patients were screened. Of the eligible participants, 59 (10.6%) met BAR criteria. Thirty-five participants were included in the BAR group and 35 matched participants were selected to be in the control group. During the follow-up, five BAR patients out of 35 (14.3%) converted to first-episode hypomania/mania as opposed to none in the non- BAR group [χ2(1) = 5.38, p = 0.020]. Four out of these five converters had a DSM- IV diagnosis of bipolar I or bipolar II disorder. Conclusions These findings support the possibility of identification of persons prior to the onset of mania/hypomania. The proposed criteria need further evaluation in larger, prospective studies with longer follow-up periods. [ABSTRACT FROM AUTHOR]

Background: The aim of the Youth Depression Alleviation–Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support. Methods/Design: YoDA-C is a double-blind, randomised controlled trial funded by the Australian government’s National Health and Medical Research Council. Participants between the ages of 15 and 25 years with moderate to severe major depressive disorder will be randomised to receive either (1) cognitive behavioural therapy (CBT) and fluoxetine or (2) CBT and placebo. The treatment duration will be 12 weeks, and follow-up will be conducted at 26 weeks. The primary outcome measure is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after 12 weeks of treatment. The MADRS will be administered at baseline and at weeks 4, 8, 12 and 26. Secondary outcome measures will address additional clinical outcomes, functioning, quality of life and safety. [ABSTRACT FROM AUTHOR]

Background: Suicidal ideation (SI) is a common feature of depression and is closely associated with suicidal behaviour. Social support is implicated as an important determinant of suicide, but it is unclear how different social support dimensions influence SI in young people with depression. This study examines relationships between social support dimensions and SI in young people with major depressive disorder (MDD).Methods: 283 Australians aged 15-25, diagnosed with MDD, were recruited from two clinical trials conducted in youth-specific outpatient mental health services. The Multidimensional Scale of Perceived Social Support (MSPSS) was used to evaluate perceived support from Family, Friends, and a Significant Other. Suicidal ideation was assessed using the Suicidal Ideation Questionnaire (SIQ). Hierarchical regression was used to explore associations between social support and SI, controlling for demographics and depression severity.Results: A hierarchical regression model predicted 9% of the variability in SI, with depression severity being the most significant predictor. Family Support was inversely related to SI and uniquely contributed 2% of the variance; β = -0.15 (95% CI -0.27 - -0.02) p < .05. Demographics and support from Friends or a Significant Other were not significantly associated with SI.Limitations: Findings are correlational; it cannot be determined that increasing family support would decrease SI severity.Conclusion: Perceived Family Support was negatively associated with SI in young people with MDD. This suggests that family members might play important roles in suicide prevention efforts. More work is needed exploring ways to empower families to develop adaptive family functioning and support. [ABSTRACT FROM AUTHOR]

Background: Personality disorder (PD) may affect the efficacy of pharmacological interventions for mood disorders, but the extent to which this occurs is uncertain. We aimed to examine the available published evidence concerning the role of PD in pharmacological treatment outcomes of randomised controlled trials (RCTs) for adults with mood disorders (i.e. depressive and bipolar spectrum disorders).Methods: A systematic search of Cochrane Central Register of Controlled Clinical Trials, PubMed, EMBASE, PsycINFO, CINAHL Complete, and Google Scholar databases was undertaken to identify studies of interest. Data were independently extracted by two reviewers. The Cochrane Risk of Bias tool was used to assess methodological quality and risk of bias. A random effects model was utilised and statistical heterogeneity was assessed using the I2 statistic. This systematic review was registered with PROSPERO (CRD42018089279) and the protocol is published.Results: The search yielded 11,640 studies. Subsequent to removing duplicates, 9657 studies were screened at title and abstract stage and 1456 were assessed at full-text stage. Eighteen studies met criteria for inclusion in this review. Meta-analysis did not reveal a significant difference between groups for treatment outcome (standardised mean difference 0.22 [-0.09, 0.54]; I2: 69%, p=0.17) and remission (risk ratio 0.84 [0.64, 1.11]; I2: 51%, p=0.22).Limitations: This review was limited by lack of studies on bipolar disorder.Conclusion: PD comorbidity does not appear to affect treatment efficacy of pharmacological interventions for adults with mood disorders. [ABSTRACT FROM AUTHOR]