Search

BACKGROUND: Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up-skill patients and their families. The benefits of SEI over the first few years have been demonstrated. While early recovery can be expected to translate to better long-term outcomes by analogy with other illnesses, there is limited evidence to support this from follow-up studies. The current study involves the long-term follow-up of a sub-set of first episode psychosis (FEP) patients, with a range of diagnoses, who were first treated at Orygen's Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. The aim of this paper is to present the methodology for this follow-up study. METHODS: Between January 1998 and December 2000, 786 patients between the ages of 15-29 years were treated at EPPIC, located in Melbourne, Australia. Our cohort consists of 661 people (82 were transferred/discharged and 43 were not diagnosed with a psychotic disorder at time of discharge). The 18-month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The ≥15 year outcomes of this cohort are being examined in this study, known as FEPOS15. RESULTS: Participant follow-up is ongoing. In order to extend and assess broader outcomes of the cohort, data linkage with health-related databases will be conducted. CONCLUSION: This study will provide a comprehensive evaluation of the long-term trajectory of psychotic disorders after treatment for FEP in a SEI service.

Major depressive disorder is a common, recurrent, disabling and costly disorder that is often severe and/or chronic, and for which non-remission on guideline concordant first-line antidepressant treatment is the norm. A sizeable percentage of patients diagnosed with MDD do not achieve full remission after receiving antidepressant treatment. How to understand or approach these 'refractory', 'TRD' or 'difficult to treat' patients need to be revisited. Treatment resistant depression (TRD) has been described elsewhere as failure to respond to adequate treatment by two different antidepressants. This definition is problematic as it suggests that TRD is a subtype of major depressive disorder (MDD), inferring a boundary between TRD and depression that is not treatment resistant. However, there is scant evidence to suggest that a discrete TRD entity exists as a distinct subtype of MDD, which itself is not a discrete or homogeneous entity. Similarly, the boundary between TRD and other forms of depression is predicated at least in part on regulatory and research requirements rather than biological evidence or clinical utility.This paper aims to investigate the notion of treatment failure in order to understand (i) what is TRD in the context of a broader formulation based on the understanding of depression, (ii) what factors make an individual patient difficult to treat, and (iii) what is the appropriate and individualised treatment strategy, predicated on an individual with refractory forms of depression?Expert contributors to this paper were sought internationally by contacting representatives of key professional societies in the treatment of MDD - World Federation of Societies for Biological Psychiatry, Australasian Society for Bipolar and Depressive Disorders, International Society for Affective Disorders, Collegium Internationale Neuro-Psychopharmacologium and the Canadian Network for Mood and Anxiety Treatments. The manuscript was prepared through iterative editing.The concept of TRD as a discrete subtype of MDD, defined by failure to respond to pharmacotherapy, is not supported by evidence. Between 15 and 30% of depressive episodes fail to respond to adequate trials of 2 antidepressants, and 68% of individuals do not achieve remission from depression after a first-line course of antidepressant treatment. Failure to respond to antidepressant treatment, somatic therapies or psychotherapies may often reflect other factors including; biological resistance, diagnostic error, limitations of current therapies, psychosocial variables, a past history of exposure to childhood maltreatment or abuse, job satisfaction, personality disorders, co-morbid mental and physical disorders, substance use or non-adherence to treatment. Only a subset of patients not responding to antidepressant treatment can be explained through pharmacokinetic or pharmacodynamics mechanisms. We propose that non remitting MDD should be personalised, and propose a strategy of 'deconstructing depression'. By this approach, the clinician considers which factors contribute to making this individual both depressed and 'resistant' to previous therapeutic approaches. Clinical formulation is required to understand the nature of the depression. Many predictors of response are not biological, and reflect a confluence of biological, psychological, and sociocultural factors, which may influence the illness in a particular individual. After deconstructing depression at a personalised level, a personalised treatment plan can be constructed. The treatment plan needs to address the factors that have contributed to the individual's hard to treat depression. In addition, an individual with a history of illness may have a lot of accumulated life issues due to consequences of their illness, and these should be addressed in a recovery plan.A 'deconstructing depression' qualitative rubric does not easily provide clear inclusion and exclusion criteria for researchers wanting to investigate TRD.MDD is a polymorphic disorder and many individuals who fail to respond to standard pharmacotherapy and are considered hard to treat. These patients are best served by personalised approaches that deconstruct the factors that have contributed to the patient's depression and implementing a treatment plan that adequately addresses these factors. The existence of TRD as a discrete and distinct subtype of MDD, defined by two treatment failures, is not supported by evidence.

Aim Prevention and early intervention efforts of serious mental illnesses has yielded promising results. However, alongside benefits, several ethical concerns have been raised, including the effects of being identified as being at-risk. In these debates, the voice of parents or carers is conspicuously absent. This is especially concerning as several at-risk interventions are trialled in under-age youth where parents consent on behalf of young people. Therefore, this study aimed to understand carer's experiences of their teenager being identified as at risk for psychosis. Methods Semi-structured interviews were conducted with seven carers who had provided consent for their teenager to participate in a stepped intervention study for youth at-risk for psychosis. Questions explored their experiences regarding having their teenager being identified as at-risk. Transcripts were analysed using thematic analysis. Results We identified five main themes from seven female carers' experiences of risk identification including: (a) recall of risk information was limited, or variable, (b) goal of risk disclosure was perceived to be positive, (c) negative emotions were associated with knowledge of risk, (d) relief from uncertainty and helplessness and (e) effects of risk disclosure were mediated by individual circumstance. Conclusion Overall, the results demonstrate that carers' experience of risk disclosure varied with factors surrounding their individual circumstances, and the process of disclosure. Whilst participants acknowledged potential adverse effects associated with risk disclosure, many still adopted a positive outlook. Tailoring safe and effective disclosure of risk to suit the needs of youth and carers could outweigh the potential risks.

Background Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. Methods We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. Results We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. Limitation The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. Conclusions There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

The care of people with first-episode mania has been overlooked in comparison with the care of patients with other non-affective psychoses, despite evidence suggesting targeted treatments might be of benefit for this patient group. In this Personal View, we outline the general epidemiology of first-episode mania in the context of bipolar disorder, the natural history of mania (with an emphasis on its recurrent nature), current evidence for pharmacological, psychological, and service-level interventions, current guidelines for the treatment of first-episode mania, and provide a patient's point of view of the care pathway (appendix). We note the paucity of high-quality evidence for interventions in first-episode mania and the lack of agreement among treatment guidelines in relation to treatment, especially maintenance treatment. We suggest that, based on high morbidity and clinical need, research evidence to inform guideline development is necessary, and in the interim, clearer guidance on treatment and diagnosis should be given; specifically, we have suggested that patients should be cared for within a first-episode psychosis service, when such a service exists.

Aim Young people with bipolar disorder (BD) commonly experience reduced quality of life, persistent symptoms and impaired functional recovery despite often superior school performance. Compromised long-term functioning can ensue. There is evidence that psychological therapies alongside pharmacology may be more efficacious earlier in the course of the disorder. Intervention in the early stages may thus reduce the burden and risk associated with BD and mitigate the impact of the disorder on normal developmental trajectories. To date, however, the availability of evidence-based psychological therapies for young people with early BD is limited. Furthermore, there are no large-scale randomized controlled trials (RCTs) of such interventions. Methods The study is a prospective, single-blind, RCT examining the effectiveness of an adjunctive individualized and manualized psychological intervention, compared with treatment as usual within youth-specific early intervention services. The REsearch into COgnitive and behavioural VERsatility (RECOVER) intervention is delivered over a 6-month period. About 122 young people in the early stages of BD-I (at least one manic episode in the previous 2 years, with no more than five lifetime treated/untreated manic or hypomanic episodes) will be recruited. The assessments will occur at baseline, 3, 6 (primary endpoint, end of treatment), 9, 12, 15 and 18 months. Results Recruitment will commence in January 2019 and is anticipated to occur over a 3.5-year period. Conclusions To date, there are no evidence-based psychological therapies tailored to young people with early BD. We will test whether early psychological intervention in the course of BD can reduce the symptomatic, psychological, vocational and social impacts that are seen in entrenched disorder.

Background Community treatment orders (CTOs) are a controversial form of involuntary treatment for individuals affected by mental health disorders and yet little is known about the use of CTOs in first presentations. Therefore, this study aimed to determine the rates, determinants and outcomes associated with the use of CTOs in young people with a first episode of psychosis (FEP). Methods This epidemiological cohort study included all individuals aged 15–24 who presented with a FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne between 01.01.2011 and 31.12.13. Results A total of 544 young people presented with a FEP during the study period and of these, 93 (17.3%) were subject to a CTO during their episode of care. A total of 69.7% of CTOs were commenced after the first three months of treatment and the median duration of CTOs was 168.5 days. Males, a diagnosis of a schizophrenia spectrum disorder and a concurrent substance abuse disorder were associated with the use of CTOs. Additionally, young people with more severe positive psychotic symptoms were more likely to be subject to a CTO. At the time of discharge, only 38.7% of those subject to a CTO were in education or employment compared to 65.4% of those who had not been subject to a CTO. Conclusions The majority of CTOs are commenced after at least three months of treatment, however the optimal timing of CTO implementation needs to be determined. The poor functioning of young people on a CTO should be the focus of future interventional studies.

OBJECTIVE: There is a lack of existing research regarding young people with bipolar I disorder (BD-I) and psychotic features, who are not in education, employment, and training (NEET). Thus, the aims of the study were to: (a) establish rates of NEET at service entry to a specialist early intervention service; (b) delineate premorbid and current variables associated with NEET status at service entry and (c) examine correlates of NEET status at discharge. METHOD: Medical file audit methodology was utilized to collect information on 118 patients with first episode psychotic mania treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. NEET status was determined using the modified vocation status index (MVCI). Bivariate and multivariable logistic variables were used to examine relationships between premorbid, service entry and treatment variables, and NEET status at service entry and discharge. RESULTS: The NEET rate was 33.9% at service entry, and 39.2% at discharge. Variables associated with NEET status at service entry were premorbid functioning and polysubstance use. NEET status at service entry was the only significant correlate of NEET status at discharge. When service entry NEET was taken out of the model, substance use during treatment was predictive of NEET status at discharge. CONCLUSIONS: NEET status at service entry was related to a history of premorbid decline, and risk factors such as substance use and forensic issues. NEET status can decline during treatment, and utility of vocational intervention programs specifically for BD, in addition to specialist early intervention, needs to be examined.

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.

Background The impact of guideline concordance on naturalistic maintenance treatment outcomes in BD is not known. We sought to evaluate the effect of guideline-concordant care on symptomatic, course and functional outcomes in youth with early-stage BD-I. Methods In this file audit study, we examined the prospective course of 64 clients with first treatment seeking manic episode of BD-I. Eighteen-month outcome measures included Clinical Global Impressions Scale - Bipolar Version (CGI-BP), Social and Occupational Functioning Assessment Scale (SOFAS) and number of relapses. Correlations and hierarchical linear regressions were used to examine the relationships between guideline concordance and outcomes, while controlling for potential confounders. Results Although higher guideline-concordant care in the maintenance phase was associated with a higher discharge CGI-BP score and thus worse outcome, baseline CGI-BP and insight were more predictive of illness severity at follow-up than guideline concordance. There was no association with SOFAS and guideline-concordant care at follow-up. Greater concordance with maintenance medication guideline statements was also associated with greater number of relapses even after controlling for sex, medication adherence, duration of care and baseline illness severity. Limitations This study was limited by sample size and its single pool of clients which may limit generalizability. Conclusions Contrary to our hypotheses, higher guideline concordance was associated with worse outcomes, although this relationship was moderated by the client's illness characteristics, severity and insight. More unwell youth with poor insight, greater severity, and mixed/rapid cycling features may need other interventions or modified guidelines.

Most psychiatric disorders develop during adolescence and young adulthood and are preceded by a phase during which attenuated or episodic symptoms and functional decline are apparent. The introduction of the ultra-high risk (UHR) criteria two decades ago created a new framework for identification of risk and for pre-emptive psychiatry, focusing on first episode psychosis as an outcome. Research in this paradigm demonstrated the comorbid, diffuse nature of emerging psychopathology and a high degree of developmental heterotopy, suggesting the need to adopt a broader, more agnostic approach to risk identification. Guided by the principles of clinical staging, we introduce the concept of a pluripotent at-risk mental state. The clinical high at risk mental state (CHARMS) approach broadens identification of risk beyond psychosis, encompassing multiple exit syndromes such as mania, severe depression, and personality disorder. It does not diagnostically differentiate the early stages of psychopathology, but adopts a “pluripotent” approach, allowing for overlapping and heterotypic trajectories and enabling the identification of both transdiagnostic and specific risk factors. As CHARMS is developed within the framework of clinical staging, clinical utility is maximized by acknowledging the dimensional nature of clinical phenotypes, while retaining thresholds for introducing specific interventions. Preliminary data from our ongoing CHARMS cohort study (N = 114) show that 34% of young people who completed the 12-month follow-up assessment (N = 78) transitioned from Stage 1b (attenuated syndrome) to Stage 2 (full disorder). While not without limitations, this broader risk identification approach might ultimately allow reliable, transdiagnostic identification of young people in the early stages of severe mental illness, presenting further opportunities for targeted early intervention and prevention strategies.

Among the diverse risk factors for psychosis, clinical markers are the most commonly used in research settings and clinical practice. Such markers have been studied in high-risk populations such as participants with a familial history of psychosis or those with “basic symptoms” or a syndrome of clinical or ultra high risk. A range of clinical risk factors have been identified in these populations including subtypes of psychotic symptoms such as disorganization and unusual thought content; markers of general and social functioning; family history of psychosis; early-life trauma; obstetric complications; and cannabis abuse. These factors should be considered in terms of their impact on the risk of diverse future outcomes including psychotic symptomatology, psychosocial functioning, and other mental disorders. Consideration of factors that affect the base rates of such outcomes in individual populations and how these clinical risk factors affect these rates are important for clinicians and researchers in interpreting risk.

Background Clinical guidelines recommend maintenance treatment with antipsychotic medication for one to two years following remission of symptoms after a first episode of psychosis. However, recent research has suggested that this may not be indicated. Consistent predictors of outcome would be beneficial to guide clinicians as to which individuals are likely to have a successful discontinuation. Objectives This study reviews the literature with the aim of identifying demographic and clinical predictors of either relapse or continued remission in those with a first episode of psychosis following discontinuation of antipsychotic medication. Methodology Data Sources: A systematic search of PubMed, CINAHL, and PsychInfo databases was performed. Eligibility Criteria: Cohort, case-control and clinical trials that were published in English, included participants with a first episode of psychosis, and examined clinical and demographic predictors of relapse or continued remission after antipsychotic discontinuation. Results Eleven studies fulfilled inclusion criteria. No positive findings were replicated across cohorts. Predictors of relapse: male sex, unemployment, prior psychiatric admission, premorbid adjustment, childhood isolation, premorbid functioning, schizoid-schizotypal traits, schizophrenia diagnosis, concomitant medication, and more severe negative symptoms. Some positive findings must be interpreted in the context of conflicting and replicated negative findings: sex, employment status, level of education, premorbid functioning, symptom severity, and schizophrenia diagnosis. Other replicated non-predictive findings: age, ethnicity, marital status, family history, disorganized thoughts, affective symptoms, cannabis abuse, clinical global impression, social integration, duration and dose of antipsychotic treatment, and compliance. Conclusion No positive findings have been replicated across study cohorts. Non-predictive findings have been replicated.

Background There is uncertainty about the required duration of long-term antipsychotic maintenance medication after a first episode of psychosis. Robust predictors of relapse after discontinuation are yet to be identified. The present study aimed to determine the proportion of young people who discontinue their antipsychotic medication after a first episode of psychosis, the proportion who experience relapse, and predictors of relapse. Methods A retrospective study of all individuals presenting to the Early Psychosis Prevention and Intervention Centre between 01/01/11 and 31/12/13 was conducted. A Cox regression analysis was conducted to identify predictors of relapse. Results A total of 544 young people with a FEP were included. A trial of discontinuation was undertaken by 61% of the cohort. Median duration of antipsychotic medication prior to first trial of discontinuation was 174.50 days. Amongst those trialing discontinuation, 149 (45.8%) experienced relapse in a median follow-up time post discontinuation of 372 days. On multivariate analysis, predictors of relapse were a diagnosis of cannabis abuse disorder (HR: 1.40), and longer duration of antipsychotic medication (HR: 1.05). Conclusion Antipsychotic discontinuation frequently occurs earlier than guidelines recommend. Individuals with a diagnosis of cannabis abuse are more likely to experience relapse and addressing this substance abuse prior to discontinuation could possibly reduce relapse rates.

Introduction Psychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis. Methods Among a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13 years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments. Results Eighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning. Discussion In addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase.

Aim The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. Methods This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. Conclusions This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at‐risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end‐stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage‐specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage‐specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at‐risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative‐type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

Background Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. Methods We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs’ Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. Results The social adjustment component of the PAS correlated with the interpersonal relations ( r s = −0.46, p r s =−0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning. Limitations Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Conclusions Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions.

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

Background Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up skill patients and their families. While the immediate benefits of SEI are clear, and have been demonstrated, the long-term impact of SEI on illness course is less clear. The First Episode Outcome Study involves the long-term follow-up of a representative sample of first episode psychosis patients who were first treated at the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. In this presentation the preliminary data on physical health outcomes are reported. Methods Between January 1998 and December 2000, 661 patients between the ages of 15–29 years were treated at the Early Psychosis Prevention and Intervention Centre, Melbourne Australia. The 18-month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The long-term outcomes of this cohort are now being examined in a new study (known as FEPOS15). Results The rates of self-report physical health problems in 100 participants 15 years after being treated for a first episode psychosis were significant for high cholesterol (41%), asthma (33.7%), chronic pain (25.3%), allergies (19.3%), respiratory problems (16.9%) anemia (12.2%), arthritis (12.0%), hepatitis C (10.8%) and diabetes (6.3%). Cardiovascular problems were also noted including heart attack (2.4%), other heart problems (8.4%), and stroke (3.6%). Sexual health problems are explored. Physical health findings pertaining to Coroners’ findings on those who had died will be also used to describe the long-term impacts of psychotic disorder. Discussion This follow-up study is one of the longest, largest and most comprehensive studies of the multidimensional outcomes of a SEI service for psychosis. The physical health outcomes of individuals 15-years after the first episode psychosis are poor. The importance of monitoring and managing physical health problems in those with psychotic disorder is highlighted.

Aim Early intervention and prevention of serious mental disorders such as bipolar disorder has the promise of decreasing the burden associated with these disorders. With increasing early and preventive intervention efforts among cohorts such as those with a familial risk for bipolar disorder, there is a need to examine the associated ethical concerns. The aim of this review was to examine the ethical issues underpinning the clinical research on pre-onset identification and preventive interventions for bipolar disorder. Methods We undertook a PubMed search updated to November 2014 incorporating search terms such as bipolar, mania, hypomania, ethic*(truncated), early intervention, prevention, genetic and family. Results Fifty-six articles that were identified by this method as well as other relevant articles were examined within a framework of ethical principles including beneficence, non-maleficence, respect for autonomy and justice. The primary risks associated with research and clinical interventions include stigma and labelling, especially among familial high-risk youth. Side effects from interventions are another concern. The benefits of preventive or early interventions were in the amelioration of symptoms as well as the possibility of minimizing disability, cognitive impairment and progression of the illness. Supporting the autonomy of individuals and improving access to stigma-free care may help moderate the potential challenges associated with the risks of interventions. Conclusions Concerns about the risks of early identification and pre-onset interventions should be balanced against the potential benefits, the individuals' right to choice and by improving availability of services that balance such dilemmas.

Identifying young people at risk of developing serious mental illness and identifying predictors of onset of illness has been a focus of psychiatric prediction research, particularly in the field of psychosis. Work in this area has facilitated the adoption of the clinical staging model of early clinical phenotypes, ranging from at-risk mental states to chronic and severe mental illness. It has been a topic of debate if these staging models should be conceptualised as disorder-specific or transdiagnostic. In order to inform this debate and facilitate cross-diagnostic discourse, the present scoping review provides a broad overview of the body of literature of (a) longitudinal at-risk approaches and (b) identified antecedents of (homotypic) illness progression across three major mental disorders [psychosis, bipolar disorder (BD) and depression], and places these in the context of clinical staging. Stage 0 at-risk conceptualisations (i.e. familial high-risk approaches) were identified in all three disorders. However, formalised stage 1b conceptualisations (i.e. ultra-high-risk approaches) were only present in psychosis and marginally in BD. The presence of non-specific and overlapping antecedents in the three disorders may support a general staging model, at least in the early stages of severe psychotic or mood disorders.

Aim Up to half of patients with borderline personality disorder report auditory verbal hallucinations that are phenomenologically indistinguishable from those in schizophrenia, occur early in the course of the disorder, and are enduring, distressing and disabling. In clinical practice, this symptom is widely assumed to be unresponsive to treatment with antipsychotic medication and early intervention is rarely offered. The Verbal Experiences Response in Borderline personality disorder to Aripiprazole TrIal Medication (VERBATIM) study aims to be the first controlled trial to investigate the effectiveness of conventional pharmacotherapy for this symptom in this patient group. Method VERBATIM is a 12-week, triple-blind, single-centre, parallel groups randomised controlled trial, with a 27-week follow-up period. Participants between the ages of 15 and 25 years receive either aripiprazole or placebo daily, commencing at 2 mg and increasing to 10 mg by day 15. Further dose escalations (up to 30 mg) may occur, as clinically indicated. This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616001192471 on 30/08/2016. Results The primary outcome is severity of auditory verbal hallucinations assessed using the Psychotic Symptom Rating Scale. Secondary outcomes include the severity of general psychopathology, borderline personality pathology, social and occupational functioning and change in brain resting state connectivity. The primary endpoint is week 12 and secondary endpoint is week 39. Conclusion The results will inform treatment decisions for individuals with borderline personality disorder who present with auditory verbal hallucinations.

Aim It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. Methods This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. Results Ninety participants have been recruited and baseline characteristics are presented. Conclusions Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.

Background:\ud \ud A clinical and research challenge is to identify which depressed youth are at risk of “early transition to bipolar disorders (ET-BD).” This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings.\ud \ud Methods:\ud \ud Fifty cases with reliably ascertained, ET-BD I and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes.\ud \ud Results:\ud \ud Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these “BAR-Depression” criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7.\ud \ud Conclusions:\ud \ud Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening.

Background: Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up skill patients and their families. While the immediate benefits of SEI are clear, and have been demonstrated, the long-term impact of SEI on illness course is less clear. The First Episode Outcome Study involves the long-term follow-up of a representative sample of first-episode psychosis patients who were treated at the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. The aim of this presentation is 3-fold: (1) to describe the methodology of FEPOS long-term follow-up; (2) to present preliminary mortality data; and (3) examine the preliminary characteristics of those who have been contacted and interviewed. Methods: Between January 1998 and December 2000, 661 patients between the ages of 15 and 29 years were treated at the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The 18-month treatment characteristics of this cohort have been extensively examined in the FEPOS. The long-term outcomes of this cohort are now being examined in a new study (known as FEPOS15). Results: Characteristics of 46 individuals who are deceased will be described. The clinical, functional, physical health, and quality-of-life characteristics of the first 100 individuals who have been contacted will also be discussed. Conclusion: This follow-up study is one of the longest, largest, and most comprehensive studies of the multidimensional outcomes of an SEI service for psychosis.

Background The development of the ultra-high risk (UHR) criteria for psychosis over 20 years ago created a new framework for research into subthreshold states in psychiatry. Since (i) early clinical phenotypes are overlapping and non-specific, and (ii) prevention research faces the challenge of achieving adequate statistical power when focusing on low incidence syndromes such as schizophrenia, we introduce an extension of the UHR approach in order to encompass trans-diagnostic targets. The ‘CHARMS’ (Clinical High at Risk Mental State) study aims to validate a set of pluripotential criteria to prospectively identify help-seeking young people at risk of developing a range of serious mental disorders. Methods The CHARMS study is a cohort study of help-seeking young people aged 12–25 attending youth mental health services in Melbourne, Australia. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals under CHARMS threshold are allocated to CHARMS- (control) group. Transition status and clinical/functional outcomes are re-assessed at 6 and 12 months. The CHARMS criteria consist of subthreshold states for psychosis, mania, severe depression and borderline personality disorder. A range of clinical predictors, including anxiety, stress, sleep/circadian disturbance, and cognitive biases are being assessed as well. Results To date, a sample of N=73 participants have been recruited: N=49 (67%) met CHARMS criteria (CHARMS+) at baseline with N=24 (33%) allocations to the control group (CHARMS-). Of these, N=48 participants have been followed up to 6 months and a sample of N=35 has been followed up to 12 months. At 6 months, 32% of the CHARMS+ group have transitioned to a full-threshold mental disorder which increased to 37% at 12 month follow-up. 0% of the CHARMS- control group has transitioned. Discussion Our initial results indicate that the CHARMS criteria can be applied in the context of a youth mental health service and validly identify help-seeking young people at substantial risk of progressing to serious mental disorder over a short time frame (within 12 months). This study is the first to introduce and validate a set of clinical criteria to identify a broader ‘at risk’ patient population, and represents an important advance from the UHR for psychosis approach. It will foster understanding of risk factors and pathogenic mechanisms that drive the onset of severe mental disorder transdiagnostically and introduce a new case identification paradigm for the next generation of preventive intervention trials.

Background Cognitive deficits have been well documented in individuals with bipolar disorder (BD) after the first episode of mania. However, little is known about the presence of such deficits prior to the initial manic episode. Methods Participants were recruited from a cohort of 416 young people who were at ultra-high risk (UHR) for psychosis and were followed up between 4 and 13 years later. The current report is of 16 participants who developed BD over a mean follow-up period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive assessment scores were compared with those of 46 age and gender matched UHR subjects who did not transition to psychosis or BD over the follow-up period (UHR-NT) and 66 healthy comparison subjects. Results UHR-BD subjects had lower global functioning at baseline compared with UHR-NT subjects. There were no significant differences between UHR-BD and UHR-NT subjects on baseline demographic and neurocognitive characteristics. UHR-BD subjects had lower test performance than HC on picture completion, Trail-Making Tests and measures of global intelligence. Limitations Small sample size, limited and variable neurocognitive tests utilised and the confounding effects of psychotic symptoms might have impacted on the ability to detect meaningful clinical and neurocognitive differences. Conclusions In this exploratory study, neurocognition in young people who later develop BD is similar to those of subjects who are at a high risk for psychotic disorders, but there may be certain neurocognitive markers that distinguish this group from unaffected and healthy young people.

Objective Some people with major depressive disorder (MDD) may be at a pre-onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. Methods Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors. Results From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12–18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01–4.14, N = 7), earlier age of onset of depression (g = −0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79–12.66, N = 5). Conclusions Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.

Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for individuals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk criteria (BAR). This criteria comprises the peak age range of the first onset of bipolar disorder, genetic risk, presenting with sub-threshold mania, cyclothymic features or depressive symptoms. An initial pilot evaluation of the BAR criteria in 22 subjects indicated conversion rates to proxies of first-episode mania of 23% within 265 days on average, and high specificity and sensitivity of the criteria. If prospective studies confirm the validity of the BAR criteria, then the criteria would have the potential to open up new avenues of research for indicated prevention in BD and might therefore offer opportunities to ameliorate the severity of, or even prevent BD.

IMPORTANCE: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. OBJECTIVE: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. DATA SOURCES: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. STUDY SELECTION: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. DATA EXTRACTION AND SYNTHESIS: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. MAIN OUTCOMES AND MEASURES: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. RESULTS: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P

BackgroundCognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.MethodsThe design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.ResultsThere was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.ConclusionAlthough the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Background: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. Methods: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. Results: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ 2 ¼14.1, po0.001) or a family history of SUD (67% vs 12.5%, χ 2 ¼6.0, p¼0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. Conclusions and limitations: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders.

Specialised early intervention (SEI) programs have offered individuals with psychotic disorders and their families new hope for improving illness trajectories and outcomes. The Early Psychosis Prevention and Intervention Centre (EPPIC) was one of the first SEI programs developed in the world, providing services for young people experiencing their first episode of psychosis. We conducted a narrative synthesis of controlled and uncontrolled studies that have been conducted at EPPIC. The history of the EPPIC model is first described. This is followed by a discussion of clinical research emerging from EPPIC, including psychopharmacological, psychotherapeutic trials and outcome studies. Neurobiological studies are also described. Issues pertaining to the conduct of clinical research and future research directions are then described. Finally, the impact of the EPPIC model on the Australian environment is discussed.

BACKGROUND: Identification of earlier stages of Bipolar Disorder (BD), even prior to the first manic episode, may help develop interventions to prevent or delay the onset of BD. However, reliable and valid instruments are necessary to ascertain such earlier stages of BD. The aim of the current review was to identify instruments that had predictive validity and utility for BD for use in early intervention (EI) settings for the prevention of BD. METHODS: We undertook a systematic examination of studies that examined participants without BD I or II at baseline and prospectively explored the predictive abilities of instruments for BD onset over a period of 6 months or more. The instruments and the studies were rated with respect to their relative validity and utility predicting onset of BD for prevention or early intervention. Odds ratios and area under the curve (AUC) values were derived when not reported. RESULTS: Six studies were included, identifying five instruments that examined sub-threshold symptoms, family history, temperament and behavioral regulation. Though none of the identified instruments had been examined in high-quality replicated studies for predicting BD, two instruments, namely the Child Behavioral Checklist - Pediatric BD phenotype (CBCL-PBD) and the General Behavioral Inventory - Revised (GBI-R), had greater levels of validity and utility. LIMITATION: Non-inclusion of studies and instruments that incidentally identified BD on follow-up limited the breadth of the review. CONCLUSION: Instruments that test domains such as subthreshold symptoms, behavioral regulation, family history, and temperament hold promise in predicting BD onset.

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. Trial registration Australian and New Zealand Clinical Trials Registry ID: ACTRN12612001281886 (registered on 11 December 2012)

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.

Background: Anxiety disorders are common among children and adolescents with bipolar disorder. Among adults, anxiety disorder comorbidity is associated with a more severe form of bipolar disorder and a poorer outcome. There is limited data on the effect of comorbid anxiety disorder on bipolar disorder among children and adolescents. Aim: To study the prevalence of anxiety disorders among adolescents with remitted bipolar disorder and examine their association with the course and severity of illness, global functioning, and quality of life. Materials and Methods: We evaluated 46 adolescents with DSM IV bipolar disorder (I and II) who were in remission, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. We measured quality of life using the Pediatric Quality of Life Inventory and global functioning using the Children's Global Assessment Scale, and then compared these parameters between adolescents with and without current anxiety disorders. We also compared the two groups on other indicators of severity such as number of episodes, suicidal ideation, presence of psychotic symptoms, and response to treatment. Results: Among the 46 subjects, the prevalence of current and lifetime anxiety disorders were 28% (n=13) and 41% (n=19), respectively. Compared with others, adolescents with anxiety had more lifetime suicidal ideation, more number of episodes, lower physical, psychosocial, and total subjective quality of life, and lower global functioning. Conclusions: Among adolescents with bipolar disorder, anxiety disorders are associated with a poorer course, lower quality of life, and global functioning. In these subjects, anxiety disorders should be promptly recognized and treated.