Psychiatry - Research Publications

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    A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder
    Ratheesh, A ; Davey, C ; Hetrick, S ; Alvarez-Jimenez, M ; Voutier, C ; Bechdolf, A ; McGorry, PD ; Scott, J ; Berk, M ; Cotton, SM (WILEY, 2017-04)
    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.
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    Ethical considerations in preventive interventions for bipolar disorder
    Ratheesh, A ; Cotton, SM ; Davey, CG ; Adams, S ; Bechdolf, A ; Macneil, C ; Berk, M ; McGorry, PD (WILEY, 2017-04)
    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.
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    Improving functional outcomes in early-stage bipolar disorder: The protocol for the REsearch into COgnitive and behavioural VERsatility trial
    Cotton, SM ; Berk, M ; Jackson, H ; Murray, G ; Filia, K ; Hasty, M ; Chanen, A ; Davey, C ; Nelson, B ; Ratheesh, A ; MacNeil, C (WILEY, 2019-12)
    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.
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    Aripiprazole compared with placebo for auditory verbal hallucinations in youth with borderline personality disorder: Protocol for the VERBATIM randomized controlled trial
    Chanen, AM ; Betts, J ; Jackson, H ; McGorry, P ; Nelson, B ; Cotton, SM ; Bartholomeusz, C ; Jovev, M ; Ratheesh, A ; Davey, C ; Pantelis, C ; McCutcheon, L ; Francey, S ; Bhaduri, A ; Lowe, D ; Rayner, V ; Thompson, K (WILEY, 2019-12)
    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.
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    Factors associated with vocational disengagement among young people entering mental health treatment
    Caruana, E ; Allott, K ; Farhall, J ; Parrish, EM ; Davey, CG ; Chanen, AM ; Killackey, E ; Cotton, SM (WILEY, 2019-08)
    AIM: Most mental disorders have their onset by age 25, disrupting normative vocational engagement. Factors associated with vocational disengagement at first contact with specialist treatment are important for service planning. The aim of this paper was to investigate the association between theoretically important factors and vocational disengagement for youth entering mental health treatment. METHODS: A file audit was used to extract vocational data of 145 young people aged 15 to 25 years entering treatment in 2011 at a public youth mental health service in Melbourne, Australia. Comparisons were made across three specialist programs for: psychosis (n = 50), mood disorders (n = 52) and borderline personality pathology (n = 43). Individual characteristics were entered into univariate and multivariate logistic regressions to investigate their associations with vocational disengagement. RESULTS: Educational disengagement was associated with being older (OR = 4.38, P = 0.004) and not living with parents (OR = 2.87, P = 0.038). Unemployment and being NEET (Not in Education, Employment or Training) were both associated with not having commenced tertiary education (OR = 0.23, P = 0.022; OR = 0.05, P = 0.002; respectively). Being NEET was also associated with being older (OR = 6.18, P = 0.004). Primary diagnostic grouping was not associated with vocational disengagement, once accounting for other factors. CONCLUSIONS: The likelihood of vocational disengagement did not differ across disorder groups, implying that intervention should be "transdiagnostic" and might best target education first, specifically post-secondary qualifications. Other domains or variables not measured in this study are also likely to be important, and this might include young people's support systems and symptom severity. Qualitative studies may be useful for exploring further factors relevant to vocational engagement.
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    Vocational engagement among young people entering mental health treatment compared with their general population peers
    Caruana, E ; Farhall, J ; Cotton, SM ; Parrish, E ; van-der-EL, K ; Davey, CG ; Chanen, AM ; Bryce, SD ; Killackey, E ; Allott, K (WILEY, 2019-06)
    AIM: To compare rates of vocational engagement for youth entering specialist mental health treatment with the general population. METHODS: A file audit retrieved vocational data for 145 youth aged 15 to 25 entering treatment. Clinical and population data were stratified by age and sex and compared between cohorts. RESULTS: Compared to the population, young people entering mental health treatment were less likely to have completed at least Year 11 in school (77% vs 42%, P < 0.001); and demonstrated higher rates of "Not in Education, Employment or Training" (9% vs 33%, P < 0.001). Individuals aged 15 to 18 years entering treatment experienced greater rates of educational disengagement than the population (30% vs 11%, P < 0.001), whereas people aged 19 to 25 years showed higher unemployment rates (52% vs 35%, P = 0.003). CONCLUSIONS: Youth entering specialist mental health treatment have marked levels of vocational disengagement compared to demographically-matched peers. Early vocational intervention for these young people is essential.
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    A Comparison of Vocational Engagement Among Young People with Psychosis, Depression and Borderline Personality Pathology
    Caruana, E ; Cotton, SM ; Farhall, J ; Parrish, EM ; Chanen, A ; Davey, CG ; Killackey, E ; Allott, K (SPRINGER, 2018-08)
    Poor vocational engagement is well documented among young people experiencing first-episode psychosis (FEP). The aim of the present study was to establish and compare rates of vocational engagement across young people with first-episode psychosis, depression, and borderline personality pathology. A file audit was used to collect vocational data of young people aged 15-25 entering tertiary mental health treatment in 2011. Rates of vocational engagement were similar across groups, indicating that like those with FEP, young people with depression and borderline personality pathology experience impaired vocational engagement and are in need of targeted vocational interventions. Post hoc analysis indicated that that the depression group had significantly more people who were partially vocationally engaged compared with the psychosis group, suggesting that vocational interventions might need to be targeted differently across different diagnostic groups. Future research should explore risk factors for vocational disengagement across diagnostic groups in order to inform intervention development.
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    A psychoeducational group intervention for family and friends of youth with borderline personality disorder features: protocol for a randomised controlled trial
    Betts, J ; Pearce, J ; McKechnie, B ; McCutcheon, L ; Cotton, SM ; Jovev, M ; Rayner, V ; Seigerman, M ; Hulbert, C ; Mcnab, C ; Chanen, AM (BMC, 2018-07-25)
    BACKGROUND: Caring for a person with borderline personality disorder is associated with poor outcomes including elevated psychological distress and burden. This study will compare the effectiveness of two brief psychoeducational programs for carers of youth presenting for early intervention for borderline personality disorder features. The protocol for this study is presented here. METHODS: The study is a single-centre parallel group, randomised controlled trial. As a family unit, relatives, partners and friends ('carers') are randomly allocated to one of two treatment arms to receive either an online borderline personality disorder psychoeducation program, or both the online psychoeducation group and a face-to-face group program, Making Sense of Borderline Personality Disorder. Carers are assessed at baseline and follow-up (4 weeks after the intervention). It is expected that participants who received the combined group and online programs will have better outcomes than those who received the online program alone. The primary outcome is carer burden, assessed using the negative appraisal subscales of the Experience of Caregiving Inventory. Secondary outcomes include positive experiences of caregiving, coping, self-rated personality disorder knowledge, psychological distress, expressed emotion and quality of life. DISCUSSION: This will be the first published evaluation of a psychoeducational intervention for carers of youth with borderline personality disorder features using a randomised controlled trial design. The results have the potential to inform clinicians and carers about the effectiveness of brief interventions designed to support families and friends of young people with borderline personality disorder, and what medium those interventions should utilise. TRIAL REGISTRATION: Prospectively registered with the Australian New Zealand Clinical Trial Registry ACTRN12616000304437 on 08 March 2016.
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    Web-based intervention to improve quality of life in late stage bipolar disorder (ORBIT): randomised controlled trial protocol
    Fletcher, K ; Foley, F ; Thomas, N ; Michalak, E ; Berk, L ; Berk, M ; Bowe, S ; Cotton, S ; Engel, L ; Johnson, SL ; Jones, S ; Kyrios, M ; Lapsley, S ; Mihalopoulos, C ; Perich, T ; Murray, G (BMC, 2018-07-13)
    BACKGROUND: The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The intervention is a guided self-help, mindfulness based intervention (MBI) developed in consultation with consumers, designed specifically for web-based delivery, with email coaching support. METHODS/DESIGN: This international RCT will involve a comparison of the effectiveness and cost-effectiveness of two 5-week adjunctive online self-management interventions: Mindfulness for Bipolar 2.0 and an active control (Psychoeducation for Bipolar). A total of 300 participants will be recruited primarily via social media channels. Main inclusion criteria are: a diagnosis of BD (confirmed via a phone-administered structured diagnostic interview), no current mood episode, history of 10 or more mood episodes, no current psychotic features or active suicidality, under the care of a medical practitioner. Block randomisation will be used for allocation to the interventions, and participants will retain access to the program for 6 months. Evaluations will be conducted at pre- and post- treatment, and at 3- and 6- months follow-up. The primary outcome measure will be the Brief Quality of Life in Bipolar Disorder Scale (Brief QoL.BD), collected immediately post-intervention at 5 weeks (T1). Secondary measures include BD-related symptoms (mania, depression, anxiety, stress), time to first relapse, functioning, sleep quality, social rhythm stability and resource use. Measurements will be collected online and via telephone assessments at baseline (T0), 5 weeks (T1), three months (T2) and six months (T3). Candidate moderators (diagnosis, anxiety or substance comorbidities, demographics and current treatments) will be investigated as will putative therapeutic mechanisms including mindfulness, emotion regulation and self-compassion. A cost-effectiveness analysis will be conducted. Acceptability and any unwanted events (including adverse treatment reactions) will be documented and explored. DISCUSSION: This definitive trial will test the effectiveness and cost-effectiveness of a novel QoL focused, mindfulness based, online guided self-help intervention for late stage BD, and investigate its putative mechanisms of therapeutic action. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03197974 . Registered 23 June 2017.
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    Gender differences in first episode psychotic mania
    Cotton, SM ; Lambert, M ; Berk, M ; Schimmelmann, BG ; Butselaar, FJ ; McGorry, PD ; Conus, P (BIOMED CENTRAL LTD, 2013-03-13)
    BACKGROUND: The aim of this paper was to delineate the impact of gender on premorbid history, onset, and 18 month outcomes of first episode psychotic mania (FEPM) patients. METHODS: Medical file audit assessment of 118 (male = 71; female = 47) patients with FEPM aged 15 to 29 years was undertaken on clinical and functional measures. RESULTS: Males with FEPM had increased likelihood of substance use (OR = 13.41, p <.001) and forensic issues (OR = 4.71, p = .008), whereas females were more likely to have history of sexual abuse trauma (OR = 7.12, p = .001). At service entry, males were more likely to be using substances, especially cannabis (OR = 2.15, p = .047), had more severe illness (OR = 1.72, p = .037), and poorer functioning (OR = 0.96, p = .045). During treatment males were more likely to decrease substance use (OR = 5.34, p = .008) and were more likely to be living with family (OR = 4.30, p = .009). There were no gender differences in age of onset, psychopathology or functioning at discharge. CONCLUSIONS: Clinically meaningful gender differences in FEPM were driven by risk factors possibly associated with poor outcome. For males, substance use might be associated with poorer clinical presentation and functioning. In females with FEPM, the impact of sexual trauma on illness course warrants further consideration.