A naturalistic study of treatment outcomes with aripiprazole in young people with first episode psychosis

Objective: Adequate treatment of a first psychotic episode in young people is a difficult challenge but may be of critical importance for changing the course of psychotic illness. Pharmacotherapy is the standard treatment of psychosis, however there is a paucity of data specific to first-episode psychosis.
Methods: In this study 12 young people who presented with a psychotic episode at a specialised early intervention service were commenced on treatment with aripiprazole. They were assessed at baseline and weeks 4, 6, 24 and 48 using a broad battery of outcome measures. Case notes were also examined.
Results: Data was available for 6 participants at week 48, and of those, one remained on treatment with Aripiprazole at endpoint. Case histories were typified by presentations that included illicit substance use and treatments characterised by several changes in medications. No single treatment choice predominated. Most participants tolerated treatment and showed symptomatic improvement with individualised therapy.
Conclusion: Most participants showed improvement during the treatment period. Aripiprazole was one of many medications used in this study and may have been useful for the treatment of some individuals with first episode psychosis.

A randomized controlled trial of vocational intervention for young people with first-episode psychosis : method

Young people who are experiencing first-episode psychosis (FEP) are at increased risk of being unemployed compared to either their same age peers in the general population, or those with other mental illnesses. Significant research has been conducted examining employment interventions for those with chronic psychotic illness. This has yielded strong results in favour of an intervention called individual placement and support (IPS). However, significantly less work has examined the benefit of this approach to those in FEP when the potential for vocational rehabilitation is perhaps greater. This study adds to the knowledge of vocational intervention in first-episode psychotic illness. Additionally, it expands this work into the areas of cognition, social cognition, social inclusion and economics.

Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids.

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings.

First aid recommendations for psychosis: using the Delphi method to gain consensus between mental health consumers, carers, and clinicians.

BACKGROUND: Members of the general public often lack the knowledge and skills to intervene effectively to help someone who may be developing a psychotic illness before appropriate professional help is received. METHODS: We used the Delphi method to determine recommendations on first aid for psychosis. An international panel of 157 mental health consumers, carers, and clinicians completed a 146-item questionnaire about how a member of the public could help someone who may be experiencing psychosis. The panel members rated each questionnaire item according to whether they believed the statement should be included in the first aid recommendations. The results were analyzed by comparing consensus rates across the 3 groups. Three rounds of ratings were required to consolidate consensus levels. RESULTS: Eighty-nine items were endorsed by >or=80% of panel members from all 3 groups as essential or important for psychosis first aid. These items were grouped under the following 9 headings: how to know if someone is experiencing psychosis; how to approach someone who may be experiencing psychosis; how to be supportive; how to deal with delusions and hallucinations; how to deal with communication difficulties; whether to encourage the person to seek professional help; what to do if the person does not want help; what to do in a crisis situation when the person has become acutely unwell; what to do if the person becomes aggressive. CONCLUSIONS: These recommendations will improve the provision of first aid to individuals who are developing a psychotic disorder by informing the content of training courses.

Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial

IMPORTANCE: A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. OBJECTIVE: To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. INTERVENTIONS: Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. RESULTS: Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. CONCLUSIONS AND RELEVANCE: Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00361543.

Evaluation of Bayesian belief networks for diagnosis of psychotic disorders

The thesis examined the inter-rater reliability and procedural validity of four computerised Bayesian belief networks (BBNs) which were developed to assist with the diagnosis of psychotic disorders. The results of this research indicated that BBNs can significantly improve diagnostic reliability and may represent an important advance over current diagnostic methods. The professional portfolio investigated, through the presentation of case studies and review of literature relevant to each case study, how comorbidity and context of depression may impact on cognitive behavioural therapy treatment.

Gender differences in first episode psychotic mania

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.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania

Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania.

Associations of obsessive-compulsive symptoms with clinical and neurocognitive features in schizophrenia according to stage of illness

This study aimed to investigate the association of obsessive-compulsive symptoms with clinical and neurocognitive features in patients with schizophrenia. This study enrolled 163 people with schizophrenia who were receiving risperidone monotherapy. Comorbid obsessive-compulsive symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale, and subjects with a score≥10 constituted the obsessive-compulsive symptom group (n=30, 18.4%). The learning index was significantly higher in patients with obsessive-compulsive symptoms than in those without such symptoms after adjusting for age, stage (early and chronic), duration of illness, and CDSS score. However, there was no significant interaction between obsessive-compulsive symptoms and stage of illness. Scores on Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Beck Depression Inventory were significantly higher in the obsessive-compulsive symptom group. In addition, the Subjective Well-being under Neuroleptic Treatment score was significantly lower in the obsessive-compulsive symptom group. In conclusion, comorbid obsessive-compulsive symptoms in patients with schizophrenia were associated with a higher learning ability without a significant interaction with stage of illness. However, schizophrenia patients with obsessive-compulsive symptoms had more severe psychotic and depressive symptoms and poorer quality of life.

Associations of obsessive-compulsive symptoms with clinical and neurocognitive features in schizophrenia according to stage of illness

This study aimed to investigate the association of obsessive-compulsive symptoms with clinical and neurocognitive features in patients with schizophrenia. This study enrolled 163 people with schizophrenia who were receiving risperidone monotherapy. Comorbid obsessive-compulsive symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale, and subjects with a score ≥ 10 constituted the obsessive-compulsive symptom group (n=30, 18.4%). The learning index was significantly higher in patients with obsessive-compulsive symptoms than in those without such symptoms after adjusting for age, stage (early and chronic), duration of illness, and CDSS score. However, there was no significant interaction between obsessive-compulsive symptoms and stage of illness. Scores on Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Beck Depression Inventory were significantly higher in the obsessive-compulsive symptom group. In addition, the Subjective Well-being under Neuroleptic Treatment score was significantly lower in the obsessive-compulsive symptom group. In conclusion, comorbid obsessive-compulsive symptoms in patients with schizophrenia were associated with a higher learning ability without a significant interaction with stage of illness. However, schizophrenia patients with obsessive-compulsive symptoms had more severe psychotic and depressive symptoms and poorer quality of life.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Journeys through illness: suffering and resilience

This chapter:
•  explores the notion of living with chronic illness as a journey;
•  explores the concepts of enduring and uncertainity as aspects of the
   suffering associated with living with chronic illness;
•  defines resilience
•  explores the ways in which people develop and use resilient strategies
    in the face of chronic illness;
•  describes survivorship as an outcome of resilience; and
•  discusses the role of nurses and other caring professionals in relation to
    supporting a person through their suffering, and to develop their resilience
    in the face of that suffering.