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Abstract: Intervening to shorten the pre-psychotic and pre-treatment phases has been attractive as a possible way to improve long-term outcome. Several types of prodrome to schizophrenia have been identified and there is evidence that treating them prevents transition to psychosis during medium-term follow-up. These experimental treatments include antipsychotics and cognitive-behavioural therapy (CBT). New services to treat psychosis earlier and more effectively have been springing up, though evidence for their relative benefits is not yet unequivocal. They rely on characteristic antipsychotic regimes and psychosocial interventions. [Copyright &y& Elsevier]

Abstract: Diffusion tensor imaging (DTI) studies have identified changes in white matter tracts in schizophrenia patients and those at high risk of transition. Schizotypal samples represent a group on the schizophrenia continuum that share some aetiological risk factors but without the confounds of illness. The aim of the current study was to compare tract microstructural coherence as measured by fractional anisotropy (FA) between 12 psychometrically defined schizotypes and controls. We investigated bilaterally the uncinate and arcuate fasciculi (UF and AF) via a probabilistic tractography algorithm (PICo), with FA values compared between groups. Partial correlations were also examined between measures of subclinical hallucinatory/delusional experiences and FA values. Participants with schizotypal features were found to have increased FA values in the left hemisphere UF only. In the whole sample there was a positive correlation between FA values and measures of hallucinatory experience in the right AF. These findings suggest subtle changes in microstructural coherence are found in individuals with schizotypal features, but are not similar to changes predominantly observed in clinical samples. Correlations between mild hallucinatory experience and FA values could indicate increasing tract coherence could be associated with symptom formation. [Copyright &y& Elsevier]

Abstract: Suicide risk is high in early psychosis. Recent research has suggested that mood variability may be associated with levels of suicidal thoughts and behaviour. This has not been investigated in individuals during and following a first or second episode of non-affective psychosis. Repeated-measures data over 18 months from a large randomised controlled trial for cognitive behaviour therapy (N=309) were analysed using latent growth curve modelling, whereby both the variability and the level of depression, anxiety and guilt were entered as predictors of suicidality. The variability of depression, but not guilt and anxiety, predicted the course of suicidality even when controlling for a large range of potential confounders. The level of depression, anxiety and guilt for each participant also strongly predicted the development of suicidality. The findings support the theory that variability in depression may contribute to the formation of suicidal ideation and related behaviour. More variable depression may be harder to predict and intervene against, and therefore increase the likelihood that suicidality escalates. The levels of emotions may also be an important determinant. This has implications for the treatment and assessment of suicidality in early psychosis. [Copyright &y& Elsevier]

Abstract: Major problems with existing RCTs evaluating psychosocial interventions for psychosis and substance misuse have been identified, in particular small sample sizes, high attrition rates, and short follow up periods. With a sample size of 327 and a follow up of 2 years, the MIDAS trial in the UK is to date the largest RCT for people with psychosis and substance use and is evaluating an integrated MI and CBT (“MiCBT”) client therapy. Whilst the outcomes of the study are not yet available, data on recruitment and retention indicate that attrition rates in MIDAS are low and the majority of those allocated to treatment received a substantial number of therapy sessions. Sample characteristics are in line with those reported in epidemiological studies and are indicative of the challenges facing mental health services attempting to manage the client group: substance use is often longstanding, with frequent use at moderate or severe level and low motivation for change, and seen in the context of low levels of functioning and significant psychopathology. We conclude that this is a methodologically robust study that will have results generalisable to mental health services. [Copyright &y& Elsevier]

Objective: To assess whether clozapine is likely to be more cost-effective than other second-generation antipsychotics (SGAs) in people with schizophrenia. Methods: An integrated clinical and economic multicenter, rater-blind, randomized controlled trial (RCT) compared clozapine to the class of other SGAs, using the perspectives of the National Health Service, social support services, and patients. The practice setting was secondary and primary care in the United Kingdom; patients were followed for 1 year. Incremental cost-effectiveness ratios (ICERs), net benefit statistics, and cost acceptability curves were estimated. Results: The ICER for clozapine was £33,240 per quality-adjusted life-year (QALY) (range £23,000–70,000 for the sensitivity analyses). The proportion of simulations when clozapine was more cost-effective than other SGAs reached 50% if decision-makers are prepared to pay £30,000 to £35,000 per QALY. This is at the top of the range of acceptable willingness-to-pay values per QALY implied by decisions taken by the National Institute for Health and Clinical Excellence (NICE). Conclusions: This study adds to a limited body of evidence comparing clozapine to other SGAs and is the first economic and clinical RCT to compare clozapine to the class of other SGAs using the lower cost of generic clozapine and a pragmatic trial design. Policy decisions by the NICE suggest that additional reasons would be needed to accept clozapine as effective and efficient if it had a high probability of having ICERs more than £35,000 per QALY. The results and limitations of the analysis suggest that there is still a need for further economic evaluation of clozapine. [ABSTRACT FROM AUTHOR]

We used UK CUtLASS RCT data to establish that patients’ rating of mental health improvement (baseline to week 12) correlated significantly with percentage symptom improvement (PANSS). In a regression analysis predictors of the patient’s week 12 mental health rating were percentage change in positive symptoms (PANSS), DAI score and the patient's rating of side effects. Patients in an RCT were able to subjectively rate their mental health status, validated by objective improvement on the PANSS. [ABSTRACT FROM AUTHOR]