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Background: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved., Methods: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I., Findings: Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group)., Interpretation: Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy., Funding: National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Digital technology has the potential to improve outcomes for people with psychosis. However, to date, research has largely ignored service user views on digital health interventions (DHIs)., Objective: The objective of our study was to explore early psychosis service users' subjective views on DHIs., Methods: Framework analysis was undertaken with data obtained from 21 semistructured interviews with people registered with early intervention for psychosis services. Robust measures were used to develop a stable framework, including member checking, triangulation, independent verification of themes, and consensus meetings., Results: The following 4 themes were established a priori: acceptability of technology in psychosis and mental health; technology increasing access to and augmenting mental health support; barriers to adopting DHIs; and concerns about management of data protection, privacy, risk, and security of information. The following 2 themes were generated a posteriori: blending DHIs with face-to-face treatment and empowerment, control, and choice. DHIs were also viewed as potentially destigmatizing, overcoming barriers faced in traditional service settings, facilitating communication, and empowering service users to take active control of their health care., Conclusions: In the first study of its kind, early psychosis service users' were largely positive about the potential use of DHIs supporting and managing mental health. Overall, service users felt that DHIs were a progressive, modern, and relevant platform for health care delivery. Concerns were expressed around privacy and data security and practical barriers inherent within DHIs, all of which require further attention. Future research should explore whether findings transfer to other service user groups, other technology delivery formats, and across a range of treatment modalities., (©Sandra Bucci, Rohan Morris, Katherine Berry, Natalie Berry, Gillian Haddock, Christine Barrowclough, Shôn Lewis, Dawn Edge. Originally published in JMIR Mental Health (http://mental.jmir.org), 31.10.2018.)

Mental and brain disorders represent the greatest health burden to Europe-not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5-10 years, help to close the biggest gaps in mental health research in Europe, and in turn overcome the substantial challenges caused by mental disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafinil as the pharmacological augmenting agent, as it is known to have beneficial effects on learning and cognition. 49 participants with chronic schizophrenia were enroled in a double-blind, placebo-controlled study across two sites and were randomised to either modafinil (200mg/day) or placebo. All participants engaged in a cognitive training program for 10 consecutive weekdays. The primary outcome measure was the performance on the trained tasks and secondary outcome measures included MATRICS cognitive battery, proxy measures of everyday functioning and symptom measures. 84% of the participants completed all study visits. Both groups showed significant improvement in the performance of the trained tasks suggesting potential for further learning. Modafinil did not induce differential enhancement on the performance of the trained tasks or any differential enhancement of the neuropsychological and functional measures compared to placebo. Modafinil showed no significant effects on symptom severity. Our study demonstrated that combining pharmacological compounds with cognitive training is acceptable to patients and can be implemented in large double-blind randomised controlled trials. The lack of differential enhancement of training-induced learning raises questions, such as choice and optimal dose of drug, cognitive domains to be trained, type of cognitive training, intervention duration and chronicity of illness that require systematic investigation in future studies., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Background: Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia., Methods: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial., Results: We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence., Discussion: Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded-beside markers for metabolism of antipsychotics-no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Current approaches to the management of severe mental illness have four major limitations: 1) symptom reporting is intermittent and subject to problems with reliability; 2) service users report feelings of disengagement from their care planning; 3) late detection of symptoms delay interventions and increase the risk of relapse; and 4) care systems are held back by the costs of unscheduled hospital admissions that could have been avoided with earlier detection and intervention. The ClinTouch system was developed to close the loop between service users and health professionals. ClinTouch is an end-to-end secure platform, providing a validated mobile assessment technology, a web interface to view symptom data and a clinical algorithm to detect risk of relapse. ClinTouch integrates high-resolution, continuous longitudinal symptom data into mental health care services and presents it in a form that is easy to use for targeting care where it is needed. The architecture and methodology can be easily extended to other clinical domains, where the paradigm of targeted clinical interventions, triggered by the early detection of decline, can improve health outcomes.

Background: It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations., Aims: To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence., Method: Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study)., Results: Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA., Conclusions: A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible., (Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.)

Background: Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed., Aims: To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway., Method: Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed., Results: A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP., Conclusions: Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.

The impact of non-neurological and metabolic side effects (NNSEs) on the prescription of antipsychotics in real clinical practice remains unclear. We conducted an intention-to-treat, secondary analysis of data from a randomised, controlled trial (CUtLASS-1; n=227) to examine NNSEs emergent at 12 weeks and 52 weeks. A clinically significant difference was defined as double or half the symptoms in groups prescribed first- versus second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). There were no differences between the treatment groups at baseline. At both 12 and 52 weeks follow-up, patients on second-generation drugs were more likely than their first-generation counterparts to experience cardiovascular problems and anticholinergic side effects, as well as increased sexual side effects in men. Objective weight gain was equivalent between the two groups at 12 weeks, but by one year fewer patients in the second-generation arm experienced weight gain and there was no significant difference with regard to percent change in BMI. These results suggest that there may be clinically significant increases in anticholinergic, cardiovascular, and sexual side effects for patients on second-generation drugs. The expected increased weight gain in the second-generation arm did not occur. This study provides evidence that clinicians should take a more nuanced approach toward expert antipsychotic prescription, rather than viewing the drugs as distinct classes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence., Aims: To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs., Method: We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points., Results: At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS., Conclusions: The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.

Objective: To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia., Design: Multisite single blind randomised controlled trial., Setting: Diverse services at five UK sites., Participants: 288 participants aged 14-35 years (mean 20.74, SD 4.34 years) at high risk of psychosis: 144 were assigned to cognitive therapy plus monitoring of mental state and 144 to monitoring of mental state only. Participants were followed-up for a minimum of 12 months and a maximum of 24 months., Intervention: Cognitive therapy (up to 26 (mean 9.1) sessions over six months) plus monitoring of mental state compared with monitoring of mental state only., Main Outcome Measures: Primary outcome was scores on the comprehensive assessment of at risk mental states (CAARMS), which provides a dichotomous transition to psychosis score and ordinal scores for severity of psychotic symptoms and distress. Secondary outcomes included emotional dysfunction and quality of life., Results: Transition to psychosis based on intention to treat was analysed using discrete time survival models. Overall, the prevalence of transition was lower than expected (23/288; 8%), with no significant difference between the two groups (proportional odds ratio 0.73, 95% confidence interval 0.32 to 1.68). Changes in severity of symptoms and distress, as well as secondary outcomes, were analysed using random effects regression (analysis of covariance) adjusted for site and baseline symptoms. Distress from psychotic symptoms did not differ (estimated difference at 12 months -3.00, 95% confidence interval -6.95 to 0.94) but their severity was significantly reduced in the group assigned to cognitive therapy (estimated between group effect size at 12 months -3.67, -6.71 to -0.64, P=0.018)., Conclusions: Cognitive therapy plus monitoring did not significantly reduce transition to psychosis or symptom related distress but reduced the severity of psychotic symptoms in young people at high risk. Most participants in both groups improved over time. The results have important implications for the at risk mental state concept., Trial Registration: Current Controlled Trials ISRCTN56283883.

Context: Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions., Objective: To develop a differential predictive clinical model of transition to first-episode psychosis., Design: Prospective multicenter, naturalistic field study with a total follow-up time of 18 months., Setting: Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England., Participants: Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom-based criterion cognitive disturbances (COGDIS)., Main Outcome Measure: Incidence of transition to psychosis., Results: At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition., Conclusions: The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Background: The nosological status of auditory hallucinations in non-clinical samples is unclear., Aims: To investigate the functional neural basis of non-clinical hallucinations., Method: After selection from 1206 people, 68 participants of high, medium and low hallucination proneness completed a task designed to elicit verbal hallucinatory phenomena under conditions of stimulus degradation. Eight subjects who reported hearing a voice when none was present repeated the task during functional imaging., Results: During the signal detection task, the high hallucination-prone participants reported a voice to be present when it was not (false alarms) significantly more often than the average or low participants (P<0.03, d.f.=2). On functional magnetic resonance imaging, patterns of activation during these false alarms showed activation in the superior and middle temporal cortex (P<0.001)., Conclusions: Auditory hallucinatory experiences reported in non-clinical samples appear to be mediated by similar patterns of cerebral activation as found during hallucinations in schizophrenia.

There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis. A randomized controlled trial compared cognitive therapy (CT) over 6 months with monthly monitoring in 58 patients meeting criteria for ultrahigh risk of developing a first episode of psychosis. Participants were followed up over a 3-year period. Logistic regression demonstrated that CT significantly reduced likelihood of being prescribed antipsychotic medication over a 3-year period, but it did not affect transition to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. However, exploratory analyses revealed that CT significantly reduced the likelihood of making progression to psychosis as defined on the PANSS over 3 years after controlling for baseline cognitive factors. Follow-up rate at 3 years was 47%. There appear to be enduring benefits of CT over the long term, suggesting that it is an efficacious intervention for people at high risk of developing psychosis.

Context: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms., Objective: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs., Design: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis., Setting: Fourteen community psychiatric services in the English National Health Service., Participants: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects., Interventions: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist., Main Outcome Measures: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care., Results: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar., Conclusions: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.

Neurological soft signs have been observed in patients with schizophrenia and their relatives. However, it has not been considered whether the increased rates of neurological soft signs are related to measures of psychosis proneness in the general population. We tested this hypothesis in a group of normal volunteers (n = 28) who scored highly for positive schizotypy when assessed online and a control group (n = 33) who scored below the mean. Compared with the controls, high psychosis-prone individuals showed significantly higher Total and Other Soft Signs subscale scores on the Neurological Evaluation Scale. It appears that soft signs are also associated with psychosis proneness when measured in the general population, which suggests that soft signs are distributed along a continuum of risk for schizophrenia.

Background: Psychological treatments have been shown to be effective in patients with psychosis. However, the studies published to date have included participants across wide age ranges, so few conclusions can be reached about the effectiveness of such treatments in relation to age., Aims: To evaluate outcomes by age in a randomised controlled trial designed to evaluate the effectiveness of cognitive-behavioural therapy (CBT), supportive counselling and treatment as usual., Method: Outcomes were evaluated in terms of symptoms, social functioning, insight and therapeutic alliance according to age at 3- and 18-month follow-up., Results: Younger participants responded better to supportive counselling than to treatment as usual and CBTover 3 months. Older participants responded better to CBT than to supportive counselling over 18 months. Younger participants showed a greater increase in insight after CBT compared with treatment as usual and supportive counselling, and were more difficult to engage in therapy., Conclusions: Young people may have different needs with regard to engagement in psychological treatments. Treatment providers need to take age-specific factors into account.

There is a range of psychological interventions for established schizophrenia. These include family interventions, motivational interventions for substance misuse and for non-adherence to medication, cognitive remediation for neurocognitive deficits and cognitive-behavioural therapy for symptoms. Psychological interventions may explicitly target risk factors for poor outcome, such as substance use, or protective factors, such as adherence to medication, or be directed at specific symptoms or deficits. There is emerging evidence for efficacy of psychological treatments during, following and even prior to the first episode. Important areas for further study are how different treatment modalities can interact productively, and patient and carer preferences for treatment. Many trials of psychological treatments have design flaws and this tends to overestimate the treatment effect.

Background: A major reason for interest in early intervention for psychotic disorders is the hypothesised relationship between longer duration of untreated psychosis (DUP) and poorer outcome of treatment., Aims: To critically examine the evidence concerning DUP being related to treatment outcome and possible mediators of any such relationship., Method: A systematic review of studies in which DUP is assessed and its relationship to treatment outcome is examined. In addition, studies relevant to possible neurotoxic effects of DUP were reviewed., Results: The research is entirely of a correlational nature and, therefore, firm conclusions regarding causation are not possible. There is, however, substantial evidence of DUP being an independent predictor of treatment outcome, particularly remission of positive symptoms, over the first year or so of treatment. Findings regarding the possible neurotoxic effects of DUP are inconsistent., Conclusions: There continues to be evidence consistent with DUP influencing aspects of treatment outcome. Non-correlational studies, such as quasi-experimental designs, could provide stronger evidence regarding causality.

Background: Advances in the ability to identify people at high risk of developing psychosis have generated interest in the possibility of preventing psychosis., Aims: To evaluate the efficacy of cognitive therapy for the prevention of transition to psychosis., Method: A randomised controlled trial compared cognitive therapy with treatment as usual in 58 patients at ultra-high risk of developing a first episode of psychosis. Therapy was provided over 6 months, and all patients were monitored on a monthly basis for 12 months., Results: Logistic regression demonstrated that cognitive therapy significantly reduced the likelihood of making progression to psychosis as defined on the Positive and Negative Syndrome Scale over 12 months. In addition, it significantly reduced the likelihood of being prescribed antipsychotic medication and of meeting criteria for a DSM-IV diagnosis of a psychotic disorder. Analysis of covariance showed that the intervention also significantly improved positive symptoms of psychosis in this population over the 12-month period, Conclusions: Cognitive therapy appears to be an acceptable and efficacious intervention for people at high risk of developing psychosis.

Background: Comorbid substance misuse in people with schizophrenia is associated with poor clinical and social outcomes. There are few studies of psychological treatments for this population and little long-term follow-up of their benefits., Aims: To investigate symptom, substance use, functioning and health economy outcomes for patients with schizophrenia and their carers 18 months after a cognitive-behavioural treatment (CBT) programme., Method: Patients with dual diagnosis from a randomised controlled trial of motivational intervention, individual CBT and family intervention were assessed on multiple outcomes at 18-month follow-up. Carers were assessed on symptom, functioning and needs over 12 months. Health economy data were collected over 18 months., Results: There were significant improvements in patient functioning compared with routine care over 18 months. No significant differences between treatment groups were found in carer or cost outcomes., Conclusions: The treatment programme was superior to routine care on outcomes relating to illness and service use, and the cost was comparable to the control treatment.

The relationship between neurocognitive impairments in schizophrenia remains unclear. Recent literature was reviewed and the most consistent finding was an association between perseverative errors on the Wisconsin Card Sort Test (WCST) and poor insight. The aim was to confirm and extend this finding using a range of assessments relevant to perseveration, and different dimensions of insight, in a sample of 33 acutely psychotic subjects within 5 years of onset of schizophrenia and related disorders. Results showed a correlation (r=-0.59) between insight and perseverative errors, rather than more general measures of abstraction. A factor representing relabelling symptoms, derived from insight scale items, correlated even more strongly; however, other insight factors correlated more weakly, suggesting they are less dependent on neuropsychological deficits. The ability to monitor output and correct errors appears to be closely related to the core features of insight in psychosis.