A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Acute-phase and 1-year follow-up results of a randomized controlled trial of CBT versus Befriending for first-episode psychosis: the ACE project. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. The Lambeth Early Onset Crisis Assessment Team Study: general practitioner education and access to an early detection team in first-episode psychosis. Randomized controlled trial of a cannabis-focused intervention for young people with first-episode psychosis. Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis. A randomized controlled trial of a brief intervention for families of patients with a first episode of psychosis. Early intervention and a five year follow up in young adults with a short duration of untreated psychosis: ethical implications. Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment. A preliminary trial of adherence-coping-education (ACE) therapy for early psychosis.
To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness.
                Randomised clinical trial.
                Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus, Denmark.
                547 patients with first episode of schizophrenia spectrum disorder.
                Integrated treatment and standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre.
                Psychotic and negative symptoms (each scored from 0 to a maximum of 5) at one and two years' follow-up.
                At one year's follow-up, psychotic symptoms changed favourably to a mean of 1.09 (standard deviation 1.27) with an estimated mean difference between groups of -0.31 (95% confidence interval -0.55 to -0.07, P = 0.02) in favour of integrated treatment. Negative symptoms changed favourably with an estimated difference between groups of -0.36 (-0.54 to -0.17, P < 0.001) in favour of integrated treatment. At two years' follow-up the estimated mean difference between groups in psychotic symptoms was -0.32 (-0.58 to -0.06, P = 0.02) and in negative symptoms was -0.45 (-0.67 to -0.22, P < 0.001), both in favour of integrated treatment. Patients who received integrated treatment had significantly less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment.
                Integrated treatment improved clinical outcome and adherence to treatment. The improvement in clinical outcome was consistent at one year and two year follow-ups. Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase.
                A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months.
                By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use.
                More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence. The ACE project involved 62 participants with a first episode of psychosis randomly assigned to either a cognitive behaviour therapy (CBT) intervention known as Active Cognitive Therapy for Early Psychosis (ACE) or a control condition known as Befriending. The study hypotheses were that: (1) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending; (2) these improvements in symptoms and functioning would be sustained at a 1-year follow-up; and (3) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up.
                Two therapists treated the participants across both conditions. Participants could not receive any more than 20 sessions within 14 weeks. Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning: at pretreatment, the middle of treatment, the end of treatment and at 1-year follow-up. An independent pair of raters assessed treatment integrity.
                Both groups improved significantly over time. ACE significantly outperformed Befriending by improving functioning at mid-treatment, but it did not improve positive or negative symptoms. Past the mid-treatment assessment, Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up.
                There is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger samples. This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia.
                This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores.
                During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24).
                A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted. There are few evaluations of strategies to improve rates of early detection and treatment of patients with first-episode psychosis.
                To evaluate the effectiveness of a general practitioner (GP) education programme and an early detection assessment team (the Lambeth Early Onset Crisis Assessment Team; LEO CAT) in reducing delays in accessing treatment for first-episode psychosis patients.
                46 clusters of GP practices randomised to GP education in early detection with direct access to LEO CAT v. care as usual. Primary outcome measures were GP referral rates, duration of untreated psychosis (DUP) and delays in receiving treatment.
                150 patients with first-episode psychosis were recruited; 113 were registered with the study GPs, who referred 54 (47.7%) directly to mental health services. Significantly more intervention group GPs (86.1% v. 65.7%) referred their patients directly to mental health services and fewer patients experienced long delays in receiving treatment. However, their overall DUP was unaffected.
                Educating GPs improves detection and referral rates of first-episode psychosis patients. An early detection team reduces the long delays in initial assessment and treatment. However, these only impact on the later phases of the DUP. Broader measures, such as public health education, are needed to reduce the earlier delays in DUP. To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP).
                Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention.
                There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time.
                PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population. Advances in the ability to identify people at high risk of developing psychosis have generated interest in the possibility of preventing psychosis.
                To evaluate the efficacy of cognitive therapy for the prevention of transition to psychosis.
                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.
                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
                Cognitive therapy appears to be an acceptable and efficacious intervention for people at high risk of developing psychosis. Young people with early psychosis are at particularly high risk of suicide. However, there is evidence that early intervention can reduce this risk. Despite these advances, first episode psychosis patients attending these new services still remain at risk. To address this concern, a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre (EPPIC). The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy (LifeSPAN therapy) for acutely suicidal patients with psychosis. We describe the development of these interventions in this paper.
                Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC. Second, staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service. Third, a suicide risk monitoring system was introduced to identify those at highest risk. Finally, patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a randomised controlled trial.
                Fifty-six suicidal patients with first episode psychosis were randomly assigned to standard clinical care or standard care plus LifeSPAN therapy. Forty-two patients completed the intervention. Clinical ratings and measures of suicidality and risk were assessed before, immediately after the intervention, and 6 months later. Benefits were noted in the treatment group on indirect measures of suicidality, e.g., hopelessness. The treatment group showed a greater average improvement (though not significant) on a measure of suicide ideation.
                Early intervention in psychosis for young people reduces the risk of suicide. Augmenting early intervention with a suicide preventative therapy may further reduce this risk. Carers' satisfaction with psychiatric services related to information and advice is generally poor. This may be particularly true for services trying to meet the needs of ethnically diverse communities. It is important that services attempt to ameliorate carers' concerns as early as possible. The authors aimed to assess the impact of a brief educational and advice support service on carers of patients with a first episode of psychotic illness.
                Carers of all patients identified with a first episode of psychosis in a defined psychiatric catchment area of North London were invited to participate. Following consent from patients and relatives, relatives were randomly allocated to receive (in addition to usual services) a brief intervention comprising education and advice about the disorder from a support team or to usual care from community psychiatric services.
                One hundred and six carers were recruited to the study. Take-up of the intervention was less than expected and the intervention had little impact. The authors found no differences over time between the randomized arms for relatives' satisfaction (F = 23, p = 0 .4, df = 1) or number of days spent by patients in hospital over nine months from entry to the trial (F= 1.7, p= 0.18, df = 1).
                It was found that the support and advice intervention for families had little impact on their satisfaction or on patients' outcomes. However, failure to take up the intervention threatens the conclusions as the power to show an effect was reduced. Although family interventions, in general, are considered an important adjunct to the treatment of patients with chronic psychosis, there may be difficulties in providing an educational and support intervention shortly after first onset. How and when psychiatric services provide information and advice to carers of people newly diagnosed with a psychosis requires further study. In a Dutch treatment intervention study of patients (n=76) with first psychotic episodes of schizophrenia the hypothesis tested was whether early differential treatment after an acute psychotic break improved outcome as compared with other studies. Patients had a relatively short duration of untreated psychosis. No significant effect between two treatment conditions on relapse rate was found. The 15-month intervention program kept the psychotic relapse rate as low as 15%; lower than comparable studies. Thus, the initial results were in support of the hypothesis. After completion of the 15 months study, patients were referred to other agencies and followed for five years. Results of the follow up study showed that the low relapse rate could not be maintained. Of the remaining 71 patients of the initial sample, 52% had one or more psychotic relapses, 25% developed chronic positive symptoms and 23% did not have another psychotic episode. In addition, the level of social functioning turned out to be low: the majority of patients were dependent upon their parents, few held down a skilled or paid job and also their quality of life seemed low, results indicate that early intervention may improve short term but not long term outcome in schizophrenia. Our results also suggest that referral to other mental health agencies after intervention is not sufficient. Continuity of outpatient care, including continuity of a professional relationship, continuity of support for the family, and the continuity in management of illness, medication and stress may be a key issue in the first five years after the onset of psychosis in schizophrenia. Early recognition and intervention may not nearly be as important for outcome as continuity in care and caregivers. At present, however, it remains questionable whether early intervention programs in first-episode patients with a short duration of untreated psychosis can offer the prospect of altering the course of schizophrenia without a sustained comprehensive treatment program. The Early Detection and Intervention Programme of the German Research Network on Schizophrenia (GRNS) investigates the initial prodromal phase of psychosis in a multidimensional approach. Two intervention strategies are being studied by two large-scale multicentre projects.
                To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure.
                Comprehensive cognitive-behavioural therapy has been developed for patients in the "early initial prodromal state". For patients in the "late initial prodromal state" the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition.
                Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48.5%) gave informed consent to participate in the trials.
                The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis. A pilot randomized controlled trial was conducted to examine the effectiveness of adherence-coping-education (ACE) therapy. Twenty-four individuals with early psychosis were randomized to receive 14 sessions of either ACE therapy in addition to treatment as usual, or supportive therapy in addition to treatment as usual. Participants were assessed at baseline, midtreatment, and posttreatment on measures of medication attitudes, psychotic and depressive symptoms, and social functioning. ACE therapy was well tolerated and was associated with significant decrease in symptoms, as well as trend-level improvements in attitudes toward treatment. These results lend initial support for the feasibility of ACE Therapy, and suggest that it may have promise in facilitating recovery for individuals recovering from an initial psychotic episode.
There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials.