Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase. Early detection and assertive community treatment of young psychotics: the Opus Study Rationale and design of the trial. A randomized controlled trial of a brief intervention for families of patients with a first episode of psychosis. Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial. Acute-phase and 1-year follow-up results of a randomized controlled trial of CBT versus Befriending for first-episode psychosis: the ACE project. Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. Cognitive therapy and recovery from acute psychosis: a controlled trial. 3. Five-year follow-up. A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis. Early intervention and a five year follow up in young adults with a short duration of untreated psychosis: ethical implications. Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis.
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. 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. A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published.
                Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used.
                Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide).
                CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome. Recent research indicates that early detection of young persons suffering from psychosis and subsequent intensive intervention enhances treatment response and prognosis, but the data are only preliminary and suggestive.
                We present the rationale and design of the largest study to date to evaluate two major issues in the field of secondary prevention: (1) Does education and intensified collaboration with general practice, social services etc. reduce the duration of untreated psychosis? and (2) Can modified assertive community treatment improve the course and outcome in young persons suffering from psychosis as compared to treatment in community mental health centres? The article aims additionally to put the study in context and assist in designing future studies.
                Preliminary experiences are described. The findings of the first 312 patients show that modified assertive community treatment results in patients adhering to treatment significantly better than standard treatment in community mental health centres.
                The surge of interest in preventively oriented detection and treatment models for untreated psychosis in young people calls for research programmes and evidence. The obstacles to this are manifold. The initial findings of the OPUS study suggest, however, that better adherence to treatment is possible. 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. Family intervention reduces relapse rates in psychosis. Cognitive-behavioural therapy (CBT) improves positive symptoms but effects on relapse rates are not established.
                To test the effectiveness of CBT and family intervention in reducing relapse, and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis.
                A multicentre randomised controlled trial (ISRCTN83557988) with two pathways: those without carers were allocated to treatment as usual or CBT plus treatment as usual, those with carers to treatment as usual, CBT plus treatment as usual or family intervention plus treatment as usual. The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months.
                A total of 301 patients and 83 carers participated. Primary outcome data were available on 96% of the total sample. The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months. For secondary outcomes, CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention. In people with carers, CBT significantly improved delusional distress and social functioning. Therapy did not change key psychological processes.
                Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms. Any CBT targeted at this acute population requires development. The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers. 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. 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. This paper describes the 5-year outcome of a cohort of patients who had received a cognitive therapy intervention during an acute episode of non-affective psychosis.
                Thirty-four out of the original 40 patients who had taken part in a randomised controlled trial of a cognitive intervention were assessed, using standardised instruments completed at entry into the study. In the original trial, half the patients received a cognitive therapy programme (CT group) and the other half received recreational activities and support (ATY group).
                At follow-up no significant differences in relapse rate, positive symptoms or insight between the groups were found, although the CT group did show significantly greater perceived 'Control over illness' than the ATY group. For individuals who had experienced a maximum of one relapse in the follow-up period, self-reported residual delusional beliefs and observer-rated hallucinations and delusions were significantly less in the CT than in the ATY group.
                Cognitive therapy applied in the acute phase of a psychotic disorder can produce enduring and significant clinical benefits if experience of relapse can be minimised. Recent research indicates that cognitive-behaviour therapy (CBT) can be effective in ameliorating persistent positive symptoms in chronic psychotic patients. The effectiveness of CBT in acute and recent-onset psychosis has been little explored, although a recent pilot study indicated that CBT could significantly improve recovery in acutely psychotic inpatients.
                Short-term individual CBT was compared to supportive counselling/psychoeducation (SC) as an adjunct to standard inpatient hospital care and medication in 21 inpatients experiencing a recent-onset acute schizophrenic episode.
                Both groups showed significant reductions in Brief Psychiatric Rating Scale (BPRS) scores following treatment, although there were no group differences. Time to discharge did not differ significantly between the groups, although there was a greater variance for the SC patients. Two-year follow-up showed no significant differences between the groups, although the number of patients who relapsed, the number of relapses and the time to recurrence of psychotic symptoms was lower in the CBT group than the SC group. Interestingly, the time to readmission was shorter in the CBT group.
                CBT and SC are acceptable treatments for recent-onset acutely psychotic inpatients. A larger randomised controlled trial over multiple hospital sites is warranted. 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. 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.
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.