Effectiveness and optimal duration of early intervention treatment in adult-onset psychosis: a randomized clinical trial.

BACKGROUND: Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention. METHODS: 360 psychosis patients aged 26-55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years. RESULTS: Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001-0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004-0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year. CONCLUSIONS: Specialized EI treatment for psychosis patients aged 26-55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.

Achieving better outcomes for schizophrenia patients in Hong Kong: Strategies for improving treatment adherence.

Recent research on second-generation long-acting injectable antipsychotics (LAI SGAs) has proven its effectiveness in minimizing medication nonadherence problem and reducing relapses. Administered by medical professionals, making quick detection of nonadherence possible, long-acting injectable antipsychotics (LAIs) facilitate immediate intervention and recovery process, and thus are favored by psychiatrists. Despite a higher initial cost with LAIs, the subsequent schizophrenia-related health costs for hospitalizations and outpatients are greatly reduced. With reference to guidelines published by psychiatric associations around the globe, this article looks at scenarios in Hong Kong on the management of severe mentally ill patients with regard to the use of a host of psychosocial interventions as well as LAI SGAs as a preferable treatment. In particular, it examines the benefits of using LAI SGAs for Hong Kong patients who demonstrated high nonadherence treatment rates due to their social environment. It assesses the rationale behind the early usages of LAI SGAs, which help to provide better recovery outcomes for patients.

The role of symptoms and insight in mediating cognition and functioning in first episode psychosis.

INTRODUCTION: Achieving functional recovery in patients with psychosis is a challenge in clinical practice. Investigating the complex interplay between cognition, symptoms, insight and functional outcome in first episode psychosis will be crucial to understanding the factors leading to better functioning. METHODS: In this 12-month prospective follow-up study, we investigated how cognition, clinical symptoms, and insight into illness affected overall functioning in 160 patients with first episode psychosis recruited from the Early Assessment Service for Young People with Psychosis (EASY) in Hong Kong from July 1, 2014 to June 30, 2016. Cognition was assessed at baseline while symptoms, insight, and functioning were assessed at 12-month follow-up. Structural equation modelling was used to examine the direct and indirect relationships between functioning and other latent constructs. RESULTS: Symptoms (negative symptoms and general psychopathology) and insight were shown to be significant mediators between cognition and functioning. The significant direct relationship between cognition and functioning (ß = 0.387; p < 0.001) became insignificant (ß = 0.079; p = 0.578) after including symptoms and insight in the model. Symptoms and insight were significantly associated with cognition (symptoms, ß = -0.469; p < 0.001; insight, ß = -0.372; p < 0.001) and predicted functioning (symptoms, ß = -0.558; p < 0.001; insight, ß = -0.264; p < 0.01). CONCLUSION: Symptoms and insight mediated the effects of cognition on functioning. Interventions for improving functioning in patients with first episode psychosis should target not only cognition but also symptoms and insight.

Predicting first-episode psychosis patients who will never relapse over 10 years.

BACKGROUND: Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode. METHOD: Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning. RESULTS: Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders. CONCLUSIONS: Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.

Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial.

BACKGROUND: The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years. METHODS: This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n=89; oral quetiapine 400 mg daily) or early treatment discontinuation (n=89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340. FINDINGS: Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1·84, 95% CI 1·15-2·96; p=0·012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group). INTERPRETATION: In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome. FUNDING: Food and Health Bureau, Research Grants Council of Hong Kong, and AstraZeneca.

Metacognitive training for delusions (MCTd): effectiveness on data-gathering and belief flexibility in a Chinese sample.

Metacognitive training (MCT) was developed to promote awareness of reasoning biases among patients with schizophrenia. While MCT has been translated into 31 languages, most MCT studies were conducted in Europe, including newer evidence recommending an individualized approach of delivery. As reasoning biases covered in MCT are separable processes and are associated with different symptoms, testing the effect of selected MCT modules would help to develop a targeted and cost-effective intervention for specific symptoms and associated mechanisms. This study tested the efficacy of a four-session metacognitive training for delusions, MCTd (in Traditional Chinese with cultural adaptations, provided individually), as an adjunct to antipsychotics in reducing severity and conviction of delusions, jumping to conclusions (JTC) bias and belief inflexibility. Forty-four patients with delusions were randomized into the MCTd or the wait-list control condition. Patients on wait-list received the same MCTd after 4 weeks of treatment as usual (TAU). Assessment interviews took place before and after the treatment, and at 4-week follow-up. There was an additional baseline assessment for the controls. JTC and belief flexibility were measured by the beads tasks and the Maudsley Assessment of Delusions Scale. Attendance rate of the MCTd was satisfactory (84.5%). Compared to TAU, there was a greater reduction in psychotic symptoms, delusional severity and conviction following MCTd. There was a large treatment effect size in improvement in belief flexibility. Improvement in reaction to hypothetical contradiction predicted treatment effect in positive symptoms and delusions. JTC bias was reduced following MCTd, although the treatment effect was not significantly larger than TAU. Our results support the use of process-based interventions that target psychological mechanisms underlying specific psychotic symptoms as adjuncts to more conventional approaches.

Effect of aerobic exercise training on chinese population with mild to moderate depression in Hong Kong.

Background. Exercise has been suggested to be a viable treatment for depression. This study investigates the effect of supervised aerobic exercise training on depressive symptoms and physical performance among Chinese patients with mild to moderate depression in early in-patient phase. Methods. A randomized repeated measure and assessor-blinded study design was used. Subjects in aerobic exercise group received 30 minutes of aerobic training, five days a week for 3 weeks. Depressive symptoms (MADRS and C-BDI) and domains in physical performance were assessed at baseline and program end. Results. Subjects in aerobic exercise group showed a more significant reduction in depressive scores (MADRS) as compared to control (between-group mean difference = 10.08 ± 9.41; P = 0.026) after 3 weeks training. The exercise group also demonstrated a significant improvement in flexibility (between-group mean difference = 4.4 ± 6.13; P = 0.02). Limitations. There was lack of longitudinal followup to examine the long-term effect of aerobic exercise on patients with depression. Conclusions. Aerobic exercise in addition to pharmacological intervention can have a synergistic effect in reducing depressive symptoms and increasing flexibility among Chinese population with mild to moderate depression. Early introduction of exercise training in in-patient phase can help to bridge the gap of therapeutic latency of antidepressants during its nonresponse period.

Predicting 1-year risk for relapse in patients who have discontinued or continued quetiapine after remission from first-episode psychosis.

OBJECTIVE: Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication. METHOD: Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year. RESULTS: Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms. CONCLUSION: Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group.

Duration of untreated psychosis: relationship with baseline characteristics and three-year outcome in first-episode psychosis.

Duration of untreated psychosis (DUP) has been considered as one of the few potentially malleable prognostic factors in psychotic illness. The literature demonstrated that prolonged DUP predicted the level of positive symptoms, but its relationships with negative symptoms and functional outcome were less clear-cut. Thus far, most first-episode studies have been conducted in western countries. Yet, it is known that illness outcome might be modified by socio-cultural factors. In this study, we aimed to examine the impact of DUP on baseline characteristics, clinical and vocational outcomes over 3 years in 700 Chinese young people who presented with first-episode psychosis to a specialized early intervention service in Hong Kong. Our results showed that prolonged DUP was associated with male sex, younger age of onset, schizophrenia-spectrum diagnosis, insidious development of psychosis, fewer baseline positive symptoms and less likelihood of hospitalization at intake. Regression analyses revealed that prolonged DUP was significantly predictive of outcome on positive symptoms, recovery and sustained full-time employment in our first-episode psychosis cohort. Taken together, our study provided further supportive evidence regarding the prognostic value of DUP on illness outcome. Additionally, it suggested that an adverse impact of treatment delay for psychosis may likely be applied across regions of various ethno-cultural backgrounds.

Early intervention for psychotic disorders: Real-life implementation in Hong Kong.

Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education.

Three-year outcome of phase-specific early intervention for first-episode psychosis: a cohort study in Hong Kong.

AIM: Although phase-specific early intervention for first-episode psychosis has been implemented in many different parts of the world, limited medium-term outcome data are available in non-Western populations with relatively low mental health resources. The study aimed to determine the effectiveness of phase-specific early intervention in first-episode psychosis. METHOD: In this cohort study, we compared the 3-year outcome of 700 first-episode psychosis patients who received phase-specific early intervention with that of 700 patients matched for age, sex and diagnosis who received standard psychiatric care prior to early intervention. Using a structured data acquisition procedure, we determined functional outcome, symptom levels, relapse, recovery, suicidal behaviour and service utilization from clinical records. RESULTS: Patients in the early intervention group had longer full-time employment or study (P<0.001), fewer days of hospitalization (P<0.001), less severe positive symptoms (P=0.006), less severe negative symptoms (P =0.001), fewer suicides (P=0.009) and fewer disengagements (P=0.002) than the historical control group. Additionally, more patients in the early intervention group experienced a period of recovery (P=0.001), but the two groups had similar rates of relapse (P=0.08) and durations of untreated psychosis (P=0.72). CONCLUSIONS: The 3-year outcome in phase-specific early intervention compared favourably with that of standard psychiatric care, particularly with respect to functional outcome and reduction in hospitalizations, suicides and disengagements. However, intervention did not appear to reduce the rate of relapse.

Gender differences in patients presenting with first-episode psychosis in Hong Kong: a three-year follow up study.

OBJECTIVE: The aim of the current study was to investigate gender differences with respect to pre-treatment characteristics, clinical presentation, service utilization and functional outcome in patients presenting with first-episode psychosis. METHODS: A total of 700 participants (men, n = 360; women, n = 340) aged 15 to 25 years consecutively enrolled in a territory-wide first-episode psychosis treatment programme in Hong Kong from July 2001 to August 2003 were studied. Baseline and three-year follow up variables were collected via systematic medical file review. RESULTS: At service entry, men had significantly lower educational attainment (p < 0.01), longer median duration of untreated psychosis (p < 0.001), fewer past suicidal attempts (p < 0.01), more severe negative symptoms (p < 0.05) and fewer affective symptoms (p < 0.01) than women. There was no significant gender difference in age of onset. In three-year follow up, men had more prominent negative symptoms (p < 0.001), fewer affective symptoms (p < 0.01), more violent behaviour and forensic records (p < 0.01), and higher rate of substance abuse (p < 0.01). Women achieved higher levels of functioning than men (Social Occupational Functioning Assessment Scale (SOFAS), p < 0.001) and a significantly higher proportion of women than men engaged in full-time employment or study for at least 12 consecutive months (p < 0.001) in the initial three years after psychiatric treatment. CONCLUSION: Notable gender differences in clinical profiles, illness trajectory and functional outcome were demonstrated in Chinese young people suffering from first-episode psychosis. Differential needs between men and women and hence gender-specific therapeutic strategies should be considered in early intervention service.

Naming psychosis: the Hong Kong experience.

AIM: Schizophrenia translates in Chinese as 'Mind Split Disease' which is heavily stigmatizing. The narrow conceptualization for schizophrenia alone was insufficient, in the context of early detection and intervention for psychosis. The need for an effective Chinese translation for psychotic disorders was imminent upon the launch of the Early Assessment Service for Young People with Psychosis in Hong Kong, where public awareness strategies had to be built upon effective communication of the disorder. METHODS: 'Si Jue Shi Tiao', the new term for psychosis, described 'thought and perceptual dysregulation'. This new terminology and concept was strategically introduced to the local community. RESULTS: The term 'Si Jue Shi Tiao' was taken up well locally and had demonstrated interactions within the Chinese and East Asian communities. The public has taken in the broader concept of psychosis, in contrary to the previous concept of schizophrenia per se. CONCLUSIONS: In Hong Kong, the restrictive view of perceiving psychotic disorders as schizophrenia was broadened upon the introduction of a more embracing, less stigmatizing term 'Si Jue Shi Tiao'. Effective establishment of this term to the local vocabulary allowed a basis for communication as well as public education work. Further evaluation is necessary to determine the effectiveness of the naming and to guide further public awareness strategies.

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial.

OBJECTIVE: To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment. DESIGN: 12 month randomised, double blind, placebo controlled trial. SETTING: Early psychosis outpatient clinics in Hong Kong. PARTICIPANTS: 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis. INTERVENTIONS: Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred. MAIN OUTCOME MEASURE: Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds. RESULTS: 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07). CONCLUSION: In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.

Early intervention for psychosis in Hong Kong--the EASY programme.

AIM: This article aims to describe the Hong Kong experience in developing and implementing an early psychosis programme. METHODS: In 2001, the Early Assessment Service for Young People with Psychosis programme was launched in Hong Kong, providing both educational and service components. Public education includes promotion of timely help-seeking, accessible channels to service and knowledge of psychosis. The 2-year phase-specific intervention includes intensive medical follow-up and individualized psychosocial intervention. The programme has adopted the case-management approach, in which case managers provide protocol-based psychosocial intervention. The programme collaborates with non-governmental organizations and community networks in the provision of rehabilitation service. RESULTS: An average of over 600 young patients enter the programme for intensive treatment each year. Based on preliminary data from a 3-year outcome study, patients in the programme have remarkable reductions in hospital stay accompanied by improvements in vocational functioning. CONCLUSIONS: The results suggested that the programme improved patients' outcome. Additional costs such as extra medical staff and medications may be offset by the shortened hospital stay. Further directions in early intervention are also discussed.

Five-year stability of ICD-10 diagnoses among Chinese patients presented with first-episode psychosis in Hong Kong.

BACKGROUND: Diagnostic stability is one measure of predictive validity for psychiatric syndromes. It is an under-studied area in functional psychosis despite its clinical and research implications. We aimed at evaluating the stability of ICD-10 diagnoses in a sample of young people with first-episode psychosis. METHOD: One hundred and sixty-six Hong Kong Chinese enrolled in a regional first-episode psychosis treatment program were studied. Subjects' baseline and final 5-year consensus diagnoses were established via systematic medical records' review to determine diagnostic stability and to identify predictors of diagnostic shift towards schizophrenia spectrum. RESULTS: The overall diagnostic consistency was 80.7%. Bipolar affective disorder and schizophrenia were the most stable diagnostic categories over 5 years with prospective consistency of 100% and 95.8% respectively. The least stable baseline diagnoses were unspecified non-organic psychosis, acute and transient psychotic disorders and delusional disorder. Around one-fifth (19.3%) of subjects had diagnostic revision in 5 years. The predominant pattern of diagnostic shift was towards schizophrenia spectrum disorder. Family history of psychosis and longer duration of untreated psychosis were associated with diagnostic transition towards schizophrenia spectrum. CONCLUSIONS: Schizophrenia and bipolar affective disorder were diagnostically stable and could be reliably classified at intake in a Chinese first-episode psychosis sample using the ICD-10 criteria. Diagnostic instability in the least prevalent categories of functional psychosis highlights the limitations of current taxonomies and calls for ongoing revision of diagnostic criteria. In the absence of biological marker, longitudinal validation across consecutive episodes is necessary for accurate diagnostic ascertainment.