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.

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.

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.