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.

Elucidating the relationship between internalized stigma, cognitive insight, illness severity, and functioning in patients with schizophrenia using a path analysis approach.

BACKGROUND: There is a paucity of studies examining the interrelationship between internalized stigma, cognitive insight, illness severity, and functioning. AIMS: This study examined the dynamics of the relationship between these factors using a path modelling approach. METHODS: Two hundred and seven patients with schizophrenia spectrum disorders were recruited in this cross-sectional study. Patients were assessed on internalized stigma, cognitive insight (including its two domains, self-reflectiveness and self-certainty), illness severity and functioning. Path analysis was used to test the hypothesized model for the interrelationship between the variables. RESULTS: A direct positive association was observed between self-certainty and internalized stigma. This was also observed via the paths running through illness severity and functioning. Self-reflectiveness was only associated with self-certainty in the model. The residual variance of internalized stigma in the path model was relatively high. CONCLUSION: Our findings highlight that self-certainty is associated with internalized stigma along with illness severity and functioning in individuals with schizophrenia. Therefore, interventions on reduction of internalized stigma may benefit from a multipronged approach targeting self-certainty, illness severity and functioning. The relatively high residual variance of internalized stigma in the model highlights the need for further research to provide better understanding on the mechanisms underlying internalized stigma.

Effectiveness of a structured physical rehabilitation program on the physical fitness, mental health and pain for Chinese patients with major depressive disorders in Hong Kong - a randomized controlled trial with 9-month follow-up outcomes.

PURPOSE: The long-term and specific impacts on the physical and mental health for Chinese people with major depressive disorders (MDD) are not well-studied. The aim of the study is to investigate both short-and long-term effects of a structured physical rehabilitation program on the physical and mental health and pain for Chinese patients with MDD. METHODS: 84 Chinese patients with MDD were randomized to intervention (n = 42) or control group (n = 42). Intervention group received a 12-week physical rehabilitation program and the control group with 12-week waiting period followed the same pathway as the intervention group afterwards for longitudinal analysis. Data were collected at baseline (T1), end of 12-week program (T2) and 9-month follow-up period (T3). RESULTS: Significant pre- and post-intervention improvements were noted in cardiopulmonary function, depressive symptoms, pain, body composition, muscle strength and flexibility for the intervention group. Although mild attenuation is noted from T2 to T3, subjects without exercise habit experienced significant decline in cardiopulmonary function, depressive symptoms and pain (p < 0.05) but not in those who developed exercise habit (p > 0.05). CONCLUSION: Structured physical rehabilitation program could improve physical and mental fitness and pain for Chinese MDD patients. Its effects could be sustained up to 9 months after cessation of the program provided that people establish their own exercise habit.IMPLICATIONS FOR REHABILITATIONExercise is an effective means of improving physical and mental health and pain for people with major depressive disorders (MDD).People with MDD have multiple reasons, both physically and psychosocially, for physical deconditioning and hurdles for exercise.Structured supervised exercise program can enhance physical and mental health and may likely enhance exercise compliance in this population.

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.

Guidance on the clinical understanding and use of long-acting injectable antipsychotics in Schizophrenia: Hong Kong Consensus Statements.

AIMS: There is increasing evidence showing the importance of long-acting injectable antipsychotics in the management of schizophrenia, especially in terms of improving patient medication compliance. A panel of experienced clinicians in Hong Kong mapped out a set of consensus statements with an aim to facilitate the understanding and use of long-acting injectable antipsychotics among local physicians. METHODS: Eight discussion areas regarding long-acting injectable antipsychotics were selected by the chairman of the consensus group. A series of meetings were held for the panelists to discuss the published literature and their clinical experience, followed by the drafting of consensus statements. At the final meeting, each consensus statement was voted on anonymously by all members based on its practicability of recommendation in Hong Kong. RESULTS: A total of 12 consensus statements on the rational use of long-acting injectable antipsychotics were established and accepted by the consensus group. CONCLUSION: The consensus statements aim to provide practical guidance for Hong Kong physicians on the use of long-acting injectable antipsychotics in schizophrenia patients. These statements may also serve as a reference for doctors in other parts of the Asia-Pacific region.

Relationship between subjective quality of life and perceptions of recovery orientation of treatment service in patients with schizophrenia and major depressive disorder.

OBJECTIVE: This study aimed to investigate the relationship between subjective quality of life (QOL) and the specific domains of perceptions of recovery orientation of treatment services in patients with schizophrenia and major depressive disorder (MDD). METHODS: One hundred and seventy-nine patients with schizophrenia spectrum disorders and fifty-seven patients with MDD were recruited. Patients were assessed on subjective QOL, self-reported depressive symptoms, illness severity, functioning, and perception of recovery orientation of the service environment (RSA). A multiple linear regression model was used to assess the relationship between QOL and RSA score, controlling for all other factors. Spearman correlation analysis was used to examine the relationship between RSA domains and total QOL in each diagnostic group separately. RESULTS: The regression model explained 47.4 % of the variance observed in total QOL. Depressive symptoms, functioning and RSA were significantly associated with total QOL in the model. Domains one (life goals) and five (individually tailored services) of the RSA were associated with QOL in both groups. Domains two (patient involvement) and three (diversity of treatment options) were associated with total QOL only in patients with schizophrenia. CONCLUSION: Our findings highlight that perceptions of recovery orientation of service, depressive symptoms and functioning significantly affected the subjective QOL of patients with serious mental illness. The differential relationship observed between QOL and domains of RSA in patients with MDD and schizophrenia suggests that targeted interventions meeting the needs of different patient groups may be crucial to improve QOL of patients.

A structured review of psychiatric rehabilitation for individuals living with severe mental illness within three regions of the Asia-Pacific: Implications for practice and policy.

INTRODUCTION: Psychiatric rehabilitation can provide and support recovery-oriented care by assisting individuals living with severe mental illness to lead full lives. Despite a well-established evidence-base, implementation and access to these interventions in clinical practice for people with severe mental illness in the Asia-Pacific region is low. We therefore aimed to evaluate prominent themes impacting on clinical practice, policy, and the implementation of psychiatric rehabilitation across the Asia-Pacific region. METHODS: A comprehensive review of relevant literature on psychiatric rehabilitation of three regions within the Asia-Pacific was conducted using a structured search of PubMed and other databases. Eligible articles were selected which focussed on how psychiatric rehabilitation is defined and implemented across the Asia-Pacific region, as well as the associated successes and challenges. Common themes were generated. RESULTS: Six themes emerged: the impact of policy, legislation, and human rights; access difficulties; the important role of family; the significance of culture, religion, and spiritual beliefs; the widespread impact of stigma; and the indigenous models of excellence being developed. DISCUSSION: Consideration of the six themes and their implications should help raise awareness of the issues involved in the provision of psychiatric rehabilitation in the Asia-Pacific region and may improve outcomes for people living with severe mental illness. Suggested strategies include: developing a shared understanding of psychiatric rehabilitation; establishing quality legislation that's well implemented; adapting evidence-based models to develop culturally appropriate services; implementing stigma reduction and empowerment-based interventions; and, ensuring coordinated action among all stakeholders, combined with effective leadership.

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.

Electroacupuncture for tapering off long-term benzodiazepine use: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of using electroacupuncture as an adjunct treatment in enhancing the benzodiazepine cessation rate in long-term benzodiazepine users. METHODS: This was a randomized, assessor- and subject-blinded, controlled trial. One hundred and forty-four long-term benzodiazepine users were randomly assigned to receive either electroacupuncture or placebo acupuncture (a sham itervention using non-invasive placebo needles) combined with a gradual benzodiazepine tapering schedule for 4 weeks. The primary outcome was the cessation rate of benzodiazepine use. Subjects were assessed on their benzodiazepine usage, benzodiazepine withdrawal symptoms, insomnia severity, and anxiety and depressive symptoms at baseline, week 6 and week 16. RESULTS: The cessation rates of the electroacupuncture and placebo acupuncture groups at 12 weeks post-treatment were 9.17% and 10.83%, respectively. Both groups showed a reduction in benzodiazepine usage by a self-completed drug record at week 16 (compared to baseline: electroacupuncture group -40.23% versus placebo acupuncture group -48.76%). However, no significant between-group differences were found in the benzodiazepine cessation rate, reduction in benzodiazepine usage, and other secondary measures across all the study time points. CONCLUSIONS: Electroacupuncture showed a similar cessation rate in benzodiazepine use to that of non-invasive placebo acupuncture in long-term users during a 4-week gradual tapering schedule. The evidence did not support advantages of electroacupuncture over non-invasive placebo acupuncture on reducing insomnia, anxiety, depression, or other withdrawal symptoms during the gradual tapering schedule. Despite a 40% decrease in the benzodiazepine usage in both groups, the effects may be attributed to the non-specific effects of acupuncture. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02475538.

Acupuncture with or without combined auricular acupuncture for insomnia: a randomised, waitlist-controlled trial.

BACKGROUND: Few high-quality, large-scale, controlled trials comparing the effectiveness and safety of acupuncture, auricular acupuncture and combined acupuncture treatment for insomnia are available. OBJECTIVE: To carry out a randomised, assessor-blinded, waitlist-controlled trial to test the superiority of combination treatment. METHODS: After in-person and polysomnography screening, 224 subjects (mean age 53.4 years; 75.4% female) with DSM-5 insomnia disorder, who were free from major psychiatric disorders and with sleep-diary-derived sleep efficiency averaged over 1 week of <85%, were randomised to acupuncture alone, acupuncture plus auricular acupuncture (combination treatment), or a waitlist in a 3:3:1 ratio. Standardised acupuncture and combination treatment were provided three times weekly for 3 weeks. The primary outcome was sleep-diary-derived sleep efficiency. Secondary outcomes included wrist actigraphy and self-reported scales on insomnia, anxiety and depression, fatigue, sleepiness and functioning. Assessments were conducted at baseline, 1 week, 4 weeks and 13 weeks after treatment. Participants on the waitlist were re-randomised to receive acupuncture or combination treatment after the second post-baseline assessment. RESULTS: There was no significant difference between acupuncture and combination treatment in the primary outcome and most secondary outcomes at all time points. However, both treatments were better than waitlist in reducing insomnia, anxiety/depressive symptoms and fatigue, and improving function. Within-group improvements were maintained at 13 weeks after treatment. Of 260 adverse events, 243 were mild (93.5%). Discontinuation due to adverse events was 2.1% and 3.1% for acupuncture and combination treatment, respectively. CONCLUSIONS: Limited by short-term treatment and follow-up, the attempt to augment acupuncture by auricular acupuncture was not supported. Acupuncture and combination treatment were safe and had mild hypnotic effects, which lasted for at least 13 weeks. TRIAL REGISTRATION NUMBER: NCT01891097; Results.

Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

BACKGROUND: Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. METHODS/DESIGN: The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. DISCUSSION: Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. TRIAL REGISTRATION: ClinicalTrials.gov NCT02475538 .

Prevalence of anxiety disorders in community dwelling older adults in Hong Kong.

BACKGROUND: Anxiety disorders are prevalent yet under-recognized in late life. We examined the prevalence of anxiety disorders in a representative sample of community dwelling older adults in Hong Kong. METHOD: Data on 1,158 non-demented respondents aged 60-75 years were extracted from the Hong Kong Mental Morbidity survey (HKMMS). Anxiety was assessed with the revised Clinical Interview Schedule (CIS-R). RESULT: One hundred and thirty-seven respondents (11.9%, 95% CI = 10-13.7%) had common mental disorders with a CIS-R score of 12 or above. 8% (95% CI = 6.5-9.6%) had anxiety, 2.2% (95% CI = 1.3-3%) had an anxiety disorder comorbid with depressive disorder, and 1.7% (95% CI = 1-2.5%) had depression. Anxious individuals were more likely to be females (χ 2 = 25.3, p < 0.001), had higher chronic physical burden (t = -9.3, p < 0.001), lower SF-12 physical functioning score (t = 9.2, p < 0.001), and poorer delayed recall (t = 2.3, p = 0.022). The risk of anxiety was higher for females (OR 2.8, 95% C.I. 1.7-4.6, p < 0.001) and those with physical illnesses (OR 1.4, 95% C.I. 1.3-1.6, p < 0.001). The risk of anxiety disorders increased in those with disorders of cardiovascular (OR 1.9, 95% C.I. 1.2-2.9, p = 0.003), musculoskeletal (OR 2.0, 95% C.I. 1.5-2.7, p < 0.001), and genitourinary system (OR 2.0, 95% C.I. 1.3-3.2, p = 0.002). CONCLUSIONS: The prevalence of anxiety disorders in Hong Kong older population was 8%. Female gender and those with poor physical health were at a greater risk of developing anxiety disorders. Our findings also suggested potential risk for early sign of memory impairment in cognitively healthy individuals with anxiety disorders.

Bipolar risk and mental imagery susceptibility in a representative sample of Chinese adults residing in the community.

BACKGROUND: We need to better understand the cognitive factors associated with risk for bipolar disorders. Recent research suggests that increased susceptibility to mental imagery may be one such factor. However, since this research was primarily conducted with Western students and at a single time-point, it is not known whether the relationship between imagery susceptibility and bipolar symptoms exists across cultures or within the general community, or whether this relationship remains stable over time. AIM: This study evaluated whether Chinese adults identified as being at high (HR) versus low (LR) risk of developing bipolar disorders showed greater mental imagery susceptibility. We aimed to test whether such a relationship was stable over time by measuring imagery characteristics at baseline and at the 7-week follow-up. METHOD: This prospective study recruited a community sample of N = 80 Chinese adults screened for the absence of neurotic and psychotic disorders. The sample was split into HR (n = 18) and LR (n = 62) groups at baseline based on a criterion cut-off score on a measure of hypomania, the Mood Disorder Questionnaire (MDQ). Participants completed measures of imagery susceptibility and its impact: the Spontaneous Use of Imagery Scale (SUIS) and the Impact of Future Events Scale (IFES), at baseline and 7 weeks later. RESULTS: HR group reported greater tendency to use imagery in daily life (SUIS) and greater emotional impact of prospective imagery (IFES) than LR group at baseline. These results remained stable at follow-up. CONCLUSION: This study provides preliminary evidence for increased susceptibility to mental imagery in individuals at high risk of bipolar disorders recruited from a community sample of Chinese adults. This extends previous research in Western student samples suggesting that imagery (both levels of use and its emotional impact) may be a cognitive factor with cross-cultural relevance that is stable over time.

Prevalence, psychosocial correlates and service utilization of depressive and anxiety disorders in Hong Kong: the Hong Kong Mental Morbidity Survey (HKMMS).

PURPOSE: Data on mental disorder prevalence and health service utilization required to inform healthcare management and planning are lacking in Hong Kong. The current study determined the prevalence of common mental disorders (CMD), and examined the patterns of mental health service utilization and associated factors. METHODS: We analyzed data from the Hong Kong Mental Morbidity Survey (HKMMS) of 5,719 Chinese adults aged 16-75 years in the general Hong Kong population, using the Chinese Revised Clinical Interview Schedule (CIS-R). RESULTS: The weighted prevalence estimate for any past-week CMD was 13.3 %, with mixed anxiety and depressive disorder being the most frequent diagnoses. CMD was positively associated with female gender, being divorced or separated, alcohol misuse, substance dependence, lack of regular physical exercise, and a family history of mental disorder. Among individuals with CMD, only 26 % had consulted mental health services in the past year; less than 10 % consulted general practitioners or family physicians. Lack of mental health service usage was significantly more likely in men and those with lower educational attainment. CONCLUSIONS: Apart from attention to psychosocial risks, health and lifestyle factors are important considerations for mental health promotion. Service utilization for individuals with CMD in Hong Kong remains suboptimal, and would be enhanced by strengthening community primary care.

Prospective relationship between duration of untreated psychosis and 13-year clinical outcome: a first-episode psychosis study.

BACKGROUND: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined. OBJECTIVE: To explore the relationship between DUP and long-term symptomatic remission. METHODS: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤30days), medium (31-180days) and long (>180days) DUP groups. RESULTS: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission. CONCLUSION: The findings support the threshold theory that DUP longer than 30days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment.

Plasma clozapine levels and clinical response in treatment-refractory Chinese schizophrenic patients.

PURPOSE: To evaluate clinical efficacy of clozapine in relation with its plasma level in a group of Chinese patients with treatment-resistant schizophrenia. In addition, the relationship between plasma level and side effects were examined. METHOD: Fifty-one patients with treatment-resistant schizophrenia were put on a fixed dose of clozapine at 300 mg/day for 6 weeks. Non-responders to week 6 received 500 mg/day in subsequent 6 weeks. Responders to week 6 continued to receive 300 mg/day. Clozapine plasma levels were checked at weeks 6 and 12. FINDINGS: No association was found between clozapine plasma level, response and side effects. Sodium valproate was found to elevate clozapine plasma level while lowering norclozapine/clozapine ratio. CONCLUSION: Clozapine plasma level was not found to be associated with response and side effect in Chinese treatment-resistant schizophrenic patients. Various explanations were postulated for the lack of relationship observed between clozapine plasma level and response in this population.