Improving mental health literacy using web- or app-based interventions: A scoping review.

Background: Given the rapid advancement in technology, the Internet has grown to play a significant role in the field of healthcare. Individuals can now access a profusion of easily available materials for self-management of their health. The purpose of this review is to describe Web/App-based interventions that are primarily or secondarily designed to improve mental health literacy (MHL) and to investigate the effectiveness of online interventions for improving mental health. Materials and Method: A scoping review was conducted by searching five databases: PsycINFO, EMBASE, PubMed, CINAHL, and Web of Science. The search was limited to peer-reviewed journals published in English between 2000 and 2022. Studies focusing on enhancements of MHL or its constituent components were included. Results: Twenty-four studies met the inclusion criteria. The interventions primarily targeted patients or individuals exhibiting symptoms of mental disorders, with a higher representation of female participants. All the interventions yielded positive outcomes. The included studies were categorized according to three themes: knowledge, attitude, and self-care skills. Although numerous studies have focused on knowledge improvement, research on interventions targeting self-care skills is scarce. Furthermore, existing literature on knowledge enhancement is limited in terms of the coverage of risk factors. Conclusion: This review indicates gaps in web/app interventions including limited evidence on risk factors, inconsistent help-seeking awareness, and inadequate self-care skills training. Further research is critically needed to address these deficiencies and promote comprehensive MHL.

Age-related differences in the impact of resilience on mental health outcomes during the COVID-19 pandemic in Hong Kong.

OBJECTIVE: This study investigated changes in mental health in Hong Kong over two years and examined the role of resilience and age in mitigating the negative effects of public health emergencies, particularly the COVID-19 pandemic. METHODS: Complete data of interest from two telephone surveys conducted in 2020 (n = 1182) and 2021 (n = 1108) were analysed. Participants self-reported depressive and anxiety symptoms using the Patient Health Questionnaire 4-item version (PHQ), psychotic-like experiences (PLEs) using three items from the Prodromal Questionnaire Brief (PQB), and resilience using the Connor-Davidson Resilience Scale 2-item version (CD-RISC-2). RESULTS: We observed an increase in the percentage of participants with high depressive and anxiety symptoms and PLEs from 1.6% to 6.5% between 2020 and 2021. The likelihood of having high depressive and anxiety symptoms or PLEs depended on resilience and age, with no significant between-year differences. Resilience and age interaction effects were significant when comparing the high PHQ-high PQB group to the low PHQ-low PQB group only in 2021 but not in 2020. CONCLUSIONS: This study provides valuable insights into the impact of the COVID-19 pandemic on mental health in Hong Kong, emphasising the age-dependent nature of resilience in mitigating negative effects. Future research should explore the mechanisms by which resilience promotes mental health and well-being and identify ways to enhance resilience among older individuals during public health crises.

Systematic review and meta-analysis of internalised stigma and stigma resistance in patients with psychosis: The impact of individualism-collectivism culture and other individual factors.

PURPOSE: This study aimed to meta-analysis the level of internalised stigma experienced by individuals with psychosis worldwide, and the impact of cultural differences, economic status of the studied regions and duration of illness on their levels of internalised stigma. Clinical and individual level factors associated with internalised stigma and stigma resistance were also systematically reviewed. METHODS: A systematic search of keywords on two scholarly databases were conducted. The individualism index of the countries or regions where the studies were conducted was retrieved from Hofstede's updated measurement of individualism. Economic status of regions was categorised based on their per capita gross national income. Meta-analysis and meta-regression were conducted using the 'metafor' package in R. Factors associated with internalised stigma and stigma resistance were also systematically consolidated. RESULTS: Seventy-three articles were included in the meta-analysis and the pooled score of both internalised stigma and stigma resistance of individuals with psychosis were within the mild range (2.20 and 2.44, respectively). The meta-regression analysis found high collectivism culture is significantly related to a higher level of internalised stigma. Economic status was not significant. Thirty-five articles were included in the systematic review and clinical, psychological, psychosocial variables, cognition and sociodemographic factors were found to be associated with internalised stigma. CONCLUSION: Internalised stigma in psychosis is ubiquitous worldwide and high collectivism culture may be related with high internalised stigma. With the presence of multiple individual factors related to internalised stigma, intervention programmes to reduce internalised stigma should consider focussing on both macro- and micro-level factors.

Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.

About 15-40% of patients with schizophrenia are treatment resistance (TR) and require clozapine. Identifying individuals who have higher risk of development of TR early in the course of illness is important to provide personalized intervention. A total of 1400 patients with FEP enrolled in the early intervention for psychosis service or receiving the standard psychiatric service between July 1, 1998, and June 30, 2003, for the first time were included. Clozapine prescriptions until June 2015, as a proxy of TR, were obtained. Premorbid information, baseline characteristics, and monthly clinical information were retrieved systematically from the electronic clinical management system (CMS). Training and testing samples were established with random subsampling. An automated machine learning (autoML) approach was used to optimize the ML algorithm and hyperparameters selection to establish four probabilistic classification models (baseline, 12-month, 24-month, and 36-month information) of TR development. This study found 191 FEP patients (13.7%) who had ever been prescribed clozapine over the follow-up periods. The ML pipelines identified with autoML had an area under the receiver operating characteristic curve ranging from 0.676 (baseline information) to 0.774 (36-month information) in predicting future TR. Features of baseline information, including schizophrenia diagnosis and age of onset, and longitudinal clinical information including symptoms variability, relapse, and use of antipsychotics and anticholinergic medications were important predictors and were included in the risk calculator. The risk calculator for future TR development in FEP patients (TRipCal) developed in this study could support the continuous development of data-driven clinical tools to assist personalized interventions to prevent or postpone TR development in the early course of illness and reduce delay in clozapine initiation.

Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults.

Autism spectrum (ASD) and attention deficit/hyperactivity disorders (ADHD) share genetic, neurological, and behavioural features. However, related research in Asia is limited. We collected self-reported ASD and ADHD symptoms from 2186 Hong Kong adolescents and young adults aged 15-24 years, among whom, 1200 provided 1-year data on mental health-related outcomes. Comparative and network analyses were performed. Rating scale cutoff scores were used to divide participants into ASD, ADHD, comorbid, and control groups. The prevalence rates of ASD, ADHD, and comorbidities in Hong Kong were 13.3 %, 10.6 %, and 2.7 %, respectively. Compared with the control group, the comorbid group experienced more psychotic-like experiences (PLEs), the ASD group had poorer functioning, and the ADHD group had higher depression and anxiety symptoms and a lower quality of life after 1 year. The ability to switch attention, preference for routines and difficulty with change, and problems with organisation and planning were positively associated with depressive symptoms, forgetfulness and working memory issues with anxiety symptoms, and heightened sensory input and difficulties in sustaining attention and task completion with PLEs after 1 year. Our findings provide insight into support strategies to address the needs of young Asians to improving their well-being and long-term outcomes.

Stigma towards mental illness, resilience, and help-seeking behaviours in undergraduate students in Hong Kong.

AIM: Early interventions have great impact on reducing burden of mental illness. Young people are however the least likely to seek help for psychological issues. Resilience and stigma towards mental illness have been identified as contributing factors, although previous findings were mixed with potentially complex interaction with symptom severity. We investigated the relationship between stigma, resilience, depressive symptom severity, and help-seeking behaviours in undergraduate students in Hong Kong. METHODS: A cross-sectional online survey was conducted among undergraduates from a university in Hong Kong (n = 945). The 21-item Stigma and Acceptance Scale, Connor-Davidson Resilience Scale, and the Patient Health Questionnaire-9 were used. History of help-seeking for psychological issues was self-reported. Path analysis was conducted to test a conceptual model of their relationships. RESULTS: Among those with moderate-to-severe depressive symptoms (39.5%), only one-fourth had sought professional help. The path model showed that depressive symptom severity and stigma were positively associated with help-seeking behaviours, while resilience was negatively associated with help-seeking behaviours independently (all p < .001). Subgroup analyses showed differential contribution of stigma and resilience to a history of help-seeking in those with minimal-to-mild symptoms compared with moderate-to-severe symptoms. CONCLUSIONS: Stigma may be a barrier for help-seeking particularly in students with moderate-to-severe depression. Higher levels of resilience in young people may be protective and reduce the unnecessary seeking of professional help. Therefore, enhancing resilience among students in general, and reducing stigma and promoting help-seeking behaviours for those who have moderate-to-severe symptoms should be consider in parallel as strategies to enhance mental wellbeing of students.

Impact of community mental health services on the adult psychiatric admission through the emergency unit: a 20-year population-based study.

Background: There is a lack of real-life population-based study examining the effect of community mental health services on psychiatric emergency admission. In Hong Kong, Integrated Community Center for Mental Wellness (ICCMW) and telecare service were introduced in 2009 and 2012, respectively. We examined the real-life impact of these services on psychiatric emergency admissions over 20 years. Methods: Number of psychiatric emergency admissions between 2001 and 2020 was retrieved from the Hong Kong Clinical Data Analysis & Reporting System. We used an interrupted time series analysis to examine monthly psychiatric admission trend before and after service implementation, considering socioeconomic and environmental covariates. Findings: A total of 108,492 psychiatric emergency admissions (47.8% males; 64.9% aged 18-44 years) were identified from the study period, of which 56,858, 12,506, 12,295, 11,791, and 15,051 were that for schizophrenia-spectrum disorders, bipolar affective disorders, unipolar mood disorders, neuroses, and substance use disorders. ICCMW introduction has an immediate effect on psychiatric emergency admission (adjusted estimate per 100,000: -10.576; 95% CI, -16.635 to -4.518, p < 0.001), particularly among adults aged 18-44 years (-8.543; 95% CI, -13.209 to -3.877, p < 0.001), females (-5.843; 95% CI, -9.647 to -2.039, p = 0.003), and with neuroses (-3.373; 95% CI, -5.187 to -1.560, p < 0.001), without a significant long-term effect. Unemployment, seasonality, and infectious disease outbreak were significant covariates. Interpretation: ICCMW reduced psychiatric emergency admission, but no further reduction following full implementation. Community mental health services should be dynamically tailored for different populations and socioeconomic variations over time. Funding: None.

Impact of Severe Acute Respiratory Syndrome, Coronavirus Disease 2019, and Social Unrest on Adult Psychiatric Admissions in Hong Kong: A Comparative Population-Based Study.

ABSTRACT: In Hong Kong, two infectious disease outbreaks occurred in 2003 (SARS) and 2020 (COVID-19), and a large-scale social unrest happened in 2019. These were stressful societal events that influenced the mental well-being of the public. We aimed to explore the impact of these events on psychiatric admissions in Hong Kong. Socioeconomic and population-based psychiatric hospital admission data were retrieved from the government and Hospital Authority. Negative binomial time-series regression analysis was applied and we found overall significant reductions of psychiatric admissions during both the SARS and COVID-19 periods (-7.4% to -16.8%). Particularly, the admissions for unipolar disorders (-16.2% to -39.7%) and neuroses (-20.9% to -31.9%) were greatly reduced during the infection outbreaks. But an increase of admissions for schizophrenia (12.0%) was seen during the social unrest period. These findings support introducing early and targeted community mental health care strategies to the vulnerable people during the stressful societal events.

Age-matched versus non-age-matched comparison of clinical and functional differences between delusional disorder and schizophrenia: a systematic review.

Background: It has been widely suggested that delusional disorder (DD) differs from schizophrenia (SZ). However, whether the two disorders are truly distinct from each other is inconclusive as an older age of onset is closely linked to a better prognosis in psychotic disorders. In order to delineate the potential influence of age on outcomes, we undertook a systematic review on the clinical and functional differences between DD and SZ in age-matched and non-age-matched cohorts. Methods: Electronic databases were retrieved up to May 2022. Included studies were analyzed with reference to statements about clinical, cognitive and functional differences between DD and SZ. Results: Data synthesized from 8 studies showed (1) extensive effects of age on positive, general psychopathological symptoms and functioning, but (2) consistent differences between the two disorders in terms of negative symptoms and hospitalizations regardless of age matching. Conclusion: There is currently insufficient evidence to conclude whether DD is completely distinct from SZ, but our review showed support for the confounding effect of age in comparisons of psychotic disorders with different ages of onset. Future studies shall take note of other possible confounding variables, methods of age-matching and the importance of longitudinal information in deducing whether the two disorders differ from each other in course and outcome.

A systematic review and meta-analysis of the effect of clozapine on cognitive functions in patients with treatment-resistant schizophrenia.

BACKGROUND: This study aimed to conduct a systematic review and meta-analysis on cognitive performances of patients with treatment-resistant schizophrenia (TRS) after clozapine treatment and to examine the potential effect of follow-up duration and clozapine dosage. METHODS: Five electronic databases were searched and studies were included if treatment-resistant schizophrenia patients were treated with clozapine and with baseline and follow-up cognitive functions assessments. Cognitive measures were categorised into six domains based on DSM-5-TR. Random-effect model analysis was used to pool the effect estimates. Moderator effects of clozapine dosage, follow up duration, duration of illness, age, years of education and change in positive symptoms severity were examined with meta-regression. FINDINGS: Nineteen articles were included with 50 cognitive measures reported. Systematic review found inconsistent results. Twelve cognitive measures were included for meta-analysis and found overall improvement of cognitive performances after clozapine treatment SMD = 0.11 [95 % CI 0.02, 0.20] (p = 0.021). Patients with younger age, more years of education and improvements in positive symptoms are more likely to improve in cognitive performances. Subgroup analysis found significant improvement in studies with follow-up periods of 6-months or longer but not for studies with shorter follow-up periods. CONCLUSION: Clozapine may improve some domains of cognitive function, particularly over a longer period. However, the overall inconsistent results suggest that more studies with larger sample size and standard cognitive function assessments would be needed to enhance our understanding of the impact of clozapine on the cognitive functions in the TRS patients.

A systematic review of neuroimaging studies of clozapine-resistant schizophrenia.

This systematic review aimed to review neuroimaging studies comparing clozapine-resistant schizophrenia patients with clozapine-responding patients, and with first-line antipsychotic responding (FLR) patients. A total of 19 studies including 6 longitudinal studies were identified. Imaging techniques comprised computerized tomography (CT, n = 3), structural magnetic resonance imaging (MRI, n = 7), magnetic resonance spectroscopy (MRS, n = 5), functional MRI (n = 1), single-photon emission computerized tomography (SPECT, n = 3) and diffusion tensor imaging (DTI, n = 1). The most consistent finding was hypo-frontality in the clozapine-resistant group compared with the clozapine-responding group with possible differences in frontal-striatal-basal ganglia circuitry as well as the GABA level between the two treatment-resistant groups. Additional statistically significant findings were reported when comparing clozapine-resistant patients with the FLR group, including lower cortical thickness and brain volume of multiple brain regions as well as lower Glx/Cr level in the dorsolateral prefrontal cortex. Both treatment-resistant groups were found to have extensive differences in neurobiological features in comparison with the FLR group. Overall results suggested treatment-resistant schizophrenia is likely to be a neurobiological distinct type of the illness. Clozapine-resistant and clozapine-responding schizophrenia are likely to have both shared and distinct neurobiological features. However, conclusions from existing studies are limited, and future multi-center collaborative studies are required with a consensus clinical definition of patient samples, multimodal imaging tools, and longitudinal study designs.

Prevalence, time trends, and correlates of major depressive episode and other psychiatric conditions among young people amid major social unrest and COVID-19 in Hong Kong: a representative epidemiological study from 2019 to 2022.

Background: Hong Kong is among the many populations that has experienced the combined impacts of social unrest and the COVID-19 pandemic. Despite concerns about further deteriorations in youth mental health globally, few epidemiological studies have been conducted to examine the prevalence and correlates of major depressive episode (MDE) and other major psychiatric disorders across periods of population-level changes using diagnostic interviews. Methods: We conducted a territory-wide household-based epidemiological study from 2019 to 2022 targeting young people aged 15-24 years. MDE, generalised anxiety disorder (GAD), panic disorder (PD), and bipolar disorder (BD) were assessed using the Composite International Diagnostic Interview-Screening Scales in 3340 young people. Psychotic disorders were assessed by experienced psychiatrists according to the DSM. Help-seeking patterns were also explored. Findings: 16.6% had any mental disorder (13.7% 12-month MDE, 2.3% BD, 2.1% GAD, 1.0% PD, 0.6% psychotic disorder). The prevalence of MDE increased from 13.2% during period 1 (May 2019-June 2020) to 18.1% during period 2 (July-December 2020), followed by 14.0% during period 3 (January-June 2021) and 13.2% during period 4 (July 2021-June 2022). Different stressors uniquely contributed to MDE across periods: social unrest-related stressors during period 1, COVID-19 stressors during period 2, and personal stressors during periods 3-4. Lower resilience, loneliness, frequent nightmares, and childhood adversity were consistently associated with MDE. Compared to other conditions, those with MDE showed the lowest service utilisation rate (16.7%). Perceiving services to "cost too much" and "talked to friends or relatives instead" were among the major reasons for not seeking help. MDE was also significantly associated with poorer functioning and health-related quality of life. Interpretation: MDE can be sensitive to population-level changes, although its persistently elevated prevalence across the study period is of concern. Efforts to mitigate their impacts on youth mental health alongside personal risk factors are needed. Further work is required to increase the availability and acceptability of youth-targeted mental health services. Funding: Food and Health Bureau (HKSAR Government).

Resilient, undercontrolled, and overcontrolled personality types in Hong Kong youths and the association with mental health outcomes.

OBJECTIVE: This study aimed to investigate the relationship between RUO types and mental health in a youth sample in Hong Kong. BACKGROUND: Previous research has found that Resilient, Undercontrolled, and Overcontrolled (RUO) personality types derived from Big Five personality traits are associated with mental health outcomes. Most studies, however, have predominantly been conducted in Western societies. METHOD: Clinical diagnostic interviews and self-rated measures of psychological constructs, covering resilience, rumination, self-esteem and more, were administered to 860 youths aged 15 to 24 recruited from an ongoing epidemiological youth mental health study in Hong Kong. RESULTS: Three personality clusters were identified. The first (mean age = 19.6, 63.3% female) and second (mean age = 19.5, 60.7% female) cluster both have characteristics of the under- and overcontrolled personalities. The third personality type resembled the resilient profile in RUO typology (mean age = 19.6, 50.5% female) and showed the lowest prevalence of poor mental health. CONCLUSIONS: The results suggest that the replicability of the RUO profiles was only partial in a Hong Kong sample predominantly Chinese. The resilient profile was replicated but not the undercontrolled and overcontrolled profiles proposed by previous studies. The findings of the current study implicated that culturally contextual considerations are necessary when relating mental health to personality.

COVID-19 exposure and psychosis: A comparison of clinical, functional, and cognitive profiles in remitted patients with psychosis.

The impact of Coronavirus Disease 2019 (COVID-19) on psychiatric care in remitted patients with first-episode psychosis (FEP) remains unknown. This study compared the demographic, clinical, functional, and cognitive profiles of patients recruited before and during the pandemic. The results showed that COVID patients were significantly older, smokers, alcohol users, experienced more stressors, with better functioning than pre-COVID patients. The former also had fewer severe negative and general psychopathological symptoms, more impaired insight, poorer medication compliance, and worse cognitive performance. Our findings highlighted a timely need to improve awareness into the illness and treatment in FEP patients experiencing pandemic related stressors.

Cognitive subgroups and the relationships with symptoms, psychosocial functioning and quality of life in first-episode non-affective psychosis: a cluster-analysis approach.

Introduction: Prior research examining cognitive heterogeneity in psychotic disorders primarily focused on chronic schizophrenia, with limited data on first-episode psychosis (FEP). We aimed to identify distinct cognitive subgroups in adult FEP patients using data-driven cluster-analytic approach, and examine relationships between cognitive subgroups and a comprehensive array of illness-related variables. Methods: Two-hundred-eighty-nine Chinese patients aged 26-55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing premorbid adjustment, illness-onset profile, symptom severity, psychosocial functioning, subjective quality-of-life, and a battery of cognitive tests were conducted. Hierarchical cluster-analysis was employed, optimized with k-means clustering and internally-validated by discriminant-functional analysis. Cognitive subgroup comparisons in illness-related variables, followed by multivariable multinominal-regression analyzes were performed to identify factors independently predictive of cluster membership. Results: Three clusters were identified including patients with globally-impaired (n = 101, 34.9%), intermediately-impaired (n = 112, 38.8%) and relatively-intact (n = 76, 26.3%) cognition (GIC, IIC and RIC subgroups) compared to demographically-matched healthy-controls' performance (n = 50). GIC-subgroup was older, had lower educational attainment, greater positive, negative and disorganization symptom severity, poorer insight and quality-of-life than IIC- and RIC-subgroups, and higher antipsychotic-dose than RIC-subgroup. IIC-subgroup had lower education levels and more severe negative symptoms than RIC-subgroup, which had better psychosocial functioning than two cognitively-impaired subgroups. Educational attainment and disorganization symptoms were found to independently predict cluster membership. Discussion: Our results affirmed cognitive heterogeneity in FEP and identified three subgroups, which were differentially associated with demographic and illness-related variables. Further research should clarify longitudinal relationships of cognitive subgroups with clinical and functional outcomes in FEP.

A systematic review of the role of clozapine for severe borderline personality disorder.

RATIONALE: Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD). OBJECTIVES: The review examines the effectiveness of clozapine as a medication for management for severe BPD with high risk of suicide, violence or imprisonment, and aims to help guide clinical practice in managing severe BPD. METHODS: A database search of the terms "Clozapine" AND "BPD"; "Antipsychotics" AND "BPD"; "Clozapine" AND "Borderline Personality Disorder"; and "Antipsychotics" AND "Borderline Personality Disorder" were performed in CINAHL, Cochrane Library, Embase, Medline, PsychINFO, PubMed, and Web of Science. Full-text articles of clinical clozapine use for BPD were included for review. RESULTS: A total of 24 articles consisting of 1 randomised control trial, 10 non-controlled trials, and 13 case reports were identified. Most of the studies reported benefits from clozapine when used for severe BPD. Many of the studies focused on clozapine use in BPD patients at high risk of suicide. Results from these non-controlled and case reports support the use of clozapine in patients with severe BPD at high risk of suicide. CONCLUSION: There may be a role for clozapine in treating severe treatment refractory BPD, especially for those patients at high risk of suicide and frequent hospitalisations.

Excessive fear of clusters of holes, its interaction with stressful life events and the association with anxiety and depressive symptoms: large epidemiological study of young people in Hong Kong.

BACKGROUND: Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples. AIMS: To examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress. METHOD: A total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested. RESULTS: The prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32-2.53), depression (OR = 1.78, 95% CI = 1.24-2.56) and stress (OR = 1.68, 95% CI = 1.11-2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose-response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life. CONCLUSIONS: Screening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.

Clozapine dosing patterns and clinical outcomes in patients with treatment resistant schizophrenia.

Clozapine is the only medication found to be effective for patients with treatment resistant schizophrenia-spectrum disorders (TRS) and its prescription patterns may impact on their outcomes. The study aims to explore the impact of clozapine dosing frequency, dose level and presence of pharmacological augmentation on the clinical, social and cognitive outcomes in patients with TRS. Patients with TRS and on clozapine were interviewed. Daily defined dose (DDD) and anticholinergic burden were calculated. Patients were categorized in three ways: the single daily dose (SDD) and multiple daily dose (MDD), ≤300 mg/day (LD) and >300 mg/day (HD) of clozapine, and clozapine monotherapy (MT) and augmentation therapy (AT). The impact of these clozapine prescription patterns and their interaction on patient outcomes were examined with ANOVA. Of 124 patients on clozapine, 98 patients (79%) had SDD, 59 patients (47.6%) received LD, and 58 patients (46.8%) had MT. Patients in the LD group had significantly better cognitive functions. Though no significant effect of clozapine dosing frequency on outcomes, among patients on LD, those on MDD had better processing speed, short-term and visual memory. Patients with MT had better motivation. Among patients on HD, those with MT had better motivation and vocational functioning. These results provide guidance to the clozapine prescription in a naturalistic setting to achieve optimizing outcomes for patients with TRS in social and cognitive functions. Further longitudinal studies are needed to verify the results.