Association between sleep quality and domains of quality of life amongst patients with first episode psychosis.

BACKGROUND: There is a lack of studies exploring associations between sleep and quality of life (QOL) among patients with schizophrenia who have limited exposure to antipsychotics and are in the early stage of their illness. Our study investigates the association of poor sleep quality and its components with domains of QOL amongst patients with first episode psychosis (FEP). METHODS: Data was utilized from a longitudinal study that examined sleep, smoking and alcohol use amongst patients with FEP who were enrolled in the Early Psychosis Intervention Programme (EPIP). The data were collected during the patients' baseline visit; i.e., within 3 months of admission into the EPIP. The Pittsburgh Sleep Quality Index (PSQI) was employed to examine sleep quality and its 7 components over the last month. The WHO quality of life-BREF was used to examine QOL and its 4 domains: physical health, psychological, social relationship, and environment. Clinical data such as Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores were obtained from a clinical data base. Linear regression analyses were conducted to investigate the association between poor sleep quality and the domains of QOL. RESULTS: Amongst the 280 recruited patients, 62.9% suffered from poor sleep quality. Poor sleep quality was associated with significantly lower scores in all domains of QOL, despite controlling for socio-demographics and clinical variables. Respondents with higher scores in subjective sleep quality and daytime dysfunction were associated with lower scores in the physical health and social relationship domain. Furthermore, respondents with higher scores in subjective sleep quality, sleep latency and daytime dysfunction were associated with lower scores in the psychological domain of QOL. Finally, respondents with higher scores in subjective sleep quality were associated with lower scores in the environment domain of QOL. CONCLUSIONS: Our findings highlight the importance of monitoring sleep quality amongst patients with FEP to improve their QOL. Clinical programmes should also pay more attention to sleep components in order to maintain satisfactory QOL amongst patients with FEP. Future interventions should focus on improving the relevant sleep components to ensure better treatment outcomes.

The Impact of Clozapine Delay on Clinical Outcomes in Schizophrenia.

Background: Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes.Methods: This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks. All patients were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID-I) to ascertain diagnoses of schizophrenia and schizoaffective disorder. Each patient was assessed on the Positive and Negative Syndrome Scale (PANSS) and Social Occupational Functioning Assessment Scale (SOFAS). Past antipsychotic treatment trials were obtained from the medical records. Symptom remission status was defined using the PANSS symptom criteria proposed by Andreasen and colleagues in 2005. Functional remission was defined as a SOFAS score ≥ 60.Results: A total of 159 individuals with schizophrenia or schizoaffective disorder were recruited. The mean age of patients was 40.01 years, and the majority of patients were male (64.2%) and Chinese (85.5%). Thirty-seven patients (23.3%) achieved symptom remission, and 101 (63.5%) achieved functional remission. The median number of antipsychotic trials before clozapine initiation was 6 (interquartile range, 5-8). Patients in either symptom or functional remission had shorter time periods and fewer numbers of antipsychotic trials before first clozapine initiation. However, the trend was statistically significant only for median number of antipsychotic trials in the functional remission (P = .027) and symptom remission (P = .011) groups.Conclusion: Our study found a significant delay in the initiation of clozapine despite current guidelines indicating it for TRS. This delay might have contributed to the poorer clinical outcomes. Further research is needed to provide a clearer understanding of clozapine delay, evaluate its impact on outcomes, and find ways to improve access to clozapine.

Deconstructing the genetic architecture of treatment-resistant schizophrenia in East Asian ancestry.

BACKGROUND: Treatment-resistant schizophrenia (TRS) affects a substantial proportion of patients who do not respond adequately to antipsychotic medications, yet the underlying biological mechanism remains poorly understood. This study investigates the link between the genetic predisposition to schizophrenia and TRS. METHODS: 857 individuals diagnosed with schizophrenia were divided into TRS (n = 142) and non-TRS (n = 715) based on well-defined TRS criteria. Polygenic risk scores (PRS) were calculated using schizophrenia genome-wide association summary statistics from East-Asian and European ancestry populations. PRS was estimated using both P-value thresholding and Bayesian framework methods. Logistic regression analyses were performed to differentiate between TRS and non-TRS individuals. RESULTS: The schizophrenia PRS derived from the East-Asian training dataset effectively distinguished between TRS and non-TRS individuals (R2 = 0.029, p = 4.86 ×10-5, pT = 0.1, OR = 1.52, 95% CI = 1.242-1.861), with higher PRS values observed in the TRS group. Similar PRS analysis was conducted based on the European ancestry GWAS summary statistics, but we found superior prediction based on the East-Asian ancestry discovery data. CONCLUSION: This study reveals an association between common risk variants for schizophrenia and TRS status, suggesting that the genetic burden of schizophrenia may partly contribute to treatment resistance in individuals with schizophrenia. These findings propose the potential use of genetic risk factors for early TRS identification and timely access to clozapine. However, the ancestral background of the discovery sample is crucial for successfully implementing PRS in clinical settings.

Obsessive-compulsive symptoms and disorder in clozapine-treated schizophrenia.

BACKGROUND: Obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) are commonly reported in patients with schizophrenia. Furthermore, the use of clozapine in treatment-resistant schizophrenia has been thought to induce or aggravate these disorders. To date, there is a paucity of research regarding the prevalence and associated factors. Hence, this study aims to report the prevalence of OCS and OCD, and examine potential risk factors, in clozapine-treated schizophrenia. METHODS: This is a cross-sectional study conducted in the only tertiary hospital for psychiatric patients in Singapore. In total, 162 patients on a stable dose of clozapine were recruited for this study; 159 patients with a diagnosis of schizophrenia or schizoaffective disorder were included in the current analysis. Sociodemographic, clinical and treatment factors were analysed to identify factors associated with OCS and OCD. RESULTS: The prevalence of OCS and OCD is 21.4% and 12.6% respectively. Factors associated with OCS include younger age (OR:0.96, p=0.033) and younger age of onset of psychosis (OR:0.92, p=0.017). There were no significant factors associated with OCD. However, in an analysis of both OCS and/or OCD, factors associated include younger age (OR:0.96, p=0.027) and younger age of onset of psychosis (OR:0.91, p=0.016). Severity of psychotic illness and Clozapine dose were not associated with OCS or OCD in clozapine-treated schizophrenia. DISCUSSION & CONCLUSIONS: Our results suggest a high prevalence of OCS and OCD in clozapine-treated schizophrenia which clinicians should routinely screen for. Further research is warranted to establish the link between the factors identified in this study and OCS/OCD in clozapine-treated schizophrenia.

Once-daily versus divided dosing regimens of clozapine: A cross-sectional study in Singapore.

INTRODUCTION: Clozapine is recognized as the gold standard medication for treatment-resistant schizophrenia. Despite the general recommendation of administering in a divided dosing regimen, clozapine is often prescribed once daily at night in clinical practice. This study aims to compare patient characteristics, psychiatric symptoms, side effects, and plasma concentration of clozapine between once-daily dosing and divided dosing regimens. METHODS: This cross-sectional study included 159 participants with treatment-resistant schizophrenia or schizoaffective disorder. Participant's demographic information, anthropometric data, and medical history were collected. Their psychiatric symptoms, cognition, functioning, and side effects were evaluated. RESULTS: Once-daily dosing regimen was associated with younger age and competitive employment. Lower clinical symptom severity, better functioning and cognitive performance were observed in the once-daily dosing group. Lower daily dose of clozapine, trough plasma concentrations of clozapine and norclozapine were also significantly associated with once-daily dosing regimen. CONCLUSION: The study results support once-daily dosing of clozapine as a viable option to selected patients in clinical practice, as no association of severe symptoms or side effects were associated with once-daily dosing regimen. More studies are needed to examine the relationship between clinical outcomes and clozapine dosing regimen.

Metabolic syndrome and cardiovascular risk between clozapine and non-clozapine antipsychotic users with schizophrenia.

INTRODUCTION: Clozapine use is associated with higher risks of metabolic side effects and cardiovascular diseases (CVD). Thus, this study aims to establish and compare the cardiometabolic profiles between non-clozapine antipsychotic and clozapine users with schizophrenia. METHODS: Data from 88 non-clozapine and 166 clozapine users were extracted from existing databases - demographics, medications, smoking and medical histories, anthropometric parameters, serum lipid and fasting glucose levels. Prevalence of metabolic syndrome (MetS) was established using the AHA/NHLBI criteria. Cardiovascular risk profiles were established using the Framingham risk score (FRS). RESULTS: The clozapine group had significantly higher proportions of diagnosed hypertension (10.8 % vs. 3.4 %, p = 0.041), diabetes mellitus (15.7 % vs. 3.4 %, p = 0.003) and dyslipidemia (36.7 % vs. 12.5 %, p < 0.001). However, the non-clozapine antipsychotic group had poorer anthropometric, serum lipids and glucose levels. The prevalence rates of MetS in the clozapine and non-clozapine antipsychotic groups were not statistically significant at 42.8 % and 43.2 %, respectively. As for CVD risk, the non-clozapine antipsychotic group had significantly higher FRS (6.59 % vs. 6.12 %, p = 0.001). CONCLUSION: Although clozapine users had higher rates of diagnosed metabolic conditions, other cardiometabolic parameters appeared better compared to non-clozapine antipsychotic users, which could be due to greater awareness, earlier detection and treatment. Regardless of the type of antipsychotic used, metabolic abnormalities are prevalent in individuals with schizophrenia; physical healthcare should be prioritised alongside mental healthcare in this group.

Global emotion dysregulation and maladaptive cognitive emotion regulation strategies mediate the effects of severe trauma on depressive and positive symptoms in early non-affective psychosis.

BACKGROUND: Previous research has shown that childhood trauma contributes to the onset and maintenance of psychosis. However, few studies have accounted for the effects of lifetime trauma and post-traumatic stress disorder (PTSD), and none have examined the mediating role of emotion dysregulation in symptom maintenance after severe trauma. The purpose of this study is to determine whether maladaptive cognitive emotion regulation strategies (CERS) and global emotion dysregulation mediate the effects of probable PTSD on depressive symptoms, and whether this pathway extends to influence positive symptoms in patients with early non-affective psychotic disorders. METHODS: A total of 150 outpatients with early non-affective psychosis were assessed for trauma exposure, DSM-5 PTSD symptoms, CERS, global emotion dysregulation, and current depressive and positive symptoms. Parallel and serial mediation analyses based on ordinary least squares regressions were used to test the hypothesized models. RESULTS: Mediation analyses controlling for gender, psychiatric comorbidities, antipsychotic medication dosage, duration of untreated psychosis (DUP), family history of mental illness, and cumulative trauma revealed that maladaptive CERS (rumination, catastrophic thinking, and self-blame) and global emotion dysregulation mediated the effects of probable PTSD on depressive symptoms (R2 = 41%), while maladaptive CERS, global emotion dysregulation, and depressive symptoms mediated the effects of probable PTSD on positive symptoms (R2 = 30%). CONCLUSIONS: Our results demonstrate the indirect effects of maladaptive CERS and global emotion dysregulation on maintaining depressive and positive symptoms. Emotion dysregulation may be a potential transdiagnostic treatment target to alleviate depressive and positive symptoms in traumatized patients with early non-affective psychosis.

Prevalence, correlates and outcomes of insomnia in patients with first episode psychosis from a tertiary psychiatric institution in Singapore.

OBJECTIVES: The study aimed to evaluate the prevalence of insomnia in patients with first episode psychosis (FEP) and to explore the relationship between insomnia and socio-demographic and clinical variables as well as quality of life (QOL) and functioning in Singapore. METHODS: Data on sleep, smoking, alcohol habits, QOL and socio-demographics were collected from 280 FEP patients who were enrolled in the Early Psychosis Intervention Programme (EPIP) within 3months of joining the programme. Multiple logistic regression analyses were performed to determine the socio-demographic and clinical correlates of insomnia. The association of insomnia with QOL as well as functioning was examined using multiple linear regression analyses. RESULTS: The prevalence of clinical insomnia was 22.6%. Older age and higher dosage of antipsychotic medication were significantly associated with a lower risk of insomnia while hazardous alcohol use, current smoking and a longer duration of untreated psychosis were significantly associated with a higher risk of insomnia. Insomnia was associated with significant decreases in all QOL domains assessed in the study even after adjusting for confounders. CONCLUSIONS: FEP patients with insomnia must be screened for hazardous alcohol use and smoking. Patients must be referred concurrently for treatment of insomnia, smoking cessation as well as brief intervention for hazardous alcohol use when needed.

Clozapine Use in First-Episode Psychosis: The Singapore Early Psychosis Intervention Programme (EPIP) Perspective.

OBJECTIVE: Early symptomatic response is pertinent in improving outcomes in first-episode psychosis. One of the ways in which this may be achieved is by reducing inappropriate delays in clozapine initiation. This study aimed to examine clozapine prescribing practices among clinicians by establishing the prevalence of clozapine use, identifying baseline clinical and demographic factors that were associated with clozapine use, examining outcomes in clozapine users versus nonusers, and identifying inappropriate antipsychotic prescription patterns prior to clozapine initiation. METHODS: A retrospective study including all consecutive patients who had presented to the Singapore Early Psychosis Intervention Programme (EPIP) from April 2001 to June 2012 was conducted. Clinical and demographic data were extracted from the EPIP database. Incident cases of clozapine users were identified, and additional treatment histories were obtained from medical records. In addition to descriptive statistics, multivariate analysis was performed to identify factors associated with clozapine initiation. RESULTS: Data from 1,603 patients were available for baseline analyses. Of these, 69 patients (4.3%) had been prescribed clozapine. Having a younger age at onset, lack of employment, a lower Global Assessment of Functioning disability score, and a higher Positive and Negative Syndrome Scale total score at baseline were factors associated with clozapine use. After adjustment was made for confounders, clozapine users were found to have attained similar rates of remission and recovery as patients who did not use clozapine. Clozapine initiation was delayed by a mean of 19.3 weeks (SD = 27.1; range, 0-117). Prior to commencing clozapine, 29.4% of patients had received antipsychotic treatments above maximum limits, whereas 75% of patients were prescribed ≥ 3 different antipsychotics (median = 3; range, 2-7). CONCLUSIONS: This study has confirmed that the prescribing of clozapine is low, delayed, and preceded by dosing of antipsychotic drugs above maximum limits. Identification of the factors found to be associated with clozapine use may encourage clinicians to consider clozapine sooner in relevant patients in hopes of achieving early symptomatic response.