Understanding cannabis use in Singapore: profile of users and drug progression.

Introduction: Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression. Methods: A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted. Results: The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug. Conclusion: In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.

A new paradigm in management of frequent attenders to emergency departments with severe alcohol use disorder-A pilot study for assertive community treatment in Singapore.

Introduction: A majority of frequent users of emergency medical services in Singapore present with alcohol-related problems. These patients are known to engage poorly with traditional addiction services and frequently attend Emergency Departments (EDs) instead, resulting in high healthcare burden. Assertive Community Treatment (ACT) is an alternative intervention to traditional addiction management. ACT involves community visits with focus on holistic care and harm-reduction. Materials and methods: We conducted a prospective before-and-after cohort study at the major tertiary center for addiction disorders in Singapore. The main objective was to evaluate effectiveness of ACT in reducing alcohol-related attendances at EDs nationwide. Socio-demographics, alcohol-related ED attendances, and the Christo Inventory for Substance-misuse Services (CISS) scores were collected for the patients recruited from April 2018 to March 2019. Descriptive analyses and the Wilcoxon Signed-Rank Test were performed. Results: All 14 patients were male with a mean age of 55 years. There was a significant 45.3% reduction in average alcohol-related ED attendances from 6.8 (range 3-22, median 5.5) in the pre-intervention 6-month period, to 3.7 (range 0-28, median 1.5) in the post-intervention 6-month period (Z = -2.244, p = 0.025). CISS scores showed significant improvement from a pre-intervention median of 13.5 (range 9-16) to a post-intervention median of 6.5 (range 1-10, p = 0.001), corresponding to reduction in alcohol-related problem severity. Conclusion: This pilot study suggests that ACT can be effective in reducing alcohol-related ED attendances and alcohol-related problem severity in patients with AUD who frequently attend ED. A multicenter, prospective study using ACT for such patients across four hospitals in Singapore is currently underway.

Negative affect moderates the link between body image dissatisfaction and disordered eating among psychiatric outpatients in a multi-ethnic Asian setting.

INTRODUCTION: Few studies have investigated the factors that affect the relationship between body image dissatisfaction and disordered eating locally. Our study aimed to investigate the moderating effects of depression and anxiety levels on the body dissatisfaction-disordered eating link in Singapore. METHODS: A total of 329 participants completed a set of questionnaires that included various scales pertaining to eating behaviours, body image, psychological distress and quality of life. RESULTS: Participants were diagnosed with schizophrenia (47.4%), depression (46.8%) and substance use disorders (5.8%). Moderation analyses revealed that depression (F [9, 251] = 18.50, p < 0.001, R2 change = 0.021) and anxiety levels (F [9, 268] = 19.54, p < 0.001, R2 change = 0.014) were significant moderators of the relationship between body dissatisfaction and disordered eating scores. Subsequent multivariate linear logistic regression analyses showed that high disordered eating scores were significantly associated with lower physical (F [8, 273] = 9.59, R2 = 0.22, p < 0.001, ß = -0.27, p < 0.001), psychological (F [8, 273] = 10.51, R2 = 0.49, p < 0.001, ß = -0.27, p < 0.001), social (F [8, 256] = 6.78, R2 = 0.18, p < 0.001, ß = -0.18, p = 0.004) and environment (F [8, 273] = 5.29, R2 = 0.13, p < 0.001, ß = -0.19, p = 0.001) quality of life scores after controlling for sociodemographic covariates. CONCLUSION: Greater effort should be dedicated to the screening of disordered eating behaviours in psychiatric outpatients presenting with greater psychological distress.

Prevalence of Internet Addiction and Gaming Disorders in Southeast Asia: A Meta-Analysis.

This meta-analytic review aimed to examine the pooled prevalence rates of Internet addiction and gaming disorders in Southeast Asia. Several databases including PubMed, MEDLINE, PsycINFO, Web of Science, Embase, and Cochrane Central were searched and a total of 24 studies were included in this study. The selection of studies was conducted in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Two meta-analyses were conducted to examine data on Internet addiction and gaming disorders separately. A random-effects model was employed to derive the pooled prevalence rate. Mixed-effects meta-regression and subgroup analyses were performed to examine the moderators of the between-study heterogeneity. Publication bias was tested using the Egger's regression test and funnel plot. Only seven out of the 11 Southeast Asian countries were represented in the literature. All except for two of the included studies were cross-sectional in nature. The findings revealed a pooled prevalence rate of 20.0% (95% confidence interval: 14.5%-27.0%) and 10.1% (95% confidence interval: 7.3%-13.8%) for Internet addiction and gaming disorders respectively. Mean age and study population were significant moderators of the between-study heterogeneity in the prevalence rates of gaming disorders such that samples involving older participants showed higher prevalence rate than those involving younger individuals. Country of study was found to be significant moderator of the between-heterogeneity for both Internet addiction and gaming disorders, however the findings should be interpreted with caution due to the small and unbalanced sample sizes. There was no significant publication bias. Such epidemiology research should be extended to the Southeast Asian countries that have not been studied or are under-studied. Given that the prevalence rates appear to be higher in Southeast Asia than in other world regions, future research should also explore the factors behind these inter-regional differences. Further longitudinal studies should also be conducted to examine the trajectories of such disorders.

Unnatural Death among Treatment Seeking Substance Users in Singapore: A Retrospective Study.

Substance use carries a higher risk of unnatural death. A retrospective analysis of 42 treatment seekers between 2011-2015 was conducted through medical record review to understand the profile and circumstances leading to premature deaths. Ninety percent of the subjects were males. The mean age at death was 44.9 (SD ± 13.1). Opioids (52.4%), benzodiazepines (45.2%) and alcohol (35.7%) were the main substances used by the group. Suicide was the most common cause of death (n = 27, 64.3%) followed by accidents (n = 15; 35.7%). Among the suicide cases, alcohol was the main substance used (33.3%) followed by opioids (25.9%). A total of 58.5% (n = 24) deaths occurred within a year of their last visit while 41.5% (n = 17) were dead more than a year after their last visit. Of the total cases (n = 41), 63% had a history of mental illness with depressive disorder (53.8%) being the most common. History of suicide attempts were reported in 34.1% (n = 14) of cases and 50% of the subjects (n = 21) had a history of suicidal ideation. Drug related offences were reported in 57.1% of the subjects, of which 60% (n = 18) committed suicide. The findings support the need for appropriate treatment resources to reduce the untimely deaths among substance users.

Online Gambling among Treatment-Seeking Patients in Singapore: A Cross-Sectional Study.

Given that technology has greatly facilitated easier access to gambling in previous years, it is timely to look in-depth into online gambling activities and behaviors. There have been several studies that examined online gambling. However, most of the current studies to date have focused on determining the prevalence and the epidemiology of problem gambling arising from online gambling in Western cohorts. There remains a paucity of research looking at the problem of online gambling among Asian individuals. The objectives of the current study are to elucidate the characteristics of online gambling among an Asian cohort and to explore the harm associated with online gambling and the potential mechanisms by which harm associated with online gambling could be minimized. It is hoped that the findings of the current paper will bridge the existing gaps in the research literature. A cross-sectional study design was utilized to recruit 100 participants who were attending outpatient services at the National Addictions Management Service (NAMS) from March 2014 to October 2015. The majority of the participants were male, of Chinese ethnicity and under the age of 30 years old (48%). Mobile phones and smartphones were the most commonly utilized platforms for gambling online. The median largest ever debt incurred as a result of online gambling ($20,000) was significantly more than that due to offline gambling ($500) (Z = −4.17, p < 0.001). As for the biggest ever loss, participants had incurred a significantly larger median loss from online gambling ($7000) (Z = −2.73, p < 0.01) compared to offline gambling ($2000). A total of 18.4% of participants had waited between 1 to 2 years from their first online gambling experience to seek treatment and 17.3% had waited for more than 10 years. This is perhaps one of the first Asian studies to investigate the serious harm involved in online gambling. The findings from our study are intended to guide further interventions in the treatment of online gambling related disorders; and would be of interest to governmental organizations in their planning of regulations for online gambling.

Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore.

BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS: Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia.

BACKGROUND: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. METHODS: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. RESULTS: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. CONCLUSION: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.

Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample.

BACKGROUND: Linkage studies have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. It was then claimed that markers at the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) gene showed allelic association with schizophrenia in Canadian families. A second Chinese study found a base pair polymorphism at the CAPON gene also associated with schizophrenia. METHODS: We attempted replication using eight markers from the Canadian study in a UK based sample of 450 cases and 450 supernormal controls. RESULTS: We found no evidence for allelic or haplotypic association with schizophrenia for any of the markers found to be associated in the Canadian sample. CONCLUSIONS: The negative results might reflect genetic heterogeneity between the Canadian, Chinese and UK samples or be due to methodological problems. The present finding weakens the evidence that mutations or variation in the CAPON gene are causing genetic susceptibility to schizophrenia in European populations.

Suicidal ideation and lifetime attempts in substance and gambling disorders.

Suicidality is more commonly reported among individuals with addictions relative to the general population, though data from Asian countries remain scarce. The medical records of 2187 Singaporean patients with drug (n=879), alcohol (n=754) or gambling (n=554) disorders entering an outpatient treatment service were examined to explore differences in suicidal ideation and lifetime attempts between substance and gambling addictions. The relationship between suicidality, co-morbidity and addiction severity were also examined. 25.0% reported thoughts of suicide in the past month, 11.8% had a suicide plan and 12.2% reported lifetime attempts. Rates of suicidal ideation (thoughts, and plan) but not lifetime attempts were significantly higher among gambling than substance use patients. Co-morbid (DSM-IV axis-1) disorders were found among 32.5%, 38% and 40% of those reporting thoughts, plan and lifetime attempts respectively. Addiction severity was higher and quality of life lower among those reporting suicidal behaviors. Logistic regression revealed co-morbidity, debt, gender (being female) and being a gambling patient as significant predictors of suicidal behaviors. The findings highlight the importance of screening for suicidality, even in the absence of co-morbidity, particularly among gambling disorder patients with debts. Suicide risk should be assessed periodically and referral to suicidal prevention interventions routinely offered to this vulnerable population.

Treatment outcome and its predictors among Asian problem drinkers.

INTRODUCTION AND AIMS: Evidence of treatment effectiveness for alcohol use disorders (AUD) have emerged predominantly from Western studies, using highly controlled trials that may not reflect real-world settings. This paper examines treatment outcome and its predictors among Asian problem drinkers participating in a treatment outcome monitoring program at an addiction treatment centre in Singapore. DESIGN AND METHODS: Data were collected at intake and 3, 6 and 12 months, although the focus of this paper is on reliable change at 3 months among the 70% who were followed up. Five hundred and forty-one AUD-diagnosed outpatients presenting for treatment, over a 2-year period, were assessed on drinking behaviours and administered the Addiction Severity Index-Lite, Personal Wellbeing Index (PWI) and Treatment Perceptions Questionnaire. RESULTS: At 3 months, drinking days, alcohol units and alcohol use severity had more than halved and 69% were either abstinent or had reliably reduced their drinking days. Baseline drinking days and treatment satisfaction predicted 3-month drinking frequency but not severity. Positive alcohol outcomes observed at 3 months were sustained among those followed up until 12 months. Mean PWI score improved significantly and fell within the 'normal' range. Treatment satisfaction also emerged as the only significant predictor of reliable positive change in both drinking days and PWI score. DISCUSSION AND CONCLUSIONS: Significant reductions in drinking frequency and severity are possible for Asian problem drinkers after 12 weeks of outpatient treatment. The identified predictors suggest that more frequent drinkers and patients with past/current psychiatric comorbidities may require a more intensive treatment approach to optimise treatment outcomes.

Failure to confirm genetic association between schizophrenia and markers on chromosome 1q23.3 in the region of the gene encoding the regulator of G-protein signaling 4 protein (RGS4).

The chromosome 1q23.3 region, which includes the RGS4 gene has been implicated in genetic susceptibility to schizophrenia by two linkage studies with lod scores of 6.35 and 3.20 and with positive lod between 2.00 and 3.00 scores in several other studies. Reduced post mortem RGS4 gene expression in the brain of schizophrenics was reported as well as positive allelic association between markers at the RGS4 gene locus and schizophrenia. We have attempted to replicate the finding of allelic association with schizophrenia in a UK based sample of 450 subjects with schizophrenia and 450 supernormal controls. We genotyped the same SNP marker alleles investigated in the earlier studies and also a di-nucleotide (GT)14 repeat microsatellite marker, which was 7 kb distal to RGS4. In the new UK sample there was no evidence for allelic or haplotypic association between RGS4 markers and schizophrenia. This might reflect genetic heterogeneity between the population samples, genotyping or other methodological problems. The finding weakens the evidence that mutations or variation in the RGS4 gene have an effect on schizophrenia susceptibility.