Long-term Safety and Efficacy of Esketamine Nasal Spray Plus an Oral Antidepressant in Patients with Treatment-resistant Depression– an Asian Sub-group Analysis from the SUSTAIN-2 Study

Objective@#To evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study. @*Methods@#SUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period. @*Results@#The incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan: 33, Korea: 26, Malaysia: 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study. @*Conclusion@#The safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.

Effects Of A School-Based Substance Use Prevention Program On Students In Malaysia

Background: The rise in substance-use-related problems among Malaysian adolescents called for a study to assess the efficacy of an anti-drug educational program to improve the knowledge, attitudeand perception (KAP) of Malaysian students regarding substance use. Methods: This study involved 573 students from four Malaysian Chinese schools in Malacca. Each student filled out a Likert-scale mandarin translated questionnaire (KAP-C) on substance use ( Pre-test). Following an educational program on substance use, the KAP-C questionnaire was given again to the students, immediately following the program (PT 1), and after a month (PT 2) and two months (PT3) of the programme. Results: The students showed improvement in knowledge of the types of substance use in PT 1 (p<0.001), PT 2 (p<0.001) and PT 3 (p<0.001). The study also showed persistent changes in their attitude towards drug treatment strategies at two months following the program (p < 0.05). Changes were also noted in their attitudestowards harm reduction strategies. Perceptions towards the substance-related problems changed following the module (p=0.001), and remained even after two months (p<0.001). Conclusion: This module effectively changed the KAP of students on substance use.

Is early-onset in major depression a predictor of specific clinical features with more impaired social function? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.</p><p><b>METHODS</b>In total, 547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator.</p><p><b>RESULTS</b>Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies.</p><p><b>CONCLUSIONS</b>EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment.</p>

Seropositivity and Serointensity of Toxoplasma gondii Antibodies and DNA among Patients with Schizophrenia

The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

Seropositivity and Serointensity of Toxoplasma gondii Antibodies and DNA among Patients with Schizophrenia

The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

Validation of Malay Version of Snaith-Hamilton Pleasure Scale: Comparison between Depressed Patients and Healthy Subjects at an Out-Patient Clinic in Malaysia

Background: The Snaith-Hamilton Pleasure Scale (SHAPS) is a self-assessment scale designed to evaluate anhedonia in various psychiatric disorders. In order to facilitate its use in Malaysian settings, our current study aimed to examine the validity of a Malay-translated version of the SHAPS (SHAPS-M). Methods: In this cross-sectional study, a total of 44 depressed patients and 82 healthy subjects were recruited from a university out-patient clinic. All participants were given both the Malay and English versions of the SHAPS, Fawcett-Clark Pleasure Scale (FCPS), General Health Questionnaire 12 (GHQ-12), and the Beck Depression Inventory (BDI) to assess their hedonic state, general mental health condition and levels of depression. Results: The results showed that the SHAPS-M has impressive internal consistency (α = 0.96), concurrent validity and good parallel-form reliability (intraclass coefficient, ICC = 0.65). Conclusion: In addition to demonstrating good psychometric properties, the SHAPS-M is easy to administer. Therefore, it is a valid, reliable, and suitable questionnaire for assessing anhedonia among depressed patients in Malaysia.

Metabolic syndrome and cardiovascular risk among patients with schizophrenia receiving antipsychotics in Malaysia

<p><b>INTRODUCTION</b>This study aimed to determine the prevalence of metabolic syndrome and risk of coronary heart disease (CHD) in patients with schizophrenia receiving antipsychotics in Malaysia.</p><p><b>METHODS</b>This cross-sectional study, conducted at multiple centres, involved 270 patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR diagnostic criteria for schizophrenia, were on antipsychotic medications for at least one year, and were screened for metabolic syndrome. Patients receiving mood stabilisers were excluded. Metabolic syndrome was defined according to the National Cholesterol Education Program ATP III criteria modified for Asian waist circumference. Risk for cardiovascular disease was assessed by using Framingham function (all ten-year CHD events).</p><p><b>RESULTS</b>The prevalence of metabolic syndrome was 46.7% (126/270). Among all the antipsychotics used, atypical antipsychotics (monotherapy) were most commonly used in both the metabolic and non-metabolic syndrome groups (50.8% vs. 58.3%). The ten-year risk for CHD was significantly higher in patients with metabolic syndrome. The proportion of patients with high/very high risk for CHD (Framingham ≥ 10%) was greater in patients with metabolic syndrome than in those with non-metabolic syndrome (31.5% vs. 11.0%, odds ratio 3.9, 95% confidence interval 2.0-7.6; p < 0.001). The mean body mass index was higher in patients with metabolic syndrome than in those without (29.4 ± 5.1 kg/m2 vs. 25.0 ± 5.6 kg/m2; p < 0.001).</p><p><b>CONCLUSION</b>Patients with schizophrenia receiving antipsychotics in Malaysia have a very high incidence of metabolic syndrome and increased cardiovascular risk. Urgent interventions are needed to combat these problems in patients.</p>

Schizophrenia, substance use and aggressions: What are the relationships?

Objectives: The objective of the study is to determine the prevalence of substance abuse for alcohol, cannabis, opiates, stimulants, solvent and other substances among patients with schizophrenia in Hospital Bahagia Ulu Kinta (HBUK), Perak , Central Peninsular of Malaysia. This study also aims to determine the association of substance abuse with aggression, the demographic characteristics and total duration of hospitalization. Methods: This was a retrospective cross-sectional study whereby the first 194 subjects diagnosed to have schizophrenia based on International Classification of Disease, 10th edition (ICD-10) criteria were taken from data registry of patients admitted to HBUK from January until February 2004. The subjects’ medical files were examined for documentation of substances abuse, aggression and accumulative duration of hospitalization. Results: The results showed the prevalence of substances misuse among patients with schizophrenia in general (including alcohol) was 24.7%. Cannabis 16.7%, alcohol 13.4%, opiates(heroin) 6.7%, Amphetamine type stimulants (amphetamine, metamphetamine, ecstacy) 5.7%, and other substances (benzodiazepine, solvents) 1.5%. Conclusion: There is higher prevalence of substance misuse in patients with schizophrenia as compared to general population. Male patients with history of substance misuse are more likely to have aggression than female. This group needs special precaution and probably in need of specialist help.

The first methadone programme in Malaysia: overcoming obstacles and achieving the impossible

Objectives: To determine the best possible programme that suits our local setting, to determine the average dose required, and to determine possible problems that can arise from implementing such a programme locally and how best to address them. Methods: The inclusion criteria were those above 18, a positive urine test, the presence of a supportive carer and willing to engage in the programme. Methadone was initiated and observations relating to dose, adverse events, relationship with carers, work performance, crime and high risk behaviours were monitored for 18 weeks. Results: Two thirds of the 45 subjects completed the trial over the 18 week period. No significant adverse events occurred and improvement in relationship with carers and work performance were noted with reduction in crime and high risk behaviours. Conclusion: Methadone is a safe and effective drug that can be used in the local Malaysian setting.