A double-blind, randomized comparison study of efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in patients with schizophrenia and acute agitated behavior.

Studies of intramuscular (IM) olanzapine in Asian and Taiwanese populations are limited. This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior.This was a multicenter, double-blind, randomized, parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine (n = 25) against 7.5 mg/d haloperidol (n = 24). The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale-Excited Component Scale.The changes of Positive and Negative Symptom Scale-Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups (olanzapine -9.0 ± 5.7, haloperidol -7.9 ± 4.0, P = 0.254). Both groups reported insomnia as the most common treatment-emergent adverse event, and no serious adverse event was reported.Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia. Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated, which also provided alternative options in the treatment of patients with schizophrenia with agitation.

Prevalence of psychiatric disorders among heroin users who received methadone maintenance therapy in Taiwan.

BACKGROUND: Many patients under methadone maintenance treatment are present with comorbid psychiatric symptoms. OBJECTIVE: We wish to examine the prevalence of psychiatric disorders among heroin users who received methadone maintenance therapy (MMT) in Taiwan. METHODS: By combining the National Health Insurance Research database and Center for Disease Control database, 18,271 heroin users who received MMT were defined as the subject group and after matching age and sex, 73,084 patients were randomly selected as the control group. RESULTS: The 1 year prevalence of any psychiatric disorder, any psychotic disorder, neurotic and other nonpsychotic disorder among MMT patients and control group were 13.14% versus 2.50% (OR 5.89, CI 5.53-6.27), 4.21% versus 1.29% (OR 3.38, CI 3.07-3.72), and 9.89% versus 1.31% (OR 8.25, CI 7.62-8.94), respectively. CONCLUSION: The prevalence of any co-morbid psychiatric disorder among MMT patients is almost six times higher than the control group. SCIENTIFIC SIGNIFICANCE: A thorough psychiatric screening and appropriate aggressive intervention should be incorporated into an effective methadone treatment program.

Factors Affecting Changes of Cluster of Differentiation 4 Cell Counts Among Human Immunodeficiency Virus-positive People Who Inject Heroin and Receive Methadone Maintenance Treatment.

AIMS: Opioids have been hypothesized to suppress the immune function and worsen outcomes among people living with human immunodeficiency virus (HIV). The study aimed to identify key factors associated with the increased cluster of differentiation 4 (CD4) cell counts among HIV-positive people who inject heroin and receive methadone maintenance treatment (MMT). METHODS: This longitudinal study was conducted at a psychiatric hospital in Northern Taiwan. Participants were recruited from 2006 through 2011, and received CD4 cell counts and HIV viral load monitoring once every 4 to 6 months. Trend in CD4 cell counts, defined as change in CD4 cell count over time, was used as the outcome measure. Independent variables included MMT-related factors and baseline characteristics. Baseline characteristics included age, gender, CD4 cell count, HIV viral load, tests for other infections, liver function tests, and urine drug screens. RESULTS: Three hundred and fifty one participants were recruited during the study period. The multivariate linear mixed model analysis revealed a higher MMT attendance rate, a higher baseline CD4 cell count, and a shorter duration of MMT were associated with an increase in CD4 cell count over time. CONCLUSIONS: The study showed better adherence to MMT was associated with better preserved immune functions. The negative impact of duration of MMT on CD4 cell counts may be ameliorated by improving the attendance rate, initiation of MMT earlier when the baseline CD4 cell count is still relatively high and by the other beneficial effects of MMT, such as healthier lifestyles with reduced use of short-acting opioids.

Suicide and other-cause mortality among heroin users in Taiwan: a prospective study.

AIMS: The present study investigates one-year incidence of mortality from suicide and other causes among heroin users in Taiwan. DESIGN: A prospective national register-based cohort study. SETTING: All heroin users who attended the methadone maintenance treatment (MMT) programs in all treatment centers in Taiwan. PARTICIPANTS: The sample comprised 10,842 heroin users attending MMT. Between Jan 2006 and Dec 2007, cases were identified through the multiple-center register system and followed until Dec 2008 for date and cause of death on the Taiwan national mortality database. MEASUREMENTS: Standardized mortality ratios within one year of starting MMT were calculated as a ratio of actual versus expected numbers of deaths in the general population in Taiwan. Cox regression models were fitted to estimate the effects of gender, age, education and marital status as well as heroin related behaviors. FINDINGS: In total, 256 cases died, 67 through suicide. The mortality rate (per 100 person-years) in the first year of all-cause and suicide was 1.71 and 0.45 respectively, representing 7.5- and 18.4-fold age- and gender-standardized mortality ratio (SMR) compared to the general population. Besides, the mortality rate in the first year of overdoses, murder, HIV, somatic was 0.19, 0.02, 0.07, and 0.75 respectively, representing 68.4-, 27.7-, 76.8-, and 4.3-fold SMR increases to the general population. Older age and unemployment were independent risk factors for mortality. Females had higher standardized mortality ratio than males for suicide and all-cause mortality. CONCLUSIONS: Results showed higher risk of suicide and other-cause mortality among heroin users in MMT than general population. Suicide is an important contributor to overall excess mortality among heroin users in MMT, and especially among women. Suicide prevention and physical health monitoring are important components of MMT programs.

Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients.

Methadone, a synthetic racemic opioid that primarily works as a µ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients.

Alcohol use problem among patients in methadone maintenance treatment in Taiwan.

AIMS: To examine the prevalence rate and predictors of alcohol use problems among patients undergoing methadone maintenance treatment (MMT). DESIGN: This was a prospective follow-up study. PARTICIPANTS: Study population included 438 patients who underwent more than 6 months of MMT. MEASUREMENTS: Demographic and clinical characteristics were collected for each patient prior to treatment, and treatment-related variables were collected during treatment process. Hazardous drinking, alcohol abuse, and dependence were measured using a Chinese version of the Alcohol Use Disorders Identification Test (AUDIT) and by measuring breath alcohol concentration. FINDINGS: The prevalence rates of alcohol use problems, indicated by hazardous drinking are 31.4%. The protective predictors of alcohol use problems among MMT patients include an attendance rate of more than 90% (odds ratio [OR] = 0.54, 95% confidence interval [CI] = 0.30-0.97) and being older than 36 years (OR = 0.48, 95% CI = 0.27-0.86), and alcohol drinking problem at intake of study is a risk factor (OR = 5.30, 95% CI = 2.87-9.76). CONCLUSIONS: High attendance rate, which is regarded as a component of clinical policy and a key component of therapeutic context, should be incorporated with brief interventions to lower alcohol use problems among MMT patients.

Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and adverse reactions in methadone maintenance patients.

AIM: Methadone maintenance therapy is one of the standard treatments for heroin addiction. The isozyme CYP3A4 of the CYP system is one of the metabolic enzymes, as well as CYP2B6, responsible for the metabolism of methadone. The aim of the present study is to evaluate the potential use of genetic polymorphisms in CYP3A4 as biomarkers for the prediction of methadone treatment responses. MATERIALS & METHODS: A total of 366 Han Chinese methadone maintenance treatment patients in Taiwan were recruited in this study. Main clinical assessments included the clinical opioid withdrawal scale (COWS), the treatment emergent symptom scale (TESS) and the plasma concentrations of methadone and its metabolites. Genetic associations of six SNPs in the CYP3A4 gene were calculated using a general linear model. RESULTS: Genotypes and allele types of rs4646440 and rs2242480 were found to be significantly associated with the severity of withdrawal symptoms rated by COWS (p = 0.012, 0.0096, 0.017 and 0.012, respectively) as well as the side effects rated by TESS (p = 0.0089, 0.028, 0.0027 and 0.0085, respectively). The allele types associated with more severe withdrawal symptoms are also associated with more severe side effects and less betel nut (Areca catechu) use (p = 0.009 for rs4646440, p = 0.0063 for rs2242480). Further analyses on specific withdrawal symptoms in COWS showed that the genetic variants in rs4646440 are significantly associated with heart rate (allele type p = 0.0019). CONCLUSION: These results suggested that genetic variants in the CYP3A4 gene may be useful indicators for the severity of side effects and withdrawal symptoms for methadone treatment.