Behavioral counseling and abstinence-contingent take-home buprenorphine in general practitioners' offices in Malaysia: a randomized, open-label clinical trial.

BACKGROUND AND AIM: To address the widespread severe problems with opioid use disorder, buprenorphine-naloxone treatment provided by primary care physicians has greatly expanded treatment access; however, treatment is often provided with minimal or no behavioral interventions. Whether or which behavioral interventions are feasible to implement in various settings and improve treatment outcomes has not been established. This study aimed to evaluate two behavioral interventions to improve buprenorphine-naloxone treatment. DESIGN: A 2 × 2 factorial, repeated-measures, open-label, randomized clinical trial. SETTINGS: General medical practice offices in Muar, Malaysia. PARTICIPANTS: Opioid-dependent individuals (n = 234). INTERVENTIONS: Participants were randomly assigned to one of four treatment conditions and received study interventions for 24 weeks: (1) physician management with or without behavioral counseling and (2) physician management with or without abstinence-contingent buprenorphine-naloxone (ACB) take-home doses. MEASUREMENTS: The primary outcomes were proportions of opioid-negative urine tests and HIV risk behaviors [assessed by audio computer-assisted AIDS risk inventory (ACASI-ARI)]. FINDINGS: The rates of opioid-negative urine tests over 24 weeks of treatment were significantly higher with [68.2%, 95% confidence interval (CI) = 65-71] than without behavioral counseling (59.2%, 95% CI = 56-62, P < 0.001) and with (71.0%, 95% CI = 68-74) than without ACB (56.4%, 95% CI = 53-59, P < 0.001); interaction effects between and among behavioral interventions and time were not statistically significant. Scores on ACASI-ARI decreased significantly from baseline across all treatment groups (P < 0.001) and did not differ significantly with or without behavioral counseling (P = 0.099) or with or without ACB (P = 0.339). CONCLUSIONS: Providing opioid-dependent patients in Muar, Malaysia with buprenorphine-naloxone and physician management plus behavioral counseling or abstinence-contingent buprenorphine-naloxone (ACB) resulted in greater reductions of opioid use compared with providing buprenorphine-naloxone and physician management without behavioral counseling or ACB.

Cost-effectiveness of buprenorphine and naltrexone treatments for heroin dependence in Malaysia.

AIMS: To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia. DESIGN: We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants' time were estimated using Malaysia's minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars. SETTING: Muar, Malaysia. PARTICIPANTS: 126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003-2005) receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence. MEASUREMENTS: Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores. FINDINGS: Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine. CONCLUSIONS: Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term.

Lifetime ATS use and increased HIV risk among not-in-treatment opiate injectors in Malaysia.

BACKGROUND: Malaysia has been experiencing significant drug abuse problems since the 1970s, and drug abuse is the major driver of HIV transmission in Malaysia. We investigated risk factors for HIV associated with use of amphetamine type stimulants (ATS) among not-in-treatment opiate injectors in Malaysia. METHODS: Between October of 2006 and May of 2008, we conducted a series of surveys in three major urban areas of Malaysia. A total of 732 opiate IDUs (679 males and 53 females) were enrolled in the three surveys. The survey instruments consisted of a structured interview on demographic characteristics, drug use history (including year of first use, and past month history of use of illicit drugs; lifetime and past month history of IDU or needle or equipment sharing), and HIV status. RESULTS: There were 194/704 (27.6%) HIV positive participants in the sample. Two factors were significantly associated with HIV infection in this sample: lifetime history of ATS use (OR [95%CI]: 2.3 [1.5-3.6]) and lifetime history of sharing of injection equipment (OR [95% CI]: 4.2 [1.8-9.8]). Both HIV-positive and HIV-negative participants reported high levels of current needle/equipment sharing practices: 82% vs. 75%, respectively. CONCLUSIONS: ATS use spread rapidly in the study sample after 1997 and is associated with an increased risk of HIV infection in this population already at high risk because of opiate IDU. Out-of-treatment IDUs in Malaysia engage in high risk behaviors regardless of their HIV status. Increased education and public health prevention measures are needed to reduce HIV transmission risks in this population.

Costs of addressing heroin addiction in Malaysia and 32 comparable countries worldwide.

OBJECTIVE: Develop and apply new costing methodologies to estimate costs of opioid dependence treatment in countries worldwide. DATA SOURCES/STUDY SETTING: Micro-costing methodology developed and data collected during randomized controlled trial (RCT) involving 126 patients (July 2003-May 2005) in Malaysia. Gross-costing methodology developed to estimate costs of treatment replication in 32 countries with data collected from publicly available sources. STUDY DESIGN: Fixed, variable, and societal cost components of Malaysian RCT micro-costed and analytical framework created and employed for gross-costing in 32 countries selected by three criteria relative to Malaysia: major heroin problem, geographic proximity, and comparable gross domestic product (GDP) per capita. PRINCIPAL FINDINGS: Medication, and urine and blood testing accounted for the greatest percentage of total costs for both naltrexone (29-53 percent) and buprenorphine (33-72 percent) interventions. In 13 countries, buprenorphine treatment could be provided for under $2,000 per patient. For all countries except United Kingdom and Singapore, incremental costs per person were below $1,000 when comparing buprenorphine to naltrexone. An estimated 100 percent of opiate users in Cambodia and Lao People's Democratic Republic could be treated for $8 and $30 million, respectively. CONCLUSIONS: Buprenorphine treatment can be provided at low cost in countries across the world. This study's new costing methodologies provide tools for health systems worldwide to determine the feasibility and cost of similar interventions.

Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission. We compared the efficacy of naltrexone, buprenorphine, and no additional treatment, in patients receiving detoxification and subsequent drug counselling, for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviours. METHODS: 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification programme in Malaysia, were randomly assigned by a computer-generated randomisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Medications were administered on a double-blind and double-dummy basis. Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviours over 6 months. The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00383045. FINDINGS: We observed consistent, linear contrasts in days to first heroin use (p=0.0009), days to heroin relapse (p=0.009), and maximum consecutive days abstinent (p=0.0007), with all results best for buprenorphine and worst for placebo. Buprenorphine was associated with greater time to first heroin use than were naltrexone (hazard ratio 1.87 [95% CI 1.21-2.88]) or placebo (2.02 [1.29-3.16]). With buprenorphine, we also recorded significantly greater time to heroin relapse (2.17 [1.38-3.42]), and maximum consecutive days abstinent than with placebo (mean days 59 [95% CI 43-76] vs 24 [13-35]; p=0.003); however, for these outcomes, differences between buprenorphine and naltrexone were not significant. Differences between naltrexone and placebo were not significant for any outcomes. HIV risk behaviours were significantly reduced from baseline across all three treatments (p=0.003), but the reductions did not differ significantly between the three groups. INTERPRETATION: Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence.

New challenges and opportunities in managing substance abuse in Malaysia.

Until recently, Malaysia has lagged behind in the treatment of drug addiction and related disorders, despite experiencing severe drug problems. By the end of 2004, 234,000 heroin users or heroin-dependent individuals had been registered in the official government registry, but other estimates exceed 500,000 for heroin abusers in the country. Amphetamine-type stimulant abuse is also increasing and of considerable public and government concern. Among the population of drug users, HIV and other infectious diseases rates are very high. In the Western Pacific regions, Malaysia has the second highest HIV prevalence (after Vietnam) among adult populations (0.62%) and the highest proportion of HIV cases resulting from injection drug use (76.3%). Drug use and related disorders exert a heavy burden on the country's health care and legal systems. Historically, drug abusers were rehabilitated involuntarily in correctional, rather than health-care, facilities. This primarily criminal treatment approach had limited effectiveness which led to widespread public dissatisfaction and the recent introduction of medical treatments for addiction. Naltrexone was introduced in 1999; buprenorphine was introduced in 2001 and methadone in 2003. Agonist maintenance programmes were embraced rapidly by the medical community in Malaysia. Currently, over 30,000 opiate-dependent patients are treated with agonist maintenance treatments by more than 500 medical practitioners in Malaysia. Despite these recent advances, treatments for amphetamine-type stimulant abuse or dependence are underdeveloped, and diversion of agonist medications is an emerging concern.

Heroin dependence and HIV infection in Malaysia.

BACKGROUND: Malaysia is experiencing severe problems with heroin dependence and HIV infection. This, study evaluated drug use and other HIV risk behaviors and their association with HIV and other infectious diseases in heroin-dependent subjects enrolled in a clinical trial of drug abuse treatment in Muar, Malaysia. METHODS: Baseline assessment of treatment-seeking subjects (n=177) included the Addiction Severity Index; AIDS Risk Inventory; serological tests for HIV, hepatitis B, and hepatitis C; and chest X-ray. RESULTS: All of the subjects were male; 67.8% were Malays, 28.8% Chinese, and 2.3%. Indian. Subjects had a mean (SD) age of 37.2 (9.1) years and 14.4 (8.5) years of using heroin; 76.3% reported lifetime injection drug use (IDU), and 41.5% reported current IDU; 30 of 156 (19.2%) tested HIV positive, 143 of 159 (89.9%) tested hepatitis C positive, and 25 of 159 (15.7%) had radiological evidence of pulmonary tuberbulosis. Malay subjects had a significantly higher prevalence of current IDU, needle sharing (p<0.01), and HIV infection (p<0.05) compared with Chinese subjects. Lifetime IDU, needle sharing, lack of consistent condom use, and Malay ethnicity were significantly associated with HIV infection. CONCLUSIONS: The high prevalence of HIV infection among heroin-dependent individuals, in Malaysia supports the important of interventions to reduce the major risk factors for HIV, including IDU, needle sharing, and unprotected sex.

First episode schizophrenia: an open clinical trial using risperidone in Malaysia

Objective: This study aims to determine: the safety and efficacy of risperidone on treatment naive first episode schizophrenia for first episode schizophrenia; and the social and occupational outcome of these patients. Methodology: This trial was an open clinical study using oral risperidone for 8 weeks, in treatment naive first episode schizophrenia in Malaysia. All first episode schizophrenic patients from 3 general hospitals in Northern Johor that fulfilled the entry criteria were included in this study. They were assessed by using PANNS, CGI, HoNos, AIMS and Adverse rating scale. They were seen at week 0, 1, 2, 4, and 8 weeks. In the first week, risperidone was given given at 1mg per day and subsequently adjusted by no more than 1mg per week up to maximum of 8mg/day. Results: During the 9 month trial, 44 patients were diagnosed to have first episode schizophrenia, but only consented to be in the study. Nine patients had to dropped out because they required parentheral antipsychotic treatment. Thirty-one patients completed this 8 week trial. Using 20% reduction of PANSS score, 27 patients (87.1%) improved at 8 weeks. Using 50% reduction of PANSS initial score and CGI-S score of 1 or 2, 16 patients (51.6%) improved at 8 weeks.Adverse effects were reported in 8 of the patients (25.8%). The mean dose required was 2.69 mg/day, with maximum dose of 8 mg/day. Conclusion: Risperidone is an effective and safe antipsychotic for first episode schizophrenia in Malaysia. The doses required are substantially less than usually needed for chronic schizophrenia.

Switching to olanzapine from previous antipsychotics: a regional collaborative multicenter trial assessing 2 switching techniques in Asia Pacific.

BACKGROUND: This open-label, multicenter, randomized study compared the efficacy and safety of switching moderately ill Asian patients with schizophrenia from their current regimen of antipsychotic medication to the atypical antipsychotic olanzapine using either a direct switch method or a start-taper switch method. METHOD: Asian inpatients and outpatients with DSM-IV schizophrenia (N = 108) currently treated with predominantly typical antipsychotics were switched to olanzapine (initial dose of 10 mg/day) for 6 weeks. Patients were randomly assigned to 1 of 2 groups: the direct switch group (N = 54) received only olanzapine, while the start-taper switch group (N = 54) received olanzapine and their usual antipsychotic in decreasing doses for the first 2 weeks. A successful switch was defined as completing 6 weeks of therapy without worsening of symptoms (Clinical Global Impressions-Severity of Illness scale [CGI-S]) or extrapyramidal side effects (Simpson-Angus Scale). Overall efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and safety was assessed by recording adverse events and measuring vital signs. RESULTS: Statistically significant (p < .001) improvements from baseline to endpoint occurred in both switch groups in the CGI-S score and the PANSS total score and subscores. However, no significant differences were observed between the switch groups for any efficacy measure. Both techniques had comparable rates of successful switching (direct switch, 74.1% vs. start-taper switch, 67.9%). The frequency of treatment-emergent adverse events was similar between switch groups with no clinically significant differences in any laboratory value or vital sign. Weight gain occurred in both switch groups (p < .001), but the groups were not statistically different from each other. Both switch groups showed statistically significant (p < .01) improvements from baseline to endpoint on the Simpson-Angus Scale and Barnes Akathisia Scale. CONCLUSION: Moderately ill Asian patients with schizophrenia may experience a decrease in symptom severity and improvement in extrapyramidal symptoms when switched from their current medication to olanzapine therapy.