An Open-label Study of Oral Paliparidone for the Treatment of Patients With Co-occurring Opioid and Amphetamine-type Stimulant Dependence

Malaysia has been struggling in fighting drug addiction in the country (NADI, 2005). Opioids predominantly heroin and morphine and ATS (Chawarski et al, 2006). dependence are the primary drugs of abuse for most drug users in Malaysia There are more than 300,000 registered drug users in Malaysia, most are opioid dependent and current intravenous drug users (IVDU). Drug abuse comes together with other medical and social problems, as 25-30% of IVDU are infected with HIV; and IVDU accounts for 70% of HIV infections in Malaysia. There are more than 90, 000 registered HIV positives between 1986 and 2010. (National Anti-Drug Agency of Malaysia, 2010).

Over the past decade, amphetamine-type stimulant (ATS) has also emerged as a major drug problem. Globally, ATS is now the second most commonly used illicit drug type and is more widely used than heroin. ATS abuse is especially prevalent and problematic in the Asian region, where ATS production, use, drug seizures, and demand for treatment have continued to increase. Injection of methamphetamine has been reported in Malaysia (Chawarski et al, 2006) and other south-east Asian countries (McKetin, 2008). In the most recent survey of out-of-treatment heroin IVDU in cities across Malaysia, more than 60% report current ATS use, and 29% inject ATS (Chawarski et al, 2012).

ATS use is associated with increased HIV transmission behavioral risks. The connection of heroin, methamphetamine and HIV in Malaysia is well documented (Chawarski et al, 2006). Increased needle sharing and risky sexual behaviors lead to increased prevalence of HIV infection. ATS use exacerbates HIV transmission risk through a number of mechanisms: ATS users report engaging in more frequent and more risky sexual behaviors while using ATS and in more frequent needle sharing. ATS is also associated with impairments of mood and executive functioning that may persist for prolonged periods and may contribute to relapse to drug use, thus all other problems.

Drug abuse has been a major problem in Kelantan for the past several decades (Suarn & NorAdam,1993) and ATS has been gaining momentum over the past decade. The number of individuals arrested annually for ATS in Kelantan increased over the past 5 years from 2900 in 2007 to 5300 in 2010. For the past 5 years, Kelantan has also led Malaysia in having the highest population prevalence of HIV infection, at 47 per 100,000 in 2008, nearly 4 times the prevalence reported for the rest of Malaysia. Kelantan also has the highest number of women with HIV in Malaysia with more than 1200 reported in 2008, suggesting that HIV is making the transition to the general population. A large proportion of treatment seeking drug users in Kelantan are HIV positives and are susceptible to high mortality (JKNK, 2012).

Paliperidone, the primary active metabolite of risperidone, is a long-acting atypical neuroleptic (antipsychotic) medication. It blocks dopamine 2 (D2) receptors and serotonin 2A receptors and acts as an alpha2 antagonist. Blockade of the D2 receptors may reduce the reinforcing effects of ATS or other stimulants; blockade of the serotonin 2A receptor leads to increased DA release in the prefrontal cortex and motor regions and may thus improve cognitive performance and mood and reduce motor impairments associated with blockade of D2 receptors; and alpha2 antagonist actions may provide antidepressant effects.