Heroin Dependence Clinical Trial
Official title:
An Open-label Study of Oral Paliparidone for the Treatment of Patients With Co-occurring Opioid and Amphetamine-type Stimulant Dependence
The proposed study will evaluate the tolerability, acceptability and potential efficacy of paliparidone for the treatment of co-occurring opioid and amphetamine-type stimulant (ATS) dependence. In the proposed clinical trial, all patients will first discontinue illicit opioid and ATS and be inducted onto buprenorphine maintenance treatment (BMT) in the inpatient ward at the department of psychiatry before beginning to receive paliparidone. Tolerability and acceptability will be evaluated by assessing the rates of patient retention during treatment, patient satisfaction with treatment and adverse effects during treatment. The potential efficacy of paliparidone will be evaluated with regard to the primary outcome measure: reductions in illicit ATS use, based on urine toxicology testing and self-report. Secondary outcome measures include treatment retention, reduction in HIV risk behaviors and improvements in functional status.
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.
Paliperidone's potential efficacy for treating ATS dependence was suggested both by its
potential for blocking or attenuating the rewarding effects of ATS use and by its potential
for improving cognitive functioning in patients recovering from ATS dependence. An open
label pilot study of oral risperidone for the treatment of methamphetamine dependence
provided preliminary evidence for the safety, tolerability and potential efficacy of
risperidone. Risperidone was generally well-tolerated and associated with decreased
methamphetamine use and improvements in fine motor function and mood. A subsequent open
trial of injectable ripseridone found that injectable risperidone was associated with
reductions in methamphetamine use and improvements in verbal memory.
However to date there have been no published replication studies or studies of paliperidone
for treating ATS dependence in other populations and setting. This proposed pilot study of
paliperidone for the treatment of ATS dependence would extend this work and provide specific
data regarding the tolerability and efficacy of paliperidone in opioid-agonist maintained
patients with co-occurring ATS and opioid dependence (COATS).
In addition to detoxification and treatment medications, a manual-guided educational drug
and HIV risk reduction counseling (EDRC) will be provided to all participants. EDRC provides
education about medical understanding of opioid and ATS addiction, highly effective
strategies used in successful drug recovery efforts, medical and other harmful consequences
of drug use including HIV and other infectious disease transmission, as well as about
effective prevention of all negative consequences of illicit drug use (Chawarski et al,
2008). It helps patient to remain in treatment, adhere to prescribed medications, abstain
from or reduce illicit opioid and ATS use and HIV risk behaviors, and make life-style
changes fostering sustained recovery. It also teaches basic cognitive and behavioral coping
skills that increase the patients' chances to reach sustained and prolonged recovery from
drugs. For HIV positive patients, EDRC encourages patients to attend the HIV clinic and
adhere to monitoring, medication, and other treatment recommendations. EDRC will be provided
by trained and supervised nursing personnel, drug counselors, or therapists. It will be
offered in individual format with the frequency ranging from 3 times per week during
detoxification to once per week during the outpatient phase of treatment.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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