NDARC Technical Report No. 75 (1999)
This feasibility study was a randomised controlled trial to test the reliability of urinary isomer monitoring to see whether individuals who consume street amphetamine could be distinguished from those who consume pharmaceutical amphetamine and those who consume amphetamine of both street and pharmaceutical origin. The study was conducted at the Kirketon Road Centre (KRC), a primary health care centre in Kings Cross in the inner city area of Sydney. KRC is involved in the care of injecting drug users, sex workers, 'at risk' youth and other disadvantaged or 'at risk' inner city communities primarily in the prevention and treatment of blood borne viruses and other transmissible infections. The centre offers both on-site and outreach medical, counselling and social welfare services, a methadone access program and a needle and syringe service.
Forty-one subjects, assessed as long-term dependent amphetamine users, were enrolled in the study over a period of 10 months from February to December 1998. Subjects were carefully assessed for amphetamine dependence, a history of chronic amphetamine use, and were only included if they gave a urine sample tested positive for amphetamine. Subjects were screened for active psychosis or any history of psychotic disorders (including schizophrenia) and underwent a medical assessment for any other chronic illness. Subjects who met the inclusion criteria were randomised after assessment to treatment (21 subjects) or control groups (20 subjects). Both groups were offered usual care including standard counselling offered by the KRC counselling unit for amphetamine users. The treatment group was in addition prescribed dexamphetamine to a maximum daily supervised oral dose of 60 mg for a period of up to 12 weeks.
The main finding of the study was that urinary isomer analysis did not distinguish pharmaceutical from street amphetamine in this study population. Methylamphetamine, which was not pharmaceutically available in Australia, was present in all baseline urine samples and could, therefore, be used as a marker of illicit amphetamine. Fortunately, this allowed the original aims of the study to be achieved with some minor changes to the study protocol. The urinalysis results obtained by testing for methylamphetamine rather than isomer monitoring confirmed that it was possible to use urinalysis to detect continued street amphetamine use in subjects who were receiving pharmaceutical dexamphetamine.
The study was designed in 1995. A pilot study conducted in 1996 confirmed the expected proportions of d:l urinary amphetamine isomers obtained in samples taken from subjects consuming street amphetamine and patients prescribed dexamphetamine for attention deficit hyperactivity disorder. The start of the study was considerably delayed by requirements to satisfy all relevant authorities that the present study met an important need, was sufficiently rigorous and did not infringe any policy or ethical requirements. During this period the availability of amphetamine precursors became more restricted presumably leading to changes in the main method used to synthesise street amphetamine. Urine tests indicated that, at the time of the study was conducted in 1998, illicit amphetamine was manufactured using pseudoephedrine as the major precursor, producing levels of d-amphetamine isomer equivalent to that produced by the ingestion of pharmaceutical dexamphetamine. Thus, changes in local illicit amphetamine supplies are an important consideration in selecting reliable monitoring techniques in future dexamphetamine trials.
This study also demonstrated that a trial to evaluate the effectiveness of controlled prescribing of amphetamine as substitution therapy for problematic amphetamine users was feasible. A number of components of such a study were tested and performed well. These included: subject recruitment, assessment, and retention; measurement of changes in amphetamine use and associated harms; the response of subjects to the control condition; the attractiveness of the intervention to potential subjects; its acceptability to clinical staff and the cost of the intervention. The study design was found to be appropriate as evidenced by acceptable recruitment, retention and outcome data. Recruitment proved the most difficult aspect of the study suggesting that the intervention may only be attractive to a sub-set of amphetamine users who experience the most severe physical and psychological harms associated with long-term, chronic amphetamine use. The overall study design, with some modifications, is feasible for a larger trial of efficacy and safety.
Assessment of the risks involved in providing dexamphetamine substitution therapy was an important concern of the investigators. It was reassuring that there were no serious adverse events reported during the course of the study. No psychotic symptoms or episodes were reported in the treatment group: a finding also reported in similar studies in the United Kingdom. The risk of psychotic symptoms developing in carefully screened and monitored subjects on the maximum dose used in this study appeared to be low. The recruitment experience gained in this study also suggested that the risk of inadvertently creating amphetamine dependence by treating non-dependent users was also very low. A concern that recreational users would be irresistibly attracted to substitution prescribing programs to increase their drug consumption was not supported in this study. There were no incidents of dexamphetamine being diverted from KRC with all doses dispensed under supervision and crushed in orange juice. The program proceeded with minimal disruption to KRC clinical services including the centre's methadone program.
Indications of the efficacy of an amphetamine substitution program were secondary aims of the study. Assessment of the effectiveness of this intervention was substantially limited by the relatively small sample size, short study duration and some important potential sources of bias. After 12 weeks, 61.5% of urine samples from the control group and 52.9% of urine samples from the treatment group tested positive for illicit amphetamine. According to an intention-to-treat analysis this difference was not statistically significant. The only statistically significant difference between study groups was in the uptake of counselling which was greater in the treatment group. This finding may, however, have been explained by the significantly higher proportion of females in the treatment group. Statistically significant improvements were found between baseline and follow-up in both groups in HIV risk behaviour (due to reduced injecting) and in the degree of amphetamine dependence as measured by the Severity of Dependence Scale. In the treatment group expenditure on illicit amphetamine also fell significantly.
Urinalysis and self-report were consistent in identifying a reduction in amphetamine use and related harms in both groups over the course of the study. Whether these changes endure or a difference exists between treatment and control groups can only be answered by an appropriately designed efficacy trial with a larger sample and longer duration of follow-up. The present study found that urinalysis can be used to distinguish illicit from pharmaceutical amphetamine consumption and therefore that it has a role in the evaluation of the efficacy of dexamphetamine as substitution therapy.