CNS stimulants have been proposed as beneficial in the management of psychostimulant dependence as substitution therapy and withdrawal management and in the treatment of underlying Attention Deficit Hyperactivity Disorder (ADHD).
Amphetamine dependenceDexamphetamine substitution programs have been available for amphetamine users in the UK although the efficacy and safety of the practice has not been adequately tested by randomised controlled trials (Bradbeer et al., 1998; Shearer, Sherman, Wodak & van Beek, 2002). Substitution therapies aim to replace harmful drug use with safer modes of drug use in terms of dose, route of administration and adverse effects. Effective substitutes may allow patients to stabilise on doses that prevent withdrawal and craving and to reduce the harms associated with illicit drug use. Attracting and retaining problematic cocaine users in treatment may also facilitate engagement with health care services, including psychosocial interventions. Mattick and Darke (1995) have suggested that amphetamine maintenance may be appropriate where amphetamine use is frequent (usually daily), attempts to achieve abstinence have been unsuccessful, dependence is evident, severe adverse complications have occurred and maintenance is likely to cause less harm than continued illicit use. Risks associated with maintenance include psychiatric and cardiovascular complications, particularly when additional illicit psychostimulants are consumed. Carnwath et al. (2002) reported that six out of eight patients with schizophrenia who had received prescribed dexamphetamine both reduced amphetamine use and improved psychiatric health. There was no exacerbation of psychosis in any patient while compliance with neuroleptics improved in most cases. A retrospective case note evaluation of a Welsh dexamphetamine program found three episodes of psychosis in 63 patients receiving amphetamine substitution treatment over two years, all associated with additional use of street amphetamines (McBride, Sullivan, Blewett & Morgan, 1997). In a large cohort study, five cases of psychosis in 220 patients over four years were reported, all with prior histories of psychosis and continuing injecting drug use (White, 2000).
Evaluations of amphetamine prescription conducted in the 1960s and early 1970s in London concluded that the modest benefits were outweighed by serious negative consequences including psychosis, continuing illicit use and diversion of prescribed amphetamines (Gardner & Connell, 1972; Hawks, Mitcheson, Ogborne & Edwards, 1969). More recent evaluations of clinical programs have suggested that amphetamine users are attracted to services offering amphetamine prescription where they can also be provided with advice, counselling and harm minimisation interventions such as needle and syringe programs (Fleming & Roberts, 1994; Klee et al., 2001; McBride et al., 1997). Reported positive outcomes of amphetamine prescribing included reduced illicit amphetamine use, reduced injecting, reduced sharing of injecting equipment, improved social functioning and retention in treatment (Charnaud & Griffiths, 1998; Fleming & Roberts, 1994; Klee et al., 2001; McBride et al., 1997; Pates, Coombes & Ford, 1996; Shearer,Wodak, Mattick, van Beek et al., 2001; Sherman, 1990; White, 2000). A retrospective comparison of discharge notes for 60 dexamphetamine program patients (mean dose 43 mg/day) and 120 methadone program patients (mean dose 44 mg/day) found both treatments equally effective in reducing injecting behaviour, with 70% of amphetamine users showing no physical evidence of injecting compared to 67% of methadone patients (Charnaud & Griffiths, 1998). The first published prospective pilot RCT (Shearer et al., 2001) found modest gains in favour of dexamphetamine treatment (60 mg/day) compared to counselling alone but these did not reach statistical significance, possibly due to the small sample size.Top of page
Cocaine dependenceDexamphetamine has also been investigated for cocaine dependence in two studies. A 13-week controlled study (N=128) of sustained release dexamphetamine (placebo, 15–30 mg/day dexamphetamine and 30-60 mg/day dexamphetamine) found dose related changes in retention and cocaine use in favour of dexamphetamine treatment with no serious adverse events or cardiovascular complications (Grabowski, Rhoades, Schmitz, Stotts & Daruzska, 2001). Findings were limited by high study attrition. An Australian 14-week placebo controlled study (N=30 cocaine injectors) of dexamphetamine 60 mg/day found outcomes (cocaine use, crime, cocaine craving and severity of dependence) favoured dexamphetamine treatment with no improvement in the placebo group (Shearer, Wodak, van Beek, Mattick & Lewis, 2003).
Other agonist agents used in cocaine dependence have included methylphenidate (RitalinTM) and oral forms of cocaine. Levin et al. (1998) reported significantly reduced cocaine use and cravings in a group of 12 patients diagnosed with comorbid adult ADHD and cocaine dependence receiving 40 mg/day sustained release methylphenidate. However, a placebo controlled trial of 48 cocaine-dependent adult ADHD patients found improvements in reported ADHD symptoms in subjects receiving active methylphenidate but none between group differences in cocaine use or cravings (Schubiner, Saules, Arfken, Johansen et al., 2002). Further, in a randomised placebo controlled trial of 49 patients without adult ADHD, methylphenidate (20 mg twice daily slow release) was ineffective in reducing cocaine use (Grabowski et al., 1998). Grabowski et al. suggested consideration of other psychostimulants that may be more adequate reinforcers.
Oral formulations of cocaine including coca tea infusions and tablets have been investigated in Peru for coca paste smokers (Llosa, 1994a; Llosa, 1994b; Llosa, 1996). Overall results suggested that a low dose of oral cocaine (20-60 mg/day) significantly reduced relapse to heavy use and cravings (Llosa, 1994a). Interestingly, in the open trial involving 23 subjects, while all accepted coca tea as a treatment, 78% agreed they would have preferred to take the same medication in capsules. Walsh et al. (2000) tested the safety and utility of oral cocaine in a laboratory study where oral cocaine was administered in a range of doses (0-100 mg/day) to eight subjects with cocaine use histories. Intravenous cocaine challenges (0-50 mg) were administered during each new dose sequence. They found that oral cocaine modestly attenuated the subjective and physiological responses to intravenous cocaine and was safely tolerated.